• A meta-analytic review of the relationship of cancer coping selfefficacy with distress and quality of life

      Chirico, A; Lucidi, F; Merluzzi, T; Alivernini, F; Laurentiis, MD; Botti, G; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2017-02-27)
      © Chirico et al. Self-efficacy for coping with cancer is a specific construct that refers to behaviors that occur in the course of dealing with a cancer diagnosis, cancer treatments, and transitioning to survivorship. One of the more widely used measures of self-efficacy for coping strategies with cancer is the Cancer Behavior Inventory. The following general questions provide a framework for this research: 1. Is self-efficacy for coping with cancer related to distress and quality of life of a cancer patient?. 2. Do self-efficacy for coping with cancer and the target psychological outcomes (i.e., distress and quality of life) change in longitudinal studies, with or without intervention? One-hundred eighty studies cited the different versions of the Cancer Behavior Inventory and 47 used the scale. Result showed an inverse relationship between self-efficacy for coping with cancer and distress, and a positive relationship between self-efficacy for coping with cancer and Quality of Life, both with a large effect size. The strong relationship of self-efficacy and outcomes, resulted of the specificity of the instrument, which targets specific coping strategies that are closely aligned with positive outcomes in adjusting to cancer. However, the results are consistent with the theory, which states that compared to those with low efficacy, highly efficacious people demonstrate less anxiety and better adjustment in stressful situations and consistent with prior results in which self-efficacy is positively related to quality of life.
    • A nuclear mtDNA concatemer (Mega-NUMT) could mimic paternal inheritance of mitochondrial genome

      Balciuniene, J; Balciunas, D; Balciunas, Darius|0000-0003-1938-3243 (2019-01-01)
    • Accessing the inaccessible: Redefining play as a spectrum

      Zosh, JM; Hirsh-Pasek, K; Hopkins, EJ; Jensen, H; Liu, C; Neale, D; Solis, SL; Whitebread, D (2018-08-02)
      © 2018 Zosh, Hirsh-Pasek, Hopkins, Jensen, Liu, Neale, Solis and Whitebread. Defining play has plagued researchers and philosophers for years. From describing play as an inaccessible concept due to its complexity, to providing checklists of features, the field has struggled with how to conceptualize and operationalize "play." This theoretical piece reviews the literature about both play and learning and suggests that by viewing play as a spectrum - that ranges from free play (no guidance or support) to guided play and games (including purposeful adult support while maintaining playful elements), we better capture the true essence of play and explain its relationship to learning. Insights from the Science of Learning allow us to better understand why play supports learning across social and academic domains. By changing the lens through which we conceptualize play, we account for previous findings in a cohesive way while also proposing new avenues of exploration for the field to study the role of learning through play across age and context.
    • Aging of the inceptive cellular population: the relationship between stem cells and aging.

      Symonds, CE; Galderisi, U; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2009-01-01)
      The average life expectancy worldwide has about doubled and the global population has increased six fold over the past century. With improving health care in the developed world there is a proportional augmentation in the treatment necessary for elderly patients occasioning the call for increased research in the area of aging and age-related diseases. The manifestation of this research has been focalized on the causative cellular processes and molecular mechanisms involved. Here we will discuss the efforts of this research in the area of stem cells, delving into the regulatory mechanisms and how their de-regulation could be attributed to aging and age-related diseases.
    • Array programming with NumPy

      Harris, CR; Millman, KJ; van der Walt, SJ; Gommers, R; Virtanen, P; Cournapeau, D; Wieser, E; Taylor, J; Berg, S; Smith, NJ; Kern, R; Picus, M; Hoyer, S; van Kerkwijk, MH; Brett, M; Haldane, A; del Río, JF; Wiebe, M; Peterson, P; Gérard-Marchant, P; Sheppard, K; Reddy, T; Weckesser, W; Abbasi, H; Gohlke, C; Oliphant, TE (2020-09-17)
      © 2020, The Author(s). Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves1 and in the first imaging of a black hole2. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.
    • Biogeography and potential exchanges among the atlantic equatorial belt cold-seep faunas

