Genome-Wide Detection and Analysis of Multifunctional Genes

PubMed Central

Pritykin, Yuri; Ghersi, Dario; Singh, Mona

2015-01-01

Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms—H. sapiens, D. melanogaster, and S. cerevisiae—and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential. We also find that multifunctional genes are significantly more likely to be involved in human disorders. These same features also hold when multifunctionality is defined with respect to molecular functions instead of biological processes. Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality. PMID:26436655

Psychometrics of Multiple Choice Questions with Non-Functioning Distracters: Implications to Medical Education.

PubMed

Deepak, Kishore K; Al-Umran, Khalid Umran; AI-Sheikh, Mona H; Dkoli, B V; Al-Rubaish, Abdullah

2015-01-01

The functionality of distracters in a multiple choice question plays a very important role. We examined the frequency and impact of functioning and non-functioning distracters on psychometric properties of 5-option items in clinical disciplines. We analyzed item statistics of 1115 multiple choice questions from 15 summative assessments of undergraduate medical students and classified the items into five groups by their number of non-functioning distracters. We analyzed the effect of varying degree of non-functionality ranging from 0 to 4, on test reliability, difficulty index, discrimination index and point biserial correlation. The non-functionality of distracters inversely affected the test reliability and quality of items in a predictable manner. The non-functioning distracters made the items easier and lowered the discrimination index significantly. Three non-functional distracters in a 5-option MCQ significantly affected all psychometric properties (p < 0.5). The corrected point biserial correlation revealed that the items with 3 functional options were psychometrically as effective as 5-option items. Our study reveals that a multiple choice question with 3 functional options provides lower most limit of item format that has adequate psychometric property. The test containing items with less number of functioning options have significantly lower reliability. The distracter function analysis and revision of nonfunctioning distracters can serve as important methods to improve the psychometrics and reliability of assessment.

Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function.

PubMed

Lenz, Kathryn M; Nelson, Lars H

2018-01-01

Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

A Multiple Case Study: Gauging the Effects of Poverty on School Readiness amongst Preschoolers

ERIC Educational Resources Information Center

Onesto, Melissa J.

2017-01-01

The home environment, which includes the level of organization and stability in the home, plays a crucial role in the development of executive function and oral language skills. For children who live in a low-SES environment, executive function and oral language acquisition are inferior compared to that of students living at other economic levels.…

Remedying Social Skills Deficits in a Chronic Schizophrenic-Retarded Person.

ERIC Educational Resources Information Center

Jackson, Henry J.; Martin, Rose

1983-01-01

An adult chronic schizophrenic, residual type, with an additional diagnosis of mild-moderate retardation, received social skills training (SST). Videotaped role-play assessments showed change occurred following SST, while a multiple-baseline design demonstrated functional control over the behaviors. (Author/CL)

[The possibility of using music therapy in neurology on the example of multiple sclerosis].

PubMed

Boiko, E A; Ivanchuk, E V; Gunchenko, M M; Batysheva, T T

2016-01-01

Currently music therapy plays an important role in the drug-free treatment and rehabilitation of children and adults with acute and chronic neurological and somatic diseases including demyelinating diseases. Existing studies show the effectiveness of music therapy in the improvement of social skills, cognitive function and sleep as well as in the reduction in the severity of depression, anxiety and pain in patients with multiple sclerosis.

Social play among juvenile wild Japanese macaques (Macaca fuscata) strengthens their social bonds.

PubMed

Shimada, Masaki; Sueur, Cédric

2018-01-01

Social play and grooming are typical affiliative interactions for many primate species, and are thought to have similar biological functions. However, grooming increases with age, whereas social play decreases. We proposed the hypothesis that both social grooming and social play in juveniles strengthen their social bonds in daily activities. We carried out field research on the social relationships among juvenile wild Japanese macaques in a troop in Kinkazan, Miyagi Prefecture, Japan, from fall 2007 to spring 2008 to investigate this hypothesis. We evaluated three relationships among juveniles, play indices (PI), grooming indices (GI), and 3-m-proximity indices (3mI) of each dyad (i.e., interacting pair), and compared these social networks based on the matrices of the indices. The play and grooming networks were correlated with the association network throughout the two research periods. The multiple network level measurements of the play network, but not the grooming network, resembled those of the association network. Using a causal step approach, we showed that social play and grooming interactions in fall seem to predict associations in the following spring, controlling for the PI and GI matrix in spring, respectively. Social play and grooming for each juvenile were negatively correlated. The results partially support our predictions; therefore, the hypothesis that the biological function of social play among immature Japanese macaques is to strengthen their social bonds in the near future and develop their social life appears to be correct. For juvenile macaques, social play, rather than grooming, functions as an important social mechanism to strengthen affiliative relationships. © 2017 Wiley Periodicals, Inc.

Hurricane Hugo blows down the broccoli: preschoolers' post-disaster play and adjustment.

PubMed

Saylor, C F; Swenson, C C; Powell, P

1992-01-01

This article reports highlights from over 200 parents' observations of their preschoolers' play and verbalizations in the year following Hurricane Hugo. Commonly reported activities included reenactment and discussion of the event in multiple mediums, personification of "Hugo", and expression of fears related to storms. Precocious concern for others, insight, and vocabulary were also noted. In these intact, relatively high functioning families, parents seemed able to facilitate their youngsters' adjustment without outside intervention.

Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children

USDA-ARS?s Scientific Manuscript database

Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain. The aim of this study was to identify and characterize the effects of MC4R variants in Hispani...

Expanding frontiers in materials chemistry and physics with multiple anions.

PubMed

Kageyama, Hiroshi; Hayashi, Katsuro; Maeda, Kazuhiko; Attfield, J Paul; Hiroi, Zenji; Rondinelli, James M; Poeppelmeier, Kenneth R

2018-02-22

During the last century, inorganic oxide compounds laid foundations for materials synthesis, characterization, and technology translation by adding new functions into devices previously dominated by main-group element semiconductor compounds. Today, compounds with multiple anions beyond the single-oxide ion, such as oxyhalides and oxyhydrides, offer a new materials platform from which superior functionality may arise. Here we review the recent progress, status, and future prospects and challenges facing the development and deployment of mixed-anion compounds, focusing mainly on oxide-derived materials. We devote attention to the crucial roles that multiple anions play during synthesis, characterization, and in the physical properties of these materials. We discuss the opportunities enabled by recent advances in synthetic approaches for design of both local and overall structure, state-of-the-art characterization techniques to distinguish unique structural and chemical states, and chemical/physical properties emerging from the synergy of multiple anions for catalysis, energy conversion, and electronic materials.

Fatigue is not associated with impaired function of regulatory T cells in untreated patients with multiple sclerosis.

PubMed

Yaldizli, Ozguer; Kumar, Manoj; Vago, Susanne; Kreuzfelder, Erich; Limmroth, Volker; Putzki, Norman

2009-01-01

The pathophysiology of multiple sclerosis (MS)-associated fatigue is poorly understood. Immunological mechanisms may play a role. Alterations in immunological profile indicate a chronic immune activation in MS patients with fatigue. T-regulatory (Treg) cells seem to play a key role in coordinating autoimmune mechanisms in MS. This is the first study investigating the relationship between Treg cell function and fatigue in MS patients. In this cross-sectional in vitro, ex vivo study, we isolated peripheral blood mononuclear cells (PBMCs) from 20 MS patients with fatigue, determined lymphocyte subsets by flow cytometry and suppressive function of Treg cells in PBMC cultures with antigen stimulation. Forkhead box protein 3 expression was evaluated by PCR. Results were compared with 20 MS patients without fatigue and with 19 healthy controls. Leukocytes and lymphocyte subsets including Treg cell frequency did not differ in patients with and without fatigue. Co-culturing of Treg cells with CD4+CD25- cells did not lead to a significant suppression of myelin basic protein- and pokeweed mitogen-induced proliferation in MS patients in contrast to healthy controls. There were no statistical differences between MS patients with and without fatigue regarding this suppression activity. Fatigue seems not to be associated with impaired function of Treg cells in untreated MS patients.

Rotor noise due to blade-turbulence interaction

NASA Astrophysics Data System (ADS)

Ishimaru, K.

1983-01-01

The time-averaged intensity density function of the acoustic radiation from rotating blades is derived by replacing blades with rotating dipoles. This derivation is done under the following turbulent inflow conditions: turbulent ingestion with no inlet strut wakes, inflow turbulence elongation and contraction with no inlet strut wakes, and inlet strut wakes. Dimensional analysis reveals two non-dimensional parameters which play important roles in generating the blade-passing frequency tone and its multiples. The elongation and contraction of inflow turbulence has a strong effect on the generation of the blade-passing frequency tone and its multiples. Increasing the number of rotor blades widens the peak at the blade-passing frequency and its multiples. Increasing the rotational speed widens the peak under the condition that the non-dimensional parameter involving the rotational speed is fixed. The number of struts and blades should be chosen so that (the least common multiple of them)-(rotational speed) is in the cutoff range of Sears' function, in order to minimize the effect of the mean flow deficit on the time averaged intensity density function.

Cluster analysis differentiates high and low community functioning in schizophrenia: Subgroups differ on working memory but not other neurocognitive domains.

PubMed

Alden, Eva C; Cobia, Derin J; Reilly, James L; Smith, Matthew J

2015-10-01

Schizophrenia is characterized by impairment in multiple aspects of community functioning. Available literature suggests that community functioning may be enhanced through cognitive remediation, however, evidence is limited regarding whether specific neurocognitive domains may be treatment targets. We characterized schizophrenia subjects based on their level of community functioning through cluster analysis in an effort to identify whether specific neurocognitive domains were associated with variation in functioning. Schizophrenia (SCZ, n=60) and control (CON, n=45) subjects completed a functional capacity task, social competence role-play, functional attainment interview, and a neuropsychological battery. Multiple cluster analytic techniques were used on the measures of functioning in the schizophrenia subjects to generate functionally-defined subgroups. MANOVA evaluated between-group differences in neurocognition. The cluster analysis revealed two distinct groups, consisting of 36 SCZ characterized by high levels of community functioning (HF-SCZ) and 24 SCZ with low levels of community functioning (LF-SCZ). There was a main group effect for neurocognitive performance (p<0.001) with CON outperforming both SCZ groups in all neurocognitive domains. Post-hoc tests revealed that HF-SCZ had higher verbal working memory compared to LF-SCZ (p≤0.05, Cohen's d=0.78) but the two groups did not differ in remaining domains. The cluster analysis classified schizophrenia subjects in HF-SCZ and LF-SCZ using a multidimensional assessment of community functioning. Moreover, HF-SCZ demonstrated rather preserved verbal working memory relative to LF-SCZ. The results suggest that verbal working memory may play a critical role in community functioning, and is a potential cognitive treatment target for schizophrenia subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

FULL-GENOME ANALYSIS OF ALTERNATIVE SPLICING IN MOUSE LIVER AFTER HEPATOTOXICANT EXPOSURE

EPA Science Inventory

Alternative splicing plays a role in determining gene function and protein diversity. We have employed whole genome exon profiling using Affymetrix Mouse Exon 1.0 ST arrays to understand the significance of alternative splicing on a genome-wide scale in response to multiple toxic...

MUD for Learning: Classification and Instruction

ERIC Educational Resources Information Center

Hsieh, Chung-Hsiang; Sun, Chuen-Tsai

2006-01-01

From a constructivist point of view, the importance of MUDs (Multiple User Dungeons) in education is justified based on their community-forming, learning, and role-playing functions. The authors propose a typology for educational MUDs and discuss their individual instructional approaches in order to measure MUD potential in ten-os of…

Engineering Play: Exploring Associations with Executive Function, Mathematical Ability, and Spatial Ability in Preschool

NASA Astrophysics Data System (ADS)

Gold, Zachary Samuel

Engineering play is a new perspective on preschool education that views constructive play as an engineering design process that parallels the way engineers think and work when they develop engineered solutions to human problems (Bairaktarova, Evangelou, Bagiati, & Brophy, 2011). Early research from this perspective supports its use in framing play as a key learning context. However, no research to date has examined associations between engineering play and other factors linked with early school success, such as executive function, mathematical ability, and spatial ability. Additionally, more research is needed to further validate a new engineering play observational measure. This study had two main goals: (1) to gather early validity data on the engineering play measure as a potentially useful instrument for documenting the occurrence of children's engineering play behaviors in educational contexts, such as block play. This was done by testing the factor structure of the engineering play behaviors in this sample and their association with preschoolers' planning, a key aspect of the engineering design process; (2) to explore associations between preschoolers' engineering play and executive function, mathematical ability, and spatial ability. Participants included 110 preschoolers (62 girls; 48 boys; M = 58.47 months) from 10 classrooms in the Midwest United States coded for their frequency of engagement in each of the nine engineering play behaviors. A confirmatory factor analysis resulted in one engineering play factor including six of the engineering play behaviors. A series of marginal regression models revealed that the engineering play factor was significantly and positively associated with the spatial horizontal rotation transformation. However, engineering play was not significantly related to planning ability, executive function, informal mathematical abilities, or other spatial transformation skills. Follow-up analyses revealed significant positive associations between engineering play and planning, executive function, and geometry for only a subgroup of children (n = 27) who had individualized education program (IEP) status. This was the first of a series of studies planned to evaluate the potential of the engineering play perspective as a tool for understanding young children's development and learning across multiple developmental domains. Although most hypotheses regarding engineering play and cognitive skills were not supported, the study provided partial evidence for the reliability and validity of the engineering play observation measure. Future research should include larger sample sizes with more statistical power, continued refinement of the engineering play observation measure, examination of potential associations with specific early learning domains, including spatial ability and language, and more comparisons of engineering play between typically developing children and children with disabilities.

An epigenetic view of developmental diseases: new targets, new therapies.

PubMed

Xie, Pei; Zang, Li-Qun; Li, Xue-Kun; Shu, Qiang

2016-08-01

Function of epigenetic modifications is one of the most competitive fields in life science. Over the past several decades, it has been revealed that epigenetic modifications play essential roles in development and diseases including developmental diseases. In the present review, we summarize the recent progress about the function of epigenetic regulation, especially DNA and RNA modifications in developmental diseases. Original research articles and literature reviews published in PubMed-indexed journals. DNA modifications including methylation and demethylation can regulate gene expression, and are involved in development and multiple diseases including Rett syndrome, Autism spectrum disorders, congenital heart disease and cancer, etc. RNA methylation and demethylation play important roles in RNA processing, reprogramming, circadian, and neuronal activity, and then modulate development. DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

The porous borders of the protein world.

PubMed

Cordes, Matthew H J; Stewart, Katie L

2012-02-08

Fold switching may play a role in the evolution of new protein folds and functions. He et al., in this issue of Structure, use protein design to illustrate that the same drastic change in a protein fold can occur via multiple different mutational pathways. Copyright © 2012 Elsevier Ltd. All rights reserved.

Free energy landscape and transition pathways from Watson–Crick to Hoogsteen base pairing in free duplex DNA

PubMed Central

Yang, Changwon; Kim, Eunae; Pak, Youngshang

2015-01-01

Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson–Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine–thymine (A–T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events. PMID:26250116

Functional Connectivity in Multiple Cortical Networks Is Associated with Performance Across Cognitive Domains in Older Adults.

PubMed

Shaw, Emily E; Schultz, Aaron P; Sperling, Reisa A; Hedden, Trey

2015-10-01

Intrinsic functional connectivity MRI has become a widely used tool for measuring integrity in large-scale cortical networks. This study examined multiple cortical networks using Template-Based Rotation (TBR), a method that applies a priori network and nuisance component templates defined from an independent dataset to test datasets of interest. A priori templates were applied to a test dataset of 276 older adults (ages 65-90) from the Harvard Aging Brain Study to examine the relationship between multiple large-scale cortical networks and cognition. Factor scores derived from neuropsychological tests represented processing speed, executive function, and episodic memory. Resting-state BOLD data were acquired in two 6-min acquisitions on a 3-Tesla scanner and processed with TBR to extract individual-level metrics of network connectivity in multiple cortical networks. All results controlled for data quality metrics, including motion. Connectivity in multiple large-scale cortical networks was positively related to all cognitive domains, with a composite measure of general connectivity positively associated with general cognitive performance. Controlling for the correlations between networks, the frontoparietal control network (FPCN) and executive function demonstrated the only significant association, suggesting specificity in this relationship. Further analyses found that the FPCN mediated the relationships of the other networks with cognition, suggesting that this network may play a central role in understanding individual variation in cognition during aging.

A unique role of endogenous visual-spatial attention in rapid processing of multiple targets

PubMed Central

Guzman, Emmanuel; Grabowecky, Marcia; Palafox, German; Suzuki, Satoru

2012-01-01

Visual spatial attention can be exogenously captured by a salient stimulus or can be endogenously allocated by voluntary effort. Whether these two attention modes serve distinctive functions is debated, but for processing of single targets the literature suggests superiority of exogenous attention (it is faster acting and serves more functions). We report that endogenous attention uniquely contributes to processing of multiple targets. For speeded visual discrimination, response times are faster for multiple redundant targets than for single targets due to probability summation and/or signal integration. This redundancy gain was unaffected when attention was exogenously diverted from the targets, but was completely eliminated when attention was endogenously diverted. This was not due to weaker manipulation of exogenous attention because our exogenous and endogenous cues similarly affected overall response times. Thus, whereas exogenous attention is superior for processing single targets, endogenous attention plays a unique role in allocating resources crucial for rapid concurrent processing of multiple targets. PMID:21517209

Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms.

PubMed

Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-E; Zhang, Xiaochu

2017-01-01

Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs' appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers' attention from different fields and many studies have validated MMORPGs' positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational application of the MMORPGs based on relevant macroscopic and microscopic studies, showing that gamers' overall language proficiency or some specific language skills can be enhanced by real-time online interaction with peers and game narratives or instructions embedded in the MMORPGs. Mechanisms underlying the educational assistant role of MMORPGs in second language learning are discussed from both behavioral and neural perspectives. We suggest that attentional bias makes gamers/learners allocate more cognitive resources toward task-related stimuli in a controlled or an automatic way. Moreover, with a moderating role played by activation of reward circuit, playing the MMORPGs may strengthen or increase functional connectivity from seed regions such as left anterior insular/frontal operculum (AI/FO) and visual word form area to other language-related brain areas.

The Case for Musical Instrument Training in Cerebral Palsy for Neurorehabilitation

PubMed Central

2016-01-01

Recent imaging studies in cerebral palsy (CP) have described several brain structural changes, functional alterations, and neuroplastic processes that take place after brain injury during early development. These changes affect motor pathways as well as sensorimotor networks. Several of these changes correlate with behavioral measures of motor and sensory disability. It is now widely acknowledged that management of sensory deficits is relevant for rehabilitation in CP. Playing a musical instrument demands the coordination of hand movements with integrated auditory, visual, and tactile feedback, in a process that recruits multiple brain regions. These multiple demands during instrument playing, together with the entertaining character of music, have led to the development and investigation of music-supported therapies, especially for rehabilitation with motor disorders resulting from brain damage. We review scientific evidence that supports the use of musical instrument playing for rehabilitation in CP. We propose that active musical instrument playing may be an efficient means for triggering neuroplastic processes necessary for the development of sensorimotor skills in patients with early brain damage. We encourage experimental research on neuroplasticity and on its impact on the physical and personal development of individuals with CP. PMID:27867664

The Case for Musical Instrument Training in Cerebral Palsy for Neurorehabilitation.

PubMed

Alves-Pinto, Ana; Turova, Varvara; Blumenstein, Tobias; Lampe, Renée

2016-01-01

Recent imaging studies in cerebral palsy (CP) have described several brain structural changes, functional alterations, and neuroplastic processes that take place after brain injury during early development. These changes affect motor pathways as well as sensorimotor networks. Several of these changes correlate with behavioral measures of motor and sensory disability. It is now widely acknowledged that management of sensory deficits is relevant for rehabilitation in CP. Playing a musical instrument demands the coordination of hand movements with integrated auditory, visual, and tactile feedback, in a process that recruits multiple brain regions. These multiple demands during instrument playing, together with the entertaining character of music, have led to the development and investigation of music-supported therapies, especially for rehabilitation with motor disorders resulting from brain damage. We review scientific evidence that supports the use of musical instrument playing for rehabilitation in CP. We propose that active musical instrument playing may be an efficient means for triggering neuroplastic processes necessary for the development of sensorimotor skills in patients with early brain damage. We encourage experimental research on neuroplasticity and on its impact on the physical and personal development of individuals with CP.

Mammalian Polyamine Metabolism and Function

PubMed Central

Pegg, Anthony E.

2009-01-01

Summary Polyamines are ubiquitous small basic molecules that play multiple essential roles in mammalian physiology. Their cellular content is highly regulated and there is convincing evidence that altered metabolism is involvement in many disease states. Drugs altering polyamine levels may therefore have a variety of important targets. This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism. PMID:19603518

Epithelial Integrity Is Maintained by a Matriptase-Dependent Proteolytic Pathway

PubMed Central

List, Karin; Kosa, Peter; Szabo, Roman; Bey, Alexandra L.; Wang, Chao Becky; Molinolo, Alfredo; Bugge, Thomas H.

2009-01-01

A pericellular proteolytic pathway initiated by the transmembrane serine protease matriptase plays a critical role in the terminal differentiation of epidermal tissues. Matriptase is constitutively expressed in multiple other epithelia, suggesting a putative role of this membrane serine protease in general epithelial homeostasis. Here we generated mice with conditional deletion of the St14 gene, encoding matriptase, and show that matriptase indeed is essential for the maintenance of multiple types of epithelia in the mouse. Thus, embryonic or postnatal ablation of St14 in epithelial tissues of diverse origin and function caused severe organ dysfunction, which was often associated with increased permeability, loss of tight junction function, mislocation of tight junction-associated proteins, and generalized epithelial demise. The study reveals that the homeostasis of multiple simple and stratified epithelia is matriptase-dependent, and provides an important animal model for the exploration of this membrane serine protease in a range of physiological and pathological processes. PMID:19717635

Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans

PubMed Central

Romeo, Stefano; Yin, Wu; Kozlitina, Julia; Pennacchio, Len A.; Boerwinkle, Eric; Hobbs, Helen H.; Cohen, Jonathan C.

2008-01-01

The relative activity of lipoprotein lipase (LPL) in different tissues controls the partitioning of lipoprotein-derived fatty acids between sites of fat storage (adipose tissue) and oxidation (heart and skeletal muscle). Here we used a reverse genetic strategy to test the hypothesis that 4 angiopoietin-like proteins (ANGPTL3, -4, -5, and -6) play key roles in triglyceride (TG) metabolism in humans. We re-sequenced the coding regions of the genes encoding these proteins and identified multiple rare nonsynonymous (NS) sequence variations that were associated with low plasma TG levels but not with other metabolic phenotypes. Functional studies revealed that all mutant alleles of ANGPTL3 and ANGPTL4 that were associated with low plasma TG levels interfered either with the synthesis or secretion of the protein or with the ability of the ANGPTL protein to inhibit LPL. A total of 1% of the Dallas Heart Study population and 4% of those participants with a plasma TG in the lowest quartile had a rare loss-of-function mutation in ANGPTL3, ANGPTL4, or ANGPTL5. Thus, ANGPTL3, ANGPTL4, and ANGPTL5, but not ANGPTL6, play nonredundant roles in TG metabolism, and multiple alleles at these loci cumulatively contribute to variability in plasma TG levels in humans. PMID:19075393

Catalytic bismetallative multicomponent coupling reactions: scope, applications, and mechanisms

PubMed Central

Cho, Hee Yeon

2014-01-01

Catalytic reactions have played an indispensable role in organic chemistry for the last several decades. In particular, catalytic multicomponent reactions have attracted a lot of attention due to their efficiency and expediency towards complex molecule synthesis. The presence of bismetallic reagents (e.g. B–B, Si–Si, B–Si, Si–Sn, etc.) in this process renders the products enriched with various functional groups and multiple stereocenters. For this reason, catalytic bismetallative coupling is considered an effective method to generate the functional and stereochemical complexity of simple hydrocarbon substrates. This review highlights key developments of transition-metal catalyzed bismetallative reactions involving multiple π components. Specifically, it will highlight the scope, synthetic applications, and proposed mechanistic pathways of this process. PMID:24736839

Rising tides, cumulative impacts and cascading changes to estuarine ecosystem functions.

PubMed

O'Meara, Theresa A; Hillman, Jenny R; Thrush, Simon F

2017-08-31

In coastal ecosystems, climate change affects multiple environmental factors, yet most predictive models are based on simple cause-and-effect relationships. Multiple stressor scenarios are difficult to predict because they can create a ripple effect through networked ecosystem functions. Estuarine ecosystem function relies on an interconnected network of physical and biological processes. Estuarine habitats play critical roles in service provision and represent global hotspots for organic matter processing, nutrient cycling and primary production. Within these systems, we predicted functional changes in the impacts of land-based stressors, mediated by changing light climate and sediment permeability. Our in-situ field experiment manipulated sea level, nutrient supply, and mud content. We used these stressors to determine how interacting environmental stressors influence ecosystem function and compared results with data collected along elevation gradients to substitute space for time. We show non-linear, multi-stressor effects deconstruct networks governing ecosystem function. Sea level rise altered nutrient processing and impacted broader estuarine services ameliorating nutrient and sediment pollution. Our experiment demonstrates how the relationships between nutrient processing and biological/physical controls degrade with environmental stress. Our results emphasise the importance of moving beyond simple physically-forced relationships to assess consequences of climate change in the context of ecosystem interactions and multiple stressors.

A compensatory role for declarative memory in neurodevelopmental disorders.

PubMed

Ullman, Michael T; Pullman, Mariel Y

2015-04-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

A compensatory role for declarative memory in neurodevelopmental disorders

PubMed Central

Ullman, Michael T.; Pullman, Mariel Y.

2015-01-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional, and because this system can learn and retain numerous types of information, functions, and tasks, it should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. PMID:25597655

International Association of Counseling Services: Standards for University and College Counseling Services

ERIC Educational Resources Information Center

Journal of College Student Psychotherapy, 2011

2011-01-01

University and college counseling services have played a vital role in higher education for many years. In the last 40 years, there has been a dramatic increase in the number of campus counseling services and the multiplicity of functions that are performed. Guidelines for university and college counseling services were first developed in 1970 by…

GLABROUS (CmGL) encodes a HD-ZIP IV transcription factor playing roles in multicellular trichome initiation in melon

USDA-ARS?s Scientific Manuscript database

Trichomes are small hairs covering the above-ground parts of plants that serve multiple functions in plant life such as protection against insects and pathogens. Little is known about the genetic control and regulation of trichome development in melon. In this study, we identified a melon mutant, cm...

Perilipin-2 null mice are protected against diet-induced obesity, adipose inflammation, and fatty liver disease

USDA-ARS?s Scientific Manuscript database

The cytoplasmic lipid droplet (CLD) protein perilipin-2 (Plin2) is expressed in multiple nonadipose tissues, where it is thought to play a role in regulating their lipid storage properties. However, the extent to which Plin2 functions in nutrient utilization and metabolism, or how it influences the ...

Improving Preschoolers' Theory of Mind Skills with Digital Games: A Training Study

ERIC Educational Resources Information Center

Nikolayev, Mariya

2015-01-01

This single-subject research study examined functional relation between digital games enriched with voice-overs and theory of mind (ToM) when game play was either followed or not followed by a discussion focused on the game's content. The study employed multiple baseline design across participants to evaluate the effects of games with mental state…

Two Sides of the Same Coin: Student-Faculty Perspectives of the Course Syllabus

ERIC Educational Resources Information Center

McDonald, Jeanette; Siddall, Gillian; Mandell, Deena; Hughes, Sandy

2010-01-01

Course syllabi play an important role in teaching, learning, and course design. They serve multiple functions and audiences and represent the end product of a scholarly process. In the following article, select findings from a mixed methods study examining how faculty and students conceptualize course syllabi are presented, specifically the design…

Multiple Case Studies of Public Library Systems in New York State: Service Decision-Making Processes

ERIC Educational Resources Information Center

Ren, Xiaoai

2012-01-01

This research examined the functions and roles of public library systems in New York State and the services they provide for individual libraries and the public. The dissertation further studied the service decision-making processes at three selected New York State cooperative public library systems. Public library systems have played an important…

[Epidemiology of infections after liver transplantation in children].

PubMed

Pawłowska, J

2001-01-01

One of the most important problems after solid organ transplantation including liver, remains infections. Multiple risk factors play a role among which the most important are: general patients health before transplantation, prolong operative time, graft function and type of immunosuppression. The most important problems with bacterial, fungal and viral infections was described as well as treatment and profilaxis.

Loop-loop interactions govern multiple steps in indole-3-glycerol phosphate synthase catalysis

PubMed Central

Zaccardi, Margot J; O'Rourke, Kathleen F; Yezdimer, Eric M; Loggia, Laura J; Woldt, Svenja; Boehr, David D

2014-01-01

Substrate binding, product release, and likely chemical catalysis in the tryptophan biosynthetic enzyme indole-3-glycerol phosphate synthase (IGPS) are dependent on the structural dynamics of the β1α1 active-site loop. Statistical coupling analysis and molecular dynamic simulations had previously indicated that covarying residues in the β1α1 and β2α2 loops, corresponding to Arg54 and Asn90, respectively, in the Sulfolobus sulfataricus enzyme (ssIGPS), are likely important for coordinating functional motions of these loops. To test this hypothesis, we characterized site mutants at these positions for changes in catalytic function, protein stability and structural dynamics for the thermophilic ssIGPS enzyme. Although there were only modest changes in the overall steady-state kinetic parameters, solvent viscosity and solvent deuterium kinetic isotope effects indicated that these amino acid substitutions change the identity of the rate-determining step across multiple temperatures. Surprisingly, the N90A substitution had a dramatic effect on the general acid/base catalysis of the dehydration step, as indicated by the loss of the descending limb in the pH rate profile, which we had previously assigned to Lys53 on the β1α1 loop. These changes in enzyme function are accompanied with a quenching of ps-ns and µs-ms timescale motions in the β1α1 loop as measured by nuclear magnetic resonance studies. Altogether, our studies provide structural, dynamic and functional rationales for the coevolution of residues on the β1α1 and β2α2 loops, and highlight the multiple roles that the β1α1 loop plays in IGPS catalysis. Thus, substitution of covarying residues in the active-site β1α1 and β2α2 loops of indole-3-glycerol phosphate synthase results in functional, structural, and dynamic changes, highlighting the multiple roles that the β1α1 loop plays in enzyme catalysis and the importance of regulating the structural dynamics of this loop through noncovalent interactions with nearby structural elements. PMID:24403092

Ontogenetic Trajectories of Chimpanzee Social Play: Similarities with Humans

PubMed Central

Cordoni, Giada; Palagi, Elisabetta

2011-01-01

Social play, a widespread phenomenon in mammals, is a multifunctional behavior, which can have many different roles according to species, sex, age, relationship quality between playmates, group membership, context, and habitat. Play joins and cuts across a variety of disciplines leading directly to inquiries relating to individual developmental changes and species adaptation, thus the importance of comparative studies appears evident. Here, we aim at proposing a possible ontogenetic pathway of chimpanzee play (Pan troglodytes) and contrast our data with those of human play. Chimpanzee play shows a number of changes from infancy to juvenility. Particularly, solitary and social play follows different developmental trajectories. While solitary play peaks in infancy, social play does not show any quantitative variation between infancy and juvenility but shows a strong qualitative variation in complexity, asymmetry, and playmate choice. Like laughter in humans, the playful expressions in chimpanzees (at the different age phases) seem to have a role in advertising cooperative dispositions and intentions thus increasing the likelihood of engaging in solid social relationships. In conclusion, in chimpanzees, as in humans, both play behavior and the signals that accompany play serve multiple functions according to the different age phases. PMID:22110630

Ontogenetic trajectories of chimpanzee social play: similarities with humans.

PubMed

Cordoni, Giada; Palagi, Elisabetta

2011-01-01

Social play, a widespread phenomenon in mammals, is a multifunctional behavior, which can have many different roles according to species, sex, age, relationship quality between playmates, group membership, context, and habitat. Play joins and cuts across a variety of disciplines leading directly to inquiries relating to individual developmental changes and species adaptation, thus the importance of comparative studies appears evident. Here, we aim at proposing a possible ontogenetic pathway of chimpanzee play (Pan troglodytes) and contrast our data with those of human play. Chimpanzee play shows a number of changes from infancy to juvenility. Particularly, solitary and social play follows different developmental trajectories. While solitary play peaks in infancy, social play does not show any quantitative variation between infancy and juvenility but shows a strong qualitative variation in complexity, asymmetry, and playmate choice. Like laughter in humans, the playful expressions in chimpanzees (at the different age phases) seem to have a role in advertising cooperative dispositions and intentions thus increasing the likelihood of engaging in solid social relationships. In conclusion, in chimpanzees, as in humans, both play behavior and the signals that accompany play serve multiple functions according to the different age phases.

Functional profiles reveal unique ecological roles of various biological soil crust organisms

USGS Publications Warehouse

Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

2011-01-01

1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining species-rich BSC communities is crucial to maintain the overall functionality of ecosystems dominated by these organisms, and that dominance and the outcome of competition could be highly influential in the determination of such functionality. ?? 2011 The Authors. Functional Ecology ?? 2011 British Ecological Society.

Structural disconnection is responsible for increased functional connectivity in multiple sclerosis.

PubMed

Patel, Kevin R; Tobyne, Sean; Porter, Daria; Bireley, John Daniel; Smith, Victoria; Klawiter, Eric

2018-06-01

Increased synchrony within neuroanatomical networks is often observed in neurophysiologic studies of human brain disease. Most often, this phenomenon is ascribed to a compensatory process in the face of injury, though evidence supporting such accounts is limited. Given the known dependence of resting-state functional connectivity (rsFC) on underlying structural connectivity (SC), we examine an alternative hypothesis: that topographical changes in SC, specifically particular patterns of disconnection, contribute to increased network rsFC. We obtain measures of rsFC using fMRI and SC using probabilistic tractography in 50 healthy and 28 multiple sclerosis subjects. Using a computational model of neuronal dynamics, we simulate BOLD using healthy subject SC to couple regions. We find that altering the model by introducing structural disconnection patterns observed in those multiple sclerosis subjects with high network rsFC generates simulations with high rsFC as well, suggesting that disconnection itself plays a role in producing high network functional connectivity. We then examine SC data in individuals. In multiple sclerosis subjects with high network rsFC, we find a preferential disconnection between the relevant network and wider system. We examine the significance of such network isolation by introducing random disconnection into the model. As observed empirically, simulated network rsFC increases with removal of connections bridging a community with the remainder of the brain. We thus show that structural disconnection known to occur in multiple sclerosis contributes to network rsFC changes in multiple sclerosis and further that community isolation is responsible for elevated network functional connectivity.

Podocalyxin Is a Novel Polysialylated Neural Adhesion Protein with Multiple Roles in Neural Development and Synapse Formation

PubMed Central

Vitureira, Nathalia; Andrés, Rosa; Pérez-Martínez, Esther; Martínez, Albert; Bribián, Ana; Blasi, Juan; Chelliah, Shierley; López-Doménech, Guillermo; De Castro, Fernando; Burgaya, Ferran; McNagny, Kelly; Soriano, Eduardo

2010-01-01

Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-of-function reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development. PMID:20706633

MiR-218 Mediates tumorigenesis and metastasis: Perspectives and implications

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

Lu, Ying-fei; Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong; Zhang, Li

2015-05-15

MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. As a highly conserved miRNA across a variety of species, microRNA-218 (miR-218) was found to play pivotal roles in tumorigenesis and progression. A group of evidence has demonstrated that miR-218 acts as a tumor suppressor by targeting many oncogenes related to proliferation, apoptosis and invasion. In this review, we provide a complex overview of miR-218, including its regulatory mechanisms, known functions in cancer and future challenges as a potential therapeutic target in human cancers. - Highlights: • miR-218 is frequently down regulatedmore » in multiple cancers. • miR-218 plays pivotal roles in carcinogenesis. • miR-218 mediates proliferation, apoptosis, metastasis, invasion, etc. • miR-218 mediates tumorigenesis and metastasis via multiple pathways.« less

Functional competency and cognitive ability in mild Alzheimer's disease: relationship between ADL assessed by a relative/ carer-rated scale and neuropsychological performance.

PubMed

Matsuda, Osamu; Saito, Masahiko

2005-06-01

Alzheimer's disease (AD) is characterized by multiple cognitive deficits and affects functional competency to perform daily activities (ADL). As this may contribute to the patient's overall disability, it is important to identify factors that compromise competency. The relationship between different cognitive domains and functional activities in AD was studied. The functional competency of 73 Japanese AD patients, most with mild dementia, was assessed using a 27-item relative/carer-rating scale covering 7 ADL: managing finances, using transportation, taking precautions, self-care, housekeeping, communication and taking medicine. Cognitive assessment used 16 neuropsychological tests from the Japanese version of the WAIS-R and COGNISTAT, covering 9 cognitive domains: orientation, attention, episodic memory, semantic memory, language, visuoperceptual and construction abilities, computational ability, abstract thinking, and psychomotor speed. Multiple regression analysis by the stepwise method indicated that functional competency could, for the most part, be predicted from test scores for orientation, abstract thinking and psychomotor speed. The results of this study suggest that impairment of these three cognitive domains plays an important role in the functional deterioration of AD.

Human spleen and red blood cells

NASA Astrophysics Data System (ADS)

Pivkin, Igor; Peng, Zhangli; Karniadakis, George; Buffet, Pierre; Dao, Ming

2016-11-01

Spleen plays multiple roles in the human body. Among them is removal of old and altered red blood cells (RBCs), which is done by filtering cells through the endothelial slits, small micron-sized openings. There is currently no experimental technique available that allows us to observe RBC passage through the slits. It was previously noticed that people without a spleen have less deformable red blood cells, indicating that the spleen may play a role in defining the size and shape of red blood cells. We used detailed RBC model implemented within the Dissipative Particle Dynamics (DPD) simulation framework to study the filter function of the spleen. Our results demonstrate that spleen indeed plays major role in defining the size and shape of the healthy human red blood cells.

Language and Play in Students with Multiple Disabilities and Visual Impairments or Deaf-Blindness

ERIC Educational Resources Information Center

Pizzo, Lianna; Bruce, Susan M.

2010-01-01

This article investigates the relationships between play and language development in students with multiple disabilities and visual impairments or deaf-blindness. The findings indicate that students with higher levels of communication demonstrate more advanced play skills and that the use of play-based assessment and exposure to symbolic play are…

Gender-specific association between dietary acid load and total lean body mass and its dependency on protein intake in seniors

USDA-ARS?s Scientific Manuscript database

Background: Sarcopenia, the age-related decline of muscle mass, is one of the most important causes of loss of physical function and falls in seniors. Causes of sarcopenia are multiple, but there is evidence that diet-related mild metabolic acidosis may play a role in the development of skeletal mus...

A basic helix-loop-helix transcription factor, PhFBH4, regulates flower senescence by modulating ethylene biosynthesis pathway in petunia

USDA-ARS?s Scientific Manuscript database

The basic helix-loop-helix (bHLH) transcription factors (TFs) play important roles in regulating multiple biological processes in plants. However, there are few reports about the function of bHLHs in flower senescence. In this study, a bHLH TF, PhFBH4, was found to be dramatically upregulated during...

Free energy landscape and transition pathways from Watson-Crick to Hoogsteen base pairing in free duplex DNA.

PubMed

Yang, Changwon; Kim, Eunae; Pak, Youngshang

2015-09-18

Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson-Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine-thymine (A-T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Volatile terpenoids: multiple functions, biosynthesis, modulation and manipulation by genetic engineering.

PubMed

Abbas, Farhat; Ke, Yanguo; Yu, Rangcai; Yue, Yuechong; Amanullah, Sikandar; Jahangir, Muhammad Muzammil; Fan, Yanping

2017-11-01

Terpenoids play several physiological and ecological functions in plant life through direct and indirect plant defenses and also in human society because of their enormous applications in the pharmaceutical, food and cosmetics industries. Through the aid of genetic engineering its role can by magnified to broad spectrum by improving genetic ability of crop plants, enhancing the aroma quality of fruits and flowers and the production of pharmaceutical terpenoids contents in medicinal plants. Terpenoids are structurally diverse and the most abundant plant secondary metabolites, playing an important role in plant life through direct and indirect plant defenses, by attracting pollinators and through different interactions between the plants and their environment. Terpenoids are also significant because of their enormous applications in the pharmaceutical, food and cosmetics industries. Due to their broad distribution and functional versatility, efforts are being made to decode the biosynthetic pathways and comprehend the regulatory mechanisms of terpenoids. This review summarizes the recent advances in biosynthetic pathways, including the spatiotemporal, transcriptional and post-transcriptional regulatory mechanisms. Moreover, we discuss the multiple functions of the terpene synthase genes (TPS), their interaction with the surrounding environment and the use of genetic engineering for terpenoid production in model plants. Here, we also provide an overview of the significance of terpenoid metabolic engineering in crop protection, plant reproduction and plant metabolic engineering approaches for pharmaceutical terpenoids production and future scenarios in agriculture, which call for sustainable production platforms by improving different plant traits.

PPAR-γ in innate and adaptive lung immunity.

PubMed

Nobs, Samuel Philip; Kopf, Manfred

2018-05-16

The transcription factor PPAR-γ (peroxisome proliferator-activated receptor-γ) is a key regulator of lung immunity exhibiting multiple cell type specific roles in controlling development and function of the lung immune system. It is strictly required for the generation of alveolar macrophages by controlling differentiation of fetal lung monocyte precursors. Furthermore, it plays an important role in lung allergic inflammation by licensing lung dendritic cell t helper 2 (Th2) priming capacity as well as acting as a master transcription factor for pathogenic Th2 cells. Due to this plethora of functions and its involvement in multiple pulmonary diseases including asthma and pulmonary alveolar proteinosis, understanding the role of PPAR-γ in lung immunity is an important subject of ongoing research. ©2018 Society for Leukocyte Biology.

Rotor Noise due to Blade-Turbulence Interaction.

NASA Astrophysics Data System (ADS)

Ishimaru, Kiyoto

The time-averaged intensity density function of the acoustic radiation from rotating blades is derived by replacing blades with rotating dipoles. This derivation is done under the following turbulent inflow conditions: turbulent ingestion with no inlet strut wakes, inflow turbulence elongation and contraction with no inlet strut wakes, and inlet strut wakes. Dimensional analysis reveals two non-dimensional parameters which play important roles in generating the blade-passing frequency tone and its multiples. The elongation and contraction of inflow turbulence has a strong effect on the generation of the blade-passing frequency tone and its multiples. Increasing the number of rotor blades widens the peak at the blade-passing frequency and its multiples. Increasing the rotational speed widens the peak under the condition that the non-dimensional parameter involving the rotational speed is fixed. The number of struts and blades should be chosen so that (the least common multiple of them)(.)(rotational speed) is in the cutoff range of Sears' function, in order to minimize the effect of the mean flow deficit on the time averaged intensity density function. The acoustic intensity density function is not necessarily stationary even if the inflow turbulence is homogeneous and isotropic. The time variation of the propagation path due to the rotation should be considered in the computation of the intensity density function; for instance, in the present rotor specification, the rotor radius is about 0.3 m and the rotational speed Mach number is about 0.2.

Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms

PubMed Central

Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-e; Zhang, Xiaochu

2017-01-01

Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs’ appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers’ attention from different fields and many studies have validated MMORPGs’ positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational application of the MMORPGs based on relevant macroscopic and microscopic studies, showing that gamers’ overall language proficiency or some specific language skills can be enhanced by real-time online interaction with peers and game narratives or instructions embedded in the MMORPGs. Mechanisms underlying the educational assistant role of MMORPGs in second language learning are discussed from both behavioral and neural perspectives. We suggest that attentional bias makes gamers/learners allocate more cognitive resources toward task-related stimuli in a controlled or an automatic way. Moreover, with a moderating role played by activation of reward circuit, playing the MMORPGs may strengthen or increase functional connectivity from seed regions such as left anterior insular/frontal operculum (AI/FO) and visual word form area to other language-related brain areas. PMID:28303097

Feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus™ for frail elderly: study protocol for a feasibility trial.

PubMed

Gomes, Gisele Cristine Vieira; Bacha, Jéssica Maria Ribeiro; do Socorro Simões, Maria; Lin, Sumika Mori; Viveiro, Larissa Alamino Pereira; Varise, Eliana Maria; Filho, Wilson Jacob; Pompeu, José Eduardo

2017-01-01

Frailty can be defined as a medical syndrome with multiple causes and contributors, characterized by diminished strength and endurance and reduced physiological function that increases the vulnerability to develop functional dependency and/or death. Studies have shown that the most commonly studied exercise protocol for frail older adults is the multimodal training. Interactive video games (IVGs) involve tasks in virtual environments that combine physical and cognitive demands in an attractive and challenging way. The aim of this study will be to evaluate the feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus TM (NWFP) for frail older adults. The study is a randomized controlled, parallel group, feasibility trial. Participants will be randomly assigned to the experimental group (EG) and control group (CG). The EG will participate in 14 training sessions, each lasting 50 min, twice a week. In each training session, the participants will play five games, with three attempts at each game. The first attempt will be performed with the assistance of a physical therapist to correct the movements and posture of the patients and subsequent attempts will be performed independently. Scores achieved in the games will be recorded. The participants will be evaluated by a blinded physical therapist at three moments: before and after intervention and 30 days after the end of the intervention (follow-up). We will assess the feasibility, acceptability, safety, and clinical outcomes (postural control, gait, cognition, quality of life, mood, and fear of falling). Due to the deficiencies in multiple systems, studies have shown that multimodal interventions including motor-cognitive stimulation can improve the mobility of frail elderly adults. IVGs, among them the NWFP, are considered as a multimodal motor-cognitive intervention that can potentially improve motor and cognitive functions in the frail elderly. However, there is still no evidence in the literature that proves the feasibility, safety, acceptability, and functional outcomes of this intervention in frail elderly individuals. Brazilian Registry of Clinical Trials (RBR-823rst). World Health Organization Trial Registration Data Set (Additional file 1).

Playing with the Multiple Intelligences: How Play Helps Them Grow

ERIC Educational Resources Information Center

Eberle, Scott G.

2011-01-01

Howard Gardner first posited a list of "multiple intelligences" as a liberating alternative to the assumptions underlying traditional IQ testing in his widely read study "Frames of Mind" (1983). Play has appeared only in passing in Gardner's thinking about intelligence, however, even though play instructs and trains the verbal, interpersonal,…

[Secondary osteoporosis or secondary contributors to bone loss in fracture. Endocrinological aspects of bone metabolism].

PubMed

Fukumoto, Seiji

2013-09-01

Bone works to play essential roles in mineral metabolism and hematopoiesis as well as to support our body and protect internal organs as a hard tissue. In order to accomplish these multiple functions, bone needs to communicate with other organs. Endocrine system functions as one of the communication pathways between bone and other organs. It has been known that bone is a target organ of many hormones. In addition, it has been established that bone itself produces hormones and works as an endocrine organ.

C/EBPα deregulation as a paradigm for leukemogenesis.

PubMed

Pulikkan, J A; Tenen, D G; Behre, G

2017-11-01

Myeloid master regulator CCAAT enhancer-binding protein alpha (C/EBPα) is deregulated by multiple mechanisms in leukemia. Inhibition of C/EBPα function plays pivotal roles in leukemogenesis. While much is known about how C/EBPα orchestrates granulopoiesis, our understanding of molecular transformation events, the role(s) of cooperating mutations and clonal evolution during C/EBPα deregulation in leukemia remains elusive. In this review, we will summarize the latest research addressing these topics with special emphasis on CEBPA mutations. We conclude by describing emerging therapeutic strategies to restore C/EBPα function.

Child AD/HD Severity and Psychological Functioning in Relation to Divorce, Remarriage, Multiple Transitions and the Quality of Family Relationships

ERIC Educational Resources Information Center

Heckel, Leila; Clarke, Adam R.; Barry, Robert J.; McCarthy, Rory; Selikowitz, Mark

2013-01-01

Both Attention-Deficit/Hyperactivity Disorder (AD/HD) and divorce are very prevalent in western societies, and they may occur together. AD/HD is generally viewed as a neurobiological disorder, which has led to a commonly held belief that social-environmental factors play little role in the symptom profile of children diagnosed with the disorder.…

Determinants of the rate of protein sequence evolution

PubMed Central

Zhang, Jianzhi; Yang, Jian-Rong

2015-01-01

The rate and mechanism of protein sequence evolution have been central questions in evolutionary biology since the 1960s. Although the rate of protein sequence evolution depends primarily on the level of functional constraint, exactly what constitutes functional constraint has remained unclear. The increasing availability of genomic data has allowed for much needed empirical examinations on the nature of functional constraint. These studies found that the evolutionary rate of a protein is predominantly influenced by its expression level rather than functional importance. A combination of theoretical and empirical analyses have identified multiple mechanisms behind these observations and demonstrated a prominent role that selection against errors in molecular and cellular processes plays in protein evolution. PMID:26055156

Predicting preschoolers' social-cognitive play behavior: attachment, peers, temperament, and physiological regulation.

PubMed

Porter, Christin L

2009-04-01

Research on children's social-cognitive play typologies (i.e., active and passive forms of solitary and social play) suggests links of early play behaviors and later social development and risk status. To date, few studies have examined simultaneously suspected links between children's social-cognitive play types and factors believed to shape these early social-play behaviors. This study examined a simultaneous model of individual (temperament, physiology) and relational variables (attachment, peer networks) believed to influence children's social-cognitive play types, including individual characteristics drawn from the Child Behavior Questionnaire which measures dimensions of shyness and impulsivity, a lab-based assessment of social withdrawal, and physiological markers linked to social regulation (cardiac vagal tone and vagal regulation). Children's attachment status to parents was gathered using Q-Sort methodology, and a measure of previous peer network size was obtained from parents' reports to examine potential links between relational history and social-cognitive play types. Predictive discriminant function analysis showed that children's (N = 54, age range 35 to 58 months) social-cognitive play was better predicted on the basis of multiple independent variables than individual, zero-order relations. When predicting children's social-cognitive play typologies, a multidimensional view which encompasses both individual characteristics and social-relational variables may best predict social -cognitive play types and help understanding of children's social trajectories.

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

PubMed

Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

2018-02-01

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

A molecular imaging analysis of C×43 association with Cdo during skeletal myoblast differentiation

NASA Astrophysics Data System (ADS)

Nosi, Daniele; Mercatelli, Raffaella; Chellini, Flaminia; Soria, Silvia; Pini, Alessandro; Formigli, Lucia; Quercioli, Franco

2014-02-01

Cell-to-cell contacts are crucial for cell differentiation. The promyogenic cell surface protein, Cdo, functions as a component of multiprotein clusters to mediate cell adhesion signaling. Connexin43, the main connexin forming gap junctions, also plays a key role in myogenesis. At least part of its effects are independent of the intercellular channel function, but the mechanisms underlying are unknown. Here, using multiple optical approaches, we provided the first evidence that Cx43 physically interacts with Cdo to form dynamic complexes during myoblast differentiation, offering clues for considering this interaction a structural basis of the channel-independent function of Cx43.

The RNA polymerase II CTD coordinates transcription and RNA processing

PubMed Central

Hsin, Jing-Ping; Manley, James L.

2012-01-01

The C-terminal domain (CTD) of the RNA polymerase II largest subunit consists of multiple heptad repeats (consensus Tyr1–Ser2–Pro3–Thr4–Ser5–Pro6–Ser7), varying in number from 26 in yeast to 52 in vertebrates. The CTD functions to help couple transcription and processing of the nascent RNA and also plays roles in transcription elongation and termination. The CTD is subject to extensive post-translational modification, most notably phosphorylation, during the transcription cycle, which modulates its activities in the above processes. Therefore, understanding the nature of CTD modifications, including how they function and how they are regulated, is essential to understanding the mechanisms that control gene expression. While the significance of phosphorylation of Ser2 and Ser5 residues has been studied and appreciated for some time, several additional modifications have more recently been added to the CTD repertoire, and insight into their function has begun to emerge. Here, we review findings regarding modification and function of the CTD, highlighting the important role this unique domain plays in coordinating gene activity. PMID:23028141

Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.

PubMed

Liu, Mingyuan; Hou, Xiaojun; Zhang, Ping; Hao, Yong; Yang, Yiting; Wu, Xiongfeng; Zhu, Desheng; Guan, Yangtai

2013-05-01

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

A multiple scales approach to sound generation by vibrating bodies

NASA Technical Reports Server (NTRS)

Geer, James F.; Pope, Dennis S.

1992-01-01

The problem of determining the acoustic field in an inviscid, isentropic fluid generated by a solid body whose surface executes prescribed vibrations is formulated and solved as a multiple scales perturbation problem, using the Mach number M based on the maximum surface velocity as the perturbation parameter. Following the idea of multiple scales, new 'slow' spacial scales are introduced, which are defined as the usual physical spacial scale multiplied by powers of M. The governing nonlinear differential equations lead to a sequence of linear problems for the perturbation coefficient functions. However, it is shown that the higher order perturbation functions obtained in this manner will dominate the lower order solutions unless their dependence on the slow spacial scales is chosen in a certain manner. In particular, it is shown that the perturbation functions must satisfy an equation similar to Burgers' equation, with a slow spacial scale playing the role of the time-like variable. The method is illustrated by a simple one-dimenstional example, as well as by three different cases of a vibrating sphere. The results are compared with solutions obtained by purely numerical methods and some insights provided by the perturbation approach are discussed.

Multitasking in multiple sclerosis: can it inform vocational functioning?

PubMed

Morse, Chelsea L; Schultheis, Maria T; McKeever, Joshua D; Leist, Thomas

2013-12-01

To examine associations between multitasking ability defined by performance on a complex task integrating multiple cognitive domains and vocational functioning in multiple sclerosis (MS). Survey data collection. Laboratory with referrals from an outpatient clinic. Community-dwelling individuals with MS (N=30) referred between October 2011 and June 2012. Not applicable. The modified Six Elements Test (SET) to measure multitasking ability, Fatigue Severity Scale to measure fatigue, several neuropsychological measures of executive functioning, and vocational status. Among the sample, 60% of individuals have reduced their work hours because of MS symptoms (cutback employment group) and 40% had maintained their work hours. Among both groups, SET performance was significantly associated with performance on several measures of neuropsychological functioning. Individuals in the cutback employment group demonstrated significantly worse overall performance on the SET (P=.041). Logistic regression was used to evaluate associations between SET performance and vocational status, while accounting for neuropsychological performance and fatigue. The overall model was significant (χ(2)3=8.65, P=.032), with fatigue [Exp(B)=.83, P=.01] and multitasking ability [Exp(B)=.60, P=.043] retained as significant predictors. Multitasking ability may play an important role in performance at work for individuals with MS. Given that multitasking was associated with vocational functioning, future efforts should assess the usefulness of incorporating multitasking ability into rehabilitation planning. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[Effect of preventive treatment on cognitive performance in patients with multiple sclerosis].

PubMed

Shorobura, Maria S

2018-01-01

Introduction: cognitive, emotional and psychopathological changes play a significant role in the clinical picture of multiple sclerosis and influence the effectiveness of drug therapy, working capacity, quality of life, and the process of rehabilitation of patients with multiple sclerosis. The aim: investigate the changes in cognitive function in patients with multiple sclerosis, such as information processing speed and working memory of patients before and after treatment with immunomodulating drug. Materials and methods:33 patients examined reliably diagnosed with multiple sclerosis who were treated with preventive examinations and treatment from 2012 to 2016. For all patients with multiple sclerosis had clinical-neurological examination (neurological status using the EDSS scale) and the cognitive status was evaluated using the PASAT auditory test. Patient screening was performed before, during and after the therapy. Statistical analysis of the results was performed in the system Statistica 8.0. We used Student's t-test (t), Mann-Whitney test (Z). Person evaluated the correlation coefficients and Spearman (r, R), Wilcoxon criterion (T), Chi-square (X²). Results: The age of patients with multiple sclerosis affects the growth and EDSS scale score decrease PASAT to treatment. Duration of illness affects the EDSS scale score and performance PASAT. Indicators PASAT not significantly decreased throughout the treatment. Conclusions: glatiramer acetate has a positive effect on cognitive function, information processing speed and working memory patients with multiple sclerosis, which is one of the important components of the therapeutic effect of this drug.

Effect of multiple circular holes Fraunhofer diffraction for the infrared optical imaging

NASA Astrophysics Data System (ADS)

Lu, Chunlian; Lv, He; Cao, Yang; Cai, Zhisong; Tan, Xiaojun

2014-11-01

With the development of infrared optics, infrared optical imaging systems play an increasingly important role in modern optical imaging systems. Infrared optical imaging is used in industry, agriculture, medical, military and transportation. But in terms of infrared optical imaging systems which are exposed for a long time, some contaminations will affect the infrared optical imaging. When the contamination contaminate on the lens surface of the optical system, it would affect diffraction. The lens can be seen as complementary multiple circular holes screen happen Fraunhofer diffraction. According to Babinet principle, you can get the diffraction of the imaging system. Therefore, by studying the multiple circular holes Fraunhofer diffraction, conclusions can be drawn about the effect of infrared imaging. This paper mainly studies the effect of multiple circular holes Fraunhofer diffraction for the optical imaging. Firstly, we introduce the theory of Fraunhofer diffraction and Point Spread Function. Point Spread Function is a basic tool to evaluate the image quality of the optical system. Fraunhofer diffraction will affect Point Spread Function. Then, the results of multiple circular holes Fraunhofer diffraction are given for different hole size and hole spacing. We choose the hole size from 0.1mm to 1mm and hole spacing from 0.3mm to 0.8mm. The infrared wavebands of optical imaging are chosen from 1μm to 5μm. We use the MATLAB to simulate light intensity distribution of multiple circular holes Fraunhofer diffraction. Finally, three-dimensional diffraction maps of light intensity are given to contrast.

Rate My Sleep: Examining the Information, Function, and Basis in Empirical Evidence Within Sleep Applications for Mobile Devices.

PubMed

Lee-Tobin, Peta A; Ogeil, Rowan P; Savic, Michael; Lubman, Dan I

2017-11-15

Sleep applications (apps) have proliferated in online spaces, but few studies have examined the validity of the information contained within the apps. This study aimed to examine the information and functions found within sleep apps, determine if the information is based on empirical evidence, and whether or not user ratings were affected by these factors. Sleep apps found in the Google Play store (n = 76) were coded using content analysis to examine the types of information, functions, and evidence base of each app. Only 32.9% of sleep apps contained empirical evidence supporting their claims, 15.8% contained clinical input, and 13.2% contained links to sleep literature. Apps also contained information on how sleep is affected by alcohol or drugs (23.7%), food (13.2%), daily activities (13.2), and stress (13.2%). A mean difference in average user rating was found between apps that contained at least one source of information compared those that did not. App user ratings were not associated with an app having multiple functions, or from an app drawing on multiple sources of evidence (except for sleep literature only). Last, there was a higher average user rating among apps that contained a sleep tip function. Sleep apps are increasingly popular, demonstrated by the large number of downloads in the Google Play store. Users favored apps that contained sleep tips; however, these tips and other information in the apps were generally not based on empirical evidence. Future research in the area of sleep apps should consider constructing sleep apps derived from empirical evidence and examining their effectiveness. © 2017 American Academy of Sleep Medicine

β-Ocimene, a Key Floral and Foliar Volatile Involved in Multiple Interactions between Plants and Other Organisms.

