• Development of the uncinate fasciculus: Implications for theory and developmental disorders

      Olson, IR; Heide, RJVD; Alm, KH; Vyas, G (2015-07-03)
      © 2015 The Authors. Abstract The uncinate fasciculus (UF) is a long-range white matter tract that connects limbic regions in the temporal lobe to the frontal lobe. The UF is one of the latest developing tracts, and continues maturing into the third decade of life. As such, individual differences in the maturational profile of the UF may serve to explain differences in behavior. Indeed, atypical macrostructure and microstructure of the UF have been reported in numerous studies of individuals with developmental and psychiatric disorders such as social deprivation and maltreatment, autism spectrum disorders, conduct disorder, risk taking, and substance abuse. The present review evaluates what we currently know about the UF's developmental trajectory and reviews the literature relating UF abnormalities to specific disorders. Additionally, we take a dimensional approach and critically examine symptoms and behavioral impairments that have been demonstrated to cluster with UF aberrations, in an effort to relate these impairments to our speculations regarding the functionality of the UF. We suggest that developmental disorders with core problems relating to memory retrieval, reward and valuation computation, and impulsive decision making may be linked to aberrations in uncinate microstructure.
    • Editorial: Global Education of Health Management

      Evashwick, CJ; Aaronson, WE (2019-01-01)
    • Editorial: Modeling Play in Early Infant Development

      Shaw, P; Lee, M; Shen, Q; Hirsh-Pasek, K; Adolph, KE; Oudeyer, PY; Popp, J (2020-08-06)
    • Editorial: Obesity Science and Practice (Feb 2018)

      Sarwer, DB; Sarwer, David B|0000-0003-1033-5528 (2018-02-01)
    • Effect of deinstitutionalisation for adults with intellectual disabilities on costs: A systematic review

      May, P; Lombard Vance, R; Murphy, E; O'Donovan, MA; Webb, N; Sheaf, G; McCallion, P; Stancliffe, R; Normand, C; Smith, V; McCarron, M; Mccallion, Philip|0000-0001-5129-6399 (2019-01-01)
      © 2019 Author(s). Objective To review systematically the evidence on the costs and cost-effectiveness of deinstitutionalisation for adults with intellectual disabilities. Design Systematic review. Population Adults (aged 18 years and over) with intellectual disabilities. Intervention Deinstitutionalisation, that is, the move from institutional to community settings. Primary and secondary outcome measures Studies were eligible if evaluating within any cost-consequence framework (eg, cost-effectiveness analysis, cost-utility analysis) or resource use typically considered to fall within the societal viewpoint (eg, cost to payers, service-users, families and informal care costs). Search We searched MEDLINE, PsycINFO, CENTRAL, CINAHL, EconLit, Embase and Scopus to September 2017 and supplemented this with grey literature searches and handsearching of the references of the eligible studies. We assessed study quality using the Critical Appraisals Skills Programme suite of tools, excluding those judged to be of poor methodological quality. Results Two studies were included; both were cohort studies from the payer perspective of people leaving long-stay National Health Service hospitals in the UK between 1984 and 1992. One study found that deinstitutionalisation reduced costs, one study found an increase in costs. Conclusion A wide-ranging literature review found limited evidence on costs associated with deinstitutionalisation for people with intellectual disabilities. From two studies included in the review, the results were conflicting. Significant gaps in the evidence base were observable, particularly with respect to priority populations in contemporary policy: older people with intellectual disabilities and serious medical illness, and younger people with very complex needs and challenging behaviours. PROSPERO registration number CRD42018077406
    • Embodied cognition and STEM learning: overview of a topical collection in CR:PI

      Weisberg, SM; Newcombe, NS (2017-12-01)
      © 2017, The Author(s). Embodied learning approaches emphasize the use of action to support pedagogical goals. A specific version of embodied learning posits an action-to-abstraction transition supported by gesture, sketching, and analogical mapping. These tools seem to have special promise for bolstering learning in science, technology, engineering, and mathematics (STEM) disciplines, but existing efforts need further theoretical and empirical development. The topical collection in Cognitive Research: Principles includes articles aiming to formalize and test the effectiveness of embodied learning in STEM. The collection provides guideposts, staking out the terrain that should be surveyed before larger-scale efforts are undertaken. This introduction provides a broader context concerning mechanisms that can support embodied learning and make it especially well suited to the STEM disciplines.
    • Enhancer of zeste homolog 2 (EZH2) in pediatric soft tissue sarcomas: First implications