      Olu, K; Cordes, EE; Fisher, CR; Brooks, JM; Sibuet, M; Desbruyères, D; Cordes, Erik|0000-0002-6989-2348 (2010-10-15)
      Like hydrothermal vents along oceanic ridges, cold seeps are patchy and isolated ecosystems along continental margins, extending from bathyal to abyssal depths. The Atlantic Equatorial Belt (AEB), from the Gulf of Mexico to the Gulf of Guinea, was one focus of the Census of Marine Life ChEss (Chemosynthetic Ecosystems) program to study biogeography of seep and vent fauna. We present a review and analysis of collections from five seep regions along the AEB: the Gulf of Mexico where extensive faunal sampling has been conducted from 400 to 3300m, the Barbados accretionary prism, the Blake ridge diapir, and in the Eastern Atlantic from the Congo and Gabon margins and the recently explored Nigeria margin. Of the 72 taxa identified at the species level, a total of 9 species or species complexes are identified as amphi-Atlantic. Similarity analyses based on both Bray Curtis and Hellinger distances among 9 faunal collections, and principal component analysis based on presence/absence of megafauna species at these sites, suggest that within the AEB seep megafauna community structure is influenced primarily by depth rather than by geographic distance. Depth segregation is observed between 1000 and 2000m, with the middle slope sites either grouped with those deeper than 2000m or with the shallower sites. The highest level of community similarity was found between the seeps of the Florida escarpment and Congo margin. In the western Atlantic, the highest degree of similarity is observed between the shallowest sites of the Barbados prism and of the Louisiana slope. The high number of amphi-atlantic cold-seep species that do not cluster according to biogeographic regions, and the importance of depth in structuring AEB cold-seep communities are the major conclusions of this study. The hydrothermal vent sites along the Mid Atlantic Ridge (MAR) did not appear as"stepping stones" for dispersal of the AEB seep fauna, however, the south MAR and off axis regions should be further explored to more fully test this hypothesis.© 2010 Olu et al.
    • Casting a wider net: Differentiating between inner nuclear envelope and outer nuclear envelope transmembrane proteins

      Tingey, M; Mudumbi, KC; Schirmer, EC; Yang, W; Yang, Weidong|0000-0002-3554-3035 (2019-11-01)
      © 2019 by the authors. Licensee MDPI, Basel, Switzerland. The nuclear envelope (NE) surrounds the nucleus with a double membrane in eukaryotic cells. The double membranes are embedded with proteins that are synthesized on the endoplasmic reticulum and often destined specifically for either the outer nuclear membrane (ONM) or the inner nuclear membrane (INM). These nuclear envelope transmembrane proteins (NETs) play important roles in cellular function and participate in transcription, epigenetics, splicing, DNA replication, genome architecture, nuclear structure, nuclear stability, nuclear organization, and nuclear positioning. These vital functions are dependent upon both the correct localization and relative concentrations of NETs on the appropriate membrane of the NE. It is, therefore, important to understand the distribution and abundance of NETs on the NE. This review will evaluate the current tools and methodologies available to address this important topic.
    • CDK9 inhibitors in acute myeloid leukemia

      Boffo, S; Damato, A; Alfano, L; Giordano, A; Boffo, Silvia|0000-0002-6352-160X; Giordano, Antonio|0000-0002-5959-016X (2018-02-23)
      © 2018 The Author(s). Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety.
    • Challenges in microbial ecology: Building predictive understanding of community function and dynamics

      Widder, S; Allen, RJ; Pfeiffer, T; Curtis, TP; Wiuf, C; Sloan, WT; Cordero, OX; Brown, SP; Momeni, B; Shou, W; Kettle, H; Flint, HJ; Haas, AF; Laroche, B; Kreft, JU; Rainey, PB; Freilich, S; Schuster, S; Milferstedt, K; Van Der Meer, JR; Grobkopf, T; Huisman, J; Free, A; Picioreanu, C; Quince, C; Klapper, I; Labarthe, S; Smets, BF; Wang, H; Soyer, OS; Allison, SD; Chong, J; Lagomarsino, MC; Croze, OA; Hamelin, J; Harmand, J; Hoyle, R; Hwa, TT; Jin, Q; Johnson, DR; de Lorenzo, V; Mobilia, M; Murphy, B; Peaudecerf, F; Prosser, JI; Quinn, RA; Ralser, M; Smith, AG; Steyer, JP; Swainston, N; Tarnita, CE; Trably, E; Warren, PB; Wilmes, P (2016-11-01)
      © 2016 International Society for Microbial Ecology All rights reserved. The importance of microbial communities (MCs) cannot be overstated. MCs underpin the biogeochemical cycles of the earth's soil, oceans and the atmosphere, and perform ecosystem functions that impact plants, animals and humans. Yet our ability to predict and manage the function of these highly complex, dynamically changing communities is limited. Building predictive models that link MC composition to function is a key emerging challenge in microbial ecology. Here, we argue that addressing this challenge requires close coordination of experimental data collection and method development with mathematical model building. We discuss specific examples where model-experiment integration has already resulted in important insights into MC function and structure. We also highlight key research questions that still demand better integration of experiments and models. We argue that such integration is needed to achieve significant progress in our understanding of MC dynamics and function, and we make specific practical suggestions as to how this could be achieved.
    • Child/Adolescent Anxiety Multimodal Study (CAMS): Rationale, design, and methods