PubMed

Farré-Armengol, Gerard; Filella, Iolanda; Llusià, Joan; Peñuelas, Josep

2017-07-13

β-Ocimene is a very common plant volatile released in important amounts from the leaves and flowers of many plant species. This acyclic monoterpene can play several biological functions in plants, by potentially affecting floral visitors and also by mediating defensive responses to herbivory. The ubiquity and high relative abundance of β-ocimene in the floral scents of species from most plant families and from different pollination syndromes (ranging from generalism to specialism) strongly suggest that this terpenoid may play an important role in the attraction of pollinators to flowers. We compiled abundant evidence from published studies that supports β-ocimene as a generalist attractant of a wide spectrum of pollinators. We found no studies testing behavioural responses of pollinators to β-ocimene, that could directly demonstrate or deny the function of β-ocimene in pollinator attraction; but several case studies support that the emissions of β-ocimene in flowers of different species follow marked temporal and spatial patterns of emission, which are typical from floral volatile organic compound (VOC) emissions that are involved in pollinator attraction. Furthermore, important β-ocimene emissions are induced from vegetative plant tissues after herbivory in many species, which have relevant functions in the establishment of tritrophic interactions. We thus conclude that β-ocimene is a key plant volatile with multiple relevant functions in plants, depending on the organ and the time of emission. Experimental behavioural studies on pure β-ocimene conducted with pollinating insects will be necessary to prove the assumptions made here.

The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics.

PubMed

Camara-Lemarroy, Carlos R; Metz, Luanne; Meddings, Jonathan B; Sharkey, Keith A; Wee Yong, V

2018-05-30

Biological barriers are essential for the maintenance of homeostasis in health and disease. Breakdown of the intestinal barrier is an essential aspect of the pathophysiology of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. A wealth of recent studies has shown that the intestinal microbiome, part of the brain-gut axis, could play a role in the pathophysiology of multiple sclerosis. However, an essential component of this axis, the intestinal barrier, has received much less attention. In this review, we describe the intestinal barrier as the physical and functional zone of interaction between the luminal microbiome and the host. Besides its essential role in the regulation of homeostatic processes, the intestinal barrier contains the gut mucosal immune system, a guardian of the integrity of the intestinal tract and the whole organism. Gastrointestinal disorders with intestinal barrier breakdown show evidence of CNS demyelination, and content of the intestinal microbiome entering into the circulation can impact the functions of CNS microglia. We highlight currently available studies suggesting that there is intestinal barrier dysfunction in multiple sclerosis. Finally, we address the mechanisms by which commonly used disease-modifying drugs in multiple sclerosis could alter the intestinal barrier and the microbiome, and we discuss the potential of barrier-stabilizing strategies, including probiotics and stabilization of tight junctions, as novel therapeutic avenues in multiple sclerosis.

Identification of Ind transcription activation and repression domains required for dorsoventral patterning of the CNS.

PubMed

Von Ohlen, Tonia L; Moses, Cade

2009-07-01

Specification of cell fates across the dorsoventral axis of the central nervous system in Drosophila involves the subdivision of the neuroectoderm into three domains that give rise to three columns of neural precursor cells called neuroblasts. Ventral nervous system defective (Vnd), intermediate neuroblasts defective (Ind) and muscle segment homeobox (Msh) are expressed in the three columns from ventral to dorsal, respectively. The products of these genes play multiple important roles in formation and specification of the embryonic nervous system. Ind, for example, is known to play roles in two important processes. First, Ind is essential for formation of neuroblasts conjunction with SoxB class transcription factors. Sox class transcription factors are known to specify neural stem cells in vertebrates. Second, Ind plays an important role in patterning the CNS in conjunction with, vnd and msh, which is also similar to how vertebrates pattern their neural tube. This work focuses two important aspects of Ind function. First, we used multiple approaches to identify and characterize specific domains within the protein that confer repressor or activator ability. Currently, little is known about the presence of activation or repression domains within Ind. Here, we show that transcriptional repression by Ind requires multiple conserved domains within the protein, and that Ind has a transcriptional activation domain. Specifically, we have identified a novel domain, the Pst domain, that has transcriptional repression ability and appears to act independent of interaction with the co-repressor Groucho. This domain is highly conserved among insect species, but is not found in vertebrate Gsh class homeodomain proteins. Second, we show that Ind can and does repress vnd expression, but does so in a stage specific manner. We conclude from this that the function of Ind in regulating vnd expression is one of refinement and maintenance of the dorsal border.

Mutations of RNA splicing factors in hematological malignancies.

PubMed

Shukla, Girish C; Singh, Jagjit

2017-11-28

Systematic large-scale cancer genomic studies have produced numerous significant findings. These studies have not only revealed new cancer-promoting genes, but they also have identified cancer-promoting functions of previously known "housekeeping" genes. These studies have identified numerous mutations in genes which play a fundamental role in nuclear precursor mRNA splicing. Somatic mutations and copy number variation in many of the splicing factors which participate in the formation of multiple spliceosomal complexes appear to play a role in many cancers and in particular in myelodysplastic syndromes (MDS). Mutated proteins seem to interfere with the recognition of the authentic splice sites (SS) leading to utilization of suboptimal alternative splicing sites generating aberrantly spliced mRNA isoforms. This short review is focusing on the function of the splice factors involved in the formation of splicing complexes and potential mechanisms which affect usage of the authentic splice site recognition. Copyright © 2017 Elsevier B.V. All rights reserved.

E3 ubiquitin ligase Cbl-b in innate and adaptive immunity

PubMed Central

Liu, Qingjun; Zhou, Hong; Langdon, Wallace Y; Zhang, Jian

2014-01-01

Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING finger E3 ubiquitin-protein ligase, has been demonstrated to play a crucial role in establishing the threshold for T-cell activation and controlling peripheral T-cell tolerance via multiple mechanisms. Accumulating evidence suggests that Cbl-b also regulates innate immune responses and plays an important role in host defense to pathogens. Understanding the signaling pathways regulated by Cbl-b in innate and adaptive immune cells is therefore essential for efficient manipulation of Cbl-b in emerging immunotherapies for human disorders such as autoimmune diseases, allergic inflammation, infections, and cancer. In this article, we review the latest developments in the molecular structural basis of Cbl-b function, the regulation of Cbl-b expression, the signaling mechanisms of Cbl-b in immune cells, as well as the biological function of Cbl-b in physiological and pathological immune responses in animal models and human diseases. PMID:24875217

Expansion of Protein Farnesyltransferase Specificity Using “Tunable” Active Site Interactions

PubMed Central

Hougland, James L.; Gangopadhyay, Soumyashree A.; Fierke, Carol A.

2012-01-01

Post-translational modifications play essential roles in regulating protein structure and function. Protein farnesyltransferase (FTase) catalyzes the biologically relevant lipidation of up to several hundred cellular proteins. Site-directed mutagenesis of FTase coupled with peptide selectivity measurements demonstrates that molecular recognition is determined by a combination of multiple interactions. Targeted randomization of these interactions yields FTase variants with altered and, in some cases, bio-orthogonal selectivity. We demonstrate that FTase specificity can be “tuned” using a small number of active site contacts that play essential roles in discriminating against non-substrates in the wild-type enzyme. This tunable selectivity extends in vivo, with FTase variants enabling the creation of bioengineered parallel prenylation pathways with altered substrate selectivity within a cell. Engineered FTase variants provide a novel avenue for probing both the selectivity of prenylation pathway enzymes and the effects of prenylation pathway modifications on the cellular function of a protein. PMID:22992747

Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage.

PubMed

Karimian, Ansar; Ahmadi, Yasin; Yousefi, Bahman

2016-06-01

An appropriate control over cell cycle progression depends on many factors. Cyclin-dependent kinase (CDK) inhibitor p21 (also known as p21(WAF1/Cip1)) is one of these factors that promote cell cycle arrest in response to a variety of stimuli. The inhibitory effect of P21 on cell cycle progression correlates with its nuclear localization. P21 can be induced by both p53-dependent and p53-independent mechanisms. Some other important functions attributed to p21 include transcriptional regulation, modulation or inhibition of apoptosis. These functions are largely dependent on direct p21/protein interactions and also on p21 subcellular localizations. In addition, p21 can play a role in DNA repair by interacting with proliferating cell nuclear antigen (PCNA). In this review, we will focus on the multiple functions of p21 in cell cycle regulation, apoptosis and gene transcription after DNA damage and briefly discuss the pathways and factors that have critical roles in p21 expression and activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Acid-sensing ion channels: trafficking and synaptic function.

PubMed

Zha, Xiang-ming

2013-01-02

Extracellular acidification occurs in the brain with elevated neural activity, increased metabolism, and neuronal injury. This reduction in pH can have profound effects on brain function because pH regulates essentially every single biochemical reaction. Therefore, it is not surprising to see that Nature evolves a family of proteins, the acid-sensing ion channels (ASICs), to sense extracellular pH reduction. ASICs are proton-gated cation channels that are mainly expressed in the nervous system. In recent years, a growing body of literature has shown that acidosis, through activating ASICs, contributes to multiple diseases, including ischemia, multiple sclerosis, and seizures. In addition, ASICs play a key role in fear and anxiety related psychiatric disorders. Several recent reviews have summarized the importance and therapeutic potential of ASICs in neurological diseases, as well as the structure-function relationship of ASICs. However, there is little focused coverage on either the basic biology of ASICs or their contribution to neural plasticity. This review will center on these topics, with an emphasis on the synaptic role of ASICs and molecular mechanisms regulating the spatial distribution and function of these ion channels.

The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders

PubMed Central

Dobryakova, Ekaterina; Genova, Helen M.; DeLuca, John; Wylie, Glenn R.

2015-01-01

Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research. PMID:25814977

Phosphatidic acid - a simple phospholipid with multiple faces.

PubMed

Zegarlińska, Jolanta; Piaścik, Magda; Sikorski, Aleksander F; Czogalla, Aleksander

2018-01-01

Phosphatidic acid (PA) is the simplest glycerophospholipid naturally occurring in living organisms, and even though its content among other cellular lipids is minor, it is drawing more and more attention due to its multiple biological functions. PA is a precursor for other phospholipids, acts as a lipid second messenger and, due to its structural properties, is also a modulator of membrane shape. Although much is known about interaction of PA with its effectors, the molecular mechanisms remain unresolved to a large degree. Throughout many of the well-characterized PA cellular sensors, no conserved binding domain can be recognized. Moreover, not much is known about the cellular dynamics of PA and how it is distributed among subcellular compartments. Remarkably, PA can play distinct roles within each of these compartments. For example, in the nucleus it behaves as a mitogen, influencing gene expression regulation, and in the Golgi membrane it plays a role in membrane trafficking. Here, we discuss how a biophysical experimental approach enabled PA behavior to be described in the context of a lipid bilayer and to what extent various physicochemical conditions may modulate the functional properties of this lipid. Understanding these aspects would help to unravel specific mechanisms of PA-driven membrane transformations and protein recruitment and thus would lead to a clearer picture of the biological role of PA.

Basic pharmacology of NMDA receptors.

PubMed

Gonda, Xenia

2012-01-01

NMDA receptors are ionotropic receptors mediating glutamatergic neurotransmission and play a role in several basic functions in the central nervous system, from regulating neurodevelopment and synaptic plasticity, learning and memory formation, cognitive processes, rhythm generation necessary for locomotor activity and breathing, and excitotoxicity. Due to their complex involvement in the above processes, NMDA receptors have been established to play a role in the etiopathology of several neuropsychiatric disorders such as ischaemia and traumatic brain injury, neurodegenerative disorders, pain syndromes, addiction, affective disorders and such neurodevelopmental disorders as autism or schizophrenia. NMDA receptors contain multiple types of subunits with distinct functional and pharmacological properties making the picture more complex. These receptors also offer multiple binding sites to be targeted with pharmacons, however, early broad-spectrum NMDA receptor antagonists had limited clinical use due to their intolerable adverse effect profile. The discovery of several types of subunit selective NMDA receptor antagonists may offer valuable therapeutic possibilities for several disorders, with improved clinical efficacy and decreased side effects. However, in spite of our increasing knowledge concerning the involvement of NMDA receptors in pathological processes, molecules with a selective action, tolerable side effect profile and good clinical efficacy are still only in clinical development in the majority of cases. Nevertheless, NMDA receptors offer a novel opportunity in the treatment of various neuropsychiatric conditions.

Dramatic pretend play games uniquely improve emotional control in young children.

PubMed

Goldstein, Thalia R; Lerner, Matthew D

2017-09-15

Pretense is a naturally occurring, apparently universal activity for typically developing children. Yet its function and effects remain unclear. One theorized possibility is that pretense activities, such as dramatic pretend play games, are a possible causal path to improve children's emotional development. Social and emotional skills, particularly emotional control, are critically important for social development, as well as academic performance and later life success. However, the study of such approaches has been criticized for potential bias and lack of rigor, precluding the ability to make strong causal claims. We conducted a randomized, component control (dismantling) trial of dramatic pretend play games with a low-SES group of 4-year-old children (N = 97) to test whether such practice yields generalized improvements in multiple social and emotional outcomes. We found specific effects of dramatic play games only on emotional self-control. Results suggest that dramatic pretend play games involving physicalizing emotional states and traits, pretending to be animals and human characters, and engaging in pretend scenarios in a small group may improve children's emotional control. These findings have implications for the function of pretense and design of interventions to improve emotional control in typical and atypical populations. Further, they provide support for the unique role of dramatic pretend play games for young children, particularly those from low-income backgrounds. A video abstract of this article can be viewed at: https://youtu.be/2GVNcWKRHPk. © 2017 John Wiley & Sons Ltd.

Increasing Toy Play among Toddlers with Multiple Disabilities in an Inclusive Classroom: A More-to-Less, Child-Directed Intervention Continuum.

ERIC Educational Resources Information Center

DiCarlo, Cynthia F.; Reid, Dennis H.; Stricklin, Sarintha B.

2003-01-01

A study evaluated a more-to-less, child-directed continuum of intervention to increase toy play among six toddlers with multiple disabilities. Toddlers were provided with repeated choices of preferred toys in a child-directed manner. Nonprompted toy play for two toddlers increased. Toy play also increased for another child after staff prompts and…

Brain connectivity and psychiatric comorbidity in adolescents with Internet gaming disorder.

PubMed

Han, Doug Hyun; Kim, Sun Mi; Bae, Sujin; Renshaw, Perry F; Anderson, Jeffrey S

2017-05-01

Prolonged Internet video game play may have multiple and complex effects on human cognition and brain development in both negative and positive ways. There is not currently a consensus on the principle effects of video game play neither on brain development nor on the relationship to psychiatric comorbidity. In this study, 78 adolescents with Internet gaming disorder (IGD) and 73 comparison subjects without IGD, including subgroups with no other psychiatric comorbid disease, with major depressive disorder and with attention deficit hyperactivity disorder (ADHD), were included in a 3 T resting state functional magnetic resonance imaging analysis. The severity of Internet gaming disorder, depression, anxiety and ADHD symptoms were assessed with the Young Internet Addiction Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Korean ADHD rating scales, respectively. Patients with IGD showed an increased functional correlation between seven pairs of regions, all satisfying q < 0.05 False discovery rates in light of multiple statistical tests: left frontal eye field to dorsal anterior cingulate, left frontal eye field to right anterior insula, left dorsolateral prefrontal cortex (DLPFC) to left temporoparietal junction (TPJ), right DLPFC to right TPJ, right auditory cortex to right motor cortex, right auditory cortex to supplementary motor area and right auditory cortex to dorsal anterior cingulate. These findings may represent a training effect of extended game play and suggest a risk or predisposition in game players for over-connectivity of the default mode and executive control networks that may relate to psychiatric comorbidity. © 2015 Society for the Study of Addiction.

Biological pathways, candidate genes and molecular markers associated with quality-of-life domains: an update

PubMed Central

Sprangers, Mirjam A.G.; Thong, Melissa S.Y.; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A.; Singh, Jasvinder A.; Sloan, Jeff A.

2014-01-01

Background There is compelling evidence of a genetic foundation of patient-reported QOL. Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. Objectives The objective is to provide an updated overview of the biological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. Methods We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Results Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Conclusions Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL. PMID:24604075

Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update.

PubMed

Sprangers, Mirjam A G; Thong, Melissa S Y; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A; Singh, Jasvinder A; Sloan, Jeff A

2014-09-01

There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL.

DNA is structured as a linear "jigsaw puzzle" in the genomes of Arabidopsis, rice, and budding yeast.

PubMed

Liu, Yun-Hua; Zhang, Meiping; Wu, Chengcang; Huang, James J; Zhang, Hong-Bin

2014-01-01

Knowledge of how a genome is structured and organized from its constituent elements is crucial to understanding its biology and evolution. Here, we report the genome structuring and organization pattern as revealed by systems analysis of the sequences of three model species, Arabidopsis, rice and yeast, at the whole-genome and chromosome levels. We found that all fundamental function elements (FFE) constituting the genomes, including genes (GEN), DNA transposable elements (DTE), retrotransposable elements (RTE), simple sequence repeats (SSR), and (or) low complexity repeats (LCR), are structured in a nonrandom and correlative manner, thus leading to a hypothesis that the DNA of the species is structured as a linear "jigsaw puzzle". Furthermore, we showed that different FFE differ in their importance in the formation and evolution of the DNA jigsaw puzzle structure between species. DTE and RTE play more important roles than GEN, LCR, and SSR in Arabidopsis, whereas GEN and RTE play more important roles than LCR, SSR, and DTE in rice. The genes having multiple recognized functions play more important roles than those having single functions. These results provide useful knowledge necessary for better understanding genome biology and evolution of the species and for effective molecular breeding of rice.

Evaluating the Functionality of Conceptual Models

NASA Astrophysics Data System (ADS)

Mehmood, Kashif; Cherfi, Samira Si-Said

Conceptual models serve as the blueprints of information systems and their quality plays decisive role in the success of the end system. It has been witnessed that majority of the IS change-requests results due to deficient functionalities in the information systems. Therefore, a good analysis and design method should ensure that conceptual models are functionally correct and complete, as they are the communicating mediator between the users and the development team. Conceptual model is said to be functionally complete if it represents all the relevant features of the application domain and covers all the specified requirements. Our approach evaluates the functional aspects on multiple levels of granularity in addition to providing the corrective actions or transformation for improvement. This approach has been empirically validated by practitioners through a survey.

[Teaching skills of functional assessment to medical students: why not playing games?].

PubMed

Huber, Philippe; Saber, Abdelmalek; Schnellmann, Yves; Gold, Gabriel

2012-11-07

Today, physicians take care of an aging population suffering from multiple chronic diseases and disabilities. Therefore, a good knowledge of functional assessment is required, and this topic should be addressed in the undergraduate medical curriculum. This article reports our experience with a seminar on functional assessment using an "aging game" as a pedagogic vector. This seminar is organized by geriatricians, occupational therapists and physical therapists. Medical students are exposed to situations where they experiment disabilities and try to elaborate compensatory strategies. Then, they reflect on a complex discharge project by analyzing a written clinical case. Finally, they are introduced to the use of validated functional assessment instruments. Evaluation indicated that this pedagogic approach is highly valued by students and fosters the acquisition of knowledge in functional assessment.

[Long non-coding RNAs in plants].

PubMed

Xiaoqing, Huang; Dandan, Li; Juan, Wu

2015-04-01

Long non-coding RNAs (lncRNAs), which are longer than 200 nucleotides in length, widely exist in organisms and function in a variety of biological processes. Currently, most of lncRNAs found in plants are transcribed by RNA polymerase Ⅱ and mediate gene expression through multiple mechanisms, such as target mimicry, transcription interference, histone methylation and DNA methylation, and play important roles in flowering, male sterility, nutrition metabolism, biotic and abiotic stress and other biological processes as regulators in plants. In this review, we summarize the databases, prediction methods, and possible functions of plant lncRNAs discovered in recent years.

Mitochondrial Redox Signaling and Tumor Progression.

PubMed

Chen, Yuxin; Zhang, Haiqing; Zhou, Huanjiao Jenny; Ji, Weidong; Min, Wang

2016-03-25

Cancer cell can reprogram their energy production by switching mitochondrial oxidative phosphorylation to glycolysis. However, mitochondria play multiple roles in cancer cells, including redox regulation, reactive oxygen species (ROS) generation, and apoptotic signaling. Moreover, these mitochondrial roles are integrated via multiple interconnected metabolic and redox sensitive pathways. Interestingly, mitochondrial redox proteins biphasically regulate tumor progression depending on cellular ROS levels. Low level of ROS functions as signaling messengers promoting cancer cell proliferation and cancer invasion. However, anti-cancer drug-initiated stress signaling could induce excessive ROS, which is detrimental to cancer cells. Mitochondrial redox proteins could scavenger basal ROS and function as "tumor suppressors" or prevent excessive ROS to act as "tumor promoter". Paradoxically, excessive ROS often also induce DNA mutations and/or promotes tumor metastasis at various stages of cancer progression. Targeting redox-sensitive pathways and transcriptional factors in the appropriate context offers great promise for cancer prevention and therapy. However, the therapeutics should be cancer-type and stage-dependent.

Impact of alemtuzumab treatment on the survival and function of human regulatory T cells in vitro

PubMed Central

Havari, Evis; Turner, Michael J; Campos-Rivera, Juanita; Shankara, Srinivas; Nguyen, Tri-Hung; Roberts, Bruce; Siders, William; Kaplan, Johanne M

2014-01-01

Alemtuzumab is a humanized monoclonal antibody specific for the CD52 protein present at high levels on the surface of B and T lymphocytes. In clinical trials, alemtuzumab has shown a clinical benefit superior to that of interferon-β in relapsing–remitting multiple sclerosis patients. Treatment with alemtuzumab leads to the depletion of circulating lymphocytes followed by a repopulation process characterized by alterations in the number, proportions and properties of lymphocyte subsets. Of particular interest, an increase in the percentage of T cells with a regulatory phenotype (Treg cells) has been observed in multiple sclerosis patients after alemtuzumab. Since Treg cells play an important role in the control of autoimmune responses, the effect of alemtuzumab on Treg cells was further studied in vitro. Alemtuzumab effectively mediated complement-dependent cytolysis of human T lymphocytes and the remaining population was enriched in T cells with a regulatory phenotype. The alemtuzumab-exposed T cells displayed functional regulatory characteristics including anergy to stimulation with allogeneic dendritic cells and ability to suppress the allogeneic response of autologous T cells. Consistent with the observed increase in Treg cell frequency, the CD25hi T-cell population was necessary for the suppressive activity of alemtuzumab-exposed T cells. The mechanism of this suppression was found to be dependent on both cell–cell contact and interleukin-2 consumption. These findings suggest that an alemtuzumab-mediated increase in the proportion of Treg cells may play a role in promoting the long-term efficacy of alemtuzumab in patients with multiple sclerosis. PMID:24116901

DNA Damage Repair and the Emerging Role of Poly(ADP-ribose) Polymerase Inhibition in Cancer Therapeutics.

PubMed

Rabenau, Karen; Hofstatter, Erin

2016-07-01

As a result of improved understanding of DNA repair mechanisms, poly(ADP-ribose) polymerase inhibitors (PARPi) are increasingly recognized to play an important therapeutic role in the treatment of cancer. The aim of this article is to provide a review of PARPi function in DNA damage repair and synthetic lethality and to demonstrate how these mechanisms can be exploited to provide new PARPi-based therapies to patients with solid tumors. Literature from a range of sources, including PubMed and MEDLINE, were searched to identify recent reports regarding DNA damage repair and PARPi. DNA damage repair is central to cellular viability. The family of poly(ADP-ribose) polymerase proteins play multiple intracellular roles in DNA repair, but function primarily in the resolution of repair of single-strand DNA breaks. Insights through the discovery of germline BRCA1/2 mutations led to the understanding of synthetic lethality and the potential therapeutic role of PARPi in the treatment of cancer. Further understanding of DNA damage repair and the concept of BRCA-like tumors have catalyzed PARPi clinical investigation in multiple oncologic settings. PARPi hold great promise in the treatment of solid tumors, both as monotherapy and in combination with other cancer therapeutics. Multiple PARPi clinical trials are currently underway. Further understanding of aberrant DNA repair mechanisms in the germline and in the tumor genome will allow clinicians and researchers to apply PARPi most strategically in the era of personalized medicine. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

PubMed

Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

2015-08-01

Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis

PubMed Central

Bryan, Chase D.; Chien, Chi-Bin; Kwan, Kristen M.

2016-01-01

The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1UW1) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1UW1 mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis. PMID:27339294

The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

PubMed Central

Terabe, Masaki; Berzofsky, Jay A.

2014-01-01

NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

Multi-functional quantum router using hybrid opto-electromechanics

NASA Astrophysics Data System (ADS)

Ma, Peng-Cheng; Yan, Lei-Lei; Chen, Gui-Bin; Li, Xiao-Wei; Liu, Shu-Jing; Zhan, You-Bang

2018-03-01

Quantum routers engineered with multiple frequency bands play a key role in quantum networks. We propose an experimentally accessible scheme for a multi-functional quantum router, using photon-phonon conversion in a hybrid opto-electromechanical system. Our proposed device functions as a bidirectional, tunable multi-channel quantum router, and demonstrates the possibility to route single optical photons bidirectionally and simultaneously to three different output ports, by adjusting the microwave power. Further, the device also behaves as an interswitching unit for microwave and optical photons, yielding probabilistic routing of microwave (optical) signals to optical (microwave) outports. With respect to potential application, we verify the insignificant influence from vacuum and thermal noises in the performance of the router under cryogenic conditions.

Endoreplication and polyploidy: insights into development and disease

PubMed Central

Fox, Donald T.; Duronio, Robert J.

2013-01-01

Polyploid cells have genomes that contain multiples of the typical diploid chromosome number and are found in many different organisms. Studies in a variety of animal and plant developmental systems have revealed evolutionarily conserved mechanisms that control the generation of polyploidy and have recently begun to provide clues to its physiological function. These studies demonstrate that cellular polyploidy plays important roles during normal development and also contributes to human disease, particularly cancer. PMID:23222436

Nanometric summation architecture based on optical near-field interaction between quantum dots.

PubMed

Naruse, Makoto; Miyazaki, Tetsuya; Kubota, Fumito; Kawazoe, Tadashi; Kobayashi, Kiyoshi; Sangu, Suguru; Ohtsu, Motoichi

2005-01-15

A nanoscale data summation architecture is proposed and experimentally demonstrated based on the optical near-field interaction between quantum dots. Based on local electromagnetic interactions between a few nanometric elements via optical near fields, we can combine multiple excitations at a certain quantum dot, which allows construction of a summation architecture. Summation plays a key role for content-addressable memory, which is one of the most important functions in optical networks.

Hypoxia and Mucosal Inflammation

PubMed Central

Colgan, Sean P.; Campbell, Eric L.; Kominsky, Douglas J.

2016-01-01

Sites of inflammation are defined by significant changes in metabolic activity. Recent studies have suggested that O2 metabolism and hypoxia play a prominent role in inflammation so-called “inflammatory hypoxia,” which results from a combination of recruited inflammatory cells (e.g., neutrophils and monocytes), the local proliferation of multiple cell types, and the activation of multiple O2-consuming enzymes during inflammation. These shifts in energy supply and demand result in localized regions of hypoxia and have revealed the important function off the transcription factor HIF (hypoxia-inducible factor) in the regulation of key target genes that promote inflammatory resolution. Analysis of these pathways has provided multiple opportunities for understanding basic mechanisms of inflammation and has defined new targets for intervention. Here, we review recent work addressing tissue hypoxia and metabolic control of inflammation and immunity. PMID:27193451

Soil properties, soil functions and soil security

NASA Astrophysics Data System (ADS)

Poggio, Laura; Gimona, Alessandro

2017-04-01

Soil plays a crucial role in the ecosystem functioning such as food production, capture and storage of water, carbon and nutrients and in the realisation of a number of UN Sustainable Developments Goals. In this work we present an approach to spatially and jointly assess the multiple contributions of soil to the delivery of ecosystem services within multiple land-use system. We focussed on the modelling of the impact of soil on sediment retention, carbon storage, storing and filtering of nutrients, habitat for soil organisms and water regulation, taking into account examples of land use and climate scenarios. Simplified models were used for the single components. Spatialised Bayesian Belief networks were used for the jointly assessment and mapping of soil contribution to multiple land use and ecosystem services. We integrated continuous 3D soil information derived from digital soil mapping approaches covering the whole of mainland Scotland, excluding the Northern Islands. Uncertainty was accounted for and propagated across the whole process. The Scottish test case highlights the differences in roles between mineral and organic soils and provides an example of integrated study assessing the contributions of soil. The results show the importance of the multi-functional analysis of the contribution of soils to the ecosystem service delivery and UN SDGs.

GP96 is a GARP chaperone and controls regulatory T cell functions.

PubMed

Zhang, Yongliang; Wu, Bill X; Metelli, Alessandra; Thaxton, Jessica E; Hong, Feng; Rachidi, Saleh; Ansa-Addo, Ephraim; Sun, Shaoli; Vasu, Chenthamarakshan; Yang, Yi; Liu, Bei; Li, Zihai

2015-02-01

Molecular chaperones control a multitude of cellular functions via folding chaperone-specific client proteins. CD4+FOXP3+ Tregs play key roles in maintaining peripheral tolerance, which is subject to regulation by multiple molecular switches, including mTOR and hypoxia-inducible factor. It is not clear whether GP96 (also known as GRP94), which is a master TLR and integrin chaperone, controls Treg function. Using murine genetic models, we demonstrated that GP96 is required for Treg maintenance and function, as loss of GP96 resulted in instability of the Treg lineage and impairment of suppressive functions in vivo. In the absence of GP96, Tregs were unable to maintain FOXP3 expression levels, resulting in systemic accumulation of pathogenic IFN-γ-producing and IL-17-producing T cells. We determined that GP96 serves as an essential chaperone for the cell-surface protein glycoprotein A repetitions predominant (GARP), which is a docking receptor for latent membrane-associated TGF-β (mLTGF-β). The loss of both GARP and integrins on GP96-deficient Tregs prevented expression of mLTGF-β and resulted in inefficient production of active TGF-β. Our work demonstrates that GP96 regulates multiple facets of Treg biology, thereby placing Treg stability and immunosuppressive functions strategically under the control of a major stress chaperone.

B cell biology: implications for treatment of systemic lupus erythematosus.

PubMed

Anolik, J H

2013-04-01

B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody-independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B cell activation thresholds, B cell longevity, and apoptotic cell processing. Once tolerance is broken, autoantibodies contribute to autoimmunity by multiple mechanisms including immune-complex mediated Type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread utilization of B cell depletion therapy in autoimmune diseases and the need for new therapeutic approaches in SLE, a better understanding of human B cell subsets and the balance of pathogenic and regulatory functions is of the essence.

Effects of multiple antibiotics exposure on denitrification process in the Yangtze Estuary sediments.

PubMed

Yin, Guoyu; Hou, Lijun; Liu, Min; Zheng, Yanling; Li, Xiaofei; Lin, Xianbiao; Gao, Juan; Jiang, Xiaofen; Wang, Rong; Yu, Chendi

2017-03-01

Denitrification is a dominant reactive nitrogen removal pathway in most estuarine and coastal ecosystems, and plays a significant role in regulating N 2 O release. Although multiple antibiotics residues are widely detected in aquatic environment, combined effects of antibiotics on denitrification remain indistinct. In this work, 5 classes of antibiotics (sulfonamides, chloramphenicols, tetracyclines, macrolides, and fluoroquinolones) were selected to conduct orthogonal experiments in order to explore their combined effects on denitrification. 15 N-based denitrification and N 2 O release rates were determined in the orthogonal experiments, while denitrifying functional genes were examined to illustrate the microbial mechanism of the combined antibiotics effect. Denitrification rates were inhibited by antibiotics treatments, and synergistic inhibition effect was observed for multiple antibiotics exposure. Different classes of antibiotics had different influence on N 2 O release rates, but multiple antibiotics exposure mostly led to stimulatory effect. Abundances of denitrifying functional genes were inhibited by multiple antibiotics exposure due to the antimicrobial properties, and different inhibition on denitrifiers may be the major mechanism for the variations of N 2 O release rates. Combined effects of antibiotics on denitrification may lead to nitrate retention and N 2 O release in estuarine and coastal ecosystems, and consequently cause cascading environmental problems, such as greenhouse effects and hyper-eutrophication. Copyright © 2016 Elsevier Ltd. All rights reserved.

The messenger matters: Pollinator functional group influences mating system dynamics.

PubMed

Weber, Jennifer J

2017-08-01

The incredible diversity of plant mating systems has fuelled research in evolutionary biology for over a century. Currently, there is broad concern about the impact of rapidly changing pollinator communities on plant populations. Very few studies, however, examine patterns and mechanisms associated with multiple paternity from cross-pollen loads. Often, foraging pollinators collect a mixed pollen load that may result in the deposition of pollen from different sires to receptive stigmas. Coincident deposition of self- and cross-pollen leads to interesting mating system dynamics and has been investigated in numerous species. But, mixed pollen loads often consist of a diversity of cross-pollen and result in multiple sires of seeds within a fruit. In this issue of Molecular Ecology, Rhodes, Fant, and Skogen () examine how pollinator identity and spatial isolation influence multiple paternity within fruits of a self-incompatible evening primrose. The authors demonstrate that pollen pool diversity varies between two pollinator types, hawkmoths and diurnal solitary bees. Further, progeny from more isolated plants were less likely to have multiple sires regardless of the pollinator type. Moving forward, studies of mating system dynamics should consider the implications of multiple paternity and move beyond the self- and cross-pollination paradigm. Rhodes et al. () demonstrate the importance of understanding the roles that functionally diverse pollinators play in mating system dynamics. © 2017 John Wiley & Sons Ltd.

A combined gene expression and functional study reveals the crosstalk between N-Myc and differentiation-inducing microRNAs in neuroblastoma cells

PubMed Central

Zhao, Zhenze; Ma, Xiuye; Shelton, Spencer D.; Sung, Derek C.; Li, Monica; Hernandez, Daniel; Zhang, Maggie; Losiewicz, Michael D.; Chen, Yidong; Pertsemlidis, Alexander; Yu, Xiaojie; Liu, Yuanhang; Du, Liqin

2016-01-01

MYCN amplification is the most common genetic alteration in neuroblastoma and plays a critical role in neuroblastoma tumorigenesis. MYCN regulates neuroblastoma cell differentiation, which is one of the mechanisms underlying its oncogenic function. We recently identified a group of differentiation-inducing microRNAs. Given the demonstrated inter-regulation between MYCN and microRNAs, we speculated that MYCN and the differentiation-inducing microRNAs might form an interaction network to control the differentiation of neuroblastoma cells. In this study, we found that eight of the thirteen differentiation-inducing microRNAs, miR-506-3p, miR-124-3p, miR-449a, miR-34a-5p, miR-449b-5p, miR-103a-3p, miR-2110 and miR-34b-5p, inhibit N-Myc expression by either directly targeting the MYCN 3′UTR or through indirect regulations. Further investigation showed that both MYCN-dependent and MYCN-independent pathways play roles in mediating the differentiation-inducing function of miR-506-3p and miR-449a, two microRNAs that dramatically down-regulate MYCN expression. On the other hand, we found that N-Myc inhibits the expression of multiple differentiation-inducing microRNAs, suggesting that these miRNAs play a role in mediating the function of MYCN. In examining the published dataset collected from clinical neuroblastoma specimens, we found that expressions of two miRNAs, miR-137 and miR-2110, were significantly anti-correlated with MYCN mRNA levels, suggesting their interactions with MYCN play a clinically-relevant role in maintaining the MYCN and miRNA expression levels in neuroblastoma. Our findings altogether suggest that MYCN and differentiation-inducing miRNAs form an interaction network that play an important role in neuroblastoma tumorigenesis through regulating cell differentiation. PMID:27764804

A combined gene expression and functional study reveals the crosstalk between N-Myc and differentiation-inducing microRNAs in neuroblastoma cells.

PubMed

Zhao, Zhenze; Ma, Xiuye; Shelton, Spencer D; Sung, Derek C; Li, Monica; Hernandez, Daniel; Zhang, Maggie; Losiewicz, Michael D; Chen, Yidong; Pertsemlidis, Alexander; Yu, Xiaojie; Liu, Yuanhang; Du, Liqin

2016-11-29

MYCN amplification is the most common genetic alteration in neuroblastoma and plays a critical role in neuroblastoma tumorigenesis. MYCN regulates neuroblastoma cell differentiation, which is one of the mechanisms underlying its oncogenic function. We recently identified a group of differentiation-inducing microRNAs. Given the demonstrated inter-regulation between MYCN and microRNAs, we speculated that MYCN and the differentiation-inducing microRNAs might form an interaction network to control the differentiation of neuroblastoma cells. In this study, we found that eight of the thirteen differentiation-inducing microRNAs, miR-506-3p, miR-124-3p, miR-449a, miR-34a-5p, miR-449b-5p, miR-103a-3p, miR-2110 and miR-34b-5p, inhibit N-Myc expression by either directly targeting the MYCN 3'UTR or through indirect regulations. Further investigation showed that both MYCN-dependent and MYCN-independent pathways play roles in mediating the differentiation-inducing function of miR-506-3p and miR-449a, two microRNAs that dramatically down-regulate MYCN expression. On the other hand, we found that N-Myc inhibits the expression of multiple differentiation-inducing microRNAs, suggesting that these miRNAs play a role in mediating the function of MYCN. In examining the published dataset collected from clinical neuroblastoma specimens, we found that expressions of two miRNAs, miR-137 and miR-2110, were significantly anti-correlated with MYCN mRNA levels, suggesting their interactions with MYCN play a clinically-relevant role in maintaining the MYCN and miRNA expression levels in neuroblastoma. Our findings altogether suggest that MYCN and differentiation-inducing miRNAs form an interaction network that play an important role in neuroblastoma tumorigenesis through regulating cell differentiation.

PSP: rapid identification of orthologous coding genes under positive selection across multiple closely related prokaryotic genomes.

PubMed

Su, Fei; Ou, Hong-Yu; Tao, Fei; Tang, Hongzhi; Xu, Ping

2013-12-27

With genomic sequences of many closely related bacterial strains made available by deep sequencing, it is now possible to investigate trends in prokaryotic microevolution. Positive selection is a sub-process of microevolution, in which a particular mutation is favored, causing the allele frequency to continuously shift in one direction. Wide scanning of prokaryotic genomes has shown that positive selection at the molecular level is much more frequent than expected. Genes with significant positive selection may play key roles in bacterial adaption to different environmental pressures. However, selection pressure analyses are computationally intensive and awkward to configure. Here we describe an open access web server, which is designated as PSP (Positive Selection analysis for Prokaryotic genomes) for performing evolutionary analysis on orthologous coding genes, specially designed for rapid comparison of dozens of closely related prokaryotic genomes. Remarkably, PSP facilitates functional exploration at the multiple levels by assignments and enrichments of KO, GO or COG terms. To illustrate this user-friendly tool, we analyzed Escherichia coli and Bacillus cereus genomes and found that several genes, which play key roles in human infection and antibiotic resistance, show significant evidence of positive selection. PSP is freely available to all users without any login requirement at: http://db-mml.sjtu.edu.cn/PSP/. PSP ultimately allows researchers to do genome-scale analysis for evolutionary selection across multiple prokaryotic genomes rapidly and easily, and identify the genes undergoing positive selection, which may play key roles in the interactions of host-pathogen and/or environmental adaptation.

Mitogen-activated protein kinase cascades in signaling plant growth and development.

PubMed

Xu, Juan; Zhang, Shuqun

2015-01-01

Mitogen-activated protein kinase (MAPK) cascades are ubiquitous signaling modules in eukaryotes. Early research of plant MAPKs has been focused on their functions in immunity and stress responses. Recent studies reveal that they also play essential roles in plant growth and development downstream of receptor-like protein kinases (RLKs). With only a limited number of MAPK components, multiple functional pathways initiated from different receptors often share the same MAPK components or even a complete MAPK cascade. In this review, we discuss how MAPK cascades function as molecular switches in response to spatiotemporal-specific ligand-receptor interactions and the availability of downstream substrates. In addition, we discuss other possible mechanisms governing the functional specificity of plant MAPK cascades, a question central to our understanding of MAPK functions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sports Hernia: Diagnosis, Management and Operative Treatment

PubMed Central

Emblom, Benton A.

2017-01-01

Objectives: Athletic Pubalgia, also known as sports hernia or core muscle injury, causes significant dysfunction in athletes. Increased recognition of this specific injury distinct from inguinal hernia pathology has led to better management of this debilitating condition. We hypothesize that patients who undergo our technique of athletic pubalgia repair will recover and return to high-level athletics. Methods: Using our billing and clinical database, patients who underwent sports hernia repair by single surgeon at a single institution were contacted for Harris hip score, functional outcome, and return to play data. Results: Of 101 patients who met criteria, 43 were contacted. 93% of patients were able to return to play at an average of 4.38 mo. Normal activities were rated at 95.5% and athletic function was rated at 88.9%. Negative predictors were female sex, multiple operations, and prior inguinal hernia repair. Overall complication rate was 4.6%, and reoperation rate was 4.6%. Conclusion: Our method of adductor to rectus abdominis turn up flap is a safe procedure with high return to play success. Patients who had previously undergone inguinal hernia repair or other hip/pelvic related surgery had a worse outcome.

MhYTP1 and MhYTP2 from Apple Confer Tolerance to Multiple Abiotic Stresses in Arabidopsis thaliana

PubMed Central

Wang, Na; Guo, Tianli; Wang, Ping; Sun, Xun; Shao, Yun; Jia, Xin; Liang, Bowen; Gong, Xiaoqing; Ma, Fengwang

2017-01-01

The first YTH domain-containing RNA binding protein (YTP) was found in rat, where it was related to oxidative stress. Unlike characterizations in yeast and animals, functions of plant YTPs are less clear. Malus hupehensis (Pamp.) Rehd. YTP1 and YTP2 (MhYTP1 and MhYTP2) are known to be active in leaf senescence and fruit ripening. However, no research has been published about their roles in stress responses. Here, we investigate the stress-related functions of MhYTP1 and MhYTP2 in Arabidopsis thaliana. Both of the two genes participated in salicylic acid (SA), jasmonic acid (JA), and abscisic acid (ABA) signaling and play roles in plant responses to oxidative stress, chilling, high temperature, high salinity, and mannitol induced physiological drought stress. Moreover, MhYTP1 plays leading roles in SA and ABA signaling, and MhYTP2 plays leading roles in JA signaling and oxidative stress responses. These results will fill a gap in our knowledge about plant YTPs and stress responses and provide a foundation for future attempts to improve stress tolerance in apple. PMID:28824695

Clinical and cognitive factors affecting psychosocial functioning in remitted patients with bipolar disorder.

PubMed

Konstantakopoulos, G; Ioannidi, N; Typaldou, M; Sakkas, D; Oulis, P

2016-01-01

Impaired interpersonal, social, and occupational functioning is very often observed in patients with bipolar disorder, not only at the acute stages of the illness but in remission as well. This finding raises the question of multiple factors that might affect psychosocial functioning in bipolar patients, such as residual subsyndromal symptoms and neuropsychological deficits. Social cognition impairment, especially impaired Theory of Mind (ToM), might also play an important role in bipolar patients' every-day functioning, similarly to what was found in patients with schizophrenia. The present study aimed to investigate the potential effect of clinical and cognitive factors on the psychosocial functioning of patients with bipolar disorder during remission, assessing ToM along with a broad range of basic cognitive functions. Forty-nine patients with bipolar disorder type I in remission and 53 healthy participants were assessed in general intelligence, working memory, attention, speed processing, verbal learning and memory, and executive functions using a comprehensive battery of neuropsychological tests. The Faux Pas Recognition Test was used to assess ToM. The two groups were matched for gender, age and education level. The Hamilton Rating Scale for Depression (HDRS), the Young Mania Rating Scale (YMRS), and the Brief Psychiatric Rating Scale (BPRS) were also administered to the patients. Every-day functioning was assessed with the Global Assessment of Functioning (GAF). In order to examine the contribution of many factors in psychosocial functioning, we used hierarchical multiple regression analysis. Bipolar patients presented significant impairment compared to healthy participants in all the basic cognitive functions tested with the exception of verbal memory. Moreover, patients had significant poorer performance than healthy controls in overall psyand cognitive ToM but not in affective ToM as measured by Faux Pas. Psychosocial functioning in patient group was significantly correlated to symptom severity-especially depressive (p<0.001) and psychotic symptoms (p=0.001), history of psychotic episodes (p=0.031) and ToM, overall (p=0.001) as well as its cognitive (p=0.023) and affective (p=0.004) components. Only the contribution of ToM in psychosocial functioning remained significant in the final multiple regression model. The findings of the current study indicate that residual symptoms and cognitive dysfunctions, especially deficits in social cognition, negatively affect psychosocial functioning of remitted patients with bipolar disorder. Moreover, our results suggest that ToM may play a central role in these patients' functioning. ToM is a mediator of the relationship between other clinical or cognitive variables and functioning, while it has also significant effect on social skills independently of other factors. Therefore, specific therapeutic interventions targeting social cognitive dysfunction might improve functional outcome in bipolar disorder. Putative contribution of other clinical characteristics (comorbid personality disorders, substance abuse, anxiety) and psychosocial factors (stigma, self-stigma, lack of social network) in bipolar patients' functioning should be examined in future studies.

Behavior learning in differential games and reorientation maneuvers

NASA Astrophysics Data System (ADS)

Satak, Neha

The purpose of this dissertation is to apply behavior learning concepts to incomplete- information continuous time games. Realistic game scenarios are often incomplete-information games in which the players withhold information. A player may not know its opponent's objectives and strategies prior to the start of the game. This lack of information can limit the player's ability to play optimally. If the player can observe the opponent's actions, it can better optimize its achievements by taking corrective actions. In this research, a framework to learn an opponent's behavior and take corrective actions is developed. The framework will allow a player to observe the opponent's actions and formulate behavior models. The developed behavior model can then be utilized to find the best actions for the player that optimizes the player's objective function. In addition, the framework proposes that the player plays a safe strategy at the beginning of the game. A safe strategy is defined in this research as a strategy that guarantees a minimum pay-off to the player independent of the other player's actions. During the initial part of the game, the player will play the safe strategy until it learns the opponent's behavior. Two methods to develop behavior models that differ in the formulation of the behavior model are proposed. The first method is the Cost-Strategy Recognition (CSR) method in which the player formulates an objective function and a strategy for the opponent. The opponent is presumed to be rational and therefore will play to optimize its objective function. The strategy of the opponent is dependent on the information available to the opponent about other players in the game. A strategy formulation presumes a certain level of information available to the opponent. The previous observations of the opponent's actions are used to estimate the parameters of the formulated behavior model. The estimated behavior model predicts the opponent's future actions. The second method is the Direct Approximation of Value Function (DAVF) method. In this method, unlike the CSR method, the player formulates an objective function for the opponent but does not formulates a strategy directly; rather, indirectly the player assumes that the opponent is playing optimally. Thus, a value function satisfying the HJB equation corresponding to the opponent's cost function exists. The DAVF method finds an approximate solution for the value function based on previous observations of the opponent's control. The approximate solution to the value function is then used to predict the opponent's future behavior. Game examples in which only a single player is learning its opponent's behavior are simulated. Subsequently, examples in which both players in a two-player game are learning each other's behavior are simulated. In the second part of this research, a reorientation control maneuver for a spinning spacecraft will be developed. This will aid the application of behavior learning and differential games concepts to the specific scenario involving multiple spinning spacecraft. An impulsive reorientation maneuver with coasting will be analytically designed to reorient the spin axis of the spacecraft using a single body fixed thruster. Cooperative maneuvers of multiple spacecraft optimizing fuel and relative orientation will be designed. Pareto optimality concepts will be used to arrive at mutually agreeable reorientation maneuvers for the cooperating spinning spacecraft.

Playing piano can improve upper extremity function after stroke: case studies.

PubMed

Villeneuve, Myriam; Lamontagne, Anouk

2013-01-01

Music-supported therapy (MST) is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3), prior to (week6) and after the intervention (week9), and at 3-week follow-up (week12). Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test) and gross (box and block test) manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test). Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke.

Playing Piano Can Improve Upper Extremity Function after Stroke: Case Studies

PubMed Central

Villeneuve, Myriam; Lamontagne, Anouk

2013-01-01

Music-supported therapy (MST) is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3), prior to (week6) and after the intervention (week9), and at 3-week follow-up (week12). Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test) and gross (box and block test) manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test). Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke. PMID:23533954

Nitrogen Cycle Evaluation (NiCE) Chip for the Simultaneous Analysis of Multiple N-Cycle Associated Genes.

PubMed

Oshiki, Mamoru; Segawa, Takahiro; Ishii, Satoshi

2018-02-02

Various microorganisms play key roles in the Nitrogen (N) cycle. Quantitative PCR (qPCR) and PCR-amplicon sequencing of the N cycle functional genes allow us to analyze the abundance and diversity of microbes responsible in the N transforming reactions in various environmental samples. However, analysis of multiple target genes can be cumbersome and expensive. PCR-independent analysis, such as metagenomics and metatranscriptomics, is useful but expensive especially when we analyze multiple samples and try to detect N cycle functional genes present at relatively low abundance. Here, we present the application of microfluidic qPCR chip technology to simultaneously quantify and prepare amplicon sequence libraries for multiple N cycle functional genes as well as taxon-specific 16S rRNA gene markers for many samples. This approach, named as N cycle evaluation (NiCE) chip, was evaluated by using DNA from pure and artificially mixed bacterial cultures and by comparing the results with those obtained by conventional qPCR and amplicon sequencing methods. Quantitative results obtained by the NiCE chip were comparable to those obtained by conventional qPCR. In addition, the NiCE chip was successfully applied to examine abundance and diversity of N cycle functional genes in wastewater samples. Although non-specific amplification was detected on the NiCE chip, this could be overcome by optimizing the primer sequences in the future. As the NiCE chip can provide high-throughput format to quantify and prepare sequence libraries for multiple N cycle functional genes, this tool should advance our ability to explore N cycling in various samples. Importance. We report a novel approach, namely Nitrogen Cycle Evaluation (NiCE) chip by using microfluidic qPCR chip technology. By sequencing the amplicons recovered from the NiCE chip, we can assess diversities of the N cycle functional genes. The NiCE chip technology is applicable to analyze the temporal dynamics of the N cycle gene transcriptions in wastewater treatment bioreactors. The NiCE chip can provide high-throughput format to quantify and prepare sequence libraries for multiple N cycle functional genes. While there is a room for future improvement, this tool should significantly advance our ability to explore the N cycle in various environmental samples. Copyright © 2018 American Society for Microbiology.

Cortical Networks for Visual Self-Recognition

NASA Astrophysics Data System (ADS)

Sugiura, Motoaki

This paper briefly reviews recent developments regarding the brain mechanisms of visual self-recognition. A special cognitive mechanism for visual self-recognition has been postulated based on behavioral and neuropsychological evidence, but its neural substrate remains controversial. Recent functional imaging studies suggest that multiple cortical mechanisms play self-specific roles during visual self-recognition, reconciling the existing controversy. Respective roles for the left occipitotemporal, right parietal, and frontal cortices in symbolic, visuospatial, and conceptual aspects of self-representation have been proposed.

Lipoic acid metabolism and mitochondrial redox regulation.

PubMed

Solmonson, Ashley D; DeBerardinis, Ralph J

2017-11-30

Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty acid synthesis type II, S-adenosylmethionine and iron-sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multi-enzyme complexes.  Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety.  Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity and coordination of fuel metabolism. Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty acid synthesis type II, S-adenosylmethionine and iron-sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multi-enzyme complexes.  Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety.  Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity and coordination of fuel metabolism. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

PubMed Central

Sun, Xiaolin; Rikkerink, Erik H.A.; Jones, William T.; Uversky, Vladimir N.

2013-01-01

Intrinsically disordered proteins (IDPs) are highly abundant in eukaryotic proteomes. Plant IDPs play critical roles in plant biology and often act as integrators of signals from multiple plant regulatory and environmental inputs. Binding promiscuity and plasticity allow IDPs to interact with multiple partners in protein interaction networks and provide important functional advantages in molecular recognition through transient protein–protein interactions. Short interaction-prone segments within IDPs, termed molecular recognition features, represent potential binding sites that can undergo disorder-to-order transition upon binding to their partners. In this review, we summarize the evidence for the importance of IDPs in plant biology and evaluate the functions associated with intrinsic disorder in five different types of plant protein families experimentally confirmed as IDPs. Functional studies of these proteins illustrate the broad impact of disorder on many areas of plant biology, including abiotic stress, transcriptional regulation, light perception, and development. Based on the roles of disorder in the protein–protein interactions, we propose various modes of action for plant IDPs that may provide insight for future experimental approaches aimed at understanding the molecular basis of protein function within important plant pathways. PMID:23362206

Prohibitin (PHB) roles in granulosa cell physiology

PubMed Central

Chowdhury, Indrajit; Thomas, Kelwyn; Thompson, Winston E.

2015-01-01

Ovarian granulosa cells (GC) play an important role in the growth and development of the follicle in the process known as folliculogenesis. In the present review, we focus on the recent developments in prohibitin (PHB) research in relation to GC physiological functions. PHB is a member of highly conserved eukaryotic protein family containing the repressor of estrogen activity (REA)/stomatin/prohibitin/flotillin/HflK/C (SPFH) domain [also known as the PHB domain] found in divergent species from prokaryotes to eukaryotes. PHB is ubiquitously expressed either in circulating free form or is present in multiple cellular compartments including mitochondria, nucleus and plasma membrane. In mitochondria, PHB is anchored to the mitochondrial inner membrane (IMM), and form complexes with the ATPases Associated with diverse cellular Activities (m-AAA) proteases. PHB continuously shuttles between the mitochondria, cytosol and nucleus. In the nucleus, PHB interacts with various transcription factors and modulate transcriptional activity directly or through interactions with chromatin remodeling proteins. Multiple functions have been attributed to the mitochondrial and nuclear prohibitin complexes such as cellular differentiation, anti-proliferation, morphogenesis and maintaining the functional integrity of the mitochondria. However, to date, the regulation of PHB expression patterns and GC physiological functions are not completely understood. PMID:26496733

Unraveling secrets of telomeres: one molecule at a time

PubMed Central

Lin, Jiangguo; Kaur, Parminder; Countryman, Preston; Opresko, Patricia L.; Wang, Hong

2016-01-01

Telomeres play important roles in maintaining the stability of linear chromosomes. Telomere maintenance involves dynamic actions of multiple proteins interacting with long repetitive sequences and complex dynamic DNA structures, such as G-quadruplexes, T-loops and t-circles. Given the heterogeneity and complexity of telomeres, single-molecule approaches are essential to fully understand the structure-function relationships that govern telomere maintenance. In this review, we present a brief overview of the principles of single-molecule imaging and manipulation techniques. We then highlight results obtained from applying these single-molecule techniques for studying structure, dynamics and functions of G-quadruplexes, telomerase, and shelterin proteins. PMID:24569170

INSECT FAT BODY: ENERGY, METABOLISM, AND REGULATION

PubMed Central

Arrese, Estela L.; Soulages, Jose L.

2010-01-01

The fat body plays major roles in the life of insects. It is a dynamic tissue involved in multiple metabolic functions. One of these functions is to store and release energy in response to the energy demands of the insect. Insects store energy reserves in the form of glycogen and triglycerides in the adipocytes, the main fat body cell. Insect adipocytes can store a great amount of lipid reserves as cytoplasmic lipid droplets. Lipid metabolism is essential for growth and reproduction and provides energy needed during extended nonfeeding periods. This review focuses on energy storage and release and summarizes current understanding of the mechanisms underlying these processes in insects. PMID:19725772

Exercise Benefits Coronary Heart Disease.

PubMed

Wang, Lei; Ai, Dongmei; Zhang, Ning

2017-01-01

Coronary heart disease (CHD) is a group of diseases that include: no symptoms, angina, myocardial infarction, ischemia cardiomyopathy and sudden cardiac death. And it results from multiple risks factors consisting of invariable factors (e.g. age, gender, etc.) and variable factors (e.g. dyslipidemia, hypertension, diabetes, smoking, etc.). Meanwhile, CHD could cause impact not only localized in the heart, but also on pulmonary function, whole-body skeletal muscle function, activity ability, psychological status, etc. Nowadays, CHD has been the leading cause of death in the world. However, many clinical researches showed that exercise training plays an important role in cardiac rehabilitation and can bring a lot of benefits for CHD patients.

Update in TSH Receptor Agonists and Antagonists

PubMed Central

Neumann, Susanne

2012-01-01

The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, “drug-like” TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands. PMID:23019348

Zernike Basis to Cartesian Transformations

NASA Astrophysics Data System (ADS)

Mathar, R. J.

2009-12-01

The radial polynomials of the 2D (circular) and 3D (spherical) Zernike functions are tabulated as powers of the radial distance. The reciprocal tabulation of powers of the radial distance in series of radial polynomials is also given, based on projections that take advantage of the orthogonality of the polynomials over the unit interval. They play a role in the expansion of products of the polynomials into sums, which is demonstrated by some examples. Multiplication of the polynomials by the angular bases (azimuth, polar angle) defines the Zernike functions, for which we derive transformations to and from the Cartesian coordinate system centered at the middle of the circle or sphere.

Global urban signatures of phenotypic change in animal and plant populations

PubMed Central

Correa, Cristian; Marzluff, John M.; Hendry, Andrew P.; Palkovacs, Eric P.; Hunt, Victoria M.; Apgar, Travis M.; Zhou, Yuyu

2017-01-01

Humans challenge the phenotypic, genetic, and cultural makeup of species by affecting the fitness landscapes on which they evolve. Recent studies show that cities might play a major role in contemporary evolution by accelerating phenotypic changes in wildlife, including animals, plants, fungi, and other organisms. Many studies of ecoevolutionary change have focused on anthropogenic drivers, but none of these studies has specifically examined the role that urbanization plays in ecoevolution or explicitly examined its mechanisms. This paper presents evidence on the mechanisms linking urban development patterns to rapid evolutionary changes for species that play important functional roles in communities and ecosystems. Through a metaanalysis of experimental and observational studies reporting more than 1,600 phenotypic changes in species across multiple regions, we ask whether we can discriminate an urban signature of phenotypic change beyond the established natural baselines and other anthropogenic signals. We then assess the relative impact of five types of urban disturbances including habitat modifications, biotic interactions, habitat heterogeneity, novel disturbances, and social interactions. Our study shows a clear urban signal; rates of phenotypic change are greater in urbanizing systems compared with natural and nonurban anthropogenic systems. By explicitly linking urban development to traits that affect ecosystem function, we can map potential ecoevolutionary implications of emerging patterns of urban agglomerations and uncover insights for maintaining key ecosystem functions upon which the sustainability of human well-being depends. PMID:28049817

Global urban signatures of phenotypic change in animal and plant populations.