      Ciarapica, R; Miele, L; Giordano, A; Locatelli, F; Rota, R; Giordano, Antonio|0000-0002-5959-016X (2011-05-25)
      Soft tissue sarcomas of childhood are a group of heterogeneous tumors thought to be derived from mesenchymal stem cells. Surgical resection is effective only in about 50% of cases and resistance to conventional chemotherapy is often responsible for treatment failure. Therefore, investigations on novel therapeutic targets are of fundamental importance. Deregulation of epigenetic mechanisms underlying chromatin modifications during stem cell differentiation has been suggested to contribute to soft tissue sarcoma pathogenesis. One of the main elements in this scenario is enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to the Polycomb group proteins. EZH2 catalyzes histone H3 methylation on gene promoters, thus repressing genes that induce stem cell differentiation to maintain an embryonic stem cell signature. EZH2 deregulated expression/function in soft tissue sarcomas has been recently reported. In this review, an overview of the recently reported functions of EZH2 in soft tissue sarcomas is given and the hypothesis that its expression might be involved in soft tissue sarcomagenesis is discussed. Finally, the therapeutic potential of epigenetic therapies modulating EZH2-mediated gene repression is considered. © 2011 Ciarapica et al; licensee BioMed Central Ltd.
    • Enhancer trapping in zebrafish using the Sleeping Beauty transposon

      Balciunas, D; Davidson, AE; Sivasubbu, S; Hermanson, SB; Welle, Z; Ekker, SC; Balciunas, Darius|0000-0003-1938-3243 (2004-09-03)
      Background: Among functional elements of a metazoan gene, enhancers are particularly difficult to find and annotate. Pioneering experiments in Drosophila have demonstrated the value of enhancer "trapping" using an invertebrate to address this functional genomics problem. Results: We modulated a Sleeping Beauty transposon-based transgenesis cassette to establish an enhancer trapping technique for use in a vertebrate model system, zebrafish Danio rerio. We established 9 lines of zebrafish with distinct tissue- or organ-specific GFP expression patterns from 90 founders that produced GFP-expressing progeny. We have molecularly characterized these lines and show that in each line, a specific GFP expression pattern is due to a single transposition event. Many of the insertions are into introns of zebrafish genes predicted in the current genome assembly. We have identified both previously characterized as well as novel expression patterns from this screen. For example, the ET7 line harbors a transposon insertion near the mkp3 locus and expresses GFP in the midbrain-hindbrain boundary, forebrain and the ventricle, matching a subset of the known FGF8-dependent mkp3 expression domain. The ET2 line, in contrast, expresses GFP specifically in caudal primary motoneurons due to an insertion into the poly(ADPribose) glycohydrolase (PARG) locus. This surprising expression pattern was confirmed using in situ hybridization techniques for the endogenous PARG mRNA, indicating the enhancer trap has replicated this unexpected and highly localized PARG expression with good fidelity. Finally, we show that it is possible to excise a Sleeping Beauty transposon from a genomic location in the zebrafish germline. Conclusions: This genomics tool offers the opportunity for large-scale biological approaches combining both expression and genomic-level sequence analysis using as a template an entire vertebrate genome. © 2004 Balciunas et al; licensee BioMed Central Ltd.
    • Erratum to: E-GRASP: An integrated evolutionary and GRASP resource for exploring disease associations

      Karim, S; Nour Eldin, HF; Abusamra, H; Salem, N; Alhathli, E; Dudley, J; Sanderford, M; Scheinfeldt, LB; Chaudhary, AG; Al-Qahtani, MH; Kumar, S; Kumar, Sudhir|0000-0002-9918-8212 (2017-04-06)
      © 2017 The Author(s). This article [1] unfortunately published with an author deleted in the author list. The correct author list is presented above.
    • Evaluating dosage compensation as a cause of duplicate gene retention in Paramecium tetraurelia

      Hughes, T; Ekman, D; Ardawatia, H; Elofsson, A; Liberles, DA; Liberles, David A|0000-0003-3487-8826 (2007-05-22)
      The high retention of duplicate genes in the genome of Paramecium tetraurelia has led to the hypothesis that most of the retained genes have persisted because of constraints due to gene dosage. This and other possible mechanisms are discussed in the light of expectations from population genetics and systems biology. © 2007 BioMed Central Ltd.
    • Evolution and structure of proteins and proteomes

