Developing a model for studying complex brain function using zebrafish (Danio rerio) and cavefish (Mexican tetra)

The advantage of both larval an adult zebrafish in neuroscience research has significantly increased in the past decades. In fact, this vertebrate model performed well in several conditioning memory tasks by responses to visual cues. In contrast to zebrafish, the cognitive functions of blind cavefish is well known as lacks functional visual systems and uses hydrodynamic cues to gather information about its surroundings. While rodents have traditionally been used to study the complex brain functions, the use of teleost is gaining popular as an excellent vertebrate model to complement current neuroscience research. The objective of this study is to compare the cognitive functions of both character of fish, zebrafish and cavefish using Y-maze task. Adult zebrafish (n=6, 4.5 cm length) and blind cavefish (n=6, 5.5 cm length) were tested for spatial recognition memory using the Y-maze test, which had 3 identical arms with different visual cues at the end of each arms. This task consisted of two trials separated by training-test intervals (1 h, 3 h and 6 h TTI) to assess the capabilities of the fish to respond new environments of the novel arms. Result showed that there is no significant difference on cavefish enter and time spent in all Y-maze arms. However, time spent and numbers of entries in the novel arm were significantly higher in the zebrafish. This could indicate that the zebrafish have a higher exploratory behaviour and able to recognize the preferential visual cues. Indeed, this fish demonstrating the ability to recall a spatial alternation task after several intervals hours. However, the spatial recognition memory of cavefish is based on their mechanosensory and their lateral lines, which highly sensitive to fluctuating water movement and helps them to perceive their environment surroundings. Interestingly, the cavefish have better olfactory sense and taste buds all over its head, which help them to discover novelty in complete darkness. Thus, the advantage of the Y-maze memory task and the characteristics of zebrafish and cavefish suggest that this small teleost can be a good animal model for study the brain cognitive function

Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release

Proper dialogue between presynaptic neurons and their targets is essential for correct synaptic assembly and function. At central synapses, Wnt proteins function as retrograde signals to regulate axon remodeling and the accumulation of presynaptic proteins. Loss of Wnt7a function leads to defects in the localization of presynaptic markers and in the morphology of the presynaptic axons. We show that loss of function of Dishevelled-1 (Dvl1) mimics and enhances the Wnt7a phenotype in the cerebellum. Although active zones appear normal, electrophysiological recordings in cerebellar slices from Wnt7a/Dvl1 double mutant mice reveal a defect in neurotransmitter release at mossy fiber–granule cell synapses. Deficiency in Dvl1 decreases, whereas exposure to Wnt increases, synaptic vesicle recycling in mossy fibers. Dvl increases the number of Bassoon clusters, and like other components of the Wnt pathway, it localizes to synaptic sites. These findings demonstrate that Wnts signal across the synapse on Dvl-expressing presynaptic terminals to regulate synaptic assembly and suggest a potential novel function for Wnts in neurotransmitter release

Genetic Analysis of the Cytoplasmic Dynein Subunit Families

Cytoplasmic dyneins, the principal microtubule minus-end-directed motor proteins of the cell, are involved in many essential cellular processes. The major form of this enzyme is a complex of at least six protein subunits, and in mammals all but one of the subunits are encoded by at least two genes. Here we review current knowledge concerning the subunits, their interactions, and their functional roles as derived from biochemical and genetic analyses. We also carried out extensive database searches to look for new genes and to clarify anomalies in the databases. Our analysis documents evolutionary relationships among the dynein subunits of mammals and other model organisms, and sheds new light on the role of this diverse group of proteins, highlighting the existence of two cytoplasmic dynein complexes with distinct cellular roles

Evaluating The Alternative Assessment Practices in All Current Courses Offered by WC11 Programme

WC11 Network Computing Programme offeredBachelor of Computer Science with Honours (Network Computing) since 2003. The curriculum structure covers fundamental and advance network computing concepts on the use of computers and other devices in a linked network, rather than as unconnected, stand-alone devices. Network computing is a dynamic area of study. Therefore, teaching and learning approaches for network computing has to adapt with the progressive development of the network technologies

DTI Profiles for Rapid Description of Cohorts at the Clinical-Research Interface.

Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets

Identification of the genomic mutation in Epha4rb-2J/rb-2J mice

The EphA4 receptor tyrosine kinase is involved in numerous cell-signalling activities during embryonic development. EphA4 has the ability to bind to both types of ephrin ligands, the ephrinAs and ephrinBs. The C57BL/6J-Epha4rb-2J/GrsrJ strain, denoted Epha4rb-2J/rb-2J, is a spontaneous mouse mutant that arose at The Jackson Laboratory. These mutants exhibited a synchronous hind limb locomotion defect or “hopping gait” phenotype, which is also characteristic of EphA4 null mice. Genetic complementation experiments suggested that Epha4rb-2J corresponds to an allele of EphA4, but details of the genomic defect in this mouse mutant are currently unavailable. We found a single base-pair deletion in exon 9 resulting in a frame shift mutation that subsequently resulted in a premature stop codon. Analysis of the predicted structure of the truncated protein suggests that both the kinase and sterile α motif (SAM) domains are absent. Definitive determination of genotype is needed for experimental studies of mice carrying the Epha4rb-2J allele, and we have also developed a method to ease detection of the mutation through RFLP. Eph-ephrin family members are reportedly expressed as numerous isoforms. Hence, delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein–protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype

DTI Profiles for Rapid Description of Cohorts at the Clinical-Research Interface

Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets

Underrepresented Populations in Parkinson's Genetics Research: Current Landscape and Future Directions

BACKGROUND: Human genetics research lacks diversity; over 80% of genome-wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. OBJECTIVE: This systematic review provides an overview of research involving Parkinson's disease (PD) genetics in underrepresented populations (URP) and sets a baseline to measure the future impact of current efforts in those populations. METHODS: We searched PubMed and EMBASE until October 2021 using search strings for "PD," "genetics," the main "URP," and and the countries in Latin America, Caribbean, Africa, Asia, and Oceania (excluding Australia and New Zealand). Inclusion criteria were original studies, written in English, reporting genetic results on PD from non-European populations. Two levels of independent reviewers identified and extracted information. RESULTS: We observed imbalances in PD genetic studies among URPs. Asian participants from Greater China were described in the majority of the articles published (57%), but other populations were less well studied; for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just nine studies using a genome-wide approach published up to 2021, including URPs. CONCLUSION: This review provides insight into the significant lack of population diversity in PD research highlighting the immediate need for better representation. The Global Parkinson's Genetics Program (GP2) and similar initiatives aim to impact research in URPs, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future. © 2022 International Parkinson and Movement Disorder Society