      Compton, SN; Walkup, JT; Albano, AM; Piacentini, JC; Birmaher, B; Sherrill, JT; Ginsburg, GS; Rynn, MA; McCracken, JT; Waslick, BD; Iyengar, S; Kendall, PC; March, JS (2010-01-05)
      Objective: To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents.Methods: Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described.Results: CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance.Conclusions: CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders.Trial registration: ClinicalTrials.gov NCT00052078. © 2010 Compton et al; licensee BioMed Central Ltd.
    • Clinical application prospect of umbilical cord-derived mesenchymal stem cells on clearance of advanced glycation end products through autophagy on diabetic wound

      Han, Yanfu; Sun, Tianjun; Tao, Ran; Han, Yanqing; Liu, Jing; Tao, Rongjia|0000-0001-5058-4401 (2017-03-24)
      Nowadays, wound healing delay due to diabetes is considered to be closely related to the accumulation of advanced glycation end products (AGEs). Although mesenchymal stem cells (MSCs) exhibit positive effects on diabetic wound healing, related mechanisms are still not fully elucidated. It has been reported that MSCs can improve the activity of autophagy in injured tissues, thereby playing an important role in wound healing. The autophagy induced by MSCs may be beneficial to diabetic wound healing via removing AGEs, which provide new ideas for clinical treatment of diabetic wounds with the potential of broad application prospects. In this study, the current research situation and application prospect of umbilical cord-derived MSCs on the clearance of AGEs in diabetic wound were reviewed.
    • Connecting brain responsivity and real-world risk taking: Strengths and limitations of current methodological approaches

      Sherman, L; Steinberg, L; Chein, J (2018-10-01)
      © 2017 The Authors In line with the goal of limiting health risk behaviors in adolescence, a growing literature investigates whether individual differences in functional brain responses can be related to vulnerability to engage in risky decision-making. We review this body of work, investigate when and in what way findings converge, and provide best practice recommendations. We identified 23 studies that examined individual differences in brain responsivity and adolescent risk taking. Findings varied widely in terms of the neural regions identified as relating to risky behavior. This heterogeneity is likely due to the abundance of approaches used to assess risk taking, and to the disparity of fMRI tasks. Indeed, brain-behavior correlations were typically found in regions showing a main effect of task. However, results from a test of publication bias suggested that region of interest approaches lacked evidential value. The findings suggest that neural factors differentiating riskier teens are not localized to a single region. Therefore, approaches that utilize data from the entire brain, particularly in predictive analyses, may yield more reliable and applicable results. We discuss several decision points that researchers should consider when designing a study, and emphasize the importance of precise research questions that move beyond a general desire to address adolescent risk taking.
    • Curcumin and cancer

      Giordano, A; Tommonaro, G; Giordano, Antonio|0000-0002-5959-016X (2019-10-01)
      © 2019 by the authors. Licensee MDPI, Basel, Switzerland. Curcumin, a polyphenol extracted from Curcuma longa in 1815, has gained attention from scientists worldwide for its biological activities (e.g., antioxidant, anti-inflammatory, antimicrobial, antiviral), among which its anticancer potential has been the most described and still remains under investigation. The present review focuses on the cell signaling pathways involved in cancer development and proliferation, and which are targeted by curcumin. Curcumin has been reported to modulate growth factors, enzymes, transcription factors, kinase, inflammatory cytokines, and proapoptotic (by upregulation) and antiapoptotic (by downregulation) proteins. This polyphenol compound, alone or combined with other agents, could represent an effective drug for cancer therapy.
    • Curcumin as an anticancer agent in malignant mesothelioma: A review

      Baldi, A; De Luca, A; Maiorano, P; D’angelo, C; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2020-03-01)
      © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities. The great majority of mesotheliomas originate in the pleural cavity, while the remaining cases initiate in the peritoneal cavity, in the pericardial cavity or on the tunica vaginalis. Usually, mesotheliomas grow in a diffuse pattern and tend to enclose and compress the organs in the various body cavities. Mesothelioma incidence is increasing worldwide and still today, the prognosis is very poor, with a reported median survival of approximately one year from presentation. Thus, the development of alternative and more effective therapies is currently an urgent requirement. The aim of this review article was to describe recent findings about the anti-cancer activity of curcumin and some of its derivatives on mesotheliomas. The potential clinical implications of these findings are discussed.
    • 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.
    • Disparities in the completion of steps to kidney transplantation: Protocol for a systematic review