PubMed

Alberti, Marina; Correa, Cristian; Marzluff, John M; Hendry, Andrew P; Palkovacs, Eric P; Gotanda, Kiyoko M; Hunt, Victoria M; Apgar, Travis M; Zhou, Yuyu

2017-08-22

Humans challenge the phenotypic, genetic, and cultural makeup of species by affecting the fitness landscapes on which they evolve. Recent studies show that cities might play a major role in contemporary evolution by accelerating phenotypic changes in wildlife, including animals, plants, fungi, and other organisms. Many studies of ecoevolutionary change have focused on anthropogenic drivers, but none of these studies has specifically examined the role that urbanization plays in ecoevolution or explicitly examined its mechanisms. This paper presents evidence on the mechanisms linking urban development patterns to rapid evolutionary changes for species that play important functional roles in communities and ecosystems. Through a metaanalysis of experimental and observational studies reporting more than 1,600 phenotypic changes in species across multiple regions, we ask whether we can discriminate an urban signature of phenotypic change beyond the established natural baselines and other anthropogenic signals. We then assess the relative impact of five types of urban disturbances including habitat modifications, biotic interactions, habitat heterogeneity, novel disturbances, and social interactions. Our study shows a clear urban signal; rates of phenotypic change are greater in urbanizing systems compared with natural and nonurban anthropogenic systems. By explicitly linking urban development to traits that affect ecosystem function, we can map potential ecoevolutionary implications of emerging patterns of urban agglomerations and uncover insights for maintaining key ecosystem functions upon which the sustainability of human well-being depends.

L-Arginine and Alzheimer's Disease

PubMed Central

Yi, Jing; Horky, Laura L.; Friedlich, Avi L.; Shi, Ying; Rogers, Jack T.; Huang, Xudong

2009-01-01

Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive neurodegeneration and loss of cognitive and memory functions. Although the exact causes of AD are still unclear, evidence suggests that atherosclerosis, redox stress, inflammation, neurotransmitter dysregulation, and impaired brain energy metabolism may all be associated with AD pathogenesis. Herein, we explore a possible role for L-arginine (L-arg) in AD, taking into consideration known functions for L-arg in atherosclerosis, redox stress and the inflammatory process, regulation of synaptic plasticity and neurogenesis, and modulation of glucose metabolism and insulin activity. L-arg, a precursor of nitric oxide and polyamine, exhibits multiple functions in human health and may play a prominent role in age-related degenerative diseases such as AD. PMID:19079617

Mild deficits in mice lacking pituitary adenylate cyclase-activating polypeptide receptor type 1 (PAC1) performing on memory tasks.

PubMed

Sauvage, M; Brabet, P; Holsboer, F; Bockaert, J; Steckler, T

2000-12-08

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor subtype 1 (PAC1) have been suggested to play a role in the modulation of learning and memory. However, behavioral evidence for altered mnemonic function due to altered PAC1 activity is missing. Therefore, the role of PAC1 in learning and memory was studied in mouse mutants lacking this receptor (PAC1 knock-out mice), tested in water maze two-choice spatial discrimination, one-trial contextual and cued fear conditioning, and multiple-session contextual discrimination. Water maze spatial discrimination was unaffected in PAC1 mutants, while a mild deficit was observed in multiple session contextual discrimination in PAC1 knock-out mice. Furthermore, PAC1 knock-out mice were able to learn the association between context and shock in one-trial contextual conditioning, but showed faster return to baseline than wild-type mice. Thus, the effects of PAC1 knock-out on modulating performance in these tasks were subtle and suggest that PAC1 only plays a limited role in learning and memory.

Mechanisms of lymphocyte migration in autoimmune disease.

PubMed

Norman, M U; Hickey, M J

2005-09-01

The recruitment of leukocytes to inflamed tissues plays an essential role in combating infection and promoting wound healing. However, in autoimmune diseases such as multiple sclerosis and diabetes, leukocytes enter tissues and contribute to inappropriate inflammatory responses, which cause tissue injury and dysfunction. In diseases of this type, lymphocytes play critical roles in initiating and maintaining these aberrant inflammatory responses. The aim of this review is to examine the mechanisms whereby T-lymphocytes enter tissues in autoimmune diseases and to compare these mechanisms between various organs and diseases. An overview of the mechanisms of leukocyte recruitment and the techniques used to study leukocyte trafficking is provided, focusing on the use of intravital microscopy as a tool to assess the functional microvasculature in vivo. We also discuss the series of tissue homing events which allow naïve lymphocytes to first enter lymph nodes and undergo activation, then subsequently to home to the peripheral organ where their cognate antigen is present. Finally, we examine mechanisms of leukocyte recruitment in diseases such as multiple sclerosis, autoimmune diabetes, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease and asthma.

Optimizing health system response to patient's needs: an argument for the importance of functioning information.

PubMed

Hopfe, Maren; Prodinger, Birgit; Bickenbach, Jerome E; Stucki, Gerold

2017-06-06

Current health systems are increasingly challenged to meet the needs of a growing number of patients living with chronic and often multiple health conditions. The primary outcome of care, it is argued, is not merely curing disease but also optimizing functioning over a person's life span. According to the World Health Organization, functioning can serve as foundation for a comprehensive picture of health and augment the biomedical perspective with a broader and more comprehensive picture of health as it plays out in people's lives. The crucial importance of information about patient's functioning for a well-performing health system, however, has yet to be sufficiently appreciated. This paper argues that functioning information is fundamental in all components of health systems and enhances the capacity of health systems to optimize patients' health and health-related needs. Beyond making sense of biomedical disease patterns, health systems can profit from using functioning information to improve interprofessional collaboration and achieve cross-cutting disease treatment outcomes. Implications for rehabilitation Functioning is a key health outcome for rehabilitation within health systems. Information on restoring, maintaining, and optimizing human functioning can strengthen health system response to patients' health and rehabilitative needs. Functioning information guides health systems to achieve cross-cutting health outcomes that respond to the needs of the growing number of individuals living with chronic and multiple health conditions. Accounting for individuals functioning helps to overcome fragmentation of care and to improve interprofessional collaboration across settings.

Factors associated with playing football after anterior cruciate ligament reconstruction in female football players.

PubMed

Fältström, A; Hägglund, M; Kvist, J

2016-11-01

This study investigated whether player-related factors (demographic, personality, or psychological factors) or the characteristics of the anterior cruciate ligament (ACL) injury were associated with the return to playing football in females after ACL reconstruction (ACLR). We also compared current knee function, knee related quality of life and readiness to return to sport between females who returned to football and those who had not returned. Females who sustained a primary ACL rupture while playing football and underwent ACLR 6-36 months ago were eligible. Of the 460 contacted, 274 (60%) completed a battery of questionnaires, and 182 were included a median of 18 months (IQR 13) after ACLR. Of these, 94 (52%) returned to football and were currently playing, and 88 (48%) had not returned. Multiple logistic regression analysis identified two factors associated with returning to football: short time between injury and ACLR (0-3 months, OR 5.6; 3-12 months OR 4.7 vs reference group > 12 months) and high motivation. Current players showed higher ratings for current knee function, knee-related quality of life, and psychological readiness to return to sport (P < 0.001). Undergoing ACLR sooner after injury and high motivation to return to sports may impact a player's return to football after ACLR. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Polysilicon-chromium-gold intracellular chips for multi-functional biomedical applications

NASA Astrophysics Data System (ADS)

Patiño, Tania; Soriano, Jorge; Amirthalingam, Ezhil; Durán, Sara; González-Campo, Arántzazu; Duch, Marta; Ibáñez, Elena; Barrios, Leonardo; Plaza, Jose Antonio; Pérez-García, Lluïsa; Nogués, Carme

2016-04-01

The development of micro- and nanosystems for their use in biomedicine is a continuously growing field. One of the major goals of such platforms is to combine multiple functions in a single entity. However, achieving the design of an efficient and safe micro- or nanoplatform has shown to be strongly influenced by its interaction with the biological systems, where particle features or cell types play a critical role. In this work, the feasibility of using multi-material pSi-Cr-Au intracellular chips (MMICCs) for multifunctional applications by characterizing their interactions with two different cell lines, one tumorigenic and one non-tumorigenic, in terms of biocompatibility, internalization and intracellular fate, has been explored. Moreover, the impact of MMICCs on the induction of an inflammatory response has been assessed by evaluating TNFα, IL1b, IL6, and IL10 human inflammatory cytokines secretion by macrophages. Results show that MMICCs are biocompatible and their internalization efficiency is strongly dependent on the cell type. Finally as a proof-of-concept, MMICCs have been dually functionalized with transferrin and pHrodo™ Red, SE to target cancer cells and detect intracellular pH, respectively. In conclusion, MMICCs can be used as multi-functional devices due to their high biocompatibility, non-inflammatory properties and the ability of developing multiple functions.

Polysilicon-chromium-gold intracellular chips for multi-functional biomedical applications.

PubMed

Patiño, Tania; Soriano, Jorge; Amirthalingam, Ezhil; Durán, Sara; González-Campo, Arántzazu; Duch, Marta; Ibáñez, Elena; Barrios, Leonardo; Plaza, Jose Antonio; Pérez-García, Lluïsa; Nogués, Carme

2016-04-28

The development of micro- and nanosystems for their use in biomedicine is a continuously growing field. One of the major goals of such platforms is to combine multiple functions in a single entity. However, achieving the design of an efficient and safe micro- or nanoplatform has shown to be strongly influenced by its interaction with the biological systems, where particle features or cell types play a critical role. In this work, the feasibility of using multi-material pSi-Cr-Au intracellular chips (MMICCs) for multifunctional applications by characterizing their interactions with two different cell lines, one tumorigenic and one non-tumorigenic, in terms of biocompatibility, internalization and intracellular fate, has been explored. Moreover, the impact of MMICCs on the induction of an inflammatory response has been assessed by evaluating TNFα, IL1b, IL6, and IL10 human inflammatory cytokines secretion by macrophages. Results show that MMICCs are biocompatible and their internalization efficiency is strongly dependent on the cell type. Finally as a proof-of-concept, MMICCs have been dually functionalized with transferrin and pHrodo™ Red, SE to target cancer cells and detect intracellular pH, respectively. In conclusion, MMICCs can be used as multi-functional devices due to their high biocompatibility, non-inflammatory properties and the ability of developing multiple functions.

Maintaining Bone Health in Patients With Multiple Myeloma: Survivorship Care Plan of the International Myeloma Foundation Nurse Leadership Board

PubMed Central

Miceli, Teresa S.; Colson, Kathleen; Faiman, Beth M.; Miller, Kena; Tariman, Joseph D.

2014-01-01

About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an essential adjunct to antimyeloma therapy. In addition, the maintenance of bone health in patients with multiple myeloma can significantly improve quality of life. Oncology nurses and other healthcare providers play a central role in the management of bone disease and maintenance throughout the course of treatment. Safe administration of bisphosphonates, promotion of exercise, maintenance of adequate nutrition, vitamin and mineral supplementation, scheduled radiographic examinations, and monitoring of bone complications are among the important functions that oncology nurses and healthcare providers perform in clinical practice. PMID:21816707

Maintaining bone health in patients with multiple myeloma: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

PubMed

Miceli, Teresa S; Colson, Kathleen; Faiman, Beth M; Miller, Kena; Tariman, Joseph D

2011-08-01

About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an essential adjunct to antimyeloma therapy. In addition, the maintenance of bone health in patients with multiple myeloma can significantly improve quality of life. Oncology nurses and other healthcare providers play a central role in the management of bone disease and maintenance throughout the course of treatment. Safe administration of bisphosphonates, promotion of exercise, maintenance of adequate nutrition, vitamin and mineral supplementation, scheduled radiographic examinations, and monitoring of bone complications are among the important functions that oncology nurses and healthcare providers perform in clinical practice.

shinyGISPA: A web application for characterizing phenotype by gene sets using multiple omics data combinations.

PubMed

Dwivedi, Bhakti; Kowalski, Jeanne

2018-01-01

While many methods exist for integrating multi-omics data or defining gene sets, there is no one single tool that defines gene sets based on merging of multiple omics data sets. We present shinyGISPA, an open-source application with a user-friendly web-based interface to define genes according to their similarity in several molecular changes that are driving a disease phenotype. This tool was developed to help facilitate the usability of a previously published method, Gene Integrated Set Profile Analysis (GISPA), among researchers with limited computer-programming skills. The GISPA method allows the identification of multiple gene sets that may play a role in the characterization, clinical application, or functional relevance of a disease phenotype. The tool provides an automated workflow that is highly scalable and adaptable to applications that go beyond genomic data merging analysis. It is available at http://shinygispa.winship.emory.edu/shinyGISPA/.

shinyGISPA: A web application for characterizing phenotype by gene sets using multiple omics data combinations

PubMed Central

Dwivedi, Bhakti

2018-01-01

While many methods exist for integrating multi-omics data or defining gene sets, there is no one single tool that defines gene sets based on merging of multiple omics data sets. We present shinyGISPA, an open-source application with a user-friendly web-based interface to define genes according to their similarity in several molecular changes that are driving a disease phenotype. This tool was developed to help facilitate the usability of a previously published method, Gene Integrated Set Profile Analysis (GISPA), among researchers with limited computer-programming skills. The GISPA method allows the identification of multiple gene sets that may play a role in the characterization, clinical application, or functional relevance of a disease phenotype. The tool provides an automated workflow that is highly scalable and adaptable to applications that go beyond genomic data merging analysis. It is available at http://shinygispa.winship.emory.edu/shinyGISPA/. PMID:29415010

Multi-scale modularity and motif distributional effect in metabolic networks.

PubMed

Gao, Shang; Chen, Alan; Rahmani, Ali; Zeng, Jia; Tan, Mehmet; Alhajj, Reda; Rokne, Jon; Demetrick, Douglas; Wei, Xiaohui

2016-01-01

Metabolism is a set of fundamental processes that play important roles in a plethora of biological and medical contexts. It is understood that the topological information of reconstructed metabolic networks, such as modular organization, has crucial implications on biological functions. Recent interpretations of modularity in network settings provide a view of multiple network partitions induced by different resolution parameters. Here we ask the question: How do multiple network partitions affect the organization of metabolic networks? Since network motifs are often interpreted as the super families of evolved units, we further investigate their impact under multiple network partitions and investigate how the distribution of network motifs influences the organization of metabolic networks. We studied Homo sapiens, Saccharomyces cerevisiae and Escherichia coli metabolic networks; we analyzed the relationship between different community structures and motif distribution patterns. Further, we quantified the degree to which motifs participate in the modular organization of metabolic networks.

A conserved tryptophan within the WRDPLVDID domain of yeast Pah1 phosphatidate phosphatase is required for its in vivo function in lipid metabolism.

PubMed

Park, Yeonhee; Han, Gil-Soo; Carman, George M

2017-12-01

PAH1 -encoded phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to produce diacylglycerol at the endoplasmic reticulum membrane, plays a major role in controlling the utilization of phosphatidate for the synthesis of triacylglycerol or membrane phospholipids. The conserved N-LIP and haloacid dehalogenase-like domains of Pah1 are required for phosphatidate phosphatase activity and the in vivo function of the enzyme. Its non-conserved regions, which are located between the conserved domains and at the C terminus, contain sites for phosphorylation by multiple protein kinases. Truncation analyses of the non-conserved regions showed that they are not essential for the catalytic activity of Pah1 and its physiological functions ( e.g. triacylglycerol synthesis). This analysis also revealed that the C-terminal region contains a previously unrecognized WRDPLVDID domain (residues 637-645) that is conserved in yeast, mice, and humans. The deletion of this domain had no effect on the catalytic activity of Pah1 but caused the loss of its in vivo function. Site-specific mutational analyses of the conserved residues within WRDPLVDID indicated that Trp-637 plays a crucial role in Pah1 function. This work also demonstrated that the catalytic activity of Pah1 is required but is not sufficient for its in vivo functions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

PubMed

Jetten, Anton M

2018-05-19

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

FMRI hypoactivation during verbal learning and memory in former high school football players with multiple concussions.

PubMed

Terry, Douglas P; Adams, T Eric; Ferrara, Michael S; Miller, L Stephen

2015-06-01

Multiple concussions before the age of 18 may be associated with late-life memory deficits. This study examined neural activation associated with verbal encoding and memory retrieval in former athletes ages 40-65 who received at least two concussions (median = 3; range = 2-15) playing high school football and a group of former high school football players with no reported history of concussions matched on age, education, and pre-morbid IQ. Functional magnetic resonance imaging data collected during a modified verbal paired associates paradigm indicated that those with concussive histories had hypoactivation in left hemispheric language regions, including the inferior/middle frontal gyri and angular gyrus compared with controls. However, concussive history was not associated with worse memory functioning on neuropsychological tests or worse behavioral performance during the paradigm, suggesting that multiple early-life concussions may be associated with subtle changes in the verbal encoding system that limits one from accessing higher-order semantic networks, but this difference does not translate into measurable cognitive performance deficits. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The rational parameterization theorem for multisite post-translational modification systems.

PubMed

Thomson, Matthew; Gunawardena, Jeremy

2009-12-21

Post-translational modification of proteins plays a central role in cellular regulation but its study has been hampered by the exponential increase in substrate modification forms ("modforms") with increasing numbers of sites. We consider here biochemical networks arising from post-translational modification under mass-action kinetics, allowing for multiple substrates, having different types of modification (phosphorylation, methylation, acetylation, etc.) on multiple sites, acted upon by multiple forward and reverse enzymes (in total number L), using general enzymatic mechanisms. These assumptions are substantially more general than in previous studies. We show that the steady-state modform concentrations constitute an algebraic variety that can be parameterized by rational functions of the L free enzyme concentrations, with coefficients which are rational functions of the rate constants. The parameterization allows steady states to be calculated by solving L algebraic equations, a dramatic reduction compared to simulating an exponentially large number of differential equations. This complexity collapse enables analysis in contexts that were previously intractable and leads to biological predictions that we review. Our results lay a foundation for the systems biology of post-translational modification and suggest deeper connections between biochemical networks and algebraic geometry.

Long-lasting behavioral effects in neonatal mice with multiple exposures to ketamine-xylazine anesthesia

PubMed Central

Huang, Lianyan; Hayes, Scott; Yang, Guang

2016-01-01

Anesthetic agents are often administered in the neonatal period, a time of rapid brain development and synaptogenesis. Mounting evidence suggests that anesthetics can disrupt neurocognitive development, particularly in cases of multiple or prolonged anesthetic exposure. Previous studies have shown that administering multiple doses of ketamine-xylazine (KX) anesthesia to neonatal mice can induce long-term changes to synaptic plasticity in the cortex, but the effect on neurocognitive function remains unclear. In this study, we exposed neonatal mice to single dose and multiple doses of KX anesthesia in the neonatal period (postnatal days 7, 9, 11), and conducted a series of behavioral tests in young adulthood (1 month of age). Mice receiving multiple doses of KX anesthesia showed deficits in novel object recognition, sociability, preference for social novelty and contextual fear response, but no effect on auditory-cued fear response. Single dose of KX anesthesia had no effect on these behaviors except for contextual fear response. We also observed that multiple exposures to KX anesthesia were associated with decreased CaMKII phosphorylation, which is known to play a role in synapse development and long-term potentiation, likely contributing to learning impairment. PMID:27622724

ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

PubMed Central

Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

2012-01-01

The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414

STARD6 on steroids: solution structure, multiple timescale backbone dynamics and ligand binding mechanism

NASA Astrophysics Data System (ADS)

Létourneau, Danny; Bédard, Mikaël; Cabana, Jérôme; Lefebvre, Andrée; Lehoux, Jean-Guy; Lavigne, Pierre

2016-06-01

START domain proteins are conserved α/β helix-grip fold that play a role in the non-vesicular and intracellular transport of lipids and sterols. The mechanism and conformational changes permitting the entry of the ligand into their buried binding sites is not well understood. Moreover, their functions and the identification of cognate ligands is still an active area of research. Here, we report the solution structure of STARD6 and the characterization of its backbone dynamics on multiple time-scales through 15N spin-relaxation and amide exchange studies. We reveal for the first time the presence of concerted fluctuations in the Ω1 loop and the C-terminal helix on the microsecond-millisecond time-scale that allows for the opening of the binding site and ligand entry. We also report that STARD6 binds specifically testosterone. Our work represents a milestone for the study of ligand binding mechanism by other START domains and the elucidation of the biological function of STARD6.

Prediction of rat protein subcellular localization with pseudo amino acid composition based on multiple sequential features.

PubMed

Shi, Ruijia; Xu, Cunshuan

2011-06-01

The study of rat proteins is an indispensable task in experimental medicine and drug development. The function of a rat protein is closely related to its subcellular location. Based on the above concept, we construct the benchmark rat proteins dataset and develop a combined approach for predicting the subcellular localization of rat proteins. From protein primary sequence, the multiple sequential features are obtained by using of discrete Fourier analysis, position conservation scoring function and increment of diversity, and these sequential features are selected as input parameters of the support vector machine. By the jackknife test, the overall success rate of prediction is 95.6% on the rat proteins dataset. Our method are performed on the apoptosis proteins dataset and the Gram-negative bacterial proteins dataset with the jackknife test, the overall success rates are 89.9% and 96.4%, respectively. The above results indicate that our proposed method is quite promising and may play a complementary role to the existing predictors in this area.

Resilience to Meet the Challenge of Addiction

PubMed Central

Alim, Tanja N.; Lawson, William B.; Feder, Adriana; Iacoviello, Brian M.; Saxena, Shireen; Bailey, Christopher R.; Greene, Allison M.; Neumeister, Alexander

2012-01-01

Acute and chronic stress–related mechanisms play an important role in the development of addiction and its chronic, relapsing nature. Multisystem adaptations in brain, body, behavioral, and social function may contribute to a dysregulated physiological state that is maintained beyond the homeostatic range. In addition, chronic abuse of substances leads to an altered set point across multiple systems. Resilience can be defined as the absence of psychopathology despite exposure to high stress and reflects a person’s ability to cope successfully in the face of adversity, demonstrating adaptive psychological and physiological stress responses. The study of resilience can be approached by examining interindividual stress responsibility at multiple phenotypic levels, ranging from psychological differences in the way people cope with stress to differences in neurochemical or neural circuitry function. The ultimate goal of such research is the development of strategies and interventions to enhance resilience and coping in the face of stress and prevent the onset of addiction problems or relapse. PMID:23584116

Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity

PubMed Central

Herrero-Martin, Griselda; Puri, Sapna; Taketo, Makoto Mark; Rojas, Anabel; Hebrok, Matthias; Cano, David A.

2016-01-01

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries. PMID:27736991

On the estimate of deviations of partial sums of a multiple Fourier-Walsh series of the form S2j,⋯,2jf (x ) of a function in the metric L1(Qk)

NASA Astrophysics Data System (ADS)

Igenberlina, Alua; Matin, Dauren; Turgumbayev, Mendybay

2017-09-01

In this paper, deviations of the partial sums of a multiple Fourier-Walsh series of a function in the metric L1(Qk) on a dyadic group are investigated. This estimate plays an important role in the study of equivalent normalizations in this space by means of a difference, oscillation, and best approximation by polynomials in the Walsh system. The classical classical Besov space and its equivalent normalizations are set forth in the well-known monographs of Nikolsky S.M., Besov O.V., Ilyin V.P., Triebel H.; in the works of Kazakh scientists such as Amanov T.I., Mynbaev K.T., Otelbaev M.O., Smailov E.S.. The Besov spaces on the dyadic group and the Vilenkin groups in the one-dimensional case are considered in works by Ombe H., Bloom Walter R, Fournier J., Onneweer C.W., Weyi S., Jun Tateoka.

Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms.

PubMed Central

Zhao, Xiangshan; Gan, Lixia; Pan, Haiyun; Kan, Donghui; Majeski, Michael; Adam, Stephen A; Unterman, Terry G

2004-01-01

FOXO1, a Forkhead transcription factor, is an important target of insulin and growth factor action. Phosphorylation of Thr-24, Ser-256 and Ser-319 promotes nuclear exclusion of FOXO1, yet the mechanisms regulating nuclear/cytoplasmic shuttling of FOXO1 are poorly understood. Previous studies have identified an NLS (nuclear localization signal) in the C-terminal basic region of the DBD (DNA-binding domain), and a leucine-rich, leptomycin-B sensitive NES (nuclear export signal) located further downstream. Here, we find that other elements in the DBD also contribute to nuclear localization, and that multiple mechanisms contribute to nuclear exclusion of FOXO1. Phosphorylation of Ser-319 and a cluster of nearby residues (Ser-322, Ser-325 and Ser-329) functions co-operatively with the nearby NES to promote nuclear exclusion. The N-terminal region of FOXO1 (amino acids 1-149) also is sufficient to promote nuclear exclusion, and does so through multiple mechanisms. Amino acids 1-50 are sufficient to promote nuclear exclusion of green fluorescent protein fusion proteins, and the phosphorylation of Thr-24 is required for this effect. A leucine-rich, leptomycin B-sensitive export signal is also present nearby. Phosphorylated FOXO1 binds 14-3-3 proteins, and co-precipitation studies with tagged proteins indicate that 14-3-3 binding involves co-operative interactions with both Thr-24 and Ser-256. Ser-256 is located in the C-terminal region of the DBD, where 14-3-3 proteins may interfere both with DNA-binding and with nuclear-localization functions. Together, these studies demonstrate that multiple elements contribute to nuclear/cytoplasmic shuttling of FOXO1, and that phosphorylation and 14-3-3 binding regulate the cellular distribution and function of FOXO1 through multiple mechanisms. The presence of these redundant mechanisms supports the concept that the regulation of FOXO1 function plays a critical role in insulin and growth factor action. PMID:14664696

Juvenile social experience and differential age-related changes in the dendritic morphologies of subareas of the prefrontal cortex in rats.

PubMed

Himmler, Brett T; Mychasiuk, Richelle; Nakahashi, Ayuno; Himmler, Stephanie M; Pellis, Sergio M; Kolb, Bryan

2018-04-01

Juvenile social interactions have been shown to influence the dendritic complexity of neurons in the prefrontal cortex (PFC). In particular, social play induces pruning of the cells in the medial prefrontal cortex (mPFC), whereas interacting with multiple partners, whether those interactions involve play or not, increases the complexity of cells in the orbital frontal cortex (OFC). Previous studies suggest that these changes differ in their stability during adulthood. In the present study, rats were reared in groups of either four (quads) or two (pairs) and the brains of the rats from each rearing condition were then harvested at 60 days (i.e., shortly after sexual maturity) and 100 days (i.e., fully adult). The rats housed with multiple partners had more complex neurons of the OFC at 60 days and this complexity declined to a comparable level to that of pair housed rats by 100 days. In contrast, the play-induced changes of the mPFC remained similar at both ages. These findings suggest that the changes in the PFC induced by different social experiences in the juvenile period differ in how long they are maintained in adulthood. Differences in the functions regulated by the OFC and the mPFC are considered with regard to these differences in the stability of juvenile-induced neural changes. © 2017 Wiley Periodicals, Inc.

microRNA regulation of T lymphocyte immunity: modulation of molecular networks responsible for T cell activation, differentiation and development

PubMed Central

Podshivalova, Katie; Salomon, Daniel R.

2014-01-01

MicroRNAs (miRNA) are a class of small non-coding RNAs that constitute an essential and evolutionarily conserved mechanism for post-transcriptional gene regulation. Multiple miRNAs have been described to play key roles in T lymphocyte development, differentiation and function. In this review we highlight the current literature regarding the differential expression of miRNAs in various models of mouse and human T cell biology and emphasize mechanistic understandings of miRNA regulation of thymocyte development, T cell activation, and differentiation into effector and memory subsets. We describe the participation of miRNAs in complex regulatory circuits shaping T cell proteomes in a context-dependent manner. It is striking that some miRNAs regulate multiple processes, while others only appear in limited functional contexts. It is also evident that the expression and function of specific miRNAs can differ between mouse and human systems. Ultimately, it is not always correct to simplify the complex events of T cell biology into a model driven by only one or two master regulator miRNAs. In reality, T cell activation and differentiation involves the expression of multiple miRNAs with many mRNA targets and thus, the true extent of miRNA regulation of T cell biology is likely far more vast than currently appreciated. PMID:24099302

Role of Multiple Representations in Physics Problem Solving

ERIC Educational Resources Information Center

Maries, Alexandru

2013-01-01

This thesis explores the role of multiple representations in introductory physics students' problem solving performance through several investigations. Representations can help students focus on the conceptual aspects of physics and play a major role in effective problem solving. Diagrammatic representations can play a particularly important role…

Exploration of Multi-State Conformational Dynamics and Underlying Global Functional Landscape of Maltose Binding Protein

PubMed Central

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2012-01-01

An increasing number of biological machines have been revealed to have more than two macroscopic states. Quantifying the underlying multiple-basin functional landscape is essential for understanding their functions. However, the present models seem to be insufficient to describe such multiple-state systems. To meet this challenge, we have developed a coarse grained triple-basin structure-based model with implicit ligand. Based on our model, the constructed functional landscape is sufficiently sampled by the brute-force molecular dynamics simulation. We explored maltose-binding protein (MBP) which undergoes large-scale domain motion between open, apo-closed (partially closed) and holo-closed (fully closed) states responding to ligand binding. We revealed an underlying mechanism whereby major induced fit and minor population shift pathways co-exist by quantitative flux analysis. We found that the hinge regions play an important role in the functional dynamics as well as that increases in its flexibility promote population shifts. This finding provides a theoretical explanation of the mechanistic discrepancies in PBP protein family. We also found a functional “backtracking” behavior that favors conformational change. We further explored the underlying folding landscape in response to ligand binding. Consistent with earlier experimental findings, the presence of ligand increases the cooperativity and stability of MBP. This work provides the first study to explore the folding dynamics and functional dynamics under the same theoretical framework using our triple-basin functional model. PMID:22532792

HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development

PubMed Central

Rutkowski, Timothy P.; Kohn, Anat; Sharma, Deepika; Ren, Yinshi; Mirando, Anthony J.

2016-01-01

ABSTRACT RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognized Notch signaling targets that mediate specific aspects of Notch function during development. However, whether particular HES and HEY factors play any role(s) in the processes during cartilage development is unknown. Here, for the first time, we have developed unique in vivo genetic models and in vitro approaches demonstrating that the RBPjκ-dependent Notch targets HES1 and HES5 suppress chondrogenesis and promote the onset of chondrocyte hypertrophy. HES1 and HES5 might have some overlapping function in these processes, although only HES5 directly regulates Sox9 transcription to coordinate cartilage development. HEY1 and HEYL play no discernable role in regulating chondrogenesis or chondrocyte hypertrophy, whereas none of the HES or HEY factors appear to mediate Notch regulation of cartilage matrix catabolism. This work identifies important candidates that might function as downstream mediators of Notch signaling both during normal skeletal development and in Notch-related skeletal disorders. PMID:27160681

Biology of the cell cycle inhibitor p21(CDKN1A): molecular mechanisms and relevance in chemical toxicology.

PubMed

Dutto, Ilaria; Tillhon, Micol; Cazzalini, Ornella; Stivala, Lucia A; Prosperi, Ennio

2015-02-01

The cell cycle inhibitor p21(CDKN1A) is a protein playing multiple roles not only in the DNA damage response, but also in many cellular processes during unperturbed cell growth. The main, well-known function of p21 is to arrest cell cycle progression by inhibiting the activity of cyclin-dependent kinases. In addition, p21 is involved in the regulation of transcription, apoptosis, DNA repair, as well as cell motility. However, p21 appears to a have a dual-face behavior because, in addition to its tumor suppressor functions, it may act as an oncogene, depending on the cell type and on the cellular localization. As a biomarker of the cell response to different toxic stimuli, p21 expression and functions have been analyzed in an impressive number of studies investigating the activity of several types of chemicals, in order to determine their possible harmful effects on human cells. Here, we review these studies in order to highlight the different roles p21 may play in the cell response to chemical exposure and to better evaluate the information provided by this biomarker.

Interaction between basal ganglia and limbic circuits in learning and memory processes.

PubMed

Calabresi, Paolo; Picconi, Barbara; Tozzi, Alessandro; Ghiglieri, Veronica

2016-01-01

Hippocampus and striatum play distinctive roles in memory processes since declarative and non-declarative memory systems may act independently. However, hippocampus and striatum can also be engaged to function in parallel as part of a dynamic system to integrate previous experience and adjust behavioral responses. In these structures the formation, storage, and retrieval of memory require a synaptic mechanism that is able to integrate multiple signals and to translate them into persistent molecular traces at both the corticostriatal and hippocampal/limbic synapses. The best cellular candidate for this complex synthesis is represented by long-term potentiation (LTP). A common feature of LTP expressed in these two memory systems is the critical requirement of convergence and coincidence of glutamatergic and dopaminergic inputs to the dendritic spines of the neurons expressing this form of synaptic plasticity. In experimental models of Parkinson's disease abnormal accumulation of α-synuclein affects these two memory systems by altering two major synaptic mechanisms underlying cognitive functions in cholinergic striatal neurons, likely implicated in basal ganglia dependent operative memory, and in the CA1 hippocampal region, playing a central function in episodic/declarative memory processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Coenzyme Q plays opposing roles on bacteria/fungi and viruses in Drosophila innate immunity.

PubMed

Cheng, W; Song, C; Anjum, K M; Chen, M; Li, D; Zhou, H; Wang, W; Chen, J

2011-08-01

Coenzyme Q (CoQ or ubiquinone) is a lipid-soluble component of virtually all types of cell membranes and has been shown to play multiple metabolic functions. Several clinical diseases including encephalomyopathy, cerebellar ataxia and isolated myopathy were shown to be associated with CoQ deficiency. However, the role of CoQ in immunity has not been defined. In the present study, we showed that flies defective in CoQ biosynthetic gene coq2 were more susceptible to bacterial and fungal infections, while were more resistant to viruses. We found that Drosophila contained both CoQ9 and CoQ10, and food supplement of CoQ10 could partially rescue the impaired immune functions of coq2 mutants. Surprisingly, wild-type flies fed CoQ10 became more susceptible to viral infection, which suggested that extra caution should be taken when using CoQ10 as a food supplement. We further showed that CoQ was essential for normal induction of anti-microbial peptides and amplification of viruses. Our work determined CoQ content in Drosophila and described its function in immunity for the first time. © 2011 Blackwell Publishing Ltd.

Partners in crime: The role of tandem modules in gene transcription.

PubMed

Sharma, Rajal; Zhou, Ming-Ming

2015-09-01

Histones and their modifications play an important role in the regulation of gene transcription. Numerous modifications, such as acetylation, phosphorylation, methylation, ubiquitination, and SUMOylation, have been described. These modifications almost always co-occur and thereby increase the combinatorial complexity of post-translational modification detection. The domains that recognize these histone modifications often occur in tandem in the context of larger proteins and complexes. The presence of multiple modifications can positively or negatively regulate the binding of these tandem domains, influencing downstream cellular function. Alternatively, these tandem domains can have novel functions from their independent parts. Here we summarize structural and functional information known about major tandem domains and their histone binding properties. An understanding of these interactions is key for the development of epigenetic therapy. © 2015 The Protein Society.

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

PubMed Central

Jeschke, Marc G

2009-01-01

Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury. Studies have evaluated the role and function of the liver during the postburn response and showed that liver integrity and function are essential for survival, and that hepatic acute phase proteins are strong predictors for postburn survival. This review discusses these studies and delineates the pivotal role of the liver in patients following severe thermal injury. PMID:19603107

Exosomes participate in the carcinogenesis and the malignant behavior of gastric cancer.

PubMed

Yan, Yunmeng; Fu, Guangzhen; Ye, Yafei; Ming, Liang

2017-05-01

In order to summarize the role of exosomes in invasion and metastasis in gastric cancer (GC). Exosomes are vesicles of endocytic origin ranging from 30 to 100 nm in size; they are composed of a lipid bilayer and contain DNA, mRNA, miRNA, circular RNA and multiple proteins. Recently, increasing evidence shows that exosomes play a crucial role in the tumorigenesis of GC. In this review, we focus on the latest findings on GC exosomes, mainly summarizing their role in invasion and metastasis in GC. Then, exosomes? potential functions as novel diagnostic and therapeutic biomarkers for GC are briefly discussed. At last, we prospect the clinical application perspective of exosomes in GC. Exosomes play a vital role in gastric cancer carcinogenesis and metastasis.

Genomic and Epigenomic Alterations in Cancer.

PubMed

Chakravarthi, Balabhadrapatruni V S K; Nepal, Saroj; Varambally, Sooryanarayana

2016-07-01

Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Conceptual Understanding of Multiplicative Properties through Endogenous Digital Game Play

ERIC Educational Resources Information Center

Denham, Andre

2012-01-01

This study purposed to determine the effect of an endogenously designed instructional game on conceptual understanding of the associative and distributive properties of multiplication. Additional this study sought to investigate if performance on measures of conceptual understanding taken prior to and after game play could serve as predictors of…

Professional Athletes' Return to Play and Performance After Operative Repair of an Achilles Tendon Rupture.

PubMed

Trofa, David P; Miller, J Chance; Jang, Eugene S; Woode, Denzel R; Greisberg, Justin K; Vosseller, J Turner

2017-10-01

Most Achilles tendon ruptures are sports related. However, few studies have examined and compared the effect of surgical repair for complete ruptures on return to play (RTP), play time, and performance across multiple sports. To examine RTP and performance among professional athletes after Achilles tendon repair and compare pre- versus postoperative functional outcomes of professional athletes from different major leagues in the United States. Cohort study; Level of evidence, 3. National Basketball Association (NBA), National Football League (NFL), Major League Baseball (MLB), and National Hockey League (NHL) athletes who sustained a primary complete Achilles tendon rupture treated surgically between 1989 and 2013 were identified via public injury reports and press releases. Demographic information and performance-related statistics were recorded for 2 seasons before and after surgery and compared with matched controls. Statistical analyses were used to assess differences in recorded metrics. Of 86 athletes screened, 62 met inclusion criteria including 25 NBA, 32 NFL, and 5 MLB players. Nineteen (30.6%) professional athletes with an isolated Achilles tendon rupture treated surgically were unable to return to play. Among athletes who successfully returned to play, game participation averaged 75.4% ( P < .001) and 81.9% ( P = .002) of the total games played the season before injury at 1 and 2 years postoperatively, respectively. Play time was significantly decreased and athletes performed significantly worse compared with preoperative levels at 1 and 2 years after injury ( P < .001). When players were compared with matched controls, an Achilles tendon rupture resulted in fewer games played ( P < .001), decreased play time ( P = .025), and worse performance statistics ( P < .001) at 1 year but not 2 years postoperatively ( P > .05). When individual sports were compared, NBA players were most significantly affected, experiencing significant decreases in games played, play time, and performance. An Achilles tendon rupture is a devastating injury that prevents RTP for 30.6% of professional players. Athletes who do return play in fewer games, have less play time, and perform at a lower level than their preinjury status. However, these functional deficits are seen only at 1 year after surgery compared with matched controls, such that players who return to play can expect to perform at a level commensurate with uninjured controls 2 years postoperatively.

Functional sub-division of the Drosophila genome via chromatin looping: the emerging importance of CP190.

PubMed

Ahanger, Sajad H; Shouche, Yogesh S; Mishra, Rakesh K

2013-01-01

Insulators help in organizing the eukaryotic genomes into physically and functionally autonomous regions through the formation of chromatin loops. Recent findings in Drosophila and vertebrates suggest that insulators anchor multiple loci through long-distance interactions which may be mechanistically linked to insulator function. Important to such processes in Drosophila is CP190, a common co-factor of insulator complexes. CP190 is also known to associate with the nuclear matrix, components of the RNAi machinery, active promoters and borders of the repressive chromatin domains. Although CP190 plays a pivotal role in insulator function in Drosophila, vertebrates lack a probable functional equivalent of CP190 and employ CTCF as the major factor to carry out insulator function/chromatin looping. In this review, we discuss the emerging role of CP190 in tethering genome, specifically in the perspective of insulator function in Drosophila. Future studies aiming genome-wide role of CP190 in chromatin looping is likely to give important insights into the mechanism of genome organization.

Functional sub-division of the Drosophila genome via chromatin looping

PubMed Central

Ahanger, Sajad H.; Shouche, Yogesh S.; Mishra, Rakesh K.

2013-01-01

Insulators help in organizing the eukaryotic genomes into physically and functionally autonomous regions through the formation of chromatin loops. Recent findings in Drosophila and vertebrates suggest that insulators anchor multiple loci through long-distance interactions which may be mechanistically linked to insulator function. Important to such processes in Drosophila is CP190, a common co-factor of insulator complexes. CP190 is also known to associate with the nuclear matrix, components of the RNAi machinery, active promoters and borders of the repressive chromatin domains. Although CP190 plays a pivotal role in insulator function in Drosophila, vertebrates lack a probable functional equivalent of CP190 and employ CTCF as the major factor to carry out insulator function/chromatin looping. In this review, we discuss the emerging role of CP190 in tethering genome, specifically in the perspective of insulator function in Drosophila. Future studies aiming genome-wide role of CP190 in chromatin looping is likely to give important insights into the mechanism of genome organization. PMID:23333867

The roles of the olivocerebellar pathway in motor learning and motor control. A consensus paper

PubMed Central

Lang, Eric J.; Apps, Richard; Bengtsson, Fredrik; Cerminara, Nadia L.; De Zeeuw, Chris I.; Ebner, Timothy J.; Heck, Detlef H.; Jaeger, Dieter; Jörntell, Henrik; Kawato, Mitsuo; Otis, Thomas S.; Ozyildirim, Ozgecan; Popa, Laurentiu S.; Reeves, Alexander M.B.; Schweighofer, Nicolas; Sugihara, Izumi; Xiao, Jianqiang

2016-01-01

For many decades the predominant view in the cerebellar field has been that the olivocerebellar system's primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum, and might also play a role in development. We then consider the potential problems and benefits of its having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, variable complex spike waveform) make it more or less suitable for one or the other of these functions, and why its having a dual role makes sense from an evolutionary perspective. We did not attempt to reach a consensus on the specific role(s) the olivocerebellar system plays in different types of movements, as that will ultimately be determined experimentally; however, collectively, the various contributions highlight the flexibility of the olivocerebellar system, and thereby suggest it has the potential to act in both the motor learning and motor control functions of the cerebellum. PMID:27193702

The Role of Histone Deacetylases in Neurodegenerative Diseases and Small-Molecule Inhibitors as a Potential Therapeutic Approach

NASA Astrophysics Data System (ADS)

Bürli, Roland W.; Thomas, Elizabeth; Beaumont, Vahri

Neurodegenerative disorders are devastating for patients and their social environment. Their etiology is poorly understood and complex. As a result, there is clearly an urgent need for therapeutic agents that slow down disease progress and alleviate symptoms. In this respect, interference with expression and function of multiple gene products at the epigenetic level has offered much promise, and histone deacetylases play a crucial role in these processes. This review presents an overview of the biological pathways in which these enzymes are involved and illustrates the complex network of proteins that governs their activity. An overview of small molecules that interfere with histone deacetylase function is provided.

Non-coding RNAs as regulators of gene expression and epigenetics

PubMed Central

Kaikkonen, Minna U.; Lam, Michael T.Y.; Glass, Christopher K.

2011-01-01

Genome-wide studies have revealed that mammalian genomes are pervasively transcribed. This has led to the identification and isolation of novel classes of non-coding RNAs (ncRNAs) that influence gene expression by a variety of mechanisms. Here we review the characteristics and functions of regulatory ncRNAs in chromatin remodelling and at multiple levels of transcriptional and post-transcriptional regulation. We also describe the potential roles of ncRNAs in vascular biology and in mediating epigenetic modifications that might play roles in cardiovascular disease susceptibility. The emerging recognition of the diverse functions of ncRNAs in regulation of gene expression suggests that they may represent new targets for therapeutic intervention. PMID:21558279

Essential role of grim-led programmed cell death for the establishment of corazonin-producing peptidergic nervous system during embryogenesis and metamorphosis in Drosophila melanogaster.

PubMed

Lee, Gyunghee; Sehgal, Ritika; Wang, Zixing; Nair, Sudershana; Kikuno, Keiko; Chen, Chun-Hong; Hay, Bruce; Park, Jae H

2013-03-15

In Drosophila melanogaster, combinatorial activities of four death genes, head involution defective (hid), reaper (rpr), grim, and sickle (skl), have been known to play crucial roles in the developmentally regulated programmed cell death (PCD) of various tissues. However, different expression patterns of the death genes also suggest distinct functions played by each. During early metamorphosis, a great number of larval neurons unfit for adult life style are removed by PCD. Among them are eight pairs of corazonin-expressing larval peptidergic neurons in the ventral nerve cord (vCrz). To reveal death genes responsible for the PCD of vCrz neurons, we examined extant and recently available mutations as well as RNA interference that disrupt functions of single or multiple death genes. We found grim as a chief proapoptotic gene and skl and rpr as minor ones. The function of grim is also required for PCD of the mitotic sibling cells of the vCrz neuronal precursors (EW3-sib) during embryonic neurogenesis. An intergenic region between grim and rpr, which, it has been suggested, may enhance expression of three death genes in embryonic neuroblasts, appears to play a role for the vCrz PCD, but not for the EW3-sib cell death. The death of vCrz neurons and EW3-sib is triggered by ecdysone and the Notch signaling pathway, respectively, suggesting distinct regulatory mechanisms of grim expression in a cell- and developmental stage-specific manner.

Expression of CD44 3'-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis.

PubMed

Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B

2011-04-01

The non-coding 3'-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3'-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3'-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3'-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3'-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed.

Expression of CD44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis

PubMed Central

Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B.

2011-01-01

The non-coding 3′-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3′-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3′-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3′-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3′-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3′-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed. PMID:21149267

Using time-delay to improve social play skills with peers for children with autism.

PubMed

Liber, Daniella B; Frea, William D; Symon, Jennifer B G

2008-02-01

Interventions that teach social communication and play skills are crucial for the development of children with autism. The time delay procedure is effective in teaching language acquisition, social use of language, discrete behaviors, and chained activities to individuals with autism and developmental delays. In this study, three boys with autism, attending a non-public school, were taught play activities that combined a play sequence with requesting peer assistance, using a graduated time delay procedure. A multiple-baseline across subjects design demonstrated the success of this procedure to teach multiple-step social play sequences. Results indicated an additional gain of an increase in pretend play by one of the participants. Two also demonstrated a generalization of the skills learned through the time delay procedure.

cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation

PubMed Central

2010-01-01

Background Appropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death. Results We present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1. Conclusions We propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast. PMID:21108829

The expanding universe of neurotrophic factors: therapeutic potential in aging and age-associated disorders.

PubMed

Lanni, C; Stanga, S; Racchi, M; Govoni, S

2010-01-01

Multiple molecular, cellular, structural and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively by employing multiple mechanisms in order to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands. Otherwise, they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. An important role in this balancement is played by neurotrophic factors, which are central to many aspects of nervous system function since they regulate the development, maintenance and survival of neurons and neuron-supporting cells such as glia and oligodendrocytes. A vast amount of evidence indicates that alterations in levels of neurotrophic factors or their receptors can lead to neuronal death and contribute to aging as well as to the pathogenesis of diseases of abnormal trophic support (such as neurodegenerative diseases and depression) and diseases of abnormal excitability (such as epilepsy and central pain sensitization). Cellular and molecular mechanisms by which neurotrophic factors may influence cell survival and excitability are also critically examined to provide novel concepts and targets for the treatment of physiological changes bearing detrimental functional alterations and of different diseases affecting the central nervous system during aging.

Taiwanese Married Women's Lived Experience of Zen Meditation

ERIC Educational Resources Information Center

Kang, Hsin-Ru

2014-01-01

Due to the impact of Confucianism on Taiwanese society, Taiwanese married women play multiple family roles including being a daughter-in-law, wife, mother, and working woman. Having to play multiple roles usually brings Taiwanese married women burdens and stress. It is reported that Zen meditation improves people's physical and mental wellbeing.…

Neurocognitive Basis of Racial Ingroup Bias in Empathy.

PubMed

Han, Shihui

2018-05-01

Racial discrimination in social behavior, although disapproved of by many contemporary cultures, has been widely reported. Because empathy plays a key functional role in social behavior, brain imaging researchers have extensively investigated the neurocognitive underpinnings of racial ingroup bias in empathy. This research has revealed consistent evidence for increased neural responses to the perceived pain of same-race compared with other-race individuals in multiple brain regions and across multiple time-windows. Researchers have also examined neurocognitive, sociocultural, and environmental influences on racial ingroup bias in empathic neural responses, as well as explored possible interventions to reduce racial ingroup bias in empathic brain activity. These findings have important implications for understanding racial ingroup favoritism in social behavior and for improving interracial communication. Copyright © 2018 Elsevier Ltd. All rights reserved.

Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes

PubMed Central

Pierson, Elizabeth A.

2010-01-01

Phenazines constitute a large group of nitrogen-containing heterocyclic compounds produced by a diverse range of bacteria. Both natural and synthetic phenazine derivatives are studied due their impacts on bacterial interactions and biotechnological processes. Phenazines serve as electron shuttles to alternate terminal acceptors, modify cellular redox states, act as cell signals that regulate patterns of gene expression, contribute to biofilm formation and architecture, and enhance bacterial survival. Phenazines have diverse effects on eukaryotic hosts and host tissues, including the modification of multiple host cellular responses. In plants, phenazines also may influence growth and elicit induced systemic resistance. Here, we discuss emerging evidence that phenazines play multiple roles for the producing organism and contribute to their behavior and ecological fitness. PMID:20352425

Induction of myeloma-specific cytotoxic T lymphocytes responses by natural killer cells stimulated-dendritic cells in patients with multiple myeloma.

PubMed

Nguyen-Pham, Thanh-Nhan; Im, Chang-Min; Nguyen, Truc-Anh Thi; Lim, Mi-Seon; Hong, Cheol Yi; Kim, Mi-Hyun; Lee, Hyun Ju; Lee, Youn-Kyung; Cho, Duck; Ahn, Jae-Sook; Yang, Deok-Hwan; Kim, Yeo-Kyeoung; Chung, Ik-Joo; Kim, Hyeoung-Joon; Lee, Je-Jung

2011-09-01

The interaction between dendritic cells (DCs) and natural killer (NK) cells plays a key role in inducing DC maturation for subsequent T-cell priming. We investigated to generate potent DCs by stimulated with NK cells to induce myeloma-specific cytotoxic T lymphocytes (CTLs). NK cells-stimulated-DCs exhibited high expression of costimulatory molecules and high production of IL-12p70. These DCs induce high potency of Th1 polarization and exhibit a high ability to generate myeloma-specific CTLs responses. These results suggest that functionally potent DCs can be generated by stimulation with NK cells and may provide an effective source of DC-based immunotherapy in multiple myeloma. Copyright © 2011 Elsevier Ltd. All rights reserved.

Propulsive Reaction Control System Model

NASA Technical Reports Server (NTRS)

Brugarolas, Paul; Phan, Linh H.; Serricchio, Frederick; San Martin, Alejandro M.

2011-01-01

This software models a propulsive reaction control system (RCS) for guidance, navigation, and control simulation purposes. The model includes the drive electronics, the electromechanical valve dynamics, the combustion dynamics, and thrust. This innovation follows the Mars Science Laboratory entry reaction control system design, and has been created to meet the Mars Science Laboratory (MSL) entry, descent, and landing simulation needs. It has been built to be plug-and-play on multiple MSL testbeds [analysis, Monte Carlo, flight software development, hardware-in-the-loop, and ATLO (assembly, test and launch operations) testbeds]. This RCS model is a C language program. It contains two main functions: the RCS electronics model function that models the RCS FPGA (field-programmable-gate-array) processing and commanding of the RCS valve, and the RCS dynamic model function that models the valve and combustion dynamics. In addition, this software provides support functions to initialize the model states, set parameters, access model telemetry, and access calculated thruster forces.

Harnessing glycomics technologies: integrating structure with function for glycan characterization

PubMed Central

Robinson, Luke N.; Artpradit, Charlermchai; Raman, Rahul; Shriver, Zachary H.; Ruchirawat, Mathuros; Sasisekharan, Ram

2013-01-01

Glycans, or complex carbohydrates, are a ubiquitous class of biological molecules which impinge on a variety of physiological processes ranging from signal transduction to tissue development and microbial pathogenesis. In comparison to DNA and proteins, glycans present unique challenges to the study of their structure and function owing to their complex and heterogeneous structures and the dominant role played by multivalency in their sequence-specific biological interactions. Arising from these challenges, there is a need to integrate information from multiple complementary methods to decode structure-function relationships. Focusing on acidic glycans, we describe here key glycomics technologies for characterizing their structural attributes, including linkage, modifications, and topology, as well as for elucidating their role in biological processes. Two cases studies, one involving sialylated branched glycans and the other sulfated glycosaminoglycans, are used to highlight how integration of orthogonal information from diverse datasets enables rapid convergence of glycan characterization for development of robust structure-function relationships. PMID:22522536

Fixation, transient landscape, and diffusion dilemma in stochastic evolutionary game dynamics

NASA Astrophysics Data System (ADS)

Zhou, Da; Qian, Hong

2011-09-01

Agent-based stochastic models for finite populations have recently received much attention in the game theory of evolutionary dynamics. Both the ultimate fixation and the pre-fixation transient behavior are important to a full understanding of the dynamics. In this paper, we study the transient dynamics of the well-mixed Moran process through constructing a landscape function. It is shown that the landscape playing a central theoretical “device” that integrates several lines of inquiries: the stable behavior of the replicator dynamics, the long-time fixation, and continuous diffusion approximation associated with asymptotically large population. Several issues relating to the transient dynamics are discussed: (i) multiple time scales phenomenon associated with intra- and inter-attractoral dynamics; (ii) discontinuous transition in stochastically stationary process akin to Maxwell construction in equilibrium statistical physics; and (iii) the dilemma diffusion approximation facing as a continuous approximation of the discrete evolutionary dynamics. It is found that rare events with exponentially small probabilities, corresponding to the uphill movements and barrier crossing in the landscape with multiple wells that are made possible by strong nonlinear dynamics, plays an important role in understanding the origin of the complexity in evolutionary, nonlinear biological systems.

The Importance of Being Playful.

ERIC Educational Resources Information Center

Bodrova, Elena; Leong, Deborah J.

2003-01-01

Recent research provides evidence of the strong connections between quality of play in preschool years and children's readiness for school instruction. Mature play, characterized by imaginary situations, multiple roles, clearly defined rules, flexible themes, language development, length of play, helps students' cognitive development. (Contains 12…

The presence and significance of polar meibum and tear lipids.

PubMed

Pucker, Andrew D; Haworth, Kristina M

2015-01-01

The ocular tear film is a complex structure composed of a number of elements. While all of these components serve valuable functional and structural roles, the external lipid layer has been a focus because it is known to play a critical role in dry eye. Traditionally, meibomian gland phospholipids have been considered to be the vital amphiphilic molecules needed to create an interphase between the outer nonpolar lipid layer and inner aqueous layers, yet recent work has called this theory into question. The purpose of this review is to clarify the current understanding of the origins, identity, and significance of polar tear lipids. Studies indicate that both phospholipids and ω-hydroxy fatty acids likely play a critical role in tear film stability. Studies also indicate that polar lipids likely originate from multiple sources and that they are integrally involved in ocular surface disease. Additional studies are needed to fully understand the origins and significance of polar tear lipids, because to date only correlational evidence has described their hypothesized origins and functions. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

PubMed Central

O’Connor, Sean Timothy Francis; Lan, Jiaqi; North, Matthew; Loguinov, Alexandre; Zhang, Luoping; Smith, Martyn T.; Gu, April Z.; Vulpe, Chris

2012-01-01

Benzo[a]pyrene (BaP) is a ubiquitous, potent, and complete carcinogen resulting from incomplete organic combustion. BaP can form DNA adducts but other mechanisms may play a role in toxicity. We used a functional toxicology approach in S. cerevisiae to assess the genetic requirements for cellular resistance to BaP. In addition, we examined translational activities of key genes involved in various stress response pathways. We identified multiple genes and processes involved in modulating BaP toxicity in yeast which support DNA damage as a primary mechanism of toxicity, but also identify other potential toxicity pathways. Gene ontology enrichment analysis indicated that DNA damage and repair as well as redox homeostasis and oxidative stress are key processes in cellular response to BaP suggesting a similar mode of action of BaP in yeast and mammals. Interestingly, toxicant export is also implicated as a potential novel modulator of cellular susceptibility. In particular, we identified several transporters with human orthologs (solute carrier family 22) which may play a role in mammalian systems. PMID:23403841

Major Surface Protease of Trypanosomatids: One Size Fits All? ▿

PubMed Central

Yao, Chaoqun

2010-01-01

Major surface protease (MSP or GP63) is the most abundant glycoprotein localized to the plasma membrane of Leishmania promastigotes. MSP plays several important roles in the pathogenesis of leishmaniasis, including but not limited to (i) evasion of complement-mediated lysis, (ii) facilitation of macrophage (Mø) phagocytosis of promastigotes, (iii) interaction with the extracellular matrix, (iv) inhibition of natural killer cellular functions, (v) resistance to antimicrobial peptide killing, (vi) degradation of Mø and fibroblast cytosolic proteins, and (vii) promotion of survival of intracellular amastigotes. MSP homologues have been found in all other trypanosomatids studied to date including heteroxenous members of Trypanosoma cruzi, the extracellular Trypanosoma brucei, unusual intraerythrocytic Endotrypanum spp., phytoparasitic Phytomonas spp., and numerous monoxenous species. These proteins are likely to perform roles different from those described for Leishmania spp. Multiple MSPs in individual cells may play distinct roles at some time points in trypanosomatid life cycles and collaborative or redundant roles at others. The cellular locations and the extracellular release of MSPs are also discussed in connection with MSP functions in leishmanial promastigotes. PMID:19858295

Effects of a computer-based intervention program on the communicative functions of children with autism.

