MyMedR

Displaying all 5 publications

Abstract:

Sort:

Fulltext A Novel Occulta-Type Spina Bifida Mediated by Murine Double Heterozygotes EphA2 and EphA4 Receptor Tyrosine Kinases

Abdullah NL, Mohd-Zin SW, Ahmad-Annuar A, Abdul-Aziz NM

Front Cell Dev Biol, 2017;5:105.
PMID: 29312933 DOI: 10.3389/fcell.2017.00105

Members of the Eph receptor tyrosine kinase have previously been implicated in cranial neural tube development. Failure of neural tube closure leads to the devastating conditions known as anencephaly and spina bifida. EphA2 and EphA4 are expressed at the tips of the closing spinal neural folds prior and during neural tube closure. We investigated the possible role of murine EphA2 and EphA4 during the last step of primary neural tube closure, which is adhesion and fusion. The individual mouse knockouts of EphA2 and EphA4 per se do not exhibit neural tube defects (NTDs). The embryos generated by the crossing of double heterozygotes Epha2tm1Jrui/+Epha4rb-2J/+ displayed NTDs with a wide degree of severity including close exencephaly and close spina bifida (spina bifida occulta). Interestingly, mutants displaying NTDs had skin covering the underlying lesion. The tissue sections revealed the elevated neural folds had not adhered and fused. The phenotypes seen in Epha2tm1Jrui/+Epha4rb-2J/+ double heterozygous embryos suggest both genes play a compensatory role with each other in the adhesion and fusion of the neural tube. In this study, there exists a >50% penetrance of NTDs in the mouse mutants, which genetically have a single allele each of EphA2 and EphA4 absent.
Fulltext Impact of Mobile Games-Aided Neurorehabilitation: A Systematic Literature Review

Sagary R, Malim NHAH, Abdullah NL, Mohamad WNAW, Ahmad AL

Malays J Med Sci, 2023 Dec;30(6):29-44.
PMID: 38239257 DOI: 10.21315/mjms2023.30.6.4

Neurological rehabilitation is a physician-supervised programme for individuals with nervous system diseases, injuries or disorders. Neurological rehabilitation, also known as neurorehabilitation, is part of the rehabilitation process that improves function, reduces severity and enhances a patient's well-being. Because neurological injuries occur in the brain, spine and nerves, affecting multiple body parts including organs, blood vessels, muscles and bones, rehabilitation requires a multidisciplinary approach. This study conducted a systematic literature review (SLR) on the use of mobile game in neurorehabilitation. The steps undertaken in the literature review included the collection, identification, categorisation, summarisation and synthesis of relevant studies in the research domain. A total of 50 related articles were reviewed. The study identified that the effects on cognitive skills, handgrip strength, memory, attention, visuospatial abilities, executive function tasks, motor functionality, and improvements in balance, visual perception, and functional mobility are impacts of the use of mobile games in neurological rehabilitation. Furthermore, several research challenges and recommendations for future research were identified.
Fulltext Epithelial fusion during neural tube morphogenesis

Pai YJ, Abdullah NL, Mohd-Zin SW, Mohammed RS, Rolo A, Greene ND, et al.

Birth Defects Res. Part A Clin. Mol. Teratol., 2012 Oct;94(10):817-23.
PMID: 22945349 DOI: 10.1002/bdra.23072

Adhesion and fusion of epithelial sheets marks the completion of many morphogenetic events during embryogenesis. Neural tube closure involves an epithelial fusion sequence in which the apposing neural folds adhere initially via cellular protrusions, proceed to a more stable union, and subsequently undergo remodeling of the epithelial structures to yield a separate neural tube roof plate and overlying nonneural ectoderm. Cellular protrusions comprise lamellipodia and filopodia, and studies in several different systems emphasize the critical role of RhoGTPases in their regulation. How epithelia establish initial adhesion is poorly understood but, in neurulation, may involve interactions between EphA receptors and their ephrinA ligands. Epithelial remodeling is spatially and temporally correlated with apoptosis in the dorsal neural tube midline, but experimental inhibition of this cell death does not prevent fusion and remodeling. A variety of molecular signaling systems have been implicated in the late events of morphogenesis, but genetic redundancy, for example among the integrins and laminins, makes identification of the critical players challenging. An improved understanding of epithelial fusion can provide insights into normal developmental processes and may also indicate the mode of origin of clinically important birth defects.
Identification of the genomic mutation in Epha4(rb-2J/rb-2J) mice

Mohd-Zin SW, Abdullah NL, Abdullah A, Greene ND, Cheah PS, Ling KH, et al.

Genome, 2016 Jul;59(7):439-48.
PMID: 27373307 DOI: 10.1139/gen-2015-0142

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 Epha4(rb-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 Epha4(rb-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 Epha4(rb-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.
Fulltext Cranial neural tube defect after trimethoprim exposure

Abdullah NL, Gunasekaran R, Mohd-Zin SW, Lim BH, Maniam P, Mohd-Salleh AS, et al.

BMC Res Notes, 2018 Jul 16;11(1):475.
PMID: 30012199 DOI: 10.1186/s13104-018-3593-1

OBJECTIVES: The Neural Tube Defects Research Group of University of Malaya was approached to analyze a tablet named TELSE, which may have resulted in a baby born with central nervous system malformation at the University of Malaya Medical Centre. In this animal experimental study, we investigated the content of TELSE and exposure of its contents that resulted in failure of primary neurulation.
RESULTS: Liquid Chromatography Tandem Mass spectrophotometry analysis of the TELSE tablet confirmed the presence of trimethoprim as the active compound. The TELSE tablet-treated females produced significant numbers of embryos with exencephaly (n = 8, 36.4%, *P