      Traino, HM; Nonterah, CW; Cyrus, JW; Gillespie, A; Urbanski, M; Adair-Kriz, M; Gardiner, Heather Marie|0000-0003-2017-991X (2015-01-01)
      Introduction: Disparities in access to transplantation have been well documented. The extant literature, however, focuses largely on disparities and related barriers for African-American patients and none has used the steps to transplantation as a guiding framework. This review will catalogue disparities in the steps to transplantation as well as the barriers and facilitators to completion of each step identified in the extant literature. The results of the review will be used to generate recommendations for future research to improve equity in access to kidney transplantation. Methods and analysis: Standard procedures will be used in the conduct of the review. Searches will be performed using the following electronic databases: PubMed/Medline, PsycINFO, CINHAL, EMBASE, Cochrane library and Web of Science. Reports of original research will be eligible for inclusion if they are published from 2005 to present, written or available in English language, performed in the USA, enrol adult participants (18 years of age or more), and employ descriptive or observational designs. Two authors will independently screen retrieved articles for inclusion. MaxQDA will be used for data analysis and management. All included reports will be coded for article characteristics; disparities identified; barriers and motivators of completion of steps to transplantation; and proposed solutions to disparities and barriers. Each report will be coded independently by two authors and discrepancies resolved by discussion among the full team. A qualitative approach to data analysis is planned. Risk of bias will be assessed using standard procedures. Ethics and dissemination: The findings will provide crucial information on the current status of disparities in access to transplantation. PRISMA guidelines will be followed in reporting the results of the review. It is anticipated that these results will inform research which seeks to increase parity in access to transplantation.
    • 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
    • Efficacy of antidepressive medication for depression in Parkinson disease: a network meta-analysis

      Zhuo, Chuanjun; Xue, Rong; Luo, Lanlan; Ji, Feng; Tian, Hongjun; Qu, Hongru; Lin, Xiaodong; Jiang, Ronghuan; Tao, Ran; Tao, Rongjia|0000-0001-5058-4401 (2017-06)
      BACKGROUND: Parkinson disease (PD) was considered as the 2nd most prevalent neurodegenerative disorder after Alzheimer disease, while depression is a prevailing nonmotor symptom of PD. Typically used antidepression medication includes tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), monoamine-oxidase inhibitors (MAOI), and dopamine agonists (DA). Our study aimed at evaluating the efficacy of antidepressive medications for depression of PD. METHODS: Web of Science, PubMed, Embase, and the Cochrane library were searched for related articles. Traditional meta-analysis and network meta-analysis (NMA) were performed with outcomes including depression score, UPDRS-II, UPDRS-III, and adverse effects. Surface under the cumulative ranking curve (SUCRA) was also performed to illustrate the rank probabilities of different medications on various outcomes. The consistency of direct and indirect evidence was also assessed by node-splitting method. RESULTS: Results of traditional pairwise meta-analysis were performed. Concerning depression score, significant improvement was observed in AD, MAOI, SSRI, and SNRI compared with placebo. NMA was performed and more information could be obtained. DA was illustrated to be effective over placebo concerning UPDRS-III, MAOI, and SNRI. DA demonstrated a better prognosis in UPDRS-II scores compared with placebo and MAOI. However, DA and SSRI demonstrated a significant increase in adverse effects compared with placebo. The SUCRA value was calculated to evaluate the ranking probabilities of all medications on investigated outcomes, and the consistency between direct and indirect evidences was assessed by node-splitting method. CONCLUSION: SSRI had a satisfying efficacy for the depression of PD patients and could improve activities of daily living and motor function of patient but the adverse effects are unneglectable. SNRI are the safest medication with high efficacy for depression as well while other outcomes are relatively poor.
    • 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.
    • Epidural Electrical Stimulation: A Review of Plasticity Mechanisms That Are Hypothesized to Underlie Enhanced Recovery From Spinal Cord Injury With Stimulation

      Eisdorfer, JT; Smit, RD; Keefe, KM; Lemay, MA; Smith, GM; Spence, AJ; Spence, Andrew|0000-0001-7352-0128; Lemay, Michel|0000-0002-5636-0297 (2020-09-02)
      © Copyright © 2020 Eisdorfer, Smit, Keefe, Lemay, Smith and Spence. Spinal cord injury (SCI) often results in life-long sensorimotor impairment. Spontaneous recovery from SCI is limited, as supraspinal fibers cannot spontaneously regenerate to form functional networks below the level of injury. Despite this, animal models and humans exhibit many motor behaviors indicative of recovery when electrical stimulation is applied epidurally to the dorsal aspect of the lumbar spinal cord. In 1976, epidural stimulation was introduced to alleviate spasticity in Multiple Sclerosis. Since then, epidural electrical stimulation (EES) has been demonstrated to improve voluntary mobility across the knee and/or ankle in several SCI patients, highlighting its utility in enhancing motor activation. The mechanisms that EES induces to drive these improvements in sensorimotor function remain largely unknown. In this review, we discuss several sensorimotor plasticity mechanisms that we hypothesize may enable epidural stimulation to promote recovery, including changes in local lumbar circuitry, propriospinal interneurons, and the internal model. Finally, we discuss genetic tools for afferent modulation as an emerging method to facilitate the search for the mechanisms of action.