PubMed

Hetzroni, Orit E; Tannous, Juman

2004-04-01

This study investigated the use of computer-based intervention for enhancing communication functions of children with autism. The software program was developed based on daily life activities in the areas of play, food, and hygiene. The following variables were investigated: delayed echolalia, immediate echolalia, irrelevant speech, relevant speech, and communicative initiations. Multiple-baseline design across settings was used to examine the effects of the exposure of five children with autism to activities in a structured and controlled simulated environment on the communication manifested in their natural environment. Results indicated that after exposure to the simulations, all children produced fewer sentences with delayed and irrelevant speech. Most of the children engaged in fewer sentences involving immediate echolalia and increased the number of communication intentions and the amount of relevant speech they produced. Results indicated that after practicing in a controlled and structured setting that provided the children with opportunities to interact in play, food, and hygiene activities, the children were able to transfer their knowledge to the natural classroom environment. Implications and future research directions are discussed.

The case for causal influences of action videogame play upon vision and attention.

PubMed

Kristjánsson, Árni

2013-05-01

Over the past decade, exciting findings have surfaced suggesting that routine action videogame play improves attentional and perceptual skills. Apparently, performance during multiple-object tracking, useful-field-of-view tests, and task switching improves, contrast sensitivity and spatial-resolution thresholds decrease, and the attentional blink and backward masking are lessened by short-term training on action videogames. These are remarkable findings showing promise for the training of attention and the treatment of disorders of attentional function. While the findings are interesting, evidence of causal influences of videogame play is not as strong as is often claimed. In many studies, observers with game play experience and those without are tested. Such studies do not address causality, since preexisting differences are not controlled for. Other studies investigate the training of videogame play, with some evidence of training benefits. Methodological shortcomings and potential confounds limit their impact, however, and they have not always been replicated. No longitudinal studies on videogame training exist, but these may be required to provide conclusive answers about any benefits of videogame training and any interaction with preexisting differences. Suggestions for methodological improvement are made here, including recommendations for longitudinal studies. Such studies may become crucial for the field of attentional training to reach its full potential.

Song practice as a rewarding form of play in songbirds.

PubMed

Riters, Lauren V; Spool, Jeremy A; Merullo, Devin P; Hahn, Allison H

2017-10-12

In adult songbirds, the primary functions of song are mate attraction and territory defense; yet, many songbirds sing at high rates as juveniles and outside these primary contexts as adults. Singing outside primary contexts is critical for song learning and maintenance, and ultimately necessary for breeding success. However, this type of singing (i.e., song "practice") occurs even in the absence of immediate or obvious extrinsic reinforcement; that is, it does not attract mates or repel competitors. Here we review studies that support the hypothesis that song practice is stimulated and maintained by intrinsic reward mechanisms (i.e., that it is associated with a positive affective state). Additionally, we propose that song practice can be considered a rewarding form of play behavior similar to forms of play observed in multiple young animals as they practice sequences of motor events that are used later in primary adult reproductive contexts. This review highlights research suggesting at least partially overlapping roles for neural reward systems in birdsong and mammalian play and evidence that steroid hormones modify these systems to shift animals from periods of intrinsically rewarded motor exploration (i.e., singing in birds and play in mammals) to the use of similar motor patterns in primary reproductive contexts. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploring the Behavioral Patterns of Learners in an Educational Massively Multiple Online Role-Playing Game (MMORPG)

ERIC Educational Resources Information Center

Hou, Huei-Tse

2012-01-01

Massively multiple online role-playing games (MMORPGs) are very popular among students. Educational MMORPGs, however, are very rare, as are studies on gamers' behavioral patterns during such games. The current study is an empirical observation and analysis of the behavioral patterns of 100 gamers participating in an educational MMORPG called…

Dramatic Playing beyond the Theory of Multiple Intelligences

ERIC Educational Resources Information Center

Guss, Faith Gabrielle

2005-01-01

Related to aspects of drama and theatre education, I search beyond the findings about symbolic play set forth by Dr Howard Gardner in "Frames of mind. The theory of multiple intelligences". Despite the inspiration for and solidarity with arts educators that emanate from his theory, I sensed that it did not provide a full picture of the complex…

Sex and Violence: Words at Play in the Shakespeare Classroom

ERIC Educational Resources Information Center

Paquette, Maryellen G.

2007-01-01

Maryellen G. Paquette reveals the excitement and learning that can occur when high school students are presented with multiple opportunities to play. Activities that employ playful language and the whole body allow students to embody, name, and identify with complicated emotions and situations in Shakespeare's plays. In addition, play can be…

Multiple Classes of Immune-Related Proteases Associated with the Cell Death Response in Pepper Plants

PubMed Central

Bae, Chungyun; Kim, Su-min; Lee, Dong Ju; Choi, Doil

2013-01-01

Proteases regulate a large number of biological processes in plants, such as metabolism, physiology, growth, and defense. In this study, we carried out virus-induced gene silencing assays with pepper cDNA clones to elucidate the biological roles of protease superfamilies. A total of 153 representative protease genes from pepper cDNA were selected and cloned into a Tobacco rattle virus-ligation independent cloning vector in a loss-of-function study. Silencing of 61 proteases resulted in altered phenotypes, such as the inhibition of shoot growth, abnormal leaf shape, leaf color change, and lethality. Furthermore, the silencing experiments revealed that multiple proteases play a role in cell death and immune response against avirulent and virulent pathogens. Among these 153 proteases, 34 modulated the hypersensitive cell death response caused by infection with an avirulent pathogen, and 16 proteases affected disease symptom development caused by a virulent pathogen. Specifically, we provide experimental evidence for the roles of multiple protease genes in plant development and immune defense following pathogen infection. With these results, we created a broad sketch of each protease function. This information will provide basic information for further understanding the roles of the protease superfamily in plant growth, development, and defense. PMID:23696830

Technological innovations in tissue removal during rhinologic surgery.

PubMed

Sindwani, Raj; Manz, Ryan

2012-01-01

The modern rhinologist has a wide variety of technological innovations at his/her disposal for the removal of soft tissue and bone during endoscopic surgery. We identified and critically evaluated four leading tissue removal technologies that have impacted, or are poised to impact, rhinological surgery. A literature review was conducted. Technological functions, strengths and limitations of microdebriders, radio frequency ablation, endoscopic drills, and ultrasonic aspirators were explored. The primary drawback of powered instruments continues to be the higher costs associated with their use, and their main advantage is the ability to accomplish multiple functions such as tissue removal, suction, and irrigation, all with one tool. The effective and safe use of any powered instrument requires an intimate understanding of its function, capabilities, and limitations. Powered instrumentation continues to play a significant and evolving role in soft tissue and bone removal during rhinologic surgery.

SPECT/CT in imaging foot and ankle pathology-the demise of other coregistration techniques.

PubMed

Mohan, Hosahalli K; Gnanasegaran, Gopinath; Vijayanathan, Sanjay; Fogelman, Ignac

2010-01-01

Disorders of the ankle and foot are common and given the complex anatomy and function of the foot, they present a significant clinical challenge. Imaging plays a crucial role in the management of these patients, with multiple imaging options available to the clinician. The American College of radiology has set the appropriateness criteria for the use of the available investigating modalities in the management of foot and ankle pathologies. These are broadly classified into anatomical and functional imaging modalities. Recently, single-photon emission computed tomography and/or computed tomography scanners, which can elegantly combine functional and anatomical images have been introduced, promising an exciting and important development. This review describes our clinical experience with single-photon emission computed tomography and/or computed tomography and discusses potential applications of these techniques.

The probability density function (PDF) of Lagrangian Turbulence

NASA Astrophysics Data System (ADS)

Birnir, B.

2012-12-01

The statistical theory of Lagrangian turbulence is derived from the stochastic Navier-Stokes equation. Assuming that the noise in fully-developed turbulence is a generic noise determined by the general theorems in probability, the central limit theorem and the large deviation principle, we are able to formulate and solve the Kolmogorov-Hopf equation for the invariant measure of the stochastic Navier-Stokes equations. The intermittency corrections to the scaling exponents of the structure functions require a multiplicative (multipling the fluid velocity) noise in the stochastic Navier-Stokes equation. We let this multiplicative noise, in the equation, consists of a simple (Poisson) jump process and then show how the Feynmann-Kac formula produces the log-Poissonian processes, found by She and Leveque, Waymire and Dubrulle. These log-Poissonian processes give the intermittency corrections that agree with modern direct Navier-Stokes simulations (DNS) and experiments. The probability density function (PDF) plays a key role when direct Navier-Stokes simulations or experimental results are compared to theory. The statistical theory of turbulence is determined, including the scaling of the structure functions of turbulence, by the invariant measure of the Navier-Stokes equation and the PDFs for the various statistics (one-point, two-point, N-point) can be obtained by taking the trace of the corresponding invariant measures. Hopf derived in 1952 a functional equation for the characteristic function (Fourier transform) of the invariant measure. In distinction to the nonlinear Navier-Stokes equation, this is a linear functional differential equation. The PDFs obtained from the invariant measures for the velocity differences (two-point statistics) are shown to be the four parameter generalized hyperbolic distributions, found by Barndorff-Nilsen. These PDF have heavy tails and a convex peak at the origin. A suitable projection of the Kolmogorov-Hopf equations is the differential equation determining the generalized hyperbolic distributions. Then we compare these PDFs with DNS results and experimental data.

Alternative Splicing of sept9a and sept9b in Zebrafish Produces Multiple mRNA Transcripts Expressed Throughout Development

PubMed Central

Hannibal, Mark C.; Kimelman, David

2010-01-01

Background Septins are involved in a number of cellular processes including cytokinesis and organization of the cytoskeleton. Alterations in human septin-9 (SEPT9) levels have been linked to multiple cancers, whereas mutations in SEPT9 cause the episodic neuropathy, hereditary neuralgic amyotrophy (HNA). Despite its important function in human health, the in vivo role of SEPT9 is unknown. Methodology/Principal Findings Here we utilize zebrafish to study the role of SEPT9 in early development. We show that zebrafish possess two genes, sept9a and sept9b that, like humans, express multiple transcripts. Knockdown or overexpression of sept9a transcripts results in specific developmental alterations including circulation defects and aberrant epidermal development. Conclusions/Significance Our work demonstrates that sept9 plays an important role in zebrafish development, and establishes zebrafish as a valuable model organism for the study of SEPT9. PMID:20502708

Multiple-Localization and Hub Proteins

PubMed Central

Ota, Motonori; Gonja, Hideki; Koike, Ryotaro; Fukuchi, Satoshi

2016-01-01

Protein-protein interactions are fundamental for all biological phenomena, and protein-protein interaction networks provide a global view of the interactions. The hub proteins, with many interaction partners, play vital roles in the networks. We investigated the subcellular localizations of proteins in the human network, and found that the ones localized in multiple subcellular compartments, especially the nucleus/cytoplasm proteins (NCP), the cytoplasm/cell membrane proteins (CMP), and the nucleus/cytoplasm/cell membrane proteins (NCMP), tend to be hubs. Examinations of keywords suggested that among NCP, those related to post-translational modifications and transcription functions are the major contributors to the large number of interactions. These types of proteins are characterized by a multi-domain architecture and intrinsic disorder. A survey of the typical hub proteins with prominent numbers of interaction partners in the type revealed that most are either transcription factors or co-regulators involved in signaling pathways. They translocate from the cytoplasm to the nucleus, triggered by the phosphorylation and/or ubiquitination of intrinsically disordered regions. Among CMP and NCMP, the contributors to the numerous interactions are related to either kinase or ubiquitin ligase activity. Many of them reside on the cytoplasmic side of the cell membrane, and act as the upstream regulators of signaling pathways. Overall, these hub proteins function to transfer external signals to the nucleus, through the cell membrane and the cytoplasm. Our analysis suggests that multiple-localization is a crucial concept to characterize groups of hub proteins and their biological functions in cellular information processing. PMID:27285823

Encoding Time in Feedforward Trajectories of a Recurrent Neural Network Model.

PubMed

Hardy, N F; Buonomano, Dean V

2018-02-01

Brain activity evolves through time, creating trajectories of activity that underlie sensorimotor processing, behavior, and learning and memory. Therefore, understanding the temporal nature of neural dynamics is essential to understanding brain function and behavior. In vivo studies have demonstrated that sequential transient activation of neurons can encode time. However, it remains unclear whether these patterns emerge from feedforward network architectures or from recurrent networks and, furthermore, what role network structure plays in timing. We address these issues using a recurrent neural network (RNN) model with distinct populations of excitatory and inhibitory units. Consistent with experimental data, a single RNN could autonomously produce multiple functionally feedforward trajectories, thus potentially encoding multiple timed motor patterns lasting up to several seconds. Importantly, the model accounted for Weber's law, a hallmark of timing behavior. Analysis of network connectivity revealed that efficiency-a measure of network interconnectedness-decreased as the number of stored trajectories increased. Additionally, the balance of excitation (E) and inhibition (I) shifted toward excitation during each unit's activation time, generating the prediction that observed sequential activity relies on dynamic control of the E/I balance. Our results establish for the first time that the same RNN can generate multiple functionally feedforward patterns of activity as a result of dynamic shifts in the E/I balance imposed by the connectome of the RNN. We conclude that recurrent network architectures account for sequential neural activity, as well as for a fundamental signature of timing behavior: Weber's law.

The Use of Play Expansions to Increase the Diversity and Complexity of Object Play in Young Children with Disabilities

ERIC Educational Resources Information Center

Frey, Jennifer R.; Kaiser, Ann P.

2011-01-01

The purpose of this study was to determine if an intervention consisting of contingently imitating play, modeling expansions of play actions, and describing play actions increased the diversity of object play in young children with disabilities. The multicomponent intervention was introduced in a multiple-probe design across three young children…

Nuclear localization of metabolic enzymes in immunity and metastasis.

PubMed

He, Yuchen; Gao, Menghui; Cao, Yiqu; Tang, Haosheng; Liu, Shuang; Tao, Yongguang

2017-12-01

Metabolism is essential to all living organisms that provide cells with energy, regulators, building blocks, enzyme cofactors and signaling molecules, and is in tune with nutritional conditions and the function of cells to make the appropriate developmental decisions or maintain homeostasis. As a fundamental biological process, metabolism state affects the production of multiple metabolites and the activation of various enzymes that participate in regulating gene expression, cell apoptosis, cancer progression and immunoreactions. Previous studies generally focus on the function played by the metabolic enzymes in the cytoplasm and mitochondrion. In this review, we conclude the role of them in the nucleus and their implications for cancer progression, immunity and metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Roles for Hedgehog signaling in adult organ homeostasis and repair

PubMed Central

Petrova, Ralitsa; Joyner, Alexandra L.

2014-01-01

The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner. PMID:25183867

Distribution and function of voltage-gated sodium channels in the nervous system.

PubMed

Wang, Jun; Ou, Shao-Wu; Wang, Yun-Jie

2017-11-02

Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases. In this study, the latest research findings regarding the structure, type, distribution, and function of VGSCs in the nervous system and their relationship to neurological diseases, such as epilepsy, neuropathic pain, brain tumors, neural trauma, and multiple sclerosis, are reviewed in detail.

The Roles of Protein Tyrosine Phosphatases in Hepatocellular Carcinoma

PubMed Central

Huang, Yide; Zhang, Yafei; Ge, Lilin

2018-01-01

The protein tyrosine phosphatase (PTP) family is involved in multiple cellular functions and plays an important role in various pathological and physiological processes. In many chronic diseases, for example cancer, PTP is a potential therapeutic target for cancer treatment. In the last two decades, dozens of PTP inhibitors which specifically target individual PTP molecules were developed as therapeutic agents. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and is the second most lethal cancer worldwide due to a lack of effective therapies. Recent studies have unveiled both oncogenic and tumor suppressive functions of PTP in HCC. Here, we review the current knowledge on the involvement of PTP in HCC and further discuss the possibility of targeting PTP in HCC. PMID:29558404

BIOLOGICAL AND BIOPHYSICAL PROPERTIES OF VASCULAR CONNEXIN CHANNELS

PubMed Central

Johnstone, Scott; Isakson, Brant; Locke, Darren

2010-01-01

Intercellular channels formed by connexin proteins play a pivotal role in the direct movement of ions and larger cytoplasmic solutes between vascular endothelial cells, between vascular smooth muscle cells, and between endothelial and smooth muscle cells. Multiple genetic and epigenetic factors modulate connexin expression levels and/or channel function, including cell type-independent and cell type-specific transcription factors, posttranslational modification and localized membrane targeting. Additionally, differences in protein-protein interactions, including those between connexins, significantly contribute to both vascular homeostasis and disease progression. The biophysical properties of the connexin channels identified in the vasculature, those formed by Cx37, Cx40, Cx43 and/or Cx45 proteins, are discussed in this review in the physiological and pathophysiological context of vessel function. PMID:19815177

Pharmacology of Antisense Drugs.

PubMed

Bennett, C Frank; Baker, Brenda F; Pham, Nguyen; Swayze, Eric; Geary, Richard S

2017-01-06

Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and have become an established platform technology for drug discovery. There are multiple molecular mechanisms by which antisense oligonucleotides can be used to modulate RNAs in cells, including promoting the degradation of the targeted RNA or modulating RNA function without degradation. Antisense drugs utilizing various antisense mechanisms are demonstrating therapeutic potential for the treatment of a broad variety of diseases. This review focuses on some of the advances that have taken place in translating antisense technology from the bench to the clinic.

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

Gifford, Brendan Joel; Kilina, Svetlana; Htoon, Han

Recent spectroscopic studies have revealed the appearance of multiple low-energy peaks in the fluorescence of single-walled carbon nanotubes (SWCNTs) upon their covalent functionalization by aryl groups. The photophysical nature of these low energy optical bands is of significant interest in the quest to understand their appearance and to achieve their precise control via chemical modification of SWCNTs. This theoretical study explains the specific energy dependence of emission features introduced in chemically functionalized (6,5) SWCNTs with aryl bromides at different conformations and in various dielectric media. Calculations using density functional theory (DFT) and time dependent DFT (TD-DFT) show that the specificmore » isomer geometry—the relative position of functional groups on the carbon-ring of the nanotube—is critical for controlling the energies and intensities of optical transitions introduced by functionalization, while the dielectric environment and the chemical composition of functional groups play less significant roles. Furthermore, the predominant effects on optical properties as a result of functionalization conformation are rationalized by exciton localization on the surface of the SWCNT near the dopant sp3-defect but not onto the functional group itself.« less

Unique roles of glucagon and glucagon-like peptides: Parallels in understanding the functions of adipokinetic hormones in stress responses in insects.

PubMed

Bednářová, Andrea; Kodrík, Dalibor; Krishnan, Natraj

2013-01-01

Glucagon is conventionally regarded as a hormone, counter regulatory in function to insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. Glucagon performs this function by increasing hepatic glucose output to the blood by stimulating glycogenolysis and gluconeogenesis in response to starvation. Additionally it plays a homeostatic role by decreasing glycogenesis and glycolysis in tandem to try and maintain optimal glucose levels. To perform this action, it also increases energy expenditure which is contrary to what one would expect and has actions which are unique and not entirely in agreement with its role in protection from hypoglycemia. Interestingly, glucagon-like peptides (GLP-1 and GLP-2) from the major fragment of proglucagon (in non-mammalian vertebrates, as well as in mammals) may also modulate response to stress in addition to their other physiological actions. These unique modes of action occur in response to psychological, metabolic and other stress situations and mirror the role of adipokinetic hormones (AKHs) in insects which perform a similar function. The findings on the anti-stress roles of glucagon and glucagon-like peptides in mammalian and non-mammalian vertebrates may throw light on the multiple stress responsive mechanisms which operate in a concerted manner under regulation by AKH in insects thus functioning as a stress responsive hormone while also maintaining organismal homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

A Software Defined Radio Based Airplane Communication Navigation Simulation System

NASA Astrophysics Data System (ADS)

He, L.; Zhong, H. T.; Song, D.

2018-01-01

Radio communication and navigation system plays important role in ensuring the safety of civil airplane in flight. Function and performance should be tested before these systems are installed on-board. Conventionally, a set of transmitter and receiver are needed for each system, thus all the equipment occupy a lot of space and are high cost. In this paper, software defined radio technology is applied to design a common hardware communication and navigation ground simulation system, which can host multiple airplane systems with different operating frequency, such as HF, VHF, VOR, ILS, ADF, etc. We use a broadband analog frontend hardware platform, universal software radio peripheral (USRP), to transmit/receive signal of different frequency band. Software is compiled by LabVIEW on computer, which interfaces with USRP through Ethernet, and is responsible for communication and navigation signal processing and system control. An integrated testing system is established to perform functional test and performance verification of the simulation signal, which demonstrate the feasibility of our design. The system is a low-cost and common hardware platform for multiple airplane systems, which provide helpful reference for integrated avionics design.

Ligand-guided optimization of CXCR4 homology models for virtual screening using a multiple chemotype approach

NASA Astrophysics Data System (ADS)

Neves, Marco A. C.; Simões, Sérgio; Sá e Melo, M. Luisa

2010-12-01

CXCR4 is a G-protein coupled receptor for CXCL12 that plays an important role in human immunodeficiency virus infection, cancer growth and metastasization, immune cell trafficking and WHIM syndrome. In the absence of an X-ray crystal structure, theoretical modeling of the CXCR4 receptor remains an important tool for structure-function analysis and to guide the discovery of new antagonists with potential clinical use. In this study, the combination of experimental data and molecular modeling approaches allowed the development of optimized ligand-receptor models useful for elucidation of the molecular determinants of small molecule binding and functional antagonism. The ligand-guided homology modeling approach used in this study explicitly re-shaped the CXCR4 binding pocket in order to improve discrimination between known CXCR4 antagonists and random decoys. Refinement based on multiple test-sets with small compounds from single chemotypes provided the best early enrichment performance. These results provide an important tool for structure-based drug design and virtual ligand screening of new CXCR4 antagonists.

Alkaline Phosphatase, an Unconventional Immune Protein.

PubMed

Rader, Bethany A

2017-01-01

Recent years have seen an increase in the number of studies focusing on alkaline phosphatases (APs), revealing an expanding complexity of function of these enzymes. Of the four human AP (hAP) proteins, most is known about tissue non-specific AP (TNAP) and intestinal AP (IAP). This review highlights current understanding of TNAP and IAP in relation to human health and disease. TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer's disease. IAP regulates fatty acid absorption and has been implicated in the regulation of diet-induced obesity and metabolic syndrome. IAP and TNAP can dephosphorylate bacterial-derived lipopolysaccharide, and IAP has been identified as a potential regulator of the composition of the intestinal microbiome, an evolutionarily conserved function. Endogenous and recombinant bovine APs and recombinant hAPs are currently being explored for their potential as pharmacological agents to treat AP-associated diseases and mitigate multiple sources of inflammation. Continued research on these versatile proteins will undoubtedly provide insight into human pathophysiology, biochemistry, and the human holobiont.

Specific role of impaired glucose metabolism and diabetes mellitus in endothelial progenitor cell characteristics and function.

PubMed

Yiu, Kai-Hang; Tse, Hung-Fat

2014-06-01

The disease burden of diabetes mellitus (DM) and its associated cardiovascular complications represent a growing and major global health problem. Recent studies suggest that circulating exogenous endothelial progenitor cells (EPCs) play an important role in endothelial repair and neovascularization at sites of injury or ischemia. Both experimental and clinical studies have demonstrated that hyperglycemia related to DM can induce alterations to EPCs. The reduction and dysfunction of EPCs related to DM correlate with the occurrence and severity of microvascular and macrovascular complications, suggesting a close mechanistic link between EPC dysfunction and impaired vascular function/repair in DM. These alterations to EPCs, likely mediated by multiple pathophysiological mechanisms, including inflammation, oxidative stress, and alterations in Akt and the nitric oxide pathway, affect EPCs at multiple stages: differentiation and mobilization in the bone marrow, trafficking and survival in the circulation, and homing and neovascularization. Several different therapeutic approaches have consequently been proposed to reverse the reduction and dysfunction of EPCs in DM and may represent a novel therapeutic approach to prevent and treat DM-related cardiovascular complications. © 2014 American Heart Association, Inc.

One Thing Leads to Another: Evolution, Play, and Technology

ERIC Educational Resources Information Center

Narey, Teresa A.

2010-01-01

Traditionally, we think of play as children's work, and this work is often considered trivial and meaningless. However, when the definition of play is explored, its multiple meanings encourage us to understand play as an important vehicle for the propulsion of society. Play has become a hot topic in households and classrooms and for political…

Delegation control of multiple unmanned systems

NASA Astrophysics Data System (ADS)

Flaherty, Susan R.; Shively, Robert J.

2010-04-01

Maturing technologies and complex payloads coupled with a future objective to reduce the logistics burden of current unmanned aerial systems (UAS) operations require a change to the 2-crew employment paradigm. Increased automation and operator supervisory control of unmanned systems have been advocated to meet the objective of reducing the crew requirements, while managing future technologies. Specifically, a delegation control employment strategy has resulted in reduced workload and higher situation awareness for single operators controlling multiple unmanned systems in empirical studies1,2. Delegation control is characterized by the ability for an operator to call a single "play" that initiates prescribed default actions for each vehicle and associated sensor related to a common mission goal. Based upon the effectiveness of delegation control in simulation, the U.S. Army Aeroflightdynamics Directorate (AFDD) developed a Delegation Control (DelCon) operator interface with voice recognition implementation for play selection, real-time play modification, and play status with automation transparency to enable single operator control of multiple unmanned systems in flight. AFDD successfully demonstrated delegation control in a Troops-in-Contact mission scenario at Ft. Ord in 2009. This summary showcases the effort as a beneficial advance in single operator control of multiple UAS.

Cytosolic glyceraldehyde-3-phosphate dehydrogenases play crucial roles in controlling cold-induced sweetening and apical dominance of potato (Solanum tuberosum L.) tubers.

PubMed

Liu, Tengfei; Fang, Hui; Liu, Jun; Reid, Stephen; Hou, Juan; Zhou, Tingting; Tian, Zhendong; Song, Botao; Xie, Conghua

2017-12-01

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an important enzyme that functions in producing energy and supplying intermediates for cellular metabolism. Recent researches indicate that GAPDHs have multiple functions beside glycolysis. However, little information is available for functions of GAPDHs in potato. Here, we identified 4 putative cytosolic GAPDH genes in potato genome and demonstrated that the StGAPC1, StGAPC2, and StGAPC3, which are constitutively expressed in potato tissues and cold inducible in tubers, encode active cytosolic GAPDHs. Cosuppression of these 3 GAPC genes resulted in low tuber GAPDH activity, consequently the accumulation of reducing sugars in cold stored tubers by altering the tuber metabolite pool sizes favoring the sucrose pathway. Furthermore, GAPCs-silenced tubers exhibited a loss of apical dominance dependent on cell death of tuber apical bud meristem (TAB-meristem). It was also confirmed that StGAPC1, StGAPC2, and StGAPC3 interacted with the autophagy-related protein 3 (ATG3), implying that the occurrence of cell death in TAB-meristem could be induced by ATG3 associated events. Collectively, the present research evidences first that the GAPC genes play crucial roles in diverse physiological and developmental processes in potato tubers. © 2017 John Wiley & Sons Ltd.

Transcriptional Profiling Identifies Functional Interactions of TGFβ and PPARβ/δ Signaling

PubMed Central

Kaddatz, Kerstin; Adhikary, Till; Finkernagel, Florian; Meissner, Wolfgang; Müller-Brüsselbach, Sabine; Müller, Rolf

2010-01-01

Peroxisome proliferator-activated receptors (PPARs) not only play a key role in regulating metabolic pathways but also modulate inflammatory processes, pointing to a functional interaction between PPAR and cytokine signaling pathways. In this study, we show by genome-wide transcriptional profiling that PPARβ/δ and transforming growth factor-β (TGFβ) pathways functionally interact in human myofibroblasts and that a subset of these genes is cooperatively activated by TGFβ and PPARβ/δ. Using the angiopoietin-like 4 (ANGPTL4) gene as a model, we demonstrate that two enhancer regions cooperate to mediate the observed synergistic response. A TGFβ-responsive enhancer located ∼8 kb upstream of the transcriptional start site is regulated by a mechanism involving SMAD3, ETS1, RUNX, and AP-1 transcription factors that interact with multiple contiguous binding sites. A second enhancer (PPAR-E) consisting of three juxtaposed PPAR response elements is located in the third intron ∼3.5 kb downstream of the transcriptional start site. The PPAR-E is strongly activated by all three PPAR subtypes, with a novel type of PPAR response element motif playing a central role. Although the PPAR-E is not regulated by TGFβ, it interacts with SMAD3, ETS1, RUNX2, and AP-1 in vivo, providing a possible mechanistic explanation for the observed synergism. PMID:20595396

Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina

PubMed Central

Irie, Shoichi; Sanuki, Rikako; Muranishi, Yuki; Kato, Kimiko; Chaya, Taro

2015-01-01

The Rax homeobox gene plays essential roles in multiple processes of vertebrate retina development. Many vertebrate species possess Rax and Rax2 genes, and different functions have been suggested. In contrast, mice contain a single Rax gene, and its functional roles in late retinal development are still unclear. To clarify mouse Rax function in postnatal photoreceptor development and maintenance, we generated conditional knockout mice in which Rax in maturing or mature photoreceptor cells was inactivated by tamoxifen treatment (Rax iCKO mice). When Rax was inactivated in postnatal Rax iCKO mice, developing photoreceptor cells showed a significant decrease in the level of the expression of rod and cone photoreceptor genes and mature adult photoreceptors exhibited a specific decrease in cone cell numbers. In luciferase assays, we found that Rax and Crx cooperatively transactivate Rhodopsin and cone opsin promoters and that an optimum Rax expression level to transactivate photoreceptor gene expression exists. Furthermore, Rax and Crx colocalized in maturing photoreceptor cells, and their coimmunoprecipitation was observed in cultured cells. Taken together, these results suggest that Rax plays essential roles in the maturation of both cones and rods and in the survival of cones by regulating photoreceptor gene expression with Crx in the postnatal mouse retina. PMID:25986607

Electrophysiology and Beyond: Multiple roles of Na+ channel β subunits in development and disease

PubMed Central

Patino, Gustavo A.; Isom, Lori L.

2010-01-01

Voltage-gated Na+ channel (VGSC) β subunits are not “auxiliary.” These multifunctional molecules not only modulate Na+ current (INa), but also function as cell adhesion molecules (CAMs) – playing roles in aggregation, migration, invasion, neurite outgrowth, and axonal fasciculation. β subunits are integral members of VGSC signaling complexes at nodes of Ranvier, axon initial segments, and cardiac intercalated disks, regulating action potential propagation through critical intermolecular and cell-cell communication events. At least in vitro, many β subunit cell adhesive functions occur both in the presence and absence of pore-forming VGSC α subunits, and in vivo β subunits are expressed in excitable as well as non-excitable cells, thus β subunits may play important functional roles on their own, in the absence of α subunits. VGSC β1 subunits are essential for life and appear to be especially important during brain development. Mutations in β subunit genes result in a variety of human neurological and cardiovascular diseases. Moreover, some cancer cells exhibit alterations in β subunit expression during metastasis. In short, these proteins, originally thought of as merely accessory to α subunits, are critical players in their own right in human health and disease. Here we discuss the role of VGSC β subunits in the nervous system. PMID:20600605

Stress Physiology in Infancy and Early Childhood: Cortisol Flexibility, Attunement and Coordination.

PubMed

Atkinson, L; Jamieson, B; Khoury, J; Ludmer, J; Gonzalez, A

2016-08-01

Research on stress physiology in infancy has assumed increasing importance due to its lifelong implications. In this review, we focus on measurement of hypothalamic-pituitary-adrenal (HPA) function, in particular, and on complementary autonomic processes. We suggest that the measure of HPA function has been overly exclusive, focusing on individual reactivity to single, pragmatically selected laboratory challenges. We advocate use of multiple, strategically chosen challenges and within-subject designs. By administering one challenge that typically does not provoke reactivity and another that does, it is possible to represent allostatic load in terms of "flexibility," the capacity to titrate response to challenge. We also recommend assessing infant reactivity in the context of the primary caregiver's physiological function. Infant-mother "attunement" is central to developmental psychology, permeating diverse developmental domains with varied consequences. A review of adrenocortical attunement suggests that attunement is a reliable process, manifest across varied populations. However, attunement appears stronger in the context of more highly stressful circumstances, such that administration of multiple, selected challenges may help evaluate the degree to which individuals titrate attunement to challenge and determine the correlates of this differential attunement. Finally, we advocate studying the "coordination" of HPA function with other aspects of stress physiology and variation in the degree of this coordination. The use of multiple stressors is important here because each stress system is differentially sensitive to different types of challenge. Therefore, use of single stressors in between-subject designs impedes full recognition of the role played by each system. Overall, we recommend measure of flexibility, attunement, and coordination in the context of multiple challenges to capture allostasis in environmental and physiological context. The simultaneous use of such inclusive and integrative metrics may yield more reliable findings than has hitherto been the case. The interrelation of these metrics can be understood in the context of the adaptive calibration model.. © 2016 British Society for Neuroendocrinology.

Essential role of grim-led programmed cell death for the establishment of corazonin-producing peptidergic nervous system during embryogenesis and metamorphosis in Drosophila melanogaster

PubMed Central

Lee, Gyunghee; Sehgal, Ritika; Wang, Zixing; Nair, Sudershana; Kikuno, Keiko; Chen, Chun-Hong; Hay, Bruce; Park, Jae H.

2013-01-01

Summary In Drosophila melanogaster, combinatorial activities of four death genes, head involution defective (hid), reaper (rpr), grim, and sickle (skl), have been known to play crucial roles in the developmentally regulated programmed cell death (PCD) of various tissues. However, different expression patterns of the death genes also suggest distinct functions played by each. During early metamorphosis, a great number of larval neurons unfit for adult life style are removed by PCD. Among them are eight pairs of corazonin-expressing larval peptidergic neurons in the ventral nerve cord (vCrz). To reveal death genes responsible for the PCD of vCrz neurons, we examined extant and recently available mutations as well as RNA interference that disrupt functions of single or multiple death genes. We found grim as a chief proapoptotic gene and skl and rpr as minor ones. The function of grim is also required for PCD of the mitotic sibling cells of the vCrz neuronal precursors (EW3-sib) during embryonic neurogenesis. An intergenic region between grim and rpr, which, it has been suggested, may enhance expression of three death genes in embryonic neuroblasts, appears to play a role for the vCrz PCD, but not for the EW3-sib cell death. The death of vCrz neurons and EW3-sib is triggered by ecdysone and the Notch signaling pathway, respectively, suggesting distinct regulatory mechanisms of grim expression in a cell- and developmental stage-specific manner. PMID:23519152

Roles of mTOR Signaling in Brain Development.

PubMed

Lee, Da Yong

2015-09-01

mTOR is a serine/threonine kinase composed of multiple protein components. Intracellular signaling of mTOR complexes is involved in many of physiological functions including cell survival, proliferation and differentiation through the regulation of protein synthesis in multiple cell types. During brain development, mTOR-mediated signaling pathway plays a crucial role in the process of neuronal and glial differentiation and the maintenance of the stemness of neural stem cells. The abnormalities in the activity of mTOR and its downstream signaling molecules in neural stem cells result in severe defects of brain developmental processes causing a significant number of brain disorders, such as pediatric brain tumors, autism, seizure, learning disability and mental retardation. Understanding the implication of mTOR activity in neural stem cells would be able to provide an important clue in the development of future brain developmental disorder therapies.

MicroRNA-20a is essential for normal embryogenesis by targeting vsx1 mRNA in fish

PubMed Central

Sun, Lei; Li, Heng; Xu, Xiaofeng; Xiao, Guanxiu; Luo, Chen

2015-01-01

MicroRNAs are major post-transcriptional regulators of gene expression and have essential roles in diverse developmental processes. In vertebrates, some regulatory genes play different roles at different developmental stages. These genes are initially transcribed in a wide embryonic region but restricted within distinct cell types at subsequent stages during development. Therefore, post-transcriptional regulation is required for the transition from one developmental stage to the next and the establishment of different cell identities. However, the regulation of many multiple functional genes at post-transcription level during development remains unknown. Here we show that miR-20a can target the mRNA of vsx1, a multiple functional gene, at the 3′-UTR and inhibit protein expression in both goldfish and zebrafish. The expression of miR-20a is initiated ubiquitously at late gastrula stage and exhibits a tissue-specific pattern in the developing retina. Inhibition of vsx1 3′-UTR mediated protein expression occurs when and where miR-20a is expressed. Decoying miR-20a resulted in severely impaired head, eye and trunk formation in association with excessive generation of vsx1 marked neurons in the spinal cord and defects of somites in the mesoderm region. These results demonstrate that miR-20a is essential for normal embryogenesis by restricting Vsx1 expression in goldfish and zebrafish, and that post-transcriptional regulation is an essential mechanism for Vsx1 playing different roles in diverse developmental processes. PMID:25833418

Endolysosomal Cation Channels and Cancer-A Link with Great Potential.

PubMed

Grimm, Christian; Bartel, Karin; Vollmar, Angelika M; Biel, Martin

2018-01-05

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells.

Endolysosomal Cation Channels and Cancer—A Link with Great Potential

PubMed Central

Grimm, Christian; Bartel, Karin; Vollmar, Angelika M.; Biel, Martin

2018-01-01

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells. PMID:29303993

Uridine Nucleoside Thiation: Gas-Phase Structures and Energetics

NASA Astrophysics Data System (ADS)

Hamlow, Lucas; Lee, Justin; Rodgers, M. T.; Berden, Giel; Oomens, Jos

2016-06-01

The naturally occurring thiated uridine nucleosides, 4-thiouridine (s4Urd) and 2-thiouridine (s2Urd), play important roles in the function and analysis of a variety of RNAs. 2-Thiouridine and its C5 modified analogues are commonly found in tRNAs and are believed to play an important role in codon recognition possibly due to their different structure, which has been shown by NMR to be predominantly C3'-endo. 2-Thiouridine may also play an important role in facilitating nonenzymatic RNA replication and transcription. 4-Thiouridine is a commonly used photoactivatable crosslinker that is often used to study RNA-RNA and RNA-protein cross-linking behavior. Differences in the base pairing between uracil and 4-thiouracil with adenine and guanine are an important factor in their role as a cross linker. The photoactivity of s4Urd may also aid in preventing near-UV lethality in cells. An understanding of their intrinsic structure in the gas-phase may help further elucidate the roles these modified nucleosides play in the regulation of RNAs. In this work, infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of s2Urd and s4Urd were collected in the IR fingerprint region. Structural information is determined by comparison with theoretical linear IR spectra generated from density functional theory calculations using molecular modeling to generate low-energy candidate structures. Present results are compared with analogous results for the protonated forms of uridine and 2'-deoxyuridine as well as solution phase NMR data and crystal structures.

Playing it cool: Characterizing social play, bout termination, and candidate play signals of juvenile and infant Tibetan macaques (Macaca thibetana).

PubMed

Wright, Kaitlin R; Mayhew, Jessica A; Sheeran, Lori K; Funkhouser, Jake A; Wagner, Ronald S; Sun, Li-Xing; Li, Jin-Hua

2018-07-18

Play behaviors and signals during playful interactions with juvenile conspecifics are important for both the social and cognitive development of young animals. The social organization of a species can also influence juvenile social play. We examined the relationships among play behaviors, candidate play signals, and play bout termination in Tibetan macaques (Macaca thibetana) during juvenile and infant social play to characterize the species play style. As Tibetan macaques are despotic and live in groups with strict linear dominance hierarchies and infrequent reconciliation, we predicted that play would be at risk of misinterpretation by both the individuals engaged in the play bout and by those watching, possibly leading to injury of the players. Animals living in such societies might need to frequently and clearly signal playful intent to play partners and other group members to avoid aggressive outcomes. We gathered video data on 21 individually-identified juvenile and infant macaques (one month to five years of age) from the Valley of the Wild Monkeys, Mt. Huangshan, China. We used all-occurrence sampling to record play behaviors and candidate play signals based on an ethogram. We predicted that play groups would use multiple candidate play signals in a variety of contexts and in association with the number of audience members in proximity to the players and play bout length. In the 283 playful interactions we scored, juvenile and infant macaques used multiple body and facial candidate play signals. Our data showed that juvenile and infant Tibetan macaques use a versatile repertoire of play behaviors and signals to sustain play.

Protection by dimethyl fumarate against diabetic cardiomyopathy in type 1 diabetic mice likely via activation of nuclear factor erythroid-2 related factor 2.

PubMed

Hu, Xinyue; Rajesh, Mohanraj; Zhang, Jian; Zhou, Shanshan; Wang, Shudong; Sun, Jian; Tan, Yi; Zheng, Yang; Cai, Lu

2018-05-01

Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months. Cardiac functions were determined using echocardiography. Oxidative stress, pro-inflammatory cytokines and pro-fibrotic markers were determined with commercially available kits, real-time quantitative PCR or western blot techniques. DCM was characterized by diminished cardiac function, accompanied by oxidative stress and enhanced expression of pro-inflammatory cytokines. Diabetic cardiac tissue exhibited marked fibrosis, revealed by extracellular matrix deposition as determined by Sirius red staining of the myocardial tissues. Furthermore, Nrf2 and its downstream effectors were repressed in diabetic myocardium. On the contrary, diabetic animals treated with DMF exhibited blunted oxidative stress, inflammation, fibrosis and this correlated with Nrf2 activation. Our findings suggest that DMF could potentially thwart diabetes-induced myocardial tissue injury, likely via activation of Nrf2 function, providing firm impetus for future repurposing of DMF in the management of DCM. Copyright © 2018 Elsevier B.V. All rights reserved.

Testing Associations of Plant Functional Diversity with Carbon and Nitrogen Storage along a Restoration Gradient of Sandy Grassland

PubMed Central

Zuo, Xiaoan; Zhou, Xin; Lv, Peng; Zhao, Xueyong; Zhang, Jing; Wang, Shaokun; Yue, Xiyuan

2016-01-01

The trait-based approach shows that ecosystem function is strongly affected by plant functional diversity as reflected by the traits of the most abundant species (community-weighted mean, CWM) and functional dispersion (FDis). Effects of CWM and FDis individually support the biomass ratio hypothesis and the niche complementarity hypothesis. However, there is little empirical evidence on the relative roles of CWM traits and FDis in explaining the carbon (C) and nitrogen (N) storage in grassland ecosystems. We measured plant functional traits in the 34 most abundant species across 24 sites along a restoration gradient of sandy grassland (mobile dune, semi-fixed dune, fixed dune, and grassland) in Horqin Sand Land, northern China. Thereafter, we calculated the CWM traits, the functional divergence of each single trait (FDvar) and the trait dispersion of multiple traits (FDis). We also measured the C and N storage in plant, litter, root, and soil. Using a stepwise multiple regression analysis, we further assessed which of the functional diversity components best explained C and N storage in the sandy grassland restoration. We found consistent links between C or N storage and leaf traits related to plant resource use strategy. However, the CWM of plant height was retained as an important predictor of C and N storage in plant, litter, soil, and total ecosystem in the final multiple models. CWMs of specific leaf area and plant height best predicted soil C and N storage and total ecosystem N storage. FDis was one of good predictors of litter C and N storage as well as total ecosystem C storage. These results suggest that ecosystem C and N pools in the sandy grassland restoration are primarily associated with the traits of the most abundant species in communities, thereby supporting the biomass ratio hypothesis. The positive associations of FDis with C storage in litter and total ecosystem provide evidence to support the niche complementarity hypothesis. Both functional traits of dominant species and traits’ dispersion in plant communities could contribute to explaining total ecosystem C storage. Thus, single- and multi-trait indices of functional composition play a crucial role in predicting C storage in sandy grasslands. PMID:26925089

Comprehensive Analysis of Interaction Networks of Telomerase Reverse Transcriptase with Multiple Bioinformatic Approaches: Deep Mining the Potential Functions of Telomere and Telomerase.

PubMed

Hou, Chunyu; Wang, Fei; Liu, Xuewen; Chang, Guangming; Wang, Feng; Geng, Xin

2017-08-01

Telomerase reverse transcriptase (TERT) is the protein component of telomerase complex. Evidence has accumulated showing that the nontelomeric functions of TERT are independent of telomere elongation. However, the mechanisms governing the interaction between TERT and its target genes are not clearly revealed. The biological functions of TERT are not fully elucidated and have thus far been underestimated. To further explore these functions, we investigated TERT interaction networks using multiple bioinformatic databases, including BioGRID, STRING, DAVID, GeneCards, GeneMANIA, PANTHER, miRWalk, mirTarBase, miRNet, miRDB, and TargetScan. In addition, network diagrams were built using Cytoscape software. As competing endogenous RNAs (ceRNAs) are endogenous transcripts that compete for the binding of microRNAs (miRNAs) by using shared miRNA recognition elements, they are involved in creating widespread regulatory networks. Therefore, the ceRNA regulatory networks of TERT were also investigated in this study. Interestingly, we found that the three genes PABPC1, SLC7A11, and TP53 were present in both TERT interaction networks and ceRNAs target genes. It was predicted that TERT might play nontelomeric roles in the generation or development of some rare diseases, such as Rift Valley fever and dyscalculia. Thus, our data will help to decipher the interaction networks of TERT and reveal the unknown functions of telomerase in cancer and aging-related diseases.

Teaching Generalized Pretend Play and Related Behaviors to Young Children with Disabilities

ERIC Educational Resources Information Center

Barton, Erin E.

2015-01-01

Children with disabilities play less often and demonstrate fewer varied pretend play behaviors than children with typical development. A multiple-probe design was used to examine the relation between teachers' use of the system of least prompts and contingent imitation and the acquisition, maintenance, and generalization of pretend play and…

Increasing social interaction using prelinguistic milieu teaching with nonverbal school-age children with autism.

PubMed

Franco, Jessica H; Davis, Barbara L; Davis, John L

2013-08-01

Children with autism display marked deficits in initiating and maintaining social interaction. Intervention using play routines can create a framework for developing and maintaining social interaction between these children and their communication partners. Six nonverbal 5- to 8-year-olds with autism were taught to engage in social interaction within salient play routines. Prelinguistic milieu teaching (PMT) techniques were used to teach the children to communicate intentionally during these routines. Intervention focused on the children's social interaction with an adult. The effects of intervention were evaluated using a multiple baseline design across participants. At study onset, the participants demonstrated few consistent interaction with others. With intervention, all of the children improved their ability to sustain social interactions, as evidenced by an increase in the number of communicative interactions during play routines. Participants also increased their overall rate of initiated intentional communication. Development of intentional prelinguistic communication within salient social routines creates opportunities for an adult to teach social and communication skills to young school-age children with autism who function at a nonverbal level.

Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism.

PubMed

Shi, Yuguang; Cheng, Dong

2009-07-01

Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications.

The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast

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

Tsukamoto, Yuta; Katayama, Chisako; Shinohara, Miki

Highlights: •Multiple functions of Rab5 GTPase in fission yeast were found. •Roles of Rab5 in fission yeast were discussed. •Relation between Rab5 and actin cytoskeleton were discussed. -- Abstract: Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our datamore » strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions.« less

Neuronal Lipid Metabolism: Multiple Pathways Driving Functional Outcomes in Health and Disease

PubMed Central

Tracey, Timothy J.; Steyn, Frederik J.; Wolvetang, Ernst J.; Ngo, Shyuan T.

2018-01-01

Lipids are a fundamental class of organic molecules implicated in a wide range of biological processes related to their structural diversity, and based on this can be broadly classified into five categories; fatty acids, triacylglycerols (TAGs), phospholipids, sterol lipids and sphingolipids. Different lipid classes play major roles in neuronal cell populations; they can be used as energy substrates, act as building blocks for cellular structural machinery, serve as bioactive molecules, or a combination of each. In amyotrophic lateral sclerosis (ALS), dysfunctions in lipid metabolism and function have been identified as potential drivers of pathogenesis. In particular, aberrant lipid metabolism is proposed to underlie denervation of neuromuscular junctions, mitochondrial dysfunction, excitotoxicity, impaired neuronal transport, cytoskeletal defects, inflammation and reduced neurotransmitter release. Here we review current knowledge of the roles of lipid metabolism and function in the CNS and discuss how modulating these pathways may offer novel therapeutic options for treating ALS. PMID:29410613

Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

PubMed Central

Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

2016-01-01

Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

The nonreceptor protein tyrosine phosphatase corkscrew functions in multiple receptor tyrosine kinase pathways in Drosophila.

PubMed

Perkins, L A; Johnson, M R; Melnick, M B; Perrimon, N

1996-11-25

Corkscrew (csw) encodes a nonreceptor protein tyrosine phosphatase (PTPase) that has been implicated in signaling from the Torso receptor tyrosine kinase (RTK). csw mutations, unlike tor mutations, are associated with zygotic lethality, indicating that Csw plays additional roles during development. We have conducted a detailed phenotypic analysis of csw mutations to identify these additional functions of Csw. Our results indicate that Csw operates positively downstream of other Drosophila RTKs such as the Drosophila epidermal growth factor receptor (DER), the fibroblast growth factor receptor (Breathless), and likely other RTKs. This model is substantiated by specific dosage interactions between csw and DER. It is proposed that Csw is part of the evolutionarily conserved "signaling cassette" that operates downstream of all RTKs. In support of this hypothesis, we demonstrate that SHP-2, a vertebrate PTPase similar to Csw and previously implicated in RTK signaling, encodes the functional vertebrate homologue of Csw.

In Australia: Multiple Intelligences in Multiple Settings.

ERIC Educational Resources Information Center

Vialle, Wilma

1997-01-01

In Australia, Gardner's multiple-intelligences theory has strongly influenced primary, preschool, and special education. A survey of 30 schools revealed that teachers use two basic approaches: teaching to, and teaching through, multiple intelligences. The first approach might develop children's music skills via playing an instrument. The second…

Excessive expression of miR-27 impairs Treg-mediated immunological tolerance

PubMed Central

Cruz, Leilani O.; Hashemifar, Somaye Sadat; Wu, Cheng-Jang; Cho, Sunglim; Nguyen, Duc T.; Lin, Ling-Li; Khan, Aly Azeem

2017-01-01

MicroRNAs (miRs) are tightly regulated in the immune system, and aberrant expression of miRs often results in hematopoietic malignancies and autoimmune diseases. Previously, it was suggested that elevated levels of miR-27 in T cells isolated from patients with multiple sclerosis facilitate disease progression by inhibiting Th2 immunity and promoting pathogenic Th1 responses. Here we have demonstrated that, although mice with T cell–specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology, these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous manner. Rather, dysregulation of Th1 responses and autoimmunity resulted from a perturbed Treg compartment. Excessive miR-27 expression in murine T cells severely impaired Treg differentiation. Moreover, Tregs with exaggerated miR-27–mediated gene regulation exhibited diminished homeostasis and suppressor function in vivo. Mechanistically, we determined that miR-27 represses several known as well as previously uncharacterized targets that play critical roles in controlling multiple aspects of Treg biology. Collectively, our data show that miR-27 functions as a key regulator in Treg development and function and suggest that proper regulation of miR-27 is pivotal to safeguarding Treg-mediated immunological tolerance. PMID:28067667

The effect of pelvic floor muscle training alone or in combination with electrostimulation in the treatment of sexual dysfunction in women with multiple sclerosis.

PubMed

Lúcio, A C; D'Ancona, C A L; Lopes, M H B M; Perissinotto, M C; Damasceno, B P

2014-11-01

Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS) patients and pelvic floor muscles (PFMs) play an important role in the sexual function of these patients. The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS. Thirty MS women were randomly allocated to one of three groups: pelvic floor muscle training (PFMT) with electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS) (Group III). Assessments, before and after the treatment, included: PFM function, PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and the Female Sexual Function Index (FSFI) questionnaire. After treatment, all groups showed improvements in all domains of the PERFECT scheme. PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II. All groups improved in arousal, lubrication, satisfaction and total score domains of the FSFI questionnaire. This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD. © The Author(s), 2014.

On an image reconstruction method for ECT

NASA Astrophysics Data System (ADS)

Sasamoto, Akira; Suzuki, Takayuki; Nishimura, Yoshihiro

2007-04-01

An image by Eddy Current Testing(ECT) is a blurred image to original flaw shape. In order to reconstruct fine flaw image, a new image reconstruction method has been proposed. This method is based on an assumption that a very simple relationship between measured data and source were described by a convolution of response function and flaw shape. This assumption leads to a simple inverse analysis method with deconvolution.In this method, Point Spread Function (PSF) and Line Spread Function(LSF) play a key role in deconvolution processing. This study proposes a simple data processing to determine PSF and LSF from ECT data of machined hole and line flaw. In order to verify its validity, ECT data for SUS316 plate(200x200x10mm) with artificial machined hole and notch flaw had been acquired by differential coil type sensors(produced by ZETEC Inc). Those data were analyzed by the proposed method. The proposed method restored sharp discrete multiple hole image from interfered data by multiple holes. Also the estimated width of line flaw has been much improved compared with original experimental data. Although proposed inverse analysis strategy is simple and easy to implement, its validity to holes and line flaw have been shown by many results that much finer image than original image have been reconstructed.

Development of hydrogels for regenerative engineering.

PubMed

Guan, Xiaofei; Avci-Adali, Meltem; Alarçin, Emine; Cheng, Hao; Kashaf, Sara Saheb; Li, Yuxiao; Chawla, Aditya; Jang, Hae Lin; Khademhosseini, Ali

2017-05-01

The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano- and micro-technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell-matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano- and micro-technologies. In addition, current hydrogel-based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiple functional units in the preattentive segmentation of speech in Japanese: evidence from word illusions.

PubMed

Nakamura, Miyoko; Kolinsky, Régine

2014-12-01

We explored the functional units of speech segmentation in Japanese using dichotic presentation and a detection task requiring no intentional sublexical analysis. Indeed, illusory perception of a target word might result from preattentive migration of phonemes, morae, or syllables from one ear to the other. In Experiment I, Japanese listeners detected targets presented in hiragana and/or kanji. Phoneme migrations did occur, suggesting that orthography-independent sublexical constituents play some role in segmentation. However, syllable and especially mora migrations were more numerous. This pattern of results was not observed in French speakers (Experiment 2), suggesting that it reflects native segmentation in Japanese. To control for the intervention of kanji representations (many words are written in kanji, and one kanji often corresponds to one syllable), in Experiment 3, Japanese listeners were presented with target loanwords that can be written only in katakana. Again, phoneme migrations occurred, while the first mora and syllable led to similar rates of illusory percepts. No migration occurred for the second, "special" mora (/J/ or/N/), probably because this constitutes the latter part of a heavy syllable. Overall, these findings suggest that multiple units, such as morae, syllables, and even phonemes, function independently of orthographic knowledge in Japanese preattentive speech segmentation.

Light Chain Cast Nephropathy: Practical Considerations in the Management of Myeloma Kidney-What We Know and What the Future May Hold.

PubMed

Manohar, Sandhya; Nasr, Samih H; Leung, Nelson

2018-05-03

To update and evaluate the current knowledge on pathogenesis and management of light chain cast nephropathy. Light chain cast nephropathy (LCCN) is the leading cause of acute renal failure in patients with multiple myeloma and is currently recognized as a myeloma defining event. The immunoglobulin free light chain plays an integral role in the pathogenesis of LCCN. The level of free light chain (FLC) in the blood and urine is directly associated with the risk of developing LCCN. Recovery of renal function is related to the speed and degree of the serum FLC reduction. Recently, two randomized trials using high cutoff dialyzer for the removal of serum FLC produced different results in terms of renal recovery. FLC plays a key role in the development and resolution of LCCN. Future therapies will aim to rapidly reduce its concentration or interrupt its interaction with Tamm-Horsfall protein.

Proteomes and Phosphoproteomes of Anther and Pollen: Availability and Progress.

PubMed

Zhang, Zaibao; Hu, Menghui; Feng, Xiaobing; Gong, Andong; Cheng, Lin; Yuan, Hongyu

2017-10-01

In flowering plants, anther development plays crucial role in sexual reproduction. Within the anther, microspore mother cells meiosis produces microspores, which further develop into pollen grains that play decisive role in plant reproduction. Previous studies on anther biology mainly focused on single gene functions relying on genetic and molecular methods. Recently, anther development has been expanded from multiple OMICS approaches like transcriptomics, proteomics/phosphoproteomics, and metabolomics. The development of proteomics techniques allowing increased proteome coverage and quantitative measurements of proteins which can characterize proteomes and their modulation during normal development, biotic and abiotic stresses in anther development. In this review, we summarize the achievements of proteomics and phosphoproteomics with anther and pollen organs from model plant and crop species (i.e. Arabidopsis, rice, tobacco). The increased proteomic information facilitated translation of information from the models to crops and thus aid in agricultural improvement. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Screening of differentially expressed genes between multiple trauma patients with and without sepsis.

PubMed

Ji, S C; Pan, Y T; Lu, Q Y; Sun, Z Y; Liu, Y Z

2014-03-17

The purpose of this study was to identify critical genes associated with septic multiple trauma by comparing peripheral whole blood samples from multiple trauma patients with and without sepsis. A microarray data set was downloaded from the Gene Expression Omnibus (GEO) database. This data set included 70 samples, 36 from multiple trauma patients with sepsis and 34 from multiple trauma patients without sepsis (as a control set). The data were preprocessed, and differentially expressed genes (DEGs) were then screened for using packages of the R language. Functional analysis of DEGs was performed with DAVID. Interaction networks were then established for the most up- and down-regulated genes using HitPredict. Pathway-enrichment analysis was conducted for genes in the networks using WebGestalt. Fifty-eight DEGs were identified. The expression levels of PLAU (down-regulated) and MMP8 (up-regulated) presented the largest fold-changes, and interaction networks were established for these genes. Further analysis revealed that PLAT (plasminogen activator, tissue) and SERPINF2 (serpin peptidase inhibitor, clade F, member 2), which interact with PLAU, play important roles in the pathway of the component and coagulation cascade. We hypothesize that PLAU is a major regulator of the component and coagulation cascade, and down-regulation of PLAU results in dysfunction of the pathway, causing sepsis.

Phylo: A Citizen Science Approach for Improving Multiple Sequence Alignment

PubMed Central

Kam, Alfred; Kwak, Daniel; Leung, Clarence; Wu, Chu; Zarour, Eleyine; Sarmenta, Luis; Blanchette, Mathieu; Waldispühl, Jérôme

2012-01-01

Background Comparative genomics, or the study of the relationships of genome structure and function across different species, offers a powerful tool for studying evolution, annotating genomes, and understanding the causes of various genetic disorders. However, aligning multiple sequences of DNA, an essential intermediate step for most types of analyses, is a difficult computational task. In parallel, citizen science, an approach that takes advantage of the fact that the human brain is exquisitely tuned to solving specific types of problems, is becoming increasingly popular. There, instances of hard computational problems are dispatched to a crowd of non-expert human game players and solutions are sent back to a central server. Methodology/Principal Findings We introduce Phylo, a human-based computing framework applying “crowd sourcing” techniques to solve the Multiple Sequence Alignment (MSA) problem. The key idea of Phylo is to convert the MSA problem into a casual game that can be played by ordinary web users with a minimal prior knowledge of the biological context. We applied this strategy to improve the alignment of the promoters of disease-related genes from up to 44 vertebrate species. Since the launch in November 2010, we received more than 350,000 solutions submitted from more than 12,000 registered users. Our results show that solutions submitted contributed to improving the accuracy of up to 70% of the alignment blocks considered. Conclusions/Significance We demonstrate that, combined with classical algorithms, crowd computing techniques can be successfully used to help improving the accuracy of MSA. More importantly, we show that an NP-hard computational problem can be embedded in casual game that can be easily played by people without significant scientific training. This suggests that citizen science approaches can be used to exploit the billions of “human-brain peta-flops” of computation that are spent every day playing games. Phylo is available at: http://phylo.cs.mcgill.ca. PMID:22412834

Influence of laser irradiation on demyelination of nervous fibers

NASA Astrophysics Data System (ADS)

Melnik, Nataly O.; Plaksij, Yu. S.; Mamilov, Serge A.