      Liberles, DA; Teufel, AI; Liberles, David A|0000-0003-3487-8826 (2018-12-01)
      <jats:p>This themed issue centered on the evolution and structure of proteins and proteomes is comprised of seven published manuscripts. [...]</jats:p>
    • Evolutionary sequence analysis of complete eukaryote genomes

      Blair, JE; Shah, P; Hedges, SB (2005-03-11)
      Background: Gene duplication and gene loss during the evolution of eukaryotes have hindered attempts to estimate phylogenies and divergence times of species. Although current methods that identify clusters of orthologous genes in complete genomes have helped to investigate gene function and gene content, they have not been optimized for evolutionary sequence analyses requiring strict orthology and complete gene matrices. Here we adopt a relatively simple and fast genome comparison approach designed to assemble orthologs for evolutionary analysis. Our approach identifies single-copy genes representing only species divergences (panorthologs) in order to minimize potential errors caused by gene duplication. We apply this approach to complete sets of proteins from published eukaryote genomes specifically for phylogeny and time estimation. Results: Despite the conservative criterion used, 753 panorthologs (proteins) were identified for evolutionary analysis with four genomes, resulting in a single alignment of 287,000 amino acids. With this data set, we estimate that the divergence between deuterostomes and arthropods took place in the Precambrian, approximately 400 million years before the first appearance of animals in the fossil record. Additional analyses were performed with seven, 12, and 15 eukaryote genomes resulting in similar divergence time estimates and phylogenies. Conclusion: Our results with available eukaryote genomes agree with previous results using conventional methods of sequence data assembly from genomes. They show that large sequence data sets can be generated relatively quickly and efficiently for evolutionary analyses of complete genomes. © 2005 Blair et al; licensee BioMed Central Ltd.
    • Examining Adolescence as a Sensitive Period for High-Fat, High-Sugar Diet Exposure: A Systematic Review of the Animal Literature

      Murray, S; Chen, EY (2019-10-25)
      © Copyright © 2019 Murray and Chen. Animal studies suggest that poor nutrition (e.g., high-fat, high-sugar diets) may lead to impairments in cognitive functioning. Accumulating evidence suggests that the deleterious effects of these diets appear more pronounced in animals maintained on this diet early in life, consistent with the notion that the developing brain may be especially vulnerable to environmental insults. The current paper provides the first systematic review of studies comparing the effects of high-fat, high-sugar diet exposure during adolescence and adulthood on memory performance. The majority of studies (7/8) identified here report diet-induced memory problems when diet exposure began in adolescence but not adulthood. These findings lend support to the hypothesis that adolescence is a sensitive period during which palatable diets may contribute to negative neurocognitive effects. The current review explores putative mechanisms involved in diet-induced cognitive dysfunction and highlights promising areas for further research.
    • Extracting functional trends from whole genome duplication events using comparative genomics

      Hermansen, RA; Hvidsten, TR; Sandve, SR; Liberles, DA; Liberles, David A|0000-0003-3487-8826 (2016-05-10)
      © 2016 Hermansen et al. Background: The number of species with completed genomes, including those with evidence for recent whole genome duplication events has exploded. The recently sequenced Atlantic salmon genome has been through two rounds of whole genome duplication since the divergence of teleost fish from the lineage that led to amniotes. This quadrupoling of the number of potential genes has led to complex patterns of retention and loss among gene families. Results: Methods have been developed to characterize the interplay of duplicate gene retention processes across both whole genome duplication events and additional smaller scale duplication events. Further, gene expression divergence data has become available as well for Atlantic salmon and the closely related, pre-whole genome duplication pike and methods to describe expression divergence are also presented. These methods for the characterization of duplicate gene retention and gene expression divergence that have been applied to salmon are described. Conclusions: With the growth in available genomic and functional data, the opportunities to extract functional inference from large scale duplicates using comparative methods have expanded dramatically. Recently developed methods that further this inference for duplicated genes have been described.
    • Feasibility of muscle synergy outcomes in clinics, robotics, and sports: A systematic review

