Noraishah M. Abdul-Aziz

EphrinA-EphA receptor interactions in mouse spinal neurulation: implications for neural fold fusion

The molecular basis of neural fold adhesion and fusion is a poorly understood aspect of neurulation. Cell surface glycosyl phosphatidylinositol (GPI)-anchored proteins have been implicated in neural fold adhesion, with ephrinAs particularly attractive candidates in view of the cranial neural tube defects observed in mice lacking ephrinA5 or the EphA7 receptor. Here, we demonstrate that ephrinsA1, A3 and A4, as well as several EphA receptors, are expressed in the closing mouse spinal neural tube. Most ephrinAs and EphA receptors were found to be expressed in multiple tissues in the caudal region, whereas EphA2 receptor was expressed specifically at the apices of the neural folds just prior to onset of neural tube fusion. Using mouse whole embryo culture, we found that cleavage of GPI-anchored molecules from the embryonic cell surface resulted in delay of spinal neural tube closure. Injection of EphA1 and EphA3 fusion proteins intra-amniotically into cultured embryos was used to specifically disrupt ephrinA-EphA receptor interactions, and led to inhibition of spinal neural tube closure, without adverse effects on growth or developmental progression. These treatments did not disturb neural plate bending or neural fold elevation, both of which are critical for spinal neural tube closure. Our findings demonstrate that ephrinA-EphA receptor interactions are required for closure of the mouse spinal neural tube, and support the hypothesis that ephrinA-EphA receptor interactions may participate in the molecular recognition events that culminate in adhesion and fusion of the tips of the neural folds during spinal neurulation.

Epithelial Fusion during Neural Tube Morphogenesis

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.

The first Malay database toward the ethnic-specific target molecular variation

BackgroundThe Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9th October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb).FindingsCurrently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP (http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register).ConclusionsThis database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background.

Phylogenetic study of six species of Anopheles mosquitoes in Peninsular Malaysia based on inter-transcribed spacer region 2 (ITS2) of ribosomal DNA

BackgroundMolecular techniques are invaluable for investigation on the biodiversity of Anopheles mosquitoes. This study aimed at investigating the spatial-genetic variations among Anopheles mosquitoes from different areas of Peninsular Malaysia, as well as deciphering evolutionary relationships of the local Anopheles mosquitoes with the mosquitoes from neighbouring countries using the anopheline ITS2 rDNA gene.MethodsMosquitoes were collected, identified, dissected to check infection status, and DNA extraction was performed for PCR with primers targeting the ITS2 rDNA region. Sequencing was done and phylogenetic tree was constructed to study the evolutionary relationship among Anopheles mosquitoes within Peninsular Malaysia, as well as across the Asian region.ResultsA total of 133 Anopheles mosquitoes consisting of six different species were collected from eight different locations across Peninsular Malaysia. Of these, 65 ITS2 rDNA sequences were obtained. The ITS2 rDNA amplicons of the studied species were of different sizes. One collected species, Anopheles sinensis, shows two distinct pools of population in Peninsular Malaysia, suggesting evolvement of geographic race or allopatric speciation.ConclusionAnopheles mosquitoes from Peninsular Malaysia show close evolutionary relationship with the Asian anophelines. Nevertheless, genetic differences due to geographical segregation can be seen. Meanwhile, some Anopheles mosquitoes in Peninsular Malaysia show vicariance, exemplified by the emergence of distinct cluster of An. sinensis population.

Is there a risk of suburban transmission of malaria in Selangor, Malaysia?

Background The suburban transmission of malaria in Selangor, Malaysia’s most developed and populous state still remains a concern for public health in this region. Despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. In addition, cases of simian malaria caused by Plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. The aim of this study was to investigate the possibility of local malaria transmission in suburban regions of Selangor, which are adjacent to secondary rainforests. Findings A malaria survey spanning 7 years (2006 - 2012) was conducted in Selangor. A total of 1623 laboratory confirmed malaria cases were reported from Selangor’s nine districts. While 72.6% of these cases (1178/1623) were attributed to imported malaria (cases originating from other countries), 25.5% (414/1623) were local cases and 1.9% (31/1623) were considered as relapse and unclassified cases combined. In this study, the most prevalent infection was P. vivax (1239 cases, prevalence 76.3%) followed by P. falciparum (211, 13.0%), P. knowlesi (75, 4.6%), P. malariae (71, 4.4%) and P. ovale (1, 0.06%). Mixed infections comprising of P. vivax and P. falciparum were confirmed (26, 1.6%). Entomological surveys targeting the residences of malaria patients’ showed that the most commonly trapped Anopheles species was An. maculatus. No oocysts or sporozoites were found in the An. maculatus collected. Nevertheless, the possibility of An. maculatus being the malaria vector in the investigated locations was high due to its persistent occurrence in these areas. Conclusions Malaria cases reported in this study were mostly imported cases. However the co-existence of local cases and potential Plasmodium spp. vectors should be cause for concern. The results of this survey reflect the need of maintaining closely monitored malaria control programs and continuous extensive malaria surveillance in Peninsula Malaysia.

Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans

Spina bifida is among the phenotypes of the larger condition known as neural tube defects (NTDs). It is the most common central nervous system malformation compatible with life and the second leading cause of birth defects after congenital heart defects. In this review paper, we define spina bifida and discuss the phenotypes seen in humans as described by both surgeons and embryologists in order to compare and ultimately contrast it to the leading animal model, the mouse. Our understanding of spina bifida is currently limited to the observations we make in mouse models, which reflect complete or targeted knockouts of genes, which perturb the whole gene(s) without taking into account the issue of haploinsufficiency, which is most prominent in the human spina bifida condition. We thus conclude that the need to study spina bifida in all its forms, both aperta and occulta, is more indicative of the spina bifida in surviving humans and that the measure of deterioration arising from caudal neural tube defects, more commonly known as spina bifida, must be determined by the level of the lesion both in mouse and in man.

First report of brown widow spider sightings in Peninsular Malaysia and notes on its global distribution.

BackgroundThe brown widow spider (Latrodectus geometricus Koch, 1841) has colonised many parts of the world from its continent of origin, Africa. By at least 1841, the species had successfully established populations in South America and has more recently expanded its range to the southern states of North America. This highly adaptable spider has been far more successful in finding its niche around the world than its famous cousins, the black widow, Latrodectus mactans, found in the south-eastern states of North America, and the red-back, Latrodectus hasselti, found mostly in Australia, New Zealand and Japan.MethodsWe performed an extensive web search of brown widow sightings and mapped the location of each sighting using ArcGIS. Specimens reputedly of the species L. geometricus were collected at three localities in Peninsular Malaysia. The spiders were identified and documented based on an examination of morphological characteristics and DNA barcoding.ResultsThe spiders found in Peninsular Malaysia were confirmed to be Latrodectus geometricus based on their morphological characteristics and DNA barcodes. We recorded 354 sightings of the brown widow in 58 countries, including Peninsular Malaysia.ConclusionReports from the Americas and the Far East suggest a global-wide invasion of the brown widow spider. Herein we report the arrival of the brown widow spider in Peninsular Malaysia and provide notes on the identification of the species and its recently expanded range.

First Case Report of Canthariasis in an Infant Caused by the Larvae of Lasioderma serricorne (Coleoptera: Anobiidae).

Abstract We report an unusual cause of gastrointestinal infection occurring in a 1-year-old infant patient who was brought to a public hospital in Kuala Lumpur, Malaysia. Larvae passed out in the patients feces were confirmed by DNA barcoding as belonging to the species, Lasioderma serricorne (F.), known as the cigarette beetle. We postulate that the larvae were acquired from contaminated food and were responsible for gastrointestinal symptoms in the patient. To our knowledge, this the first report of human canthariasis caused by larvae of L. serricorne.

Feeding behavior of Mimomyia (Etorleptiomyia) luzonensis (Ludlow, 1905) (Diptera, Culicidae) in Peninsular Malaysia

Mosquitoes are vectors of various human diseases in the tropics including yellow fever, dengue, malaria and West Nile virus. Mosquitoes can act as vectors between wildlife and humans, which is particularly important for diseases where wild animals serve as reservoirs of parasites in the absence of human infections. Research has mainly focused on the medical impacts of Anopheles, Aedes, Mansonia and Culex, however, very little attention has been directed towards other mosquito genera, especially those which act as vectors of diseases of wildlife. We have observed adults of Mimomyia (Etorleptiomyia) luzonensis (Ludlow, 1905) feeding on a toad, Ingerophrynus parvus, near an oil palm plantation settlement in Setia Alam, Selangor state, Peninsular Malaysia. Mimomyia is known to feed on reptiles and amphibians, and is a documented vector of several arboviruses, including West Nile virus. The observation of Mimomyia feeding on a common toad near a human settlement highlights a need to understand the relationships between mosquitoes, toads and humans from an ecological perspective. We report on-site observations of the feeding habit of Mimomyia; the first records from Malaysia.

The prevalence and distribution of spina bifida in a single major referral center in Malaysia

Background The aim of this study is to review the medical history of patients with spina bifida, encompassing both aperta and occulta types born between the years 2003 until 2016, spanning a 13-year time period. We assessed each patient and maternal parent information, details of the defects, and conditions associated with the primary defect. We also include information on patients’ ambulation and education level (where available). Methods Data from the Department of Patient Information University of Malaya Medical Centre (UMMC), Malaysia was captured from spina bifida patients (ICD10: Q05 spina bifida). Data involved patients referred to UMMC between 2003 and 2016 and/or born in UMMC within that particular time frame. We filtered and extracted the information according to the data of clinical examination, medical review, and social history provided in the medical records. Results A total of 86 patient records with spina bifida were analyzed. Spina bifida prevalence rate in this study ranged from 1.87 to 8.9 per 1,000 live births depending on weightage. We note that ethnicity was a factor whereby the highest numbers of spina bifida were from Malays (n = 36, 41.86%), followed by equal numbers of Chinese and Indians (n = 24, 27.91%). The highest number of diagnoses reported was myelomeningocele type-spina bifida (n = 39, 45.35%). The most common site of the spina bifida lesion was located at the lumbar region irrespective of aperta or occulta types (n = 23, 26.74%). Data on other associated phenotypes of spina bifida such as hydrocephalus and encephalocele was also captured at 37.21% (n = 32) and 1.16% (n = 1), respectively. In terms of mobility, 32.84% (n = 22/67) of patients between the ages 4 and 16 years old were found to be mobile. As many as 36.07% of patients ranging from 5 to 16 years of age (n = 22/61) received formal education ranging from preschool to secondary school. Conclusion The prevalence of spina bifida in UMMC is as according to international statistics which is in the range of 0.5–10 per 1,000 live births. Majority of the reported cases were males, Malays, full term babies, and of the myelomeningocele phenotype located at the lumbar region.