2000-11-01

Problem demyelinating diseases from actual in modern of neurology. Main disease of this group - multiple sclerosis, which morphological manifestation is the process demyelineation - disintegration of myelin, which covers axial cylinders of nervous filaments. The outcome of such damage is violation of realization of nervous impulses, dissonance of implement and coordination functions. Most typical the feature of a multiple sclerosis is origin of repeated remissions, which compact with indication remyelination. In development of disease the large role is played by modifications of immunological of a reactivity of an organism. The purpose of the title is development of new methods of treatment of a multiple sclerosis because of lasertherapy. For thsi purpose the influence of a laser exposure on demyelination and remyelination processes will be investigated, is investigated pathological fabrics at microscopic and submicroscopic levels. The study of proceses demyelination and remyelination will be conducted on experimental animals (rats), which are sick experimental allergic encephalomyelitis (EAE), that is the most adequate model of a multiple sclerosis. The patients' EAE animals will be subjected to treatment by a laser exposure. For want of it there will be determinate optimum lengths of waves, dozes and modes of laser radiation.

A Flexible High-Performance Photoimaging Device Based on Bioinspired Hierarchical Multiple-Patterned Plasmonic Nanostructures.

PubMed

Lee, Yoon Ho; Lee, Tae Kyung; Kim, Hongki; Song, Inho; Lee, Jiwon; Kang, Saewon; Ko, Hyunhyub; Kwak, Sang Kyu; Oh, Joon Hak

2018-03-01

In insect eyes, ommatidia with hierarchical structured cornea play a critical role in amplifying and transferring visual signals to the brain through optic nerves, enabling the perception of various visual signals. Here, inspired by the structure and functions of insect ommatidia, a flexible photoimaging device is reported that can simultaneously detect and record incoming photonic signals by vertically stacking an organic photodiode and resistive memory device. A single-layered, hierarchical multiple-patterned back reflector that can exhibit various plasmonic effects is incorporated into the organic photodiode. The multiple-patterned flexible organic photodiodes exhibit greatly enhanced photoresponsivity due to the increased light absorption in comparison with the flat systems. Moreover, the flexible photoimaging device shows a well-resolved spatiotemporal mapping of optical signals with excellent operational and mechanical stabilities at low driving voltages below half of the flat systems. Theoretical calculation and scanning near-field optical microscopy analyses clearly reveal that multiple-patterned electrodes have much stronger surface plasmon coupling than flat and single-patterned systems. The developed methodology provides a versatile and effective route for realizing high-performance optoelectronic and photonic systems. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Executive functions and consumption of fruits/ vegetables and high saturated fat foods in young adults.

PubMed

Limbers, Christine A; Young, Danielle

2015-05-01

Executive functions play a critical role in regulating eating behaviors and have been shown to be associated with overeating which over time can result in overweight and obesity. There has been a paucity of research examining the associations among healthy dietary behaviors and executive functions utilizing behavioral rating scales of executive functioning. The objective of the present cross-sectional study was to evaluate the associations among fruit and vegetable consumption, intake of foods high in saturated fat, and executive functions using the Behavioral Rating Inventory of Executive Functioning-Adult Version. A total of 240 university students completed the Behavioral Rating Inventory of Executive Functioning-Adult Version, the 26-Item Eating Attitudes Test, and the Diet subscale of the Summary of Diabetes Self-Care Activities Questionnaire. Multiple linear regression analysis was conducted with two separate models in which fruit and vegetable consumption and saturated fat intake were the outcomes. Demographic variables, body mass index, and eating styles were controlled for in the analysis. Better initiation skills were associated with greater intake of fruits and vegetables in the last 7 days (standardized beta = -0.17; p < 0.05). Stronger inhibitory control was associated with less consumption of high fat foods in the last 7 days (standardized beta = 0.20; p < 0.05) in the multiple linear regression analysis. Executive functions that predict fruit and vegetable consumption are distinct from those that predict avoidance of foods high in saturated fat. Future research should investigate whether continued skill enhancement in initiation and inhibition following standard behavioral interventions improves long-term maintenance of weight loss. © The Author(s) 2015.

Why Do the Children (Pretend) Play?

PubMed

Lillard, Angeline S

2017-11-01

Pretend play appears to be an evolved behavior because it is universal and appears on a set schedule. However, no specific functions have been determined for pretend play and empirical tests for its functions in humans are elusive. Yet animal play fighting can serve as an analog, as both activities involve as-if, metacommunicative signaling and symbolism. In the rat and some other animals, adaptive functions of play fighting include assisting social behavior and emotion regulation. Research is presented suggesting that pretend play might serve similar functions for humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children1234

PubMed Central

Cole, Shelley A; Voruganti, V Saroja; Cai, Guowen; Haack, Karin; Kent, Jack W; Blangero, John; Comuzzie, Anthony G; McPherson, John D; Gibbs, Richard A

2010-01-01

Background: Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain. Objective: The aim was to identify and characterize the effects of MC4R variants in Hispanic children. Design: MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva la Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits. Results: Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81. Conclusion: This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure. PMID:19889825

Plug-and-play, infrared, laser-mediated PCR in a microfluidic chip.

PubMed

Pak, Nikita; Saunders, D Curtis; Phaneuf, Christopher R; Forest, Craig R

2012-04-01

Microfluidic polymerase chain reaction (PCR) systems have set milestones for small volume (100 nL-5 μL), amplification speed (100-400 s), and on-chip integration of upstream and downstream sample handling including purification and electrophoretic separation functionality. In practice, the microfluidic chips in these systems require either insertion of thermocouples or calibration prior to every amplification. These factors can offset the speed advantages of microfluidic PCR and have likely hindered commercialization. We present an infrared, laser-mediated, PCR system that features a single calibration, accurate and repeatable precision alignment, and systematic thermal modeling and management for reproducible, open-loop control of PCR in 1 μL chambers of a polymer microfluidic chip. Total cycle time is less than 12 min: 1 min to fill and seal, 10 min to amplify, and 1 min to recover the sample. We describe the design, basis for its operation, and the precision engineering in the system and microfluidic chip. From a single calibration, we demonstrate PCR amplification of a 500 bp amplicon from λ-phage DNA in multiple consecutive trials on the same instrument as well as multiple identical instruments. This simple, relatively low-cost plug-and-play design is thus accessible to persons who may not be skilled in assembly and engineering.

Creating the Multiple Personality: An Experiential Demonstration for an Undergraduate Abnormal Psychology Class.

ERIC Educational Resources Information Center

Rabinowitz, Fredric E.

1989-01-01

Discusses a classroom role-playing exercise in which students and teacher re-enact interviewing techniques that cause subjects to assume characteristics of the multiple personality. Demonstrates the social psychological aspects of multiple personality disorder. Considers the pedagogical and ethical implications of creating the multiple personality…

[The mammalian oviduct revisited].

PubMed

Halter, S; Reynaud, K; Tahir, Z; Thoumire, S; Chastant-Maillard, S; Saint-Dizier, M

2011-11-01

The oviducts, or uterine tubes, support the transport and final maturation of gametes, and harbour fertilization and early embryo development. The oviduct environment is finely regulated by ovarian steroids as well as by gametes and embryos that interact with it. Previously regarded as a simple transit zone, the oviduct is now regarded as a complex organ with multiple functions in these various processes. The tubal fluid, now better characterized, is to be regarded as the first interface between the mother and the embryo. It may play a major role in the quality of the conceptus. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

T regulatory cells in contact hypersensitivity.

PubMed

Cavani, Andrea

2008-08-01

The review summarizes the recent investigations focused on T regulatory cells in hapten diseases. Multiple mechanisms ensure tolerance to small chemicals penetrating the skin. Among these, specific T regulatory cells play a major role in controlling harmful immune responses to environmental antigens. Most of the T regulatory cells involved in this process belongs to the CD4 subset and suppress hapten-specific immune response through the release of IL-10 and through direct interaction with effector T cells, blocking their function. Methods for in-vitro and in-vivo expansion of specific T regulatory cells may represent an innovative approach for the cure of contact hypersensitivity.

Perioperative Care of the Liver Transplant Patient.

PubMed

Keegan, Mark T; Kramer, David J

2016-07-01

With the evolution of surgical and anesthetic techniques, liver transplantation has become "routine," allowing for modifications of practice to decrease perioperative complications and costs. There is debate over the necessity for intensive care unit admission for patients with satisfactory preoperative status and a smooth intraoperative course. Postoperative care is made easier when the liver graft performs optimally. Assessment of graft function, vigilance for complications after the major surgical insult, and optimization of multiple systems affected by liver disease are essential aspects of postoperative care. The intensivist plays a vital role in an integrated multidisciplinary transplant team. Copyright © 2016 Elsevier Inc. All rights reserved.

[Progress on mechanism of cell apoptosis induced by rubella virus].

PubMed

Li, Zhen-mei; Chu, Fu-lu; Liu, Ying; Wang, Zhi-yu

2013-09-01

Rubella virus (RV), a member of the family Togaviridae, can induce apoptosis of host cells in vitro. Protein kinases of the Ras-Raf-MEK-ERK pathway and PI3K-Akt pathway play essential roles in virus multiplication, cell survival and apoptosis. Proteins p53 and TAp63 that bind to specific DNA sequences stimulate Bax in a manner to produce functional pores that facilitate release of mitochondrial cytochrome c and downstream caspase activation. In this review, the molecular mechanisms of RV-induced cell apoptosis, including RV-infected cell lines, pathological changes in cell components and apoptosis signaling pathways are summarized.

Virus-based nanoparticles as platform technologies for modern vaccines

PubMed Central

Lee, Karin L.; Twyman, Richard M.; Fiering, Steven

2017-01-01

Nanoscale engineering is revolutionizing the development of vaccines and immunotherapies. Viruses have played a key role in this field because they can function as prefabricated nanoscaffolds with unique properties that are easy to modify. Viruses are immunogenic through multiple pathways, and antigens displayed naturally or by engineering on the surface can be used to create vaccines against the cognate virus, other pathogens, specific molecules or cellular targets such as tumors. This review focuses on the development of virus-based nanoparticle systems as vaccines indicated for the prevention or treatment of infectious diseases, chronic diseases, cancer, and addiction. PMID:26782096

Bifid ribs and unusual vertebral anomalies diagnosed in an anatomical specimen. Gorlin syndrome?

PubMed

Oostra, Roelof-Jan; Maas, Mario

2006-10-01

A hitherto unknown combination of multiple bifid ribs, as seen in Gorlin syndrome (GS), interpedicular fusion and apparent malsegmentation of vertebral laminae at various upper thoracic levels was found in the skeleton of a newborn infant. This specific combination of anomalies is also seen in the mouse open brain (opb) mutant. Since the genes involved in GS (Patched2) and opb (rab23) both play an essential role in the hedgehog signaling pathway, it is likely that the cause of the anomalies presented here is to be sought in impaired functioning of this pathway.

Epigenetic modulation by TFII-I during embryonic stem cell differentiation.

PubMed

Bayarsaihan, Dashzeveg; Makeyev, Aleksandr V; Enkhmandakh, Badam

2012-10-01

TFII-I transcription factors play an essential role during early vertebrate embryogenesis. Genome-wide mapping studies by ChIP-seq and ChIP-chip revealed that TFII-I primes multiple genomic loci in mouse embryonic stem cells and embryonic tissues. Moreover, many TFII-I-bound regions co-localize with H3K4me3/K27me3 bivalent chromatin within the promoters of lineage-specific genes. This minireview provides a summary of current knowledge regarding the function of TFII-I in epigenetic control of stem cell differentiation. Copyright © 2012 Wiley Periodicals, Inc.

Genomics screens for metastasis genes

PubMed Central

Yan, Jinchun; Huang, Qihong

2014-01-01

Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can systemically discover metastasis genes. In this review, we summarize the genetic tools and methods that have been used to identify and characterize the genes that play critical roles in metastasis. PMID:22684367

[Research progress on ebola virus glycoprotein].

PubMed

Ding, Guo-Yong; Wang, Zhi-Yu; Gao, Lu; Jiang, Bao-Fa

2013-03-01

Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans and there are no effective therapeutic or prophylactic treatments available. The glycoprotein (GP) of EBOV is a transmembrane envelope protein known to play multiple functions including virus attachment and entry, cell rounding and cytotoxicity, down-regulation of host surface proteins, and enhancement of virus assembly and budding. GP is the primary target of protective immunity and the key target for developing neutralizing antibodies. In this paper, the research progress on genetic structure, pathogenesis and immunogenicity of EBOV GP in the last 5 years is reviewed.

Visual discrimination in the pigeon (Columba livia): effects of selective lesions of the nucleus rotundus

NASA Technical Reports Server (NTRS)

Laverghetta, A. V.; Shimizu, T.

1999-01-01

The nucleus rotundus is a large thalamic nucleus in birds and plays a critical role in many visual discrimination tasks. In order to test the hypothesis that there are functionally distinct subdivisions in the nucleus rotundus, effects of selective lesions of the nucleus were studied in pigeons. The birds were trained to discriminate between different types of stationary objects and between different directions of moving objects. Multiple regression analyses revealed that lesions in the anterior, but not posterior, division caused deficits in discrimination of small stationary stimuli. Lesions in neither the anterior nor posterior divisions predicted effects in discrimination of moving stimuli. These results are consistent with a prediction led from the hypothesis that the nucleus is composed of functional subdivisions.

Qualitative similarities in the visual short-term memory of pigeons and people.

PubMed

Gibson, Brett; Wasserman, Edward; Luck, Steven J

2011-10-01

Visual short-term memory plays a key role in guiding behavior, and individual differences in visual short-term memory capacity are strongly predictive of higher cognitive abilities. To provide a broader evolutionary context for understanding this memory system, we directly compared the behavior of pigeons and humans on a change detection task. Although pigeons had a lower storage capacity and a higher lapse rate than humans, both species stored multiple items in short-term memory and conformed to the same basic performance model. Thus, despite their very different evolutionary histories and neural architectures, pigeons and humans have functionally similar visual short-term memory systems, suggesting that the functional properties of visual short-term memory are subject to similar selective pressures across these distant species.

SHIP deficiency enhances HSC proliferation and survival but compromises homing and repopulation

PubMed Central

Desponts, Caroline; Hazen, Amy L.; Paraiso, Kim H. T.; Kerr, William G.

2006-01-01

The SH2 domain–containing inositol 5′-phosphatase-1 (SHIP) has the potential to modulate multiple signaling pathways downstream of receptors that impact hematopoietic stem cell (HSC) biology. Therefore, we postulated that SHIP might play an important role in HSC homeostasis and function. Consistent with this hypothesis, HSC proliferation and numbers are increased in SHIP–/– mice. Despite expansion of the compartment, SHIP–/– HSCs exhibit reduced capacity for long-term repopulation. Interestingly, we observe that SHIP–/– stem/progenitor cells home inefficiently to bone marrow (BM), and consistent with this finding, have reduced surface levels of both CXCR4 and vascular cell adhesion marker-1 (VCAM-1). These studies demonstrate that SHIP is critical for normal HSC function, homeostasis, and homing. PMID:16467196

Regulatory T-Cells in Chronic Lymphocytic Leukemia and Autoimmune Diseases

PubMed Central

D’Arena, Giovanni; Rossi, Giovanni; Vannata, Barbara; Deaglio, Silvia; Mansueto, Giovanna; D’Auria, Fiorella; Statuto, Teodora; Simeon, Vittorio; De Martino, Laura; Marandino, Aurelio; Del Poeta8, Giovanni; De Feo, Vincenzo; Musto, Pellegrino

2012-01-01

Regulatory T-cells (Tregs) constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL). Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in cancer and autoimmune disorders, as well. PMID:22973497

A Spatiotemporal-Chaos-Based Cryptosystem Taking Advantage of Both Synchronous and Self-Synchronizing Schemes

NASA Astrophysics Data System (ADS)

Lü, Hua-Ping; Wang, Shi-Hong; Li, Xiao-Wen; Tang, Guo-Ning; Kuang, Jin-Yu; Ye, Wei-Ping; Hu, Gang

2004-06-01

Two-dimensional one-way coupled map lattices are used for cryptography where multiple space units produce chaotic outputs in parallel. One of the outputs plays the role of driving for synchronization of the decryption system while the others perform the function of information encoding. With this separation of functions the receiver can establish a self-checking and self-correction mechanism, and enjoys the advantages of both synchronous and self-synchronizing schemes. A comparison between the present system with the system of advanced encryption standard (AES) is presented in the aspect of channel noise influence. Numerical investigations show that our system is much stronger than AES against channel noise perturbations, and thus can be better used for secure communications with large channel noise.

Exciton Localization and Optical Emission in Aryl-Functionalized Carbon Nanotubes

DOE PAGES

Gifford, Brendan Joel; Kilina, Svetlana; Htoon, Han; ...

2017-10-26

Recent spectroscopic studies have revealed the appearance of multiple low-energy peaks in the fluorescence of single-walled carbon nanotubes (SWCNTs) upon their covalent functionalization by aryl groups. The photophysical nature of these low energy optical bands is of significant interest in the quest to understand their appearance and to achieve their precise control via chemical modification of SWCNTs. This theoretical study explains the specific energy dependence of emission features introduced in chemically functionalized (6,5) SWCNTs with aryl bromides at different conformations and in various dielectric media. Calculations using density functional theory (DFT) and time dependent DFT (TD-DFT) show that the specificmore » isomer geometry—the relative position of functional groups on the carbon-ring of the nanotube—is critical for controlling the energies and intensities of optical transitions introduced by functionalization, while the dielectric environment and the chemical composition of functional groups play less significant roles. Furthermore, the predominant effects on optical properties as a result of functionalization conformation are rationalized by exciton localization on the surface of the SWCNT near the dopant sp3-defect but not onto the functional group itself.« less

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

Essential roles of Gab1 tyrosine phosphorylation in growth factor-mediated signaling and angiogenesis.

PubMed

Wang, Weiye; Xu, Suowen; Yin, Meimei; Jin, Zheng Gen

2015-02-15

Growth factors and their downstream receptor tyrosine kinases (RTKs) mediate a number of biological processes controlling cell function. Adaptor (docking) proteins, which consist exclusively of domains and motifs that mediate molecular interactions, link receptor activation to downstream effectors. Recent studies have revealed that Grb2-associated-binders (Gab) family members (including Gab1, Gab2, and Gab3), when phosphorylated on tyrosine residues, provide binding sites for multiple effector proteins, such as Src homology-2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) and phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, thereby playing important roles in transducing RTKs-mediated signals into pathways with diversified biological functions. Here, we provide an up-to-date overview on the domain structure and biological functions of Gab1, the most intensively studied Gab family protein, in growth factor signaling and biological functions, with a special focus on angiogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Multiple Perspectives on Play in Early Childhood Education. SUNY Series, Early Childhood Education.

ERIC Educational Resources Information Center

Saracho, Olivia N., Ed.; Spodek, Bernard, Ed.

This book provides research in the area of educational play for early childhood teachers and teacher educators. Following an introduction by the editors, the chapters of the book are: (1) "A Historical Overview of Theories of Play" (Olivia Saracho and Bernard Spodek); (2) "Playing with a Theory of Mind" (Angeline Lillard); (3)…

CCR4-Not Complex Subunit Not2 Plays Critical Roles in Vegetative Growth, Conidiation and Virulence in Watermelon Fusarium Wilt Pathogen Fusarium oxysporum f. sp. niveum

PubMed Central

Dai, Yi; Cao, Zhongye; Huang, Lihong; Liu, Shixia; Shen, Zhihui; Wang, Yuyan; Wang, Hui; Zhang, Huijuan; Li, Dayong; Song, Fengming

2016-01-01

CCR4-Not complex is a multifunctional regulator that plays important roles in multiple cellular processes in eukaryotes. In the present study, the biological function of FonNot2, a core subunit of the CCR4-Not complex, was explored in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt disease. FonNot2 was expressed at higher levels in conidia and germinating conidia and during infection in Fon-inoculated watermelon roots than in mycelia. Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced conidia production, abnormal conidial morphology, and reduced virulence on watermelon. Scanning electron microscopy observation of infection behaviors and qRT-PCR analysis of in planta fungal growth revealed that the ΔFonNot2 mutant was defective in the ability to penetrate watermelon roots and showed reduced fungal biomass in root and stem of the inoculated plants. Phenotypic and biochemical analyses indicated that the ΔFonNot2 mutant displayed hypersensitivity to cell wall perturbing agents (e.g., Congo Red and Calcofluor White) and oxidative stress (e.g., H2O2 and paraquat), decreased fusaric acid content, and reduced reactive oxygen species (ROS) production during spore germination. Our data demonstrate that FonNot2 plays critical roles in regulating vegetable growth, conidiogenesis and conidia morphology, and virulence on watermelon via modulating cell wall integrity, oxidative stress response, ROS production and FA biosynthesis through the regulation of transcription of genes involved in multiple pathways. PMID:27695445

An integrated modelling framework for neural circuits with multiple neuromodulators.

PubMed

Joshi, Alok; Youssofzadeh, Vahab; Vemana, Vinith; McGinnity, T M; Prasad, Girijesh; Wong-Lin, KongFatt

2017-01-01

Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. © 2017 The Authors.

Basic leucine zipper transcription factor SlbZIP1 mediates salt and drought stress tolerance in tomato.

PubMed

Zhu, Mingku; Meng, Xiaoqing; Cai, Jing; Li, Ge; Dong, Tingting; Li, Zongyun

2018-05-08

Basic region/leucine zipper (bZIP) transcription factors perform as crucial regulators in ABA-mediated stress response in plants. Nevertheless, the functions for most bZIP family members in tomato remain to be deciphered. Here we examined the functional characterization of SlbZIP1 under salt and drought stresses in tomato. Silencing of SlbZIP1 in tomato resulted in reduced expression of multiple ABA biosynthesis- and signal transduction-related genes in transgenic plants. In stress assays, SlbZIP1-RNAi transgenic plants exhibited reduced tolerance to salt and drought stresses compared with WT plants, as are evaluated by multiple physiological parameters associated with stress responses, such as decreased ABA, chlorophyll contents and CAT activity, and increased MDA content. In addition, RNA-seq analysis of transgenic plants revealed that the transcription levels of multiple genes encoding defense proteins related to responses to abiotic stress (e.g. endochitinase, peroxidases, and lipid transfer proteins) and biotic stress (e.g. pathogenesis-related proteins) were downregulated in SlbZIP1-RNAi plants, suggesting that SlbZIP1 plays a role in regulating the genes related to biotic and abiotic stress response. Collectively, the data suggest that SlbZIP1 exerts an essential role in salt and drought stress tolerance through modulating an ABA-mediated pathway, and SlbZIP1 may hold potential applications in the engineering of salt- and drought-tolerant tomato cultivars.

An integrated modelling framework for neural circuits with multiple neuromodulators

PubMed Central

Vemana, Vinith

2017-01-01

Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. PMID:28100828

Remaking collective knowledge: An analysis of the complex and multiple effects of inquiries into historical institutional child abuse.

PubMed

Wright, Katie

2017-12-01

This article provides an overview and critical analysis of inquiries into historical institutional child abuse and examines their multiple functions and complex effects. The article takes a broadly international view but focuses primarily on Australia, the UK and Ireland, jurisdictions in which there have been major national inquiries. Drawing on sociological and other social science literature, it begins by considering the forms, functions, and purposes of inquiries. An overview of emergent concerns with institutional abuse in the 1980s and 1990s is then provided, followed by an examination of the response of many governments since that time in establishing inquiries. Key findings and recommendations are considered. The final sections of the article explore the evaluation of inquiries, both during their operation and in their aftermath. Policy change and legislative reform are discussed but the focus is on aspects often underplayed or overlooked, including an inquiry's credibility, its role in processes of knowledge production, and the part it plays in producing social and cultural shifts. In the context of growing numbers of inquiries across Western democracies, including the Australian Royal Commission into Institutional Responses to Child Sexual Abuse, it is argued that grasping the complexity of the inquiry mechanism, with its inherent tensions and its multiple effects, is crucial to evaluating inquiry outcomes. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

A qualitative study exploring the usability of Nintendo Wii Fit among persons with multiple sclerosis.

PubMed

Plow, Matthew; Finlayson, Marcia

2014-03-01

The purpose of this study was to examine the usability of Nintendo Wii Fit to promote physical activity in adults with multiple sclerosis. Qualitative interviews were conducted as part of a pilot study that examined the health outcomes of a 14-week Wii Fit home-exercise programme in 30 adults with multiple sclerosis. We found participants reported that Wii Fit helped build confidence in abilities, achieve goals related to engagement in leisure activities and remove barriers associated with going to a gym to exercise. However, Wii Fit induced initial reactions of intimidation and worries about falling, and feedback during game play reminded participants of their impairments. Wii Fit was limited in its customizability to accommodate different functional levels. Understanding how to improve the usability and customizability of commercially available exergaming technology could be of benefit to people with disabling conditions. Before conducting randomized controlled trials of commercially available exergaming technology in adults with disabling conditions, we recommend that strategies be identified to remove usability barriers so those with moderate impairments can be included in the trial. This will reduce the likelihood of ceiling effects and clinical irrelevance. In terms of clinical recommendations, rehabilitation professionals need to consider patients' functional level, surrounding environment and preferences when prescribing a Wii Fit-based exercise programme. Copyright © 2013 John Wiley & Sons, Ltd.

Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis.

PubMed

D'Ambrosio, Alessandro; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo; Rocca, Maria A

2017-08-01

To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients. Whole and sub-regional cerebellar volumes, brain volumes, T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores. Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models. Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior-inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.

Task-Dependent Changes in Cross-Level Coupling between Single Neurons and Oscillatory Activity in Multiscale Networks

PubMed Central

Canolty, Ryan T.; Ganguly, Karunesh; Carmena, Jose M.

2012-01-01

Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP) activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC) or under direct neural control through a brain-machine interface (Brain Control, BC). In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10–45 Hz) during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to spike rate and timing may hold for models of computation and communication in distributed functional brain networks. PMID:23284276

[Analysis on "component-target-pathway" of Paeonia lactiflora in treating cardiac diseases based on data mining].

PubMed

Liu, Yang; Zhang, Fang-Bo; Tang, Shi-Huan; Wang, Ping; Li, Sen; Su, Jin; Zhou, Rong-Rong; Zhang, Jia-Qi; Sun, Hui-Feng

2018-04-01

Based on the literature review and modern application of Paeonia lactiflora in heart diseases, this article would predict the target of drug and disease by intergrative pharmacology platform of traditional Chinese medicine (TCMIP, http://www.tcmip.cn), and then explore the molecular mechanism of P. lactiflora in treatment of heart disease, providing theoretical basis and method for further studies on P. lactiflora. According to the ancient books, P. lactiflora with functions of "removing the vascular obstruction, removing the lumps, relieving pain, diuretic, nutrient qi" and other effects, have been used for many times to treat heart disease. Some prescriptions are also favored by the modern physicians nowadays. With the development of science, the chemical components that play a role in heart disease and the interrelation between these components and the body become the research hotspot. In order to further reveal the pharmacological substance base and molecular mechanism of P. lactiflora for the treatment of such diseases, TCM-IP was used to obtain multiple molecular targets and signaling pathways in treatment of heart disease. ATP1A1, a common target of drug and disease, was related to energy, and HDAC2 mainly regulated cardiomyocyte hypertrophy gene and cardiomyocyte expression. Other main drug targets such as GCK, CHUK and PRKAA2 indirectly regulated heart disease through many pathways; multiple disease-associated signaling pathways interfered with various heart diseases including coronary heart disease, myocardial ischemia and myocardial hypertrophy through influencing energy metabolism, enzyme activity and gene expression. In conclusion, P. lactiflora plays a role in protecting heart function by regulating the gene expression of cardiomyocytes directly. Meanwhile, it can indirectly intervene in other pathways of heart function, and thus participate in the treatment of heart disease. In this paper, the molecular mechanism of P. lactiflora for treatment of heart disease was in computer prediction analysis level, and the specific mechanism of action still needs further experimental verification. Copyright© by the Chinese Pharmaceutical Association.

Viral Inhibition of the Transporter Associated with Antigen Processing (TAP): A Striking Example of Functional Convergent Evolution

PubMed Central

Verweij, Marieke C.; Horst, Daniëlle; Griffin, Bryan D.; Luteijn, Rutger D.; Davison, Andrew J.; Ressing, Maaike E.; Wiertz, Emmanuel J. H. J.

2015-01-01

Herpesviruses are large DNA viruses that are highly abundant within their host populations. Even in the presence of a healthy immune system, these viruses manage to cause lifelong infections. This persistence is partially mediated by the virus entering latency, a phase of infection characterized by limited viral protein expression. Moreover, herpesviruses have devoted a significant part of their coding capacity to immune evasion strategies. It is believed that the close coexistence of herpesviruses and their hosts has resulted in the evolution of viral proteins that specifically attack multiple arms of the host immune system. Cytotoxic T lymphocytes (CTLs) play an important role in antiviral immunity. CTLs recognize their target through viral peptides presented in the context of MHC molecules at the cell surface. Every herpesvirus studied to date encodes multiple immune evasion molecules that effectively interfere with specific steps of the MHC class I antigen presentation pathway. The transporter associated with antigen processing (TAP) plays a key role in the loading of viral peptides onto MHC class I molecules. This is reflected by the numerous ways herpesviruses have developed to block TAP function. In this review, we describe the characteristics and mechanisms of action of all known virus-encoded TAP inhibitors. Orthologs of these proteins encoded by related viruses are identified, and the conservation of TAP inhibition is discussed. A phylogenetic analysis of members of the family Herpesviridae is included to study the origin of these molecules. In addition, we discuss the characteristics of the first TAP inhibitor identified outside the herpesvirus family, namely, in cowpox virus. The strategies of TAP inhibition employed by viruses are very distinct and are likely to have been acquired independently during evolution. These findings and the recent discovery of a non-herpesvirus TAP inhibitor represent a striking example of functional convergent evolution. PMID:25880312

Executive function predicts the development of play skills for verbal preschoolers with autism spectrum disorders.

PubMed

Faja, Susan; Dawson, Geraldine; Sullivan, Katherine; Meltzoff, Andrew N; Estes, Annette; Bernier, Raphael

2016-12-01

Executive function and play skills develop in early childhood and are linked to cognitive and language ability. The present study examined these abilities longitudinally in two groups with autism spectrum disorder-a group with higher initial language (n = 30) and a group with lower initial language ability (n = 36). Among the lower language group, concurrent nonverbal cognitive ability contributed most to individual differences in executive function and play skills. For the higher language group, executive function during preschool significantly predicted play ability at age 6 over and above intelligence, but early play did not predict later executive function. These results suggested that factors related to the development of play and executive function differ for subgroups of children with different language abilities and that early executive function skills may be critical in order for verbal children with autism to develop play. Autism Res 2016, 9: 1274-1284. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

PubMed

Xiao, Ran; Li, Shan; Cao, Qian; Wang, Xiuling; Yan, Qiujin; Tu, Xiaoning; Zhu, Ying; Zhu, Fan

2017-06-01

Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer.

PubMed

Han, Yi-Neng; Li, Yuan; Xia, Sheng-Qiang; Zhang, Yuan-Yuan; Zheng, Jun-Hua; Li, Wei

2017-01-01

P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a type of noncoding RNAs (ncRNAs) and interact with PIWI proteins. piRNAs were primarily described in the germline, but emerging evidence revealed that piRNAs are expressed in a tissue-specific manner among multiple human somatic tissue types as well and play important roles in transposon silencing, epigenetic regulation, gene and protein regulation, genome rearrangement, spermatogenesis and germ stem-cell maintenance. PIWI proteins were first discovered in Drosophila and they play roles in spermatogenesis, germline stem-cell maintenance, self-renewal, retrotransposons silencing and the male germline mobility control. A growing number of studies have demonstrated that several piRNA and PIWI proteins are aberrantly expressed in various kinds of cancers and may probably serve as a novel biomarker and therapeutic target for cancer treatment. Nevertheless, their specific mechanisms and functions need further investigation. In this review, we discuss about the biogenesis, functions and the emerging role of piRNAs and PIWI proteins in cancer, providing novel insights into the possible applications of piRNAs and PIWI proteins in cancer diagnosis and clinical treatment. © 2017 The Author(s). Published by S. Karger AG, Basel.

Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans

PubMed Central

Chou, Meng-Yun; Fogelstrand, Linda; Hartvigsen, Karsten; Hansen, Lotte F.; Woelkers, Douglas; Shaw, Peter X.; Choi, Jeomil; Perkmann, Thomas; Bäckhed, Fredrik; Miller, Yury I.; Hörkkö, Sohvi; Corr, Maripat; Witztum, Joseph L.; Binder, Christoph J.

2009-01-01

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis. PMID:19363291

Substance abuse and child maltreatment.

PubMed

Wells, Kathryn

2009-04-01

Pediatricians and other medical providers caring for children need to be aware of the dynamics in the significant relationship between substance abuse and child maltreatment. A caregiver's use and abuse of alcohol, marijuana, heroin, cocaine, methamphetamine, and other drugs place the child at risk in multiple ways. Members of the medical community need to understand these risks because the medical community plays a unique and important role in identifying and caring for these children. Substance abuse includes the abuse of legal drugs as well as the use of illegal drugs. The abuse of legal substances may be just as detrimental to parental functioning as abuse of illicit substances. Many substance abusers are also polysubstance users and the compounded effect of the abuse of multiple substances may be difficult to measure. Often other interrelated social features, such as untreated mental illness, trauma history, and domestic violence, affect these families.

Control of proliferation and cancer growth by the Hippo signaling pathway

PubMed Central

Ehmer, Ursula; Sage, Julien

2015-01-01

The control of cell division is essential for normal development and the maintenance of cellular homeostasis. Abnormal cell proliferation is associated with multiple pathological states, including cancer. While the Hippo/YAP signaling pathway was initially thought to control organ size and growth, increasing evidence indicates that this pathway also plays a major role in the control of proliferation independent of organ size control. In particular, accumulating evidence indicates that the Hippo/YAP signaling pathway functionally interacts with multiple other cellular pathways and serves as a central node in the regulation of cell division, especially in cancer cells. Here recent observations are highlighted that connect Hippo/YAP signaling to transcription, the basic cell cycle machinery, and the control of cell division. Furthermore, the oncogenic and tumor suppressive attributes of YAP/TAZ are reviewed which emphasizes the relevance of the Hippo pathway in cancer. PMID:26432795

TargetCompare: A web interface to compare simultaneous miRNAs targets

PubMed Central

Moreira, Fabiano Cordeiro; Dustan, Bruno; Hamoy, Igor G; Ribeiro-dos-Santos, André M; dos Santos, Ândrea Ribeiro

2014-01-01

MicroRNAs (miRNAs) are small non-coding nucleotide sequences between 17 and 25 nucleotides in length that primarily function in the regulation of gene expression. A since miRNA has thousand of predict targets in a complex, regulatory cell signaling network. Therefore, it is of interest to study multiple target genes simultaneously. Hence, we describe a web tool (developed using Java programming language and MySQL database server) to analyse multiple targets of pre-selected miRNAs. We cross validated the tool in eight most highly expressed miRNAs in the antrum region of stomach. This helped to identify 43 potential genes that are target of at least six of the referred miRNAs. The developed tool aims to reduce the randomness and increase the chance of selecting strong candidate target genes and miRNAs responsible for playing important roles in the studied tissue. Availability http://lghm.ufpa.br/targetcompare PMID:25352731

TargetCompare: A web interface to compare simultaneous miRNAs targets.

PubMed

Moreira, Fabiano Cordeiro; Dustan, Bruno; Hamoy, Igor G; Ribeiro-Dos-Santos, André M; Dos Santos, Andrea Ribeiro

2014-01-01

MicroRNAs (miRNAs) are small non-coding nucleotide sequences between 17 and 25 nucleotides in length that primarily function in the regulation of gene expression. A since miRNA has thousand of predict targets in a complex, regulatory cell signaling network. Therefore, it is of interest to study multiple target genes simultaneously. Hence, we describe a web tool (developed using Java programming language and MySQL database server) to analyse multiple targets of pre-selected miRNAs. We cross validated the tool in eight most highly expressed miRNAs in the antrum region of stomach. This helped to identify 43 potential genes that are target of at least six of the referred miRNAs. The developed tool aims to reduce the randomness and increase the chance of selecting strong candidate target genes and miRNAs responsible for playing important roles in the studied tissue. http://lghm.ufpa.br/targetcompare.

Muc4/MUC4 functions and regulation in cancer.

PubMed

Carraway, Kermit L; Theodoropoulos, George; Kozloski, Goldi A; Carothers Carraway, Coralie A

2009-12-01

The membrane mucin MUC4 (human) is abundantly expressed in many epithelia, where it is proposed to play a protective role, and is overexpressed in some epithelial tumors. Studies on the rat homologue, Muc4, indicate that it acts through anti-adhesive or signaling mechanisms. In particular, Muc4/MUC4 can serve as a ligand/modulator of the receptor tyrosine kinase ErbB2, regulating its phosphorylation and the phosphorylation of its partner ErbB3, with or without the involvement of the ErbB3 ligand neuregulin. Muc4/MUC4 can also modulate cell apoptosis via multiple mechanisms, both ErbB2 dependent and independent. Muc4/MUC4 expression is regulated by multiple mechanisms, ranging from transcriptional to post-translational. The roles of MUC4 in tumors suggest that it may be valuable as a tumor marker or target for therapy.

Implementation of acoustic demultiplexing with membrane-type metasurface in low frequency range

NASA Astrophysics Data System (ADS)

Chen, Xing; Liu, Peng; Hou, Zewei; Pei, Yongmao

2017-04-01

Wavelength division multiplexing technology, adopted to increase the information density, plays a significant role in optical communication. However, in acoustics, a similar function can be hardly implemented due to the weak dispersion in natural acoustic materials. Here, an acoustic demultiplexer, based on the concept of metasurfaces, is proposed for splitting acoustic waves and propagating along different trajectories in a low frequency range. An acoustic metasurface, containing multiple resonant units, is designed with various phase profiles for different frequencies. Originating from the highly dispersive properties, the resonant units are independent and merely work in the vicinity of their resonant frequencies. Therefore, by combing multiple resonant units appropriately, the phenomena of anomalous reflection, acoustic focusing, and acoustic wave bending can occur in different frequencies. The proposed acoustic demultiplexer has advantages on the subwavelength scale and the versatility in wave control, providing a strategy for separating acoustic waves with different Fourier components.

Nas transgenic mouse line allows visualization of Notch pathway activity in vivo.

PubMed

Souilhol, Céline; Cormier, Sarah; Monet, Marie; Vandormael-Pournin, Sandrine; Joutel, Anne; Babinet, Charles; Cohen-Tannoudji, Michel

2006-06-01

The Notch signaling pathway plays multiple and important roles in mammals. However, several aspects of its action, in particular, the precise mapping of its sites of activity, remain unclear. To address this issue, we generated a transgenic line carrying a construct consisting of a nls-lacZ reporter gene under the control of a minimal promoter and multiple RBP-Jkappa binding sites. Here we show that this transgenic line, which we termed NAS (for Notch Activity Sensor), displays an expression profile that is consistent with current knowledge on Notch activity sites in mice, even though it may not report on all these sites. Moreover, we observe that NAS transgene expression is abolished in a RBP-Jkappa-deficient background, indicating that it indeed requires Notch/RBP-Jkappa signaling pathway activity. Thus, the NAS transgenic line constitutes a valuable and versatile tool to gain further insights into the complex and various functions of the Notch signaling pathway.

Bridges or Barriers? Conceptualization of the Role of Multiple Identity Gateway Groups in Intergroup Relations.

PubMed

Levy, Aharon; Saguy, Tamar; Halperin, Eran; van Zomeren, Martijn

2017-01-01

The modern era of globalization has been accompanied by a massive growth in interconnections between groups, and has led to the sharing of multiple identities by individuals and groups. Following these developments, research has focused on the issue of multiple identities, and has shed important light on how individuals who hold these complex forms of identity feel and behave, and on the reactions they elicit from members of other groups. However, the potential of groups with such multiple identities (e.g., biracials, immigrants, etc.) to affect the intergroup relations between the groups that represent the respective sources of the different identities (e.g., Blacks and Whites, country of origin and country of residence, etc.) has not been examined to date. Accordingly, in this paper, we first systematically explore the potential of groups in which people identify with multiple social categories, or groups that are perceived as such by others, to play a role in intergroup dynamics. Next, we offer a theoretical framework outlining what functions groups of people with shared multiple identities may serve (as bridges or barriers ) by proposing how their presence may facilitate or deteriorate intergroup relations. Finally, we present recent empirical research examining how groups of people with shared multiple identities can act as gateways and bridge the cleft between two separate groups that represent the respective sources of their different identities, and discuss the theoretical and practical implications for the field of intergroup relations.

Bridges or Barriers? Conceptualization of the Role of Multiple Identity Gateway Groups in Intergroup Relations

PubMed Central

Levy, Aharon; Saguy, Tamar; Halperin, Eran; van Zomeren, Martijn

2017-01-01

The modern era of globalization has been accompanied by a massive growth in interconnections between groups, and has led to the sharing of multiple identities by individuals and groups. Following these developments, research has focused on the issue of multiple identities, and has shed important light on how individuals who hold these complex forms of identity feel and behave, and on the reactions they elicit from members of other groups. However, the potential of groups with such multiple identities (e.g., biracials, immigrants, etc.) to affect the intergroup relations between the groups that represent the respective sources of the different identities (e.g., Blacks and Whites, country of origin and country of residence, etc.) has not been examined to date. Accordingly, in this paper, we first systematically explore the potential of groups in which people identify with multiple social categories, or groups that are perceived as such by others, to play a role in intergroup dynamics. Next, we offer a theoretical framework outlining what functions groups of people with shared multiple identities may serve (as bridges or barriers) by proposing how their presence may facilitate or deteriorate intergroup relations. Finally, we present recent empirical research examining how groups of people with shared multiple identities can act as gateways and bridge the cleft between two separate groups that represent the respective sources of their different identities, and discuss the theoretical and practical implications for the field of intergroup relations. PMID:28706501

Identification of interacting proteins of the TaFVE protein involved in spike development in bread wheat.

PubMed

Zheng, Yong-Sheng; Lu, Yu-Qing; Meng, Ying-Ying; Zhang, Rong-Zhi; Zhang, Han; Sun, Jia-Mei; Wang, Mu-Mu; Li, Li-Hui; Li, Ru-Yu

2017-05-01

WD-40 repeat-containing protein MSI4 (FVE)/MSI4 plays important roles in determining flowering time in Arabidopsis. However, its function is unexplored in wheat. In the present study, coimmunoprecipitation and nanoscale liquid chromatography coupled to MS/MS were used to identify FVE in wheat (TaFVE)-interacting or associated proteins. Altogether 89 differentially expressed proteins showed the same downregulated expression trends as TaFVE in wheat line 5660M. Among them, 62 proteins were further predicted to be involved in the interaction network of TaFVE and 11 proteins have been shown to be potential TaFVE interactors based on curated databases and experimentally determined in other species by the STRING. Both yeast two-hybrid assay and bimolecular fluorescence complementation assay showed that histone deacetylase 6 and histone deacetylase 15 directly interacted with TaFVE. Multiple chromatin-remodelling proteins and polycomb group proteins were also identified and predicted to interact with TaFVE. These results showed that TaFVE directly interacted with multiple proteins to form multiple complexes to regulate spike developmental process, e.g. histone deacetylate, chromatin-remodelling and polycomb repressive complex 2 complexes. In addition, multiple flower development regulation factors (e.g. flowering locus K homology domain, flowering time control protein FPA, FY, flowering time control protein FCA, APETALA 1) involved in floral transition were also identified in the present study. Taken together, these results further elucidate the regulatory functions of TaFVE and help reveal the genetic mechanisms underlying wheat spike differentiation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of intestinal microbiota in the development of multiple sclerosis.

PubMed

Castillo-Álvarez, F; Marzo-Sola, M E

2017-04-01

Multiple sclerosis (MS) is a demyelinating disease that affects young adults; in that age group, it represents the second leading cause of disability in our setting. Its precise aetiology has not been elucidated, but it is widely accepted to occur in genetically predisposed patients who are exposed to certain environmental factors. The discovery of the regulatory role played by intestinal microbiota in various autoimmune diseases has opened a new line of research in this field, which is discussed in this review. We reviewed published studies on the role of the microbiota in the development of both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice, it has been shown that intestinal microorganisms regulate the polarisation of T helper cells from Th1-Th17 up to Th2, the function of regulatory T cells, and the activity of B cells; they participate in the pathogenesis of EAE and contribute to its prevention and treatment. In contrast, evidence in humans is still scarce and mainly based on case-control studies that point to the presence of differences in certain bacterial communities. Multiple evidence points to the role of microbiota in EAE. Extrapolation of these results to MS is still in the early stages of research, and studies are needed to define which bacterial populations are associated with MS, the role they play in pathogenesis, and the therapeutic possibilities this knowledge offers us. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Discontinuity in the responses of ecosystem processes and multifunctionality to altered soil community composition.

PubMed

Bradford, Mark A; Wood, Stephen A; Bardgett, Richard D; Black, Helaina I J; Bonkowski, Michael; Eggers, Till; Grayston, Susan J; Kandeler, Ellen; Manning, Peter; Setälä, Heikki; Jones, T Hefin

2014-10-07

Ecosystem management policies increasingly emphasize provision of multiple, as opposed to single, ecosystem services. Management for such "multifunctionality" has stimulated research into the role that biodiversity plays in providing desired rates of multiple ecosystem processes. Positive effects of biodiversity on indices of multifunctionality are consistently found, primarily because species that are redundant for one ecosystem process under a given set of environmental conditions play a distinct role under different conditions or in the provision of another ecosystem process. Here we show that the positive effects of diversity (specifically community composition) on multifunctionality indices can also arise from a statistical fallacy analogous to Simpson's paradox (where aggregating data obscures causal relationships). We manipulated soil faunal community composition in combination with nitrogen fertilization of model grassland ecosystems and repeatedly measured five ecosystem processes related to plant productivity, carbon storage, and nutrient turnover. We calculated three common multifunctionality indices based on these processes and found that the functional complexity of the soil communities had a consistent positive effect on the indices. However, only two of the five ecosystem processes also responded positively to increasing complexity, whereas the other three responded neutrally or negatively. Furthermore, none of the individual processes responded to both the complexity and the nitrogen manipulations in a manner consistent with the indices. Our data show that multifunctionality indices can obscure relationships that exist between communities and key ecosystem processes, leading us to question their use in advancing theoretical understanding--and in management decisions--about how biodiversity is related to the provision of multiple ecosystem services.

Discontinuity in the responses of ecosystem processes and multifunctionality to altered soil community composition

PubMed Central

Bradford, Mark A.; Wood, Stephen A.; Bardgett, Richard D.; Black, Helaina I. J.; Bonkowski, Michael; Eggers, Till; Grayston, Susan J.; Kandeler, Ellen; Manning, Peter; Setälä, Heikki; Jones, T. Hefin

2014-01-01

Ecosystem management policies increasingly emphasize provision of multiple, as opposed to single, ecosystem services. Management for such “multifunctionality” has stimulated research into the role that biodiversity plays in providing desired rates of multiple ecosystem processes. Positive effects of biodiversity on indices of multifunctionality are consistently found, primarily because species that are redundant for one ecosystem process under a given set of environmental conditions play a distinct role under different conditions or in the provision of another ecosystem process. Here we show that the positive effects of diversity (specifically community composition) on multifunctionality indices can also arise from a statistical fallacy analogous to Simpson’s paradox (where aggregating data obscures causal relationships). We manipulated soil faunal community composition in combination with nitrogen fertilization of model grassland ecosystems and repeatedly measured five ecosystem processes related to plant productivity, carbon storage, and nutrient turnover. We calculated three common multifunctionality indices based on these processes and found that the functional complexity of the soil communities had a consistent positive effect on the indices. However, only two of the five ecosystem processes also responded positively to increasing complexity, whereas the other three responded neutrally or negatively. Furthermore, none of the individual processes responded to both the complexity and the nitrogen manipulations in a manner consistent with the indices. Our data show that multifunctionality indices can obscure relationships that exist between communities and key ecosystem processes, leading us to question their use in advancing theoretical understanding—and in management decisions—about how biodiversity is related to the provision of multiple ecosystem services. PMID:25246582

Teacher Roles of Questioning in Early Elementary Science Classrooms: A Framework Promoting Student Cognitive Complexities in Argumentation

NASA Astrophysics Data System (ADS)

Chen, Ying-Chih; Hand, Brian; Norton-Meier, Lori

2017-04-01

The purpose of this study was to investigate the various roles that early elementary teachers adopt when questioning, to scaffold dialogic interaction and students' cognitive responses for argumentative practices over time. Teacher questioning is a pivotal contributing factor that shapes the role teachers play in promoting dialogic interaction in argumentative practice and that different roles serve different functions for promoting students' conceptual understanding. The multiple-case study was designed as a follow-up study after a 4-year professional development program that emphasized an argument-based inquiry approach. Data sources included 30 lessons focusing on whole class discussion from three early elementary teachers' classes. Data were analyzed through two approaches: (1) constant comparative method and (2) enumerative approach. This study conceptualized four critical roles of teacher questioning—dispenser, moderator, coach, and participant—in light of the ownership of ideas and activities. The findings revealed two salient changes in teachers' use of questions and the relationships between teachers' question-asking and students' cognitive responses: (1) teachers increasingly used multiple roles in establishing argumentative discourse as they persistently implemented an argument-based inquiry approach, and (2) as teachers used multiple roles in establishing patterns of questioning and framing classroom interactions, higher levels of student cognitive responses were promoted. This study suggests that an essential component of teacher professional development should include the study of the various roles that teachers can play when questioning for establishing dialogic interaction in argumentation and that this development should consist of ongoing training with systematic support.

The role of high level play as a predictor social functioning in autism.

PubMed

Manning, Margaret M; Wainwright, Laurel D

2010-05-01

Play and social abilities of a group of children diagnosed with high functioning autism were compared to a second group diagnosed with a variety of developmental language disorders (DLD). The children with autism engaged in fewer acts of high level play. The children with autism also had significantly lower social functioning than the DLD group early in the play session; however, these differences were no longer apparent by the end of the play session. In addition, a significant association existed between play and social functioning regardless of diagnosis. This suggests that play may act as a current indicator of social ability while providing an arena for social skills practice.

TgTKL1 Is a Unique Plant-Like Nuclear Kinase That Plays an Essential Role in Acute Toxoplasmosis

PubMed Central

Varberg, Joseph M.; Coppens, Isabelle; Arrizabalaga, Gustavo

2018-01-01

ABSTRACT In the protozoan parasite Toxoplasma gondii, protein kinases have been shown to play key roles in regulating parasite motility, invasion, replication, egress, and survival within the host. The tyrosine kinase-like (TKL) family of proteins are an unexplored set of kinases in Toxoplasma. Of the eight annotated TKLs in the Toxoplasma genome, a recent genome-wide loss-of-function screen showed that six are important for tachyzoite fitness. By utilizing an endogenous tagging approach, we showed that these six T. gondii TKLs (TgTKLs) localize to various subcellular compartments, including the nucleus, the cytosol, the inner membrane complex, and the Golgi apparatus. To gain insight into the function of TKLs in Toxoplasma, we first characterized TgTKL1, which contains the plant-like enhanced disease resistance 1 (EDR1) domain and localizes to the nucleus. TgTKL1 knockout parasites displayed significant defects in progression through the lytic cycle; we show that the defects were due to specific impairment of host cell attachment. Transcriptomics analysis identified over 200 genes of diverse functions that were differentially expressed in TgTKL1 knockout parasites. Importantly, numerous genes implicated in host cell attachment and invasion were among those most significantly downregulated, resulting in defects in microneme secretion and processing. Significantly, all of the mice inoculated intraperitoneally with TgTKL1 knockout parasites survived the infection, suggesting that TgTKL1 plays an essential role in acute toxoplasmosis. Together, these findings suggest that TgTKL1 mediates a signaling pathway that regulates the expression of multiple factors required for parasite virulence, underscoring the potential of this kinase as a novel therapeutic target. PMID:29559568

Problematic video game use scale: initial psychometric properties with psychiatrically hospitalized adolescents.

PubMed

Topor, David R; Swenson, Lance P; Liguori, Gina M; Spirito, Anthony; Lowenhaupt, Elizabeth A; Hunt, Jeffrey I

2011-12-01

Excessive video game use among youth has been a growing concern in the United States and elsewhere. The aims of this study are to establish validity of a video game measure in a large adolescent inpatient sample, identify clinical factors underlying problem video game use, and identify associations with measures of psychopathology. Three hundred eighty participants admitted to an adolescent inpatient psychiatric unit between November 2007 and March 2009 were administered a battery of self-report measures, including a questionnaire developed for this study that assessed reinforcers and consequences of past-year video game use (ie, Problematic Video Game Use Scale). Factor analysis was used to identify the underlying structure of behaviors associated with problem video game use. A factor analysis of the Problematic Video Game Use Scale indicated 2 primary factors. One was associated with engaging in problem behaviors that impaired the adolescent's functioning as a result of playing video games and one reflected the reinforcing effects of playing video games. Both factors were associated with measures of psychopathology, although associations were generally stronger for impairment in functioning than for reinforcing effects. Both factors were significantly correlated with self-reported daily video game use (P < .001). Two underlying factors emerged to account for problem video game playing: impairment in functioning and reinforcing effects. Initial evidence of the content validity of the video game measure was established. Findings highlight the importance of assessing video game use among an adolescent population, the factors associated with video game use, and associations with symptoms of psychopathology. Limitations include a common reporter for multiple measures and cross-sectional data that do not allow for causal links to be made. © Copyright 2011 Physicians Postgraduate Press, Inc.

Structural abnormalities and altered regional brain activity in multiple sclerosis with simple spinal cord involvement.

PubMed

Yin, Ping; Liu, Yi; Xiong, Hua; Han, Yongliang; Sah, Shambhu Kumar; Zeng, Chun; Wang, Jingjie; Li, Yongmei

2018-02-01

To assess the changes of the structural and functional abnormalities in multiple sclerosis with simple spinal cord involvement (MS-SSCI) by using resting-state functional MRI (RS-fMRI), voxel based morphology (VBM) and diffusion tensor tractography. The amplitude of low-frequency fluctuation (ALFF) of 22 patients with MS-SSCI and 22 healthy controls (HCs) matched for age, gender and education were compared by using RS-fMRI. We also compared the volume, fractional anisotropy (FA) and apparent diffusion coefficient of the brain regions in baseline brain activity by using VBM and diffusion tensor imaging. The relationships between the expanded disability states scale (EDSS) scores, changed parameters of structure and function were further explored. (1) Compared with HCs, the ALFF of the bilateral hippocampus and right middle temporal gyrus in MS-SSCI decreased significantly. However, patients exhibited increased ALFF in the left middle frontal gyrus, left posterior cingulate gyrus and right middle occipital gyrus ( two-sample t-test, after AlphaSim correction, p < 0.01, voxel size > 40). The volume of right middle frontal gyrus reduced significantly (p < 0.01). The FA and ADC of right hippocampus, the FA of left hippocampus and right middle temporal gyrus were significantly different. (2) A significant correlation between EDSS scores and ALFF was noted only in the left posterior cingulate gyrus. Our results detected structural and functional abnormalities in MS-SSCI and functional parameters were associated with clinical abnormalities. Multimodal imaging plays an important role in detecting structural and functional abnormalities in MS-SSCI. Advances in knowledge: This is the first time to apply RS-fMRI, VBM and diffusion tensor tractography to study the structural and functional abnormalities in MS-SSCI, and to explore its correlation with EDSS score.

Distributed cerebellar plasticity implements generalized multiple-scale memory components in real-robot sensorimotor tasks.

PubMed

Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A; Ferrigno, Giancarlo; D'Angelo, Egidio; Pedrocchi, Alessandra

2015-01-01

The cerebellum plays a crucial role in motor learning and it acts as a predictive controller. Modeling it and embedding it into sensorimotor tasks allows us to create functional links between plasticity mechanisms, neural circuits and behavioral learning. Moreover, if applied to real-time control of a neurorobot, the cerebellar model has to deal with a real noisy and changing environment, thus showing its robustness and effectiveness in learning. A biologically inspired cerebellar model with distributed plasticity, both at cortical and nuclear sites, has been used. Two cerebellum-mediated paradigms have been designed: an associative Pavlovian task and a vestibulo-ocular reflex, with multiple sessions of acquisition and extinction and with different stimuli and perturbation patterns. The cerebellar controller succeeded to generate conditioned responses and finely tuned eye movement compensation, thus reproducing human-like behaviors. Through a productive plasticity transfer from cortical to nuclear sites, the distributed cerebellar controller showed in both tasks the capability to optimize learning on multiple time-scales, to store motor memory and to effectively adapt to dynamic ranges of stimuli.

Gene transcription in sea otters (Enhydra lutris); development of a diagnostic tool for sea otter and ecosystem health

USGS Publications Warehouse

Bowen, Lizabeth; Miles, A. Keith; Murray, Michael; Haulena, Martin; Tuttle, Judy; van Bonn, William; Adams, Lance; Bodkin, James L.; Ballachey, Brenda E.; Estes, James A.; Tinker, M. Tim; Keister, Robin; Stott, Jeffrey L.

2012-01-01

Gene transcription analysis for diagnosing or monitoring wildlife health requires the ability to distinguish pathophysiological change from natural variation. Herein, we describe methodology for the development of quantitative real-time polymerase chain reaction (qPCR) assays to measure differential transcript levels of multiple immune function genes in the sea otter (Enhydra lutris); sea otter-specific qPCR primer sequences for the genes of interest are defined. We establish a ‘reference’ range of transcripts for each gene in a group of clinically healthy captive and free-ranging sea otters. The 10 genes of interest represent multiple physiological systems that play a role in immuno-modulation, inflammation, cell protection, tumour suppression, cellular stress response, xenobiotic metabolizing enzymes, antioxidant enzymes and cell–cell adhesion. The cycle threshold (CT) measures for most genes were normally distributed; the complement cytolysis inhibitor was the exception. The relative enumeration of multiple gene transcripts in simple peripheral blood samples expands the diagnostic capability currently available to assess the health of sea otters in situ and provides a better understanding of the state of their environment.