      Taborri, J; Agostini, V; Artemiadis, PK; Ghislieri, M; Jacobs, DA; Roh, J; Rossi, S (2018-01-01)
      Copyright © 2018 Juri Taborri et al. In the last years, several studies have been focused on understanding how the central nervous system controls muscles to perform a specific motor task. Although it still remains an open question, muscle synergies have come to be an appealing theory to explain the modular organization of the central nervous system. Even though the neural encoding of muscle synergies remains controversial, a large number of papers demonstrated that muscle synergies are robust across different tested conditions, which are within a day, between days, within a single subject, and between subjects that have similar demographic characteristics. Thus, muscle synergy theory has been largely used in several research fields, such as clinics, robotics, and sports. The present systematical review aims at providing an overview on the applications of muscle synergy theory in clinics, robotics, and sports; in particular, the review is focused on the papers that provide tangible information for (i) diagnosis or pathology assessment in clinics, (ii) robot-control design in robotics, and (iii) athletes' performance assessment or training guidelines in sports.
    • Fibronectin Mechanobiology Regulates Tumorigenesis

      Wang, K; Seo, BR; Fischbach, C; Gourdon, D; Wang, Karin|0000-0001-7812-2583 (2016-03-01)
      © 2015, The Author(s). Fibronectin (Fn) is an essential extracellular matrix (ECM) glycoprotein involved in both physiological and pathological processes. The structure–function relationship of Fn has been and is still being studied, as changes in its molecular structure are integral in regulating (or dysregulating) its biological activities via its cell, matrix component, and growth factor binding sites. Fn comprises three types of repeating modules; among them, FnIII modules are mechanically unstable domains that may be extended/unfolded upon cell traction and either uncover cryptic binding sites or disrupt otherwise exposed binding sites. Cells assemble Fn into a fibrillar network; its conformational flexibility implicates Fn as a critical mechanoregulator of the ECM. Fn has been shown to contribute to altered stroma remodeling during tumorigenesis. This review will discuss (i) the significance of the structure–function relationship of Fn at both the molecular and the matrix scales, (ii) the role of Fn mechanobiology in the regulation of tumorigenesis, and (iii) Fn-related advances in cancer therapy development.
    • Fish mutant, where is thy phenotype?

      Balciunas, D; Balciunas, Darius|0000-0003-1938-3243 (2018-02-01)
    • From snake venom’s disintegrins and C-type lectins to anti-platelet drugs

      Lazarovici, P; Marcinkiewicz, C; Lelkes, PI; Lelkes, Peter|0000-0003-4954-3498 (2019-05-01)
      © 2019 by the authors. Licensee MDPI, Basel, Switzerland. Snake venoms are attractive natural sources for drug discovery and development, with a number of substances either in clinical use or in research and development. These drugs were developed based on RGD-containing snake venom disintegrins, which efficiently antagonize fibrinogen activation of αIIbβ3 integrin (glycoprotein GP IIb/IIIa). Typical examples of anti-platelet drugs found in clinics are Integrilin (Eptifibatide), a heptapeptide derived from Barbourin, a protein found in the venom of the American Southeastern pygmy rattlesnake and Aggrastat (Tirofiban), a small molecule based on the structure of Echistatin, and a protein found in the venom of the saw-scaled viper. Using a similar drug discovery approach, linear and cyclic peptides containing the sequence K(R)TS derived from VP12, a C-type lectin protein found in the venom of Israeli viper venom, were used as a template to synthesize Vipegitide, a novel peptidomimetic antagonist of α2β1 integrin, with anti-platelet activity. This review focus on drug discovery of these anti-platelet agents, their indications for clinical use in acute coronary syndromes and percutaneous coronary intervention based on several clinical trials, as well as their adverse effects.
    • Functional genetics in the post-genomics era: building a better roadmap in Drosophila.

      Kulathinal, RJ; Kulathinal, Rob|0000-0003-1907-2744 (2013-01-01)
      In this commentary, Rob Kulathinal describes two papers from the Perrimon laboratory, each describing a new online resource that can assist geneticists with the design of their RNAi experiments. Hu et al.'s "UP-TORR: online tool for accurate and up-to-date annotation of RNAi reagents" and "FlyPrimerBank: An online database for Drosophila melanogaster gene expression analysis and knockdown evaluation of RNAi reagents" are published, respectively, in this month's issue of GENETICS and G3: Genes|Genomes|Genetics.
    • General parenting styles and children's obesity risk: Changing focus

      Larsen, JK; Sleddens, EFC; Vink, JM; Fisher, JO; Kremers, SPJ (2018-11-06)