Publications by authors named "David M James"

6 Publications

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Intestinal dysmotility in a zebrafish () mutant model of autism.

Mol Autism 2019 31;10. Epub 2019 Jan 31.

1Department of Biology, University of Miami, Coral Gables, FL USA.

Background And Aims: Autism spectrum disorder (ASD) is currently estimated to affect more than 1% of the world population. For people with ASD, gastrointestinal (GI) distress is a commonly reported but a poorly understood co-occurring symptom. Here, we investigate the physiological basis for GI distress in ASD by studying gut function in a zebrafish model of Phelan-McDermid syndrome (PMS), a condition caused by mutations in the gene.

Methods: To generate a zebrafish model of PMS, we used CRISPR/Cas9 to introduce clinically related C-terminal frameshift mutations in and zebrafish paralogues (). Because PMS is caused by haploinsufficiency, we assessed the digestive tract (DT) structure and function in zebrafish heterozygotes. Human mRNA was then used to rescue DT phenotypes in larval zebrafish.

Results: Significantly slower rates of DT peristaltic contractions ( < 0.001) with correspondingly prolonged passage time ( < 0.004) occurred in mutants. Rescue injections of mRNA encoding the longest human isoform into mutants produced larvae with intestinal bulb emptying similar to wild type (WT), but still deficits in posterior intestinal motility. Serotonin-positive enteroendocrine cells (EECs) were significantly reduced in both and mutants ( < 0.05) while enteric neuron counts and overall structure of the DT epithelium, including goblet cell number, were unaffected in larvae.

Conclusions: Our data and rescue experiments support mutations in as causal for GI transit and motility abnormalities. Reductions in serotonin-positive EECs and serotonin-filled ENS boutons suggest an endocrine/neural component to this dysmotility. This is the first study to date demonstrating DT dysmotility in a zebrafish single gene mutant model of ASD.
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http://dx.doi.org/10.1186/s13229-018-0250-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357389PMC
April 2019

Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish.

Front Mol Neurosci 2016 7;9:55. Epub 2016 Jul 7.

Department of Biology, University of Miami Coral Gables, FL, USA.

Zebrafish are a unique cell to behavior model for studying the basic biology of human inherited neurological conditions. Conserved vertebrate genetics and optical transparency provide in vivo access to the developing nervous system as well as high-throughput approaches for drug screens. Here we review zebrafish modeling for two broad groups of inherited conditions that each share genetic and molecular pathways and overlap phenotypically: neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Intellectual Disability (ID) and Schizophrenia (SCZ), and neurodegenerative diseases, such as Cerebellar Ataxia (CATX), Hereditary Spastic Paraplegia (HSP) and Charcot-Marie Tooth Disease (CMT). We also conduct a small meta-analysis of zebrafish orthologs of high confidence neurodevelopmental disorder and neurodegenerative disease genes by looking at duplication rates and relative protein sizes. In the past zebrafish genetic models of these neurodevelopmental disorders and neurodegenerative diseases have provided insight into cellular, circuit and behavioral level mechanisms contributing to these conditions. Moving forward, advances in genetic manipulation, live imaging of neuronal activity and automated high-throughput molecular screening promise to help delineate the mechanistic relationships between different types of neurological conditions and accelerate discovery of therapeutic strategies.
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http://dx.doi.org/10.3389/fnmol.2016.00055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935692PMC
July 2016

Patient-reported functioning in major depressive disorder.

Ther Adv Chronic Dis 2016 May 31;7(3):160-9. Epub 2016 Mar 31.

Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA.

Objectives: Compared with the general population, patients with major depressive disorder (MDD) report substantial deficits in their functioning that often go beyond the clinical resolution of depressive symptoms. This study examines the impact of MDD and its treatment on functioning.

Methods: From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult outpatients with MDD at entry and exit points of each level of antidepressant treatment and again 12 months post treatment. Functioning was measured using the Work and Social Adjustment Scale (WSAS).

Results: The results show that only 7% of patients with MDD reported within-normal functioning before treatment. The proportion of patients achieving within-normal functioning (WSAS) scores significantly increased after treatment. However, the majority of patients (>60%) were still in the abnormal range on functioning at exit. Although remitted patients had greater improvements compared with nonremitters, a moderate proportion of remitted patients continued to experience ongoing deficits in functioning after treatment (20-40%). Follow-up data show that the proportions of patients experiencing normal scores for functioning after 12 months significantly decreased from the end of treatment to the follow-up phase, from 60.1% to 49% (p < 0.0001), a finding that was particularly significant in nonremitters. Limitations of this study include the reliance on self-report of functioning and the lack of information on patients who dropped out.

Conclusion: This study points to the importance of functional outcomes of MDD treatment as well as the need to develop personalized interventions to improve functioning in MDD.
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http://dx.doi.org/10.1177/2040622316639769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907070PMC
May 2016

An improvement index to quantify the evolution of performance in running.

J Sports Sci 2014 30;32(7):610-22. Epub 2013 Sep 30.

a The Centre for Sports Engineering Research , Sheffield Hallam University , Sheffield , UK.

Improvements in track and field sports have been attributed to factors such as population increase, drugs and new technologies, but previous research has found it difficult to distinguish the contributions from specific influences. Here it is shown how this is possible by means of a performance improvement index based on useful work done combined with modelling of the annual top 25 performances. The index was set to 100 in 1948 and showed that, by 2012, it had increased in running events to between 110.5 and 146.7 (men's 100 m and marathon). Underlying global effects accounted for the majority of all improvements (16.2 to 46.7) with smaller influences attributable to an influx of African runners (3.6 to 9.3), and a 4-year oscillation that arose from staging of the Olympic Games (±0.2 to ±0.6). Performance decreased with the introduction of compulsory random drug testing (-0.9 to -3.9) the World Anti-Doping Agency (WADA; -0.5 to -2.5) and fully automated timing (-0.6 to -2.5). Changes in elite sporting performance since the 1890s are attributable to societal changes caused by the industrial revolution and globalisation superimposed on millennia of human evolution.
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http://dx.doi.org/10.1080/02640414.2013.841974DOI Listing
October 2014

Isolation and characterization of norharmane from Reticulitermes termites (Isoptera: Rhinotermitidae).

J Econ Entomol 2005 Oct;98(5):1669-78

Department of Bioagricultural Sciences and Pest Management, Colorado State University, Fort Collins, CO 80523, USA.

The fluorescent alkaloid norharmane has been isolated from Reticulitermes termites and characterized by 1H NMR, UV/Vis, mass spectrometry, and gas chromatography/mass spectrometry. Microcoil 1H NMR spectroscopy allowed spectra to be obtained from mass-limited material, facilitating the identification of norharmane, which is the major component in termite fluorescence under UV light. Norharmane was uniformly present at approximately 1 ng/mg in Reticulitermes tibialis Banks workers, soldiers, and alates; Reticulitermes flavipes (Kollar) workers; and Reticulitermes virginicus (Banks) workers. Some termites were observed to fluoresce with less intensity, but no differences in norharmane levels were detected. Mechanisms that may account for fluorescent differences are discussed as are the possible ecological implications of norharmane in termites.
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http://dx.doi.org/10.1093/jee/98.5.1669DOI Listing
October 2005