The parietal cortex in sensemaking: the dissociation of multiple types of spatial information.

PubMed

Sun, Yanlong; Wang, Hongbin

2013-01-01

According to the data-frame theory, sensemaking is a macrocognitive process in which people try to make sense of or explain their observations by processing a number of explanatory structures called frames until the observations and frames become congruent. During the sensemaking process, the parietal cortex has been implicated in various cognitive tasks for the functions related to spatial and temporal information processing, mathematical thinking, and spatial attention. In particular, the parietal cortex plays important roles by extracting multiple representations of magnitudes at the early stages of perceptual analysis. By a series of neural network simulations, we demonstrate that the dissociation of different types of spatial information can start early with a rather similar structure (i.e., sensitivity on a common metric), but accurate representations require specific goal-directed top-down controls due to the interference in selective attention. Our results suggest that the roles of the parietal cortex rely on the hierarchical organization of multiple spatial representations and their interactions. The dissociation and interference between different types of spatial information are essentially the result of the competition at different levels of abstraction.

The Parietal Cortex in Sensemaking: The Dissociation of Multiple Types of Spatial Information

PubMed Central

Sun, Yanlong; Wang, Hongbin

2013-01-01

According to the data-frame theory, sensemaking is a macrocognitive process in which people try to make sense of or explain their observations by processing a number of explanatory structures called frames until the observations and frames become congruent. During the sensemaking process, the parietal cortex has been implicated in various cognitive tasks for the functions related to spatial and temporal information processing, mathematical thinking, and spatial attention. In particular, the parietal cortex plays important roles by extracting multiple representations of magnitudes at the early stages of perceptual analysis. By a series of neural network simulations, we demonstrate that the dissociation of different types of spatial information can start early with a rather similar structure (i.e., sensitivity on a common metric), but accurate representations require specific goal-directed top-down controls due to the interference in selective attention. Our results suggest that the roles of the parietal cortex rely on the hierarchical organization of multiple spatial representations and their interactions. The dissociation and interference between different types of spatial information are essentially the result of the competition at different levels of abstraction. PMID:23710165

KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population.

PubMed

Hang, Dong; Yuan, Hua; Liu, Li; Wang, Lihua; Miao, Limin; Zhu, Meng; Du, Jiangbo; Dai, Juncheng; Hu, Zhibin; Chen, Ning; Shen, Hongbing; Ma, Hongxia

2017-01-01

KITLG/KIT pathway plays a vital role in multiple types of human cancer including head and neck squamous cell carcinoma (HNSCC). Genetic variations in KITLG and KIT may affect the expression or function of these genes, thereby modifying cancer risk. In this study, we evaluated the association of KITLG and KIT polymorphisms with HNSCC risk among Chinese population. Twenty-two tagging SNPs in KITLG and KIT genes were genotyped in a case-control study with 576 HNSCC patients and 1552 healthy controls. Logistic regression analyses revealed that an upstream SNP rs6554198 [additive model: adjusted odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.74-0.97, P = 0.019] and two intron SNPs rs2237025 (additive model: adjusted OR = 0.82, 95%CI = 0.70-0.95, P = 0.007), and rs17084687 (additive model: adjusted OR = 0.85, 95%CI = 0.73-0.99, P = 0.042) of KIT were significantly associated with the decreased risk of HNSCC. Combined analysis of the three SNPs showed that subjects carrying the protective alleles had decreased risk of HNSCC in a dose-response manner (P trend  = 0.001). Furthermore, interaction analyses revealed a significant multiplicative interaction between rs17084687 and drinking on HNSCC risk (P = 0.012). Luciferase activity assay indicated that the allele A of potentially functional rs6554198 led to significantly lower transcription activity of KIT compared to the risk allele G. Summarily, our findings suggested that SNPs in KIT gene may play a role in genetic susceptibility to HNSCC, which may improve our understanding of the pathogenic mechanisms of this disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Characterization and functional analysis of the Paralichthys olivaceus prdm1 gene promoter.

PubMed

Li, Peizhen; Wang, Bo; Cao, Dandan; Liu, Yuezhong; Zhang, Quanqi; Wang, Xubo

2017-10-01

PR domain containing protein 1 (Prdm1) is a transcriptional repressor identified in various species and plays multiple important roles in immune response and embryonic development. However, little is known about the transcriptional regulation of the prdm1 gene. This study aims to characterize the promoter of Paralichthys olivaceus prdm1 (Po-prdm1) gene and determine the regulatory mechanism of Po-prdm1 expression. A 2000bp-long 5'-flanking region (translation initiation site designated as +1) of the Po-prdm1 gene was isolated and characterized. The regulatory elements in this fragment were then investigated and many putative transcription factor (TF) binding sites involved in immunity and multiple tissue development were identified. A 5'-deletion analysis was then conducted, and the ability of the deletion mutants to promote luciferase and green fluorescent protein (GFP) expression in a flounder gill cell line was examined. The results revealed that the minimal promoter is located in the region between -446 and -13bp, and the region between -1415 and -13bp enhanced the promoter activity. Site-directed mutation analysis was subsequently performed on the putative regulatory elements sites, and the results indicated that FOXP1, MSX and BCL6 binding sites play negative functional roles in the regulation of the Po-prdm1 expression in FG cells. In vivo analysis demonstrated that a GFP reporter gene containing 1.4kb-long promoter fragment (-1415/-13) was expressed in the head and trunk muscle fibres of transient transgenic zebrafish embryos. Our study provided the basic information for the exploration of Po-prdm1 regulation and expression. Copyright © 2017 Elsevier Inc. All rights reserved.

An Unbiased Assessment of the Role of Imprinted Genes in an Intergenerational Model of Developmental Programming

PubMed Central

Radford, Elizabeth J.; Isganaitis, Elvira; Jimenez-Chillaron, Josep; Schroeder, Joshua; Molla, Michael; Andrews, Simon; Didier, Nathalie; Charalambous, Marika; McEwen, Kirsten; Marazzi, Giovanna; Sassoon, David; Patti, Mary-Elizabeth; Ferguson-Smith, Anne C.

2012-01-01

Environmental factors during early life are critical for the later metabolic health of the individual and of future progeny. In our obesogenic environment, it is of great socioeconomic importance to investigate the mechanisms that contribute to the risk of metabolic ill health. Imprinted genes, a class of functionally mono-allelic genes critical for early growth and metabolic axis development, have been proposed to be uniquely susceptible to environmental change. Furthermore, it has also been suggested that perturbation of the epigenetic reprogramming of imprinting control regions (ICRs) may play a role in phenotypic heritability following early life insults. Alternatively, the presence of multiple layers of epigenetic regulation may in fact protect imprinted genes from such perturbation. Unbiased investigation of these alternative hypotheses requires assessment of imprinted gene expression in the context of the response of the whole transcriptome to environmental assault. We therefore analyse the role of imprinted genes in multiple tissues in two affected generations of an established murine model of the developmental origins of health and disease using microarrays and quantitative RT–PCR. We demonstrate that, despite the functional mono-allelicism of imprinted genes and their unique mechanisms of epigenetic dosage control, imprinted genes as a class are neither more susceptible nor protected from expression perturbation induced by maternal undernutrition in either the F1 or the F2 generation compared to other genes. Nor do we find any evidence that the epigenetic reprogramming of ICRs in the germline is susceptible to nutritional restriction. However, we propose that those imprinted genes that are affected may play important roles in the foetal response to undernutrition and potentially its long-term sequelae. We suggest that recently described instances of dosage regulation by relaxation of imprinting are rare and likely to be highly regulated. PMID:22511876

Role of TRP channels in the cardiovascular system

PubMed Central

Yue, Zhichao; Xie, Jia; Yu, Albert S.; Stock, Jonathan; Du, Jianyang

2014-01-01

The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca2+-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. PMID:25416190

A mitochondrial alkaline/neutral invertase isoform (A/N-InvC) functions in developmental energy-demanding processes in Arabidopsis.

PubMed

Martín, Mariana L; Lechner, Leandra; Zabaleta, Eduardo J; Salerno, Graciela L

2013-03-01

Recent findings demonstrate that alkaline/neutral invertases (A/N-Invs), enzymes that catalyze the breakdown of sucrose into glucose and fructose, are essential proteins in plant life. The fact that different isoforms are present in multiple locations makes them candidates for the coordination of metabolic processes. In the present study, we functionally characterized the encoding gene of a novel A/N-Inv (named A/N-InvC) from Arabidopsis, which localizes in mitochondria. A/N-InvC is expressed in roots, in aerial parts (shoots and leaves) and flowers. A detailed phenotypic analysis of knockout mutant plants (invc) reveals an impaired growth phenotype. Shoot growth was severely reduced, but root development was not affected as reported for A/N-InvA mutant (inva) plants. Remarkably, germination and flowering, two energy demanding processes, were the most affected stages. The effect of exogenous growth regulators led us to suggest that A/N-InvC may be modulating hormone balance in relation to the radicle emergence. We also show that oxygen consumption is reduced in inva and invc in comparison with wild-type plants, indicating that both organelle isoenzymes may play a fundamental role in mitochondrion functionality. Taken together, our results emphasize the involvement of mitochondrial A/N-Invs in developmental processes and uncover the possibility of playing different roles for the two isoforms located in the organelle.

Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina.

PubMed

Irie, Shoichi; Sanuki, Rikako; Muranishi, Yuki; Kato, Kimiko; Chaya, Taro; Furukawa, Takahisa

2015-08-01

The Rax homeobox gene plays essential roles in multiple processes of vertebrate retina development. Many vertebrate species possess Rax and Rax2 genes, and different functions have been suggested. In contrast, mice contain a single Rax gene, and its functional roles in late retinal development are still unclear. To clarify mouse Rax function in postnatal photoreceptor development and maintenance, we generated conditional knockout mice in which Rax in maturing or mature photoreceptor cells was inactivated by tamoxifen treatment (Rax iCKO mice). When Rax was inactivated in postnatal Rax iCKO mice, developing photoreceptor cells showed a significant decrease in the level of the expression of rod and cone photoreceptor genes and mature adult photoreceptors exhibited a specific decrease in cone cell numbers. In luciferase assays, we found that Rax and Crx cooperatively transactivate Rhodopsin and cone opsin promoters and that an optimum Rax expression level to transactivate photoreceptor gene expression exists. Furthermore, Rax and Crx colocalized in maturing photoreceptor cells, and their coimmunoprecipitation was observed in cultured cells. Taken together, these results suggest that Rax plays essential roles in the maturation of both cones and rods and in the survival of cones by regulating photoreceptor gene expression with Crx in the postnatal mouse retina. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Role of TRP channels in the cardiovascular system.

PubMed

Yue, Zhichao; Xie, Jia; Yu, Albert S; Stock, Jonathan; Du, Jianyang; Yue, Lixia

2015-02-01

The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca(2+)-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca(2+) entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. Copyright © 2015 the American Physiological Society.

Light and Dark of Reactive Oxygen Species for Vascular Function: 2014 ASVB (Asian Society of Vascular Biology).

PubMed

Shimokawa, Hiroaki; Satoh, Kimio

2015-05-01

Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.

MicroRNA-like RNAs from the same miRNA precursors play a role in cassava chilling responses.

PubMed

Zeng, Changying; Xia, Jing; Chen, Xin; Zhou, Yufei; Peng, Ming; Zhang, Weixiong

2017-12-07

MicroRNAs (miRNAs) are known to play important roles in various cellular processes and stress responses. MiRNAs can be identified by analyzing reads from high-throughput deep sequencing. The reads realigned to miRNA precursors besides canonical miRNAs were initially considered as sequencing noise and ignored from further analysis. Here we reported a small-RNA species of phased and half-phased miRNA-like RNAs different from canonical miRNAs from cassava miRNA precursors detected under four distinct chilling conditions. They can form abundant multiple small RNAs arranged along precursors in a tandem and phased or half-phased fashion. Some of these miRNA-like RNAs were experimentally confirmed by re-amplification and re-sequencing, and have a similar qRT-PCR detection ratio as their cognate canonical miRNAs. The target genes of those phased and half-phased miRNA-like RNAs function in process of cell growth metabolism and play roles in protein kinase. Half-phased miR171d.3 was confirmed to have cleavage activities on its target gene P-glycoprotein 11, a broad substrate efflux pump across cellular membranes, which is thought to provide protection for tropical cassava during sharp temperature decease. Our results showed that the RNAs from miRNA precursors are miRNA-like small RNAs that are viable negative gene regulators and may have potential functions in cassava chilling responses.

Play and Literacy in Early Childhood: Research from Multiple Perspectives.

ERIC Educational Resources Information Center

Roskos, Kathleen A., Ed.; Christie, James F., Ed.

Noting that an examination of play from diverse perspectives deepens understanding and opens up new avenues for research and educational practice, this book brings together studies, research syntheses, and critical commentaries that examine play-literacy relationships from cognitive, ecological, and cultural perspectives. Each set of chapters is…

Using Playful Practice to Communicate with Special Children. David Fulton/Nasen

ERIC Educational Resources Information Center

Corke, Margaret

2011-01-01

Playfulness is important; it creates an alternative space where emotional, cognitive and social dimensions can be explored and tested. This highly practical book explores the endless possibilities of using playful, creative and interactive activities to meaningfully engage with children with multiple learning difficulties or autistic spectrum…

Bispectral analysis: comparison of two windowing functions

NASA Astrophysics Data System (ADS)

Silvagni, D.; Djerroud, C.; Réveillé, T.; Gravier, E.

2018-02-01

Amongst all the normalized forms of bispectrum, the bicoherence is shown to be a very useful diagnostic tool in experimental studies of nonlinear wave interactions in plasma, as it measures the fraction of wave power due to the quadratic wave coupling in a self-excited fluctuation spectrum [1, 2]. In order to avoid spectral leakage, the application of a windowing function is needed during the bicoherence computation. Spectral leakage from statistically dependent components are of crucial importance in the discrimination between coupled and uncoupled modes, as they will introduce in the bicoherence spectrum phase-coupled modes which in reality do not exist. Therefore, the windowing function plays a key role in the bicoherence estimation. In this paper, two windowing methods are compared: the multiplication of the initial signal by the Hanning function and the subtraction of the straight line which links the two extremities of the signal. The influence of these two windowing methods on both the power spectrum and the bicoherence spectrum is showed. Although both methods give precise results, the Hanning function appears to be the more suitable window.

How biological soil crusts became recognized as a functional unit: a selective history

USGS Publications Warehouse

Lange, Otto L.; Belnap, Jayne

2016-01-01

It is surprising that despite the world-wide distribution and general importance of biological soil crusts (biocrusts), scientific recognition and functional analysis of these communities is a relatively young field of science. In this chapter, we sketch the historical lines that led to the recognition of biocrusts as a community with important ecosystem functions. The idea of biocrusts as a functional ecological community has come from two main scientific branches: botany and soil science. For centuries, botanists have long recognized that multiple organisms colonize the soil surface in the open and often dry areas occurring between vascular plants. Much later, after the initial taxonomic and phyto-sociological descriptions were made, soil scientists and agronomists observed that these surface organisms interacted with soils in ways that changed the soil structure. In the 1970’s, research on these communities as ecological units that played an important functional role in drylands began in earnest, and these studies have continued to this day. Here, we trace the history of these studies from the distant past until 1990, when biocrusts became well-known to scientists and the public.

Involvement of the Warburg effect in non-tumor diseases processes.

PubMed

Chen, Zhe; Liu, Meiqing; Li, Lanfang; Chen, Linxi

2018-04-01

Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β-mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non-tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non-tumor diseases. © 2017 Wiley Periodicals, Inc.

A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?

PubMed

Morris, Gerwyn; Berk, Michael; Puri, Basant K

2018-04-01

There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes. Regional differences in neuronal resistance to oxidative and inflammatory insults and in the performance of antioxidant defences in the central nervous system may also play a role. Importantly, replicated experimental findings suggest that the use of high-resolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression. Further research involving this form of neuroimaging appears warranted in an attempt to overcome the problem of aetiologically heterogeneous cohorts which probably explain conflicting findings produced by investigative teams active in this field. However, the ionising radiation and relative lack of sensitivity involved probably preclude its use as a routine diagnostic tool.

An ABI3-interactor of conifers responds to multiple hormones.

PubMed

Zeng, Ying; Zhao, Tiehan; Kermode, Allison

2013-11-01

CnAIP2 (Callitropsis nootkatensis ABI3-Interacting Protein 2) was previously identified as a protein that interacts with the yellow-cedar ABI3 protein. CnAIP2 plays important roles during several key transitions of the plant lifecycle and acts as a global regulator with functions opposite to those of ABI3 proteins. Here we report that the CnAIP2 gene promoter is strongly upregulated by all of the major plant hormones. Young Arabidopsis seedlings expressing a chimeric CnAIP2pro-GUS construct were subjected to exogenously applied hormones; the maximum fold-enhancement of GUS activity was as high as 47-fold, and each hormone showed a distinctive cell/tissue-specific pattern of GUS induction. By far the greatest response was elicited by the synthetic auxin 2,4-D (47-fold induction); the other hormones tested stimulated GUS activities by 8- to 21-fold. The CnAIP2 promoter also responded to glucose and salt (NaCl), albeit to a lesser extent (2- to 3-fold induction). As well as acting in an antagonistic way to the global regulator ABI3, CnAIP2 appears to participate in multiple hormonal crosstalk pathways to carry out its functions.

Investigating the Function of Play Bows in Dog and Wolf Puppies (Canis lupus familiaris, Canis lupus occidentalis).

PubMed

Byosiere, Sarah-Elizabeth; Espinosa, Julia; Marshall-Pescini, Sarah; Smuts, Barbara; Range, Friederike

2016-01-01

Animals utilize behavioral signals across a range of different contexts in order to communicate with others and produce probable behavioral outcomes. During play animals frequently adopt action patterns used in other contexts. Researchers have therefore hypothesized that play signals have evolved to clarify communicative intent. One highly stereotyped play signal is the canid play bow, but its function remains contested. In order to clarify how canid puppies use play bows, we used data on play bows in immature wolves (ages 2.7-7.8 months) and dogs (ages 2 to 5 months) to test hypotheses evaluated in a previous study of adult dogs. We found that young dogs used play bows similarly to adult dogs; play bows most often occurred after a brief pause in play followed by complementary highly active play states. However, while the relative number of play bows and total observation time was similar between dog and wolf puppies, wolves did not follow this behavioral pattern, as play bows were unsuccessful in eliciting further play activity by the partner. While some similarities for the function of play bows in dog and wolf puppies were documented, it appears that play bows may function differently in wolf puppies in regards to re-initiating play.

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

PubMed

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Play as Regulation: Promoting Self-Regulation through Play

ERIC Educational Resources Information Center

Foley, Gilbert M.

2017-01-01

The nature of play and an overview of the stages of play in the first 5 years of childhood are discussed. The core features of sensorimotor, functional, and symbolic play are identified. Vignettes describing how play serves a regulatory function punctuate each section. A conceptual framework for the construct of regulation is presented and…

A single-sided homogeneous Green's function representation for holographic imaging, inverse scattering, time-reversal acoustics and interferometric Green's function retrieval

NASA Astrophysics Data System (ADS)

Wapenaar, Kees; Thorbecke, Jan; van der Neut, Joost

2016-04-01

Green's theorem plays a fundamental role in a diverse range of wavefield imaging applications, such as holographic imaging, inverse scattering, time-reversal acoustics and interferometric Green's function retrieval. In many of those applications, the homogeneous Green's function (i.e. the Green's function of the wave equation without a singularity on the right-hand side) is represented by a closed boundary integral. In practical applications, sources and/or receivers are usually present only on an open surface, which implies that a significant part of the closed boundary integral is by necessity ignored. Here we derive a homogeneous Green's function representation for the common situation that sources and/or receivers are present on an open surface only. We modify the integrand in such a way that it vanishes on the part of the boundary where no sources and receivers are present. As a consequence, the remaining integral along the open surface is an accurate single-sided representation of the homogeneous Green's function. This single-sided representation accounts for all orders of multiple scattering. The new representation significantly improves the aforementioned wavefield imaging applications, particularly in situations where the first-order scattering approximation breaks down.

The Effects of Point-of-View Video Modeling on Symbolic Play Actions and Play-Associated Language Utterances in Preschoolers with Autism

ERIC Educational Resources Information Center

Bonnet, Lauren Kravetz

2012-01-01

This single-subject research study was designed to examine the effects of point-of-view video modeling (POVM) on the symbolic play actions and play-associated language of four preschool students with autism. A multiple baseline design across participants was conducted in order to evaluate the effectiveness of using POVM as an intervention for…

USArray Receiver Function Imaging of Multiple-Layer Crustal Structure of the Contiguous United States

NASA Astrophysics Data System (ADS)

Ma, X.; Lowry, A. R.; Ravat, D.

2014-12-01

Thickness andseismic velocity of crustal layers are useful for understanding the history and evolution of continental lithosphere. Lowry and Pérez-Gussinyé (2011) observed that low bulk crustal seismic velocity ratio, Vp/Vs, strongly correlates with high geothermal gradient and active deformation, indicating quartz (to which Vp/Vs is most sensitive) plays a role in these processes. The lower crust (where ductile flow occurs which might explain the relationship) is commonly thought to be quartz-poor. However, layering of the crust may represent changes in either lithology or the phase of quartz. Laboratory strain-stress experiments on quartz indicate that near the a- to b-quartz phase transition, both Vp and Vp/Vs initially drop dramatically but then increase relative to the a-quartz regime because Young's modulus initially decreases by 30% before increasing by a net ~20%. Shear modulus varies only ~3% across the transition. Crustal structure is commonly represented by an upper, mid- and lower layer (e.g., Crust1.0) and conceptualized as primarily reflecting a change to more mafic lithology at greater depth, but estimates of Moho temperature indicate a quartz phase transition should be present in much of the western and central U.S. We have imaged multiple layering of the contiguous U.S. by applying a new cross-correlation and stacking method to USArray receiver functions. Synthetic models of a multiple layer crust indicate 'splitting' of converted-phase arrivals would be expected if a quartz phase transition were responsible. Preliminary imaging using cross-correlation of observed receiver functions with multiple layer synthetics demonstrates a marked improvement in correlation coefficients relative to a single-layer crust. In this presentation we will examine observational evidence for possible a- to b- phase transition layering (indicating quartz at depth) and compare with depths predicted for the quartz phase transition based on Pn-derived Moho temperatures and estimates of magnetic Curie depths.

Rereading Columbus: Critical Multicultural Analysis of Multiple Historical Storylines

ERIC Educational Resources Information Center

Bothelho, Maria Jose; Young, Sara Lewis-Bernstein; Nappi, Tara

2014-01-01

One prevalent practice of multicultural education is enlisting multiple perspectives for teaching. Oftentimes, these perspectives enter classrooms via digital texts, simulations/scenarios, primary documents, and debates. Children's and young adult literature play a critical role in these comparisons. However, these multiple perspectives are…

The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

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

Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

2006-01-13

Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, andmore » the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.« less

Glimpse into Hox and tale regulation of cell differentiation and reprogramming.

PubMed

Cerdá-Esteban, Nuria; Spagnoli, Francesca M

2014-01-01

During embryonic development, cells become gradually restricted in their developmental potential and start elaborating lineage-specific transcriptional networks to ultimately acquire a unique differentiated state. Hox genes play a central role in specifying regional identities, thereby providing the cell with critical information on positional value along its differentiation path. The exquisite DNA-binding specificity of the Hox proteins is frequently dependent upon their interaction with members of the TALE family of homeodomain proteins. In addition to their function as Hox-cofactors, TALE homeoproteins control multiple crucial developmental processes through Hox-independent mechanisms. Here, we will review recent findings on the function of both Hox and TALE proteins in cell differentiation, referring mostly to vertebrate species. In addition, we will discuss the direct implications of this knowledge on cell plasticity and cell reprogramming. Copyright © 2013 Wiley Periodicals, Inc.

Functional conservation of the human EXT1 tumor suppressor gene and its Drosophila homolog tout velu.

PubMed

Dasgupta, Ujjaini; Dixit, Bharat L; Rusch, Melissa; Selleck, Scott; The, Inge

2007-08-01

Heparan sulfate proteoglycans play a vital role in signaling of various growth factors in both Drosophila and vertebrates. In Drosophila, mutations in the tout velu (ttv) gene, a homolog of the mammalian EXT1 tumor suppressor gene, leads to abrogation of glycosaminoglycan (GAG) biosynthesis. This impairs distribution and signaling activities of various morphogens such as Hedgehog (Hh), Wingless (Wg), and Decapentaplegic (Dpp). Mutations in members of the exostosin (EXT) gene family lead to hereditary multiple exostosis in humans leading to bone outgrowths and tumors. In this study, we provide genetic and biochemical evidence that the human EXT1 (hEXT1) gene is conserved through species and can functionally complement the ttv mutation in Drosophila. The hEXT1 gene was able to rescue a ttv null mutant to adulthood and restore GAG biosynthesis.

Bim and Bmf in tissue homeostasis and malignant disease

PubMed Central

Piñon, JD; Labi, V; Egle, A; Villunger, A

2012-01-01

Among all BH3-only proteins known to date, most information is available on the biological role and function of Bim (Bcl-2 interacting mediator of cell death)/BOD (Bcl-2 related ovarian death agonist), whereas little is still known about its closest relative, Bcl-2 modifying factor (Bmf). Although Bim has been implicated in the regulation of cell death induction in multiple cell types and tissues in response to a large number of stimuli, including growth factor or cytokine deprivation, calcium flux, ligation of antigen receptors on T and B cells, glucocorticoid or loss of adhesion, Bmf seems to play a more restricted role by supporting Bim in some of these cell death processes. This review aims to highlight similarities between Bim and Bmf function in apoptosis signaling and their role in normal development and disease. PMID:19641506

Multiple Sensory-Motor Pathways Lead to Coordinated Visual Attention

PubMed Central

Yu, Chen; Smith, Linda B.

2016-01-01

Joint attention has been extensively studied in the developmental literature because of overwhelming evidence that the ability to socially coordinate visual attention to an object is essential to healthy developmental outcomes, including language learning. The goal of the present study is to understand the complex system of sensory-motor behaviors that may underlie the establishment of joint attention between parents and toddlers. In an experimental task, parents and toddlers played together with multiple toys. We objectively measured joint attention – and the sensory-motor behaviors that underlie it – using a dual head-mounted eye-tracking system and frame-by-frame coding of manual actions. By tracking the momentary visual fixations and hand actions of each participant, we precisely determined just how often they fixated on the same object at the same time, the visual behaviors that preceded joint attention, and manual behaviors that preceded and co-occurred with joint attention. We found that multiple sequential sensory-motor patterns lead to joint attention. In addition, there are developmental changes in this multi-pathway system evidenced as variations in strength among multiple routes. We propose that coordinated visual attention between parents and toddlers is primarily a sensory-motor behavior. Skill in achieving coordinated visual attention in social settings – like skills in other sensory-motor domains – emerges from multiple pathways to the same functional end. PMID:27016038

Multiple Sensory-Motor Pathways Lead to Coordinated Visual Attention.

PubMed

Yu, Chen; Smith, Linda B

2017-02-01

Joint attention has been extensively studied in the developmental literature because of overwhelming evidence that the ability to socially coordinate visual attention to an object is essential to healthy developmental outcomes, including language learning. The goal of this study was to understand the complex system of sensory-motor behaviors that may underlie the establishment of joint attention between parents and toddlers. In an experimental task, parents and toddlers played together with multiple toys. We objectively measured joint attention-and the sensory-motor behaviors that underlie it-using a dual head-mounted eye-tracking system and frame-by-frame coding of manual actions. By tracking the momentary visual fixations and hand actions of each participant, we precisely determined just how often they fixated on the same object at the same time, the visual behaviors that preceded joint attention and manual behaviors that preceded and co-occurred with joint attention. We found that multiple sequential sensory-motor patterns lead to joint attention. In addition, there are developmental changes in this multi-pathway system evidenced as variations in strength among multiple routes. We propose that coordinated visual attention between parents and toddlers is primarily a sensory-motor behavior. Skill in achieving coordinated visual attention in social settings-like skills in other sensory-motor domains-emerges from multiple pathways to the same functional end. Copyright © 2016 Cognitive Science Society, Inc.

Multiple functions of GABA A and GABA B receptors during pattern processing in the zebrafish olfactory bulb.

PubMed

Tabor, Rico; Yaksi, Emre; Friedrich, Rainer W

2008-07-01

gamma-Aminobutyric acid (GABA)ergic synapses are thought to play pivotal roles in the processing of activity patterns in the olfactory bulb (OB), but their functions have been difficult to study during odor responses in the intact system. We pharmacologically manipulated GABA(A) and GABA(B) receptors in the OB of zebrafish and analysed the effects on odor responses of the output neurons, the mitral cells (MCs), by electrophysiological recordings and temporally deconvolved two-photon Ca2+ imaging. The blockade of GABA(B) receptors enhanced presynaptic Ca2+ influx into afferent axon terminals, and changed the amplitude and time course of a subset of MC responses, indicating that GABA(B) receptors have a modulatory influence on OB output activity. The blockade of GABA(A) receptors induced epileptiform firing, enhanced excitatory responses and abolished fast oscillations in the local field potential. Moreover, the topological reorganization and decorrelation of MC activity patterns during the initial phase of the response was perturbed. These results indicate that GABA(A) receptor-containing circuits participate in the balance of excitation and inhibition, the regulation of total OB output activity, the synchronization of odor-dependent neuronal ensembles, and the reorganization of odor-encoding activity patterns. GABA(A) and GABA(B) receptors are therefore differentially involved in multiple functions of neuronal circuits in the OB.

The pleiotropic transcriptional regulator COUP-TFI plays multiple roles in neural development and disease.

PubMed

Bertacchi, Michele; Parisot, Josephine; Studer, Michèle

2018-04-27

Transcription factors are expressed in a dynamic fashion both in time and space during brain development, and exert their roles by activating a cascade of multiple target genes. This implies that understanding the precise function of a transcription factor becomes a challenging task. In this review, we will focus on COUP-TFI (or NR2F1), a nuclear receptor belonging to the superfamily of the steroid/thyroid hormone receptors, and considered to be one of the major transcriptional regulators orchestrating cortical arealization, cell-type specification and maturation. Recent data have unraveled the multi-faceted functions of COUP-TFI in the development of several mouse brain structures, including the neocortex, hippocampus and ganglionic eminences. Despite NR2F1 mutations and deletions in humans have been linked to a complex neurodevelopmental disease mainly associated to optic atrophy and intellectual disability, its role during the formation of the retina and optic nerve remains unclear. In light of its major influence in cortical development, we predict that its haploinsufficiency might be the cause of other cognitive diseases, not identified so far. Mouse models offer a unique opportunity of dissecting COUP-TFI function in different regions during brain assembly; hence, the importance of comparing and discussing common points linking mouse models to human patients' symptoms. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional brain imaging of cognitive dysfunction in Parkinson's disease.

PubMed

Hirano, Shigeki; Shinotoh, Hitoshi; Eidelberg, David

2012-10-01

Multiple factors are involved in the development of cognitive impairment in Parkinson's disease (PD) and related disorders. Notably, several underlying factors, such as monoaminergic dysfunction, Lewy body pathology, Alzheimer disease-like pathology and cerebrovascular disease are implied in the PD pathophysiology of cognitive impairment. The mesocortical dopaminergic system is associated with executive functions which are frequently affected in PD and are influenced by local levodopa concentration, dopamine metabolism and baseline performance status. The ventral striatum and frontal cortex are associated with impulse control disorders reported in PD patients treated with dopamine replacement therapy. Cholinergic impairment in PD plays a cardinal role in the development of dementia. Acetylcholinesterase positron emission tomography demonstrates that posterior brain areas are related to cognitive decline in PD patients. Amyloid radiotracer illustrates that patients with PD with severe cognitive impairment were prone to accompanied cortical amyloid deposition. Metabolism/perfusion change associated with cognitive impairment in PD, so-called PD related cognitive pattern, is characterised by reduced frontoparietal activity and is an effective way to differentiate and monitor cognitive function of individual PD patients. Cognitive impairment in PD cannot be explained by a single mechanism and is entangled by multiple factors. Imaging studies can unravel each pathological domain, further shed light on the interrelation between different pathomechanisms, not only in PD but also in other dementia related disorders, and thereby integrate its interpretation to apply to therapeutics in individual patients.

Conservation of tubulin-binding sequences in TRPV1 throughout evolution.

PubMed

Sardar, Puspendu; Kumar, Abhishek; Bhandari, Anita; Goswami, Chandan

2012-01-01

Transient Receptor Potential Vanilloid sub type 1 (TRPV1), commonly known as capsaicin receptor can detect multiple stimuli ranging from noxious compounds, low pH, temperature as well as electromagnetic wave at different ranges. In addition, this receptor is involved in multiple physiological and sensory processes. Therefore, functions of TRPV1 have direct influences on adaptation and further evolution also. Availability of various eukaryotic genomic sequences in public domain facilitates us in studying the molecular evolution of TRPV1 protein and the respective conservation of certain domains, motifs and interacting regions that are functionally important. Using statistical and bioinformatics tools, our analysis reveals that TRPV1 has evolved about ∼420 million years ago (MYA). Our analysis reveals that specific regions, domains and motifs of TRPV1 has gone through different selection pressure and thus have different levels of conservation. We found that among all, TRP box is the most conserved and thus have functional significance. Our results also indicate that the tubulin binding sequences (TBS) have evolutionary significance as these stretch sequences are more conserved than many other essential regions of TRPV1. The overall distribution of positively charged residues within the TBS motifs is conserved throughout evolution. In silico analysis reveals that the TBS-1 and TBS-2 of TRPV1 can form helical structures and may play important role in TRPV1 function. Our analysis identifies the regions of TRPV1, which are important for structure-function relationship. This analysis indicates that tubulin binding sequence-1 (TBS-1) near the TRP-box forms a potential helix and the tubulin interactions with TRPV1 via TBS-1 have evolutionary significance. This interaction may be required for the proper channel function and regulation and may also have significance in the context of Taxol®-induced neuropathy.

A Historical Journey in Science Education through Role Playing

ERIC Educational Resources Information Center

Guha, Smita

2013-01-01

In order to avoid a routine classroom environment, teachers often employ the use of role-plays. This is an effective strategy because it is essential for teachers to engage their students with information through various methods. Role-playing provides the children with the opportunity to incorporate multiple senses into a knowledge-based, fun…

Two Variations of Video Modeling Interventions for Teaching Play Skills to Children with Autism

ERIC Educational Resources Information Center

Sancho, Kimberly; Sidener, Tina M.; Reeve, Sharon A.; Sidener, David W.

2010-01-01

The current study employed an adapted alternating treatments design with reversal and multiple probe across participants components to compare the effects of traditional video priming and simultaneous video modeling on the acquisition of play skills in two children diagnosed with autism. Generalization was programmed across play sets, instructors,…

Role-Playing in Science Education: An Effective Strategy for Developing Multiple Perspectives

ERIC Educational Resources Information Center

Howes, Elaine V.; Cruz, Barbara C.

2009-01-01

Role-playing can be an engaging and creative strategy to use in the college classroom. Using official accounts, personal narratives, and diaries to recreate a particular time period, event, or personality, the instructional strategy alternately referred to as role-playing, dramatic improvisation, or first-person characterization can be an…

Relationship between output from MIDI-keyboard playing and hand function assessments on affected hand after stroke.

PubMed

Chong, Hyun Ju; Han, Soo Jeong; Kim, Yong Jae; Park, Hye Young; Kim, Soo Ji

2014-01-01

While a number of studies have tested the therapeutic effectiveness of playing musical instruments, such as the electronic keyboard using Musical Instrument Digital Interface (MIDI), it is still unclear whether outcomes of electronic keyboard playing are related to hand function tests. The purpose of this study was to investigate the correlation between MIDI-keyboard playing and hand function tests, including grip strength, Box and Block test (BBT), and Jensen-Taylor Hand Function Test (JTHF). A total of 66 stroke patients were recruited from medical centers and were classified into acute (n = 21), subacute (n = 28), and chronic (n = 17) recovery stages. The participants' mean age was 60.5 years. The MIDI-keyboard playing protocol based on sequential key pressing was implemented. All hand function tests were performed by certified occupational therapists. MIDI scores from participants at all three recovery stages were significantly correlated with BBT and grip strength. Overall, MIDI-keyboard playing scores demonstrated moderate to high correlations with hand function tests except for participants at the chronic stage and the JTHF, which showed no correlation. These findings suggest that MIDI-keyboard playing has great potential as an assessment tool of hand function, especially hand dexterity in acute and subacute stroke patients. Further studies are needed to refine the specific keyboard playing tasks that increase responsiveness to traditional hand function tests.

The intestinal microenvironment in sepsis.

PubMed

Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

2017-10-01

The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

Impact of playing American professional football on long-term brain function.

PubMed

Amen, Daniel G; Newberg, Andrew; Thatcher, Robert; Jin, Yi; Wu, Joseph; Keator, David; Willeumier, Kristen

2011-01-01

The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Nutrition Interventions in Chronic Kidney Disease.

PubMed

Anderson, Cheryl A M; Nguyen, Hoang Anh; Rifkin, Dena E

2016-11-01

Dietary modification is recommended in the management of chronic kidney disease (CKD). Individuals with CKD often have multiple comorbidities, such as high blood pressure, diabetes, obesity, and cardiovascular disease, for which dietary modification is also recommended. As CKD progresses, nutrition plays an important role in mitigating risk for cardiovascular disease and decline in kidney function. The objectives of nutrition interventions in CKD include management of risk factors, ensuring optimal nutritional status throughout all stages of CKD, preventing buildup of toxic metabolic products, and avoiding complications of CKD. Recommended dietary changes should be feasible, sustainable, and suited for patients' food preferences and clinical needs. Copyright © 2016 Elsevier Inc. All rights reserved.

The multisensory brain and its ability to learn music.

PubMed

Zimmerman, Emily; Lahav, Amir

2012-04-01

Playing a musical instrument requires a complex skill set that depends on the brain's ability to quickly integrate information from multiple senses. It has been well documented that intensive musical training alters brain structure and function within and across multisensory brain regions, supporting the experience-dependent plasticity model. Here, we argue that this experience-dependent plasticity occurs because of the multisensory nature of the brain and may be an important contributing factor to musical learning. This review highlights key multisensory regions within the brain and discusses their role in the context of music learning and rehabilitation. © 2012 New York Academy of Sciences.

Wilms' tumour 1 (WT1) in development, homeostasis and disease.

PubMed

Hastie, Nicholas D

2017-08-15

The study of genes mutated in human disease often leads to new insights into biology as well as disease mechanisms. One such gene is Wilms' tumour 1 ( WT1 ), which plays multiple roles in development, tissue homeostasis and disease. In this Primer, I summarise how this multifaceted gene functions in various mammalian tissues and organs, including the kidney, gonads, heart and nervous system. This is followed by a discussion of our current understanding of the molecular mechanisms by which WT1 and its two major isoforms regulate these processes at the transcriptional and post-transcriptional levels. © 2017. Published by The Company of Biologists Ltd.

A Mild, Ferrocene-Catalyzed C–H Imidation of (Hetero)Arenes

PubMed Central

2015-01-01

A simple method for direct C–H imidation is reported using a new perester-based self-immolating reagent and a base-metal catalyst. The succinimide products obtained can be easily deprotected in situ (if desired) to reveal the corresponding anilines directly. The scope of the reaction is broad, the conditions are extremely mild, and the reaction is tolerant of oxidizable and acid-labile functionality, multiple heteroatoms, and aryl iodides. Mechanistic studies indicate that ferrocene (Cp2Fe) plays the role of an electron shuttle in the decomposition of the perester reagent, delivering a succinimidyl radical ready to add to an aromatic system. PMID:24654983

Target oriented drugs against leishmania. Annual summary report no. 2, 1 May 1980-30 April 1981

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

Zehavi, U.; El-On, J.

1981-01-31

Excreted Factor (EF) is a carbohydrate-rich material released by different strains of Leishmania during growth. It has antigenic properties similar to those of the intact parasite and plays a role in the infective process. Isolation and purification of EF is necessary for study of its biological function, its use for diagnostic purposes, its use in immunization experiments, the study of its biosynthesis, and the preparation of inhibitors of particular biosynthetic steps. Purification of EF by affinity chromatography was markedly improved by introducing Ricinus lectin (specific for galactose) column. This enabled us to obtain more reliable amino acid and sugar analysismore » and will be instrumental in more advanced physical, chemical, and immunological studies. We have developed a radioimmunoassay for leishmaniasis utilizing purified EF. The assay can distinguish between Leishmania strains and once further developed, should prove most valuable for the diagnosis of the disease. EF plays a role in the infective process of Leishmania. We have now shown that surface carbohydrate, related to EF, plays a role in the initial attachment of Leishmania promastigots to macrophages - a stage that is a prelude to their engulfment by the macrophages followed by multiplication in their cells.« less

A Novel Role of Periostin in Postnatal Tooth Formation and Mineralization*

PubMed Central

Ma, Dedong; Zhang, Rong; Sun, Yao; Rios, Hector F.; Haruyama, Naoto; Han, Xianglong; Kulkarni, Ashok B.; Qin, Chunlin; Feng, Jian Q.

2011-01-01

Periostin plays multiple functions during development. Our previous work showed a critical role of this disulfide-linked cell adhesion protein in maintenance of periodontium integrity in response to occlusal load. In this study, we attempted to address whether this mechanical response molecule played a direct role in postnatal tooth development. Our key findings are 1) periostin is expressed in preodontoblasts, and odontoblasts; and the periostin-null incisor displayed a massive increase in dentin formation after mastication; 2) periostin is also expressed in the ameloblast cells, and an enamel defect is identified in both the adult-null incisor and molar; 3) deletion of periostin leads to changes in expression profiles of many non-collagenous protein such as DSPP, DMP1, BSP, and OPN in incisor dentin; 4) the removal of a biting force leads to reduction of mineralization, which is partially prevented in periostin-null mice; and 6) both in vitro and in vivo data revealed a direct regulation of periostin by TGF-β1 in dentin formation. In conclusion, periostin plays a novel direct role in controlling postnatal tooth formation, which is required for the integrity of both enamel and dentin. PMID:21131362

[MAIT cells in autoimmunity].

PubMed

Miyake, Sachiko

2012-01-01

Mucosal associated invariant T (MAIT) cells are restricted by a nonpolymorphic MHC-related molecule-1 (MR1), and express an invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. MAIT cells are selected in the thymus, but, interestingly, MAIT cells require B cells as well as commensal flora for their peripheral expansion. Bourhis et al demonstrated that MAIT cells display antimicrobial capacity. Both human and mouse MAIT cells have been shown to be activated by Escherichia coli-infected antigen presenting cells in an MR1-dependent manner. MAIT cells show a protective role against Mycobacteriu abscessus or E. coli infections in mice. Human MAIT cells are capable of producing IFNγ and IL-17 and are found in Mycobacterium tuberculosis-infected lung tissues. Thus, MAIT cells play an antimicrobial function under these infectious conditions. MAIT cells play a protective role against autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), whereas they play a pathogenic role in murine models of arthritis. In patients with autoimmune diseases, the frequency of MAIT cells in peripheral blood was significantly reduced. The frequency of MAIT cells reflected the disease activity in MS patients, suggesting the involvement of MAIT cells in the regulation of autoimmune diseases.

Functional Multiple-Set Canonical Correlation Analysis

ERIC Educational Resources Information Center

Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

2012-01-01

We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

Strategy Instruction and Maintenance of Basic Multiplication Facts through Digital Game Play

ERIC Educational Resources Information Center

Denham, André R.

2013-01-01

Formative instruction on multiplication primarily focuses on rote memorization. This leads to factual fluency, but also develops a narrow view of multiplication and hinders the development of conceptual understanding. Theory and research recommend the concurrent development of conceptual understanding and factual fluency during the initial stages…

A Framework for Understanding Experiments

DTIC Science & Technology

2008-06-01

operations. Experiments that emphasize free play and uncertainty in scenarios reflect conditions found in existent operations and satisfy external...validity Requirement 4, the ability to relate results. Conversely, experiments emphasizing similar conditions with diminished free play across multiple

High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development.

PubMed

Hefti, Marco M; Farrell, Kurt; Kim, SoongHo; Bowles, Kathryn R; Fowkes, Mary E; Raj, Towfique; Crary, John F

2018-01-01

The microtubule associated protein tau plays a critical role in the pathogenesis of neurodegenerative disease. Recent studies suggest that tau also plays a role in disorders of neuronal connectivity, including epilepsy and post-traumatic stress disorder. Animal studies have shown that the MAPT gene, which codes for the tau protein, undergoes complex pre-mRNA alternative splicing to produce multiple isoforms during brain development. Human data, particularly on temporal and regional variation in tau splicing during development are however lacking. In this study, we present the first detailed examination of the temporal and regional sequence of MAPT alternative splicing in the developing human brain. We used a novel computational analysis of large transcriptomic datasets (total n = 502 patients), quantitative polymerase chain reaction (qPCR) and western blotting to examine tau expression and splicing in post-mortem human fetal, pediatric and adult brains. We found that MAPT exons 2 and 10 undergo abrupt shifts in expression during the perinatal period that are unique in the canonical human microtubule-associated protein family, while exon 3 showed small but significant temporal variation. Tau isoform expression may be a marker of neuronal maturation, temporally correlated with the onset of axonal growth. Immature brain regions such as the ganglionic eminence and rhombic lip had very low tau expression, but within more mature regions, there was little variation in tau expression or splicing. We thus demonstrate an abrupt, evolutionarily conserved shift in tau isoform expression during the human perinatal period that may be due to tau expression in maturing neurons. Alternative splicing of the MAPT pre-mRNA may play a vital role in normal brain development across multiple species and provides a basis for future investigations into the developmental and pathological functions of the tau protein.

Genome-Wide Identification and Expression Analysis of WRKY Transcription Factors under Multiple Stresses in Brassica napus

PubMed Central

He, Yajun; Mao, Shaoshuai; Gao, Yulong; Zhu, Liying; Wu, Daoming; Cui, Yixin; Li, Jiana; Qian, Wei

2016-01-01

WRKY transcription factors play important roles in responses to environmental stress stimuli. Using a genome-wide domain analysis, we identified 287 WRKY genes with 343 WRKY domains in the sequenced genome of Brassica napus, 139 in the A sub-genome and 148 in the C sub-genome. These genes were classified into eight groups based on phylogenetic analysis. In the 343 WRKY domains, a total of 26 members showed divergence in the WRKY domain, and 21 belonged to group I. This finding suggested that WRKY genes in group I are more active and variable compared with genes in other groups. Using genome-wide identification and analysis of the WRKY gene family in Brassica napus, we observed genome duplication, chromosomal/segmental duplications and tandem duplication. All of these duplications contributed to the expansion of the WRKY gene family. The duplicate segments that were detected indicated that genome duplication events occurred in the two diploid progenitors B. rapa and B. olearecea before they combined to form B. napus. Analysis of the public microarray database and EST database for B. napus indicated that 74 WRKY genes were induced or preferentially expressed under stress conditions. According to the public QTL data, we identified 77 WRKY genes in 31 QTL regions related to various stress tolerance. We further evaluated the expression of 26 BnaWRKY genes under multiple stresses by qRT-PCR. Most of the genes were induced by low temperature, salinity and drought stress, indicating that the WRKYs play important roles in B. napus stress responses. Further, three BnaWRKY genes were strongly responsive to the three multiple stresses simultaneously, which suggests that these 3 WRKY may have multi-functional roles in stress tolerance and can potentially be used in breeding new rapeseed cultivars. We also found six tandem repeat pairs exhibiting similar expression profiles under the various stress conditions, and three pairs were mapped in the stress related QTL regions, indicating tandem duplicate WRKYs in the adaptive responses to environmental stimuli during the evolution process. Our results provide a framework for future studies regarding the function of WRKY genes in response to stress in B. napus. PMID:27322342

Genome-Wide Identification and Expression Analysis of WRKY Transcription Factors under Multiple Stresses in Brassica napus.

PubMed

He, Yajun; Mao, Shaoshuai; Gao, Yulong; Zhu, Liying; Wu, Daoming; Cui, Yixin; Li, Jiana; Qian, Wei

2016-01-01

WRKY transcription factors play important roles in responses to environmental stress stimuli. Using a genome-wide domain analysis, we identified 287 WRKY genes with 343 WRKY domains in the sequenced genome of Brassica napus, 139 in the A sub-genome and 148 in the C sub-genome. These genes were classified into eight groups based on phylogenetic analysis. In the 343 WRKY domains, a total of 26 members showed divergence in the WRKY domain, and 21 belonged to group I. This finding suggested that WRKY genes in group I are more active and variable compared with genes in other groups. Using genome-wide identification and analysis of the WRKY gene family in Brassica napus, we observed genome duplication, chromosomal/segmental duplications and tandem duplication. All of these duplications contributed to the expansion of the WRKY gene family. The duplicate segments that were detected indicated that genome duplication events occurred in the two diploid progenitors B. rapa and B. olearecea before they combined to form B. napus. Analysis of the public microarray database and EST database for B. napus indicated that 74 WRKY genes were induced or preferentially expressed under stress conditions. According to the public QTL data, we identified 77 WRKY genes in 31 QTL regions related to various stress tolerance. We further evaluated the expression of 26 BnaWRKY genes under multiple stresses by qRT-PCR. Most of the genes were induced by low temperature, salinity and drought stress, indicating that the WRKYs play important roles in B. napus stress responses. Further, three BnaWRKY genes were strongly responsive to the three multiple stresses simultaneously, which suggests that these 3 WRKY may have multi-functional roles in stress tolerance and can potentially be used in breeding new rapeseed cultivars. We also found six tandem repeat pairs exhibiting similar expression profiles under the various stress conditions, and three pairs were mapped in the stress related QTL regions, indicating tandem duplicate WRKYs in the adaptive responses to environmental stimuli during the evolution process. Our results provide a framework for future studies regarding the function of WRKY genes in response to stress in B. napus.

The Influence of an Educational Course on Language Expression and Treatment of Gaming Addiction for Massive Multiplayer Online Role-Playing Game (MMORPG) Players

ERIC Educational Resources Information Center

Kim, Pyoung Won; Kim, Seo Young; Shim, Miseon; Im, Chang-Hwan; Shon, Young-Min

2013-01-01

Addiction to Massive Multiple Online Role-Playing Games (MMORPGs) among juveniles has become a serious problem in Korea and has led to legislation prohibiting juveniles from playing games after midnight. One key factor in gaming addiction is the so-called narrative, or story, gamers create for themselves while playing. This study investigated how…

The hearing ear is always found close to the speaking tongue: Review of the role of the motor system in speech perception.

PubMed

Skipper, Jeremy I; Devlin, Joseph T; Lametti, Daniel R

2017-01-01

Does "the motor system" play "a role" in speech perception? If so, where, how, and when? We conducted a systematic review that addresses these questions using both qualitative and quantitative methods. The qualitative review of behavioural, computational modelling, non-human animal, brain damage/disorder, electrical stimulation/recording, and neuroimaging research suggests that distributed brain regions involved in producing speech play specific, dynamic, and contextually determined roles in speech perception. The quantitative review employed region and network based neuroimaging meta-analyses and a novel text mining method to describe relative contributions of nodes in distributed brain networks. Supporting the qualitative review, results show a specific functional correspondence between regions involved in non-linguistic movement of the articulators, covertly and overtly producing speech, and the perception of both nonword and word sounds. This distributed set of cortical and subcortical speech production regions are ubiquitously active and form multiple networks whose topologies dynamically change with listening context. Results are inconsistent with motor and acoustic only models of speech perception and classical and contemporary dual-stream models of the organization of language and the brain. Instead, results are more consistent with complex network models in which multiple speech production related networks and subnetworks dynamically self-organize to constrain interpretation of indeterminant acoustic patterns as listening context requires. Copyright © 2016. Published by Elsevier Inc.

Cell-type-specific expression of NFIX in the developing and adult cerebellum.

PubMed

Fraser, James; Essebier, Alexandra; Gronostajski, Richard M; Boden, Mikael; Wainwright, Brandon J; Harvey, Tracey J; Piper, Michael

2017-07-01

Transcription factors from the nuclear factor one (NFI) family have been shown to play a central role in regulating neural progenitor cell differentiation within the embryonic and post-natal brain. NFIA and NFIB, for instance, promote the differentiation and functional maturation of granule neurons within the cerebellum. Mice lacking Nfix exhibit delays in the development of neuronal and glial lineages within the cerebellum, but the cell-type-specific expression of this transcription factor remains undefined. Here, we examined the expression of NFIX, together with various cell-type-specific markers, within the developing and adult cerebellum using both chromogenic immunohistochemistry and co-immunofluorescence labelling and confocal microscopy. In embryos, NFIX was expressed by progenitor cells within the rhombic lip and ventricular zone. After birth, progenitor cells within the external granule layer, as well as migrating and mature granule neurons, expressed NFIX. Within the adult cerebellum, NFIX displayed a broad expression profile, and was evident within granule cells, Bergmann glia, and interneurons, but not within Purkinje neurons. Furthermore, transcriptomic profiling of cerebellar granule neuron progenitor cells showed that multiple splice variants of Nfix are expressed within this germinal zone of the post-natal brain. Collectively, these data suggest that NFIX plays a role in regulating progenitor cell biology within the embryonic and post-natal cerebellum, as well as an ongoing role within multiple neuronal and glial populations within the adult cerebellum.

Evolution analysis of Dof transcription factor family and their expression in response to multiple abiotic stresses in Malus domestica.

PubMed

Zhang, Zhengrong; Yuan, Li; Liu, Xin; Chen, Xuesen; Wang, Xiaoyun

2018-01-10

As a family of transcription factors, DNA binding with one figure (Dof) proteins play important roles in various biological processes in plants. Here, a total of 60 putative apple (Malus domestica) Dof genes (MdDof) were identified and mapped to different chromosomes. Chromosomal distribution and synteny analysis indicated that the expansion of the MdDof genes came primarily from segmental and duplication events, and from whole genome duplication, which lead to more Dof members in apples than in other plants. All 60 MdDof genes were classified into thirteen groups, according to multiple sequence alignment and the phylogenetic tree constructed of Dof genes from apple, peach (Prunus persica), Arabidopsis and rice. Within each group, the members shared a similar exon/intron and motif compositions, although the sizes of the MdDof genes and encoding proteins were quite different. Several Dof genes from the apple and peach were identified to be homologues based on their close synteny relationship, which suggested that these genes bear similar functions. Half of the MdDof genes were randomly selected to determine their responses to different stresses. The majority of MdDof genes were quite sensitive to PEG, NaCl, cold and exogenous ABA treatment. Our results suggested that MdDof family members may play important roles in plant tolerance to abiotic stress. Copyright © 2017 Elsevier B.V. All rights reserved.

nfi-1 affects behavior and life-span in C. elegans but is not essential for DNA replication or survival

PubMed Central

Lazakovitch, Elena; Kalb, John M; Matsumoto, Reiko; Hirono, Keiko; Kohara, Yuji; Gronostajski, Richard M

2005-01-01

Background The Nuclear Factor I (one) (NFI) family of transcription/replication factors plays essential roles in mammalian gene expression and development and in adenovirus DNA replication. Because of its role in viral DNA replication NFI has long been suspected to function in host DNA synthesis. Determining the requirement for NFI proteins in mammalian DNA replication is complicated by the presence of 4 NFI genes in mice and humans. Loss of individual NFI genes in mice cause defects in brain, lung and tooth development, but the presence of 4 homologous NFI genes raises the issue of redundant roles for NFI genes in DNA replication. No NFI genes are present in bacteria, fungi or plants. However single NFI genes are present in several simple animals including Drosophila and C. elegans, making it possible to test for a requirement for NFI in multicellular eukaryotic DNA replication and development. Here we assess the functions of the single nfi-1 gene in C. elegans. Results C. elegans NFI protein (CeNFI) binds specifically to the same NFI-binding site recognized by vertebrate NFIs. nfi-1 encodes alternatively-spliced, maternally-inherited transcripts that are expressed at the single cell stage, during embryogenesis, and in adult muscles, neurons and gut cells. Worms lacking nfi-1 survive but have defects in movement, pharyngeal pumping and egg-laying and have a reduced life-span. Expression of the muscle gene Ce titin is decreased in nfi-1 mutant worms. Conclusion NFI gene function is not needed for survival in C. elegans and thus NFI is likely not essential for DNA replication in multi-cellular eukaryotes. The multiple defects in motility, egg-laying, pharyngeal pumping, and reduced lifespan indicate that NFI is important for these processes. Reduction in Ce titin expression could affect muscle function in multiple tissues. The phenotype of nfi-1 null worms indicates that NFI functions in multiple developmental and behavioral systems in C. elegans, likely regulating genes that function in motility, egg-laying, pharyngeal pumping and lifespan maintenance. PMID:16242019

Additive roles of two TPS genes in trehalose synthesis, conidiation, multiple stress responses and host infection of a fungal insect pathogen.

PubMed

Wang, Juan-Juan; Cai, Qing; Qiu, Lei; Ying, Sheng-Hua; Feng, Ming-Guang

2017-05-01

Intracellular trehalose accumulation is relevant to fungal life and pathogenicity. Trehalose-6-phosphate synthase (TPS) is known to control the first step of trehalose synthesis, but functions of multiple TPS genes in some filamentous fungi are variable. Here, we examined the functions of two TPS genes (tpsA and tpsB) in Beauveria bassiana, a fungal insect pathogen widely applied in arthropod pest control. Intracellular TPS activity and trehalose content decreased by 71-75 and 72-80% in ΔtpsA, and 21-30 and 15-45% in ΔtpsB, respectively, and to undetectable levels in ΔtpsAΔtpsB, under normal and stressful conditions. The three mutants lost 33, 50, and 98% of conidiation capacity in standard cultures. Conidial quality indicated by viability, density, intracellular trehalose content, cell wall integrity, and hydrophobicity was more impaired in ΔtpsA than in ΔtpsB and mostly in ΔtpsAΔtpsB, which was also most sensitive to nutritional, chemical, and environmental stresses and least virulent to Galleria mellonella larvae. Almost all of phenotypic defects in ΔtpsAΔtpsB approached to the sums of those observed in ΔtpsA and ΔtpsB and were restored by targeted gene complementation. Altogether, TpsA and TpsB play complementary roles in sustaining trehalose synthesis, conidiation capacity, conidial quality, multiple stress tolerance, and virulence, highlighting a significance of both for the fungal adaptation to environment and host.

Biocrust-forming mosses mitigate the negative impacts of increasing aridity on ecosystem multifunctionality in drylands.

PubMed

Delgado-Baquerizo, Manuel; Maestre, Fernando T; Eldridge, David J; Bowker, Matthew A; Ochoa, Victoria; Gozalo, Beatriz; Berdugo, Miguel; Val, James; Singh, Brajesh K

2016-03-01

The increase in aridity predicted with climate change will have a negative impact on the multiple functions and services (multifunctionality) provided by dryland ecosystems worldwide. In these ecosystems, soil communities dominated by mosses, lichens and cyanobacteria (biocrusts) play a key role in supporting multifunctionality. However, whether biocrusts can buffer the negative impacts of aridity on important biogeochemical processes controlling carbon (C), nitrogen (N), and phosphorus (P) pools and fluxes remains largely unknown. Here, we conducted an empirical study, using samples from three continents (North America, Europe and Australia), to evaluate how the increase in aridity predicted by climate change will alter the capacity of biocrust-forming mosses to modulate multiple ecosystem processes related to C, N and P cycles. Compared with soil surfaces lacking biocrusts, biocrust-forming mosses enhanced multiple functions related to C, N and P cycling and storage in semiarid and arid, but not in humid and dry-subhumid, environments. Most importantly, we found that the relative positive effects of biocrust-forming mosses on multifunctionality compared with bare soil increased with increasing aridity. These results were mediated by plant cover and the positive effects exerted by biocrust-forming mosses on the abundance of soil bacteria and fungi. Our findings provide strong evidence that the maintenance of biocrusts is crucial to buffer negative effects of climate change on multifunctionality in global drylands. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Prediction of reported consumption of selected fat-containing foods.

PubMed

Tuorila, H; Pangborn, R M

1988-10-01

A total of 100 American females (mean age = 20.8 years) completed a questionnaire, in which their beliefs, evaluations, liking and consumption (frequency, consumption compared to others, intention to consume) of milk, cheese, ice cream, chocolate and "high-fat foods" were measured. For the design and analysis, the basic frame of reference was the Fishbein-Ajzen model of reasoned action, but the final analyses were carried out with stepwise multiple regression analysis. In addition to the components of the Fishbein-Ajzen model, beliefs and evaluations were used as independent variables. On the average, subjects reported liking all the products but not "high-fat foods", and thought that milk and cheese were "good for you" whereas the remaining items were "bad for you". Principal component analysis for beliefs revealed factors related to pleasantness/benefit aspects, to health and weight concern and to the "functionality" of the foods. In stepwise multiple regression analyses, liking was the predominant predictor of reported consumption for all the foods, but various belief factors, particularly those related to concern with weight, also significantly predicted consumption. Social factors played only a minor role. The multiple R's of the predictive functions varied from 0.49 to 0.74. The fact that all four foods studied elicited individual sets of beliefs and belief structures, and that none of them was rated similar to the generic "high-fat foods", emphasizes that consumers attach meaning to integrated food entities rather than to ingredients.

Cross sectional associations of screen time and outdoor play with social skills in preschool children

PubMed Central

Carson, Valerie

2018-01-01

Screen time and physical activity behaviours develop during the crucial early childhood period (0–5 years) and impact multiple health and developmental outcomes, including psychosocial wellbeing. Social skills, one component of psychosocial wellbeing, are vital for children’s school readiness and future mental health. This study investigates potential associations of screen time and outdoor play (as a proxy for physical activity) with social skills. Cross sectional data were available for 575 mothers with a child (54% boys) aged 2–5 years. Mothers reported their child’s screen time, outdoor play time and social skills (Adaptive Social Behavior Inventory; ASBI). Multiple linear regression analyses assessed associations of screen and outdoor play time (Model 1) and compliance with screen time and physical activity recommendations (Model 2) with three ASBI subscales. Boys and girls spent a mean of 2.0 and 2.2 hours per day in screen time, and 3.3 and 2.9 hours per day in outdoor play, respectively. Girls scores for express and comply skills were significantly higher than boys (p<0.005). After applying the Benjamini-Hochberg Procedure to adjust for multiple associations, children’s television/DVD/video viewing was inversely associated with their compliant scores (B = -0.35 95% CI -0.26, -0.14; p = 0.001) and outdoor play time was positively associated with both expressive (B = 0.20 95% CI 0.07, 0.34; p = 0.004) and compliant (B = 0.22 95% CI 0.08, 0.36; p = 0.002) scores. Findings indicate that television/DVD/video viewing may be adversely, and outdoor play favourably, associated with preschool children’s social skills. Future research is required to identify the direction of causation and explore potential mechanisms of association. PMID:29617366

Cross sectional associations of screen time and outdoor play with social skills in preschool children.

PubMed

Hinkley, Trina; Brown, Helen; Carson, Valerie; Teychenne, Megan

2018-01-01

Screen time and physical activity behaviours develop during the crucial early childhood period (0-5 years) and impact multiple health and developmental outcomes, including psychosocial wellbeing. Social skills, one component of psychosocial wellbeing, are vital for children's school readiness and future mental health. This study investigates potential associations of screen time and outdoor play (as a proxy for physical activity) with social skills. Cross sectional data were available for 575 mothers with a child (54% boys) aged 2-5 years. Mothers reported their child's screen time, outdoor play time and social skills (Adaptive Social Behavior Inventory; ASBI). Multiple linear regression analyses assessed associations of screen and outdoor play time (Model 1) and compliance with screen time and physical activity recommendations (Model 2) with three ASBI subscales. Boys and girls spent a mean of 2.0 and 2.2 hours per day in screen time, and 3.3 and 2.9 hours per day in outdoor play, respectively. Girls scores for express and comply skills were significantly higher than boys (p<0.005). After applying the Benjamini-Hochberg Procedure to adjust for multiple associations, children's television/DVD/video viewing was inversely associated with their compliant scores (B = -0.35 95% CI -0.26, -0.14; p = 0.001) and outdoor play time was positively associated with both expressive (B = 0.20 95% CI 0.07, 0.34; p = 0.004) and compliant (B = 0.22 95% CI 0.08, 0.36; p = 0.002) scores. Findings indicate that television/DVD/video viewing may be adversely, and outdoor play favourably, associated with preschool children's social skills. Future research is required to identify the direction of causation and explore potential mechanisms of association.

Sequence-specific backbone resonance assignments and microsecond timescale molecular dynamics simulation of human eosinophil-derived neurotoxin.

PubMed

Gagné, Donald; Narayanan, Chitra; Bafna, Khushboo; Charest, Laurie-Anne; Agarwal, Pratul K; Doucet, Nicolas

2017-10-01

Eight active canonical members of the pancreatic-like ribonuclease A (RNase A) superfamily have been identified in human. All structural homologs share similar RNA-degrading functions, while also cumulating other various biological activities in different tissues. The functional homologs eosinophil-derived neurotoxin (EDN, or RNase 2) and eosinophil cationic protein (ECP, or RNase 3) are known to be expressed and secreted by eosinophils in response to infection, and have thus been postulated to play an important role in host defense and inflammatory response. We recently initiated the biophysical and dynamical investigation of several vertebrate RNase homologs and observed that clustering residue dynamics appear to be linked with the phylogeny and biological specificity of several members. Here we report the 1 H, 13 C and 15 N backbone resonance assignments of human EDN (RNase 2) and its molecular dynamics simulation on the microsecond timescale, providing means to pursue this comparative atomic-scale functional and dynamical analysis by NMR and computation over multiple time frames.

MACF1, versatility in tissue-specific function and in human disease.

PubMed

Hu, Lifang; Xiao, Yunyun; Xiong, Zhipeng; Zhao, Fan; Yin, Chong; Zhang, Yan; Su, Peihong; Li, Dijie; Chen, Zhihao; Ma, Xiaoli; Zhang, Ge; Qian, Airong

2017-09-01

Spectraplakins are a family of evolutionarily conserved gigantic proteins and play critical roles in many cytoskeleton-related processes. Microtubule actin crosslinking factor 1 (MACF1) is one of the most versatile spectraplakin with multiple isoforms. As a broadly expressed mammalian spectraplakin, MACF1 is important in maintaining normal functions of many tissues. The loss-of-function studies using knockout mouse models reveal the pivotal roles of MACF1 in embryo development, skin integrity maintenance, neural development, bone formation, and colonic paracellular permeability. Mutation in the human MACF1 gene causes a novel myopathy genetic disease. In addition, abnormal expression of MACF1 is associated with schizophrenia, Parkinson's disease, cancer and osteoporosis. This demonstrates the crucial roles of MACF1 in physiology and pathology. Here, we review the research advances of MACF1's roles in specific tissue and in human diseases, providing the perspectives of MACF1 for future studies. Copyright © 2017. Published by Elsevier Ltd.

Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism

PubMed Central

Shi, Yuguang; Cheng, Dong

2009-01-01

Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications. PMID:19116371

Educational action in the rehabilitation of severe acquired brain injuries: the role of self-awareness.

PubMed

Silvestro, Daniela; Mazzetti, Maria; Melia, Chiara; Stagno, Maria Teresa; Carlesimo, Giovanni Augusto; Bivona, Umberto; Formisano, Rita

2017-01-01

Severe acquired brain injuries (ABI) cause a range of short-or long-term limitations in physical and neuropsychological abilities. The aim of rehabilitation is to promote the harmonious development of the individual through collaboration between medical and educational sciences, involved in the educability of the whole person, in which the aim is not only functional recovery but also social-reintegration. This "functional synergy" permits the development of the person, and establishes an indissoluble link between functions and attitudes, thus allowing the achievement of the greater possible autonomy. In this way classical and pedagogical rehabilitation may be combined in a single concept of educational action. To realize this integrated educational process it is important to evaluate and promote awareness development, based on the possibilities of brain plasticity and on the presence of multiple intelligences skillfully intertwined each other. Therefore, self-awareness plays a prime role in educational actions for the rehabilitation of persons with severe ABI.

CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.

PubMed

Huynh, Kevin W; Jiang, Jiansen; Abuladze, Natalia; Tsirulnikov, Kirill; Kao, Liyo; Shao, Xuesi; Newman, Debra; Azimov, Rustam; Pushkin, Alexander; Zhou, Z Hong; Kurtz, Ira

2018-03-02

Na + -coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na + -coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 Å resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode.

Excited state characterization of carbonyl containing carotenoids: a comparison between single and multireference descriptions

NASA Astrophysics Data System (ADS)

Spezia, Riccardo; Knecht, Stefan; Mennucci, Benedetta

Carotenoids can play multiple roles in biological photoreceptors thanks to their rich photophysics. In the present work, we have investigated six of the most common carbonyl containing carotenoids: Echinenone, Canthaxanthin, Astaxanthin, Fucoxanthin, Capsanthin and Capsorubin. Their excitation properties are investigated by means of a hybrid density functional theory (DFT) and multireference configuration interaction (MRCI) approach to elucidate the role of the carbonyl group: the bright transition is of {\\pi}{\\pi}* character, as expected, but the presence of a C=O moiety reduces the energy of n{\\pi}* transitions which may become closer to the {\\pi}{\\pi}* transition, in particular as the conjugation chain decreases. This can be related to the presence of a low-lying charge transfer state typical of short carbonyl- containing carotenoids. The DFT/MRCI results are finally used to benchmark single- reference time-dependent DFT-based methods: among the investigated functionals, the meta- GGA (and in particular M11L and MN12L) functionals show to perform the best for all six investigated systems.

[The motor organization of cerebral cortex and the role of the mirror neuron system. Clinical impact for rehabilitation].

PubMed

Sallés, Laia; Gironès, Xavier; Lafuente, José Vicente

2015-01-06

The basic characteristics of Penfield homunculus (somatotopy and unique representation) have been questioned. The existence of a defined anatomo-functional organization within different segments of the same region is controversial. The presence of multiple motor representations in the primary motor area and in the parietal lobe interconnected by parieto-frontal circuits, which are widely overlapped, form a complex organization. Both features support the recovery of functions after brain injury. Regarding the movement organization, it is possible to yield a relevant impact through the understanding of actions and intentions of others, which is mediated by the activation of mirror-neuron systems. The implementation of cognitive functions (observation, image of the action and imitation) from the acute treatment phase allows the activation of motor representations without having to perform the action and it plays an important role in learning motor patterns. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

CDK regulation of transcription by RNAP II: Not over 'til it's over?

PubMed

Fisher, Robert P

2017-03-15

Transcription by RNA polymerase (RNAP) II is regulated at multiple steps by phosphorylation, catalyzed mainly by members of the cyclin-dependent kinase (CDK) family. The CDKs involved in transcription have overlapping substrate specificities, but play largely non-redundant roles in coordinating gene expression. Novel functions and targets of CDKs have recently emerged at the end of the transcription cycle, when the primary transcript is cleaved, and in most cases polyadenylated, and transcription is terminated by the action of the "torpedo" exonuclease Xrn2, which is a CDK substrate. Collectively, various functions have been ascribed to CDKs or CDK-mediated phosphorylation: recruiting cleavage and polyadenylation factors, preventing premature termination within gene bodies while promoting efficient termination of full-length transcripts, and preventing extensive readthrough transcription into intergenic regions or neighboring genes. The assignment of precise functions to specific CDKs is still in progress, but recent advances suggest ways in which the CDK network and RNAP II machinery might cooperate to ensure timely exit from the transcription cycle.

Positive association of vitamin D receptor gene variations with multiple sclerosis in South East Iranian population.

PubMed

Narooie-Nejad, Mehrnaz; Moossavi, Maryam; Torkamanzehi, Adam; Moghtaderi, Ali

2015-01-01

Among the factors postulated to play a role in MS susceptibility, the role of vitamin D is outstanding. Since the function of vitamin D receptor (VDR) represents the effect of vitamin D on the body and genetic variations in VDR gene may affect its function, we aim to highlight the association of two VDR gene polymorphisms with MS susceptibility. In current study, we recruited 113 MS patients and 122 healthy controls. TaqI (rs731236) and ApaI (rs7975232) genetic variations in these two groups were evaluated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. All genotype and allele frequencies in both variations showed association with the disease status. However, to find the definite connection between genetic variations in VDR gene and MS disease in a population of South East of Iran, more researches on gene structure and its function with regard to patients' conditions are required.

Cell type-specific long-range connections of basal forebrain circuit.

PubMed

Do, Johnny Phong; Xu, Min; Lee, Seung-Hee; Chang, Wei-Cheng; Zhang, Siyu; Chung, Shinjae; Yung, Tyler J; Fan, Jiang Lan; Miyamichi, Kazunari; Luo, Liqun; Dan, Yang

2016-09-19

The basal forebrain (BF) plays key roles in multiple brain functions, including sleep-wake regulation, attention, and learning/memory, but the long-range connections mediating these functions remain poorly characterized. Here we performed whole-brain mapping of both inputs and outputs of four BF cell types - cholinergic, glutamatergic, and parvalbumin-positive (PV+) and somatostatin-positive (SOM+) GABAergic neurons - in the mouse brain. Using rabies virus -mediated monosynaptic retrograde tracing to label the inputs and adeno-associated virus to trace axonal projections, we identified numerous brain areas connected to the BF. The inputs to different cell types were qualitatively similar, but the output projections showed marked differences. The connections to glutamatergic and SOM+ neurons were strongly reciprocal, while those to cholinergic and PV+ neurons were more unidirectional. These results reveal the long-range wiring diagram of the BF circuit with highly convergent inputs and divergent outputs and point to both functional commonality and specialization of different BF cell types.

CDK regulation of transcription by RNAP II: Not over ‘til it's over?

PubMed Central

Fisher, Robert P.

2017-01-01

ABSTRACT Transcription by RNA polymerase (RNAP) II is regulated at multiple steps by phosphorylation, catalyzed mainly by members of the cyclin-dependent kinase (CDK) family. The CDKs involved in transcription have overlapping substrate specificities, but play largely non-redundant roles in coordinating gene expression. Novel functions and targets of CDKs have recently emerged at the end of the transcription cycle, when the primary transcript is cleaved, and in most cases polyadenylated, and transcription is terminated by the action of the “torpedo” exonuclease Xrn2, which is a CDK substrate. Collectively, various functions have been ascribed to CDKs or CDK-mediated phosphorylation: recruiting cleavage and polyadenylation factors, preventing premature termination within gene bodies while promoting efficient termination of full-length transcripts, and preventing extensive readthrough transcription into intergenic regions or neighboring genes. The assignment of precise functions to specific CDKs is still in progress, but recent advances suggest ways in which the CDK network and RNAP II machinery might cooperate to ensure timely exit from the transcription cycle. PMID:28005463

Physiological and pathological functions of acid-sensing ion channels in the central nervous system

PubMed Central

Chu, Xiang-Ping; Xiong, Zhi-Gang

2012-01-01

Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain ischemia, multiple sclerosis, epileptic seizures, and malignant glioma. Thus, targeting these channels may lead to novel therapeutic interventions for neurological disorders. The goal of this review is to provide an update on recent advances in our understanding of the functions of ASICs in the CNS. PMID:22204324

Multifunctional Mitochondrial AAA Proteases

PubMed Central

Glynn, Steven E.

2017-01-01

Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle. PMID:28589125

Multifunctional Mitochondrial AAA Proteases.

PubMed

Glynn, Steven E

2017-01-01

Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

PubMed Central

Lough, Kendall J.; Patel, Jeet H.; Descovich, Carlos Patiño; Curtis, T. Anthony

2016-01-01

Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation. PMID:27317810

NAD Kinases: Metabolic Targets Controlling Redox Co-enzymes and Reducing Power Partitioning in Plant Stress and Development

PubMed Central

Li, Bin-Bin; Wang, Xiang; Tai, Li; Ma, Tian-Tian; Shalmani, Abdullah; Liu, Wen-Ting; Li, Wen-Qiang; Chen, Kun-Ming

2018-01-01

NAD(H) and NADP(H) are essential co-enzymes which dominantly control a number of fundamental biological processes by acting as reducing power and maintaining the intracellular redox balance of all life kingdoms. As the only enzymes that catalyze NAD(H) and ATP to synthesize NADP(H), NAD Kinases (NADKs) participate in many essential metabolic reactions, redox sensitive regulation, photosynthetic performance and also reactive oxygen species (ROS) homeostasis of cells and therefore, play crucial roles in both development and stress responses of plants. NADKs are highly conserved enzymes in amino acid sequences but have multiple subcellular localization and diverse functions. They may function as monomers, dimers or multimers in cells but the enzymatic properties in plants are not well elucidated yet. The activity of plant NADK is regulated by calcium/calmodulin and plays crucial roles in photosynthesis and redox co-enzyme control. NADK genes are expressed in almost all tissues and developmental stages of plants with specificity for different members. Their transcripts can be greatly stimulated by a number of environmental factors such as pathogenic attack, irritant applications and abiotic stress treatments. Using transgenic approaches, several studies have shown that NADKs are involved in chlorophyll synthesis, photosynthetic efficiency, oxidative stress protection, hormone metabolism and signaling regulation, and therefore contribute to the growth regulation and stress tolerance of plants. In this review, the enzymatic properties and functional mechanisms of plant NADKs are thoroughly investigated based on literature and databases. The results obtained here are greatly advantageous for further exploration of NADK function in plants. PMID:29662499

Multiple Functions of Aromatic-Carbohydrate Interactions in a Processive Cellulase Examined with Molecular Simulation*

PubMed Central

Payne, Christina M.; Bomble, Yannick J.; Taylor, Courtney B.; McCabe, Clare; Himmel, Michael E.; Crowley, Michael F.; Beckham, Gregg T.

2011-01-01

Proteins employ aromatic residues for carbohydrate binding in a wide range of biological functions. Glycoside hydrolases, which are ubiquitous in nature, typically exhibit tunnels, clefts, or pockets lined with aromatic residues for processing carbohydrates. Mutation of these aromatic residues often results in significant activity differences on insoluble and soluble substrates. However, the thermodynamic basis and molecular level role of these aromatic residues remain unknown. Here, we calculate the relative ligand binding free energy by mutating tryptophans in the Trichoderma reesei family 6 cellulase (Cel6A) to alanine. Removal of aromatic residues near the catalytic site has little impact on the ligand binding free energy, suggesting that aromatic residues immediately upstream of the active site are not directly involved in binding, but play a role in the glucopyranose ring distortion necessary for catalysis. Removal of aromatic residues at the entrance and exit of the Cel6A tunnel, however, dramatically impacts the binding affinity, suggesting that these residues play a role in chain acquisition and product stabilization, respectively. The roles suggested from differences in binding affinity are confirmed by molecular dynamics and normal mode analysis. Surprisingly, our results illustrate that aromatic-carbohydrate interactions vary dramatically depending on the position in the enzyme tunnel. As aromatic-carbohydrate interactions are present in all carbohydrate-active enzymes, these results have implications for understanding protein structure-function relationships in carbohydrate metabolism and recognition, carbon turnover in nature, and protein engineering strategies for biomass utilization. Generally, these results suggest that nature employs aromatic-carbohydrate interactions with a wide range of binding affinities for diverse functions. PMID:21965672

Poor Cognitive Inhibition Predicts Rumination About Insomnia in a Clinical Sample.

PubMed

Ballesio, Andrea; Ottaviani, Cristina; Lombardo, Caterina

2018-04-20

According to the Cognitive Model of Insomnia disorder, rumination about lack of sleep and its diurnal consequences plays a crucial role in maintaining insomnia. Consolidated evidence shows that rumination is related to poor executive functions, which are cognitive control processes impacted by insomnia. Despite this evidence, no studies so far investigated the relationship between executive functions and rumination in individuals with insomnia. The aim of this pilot study was to cover this gap by investigating whether poor executive functions are associated with rumination in a sample of individuals with a diagnosis of insomnia disorder. Thirty young adults (22.67 ± 3.68 years, 73.3% females) diagnosed with insomnia disorder by clinical psychologists with expertise in behavioral sleep medicine completed the study. Measures of insomnia, depression, emotion regulation, and rumination about the daytime consequences of insomnia were collected. Executive functions were assessed using a Task Switching paradigm, measuring cognitive inhibition and set-shifting with cognitive flexibility. Hierarchical multiple regression analysis revealed that higher depression (β = 0.781, p < 0.001) and cognitive reappraisal (β = 0.329, p = 0.016), and poorer cognitive inhibition (β = -0.334, p = 0.014), significantly predicted higher rumination. Rumination about symptoms of insomnia in a clinical sample is associated with impaired inhibitory but not switching capacities above and beyond the role played by traditional predictors such as depression and emotion regulation strategies. If replicated, present preliminary results suggest the need to target cognitive inhibition deficits in insomnia treatment.

NF-κB (p65) negatively regulates myocardin-induced cardiomyocyte hypertrophy through multiple mechanisms.

PubMed

Liao, Xing-Hua; Wang, Nan; Zhao, Dong-Wei; Zheng, De-Liang; Zheng, Li; Xing, Wen-Jing; Zhou, Hao; Cao, Dong-Sun; Zhang, Tong-Cun

2014-12-01

Myocardin is well known to play a key role in the development of cardiomyocyte hypertrophy. But the exact molecular mechanism regulating myocardin stability and transactivity to affect cardiomyocyte hypertrophy has not been studied clearly. We now report that NF-κB (p65) can inhibit myocardin-induced cardiomyocyte hypertrophy. Then we explore the molecular mechanism of this response. First, we show that p65 can functionally repress myocardin transcriptional activity and also reduce the protein expression of myocardin. Second, the function of myocardin can be regulated by epigenetic modifications. Myocardin sumoylation is known to transactivate cardiac genes, but whether p65 can inhibit SUMO modification of myocardin is still not clear. Our data show that p65 weakens myocardin transcriptional activity through attenuating SUMO modification of myocardin by SUMO1/PIAS1, thereby impairing myocardin-mediated cardiomyocyte hypertrophy. Furthermore, the expression of myocardin can be regulated by several microRNAs, which play important roles in the development and function of the heart and muscle. We next investigated potential role of miR-1 in cardiac hypotrophy. Our results show that p65 can upregulate the level of miR-1 and miR-1 can decrease protein expression of myocardin in cardiac myocytes. Notably, miR-1 expression is also controlled by myocardin, leading to a feedback loop. These data thus provide important and novel insights into the function that p65 inhibits myocardin-mediated cardiomyocyte hypertrophy by downregulating the expression and SUMO modification of myocardin and enhancing the expression of miR-1. Copyright © 2014 Elsevier Inc. All rights reserved.

Complex pelvic ring injuries associated with floating knee in a poly-trauma patient: A case report.

PubMed

Zhou, Yuebin; Guo, Honggang; Cai, Zhiwei; Zhang, Yuan

2017-12-01

Complex pelvic ring fracture associated with floating knee is comparatively rare which usually results from high-energy trauma including vehicle-related accidence, falls from height, and earthquake-related injury. To our knowledge, few literatures have documented such injuries in the individual patient. Management of both injuries present challenges for surgical management and postoperative care. The purpose of this study is to prove the feasibility and benefits of damage control orthopedics (DCO). Our case involved a 45-year-old lady who was hit by a dilapidated building. The patient was anxious, pale and hemodynamically stable at the initial examination. The pelvis was unstable and there were obvious deformities in the left lower extremities. Significant degloved injuries in the left leg were noted. Her radiographs and physical examination verified the above signs. Unstable pelvic fractures, multiple fractures of bilateral lower limbs with floating knee injury, multiple pelvic and rib fractures and multiple degloving injuries and soft tissue contusion formed the characteristics of the multiple-injury. The algorithm of DCO was determined as the treatment. Early simplified procedures such as wound debridement, pelvis fixation, closed reduction and EF of the right shoulder joint, and chest wall fixation were conducted as soon as possible. After a period of time, internal fixations were applied to the fracture sites. The subsequent functional exercise was also conducted in accordance with this algorithm. This patient got recovery after the treatments which were guided by the criterion of DCO. The restoration of limb functional and the quality of life greatly improved. The DCO plays a decisive role in the first aid and follow-up treatment of this patient. The guidelines of management of complex pelvic ring injuries and floating knee should be established by authorities.

Differences in dynamic balance scores in one sport versus multiple sport high school athletes.

PubMed

Gorman, Paul P; Butler, Robert J; Rauh, Mitchell J; Kiesel, Kyle; Plisky, Phillip J

2012-04-01

Researchers have previously reported on the importance of dynamic balance in assessing an individual's risk for injury during sport. However, to date there is no research on whether multiple sport participation affects dynamic balance ability. Therefore, the purpose of this study was to determine if there was a difference in dynamic balance scores in high school athletes that competed in one sport only as compared athletes who competed in multiple sports, as tested by the Lower Quarter Y Balance Test (YBT-LQ). Ninety-two high school athletes who participated in one sport were matched, by age, gender and sport played, to athletes who participated in the same sport as well as additional sports. All individuals were assessed using the YBT-LQ to examine differences in composite reach score and reach direction asymmetry between single sport and multiple sport athletes. The greatest reach distance of three trials in each reach direction for right and left lower-extremities was normalized by limb length and used for analysis. A two-way ANOVA (gender x number of sports played) was used to statistically analyze the variables in the study. No significant interactions or main effects related to number of sports played were observed for any YBT-LQ score (p>0.05). Male athletes exhibited significantly greater normalized reach values for the posteromedial, posterolateral, and composite reach while also exhibiting a larger anterior reach difference when compared to the females. Athletes who participated in multiple sports had similar performances on the YBT-LQ when compared to athletes who participated in a single sport. The findings of this study suggest that the number of sports played by a high school athlete does not need to be controlled for when evaluating dynamic balance with the YBT-LQ.

Hereditary Multiple Exostoses: a review of clinical appearance and metabolic pattern

PubMed Central

Beltrami, Giovanni; Ristori, Gabriele; Scoccianti, Guido; Tamburini, Angela; Capanna, Rodolfo

2016-01-01

Summary Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare autosomal dominant disorder, mainly caused by loss of function mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). These genes are linked to heparan sulfate (HS) synthesis, but the specific molecular mechanism leading to the disruption of the cartilage structure and the consequent exostoses formation is still not resolved. The aim of this paper is to encounter the main aspects of HME reviewing the literature, in order to improve clinical features and evolution, and the metabolic-pathogenetic mechanisms underlying. Although MHE may be asymptomatic, a wide spectrum of clinical manifestations is found in paediatric patients with this disorder. Pain is experienced by the majority of patients, even restricted motion of the joint is often encountered. Sometimes exostoses can interfere with normal development of the growth plate, giving rise to limb deformities, low stature and scoliosis. Other many neurovascular and associated disorders can lead to surgery. The most feared complication is the malignant transformation of an existing osteochondroma into a secondary peripheral chondrosarcoma, during adulthood. The therapeutic approach to HME is substantially surgical, whereas the medical one is still at an experimental level. In conclusion, HME is a complex disease where the paediatrician, the geneticist and the orthopaedic surgeon play an interchangeable role in diagnosis, research and therapy. We are waiting for new studies able to explain better the role of HS in signal transduction, because it plays a role in other bone and cartilage diseases (in particular malignant degeneration) as well as in skeletal embryology. PMID:27920806

Galectin-3 in M2 macrophages plays a protective role in resolution of neuropathology in brain parasitic infection by regulating neutrophil turnover.

PubMed

Quenum Zangbede, Fredice O; Chauhan, Arun; Sharma, Jyotika; Mishra, Bibhuti B

2018-06-26

Macrophages/microglia with M2- activation phenotype are thought to play an important anti-inflammatory and tissue reparative functions in the brain, yet the molecular basis of their functions in the central nervous system (CNS) remain to be clearly defined. In a preclinical model of neurocysticercosis using brain infection with a parasite Mesocestoides corti , we previously reported the presence of large numbers of M2 cells in the CNS. In this study using female mice, we report that M2 macrophages in the parasite-infected brain display abundant galectin-3 expression. Disease severity was increased in Galectin-3 -/- mice correlating with increased neurological defects, augmented cell death and, importantly, massive accumulation of neutrophils and M2 macrophages in the CNS of these mice. Because neutrophil clearance by efferocytosis is an important function of M2 macrophages, we investigated a possible role of galectin-3 in this process. Indeed, galectin-3 deficient M2 macrophages exhibited a defect in efferocytic clearance of neutrophils in-vitro. Furthermore, adoptive transfer of M2 macrophages from Galectin-3 sufficient WT mice reduced neutrophilia in the CNS and ameliorated disease severity in parasite-infected Galectin-3 -/- mice. Together, these results demonstrate for the first time a novel role of galectin-3 in M2 macrophage function in neutrophil turnover and resolution of inflammatory pathology in the CNS. This likely will have implications in neurocysticercosis and neuro-inflammatory diseases. SIGNIFICANCE STATEMENT Macrophages/microglia with M1-activation phenotype are thought to promote CNS pathology, whereas M2-anti-inflammatory phenotype promote CNS repair. However, the mechanisms regulating M2 cell protective functions in the CNS microenvironment are undefined. Quenum Zangbede et. al., report that helminth infection of the brain induces an increased expression of galectin-3 in M2 macrophages accumulated in the CNS. Using multiple experimental models in vivo and in vitro , they show that galectin-3 in M2 macrophages functions to clear neutrophils accumulated in the CNS. Importantly, galectin-3 in M2 macrophages plays a central role in the containment of neuropathology and disease severity. These results provide a direct mechanistic evidence of the protective function of M2- macrophages in the CNS. Copyright © 2018 the authors.

p110α and p110β isoforms of PI3K signaling: are they two sides of the same coin?

PubMed

Singh, Paramjeet; Dar, Mohd Saleem; Dar, Mohd Jamal

2016-09-01

Class-1 phosphatidylinositol-3-kinases (PI3Ks) are activated by a variety of extracellular stimuli and have been implicated in a wide range of cellular processes. p110α and p110β are the two most studied isoforms of the class-1A PI3K signaling pathway. Although these two isoforms are ubiquitously expressed and play multiple redundant roles, they also have distinct functions within the cell. More recently, p110α and p110β isoforms have been shown to translocate into the nucleus and play a role in DNA replication and repair, and in cell cycle progression. In the following Review article, we discuss the overlapping and unique roles of p110α and p110β isoforms with a particular focus on their structure, expression analysis, subcellular localization, and signaling contributions in various cell types and model organisms. © 2016 Federation of European Biochemical Societies.

Estrogens, Neuroinflammation, and Neurodegeneration

PubMed Central

Villa, Alessandro; Vegeto, Elisabetta; Poletti, Angelo

2016-01-01

Inflammatory activation of microglia is a hallmark of several disorders of the central nervous system. In addition to protecting the brain against inflammatory insults, microglia are neuroprotective and play a significant role in maintaining neuronal connectivity, but the prolongation of an inflammatory status may limit the beneficial functions of these immune cells. The finding that estrogen receptors are present in monocyte-derived cells and that estrogens prevent and control the inflammatory response raise the question of the role that this sex steroid plays in the manifestation and progression of pathologies that have a clear sex difference in prevalence, such as multiple sclerosis, Parkinson's disease, and Alzheimer's disease. The present review aims to provide a critical review of the current literature on the actions of estrogen in microglia and on the involvement of estrogen receptors in the manifestation of selected neurological disorders. This current understanding highlights a research area that should be expanded to identify appropriate replacement therapies to slow the progression of such diseases. PMID:27196727

Reduced-fat foods: the complex science of developing diet-based strategies for tackling overweight and obesity.

PubMed

McClements, David J

2015-05-01

Fat plays multiple roles in determining the desirable physicochemical properties, sensory attributes, nutritional profile, and biologic response of food products. Overconsumption of fats is linked to chronic diseases, such as obesity, coronary heart disease, diabetes, and cancer. There is therefore a need to develop reduced-fat products with physicochemical properties and sensory profiles that match those of their full-fat counterparts. In addition, foods may be redesigned to increase the feelings of satiety and satiation, and thereby reduce overall food intake. The successful design of these types of functional foods requires a good understanding of the numerous roles that fat plays in determining food attributes and the development of effective strategies to replace these attributes. This article provides an overview of the current understanding of the influence of fat on the physicochemical and physiologic attributes of emulsion-based food products and highlights approaches to create high-quality foods with reduced-fat contents. © 2015 American Society for Nutrition.

Discovery of an Inhibitor of the Proteasome Subunit Rpn11.

PubMed

Perez, Christian; Li, Jing; Parlati, Francesco; Rouffet, Matthieu; Ma, Yuyong; Mackinnon, Andrew L; Chou, Tsui-Fen; Deshaies, Raymond J; Cohen, Seth M

2017-02-23

The proteasome plays a crucial role in degradation of normal proteins that happen to be constitutively or inducibly unstable, and in this capacity it plays a regulatory role. Additionally, it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control function. Inhibitors of the proteasome have been validated in the treatment of multiple myeloma, with several FDA-approved therapeutics. Rpn11 is a Zn 2+ -dependent metalloisopeptidase that hydrolyzes ubiquitin from tagged proteins that are trafficked to the proteasome for degradation. A fragment-based drug discovery (FBDD) approach was utilized to identify fragments with activity against Rpn11. Screening of a library of metal-binding pharmacophores (MBPs) revealed that 8-thioquinoline (8TQ, IC 50 value ∼2.5 μM) displayed strong inhibition of Rpn11. Further synthetic elaboration of 8TQ yielded a small molecule compound (35, IC 50 value ∼400 nM) that is a potent and selective inhibitor of Rpn11 that blocks proliferation of tumor cells in culture.

Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment.

PubMed

Kryczek, Ilona; Wei, Shuang; Zou, Linhua; Altuwaijri, Saleh; Szeliga, Wojciech; Kolls, Jay; Chang, Alfred; Zou, Weiping

2007-06-01

Th17 cells play an active role in inflammation and autoimmune diseases. However, the nature and regulation of Th17 in the context of tumor immunity remain unknown. In this study, we show that parallel to regulatory T (Treg) cells, IL-17(+) CD4(+) and CD8(+) T cells are kinetically induced in multiple tumor microenvironments in mice and humans. Treg cells play a crucial role in tumor immune pathogenesis and temper immune therapeutic efficacy. IL-2 is crucial for the production and function of Treg cells. We now show that IL-2 reduces IL-17(+) T cell differentiation in the tumor microenvironment accompanied with an enhanced Treg cell compartment in vitro and in vivo. Altogether, our work demonstrates a dynamic differentiation of IL-17(+) T cells in the tumor microenvironment, reveals a novel role for IL-2 in controlling the balance between IL-17(+) and Treg cells, and provides new insight of IL-17(+) T cells in tumor immune pathology and therapy.

Melatonin, mitochondria and hypertension.

PubMed

Baltatu, Ovidiu C; Amaral, Fernanda G; Campos, Luciana A; Cipolla-Neto, Jose

2017-11-01

Melatonin, due to its multiple means and mechanisms of action, plays a fundamental role in the regulation of the organismal physiology by fine tunning several functions. The cardiovascular system is an important site of action as melatonin regulates blood pressure both by central and peripheral interventions, in addition to its relation with the renin-angiotensin system. Besides, the systemic management of several processes, melatonin acts on mitochondria regulation to maintain a healthy cardiovascular system. Hypertension affects target organs in different ways and cellular energy metabolism is frequently involved due to mitochondrial alterations that include a rise in reactive oxygen species production and an ATP synthesis decrease. The discussion that follows shows the role played by melatonin in the regulation of mitochondrial physiology in several levels of the cardiovascular system, including brain, heart, kidney, blood vessels and, particularly, regulating the renin-angiotensin system. This discussion shows the putative importance of using melatonin as a therapeutic tool involving its antioxidant potential and its action on mitochondrial physiology in the cardiovascular system.

Reduced-Fat Foods: The Complex Science of Developing Diet-Based Strategies for Tackling Overweight and Obesity1234

PubMed Central

McClements, David J

2015-01-01

Fat plays multiple roles in determining the desirable physicochemical properties, sensory attributes, nutritional profile, and biologic response of food products. Overconsumption of fats is linked to chronic diseases, such as obesity, coronary heart disease, diabetes, and cancer. There is therefore a need to develop reduced-fat products with physicochemical properties and sensory profiles that match those of their full-fat counterparts. In addition, foods may be redesigned to increase the feelings of satiety and satiation, and thereby reduce overall food intake. The successful design of these types of functional foods requires a good understanding of the numerous roles that fat plays in determining food attributes and the development of effective strategies to replace these attributes. This article provides an overview of the current understanding of the influence of fat on the physicochemical and physiologic attributes of emulsion-based food products and highlights approaches to create high-quality foods with reduced-fat contents. PMID:25979507

Ventromedial hypothalamic neurons control a defensive emotion state

PubMed Central

Kunwar, Prabhat S; Zelikowsky, Moriel; Remedios, Ryan; Cai, Haijiang; Yilmaz, Melis; Meister, Markus; Anderson, David J

2015-01-01

Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers. DOI: http://dx.doi.org/10.7554/eLife.06633.001 PMID:25748136

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Nucleophosmin/B23 regulates ubiquitin dynamics in nucleoli by recruiting deubiquitylating enzyme USP36.

PubMed

Endo, Akinori; Kitamura, Naomi; Komada, Masayuki

2009-10-09

The nucleolus is a subnuclear compartment with multiple cellular functions, including ribosome biogenesis. USP36 is a deubiquitylating enzyme that localizes to nucleoli and plays an essential role in regulating the structure and function of the organelle. However, how the localization of USP36 is regulated remains unknown. Here, we identified a short stretch of basic amino acids (RGKEKKIKKFKREKRR) that resides in the C-terminal region of USP36 and serves as a nucleolar localization signal for the protein. We found that this motif interacts with a central acidic region of nucleophosmin/B23, a major nucleolar protein involved in various nucleolar functions. Knockdown of nucleophosmin/B23 resulted in a significant reduction in the amount of USP36 in nucleoli, without affecting the cellular USP36 level. This was associated with elevated ubiquitylation levels of fibrillarin, a USP36 substrate protein in nucleoli. We conclude that nucleophosmin/B23 recruits USP36 to nucleoli, thereby serving as a platform for the regulation of nucleolar protein functions through ubiquitylation/deubiquitylation.

Synergistic effect of amino acids modified on dendrimer surface in gene delivery.

PubMed

Wang, Fei; Wang, Yitong; Wang, Hui; Shao, Naimin; Chen, Yuanyuan; Cheng, Yiyun

2014-11-01

Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

IFP35 Is Involved in the Antiviral Function of Interferon by Association with the Viral Tas Transactivator of Bovine Foamy Virus▿

PubMed Central

Tan, Juan; Qiao, Wentao; Wang, Jian; Xu, Fengwen; Li, Yue; Zhou, Jun; Chen, Qimin; Geng, Yunqi

2008-01-01

Interferon-induced proteins (IFPs) exert multiple functions corresponding to diverse interferon signals. However, the intracellular functions of many IFPs are not fully characterized. Here, we report that IFP35, a member of the IFP family with a molecular mass of 35 kDa, can interact with the bovine Tas (BTas) regulatory protein of bovine foamy virus (BFV). The interaction involves NID2 (IFP35/Nmi homology domain) of IFP35 and the central domain of BTas. The overexpression of IFP35 disturbs the ability of BTas to activate viral-gene transcription and inhibits viral replication. The depletion of endogenous IFP35 by interfering RNA can promote the activation of BFV, suggesting an inhibitory function of IFP35 in viral-gene expression. In addition, IFP35 can interact with the homologous regulatory protein of prototype FV and arrest viral replication and repress viral transcription. Our study suggests that IFP35 may represent a novel pathway of interferon-mediated antiviral activity in host organisms that plays a role in the maintenance of FV latency. PMID:18305040

Brain networks governing the golf swing in professional golfers.

PubMed

Kim, Jin Hyun; Han, Joung Kyue; Kim, Bung-Nyun; Han, Doug Hyun

2015-01-01

Golf, as with most complex motor skills, requires multiple different brain functions, including attention, motor planning, coordination, calculation of timing, and emotional control. In this study we assessed the correlation between swing components and brain connectivity from the cerebellum to the cerebrum. Ten female golf players and 10 age-matched female controls were recruited. In order to determine swing consistency among participants, the standard deviation (SD) of the mean swing speed time and the SD of the mean swing angle were assessed over 30 swings. Functional brain connectivity was assessed by resting state functional MRI. Pro-golfers showed greater positive left cerebellum connectivity to the occipital lobe, temporal lobe, parietal lobe and both frontal lobes compared to controls. The SD of play scores was positively correlated with the SD of the impact angle. Constant swing speed and back swing angle in professional golfers were associated with functional connectivity (FC) between the cerebellum and parietal and frontal lobes. In addition, the constant impact angle in professional golfers was associated with improved golf scores and additional FC of the thalamus.

Generation of signaling specificity in Arabidopsis by spatially restricted buffering of ligand-receptor interactions.

PubMed

Abrash, Emily B; Davies, Kelli A; Bergmann, Dominique C

2011-08-01

Core signaling pathways function in multiple programs during multicellular development. The mechanisms that compartmentalize pathway function or confer process specificity, however, remain largely unknown. In Arabidopsis thaliana, ERECTA (ER) family receptors have major roles in many growth and cell fate decisions. The ER family acts with receptor TOO MANY MOUTHS (TMM) and several ligands of the EPIDERMAL PATTERNING FACTOR LIKE (EPFL) family, which play distinct yet overlapping roles in patterning of epidermal stomata. Here, our examination of EPFL genes EPFL6/CHALLAH (CHAL), EPFL5/CHALLAH-LIKE1, and EPFL4/CHALLAH-LIKE2 (CLL2) reveals that this family may mediate additional ER-dependent processes. chal cll2 mutants display growth phenotypes characteristic of er mutants, and genetic interactions are consistent with CHAL family molecules acting as ER family ligands. We propose that different classes of EPFL genes regulate different aspects of ER family function and introduce a TMM-based discriminatory mechanism that permits simultaneous, yet compartmentalized and distinct, function of the ER family receptors in growth and epidermal patterning.

Executive functions and aphasia treatment outcomes: data from an ortho-phonological cueing therapy for anomia in Chinese.

PubMed

Yeung, Olivia; Law, Sam-Po

2010-12-01

This study examined the existence of a possible relationship between anomic treatment outcomes and executive functions. An ortho-phonological cueing method was used to facilitate object naming in 12 Cantonese-speaking anomic individuals. Treatment effectiveness for each participant was quantified and correlated with the performance of executive functions and language tasks. It was found that 10 participants showed significant improvement in naming treated items. Eight of the participants were able to maintain treatment gains for at least 1 month. Phonological generalization effects were observed in two participants. Performance on the Test of Nonverbal Intelligence (TONI-3) was significantly correlated with effect sizes of treatment, treatment generalization and maintenance and the Attention Network Test (ANT) was significantly correlated with phonological generalization. The result of a simultaneous multiple regression suggested that the performance of the ANT played an important role in phonological generalization. The findings reinforce the current view about the role of executive functions in language rehabilitation. They also shed light on the effect of inhibitory control on treatment generalization.

Validating Measurement of Knowledge Integration in Science Using Multiple-Choice and Explanation Items

ERIC Educational Resources Information Center

Lee, Hee-Sun; Liu, Ou Lydia; Linn, Marcia C.

2011-01-01

This study explores measurement of a construct called knowledge integration in science using multiple-choice and explanation items. We use construct and instructional validity evidence to examine the role multiple-choice and explanation items plays in measuring students' knowledge integration ability. For construct validity, we analyze item…

Why Use Multiple Representations in the Mathematics Classroom? Views of English and German Preservice Teachers

ERIC Educational Resources Information Center

Dreher, Anika; Kuntze, Sebastian; Lerman, Stephen

2016-01-01

Dealing with multiple representations and their connections plays a key role for learners to build up conceptual knowledge in the mathematics classroom. Hence, professional knowledge and views of mathematics teachers regarding the use of multiple representations certainly merit attention. In particular, investigating such views of preservice…

Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space.

PubMed

Kawamata, Hibiki; Manfredi, Giovanni

2010-11-01

Cu, Zn, superoxide dismutase (SOD1) is a ubiquitous enzyme localized in multiple cellular compartments, including mitochondria, where it concentrates in the intermembrane space (IMS). Similar to other small IMS proteins, the import and retention of SOD1 in the IMS is linked to its folding and maturation, involving the formation of critical intra- and intermolecular disulfide bonds. Therefore, the cysteine residues of SOD1 play a fundamental role in its IMS localization. IMS import of SOD1 involves its copper chaperone, CCS, whose mitochondrial distribution is regulated by the Mia40/Erv1 disulfide relay system in a redox-dependent manner: CCS promotes SOD1 maturation and retention in the IMS. The function of SOD1 in the IMS is still unknown, but it is plausible that it serves to remove superoxide released from the mitochondrial respiratory chain. Mutations in SOD1 cause familial amyotrophic lateral sclerosis (ALS), whose pathologic features include mitochondrial bioenergetic dysfunction. Mutant SOD1 localization in the IMS is not dictated by oxygen concentration and the Mia40/Erv1 system, but is primarily dependent on aberrant protein folding and aggregation. Mutant SOD1 localization and aggregation in the IMS might cause the mitochondrial abnormalities observed in familial ALS and could play a significant role in disease pathogenesis.

The Arabidopsis SRR1 gene mediates phyB signaling and is required for normal circadian clock function

PubMed Central

Staiger, Dorothee; Allenbach, Laure; Salathia, Neeraj; Fiechter, Vincent; Davis, Seth J.; Millar, Andrew J.; Chory, Joanne; Fankhauser, Christian

2003-01-01

Plants possess several photoreceptors to sense the light environment. In Arabidopsis cryptochromes and phytochromes play roles in photomorphogenesis and in the light input pathways that synchronize the circadian clock with the external world. We have identified SRR1 (sensitivity to red light reduced), a gene that plays an important role in phytochrome B (phyB)-mediated light signaling. The recessive srr1 null allele and phyB mutants display a number of similar phenotypes indicating that SRR1 is required for normal phyB signaling. Genetic analysis suggests that SRR1 works both in the phyB pathway but also independently of phyB. srr1 mutants are affected in multiple outputs of the circadian clock in continuous light conditions, including leaf movement and expression of the clock components, CCA1 and TOC1. Clock-regulated gene expression is also impaired during day–night cycles and in constant darkness. The circadian phenotypes of srr1 mutants in all three conditions suggest that SRR1 activity is required for normal oscillator function. The SRR1 gene was identified and shown to code for a protein conserved in numerous eukaryotes including mammals and flies, implicating a conserved role for this protein in both the animal and plant kingdoms. PMID:12533513

The olfactory pathway mediates sheltering behavior of Caribbean spiny lobsters, Panulirus argus, to conspecific urine signals.

PubMed

Horner, Amy J; Weissburg, Marc J; Derby, Charles D

2008-03-01

The "noses" of diverse taxa are organized into different subsystems whose functions are often not well understood. The "nose" of decapod crustaceans is organized into two parallel pathways that originate in different populations of antennular sensilla and project to specific neuropils in the brain-the aesthetasc/olfactory lobe pathway and the non-aesthetasc/lateral antennular neuropil pathway. In this study, we investigated the role of these pathways in mediating shelter selection of Caribbean spiny lobsters, Panulirus argus, in response to conspecific urine signals. We compared the behavior of ablated animals and intact controls. Our results show that control and non-aesthetasc ablated lobsters have a significant overall preference for shelters emanating urine over control shelters. Thus the non-aesthetasc pathway does not play a critical role in shelter selection. In contrast, spiny lobsters with aesthetascs ablated did not show a preference for either shelter, suggesting that the aesthetasc/olfactory pathway is important for processing social odors. Our results show a difference in the function of these dual chemosensory pathways in responding to social cues, with the aesthetasc/olfactory lobe pathway playing a major role. We discuss our results in the context of why the noses of many animals contain multiple parallel chemosensory systems.

Role of actin depolymerizing factor cofilin in Aspergillus fumigatus oxidative stress response and pathogenesis.

PubMed

Jia, Xiaodong; Zhang, Xi; Hu, Yingsong; Hu, Mandong; Tian, Shuguang; Han, Xuelin; Sun, Yansong; Han, Li

2018-06-01

Aspergillus fumigatus is a major fungal pathogen that is responsible for approximately 90% of human aspergillosis. Cofilin is an actin depolymerizing factor that plays crucial roles in multiple cellular functions in many organisms. However, the functions of cofilin in A. fumigatus are still unknown. In this study, we constructed an A. fumigatus strain overexpressing cofilin (cofilin OE). The cofilin OE strain displayed a slightly different growth phenotype, significantly increased resistance against H 2 O 2 and diamide, and increased activation of the high osmolarity glycerol pathway compared to the wild-type strain (WT). The cofilin OE strain internalized more efficiently into lung epithelial A549 cells, and induced increased transcription of inflammatory factors (MCP-1, TNF-α and IL-8) compared to WT. Cofilin overexpression also resulted in increased polysaccharides including β-1, 3-glucan and chitin, and increased transcription of genes related to oxidative stress responses and polysaccharide synthesis in A. fumigatus. However, the cofilin OE strain exhibited similar virulence to the wild-type strain in murine and Galleria mellonella infection models. These results demonstrated for the first time that cofilin, a regulator of actin cytoskeleton dynamics, might play a critical role in the regulation of oxidative stress responses and cell wall polysaccharide synthesis in A. fumigatus.

Programming "loose training" as a strategy to facilitate language generalization.

PubMed Central

Campbell, C R; Stremel-Campbell, K

1982-01-01

This study investigated the generalization of spontaneous complex language behavior across a nontraining setting and the durability of generalization as a result of programming and "loose training" strategy. A within-subject, across-behaviors multiple-baseline design was used to examine the performance of two moderately retarded students in the use of is/are across three syntactic structures (i.e., "wh" questions, "yes/no" reversal questions, and statements). The language training procedure used in this study represented a functional example of programming "loose training." The procedure involved conducting concurrent language training within the context of an academic training task, and establishing a functional reduction in stimulus control by permitting the student to initiate a language response based on a wide array of naturally occurring stimulus events. Concurrent probes were conducted in the free play setting to assess the immediate generalization and the durability of the language behaviors. The results demonstrated that "loose training" was effective in establishing a specific set of language responses with the participants of this investigation. Further, both students demonstrated spontaneous use of the language behavior in the free play generalization setting and a trend was clearly evident for generalization to continue across time. Thus, the methods used appear to be successful for training the use of is/are in three syntactic structures. PMID:7118759

Keratinocyte differentiation is regulated by the Rho and ROCK signaling pathway.

PubMed

McMullan, Rachel; Lax, Siân; Robertson, Vicki H; Radford, David J; Broad, Simon; Watt, Fiona M; Rowles, Alison; Croft, Daniel R; Olson, Michael F; Hotchin, Neil A

2003-12-16

The epidermis comprises multiple layers of specialized epithelial cells called keratinocytes. As cells are lost from the outermost epidermal layers, they are replaced through terminal differentiation, in which keratinocytes of the basal layer cease proliferating, migrate upwards, and eventually reach the outermost cornified layers. Normal homeostasis of the epidermis requires that the balance between proliferation and differentiation be tightly regulated. The GTP binding protein RhoA plays a fundamental role in the regulation of the actin cytoskeleton and in the adhesion events that are critically important to normal tissue homeostasis. Two central mediators of the signals from RhoA are the ROCK serine/threonine kinases ROCK-I and ROCK-II. We have analyzed ROCK's role in the regulation of epidermal keratinocyte function by using a pharmacological inhibitor and expressing conditionally active or inactive forms of ROCK-II in primary human keratinocytes. We report that blocking ROCK function results in inhibition of keratinocyte terminal differentiation and an increase in cell proliferation. In contrast, activation of ROCK-II in keratinocytes results in cell cycle arrest and an increase in the expression of a number of genes associated with terminal differentiation. Thus, these results indicate that ROCK plays a critical role in regulating the balance between proliferation and differentiation in human keratinocytes.

Ectopic expression of an apple cytochrome P450 gene MdCYPM1 negatively regulates plant photomorphogenesis and stress response in Arabidopsis.

PubMed

An, Jian-Ping; Li, Rui; Qu, Feng-Jia; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-01-29

Cytochrome P450s play an important role in plant growth and are involved in multiple stresses response. However, little is known about the functions of cytochrome P450s in apple. Here, a Malus × domestica cytochrome P450 monooxygenase 1 gene, MdCYPM1, was identified and subsequently cloned from apple 'Gala' (Malus × domestica). To verify the functions of MdCYPM1, we generated transgenic Arabidopsis plants expressing the apple MdCYPM1 gene under the control of the Cauliflower mosaic virus 35S promoter. Four transgenic lines (#3, #5, #7 and #8) were selected for further study. The transgenic plants exhibited a series of skotomorphogenesis phenotypes relative to wild-type controls, such as reduction of the chlorophyll, anthocyanins content and hypocotyls elongation. In addition, overexpression of MdCYPM1 influenced auxin transport and flowering time in transgenic Arabidopsis. Furthermore, MdCYPM1 expression was induced by salt and mannitol treatments, and the transgenic plants were negatively regulated by salinity and osmotic stresses during germination. These results suggest that MdCYPM1 plays a vital role in plant growth and development. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreased functional connectivity in schizophrenia: The relationship between social functioning, social cognition and graph theoretical network measures.

PubMed

Erdeniz, Burak; Serin, Emin; İbadi, Yelda; Taş, Cumhur

2017-12-30

Schizophrenia is a complex disorder in which abnormalities in brain connectivity and social functioning play a central role. The aim of this study is to explore small-world network properties, and understand their relationship with social functioning and social cognition in the context of schizophrenia, by testing functional connectivity differences in network properties and its relation to clinical behavioral measures. Resting-state fMRI time series data were acquired from 23 patients diagnosed with schizophrenia and 23 healthy volunteers. The results revealed that patients with schizophrenia show significantly decreased connectivity between a range of brain regions, particularly involving connections among the right orbitofrontal cortex, bilateral putamen and left amygdala. Furthermore, topological properties of functional brain networks in patients with schizophrenia were characterized by reduced path length compared to healthy controls; however, no significant difference was found for clustering coefficient, local efficiency or global efficiency. Additionally, we found that nodal efficiency of the amygdala and the putamen were significantly correlated with the independence-performance subscale of social functioning scale (SFC), and Reading the Mind in the Eyes test; however, the correlations do not survive correction for multiple comparison. The current results help to clarify the relationship between social functioning deficits and topological brain measures in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Preschoolers' Free Play--Connections with Emotional and Social Functioning

ERIC Educational Resources Information Center

Veiga, Guida; Neto, Carlos; Rieffe, Carolien

2016-01-01

Play has an important role in various aspects of children's development. However, time for free play has declined substantially over the last decades. To date, few studies have focused on the relationship between opportunities for free play and children's social functioning. The aims of this study are to examine whether children´s free play is…

Executive Functions Development and Playing Games

ERIC Educational Resources Information Center

Petty, Ana Lucia; de Souza, Maria Thereza C. Coelho

2012-01-01

The aim of this paper is to discuss executive functions and playing games, considering Piaget's work (1967) and the neuropsychological framework (Barkley, 1997, 2000; Cypel, 2007). Two questions guide the discussion: What are the intersections between playing games and the development of executive functions? Can we stimulate children with learning…

Characterization of 14-3-3 isoforms expressed in the Echinococcus granulosus pathogenic larval stage.

PubMed

Teichmann, Aline; Vargas, Daiani M; Monteiro, Karina M; Meneghetti, Bruna V; Dutra, Cristine S; Paredes, Rodolfo; Galanti, Norbel; Zaha, Arnaldo; Ferreira, Henrique B

2015-04-03

The 14-3-3 protein family of eukaryotic regulators was studied in Echinococcus granulosus, the causative agent of cystic hydatid disease. These proteins mediate important cellular processes in eukaryotes and are expected to play important roles in parasite biology. Six isoforms of E. granulosus 14-3-3 genes and proteins (Eg14-3-3.1-6) were analyzed, and their phylogenetic relationships were established with bona fide 14-3-3 orthologous proteins from eukaryotic species. Eg14-3-3 isoforms with previous evidence of expression (Eg14-3-3.1-4) in E. granulosus pathogenic larval stage (metacestode) were cloned, and recombinant proteins were used for functional studies. These protein isoforms were detected in different components of E. granulosus metacestode, including interface components with the host. The roles that are played by Eg14-3-3 proteins in parasite biology were inferred from the repertoires of interacting proteins with each isoform, as assessed by gel overlay, cross-linking, and affinity chromatography assays. A total of 95 Eg14-3-3 protein ligands were identified by mass spectrometry. Eg14-3-3 isoforms have shared partners (44 proteins), indicating some overlapping functions; however, they also bind exclusive partners (51 proteins), suggesting Eg14-3-3 functional specialization. These ligand repertoires indicate the involvement of Eg14-3-3 proteins in multiple biochemical pathways in the E. granulosus metacestode and note some degree of isoform specialization.

[Multiple myeloma : What has been confirmed in therapy?

PubMed

Baertsch, M-A; Goldschmidt, H

2017-12-01

Multiple myeloma (MM) is a malignancy of terminally differentiated B cells/plasma cells and is primarily located in the bone marrow. Symptomatic multiple myeloma typically presents with osteolyses, anemia, reduced renal function, and/or hypercalcemia. In the case of such MM-related end organ damage, urgent systemic treatment is indicated. In order to prevent end organ damage, current guidelines now recommend treatment initiation already when certain biomarkers are met. Current first-line treatment is based on proteasome inhibition and immunomodulation. Eligible patients still benefit from the addition of high-dose chemotherapy and autologous stem cell transplantation. Radiotherapy and orthopedic interventions play an important role in the treatment of localized skeletal complications. For relapsed MM, five novel agents have been approved in Europe during the last two years. These are second-generation proteasome inhibitors (carfilzomib, ixazomib) as well as first-in-class monoclonal antibodies (daratumumab, elotuzumab) and a histone deacetylase inhibitor (panobinostat). Triple combinations based on the established regimens lenalidomide/dexamethasone and bortezomib/dexamethasone plus one of the novel agents have been shown to significantly prolong progression-free survival. Median overall survival of patients with MM has doubled since the turn of the millennium.

Gamabufotalin triggers c-Myc degradation via induction of WWP2 in multiple myeloma cells.

PubMed

Yu, Zhenlong; Li, Tao; Wang, Chao; Deng, Sa; Zhang, Baojing; Huo, Xiaokui; Zhang, Bo; Wang, Xiaobo; Zhong, Yuping; Ma, Xiaochi

2016-03-29

Deciding appropriate therapy for multiple myeloma (MM) is challenging because of the occurrence of multiple chromosomal changes and the fatal nature of the disease. In the current study, gamabufotalin (GBT) was isolated from toad venom, and its tumor-specific cytotoxicity was investigated in human MM cells. We found GBT inhibited cell growth and induced apoptosis with the IC50 values <50 nM. Mechanistic studies using functional approaches identified GBT as an inhibitor of c-Myc. Further analysis showed that GBT especially evoked the ubiquitination and degradation of c-Myc protein, thereby globally repressing the expression of c-Myc target genes. GBT treatment inhibited ERK and AKT signals, while stimulating the activation of JNK cascade. An E3 ubiquitin-protein ligase, WWP2, was upregulated following JNK activation and played an important role in c-Myc ubiquitination and degradation through direct protein-protein interaction. The antitumor effect of GBT was validated in a xenograft mouse model and the suppression of MM-induced osteolysis was verified in a SCID-hu model in vivo. Taken together, our study identified the potential of GBT as a promising therapeutic agent in the treatment of MM.

Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation

PubMed Central

Voigt, David; Scheidt, Uta; Derfuss, Tobias; Brück, Wolfgang; Junker, Andreas

2017-01-01

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage. PMID:28375164

Functional dissociation in sweet taste receptor neurons between and within taste organs of Drosophila

PubMed Central

Thoma, Vladimiros; Knapek, Stephan; Arai, Shogo; Hartl, Marion; Kohsaka, Hiroshi; Sirigrivatanawong, Pudith; Abe, Ayako; Hashimoto, Koichi; Tanimoto, Hiromu

2016-01-01

Finding food sources is essential for survival. Insects detect nutrients with external taste receptor neurons. Drosophila possesses multiple taste organs that are distributed throughout its body. However, the role of different taste organs in feeding remains poorly understood. By blocking subsets of sweet taste receptor neurons, we show that receptor neurons in the legs are required for immediate sugar choice. Furthermore, we identify two anatomically distinct classes of sweet taste receptor neurons in the leg. The axonal projections of one class terminate in the thoracic ganglia, whereas the other projects directly to the brain. These two classes are functionally distinct: the brain-projecting neurons are involved in feeding initiation, whereas the thoracic ganglia-projecting neurons play a role in sugar-dependent suppression of locomotion. Distinct receptor neurons for the same taste quality may coordinate early appetitive responses, taking advantage of the legs as the first appendages to contact food. PMID:26893070

Resolving response, decision, and strategic control: evidence for a functional topography in dorsomedial prefrontal cortex.

PubMed

Venkatraman, Vinod; Rosati, Alexandra G; Taren, Adrienne A; Huettel, Scott A

2009-10-21

The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of cognitive control and decision making. Here, we provide evidence for an anterior-to-posterior topography within the DMPFC using tasks that evoke three distinct forms of control demands--response, decision, and strategic--each of which could be mapped onto independent behavioral data. Specifically, we identify three spatially distinct regions within the DMPFC: a posterior region associated with control demands evoked by multiple incompatible responses, a middle region associated with control demands evoked by the relative desirability of decision options, and an anterior region that predicts control demands related to deviations from an individual's preferred decision-making strategy. These results provide new insight into the functional organization of DMPFC and suggest how recent controversies about its role in complex decision making and response mapping can be reconciled.

Nanoparticles as potential new generation broad spectrum antimicrobial agents.

PubMed

Yah, Clarence S; Simate, Geoffrey S

2015-09-02

The rapid emergence of antimicrobial resistant strains to conventional antimicrobial agents has complicated and prolonged infection treatment and increased mortality risk globally. Furthermore, some of the conventional antimicrobial agents are unable to cross certain cell membranes thus, restricting treatment of intracellular pathogens. Therefore, the disease-causing-organisms tend to persist in these cells. However, the emergence of nanoparticle (NP) technology has come with the promising broad spectrum NP-antimicrobial agents due to their vast physiochemical and functionalization properties. In fact, NP-antimicrobial agents are able to unlock the restrictions experienced by conventional antimicrobial agents. This review discusses the status quo of NP-antimicrobial agents as potent broad spectrum antimicrobial agents, sterilization and wound healing agents, and sustained inhibitors of intracellular pathogens. Indeed, the perspective of developing potent NP-antimicrobial agents that carry multiple-functionality will revolutionize clinical medicine and play a significant role in alleviating disease burden.

The neural correlates of reciprocity are sensitive to prior experience of reciprocity.

PubMed

Cáceda, Ricardo; Prendes-Alvarez, Stefania; Hsu, Jung-Jiin; Tripathi, Shanti P; Kilts, Clint D; James, G Andrew

2017-08-14

Reciprocity is central to human relationships and is strongly influenced by multiple factors including the nature of social exchanges and their attendant emotional reactions. Despite recent advances in the field, the neural processes involved in this modulation of reciprocal behavior by ongoing social interaction are poorly understood. We hypothesized that activity within a discrete set of neural networks including a putative moral cognitive neural network is associated with reciprocity behavior. Nineteen healthy adults underwent functional magnetic resonance imaging scanning while playing the trustee role in the Trust Game. Personality traits and moral development were assessed. Independent component analysis was used to identify task-related functional brain networks and assess their relationship to behavior. The saliency network (insula and anterior cingulate) was positively correlated with reciprocity behavior. A consistent array of brain regions supports the engagement of emotional, self-referential and planning processes during social reciprocity behavior. Published by Elsevier B.V.

The Role of Tomato WRKY Genes in Plant Responses to Combined Abiotic and Biotic Stresses

PubMed Central

Bai, Yuling; Sunarti, Sri; Kissoudis, Christos; Visser, Richard G. F.; van der Linden, C. G.

2018-01-01

In the field, plants constantly face a plethora of abiotic and biotic stresses that can impart detrimental effects on plants. In response to multiple stresses, plants can rapidly reprogram their transcriptome through a tightly regulated and highly dynamic regulatory network where WRKY transcription factors can act as activators or repressors. WRKY transcription factors have diverse biological functions in plants, but most notably are key players in plant responses to biotic and abiotic stresses. In tomato there are 83 WRKY genes identified. Here we review recent progress on functions of these tomato WRKY genes and their homologs in other plant species, such as Arabidopsis and rice, with a special focus on their involvement in responses to abiotic and biotic stresses. In particular, we highlight WRKY genes that play a role in plant responses to a combination of abiotic and biotic stresses.

Synaptic Activity and Bioenergy Homeostasis: Implications in Brain Trauma and Neurodegenerative Diseases

PubMed Central

Khatri, Natasha; Man, Heng-Ye

2013-01-01

Powered by glucose metabolism, the brain is the most energy-demanding organ in our body. Adequate ATP production and regulation of the metabolic processes are essential for the maintenance of synaptic transmission and neuronal function. Glutamatergic synaptic activity utilizes the largest portion of bioenergy for synaptic events including neurotransmitter synthesis, vesicle recycling, and most importantly, the postsynaptic activities leading to channel activation and rebalancing of ionic gradients. Bioenergy homeostasis is coupled with synaptic function via activities of the sodium pumps, glutamate transporters, glucose transport, and mitochondria translocation. Energy insufficiency is sensed by the AMP-activated protein kinase (AMPK), a master metabolic regulator that stimulates the catalytic process to enhance energy production. A decline in energy supply and a disruption in bioenergy homeostasis play a critical role in multiple neuropathological conditions including ischemia, stroke, and neurodegenerative diseases including Alzheimer’s disease and traumatic brain injuries. PMID:24376435

In-silico analysis of cis-acting regulatory elements of pathogenesis-related proteins of Arabidopsis thaliana and Oryza sativa

PubMed Central

Kaur, Amritpreet; Pati, Pratap Kumar; Pati, Aparna Maitra; Nagpal, Avinash Kaur

2017-01-01

Pathogenesis related (PR) proteins are low molecular weight family of proteins induced in plants under various biotic and abiotic stresses. They play an important role in plant-defense mechanism. PRs have wide range of functions, acting as hydrolases, peroxidases, chitinases, anti-fungal, protease inhibitors etc. In the present study, an attempt has been made to analyze promoter regions of PR1, PR2, PR5, PR9, PR10 and PR12 of Arabidopsis thaliana and Oryza sativa. Analysis of cis-element distribution revealed the functional multiplicity of PRs and provides insight into the gene regulation. CpG islands are observed only in rice PRs, which indicates that monocot genome contains more GC rich motifs than dicots. Tandem repeats were also observed in 5’ UTR of PR genes. Thus, the present study provides an understanding of regulation of PR genes and their versatile roles in plants. PMID:28910327

Role of Hippo signaling in regulating immunity.

PubMed

Hong, Lixin; Li, Xun; Zhou, Dawang; Geng, Jing; Chen, Lanfen

2018-03-22

The Hippo signaling pathway has been established as a key regulator of organ size control, tumor suppression, and tissue regeneration in multiple organisms. Recently, emerging evidence has indicated that Hippo signaling might play an important role in regulating the immune system in both Drosophila and mammals. In particular, patients bearing a loss-of-function mutation of MST1 are reported to have an autosomal recessive primary immunodeficiency syndrome. MST1/2 kinases, the mammalian orthologs of Drosophila Hippo, may activate the non-canonical Hippo signaling pathway via MOB1A/B and/or NDR1/2 or cross-talk with other essential signaling pathways to regulate both innate and adaptive immunity. In this review, we present and discuss recent findings of cellular mechanisms/functions of Hippo signaling in the innate immunity in Drosophila and in mammals, T cell immunity, as well as the implications of Hippo signaling for tumor immunity.

Transport properties of CNT/oligosilane/CNT heterojunctions

NASA Astrophysics Data System (ADS)

Yu, J.; Zhang, G. L.; Shang, Y.; Wang, K. D.; Zhang, H.; Sun, M.; Liu, B.; Zeng, T.

2013-02-01

Combining the non-equilibrium Green's function formalism with density functional theory, the transport properties of nine CNT/oligosilane/CNT heterojunctions were systematically studied. We have found that the incorporation of oligosilane linkage to the carbon nanotube mouth could significantly tune the transport properties compared with the pure oligosilane and pure CNT. The P- and B-dopings upon the oligosilane moiety could not only enhance the conductivity but also give rise to multiple negative differential resistance behavior for the CNT/oligosilane/CNT heterojunctions. The concentration of heteroatom plays an important role in the transport properties of the CNT/oligosilane/CNT heterojunctions, while the number of the oligosilane linkage exerts little effect on the conductivity. The B-doped CNT/oligosilane/CNT heterojunctions show higher conductivity than those of the P-doped ones. The p-n junction caused by B- and P-codopings exhibits a rectifying effect and the rectification ratio is up to 7.19.

Immune heterogeneity in neuroinflammation: dendritic cells in the brain.

PubMed

Colton, Carol A

2013-03-01

Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC's act as sentinels, continually sampling their local environment. They share this function with macrophages derived from the same basic hemopoietic (bone marrow-derived) precursor and with parenchymal microglia that arise from a unique non-hemopoietic origin. While multiple cells may serve as antigen presenting cells (APCs), dendritic cells present both foreign and self-proteins to naïve T cells that, in turn, carry out effector functions that serve to protect or destroy. The resulting activation of the adaptive response is a critical step to resolution of injury or infection and is key to survival. In this review we will explore the critical roles that DCs play in the brain's response to neuroinflammatory disease with emphasis on how the brain's microenvironment impacts these actions.

In-silico analysis of cis-acting regulatory elements of pathogenesis-related proteins of Arabidopsis thaliana and Oryza sativa.

PubMed

Kaur, Amritpreet; Pati, Pratap Kumar; Pati, Aparna Maitra; Nagpal, Avinash Kaur

2017-01-01

Pathogenesis related (PR) proteins are low molecular weight family of proteins induced in plants under various biotic and abiotic stresses. They play an important role in plant-defense mechanism. PRs have wide range of functions, acting as hydrolases, peroxidases, chitinases, anti-fungal, protease inhibitors etc. In the present study, an attempt has been made to analyze promoter regions of PR1, PR2, PR5, PR9, PR10 and PR12 of Arabidopsis thaliana and Oryza sativa. Analysis of cis-element distribution revealed the functional multiplicity of PRs and provides insight into the gene regulation. CpG islands are observed only in rice PRs, which indicates that monocot genome contains more GC rich motifs than dicots. Tandem repeats were also observed in 5' UTR of PR genes. Thus, the present study provides an understanding of regulation of PR genes and their versatile roles in plants.

Music-based interventions in neurological rehabilitation.

PubMed

Sihvonen, Aleksi J; Särkämö, Teppo; Leo, Vera; Tervaniemi, Mari; Altenmüller, Eckart; Soinila, Seppo

2017-08-01

During the past ten years, an increasing number of controlled studies have assessed the potential rehabilitative effects of music-based interventions, such as music listening, singing, or playing an instrument, in several neurological diseases. Although the number of studies and extent of available evidence is greatest in stroke and dementia, there is also evidence for the effects of music-based interventions on supporting cognition, motor function, or emotional wellbeing in people with Parkinson's disease, epilepsy, or multiple sclerosis. Music-based interventions can affect divergent functions such as motor performance, speech, or cognition in these patient groups. However, the psychological effects and neurobiological mechanisms underlying the effects of music interventions are likely to share common neural systems for reward, arousal, affect regulation, learning, and activity-driven plasticity. Although further controlled studies are needed to establish the efficacy of music in neurological recovery, music-based interventions are emerging as promising rehabilitation strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

MOR23 promotes muscle regeneration and regulates cell adhesion and migration

PubMed Central

Griffin, Christine A.; Kafadar, Kimberly A.; Pavlath, Grace K.

2009-01-01

Summary Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. Mouse OR23 (MOR23) expression is induced during muscle regeneration when muscle cells are extensively fusing and plays a key role in regulating migration and adhesion of muscle cells in vitro, two processes common during tissue repair. A soluble ligand for MOR23 is secreted by muscle cells in vitro and muscle tissue in vivo. MOR23 is necessary for proper skeletal muscle regeneration as loss of MOR23 leads to increased myofiber branching, commonly associated with muscular dystrophy. Together these data identify a functional role for an OR outside of the nose and suggest a larger role for ORs during tissue repair. PMID:19922870

Resolving Response, Decision, and Strategic Control: Evidence for a Functional Topography in Dorsomedial Prefrontal Cortex

PubMed Central

Venkatraman, Vinod; Rosati, Alexandra G.; Taren, Adrienne A.; Huettel, Scott A.

2009-01-01

The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of cognitive control and decision making. Here, we provide evidence for an anterior-to-posterior topography within the DMPFC using tasks that evoke three distinct forms of control demands – response, decision, and strategic – each of which could be mapped on to independent behavioral data. Specifically, we identify three spatially distinct regions within the DMPFC: a posterior region associated with control demands evoked by multiple incompatible responses, a middle region associated with control demands evoked by the relative desirability of decision options, and an anterior region that predicts control demands related to deviations from an individual's preferred decision-making strategy. These results provide new insight into the functional organization of DMPFC, and suggest how recent controversies about its role in complex decision making and response mapping can be reconciled. PMID:19846703

Emerging topics and new perspectives on HLA-G.

PubMed

Fainardi, Enrico; Castellazzi, Massimiliano; Stignani, Marina; Morandi, Fabio; Sana, Gwenaëlle; Gonzalez, Rafael; Pistoia, Vito; Baricordi, Olavio Roberto; Sokal, Etienne; Peña, Josè

2011-02-01

Following the Fifth International Conference on non-classical HLA-G antigens (HLA-G), held in Paris in July 2009, we selected some topics which focus on emerging aspects in the setting of HLA-G functions. In particular, HLA-G molecules could play a role in: (1) various inflammatory disorders, such as multiple sclerosis, intracerebral hemorrhage, gastrointestinal, skin and rheumatic diseases, and asthma, where they may act as immunoregulatory factors; (2) the mechanisms to escape immune surveillance utilized by several viruses, such as human cytomegalovirus, herpes simplex virus type 1, rabies virus, hepatitis C virus, influenza virus type A and human immunodeficiency virus 1 (HIV-1); and (3) cytokine/chemokine network and stem cell transplantation, since they seem to modulate cell migration by the downregulation of chemokine receptor expression and mesenchymal stem cell activity blocking of effector cell functions and the generation of regulatory T cells. However, the immunomodulatory circuits mediated by HLA-G proteins still remain to be clarified.

Fair Play: A Study of Scientific Workforce Trainers' Experience Playing an Educational Video Game about Racial Bias

ERIC Educational Resources Information Center

Katz, Anna; Carnes, Molly; Gutierrez, Belinda; Savoy, Julia; Samuel, Clem; Filut, Amarette; Pribbenow, Christine Maidl

2017-01-01

Explicit racial bias has decreased in the United States, but racial stereotypes still exist and conspire in multiple ways to perpetuate the underparticipation of Blacks in science careers. Capitalizing on the potential effectiveness of role-playing video games to promote the type of active learning required to increase awareness of and reduce…

Using video modeling for generalizing toy play in children with autism.

PubMed

Paterson, Claire R; Arco, Lucius

2007-09-01

The present study examined effects of video modeling on generalized independent toy play of two boys with autism. Appropriate and repetitive verbal and motor play were measured, and intermeasure relationships were examined. Two single-participant experiments with multiple baselines and withdrawals across toy play were used. One boy was presented with three physically unrelated toys, whereas the other was presented with three related toys. Video modeling produced increases in appropriate play and decreases in repetitive play, but generalized play was observed only with the related toys. Generalization may have resulted from variables including the toys' common physical characteristics and natural reinforcing properties and the increased correspondence between verbal and motor play.

Memory and cognitive control circuits in mathematical cognition and learning.

PubMed

Menon, V

2016-01-01

Numerical cognition relies on interactions within and between multiple functional brain systems, including those subserving quantity processing, working memory, declarative memory, and cognitive control. This chapter describes recent advances in our understanding of memory and control circuits in mathematical cognition and learning. The working memory system involves multiple parietal-frontal circuits which create short-term representations that allow manipulation of discrete quantities over several seconds. In contrast, hippocampal-frontal circuits underlying the declarative memory system play an important role in formation of associative memories and binding of new and old information, leading to the formation of long-term memories that allow generalization beyond individual problem attributes. The flow of information across these systems is regulated by flexible cognitive control systems which facilitate the integration and manipulation of quantity and mnemonic information. The implications of recent research for formulating a more comprehensive systems neuroscience view of the neural basis of mathematical learning and knowledge acquisition in both children and adults are discussed. © 2016 Elsevier B.V. All rights reserved.

F-box protein interactions with the hallmark pathways in cancer.

PubMed

Randle, Suzanne J; Laman, Heike

2016-02-01

F-box proteins (FBP) are the substrate specifying subunit of Skp1-Cul1-FBP (SCF)-type E3 ubiquitin ligases and are responsible for directing the ubiquitination of numerous proteins essential for cellular function. Due to their ability to regulate the expression and activity of oncogenes and tumour suppressor genes, FBPs themselves play important roles in cancer development and progression. In this review, we provide a comprehensive overview of FBPs and their targets in relation to their interaction with the hallmarks of cancer cell biology, including the regulation of proliferation, epigenetics, migration and invasion, metabolism, angiogenesis, cell death and DNA damage responses. Each cancer hallmark is revealed to have multiple FBPs which converge on common signalling hubs or response pathways. We also highlight the complex regulatory interplay between SCF-type ligases and other ubiquitin ligases. We suggest six highly interconnected FBPs affecting multiple cancer hallmarks, which may prove sensible candidates for therapeutic intervention. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lignocellulose Degradation Mechanisms Across the Tree of Life

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

Cragg, Simon M.; Beckham, Gregg T.; Bruce, Neil C.

Organisms use diverse mechanisms involving multiple complementary enzymes, particularly glycoside hydrolases (GHs), to deconstruct lignocellulose. Lytic polysaccharide monooxygenases (LPMOs) produced by bacteria and fungi facilitate deconstruction as does the Fenton chemistry of brown-rot fungi. Lignin depolymerisation is achieved by white-rot fungi and certain bacteria, using peroxidases and laccases. Meta-omics is now revealing the complexity of prokaryotic degradative activity in lignocellulose-rich environments. Protists from termite guts and some oomycetes produce multiple lignocellulolytic enzymes. We found that the Lignocellulose-consuming animals secrete some GHs, but most harbour a diverse enzyme-secreting gut microflora in a mutualism that is particularly complex in termites. Shipworms however,more » house GH-secreting and LPMO-secreting bacteria separate from the site of digestion and the isopod Limnoria relies on endogenous enzymes alone. Moreover, the omics revolution is identifying many novel enzymes and paradigms for biomass deconstruction, but more emphasis on function is required, particularly for enzyme cocktails, in which LPMOs may play an important role.« less

Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina.

PubMed

May-Simera, Helen L; Gumerson, Jessica D; Gao, Chun; Campos, Maria; Cologna, Stephanie M; Beyer, Tina; Boldt, Karsten; Kaya, Koray D; Patel, Nisha; Kretschmer, Friedrich; Kelley, Matthew W; Petralia, Ronald S; Davey, Megan G; Li, Tiansen

2016-10-25

Microtubule actin crosslinking factor 1 (MACF1) plays a role in the coordination of microtubules and actin in multiple cellular processes. Here, we show that MACF1 is also critical for ciliogenesis in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis, and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized, while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of MACF1 in adult photoreceptors causes reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for MACF1 function. MACF1 also interacts with the ciliary proteins MKKS and TALPID3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking MACF1 and that MKKS and TALPID3 are involved in the coordination of microtubule and actin interactions. Published by Elsevier Inc.

Nas transgenic mouse line allows visualization of Notch pathway activity in vivo

PubMed Central

Souilhol, Céline; Cormier, Sarah; Monet, Marie; Vandormael-Pournin, Sandrine; Joutel, Anne; Babinet, Charles; Cohen-Tannoudji, Michel

2006-01-01

The Notch signalling pathway plays multiple and important roles in mammals. However, several aspects of its action, in particular the precise mapping of its sites of activity, remain unclear. To address this issue, we have generated a transgenic line carrying a construct consisting of a nls-lacZ reporter gene under the control of a minimal promoter and multiple RBP-Jκ binding sites. Here we show that this transgenic line, we named NAS for Notch Activity Sensor, displays an expression profile that is consistent with current knowledge on Notch activity sites in mice, even though it may not report on all these sites. Moreover, we observe that NAS transgene expression is abolished in a RBP-Jκ deficient background indicating that it indeed requires Notch/RBP-Jκ signalling pathway activity. Thus, the NAS transgenic line constitutes a valuable and versatile tool to gain further insights into the complex and various functions of the Notch signalling pathway. PMID:16708386

Lignocellulose Degradation Mechanisms Across the Tree of Life

DOE PAGES

Cragg, Simon M.; Beckham, Gregg T.; Bruce, Neil C.; ...

2015-11-14

Organisms use diverse mechanisms involving multiple complementary enzymes, particularly glycoside hydrolases (GHs), to deconstruct lignocellulose. Lytic polysaccharide monooxygenases (LPMOs) produced by bacteria and fungi facilitate deconstruction as does the Fenton chemistry of brown-rot fungi. Lignin depolymerisation is achieved by white-rot fungi and certain bacteria, using peroxidases and laccases. Meta-omics is now revealing the complexity of prokaryotic degradative activity in lignocellulose-rich environments. Protists from termite guts and some oomycetes produce multiple lignocellulolytic enzymes. We found that the Lignocellulose-consuming animals secrete some GHs, but most harbour a diverse enzyme-secreting gut microflora in a mutualism that is particularly complex in termites. Shipworms however,more » house GH-secreting and LPMO-secreting bacteria separate from the site of digestion and the isopod Limnoria relies on endogenous enzymes alone. Moreover, the omics revolution is identifying many novel enzymes and paradigms for biomass deconstruction, but more emphasis on function is required, particularly for enzyme cocktails, in which LPMOs may play an important role.« less

Toward Scalable Fabrication of Hierarchical Silica Capsules with Integrated Micro-, Meso-, and Macropores.

PubMed

Zhou, Weizheng; Tong, Gangsheng; Wang, Dali; Zhu, Bangshang; Ren, Yu; Butler, Michael; Pelan, Eddie; Yan, Deyue; Zhu, Xinyuan; Stoyanov, Simeon D

2016-04-06

Hierarchical porous structures are ubiquitous in biological organisms and inorganic systems. Although such structures have been replicated, designed, and fabricated, they are often inferior to naturally occurring analogues. Apart from the complexity and multiple functionalities developed by the biological systems, the controllable and scalable production of hierarchically porous structures and building blocks remains a technological challenge. Herein, a facile and scalable approach is developed to fabricate hierarchical hollow spheres with integrated micro-, meso-, and macropores ranging from 1 nm to 100 μm (spanning five orders of magnitude). (Macro)molecules, micro-rods (which play a key role for the creation of robust capsules), and emulsion droplets have been successfully employed as multiple length scale templates, allowing the creation of hierarchical porous macrospheres. Thanks to their specific mechanical strength, these hierarchical porous spheres could be incorporated and assembled as higher level building blocks in various novel materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella.

PubMed

Ziveri, Jason; Tros, Fabiola; Guerrera, Ida Chiara; Chhuon, Cerina; Audry, Mathilde; Dupuis, Marion; Barel, Monique; Korniotis, Sarantis; Fillatreau, Simon; Gales, Lara; Cahoreau, Edern; Charbit, Alain

2017-10-11

The enzyme fructose-bisphosphate aldolase occupies a central position in glycolysis and gluconeogenesis pathways. Beyond its housekeeping role in metabolism, fructose-bisphosphate aldolase has been involved in additional functions and is considered as a potential target for drug development against pathogenic bacteria. Here, we address the role of fructose-bisphosphate aldolase in the bacterial pathogen Francisella novicida. We demonstrate that fructose-bisphosphate aldolase is important for bacterial multiplication in macrophages in the presence of gluconeogenic substrates. In addition, we unravel a direct role of this metabolic enzyme in transcription regulation of genes katG and rpoA, encoding catalase and an RNA polymerase subunit, respectively. We propose a model in which fructose-bisphosphate aldolase participates in the control of host redox homeostasis and the inflammatory immune response.The enzyme fructose-bisphosphate aldolase (FBA) plays central roles in glycolysis and gluconeogenesis. Here, Ziveri et al. show that FBA of the pathogen Francisella novicida acts, in addition, as a transcriptional regulator and is important for bacterial multiplication in macrophages.

Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction

PubMed Central

Hu, Jianfei; Neiswinger, Johnathan; Zhang, Jin; Zhu, Heng; Qian, Jiang

2015-01-01

Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process. PMID:26393507

Memory and cognitive control circuits in mathematical cognition and learning

PubMed Central

Menon, V.

2018-01-01

Numerical cognition relies on interactions within and between multiple functional brain systems, including those subserving quantity processing, working memory, declarative memory, and cognitive control. This chapter describes recent advances in our understanding of memory and control circuits in mathematical cognition and learning. The working memory system involves multiple parietal–frontal circuits which create short-term representations that allow manipulation of discrete quantities over several seconds. In contrast, hippocampal–frontal circuits underlying the declarative memory system play an important role in formation of associative memories and binding of new and old information, leading to the formation of long-term memories that allow generalization beyond individual problem attributes. The flow of information across these systems is regulated by flexible cognitive control systems which facilitate the integration and manipulation of quantity and mnemonic information. The implications of recent research for formulating a more comprehensive systems neuroscience view of the neural basis of mathematical learning and knowledge acquisition in both children and adults are discussed. PMID:27339012

Multimodality and nanoparticles in medical imaging

PubMed Central

Huang, Wen-Yen; Davis, Jason J.

2015-01-01

A number of medical imaging techniques are used heavily in the provision of spatially resolved information on disease and physiological status and accordingly play a critical role in clinical diagnostics and subsequent treatment. Though, for most imaging modes, contrast is potentially enhanced through the use of contrast agents or improved hardware or imaging protocols, no single methodology provides, in isolation, a detailed mapping of anatomy, disease markers or physiological status. In recent years, the concept of complementing the strengths of one imaging modality with those of another has come to the fore and been further bolstered by the development of fused instruments such as PET/CT and PET/MRI stations. Coupled with the continual development in imaging hardware has been a surge in reports of contrast agents bearing multiple functionality, potentially providing not only a powerful and highly sensitised means of co-localising physiological/disease status and anatomy, but also the tracking and delineation of multiple markers and indeed subsequent or simultaneous highly localized therapy (“theragnostics”). PMID:21409202

Living with uncertainty and hope: A qualitative study exploring parents' experiences of living with childhood multiple sclerosis.

PubMed

Hinton, Denise; Kirk, Susan

2017-06-01

Background There is growing recognition that multiple sclerosis is a possible, albeit uncommon, diagnosis in childhood. However, very little is known about the experiences of families living with childhood multiple sclerosis and this is the first study to explore this in depth. Objective Our objective was to explore the experiences of parents of children with multiple sclerosis. Methods Qualitative in-depth interviews with 31 parents using a grounded theory approach were conducted. Parents were sampled and recruited via health service and voluntary sector organisations in the United Kingdom. Results Parents' accounts of life with childhood multiple sclerosis were dominated by feelings of uncertainty associated with four sources; diagnostic uncertainty, daily uncertainty, interaction uncertainty and future uncertainty. Parents attempted to manage these uncertainties using specific strategies, which could in turn create further uncertainties about their child's illness. However, over time, ongoing uncertainty appeared to give parents hope for their child's future with multiple sclerosis. Conclusion Illness-related uncertainties appear to play a role in generating hope among parents of a child with multiple sclerosis. However, this may lead parents to avoid sources of information and support that threatens their fragile optimism. Professionals need to be sensitive to the role hope plays in supporting parental coping with childhood multiple sclerosis.

Correlates of video games playing among adolescents in an Islamic country

PubMed Central

2010-01-01

Background No study has ever explored the prevalence and correlates of video game playing among children in the Islamic Republic of Iran. This study describes patterns and correlates of excessive video game use in a random sample of middle-school students in Iran. Specifically, we examine the relationship between video game playing and psychological well-being, aggressive behaviors, and adolescents' perceived threat of video-computer game playing. Methods This cross-sectional study was performed with a random sample of 444 adolescents recruited from eight middle schools. A self-administered, anonymous questionnaire covered socio-demographics, video gaming behaviors, mental health status, self-reported aggressive behaviors, and perceived side effects of video game playing. Results Overall, participants spent an average of 6.3 hours per week playing video games. Moreover, 47% of participants reported that they had played one or more intensely violent games. Non-gamers reported suffering poorer mental health compared to excessive gamers. Both non-gamers and excessive gamers overall reported suffering poorer mental health compared to low or moderate players. Participants who initiated gaming at younger ages were more likely to score poorer in mental health measures. Participants' self-reported aggressive behaviors were associated with length of gaming. Boys, but not girls, who reported playing video games excessively showed more aggressive behaviors. A multiple binary logistic regression shows that when controlling for other variables, older students, those who perceived less serious side effects of video gaming, and those who have personal computers, were more likely to report that they had played video games excessively. Conclusion Our data show a curvilinear relationship between video game playing and mental health outcomes, with "moderate" gamers faring best and "excessive" gamers showing mild increases in problematic behaviors. Interestingly, "non-gamers" clearly show the worst outcomes. Therefore, both children and parents of non-game players should be updated about the positive impact of moderate video gaming. Educational interventions should also be designed to educate adolescents and their parents of the possible harmful impact of excessive video game playing on their health and psychosocial functioning. PMID:20507610

Correlates of video games playing among adolescents in an Islamic country.

PubMed

Allahverdipour, Hamid; Bazargan, Mohsen; Farhadinasab, Abdollah; Moeini, Babak

2010-05-27

No study has ever explored the prevalence and correlates of video game playing among children in the Islamic Republic of Iran. This study describes patterns and correlates of excessive video game use in a random sample of middle-school students in Iran. Specifically, we examine the relationship between video game playing and psychological well-being, aggressive behaviors, and adolescents' perceived threat of video-computer game playing. This cross-sectional study was performed with a random sample of 444 adolescents recruited from eight middle schools. A self-administered, anonymous questionnaire covered socio-demographics, video gaming behaviors, mental health status, self-reported aggressive behaviors, and perceived side effects of video game playing. Overall, participants spent an average of 6.3 hours per week playing video games. Moreover, 47% of participants reported that they had played one or more intensely violent games. Non-gamers reported suffering poorer mental health compared to excessive gamers. Both non-gamers and excessive gamers overall reported suffering poorer mental health compared to low or moderate players. Participants who initiated gaming at younger ages were more likely to score poorer in mental health measures. Participants' self-reported aggressive behaviors were associated with length of gaming. Boys, but not girls, who reported playing video games excessively showed more aggressive behaviors. A multiple binary logistic regression shows that when controlling for other variables, older students, those who perceived less serious side effects of video gaming, and those who have personal computers, were more likely to report that they had played video games excessively. Our data show a curvilinear relationship between video game playing and mental health outcomes, with "moderate" gamers faring best and "excessive" gamers showing mild increases in problematic behaviors. Interestingly, "non-gamers" clearly show the worst outcomes. Therefore, both children and parents of non-game players should be updated about the positive impact of moderate video gaming. Educational interventions should also be designed to educate adolescents and their parents of the possible harmful impact of excessive video game playing on their health and psychosocial functioning.

Play and Developmental Outcomes in Infant Siblings of Children with Autism

PubMed Central

Hutman, Ted; Rozga, Agata; Young, Gregory S.; Ozonoff, Sally; Rogers, Sally J.; Baker, Bruce; Sigman, Marian

2010-01-01

We observed infant siblings of children with autism later diagnosed with ASD (ASD siblings; n = 17), infant siblings of children with autism with and without other delays (Other Delays and No Delays siblings; n = 12 and n = 19, respectively) and typically developing controls (TD controls; n = 19) during a free-play task at 18 months of age. Functional, symbolic, and repeated play actions were coded. ASD siblings showed fewer functional and more non-functional repeated play behaviors than TD controls. Other Delays and No Delays siblings showed more non-functional repeated play than TD controls. Group differences disappeared with the inclusion of verbal mental age. Play as an early indicator of autism and its relationship to the broader autism phenotype is discussed. PMID:20112084

Effects of tennis play on executive function in 6-11-year-old children: a 12-month longitudinal study.

PubMed

Ishihara, Toru; Mizuno, Masao

2018-06-01

The present study aimed to assess the effects of 12 months of frequent tennis play on executive functions and the relationships of daily moderate-to-vigorous physical activity (MVPA), physical competence, and enjoyment of playing tennis to executive functions in children. Thirty-two children (6-11 years old) who had regularly played tennis (once a week; mean = 3 years, range = 0-6 years) before the study were enrolled in a 12-month intervention. Participants were allocated into two groups: low-dose (maintain current frequency of tennis play, N = 19) or high-dose (increased frequency of tennis play to four times per week, N = 13). Participants' MVPA, physical competence, enjoyment of playing tennis, and executive functions (i.e. inhibitory control, working memory, and cognitive flexibility) were evaluated before and after this intervention. The high-dose group demonstrated a greater improvement in working memory than the low-dose group, while there was no group difference in MVPA, physical competence, and enjoyment of playing tennis. Changes in MVPA were associated with improvements in cognitive flexibility. Changes in physical competence were associated with improvements in working memory and cognitive flexibility. Changes in the enjoyment of playing tennis were associated with improvements in inhibitory control. The current findings suggest that replacement of MVPA with sports activity, such as tennis enhances executive functions development, and suggest that sports programmes that seek to build competence and enjoyment might help support the development of executive functions in children.

MoSwi6, an APSES family transcription factor, interacts with MoMps1 and is required for hyphal and conidial morphogenesis, appressorial function, and pathogenicity of Magnaporthe oryzae

PubMed Central

Qi, Zhongqiang; Wang, Qi; Dou, Xianying; Wang, Wei; Zhao, Qian; Lv, Ruili; Zhang, Haifeng; Zheng, Xiaobo; Wang, Ping; Zhang, Zhengguang

2011-01-01

Magnaporthe oryzae MAPK MoMps1 plays a critical role in regulating various developmental processes including cell wall integrity, stress responses, and pathogenicity. To identify potential effectors of MoMps1, we characterized the function of MoSwi6, a homolog of Saccharomyces cerevisiae Swi6 downstream of MAPK Slt2 signaling. MoSwi6 interacted with MoMps1 both in vivo and in vitro, suggesting a possible functional link analogous to Swi6-Slt2 in S. cerevisiae. Targeted gene disruption of MoSWI6 resulted in multiple developmental defects, including reduced hyphal growth, abnormal formation of conidia and appressoria, and impaired appressorium function. The reduction in appressorial turgor pressure also contributed to an attenuation of pathogenicity. The ΔMoswi6 mutant also displayed a defect in cell wall integrity, was hypersensitive to the oxidative stress, and showed significant reduction in transcription and activities of extracellular enzymes including peroxidases and laccases. Collectively, these roles are similar to those of MoMps1, confirming that MoSwi6 functions in the MoMps1 pathway to govern growth, development, and full pathogenicity. PMID:22321443

Enhanced NMR Discrimination of Pharmaceutically Relevant Molecular Crystal Forms through Fragment-Based Ab Initio Chemical Shift Predictions.

PubMed

Hartman, Joshua D; Day, Graeme M; Beran, Gregory J O

2016-11-02

Chemical shift prediction plays an important role in the determination or validation of crystal structures with solid-state nuclear magnetic resonance (NMR) spectroscopy. One of the fundamental theoretical challenges lies in discriminating variations in chemical shifts resulting from different crystallographic environments. Fragment-based electronic structure methods provide an alternative to the widely used plane wave gauge-including projector augmented wave (GIPAW) density functional technique for chemical shift prediction. Fragment methods allow hybrid density functionals to be employed routinely in chemical shift prediction, and we have recently demonstrated appreciable improvements in the accuracy of the predicted shifts when using the hybrid PBE0 functional instead of generalized gradient approximation (GGA) functionals like PBE. Here, we investigate the solid-state 13 C and 15 N NMR spectra for multiple crystal forms of acetaminophen, phenobarbital, and testosterone. We demonstrate that the use of the hybrid density functional instead of a GGA provides both higher accuracy in the chemical shifts and increased discrimination among the different crystallographic environments. Finally, these results also provide compelling evidence for the transferability of the linear regression parameters mapping predicted chemical shieldings to chemical shifts that were derived in an earlier study.

Enhanced NMR Discrimination of Pharmaceutically Relevant Molecular Crystal Forms through Fragment-Based Ab Initio Chemical Shift Predictions

PubMed Central

2016-01-01

Chemical shift prediction plays an important role in the determination or validation of crystal structures with solid-state nuclear magnetic resonance (NMR) spectroscopy. One of the fundamental theoretical challenges lies in discriminating variations in chemical shifts resulting from different crystallographic environments. Fragment-based electronic structure methods provide an alternative to the widely used plane wave gauge-including projector augmented wave (GIPAW) density functional technique for chemical shift prediction. Fragment methods allow hybrid density functionals to be employed routinely in chemical shift prediction, and we have recently demonstrated appreciable improvements in the accuracy of the predicted shifts when using the hybrid PBE0 functional instead of generalized gradient approximation (GGA) functionals like PBE. Here, we investigate the solid-state 13C and 15N NMR spectra for multiple crystal forms of acetaminophen, phenobarbital, and testosterone. We demonstrate that the use of the hybrid density functional instead of a GGA provides both higher accuracy in the chemical shifts and increased discrimination among the different crystallographic environments. Finally, these results also provide compelling evidence for the transferability of the linear regression parameters mapping predicted chemical shieldings to chemical shifts that were derived in an earlier study. PMID:27829821

Unconventional binding sites and receptors for VIP and related peptides PACAP and PHI/PHM: an update.

PubMed

Muller, Jean-Marc; Debaigt, Colin; Goursaud, Stéphanie; Montoni, Alicia; Pineau, Nicolas; Meunier, Annie-Claire; Janet, Thierry

2007-09-01

The 28-amino-acid neuropeptide VIP and related peptides PACAP and PHI/PHM modulate virtually all of the vital functions in the body. These peptides are also commonly recognized as major regulators of cell growth and differentiation. Through their trophic and cytoprotective functions, they appear to play major roles in embryonic development, neurogenesis and the progression of a number of cancer types. These peptides bind to three well-characterized subtypes of G-protein coupled receptors: VPAC1 and VPAC2 share a common high affinity in the nanomolar range for VIP and PACAP; a third receptor type, PAC1, has been characterized for its high affinity for PACAP but its low affinity for VIP. Complex effects and pharmacological behaviors of these peptides suggest that multiple subtypes of binding sites may cooperate to mediate their function in target cells and tissues. In this complex response, some of these binding sites correspond to the definition of the conventional receptors cited above, while others display unexpected pharmacological and functional properties. Here we present potential clues that may lead investigators to further characterize the molecular nature and functions of these atypical binding species.

Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

PubMed Central

Liu, Zhongwu; Chopp, Michael

2015-01-01

Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

The neural correlates of risky decision making across short and long runs

PubMed Central

Rao, Li-Lin; Dunn, John C.; Zhou, Yuan; Li, Shu

2015-01-01

People frequently change their preferences for options of gambles which they play once compared to those they play multiple times. In general, preferences for repeated play gambles are more consistent with the expected values of the options. According to the one-process view, the change in preference is due to a change in the structure of the gamble that is relevant to decision making. According to the two-process view, the change is attributable to a shift in the decision making strategy that is used. To adjudicate between these two theories, we asked participants to choose between gambles played once or 100 times, and to choose between them based on their expected value. Consistent with the two-process theory, we found a set of brain regions that were sensitive to the extent of behavioral change between single and aggregated play and also showed significant (de)activation in the expected value choice task. These results support the view that people change their decision making strategies for risky choice considered once or multiple times. PMID:26516095

Antimicrobial Peptides from Plants

PubMed Central

Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

2015-01-01

Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

Effect of processor temperature on film dosimetry

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

Srivastava, Shiv P.; Das, Indra J., E-mail: idas@iupui.edu

2012-07-01

Optical density (OD) of a radiographic film plays an important role in radiation dosimetry, which depends on various parameters, including beam energy, depth, field size, film batch, dose, dose rate, air film interface, postexposure processing time, and temperature of the processor. Most of these parameters have been studied for Kodak XV and extended dose range (EDR) films used in radiation oncology. There is very limited information on processor temperature, which is investigated in this study. Multiple XV and EDR films were exposed in the reference condition (d{sub max.}, 10 Multiplication-Sign 10 cm{sup 2}, 100 cm) to a given dose. Anmore » automatic film processor (X-Omat 5000) was used for processing films. The temperature of the processor was adjusted manually with increasing temperature. At each temperature, a set of films was processed to evaluate OD at a given dose. For both films, OD is a linear function of processor temperature in the range of 29.4-40.6 Degree-Sign C (85-105 Degree-Sign F) for various dose ranges. The changes in processor temperature are directly related to the dose by a quadratic function. A simple linear equation is provided for the changes in OD vs. processor temperature, which could be used for correcting dose in radiation dosimetry when film is used.« less

MPO4:Nd3+ (M=Ca, Gd), Luminomagnetic Nanophosphors with Optical and Magnetic Features for Multimodal Imaging Applications

NASA Astrophysics Data System (ADS)

Rightsell, Chris; Mimun, Lawrence C.; Kumar, Ajith G.; Sardar, Dhiraj K.

2015-03-01

Nanomaterials with multiple functionalities play a very important role in several high technology applications. A major area of such applications is the biomedical industry, where contrast agents with multiple imaging modalities can provide better results than conventional materials. Many of the contrast agents available now have drawbacks such as toxicity, photobleaching, low contrast, size restrictions, and overall cost of the imaging system. Rare-earth doped inorganic nanophosphors are alternatives to circumvent several of these issues, together with the added advantage of super high resolution imaging due to the excellent near infrared sensitivity of the phosphors. In addition to optical imaging features, by adding a magnetic ion such as Gd3+ at suitable lattice positions, the phosphor can be made magnetic, yielding dual imaging functionalities. In this research, we are presenting the optical and magnetic imaging features of sub-nanometer size MPO4:Nd3+ (M=Ca, Gd) phosphors for the potential application of these nanophosphors as multimodal contrast agents. Cytotoxicity, in vitro and in vivo imaging, penetration depth etc. are studied for various phosphor compositions, and optimized compositions are explored. This research was funded by the National Science Foundation Partnerships for Research and Education in Materials (NSF-PREM) Grant N0-DMR-0934218.

HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy.

PubMed

Friedrichs, Frauke; Zugck, Christian; Rauch, Gerd-Jörg; Ivandic, Boris; Weichenhan, Dieter; Müller-Bardorff, Margit; Meder, Benjamin; El Mokhtari, Nour Eddine; Regitz-Zagrosek, Vera; Hetzer, Roland; Schäfer, Arne; Schreiber, Stefan; Chen, Jian; Neuhaus, Isaac; Ji, Ruiru; Siemers, Nathan O; Frey, Norbert; Rottbauer, Wolfgang; Katus, Hugo A; Stoll, Monika

2009-03-01

Human dilated cardiomyopathy (DCM), a disorder of the cardiac muscle, causes considerable morbidity and mortality and is one of the major causes of sudden cardiac death. Genetic factors play a role in the etiology and pathogenesis of DCM. Disease-associated genetic variations identified to date have been identified in single families or single sporadic patients and explain a minority of the etiology of DCM. We show that a 600-kb region of linkage disequilibrium (LD) on 5q31.2-3, harboring multiple genes, is associated with cardiomyopathy in three independent Caucasian populations (combined P-value = 0.00087). Functional assessment in zebrafish demonstrates that at least three genes, orthologous to loci in this LD block, HBEGF, IK, and SRA1, result independently in a phenotype of myocardial contractile dysfunction when their expression is reduced with morpholino antisense reagents. Evolutionary analysis across multiple vertebrate genomes suggests that this heart failure-associated LD block emerged by a series of genomic rearrangements across amphibian, avian, and mammalian genomes and is maintained as a cluster in mammals. Taken together, these observations challenge the simple notion that disease phenotypes can be traced to altered function of a single locus within a haplotype and suggest that a more detailed assessment of causality can be necessary.

HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy

PubMed Central

Friedrichs, Frauke; Zugck, Christian; Rauch, Gerd-Jörg; Ivandic, Boris; Weichenhan, Dieter; Müller-Bardorff, Margit; Meder, Benjamin; El Mokhtari, Nour Eddine; Regitz-Zagrosek, Vera; Hetzer, Roland; Schäfer, Arne; Schreiber, Stefan; Chen, Jian; Neuhaus, Isaac; Ji, Ruiru; Siemers, Nathan O.; Frey, Norbert; Rottbauer, Wolfgang; Katus, Hugo A.; Stoll, Monika

2009-01-01

Human dilated cardiomyopathy (DCM), a disorder of the cardiac muscle, causes considerable morbidity and mortality and is one of the major causes of sudden cardiac death. Genetic factors play a role in the etiology and pathogenesis of DCM. Disease-associated genetic variations identified to date have been identified in single families or single sporadic patients and explain a minority of the etiology of DCM. We show that a 600-kb region of linkage disequilibrium (LD) on 5q31.2-3, harboring multiple genes, is associated with cardiomyopathy in three independent Caucasian populations (combined P-value = 0.00087). Functional assessment in zebrafish demonstrates that at least three genes, orthologous to loci in this LD block, HBEGF, IK, and SRA1, result independently in a phenotype of myocardial contractile dysfunction when their expression is reduced with morpholino antisense reagents. Evolutionary analysis across multiple vertebrate genomes suggests that this heart failure-associated LD block emerged by a series of genomic rearrangements across amphibian, avian, and mammalian genomes and is maintained as a cluster in mammals. Taken together, these observations challenge the simple notion that disease phenotypes can be traced to altered function of a single locus within a haplotype and suggest that a more detailed assessment of causality can be necessary. PMID:19064678

Deciphering the Role of B Cells in Multiple Sclerosis—Towards Specific Targeting of Pathogenic Function

PubMed Central

Lehmann-Horn, Klaus; Kinzel, Silke; Weber, Martin S.

2017-01-01

B cells, plasma cells and antibodies may play a key role in the pathogenesis of multiple sclerosis (MS). This notion is supported by various immunological changes observed in MS patients, such as activation and pro-inflammatory differentiation of peripheral blood B cells, the persistence of clonally expanded plasma cells producing immunoglobulins in the cerebrospinal fluid, as well as the composition of inflammatory central nervous system lesions frequently containing co-localizing antibody depositions and activated complement. In recent years, the perception of a respective pathophysiological B cell involvement was vividly promoted by the empirical success of anti-CD20-mediated B cell depletion in clinical trials; based on these findings, the first monoclonal anti-CD20 antibody—ocrelizumab—is currently in the process of being approved for treatment of MS. In this review, we summarize the current knowledge on the role of B cells, plasma cells and antibodies in MS and elucidate how approved and future treatments, first and foremost anti-CD20 antibodies, therapeutically modify these B cell components. We will furthermore describe regulatory functions of B cells in MS and discuss how the evolving knowledge of these therapeutically desirable B cell properties can be harnessed to improve future safety and efficacy of B cell-directed therapy in MS. PMID:28946620

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach

PubMed Central

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions. PMID:29033978

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach.

PubMed

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions.

Vesicular transport protein Arf6 modulates cytoskeleton dynamics for polar body extrusion in mouse oocyte meiosis.

PubMed

Duan, Xing; Zhang, Hao-Lin; Pan, Meng-Hao; Zhang, Yu; Sun, Shao-Chen

2018-02-01

Arf6 (ADP-ribosylation factor 6) is known to play important roles in membrane dynamics through the regulation of actin filament reorganization for multiple cellular processes such as cytokinesis, phagocytosis, cell migration and tumor cell invasion. However, the functions of Arf6 in mammalian oocyte meiosis have not been clarified. In present study we showed that Arf6 expressed in mouse oocytes and was mainly distributed around the spindle during meiosis. Depletion of Arf6 by morpholino microinjection caused oocytes failing to extrude first polar body. Further analysis indicated that Arf6 knock down caused the aberrant actin distribution, which further induced the failure of meiotic spindle movement. And the loss of oocyte polarity also confirmed this. The regulation of Arf6 on actin filaments in mouse oocytes might be due to its effects on the phosphorylation level of cofilin and the expression of Arp2/3 complex. Moreover, we found that the decrease of Arf6 caused the disruption of spindle formation, indicating the multiple roles of Arf6 on cytoskeleton dynamics in meiosis. In summary, our results indicated that Arf6 was involved in mouse oocyte meiosis through its functional roles in actin-mediated spindle movement and spindle organization. Copyright © 2017 Elsevier B.V. All rights reserved.

A simplified implementation of edge detection in MATLAB is faster and more sensitive than fast fourier transform for actin fiber alignment quantification.

PubMed

Kemeny, Steven Frank; Clyne, Alisa Morss

2011-04-01

Fiber alignment plays a critical role in the structure and function of cells and tissues. While fiber alignment quantification is important to experimental analysis and several different methods for quantifying fiber alignment exist, many studies focus on qualitative rather than quantitative analysis perhaps due to the complexity of current fiber alignment methods. Speed and sensitivity were compared in edge detection and fast Fourier transform (FFT) for measuring actin fiber alignment in cells exposed to shear stress. While edge detection using matrix multiplication was consistently more sensitive than FFT, image processing time was significantly longer. However, when MATLAB functions were used to implement edge detection, MATLAB's efficient element-by-element calculations and fast filtering techniques reduced computation cost 100 times compared to the matrix multiplication edge detection method. The new computation time was comparable to the FFT method, and MATLAB edge detection produced well-distributed fiber angle distributions that statistically distinguished aligned and unaligned fibers in half as many sample images. When the FFT sensitivity was improved by dividing images into smaller subsections, processing time grew larger than the time required for MATLAB edge detection. Implementation of edge detection in MATLAB is simpler, faster, and more sensitive than FFT for fiber alignment quantification.

Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

PubMed Central

Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo; Giavaresi, Gianluca; Alessandro, Riccardo

2015-01-01

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes. PMID:25944696

TACC3 is a microtubule plus end–tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types

PubMed Central

Nwagbara, Belinda U.; Faris, Anna E.; Bearce, Elizabeth A.; Erdogan, Burcu; Ebbert, Patrick T.; Evans, Matthew F.; Rutherford, Erin L.; Enzenbacher, Tiffany B.; Lowery, Laura Anne

2014-01-01

Microtubule plus end dynamics are regulated by a conserved family of proteins called plus end–tracking proteins (+TIPs). It is unclear how various +TIPs interact with each other and with plus ends to control microtubule behavior. The centrosome-associated protein TACC3, a member of the transforming acidic coiled-coil (TACC) domain family, has been implicated in regulating several aspects of microtubule dynamics. However, TACC3 has not been shown to function as a +TIP in vertebrates. Here we show that TACC3 promotes axon outgrowth and regulates microtubule dynamics by increasing microtubule plus end velocities in vivo. We also demonstrate that TACC3 acts as a +TIP in multiple embryonic cell types and that this requires the conserved C-terminal TACC domain. Using high-resolution live-imaging data on tagged +TIPs, we show that TACC3 localizes to the extreme microtubule plus end, where it lies distal to the microtubule polymerization marker EB1 and directly overlaps with the microtubule polymerase XMAP215. TACC3 also plays a role in regulating XMAP215 stability and localizing XMAP215 to microtubule plus ends. Taken together, our results implicate TACC3 as a +TIP that functions with XMAP215 to regulate microtubule plus end dynamics. PMID:25187649

Functional inactivation of hypocretin 1 receptors in the medial prefrontal cortex affects the pyramidal neuron activity and gamma oscillations: An in vivo multiple-channel single-unit recording study.

PubMed

He, C; Chen, Q-H; Ye, J-N; Li, C; Yang, L; Zhang, J; Xia, J-X; Hu, Z-A

2015-06-25

The hypocretin signaling is thought to play a critical role in maintaining wakefulness via stimulating the subcortical arousal pathways. Although the cortical areas, including the medial prefrontal cortex (mPFC), receive dense hypocretinergic fibers and express its receptors, it remains unclear whether the hypocretins can directly regulate the neural activity of the mPFC in vivo. In the present study, using multiple-channel single-unit recording study, we found that infusion of the SB-334867, a blocker for the Hcrtr1, beside the recording sites within the mPFC substantially exerted an inhibitory effect on the putative pyramidal neuron (PPN) activity in naturally behaving rats. In addition, functional blockade of the Hcrtr1 also selectively reduced the power of the gamma oscillations. The PPN activity and the power of the neural oscillations were not affected after microinjection of the TCS-OX2-29, a blocker for the Hcrtr2, within the mPFC. Together, these data indicate that endogenous hypocretins acting on the Hcrtr1 are required for the normal neural activity in the mPFC in vivo, and thus might directly contribute cortical arousal and mPFC-dependent cognitive processes. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Content Representation in the Human Medial Temporal Lobe

PubMed Central

Liang, Jackson C.; Wagner, Anthony D.

2013-01-01

Current theories of medial temporal lobe (MTL) function focus on event content as an important organizational principle that differentiates MTL subregions. Perirhinal and parahippocampal cortices may play content-specific roles in memory, whereas hippocampal processing is alternately hypothesized to be content specific or content general. Despite anatomical evidence for content-specific MTL pathways, empirical data for content-based MTL subregional dissociations are mixed. Here, we combined functional magnetic resonance imaging with multiple statistical approaches to characterize MTL subregional responses to different classes of novel event content (faces, scenes, spoken words, sounds, visual words). Univariate analyses revealed that responses to novel faces and scenes were distributed across the anterior–posterior axis of MTL cortex, with face responses distributed more anteriorly than scene responses. Moreover, multivariate pattern analyses of perirhinal and parahippocampal data revealed spatially organized representational codes for multiple content classes, including nonpreferred visual and auditory stimuli. In contrast, anterior hippocampal responses were content general, with less accurate overall pattern classification relative to MTL cortex. Finally, posterior hippocampal activation patterns consistently discriminated scenes more accurately than other forms of content. Collectively, our findings indicate differential contributions of MTL subregions to event representation via a distributed code along the anterior–posterior axis of MTL that depends on the nature of event content. PMID:22275474

The importance of biodiversity and dominance for multiple ecosystem functions in a human-modified tropical landscape.

PubMed

Lohbeck, Madelon; Bongers, Frans; Martinez-Ramos, Miguel; Poorter, Lourens

2016-10-01

Many studies suggest that biodiversity may be particularly important for ecosystem multifunctionality, because different species with different traits can contribute to different functions. Support, however, comes mostly from experimental studies conducted at small spatial scales in low-diversity systems. Here, we test whether different species contribute to different ecosystem functions that are important for carbon cycling in a high-diversity human-modified tropical forest landscape in Southern Mexico. We quantified aboveground standing biomass, primary productivity, litter production, and wood decomposition at the landscape level, and evaluated the extent to which tree species contribute to these ecosystem functions. We used simulations to tease apart the effects of species richness, species dominance and species functional traits on ecosystem functions. We found that dominance was more important than species traits in determining a species' contribution to ecosystem functions. As a consequence of the high dominance in human-modified landscapes, the same small subset of species mattered across different functions. In human-modified landscapes in the tropics, biodiversity may play a limited role for ecosystem multifunctionality due to the potentially large effect of species dominance on biogeochemical functions. However, given the spatial and temporal turnover in species dominance, biodiversity may be critically important for the maintenance and resilience of ecosystem functions. © 2016 The Authors. Ecology, published by Wiley Periodicals, Inc., on behalf of the Ecological Society of America.