Biology subjects

Wickramasinghe, S.

Publications and source records attributed to Wickramasinghe, S..

3 recordsLinked to original sources

bioRxiv2023

Indigenous cattle of Sri Lanka: Genetic and phylogeographic relationship with Zebu of Indus valley and South Indian origin

The present study reports the population structure, genetic admixture and phylogeography of island cattle breeds of Sri Lanka viz. Batu Harak, Thawalam and White cattle. Moderately high level of genetic diversity was observed. Estimates of inbreeding for Thawalam and White cattle breeds were relatively high with 6.1% and 7.2% respectively. Genetic differentiation of Sri Lankan Zebu (Batu Harak and White cattle) was lowest with Red Sindhi among Indus valley zebu while it was lowest with Hallikar among the South Indian cattle. Global F statistics showed 6.5% differences among all the investigated zebu cattle breeds and 1.9% differences among Sri Lankan zebu breeds. The Sri Lankan zebu cattle breeds showed strong genetic relationships with Hallikar cattle, an ancient breed considered to be ancestor for most Mysore type draught cattle breeds of South India. Genetic admixture analysis revealed high levels of breed purity in Lanka White cattle with >97% zebu ancestry while significant taurine admixture was observed in Batu Harak and Thawalam cattle. Two major zebu haplogroups, I1 and I2 were observed in Sri Lankan zebu with the former predominating the later in all the three breeds. A total of 112 haplotypes were observed in the studied breeds, of which 50 haplotypes were found in Sri Lankan zebu cattle. Mismatch analysis revealed unimodal distribution in all the three breeds indicating population expansion. The sum of squared deviations (SSD) and raggedness index were non-significant in both the lineages of all the three breeds except for I1 lineage of Thawalam cattle (P<0.01) and I2 lineage of Batu Harak cattle (P<0.05). The results of neutrality tests revealed negative Tajimas D values for both the lineages of Batu Harak (P>0.05) and White cattle (P>0.05) indicating an excess of low frequency polymorphisms and demographic expansion. Genetic dilution of native zebu cattle germplasm is a cause for concern and it is imperative that national breeding organizations consider establishing conservation units for the three native cattle breeds to maintain breed purity and initiate genetic improvement programs.

genetics↗

bioRxiv2019

A pilot study of behavioral, environmental, and occupational risk factors for chronic kidney disease of unknown etiology in Sri Lanka

Chronic kidney disease of unknown etiology (CKDu) was first recognized in Sri Lanka in the early 1990s, and since then it has reached epidemic levels in the North Central Province of the country. The prevalence of CKDu is reportedly highest among communities that engage in chena and paddy farming, which is most often practiced in the dry zone including the North Central and East Central Provinces of Sri Lanka. Previous studies have suggested varied hypotheses for the etiology of CKDu; however, there is not yet a consensus on the primary risk factors, possibly due to disparate study designs, sample populations, and methodologies. The goal of this pilot case-control study was to evaluate the relationships between key demographic, cultural, and occupational variables as risk factors for CKDu, with a primary interest in pesticide exposure both occupationally and through its potential use as an ingredient in brewed kasippu alcohol. A total of 56 CKDu cases and 54 control individuals were surveyed using a proctored, self-reported questionnaire. Occupational pesticide exposure and alcohol consumption were not found to be significant risk factors for CKDu. However, a statistically significant association with CKDu was observed with chewing betel (OR: 6.11, 95% CI: 1.93, 19.35), age (OR: 1.07, 95% CI: 1.02, 1.13), owning a pet dog (OR: 3.74, 95% CI: 1.38, 10.11), water treatment (OR: 3.68, 95% CI: 1.09, 12.43) and pests in the house (OR: 5.81, 95% CI: 1.56, 21.60). The findings of this study suggest future research should focus on practices associated with chewing betel, potential animal interactions including pests in the home and pets, and risk factors associated with water. AUTHOR SUMMARYSince a new variant of chronic kidney disease was acknowledged in the early 1990s among those in the agricultural community of Sri Lanka, especially rice farmers, the research community has searched for causes of what has become known as chronic kidney disease of unknown etiology or CKDu. Previous studies have focused on heavy metals in the environment as they are known to be toxic to the kidneys however, a proverbial "smoking gun" has yet to be identified. Understanding that the causes is potential multifactorial we implemented a pilot case-control study using a One Health methodology administering a comprehensive interview to assess environmental, animal, and, human exposures that may be contributing to the diagnosis of CKDu. We found statistically significant odds ratio among those that reported having a pet dog, chewing betel (a traditional preparation or various ingredients wrapped in a betel leaf inserted between the teeth and cheek), pests in the home, treating drinking water, and older age. These results serve to guide further hypothesis generation regarding mechanisms behind associated exposures from infectious diseases such as hantavirus and leptospirosis to food preparation through boiling drinking water in aluminum vessels and oral pesticide exposure linked to betel preparation.

scientific communication and education↗

bioRxiv2019

A novel small molecule screening platform for disrupting toxic tau oligomers in cells

Tauopathies, including Alzheimers disease, are a group of neurodegenerative disorders characterized by pathological aggregation of the microtubule binding protein tau. Recent studies suggest that toxic tau oligomers, which are soluble and distinct from insoluble beta-sheet fibrils, are central players in neuronal cell death. To exploit this new therapeutic window, we engineered two first-in-class FRET based biosensors that monitor tau conformations in cells. Because this new technology platform operates in cells, it enables high-throughput screening of small molecules that target tau oligomers while avoiding the uncertainties of idiosyncratic in vitro preparations of tau assemblies from purified protein. We found a small molecule, MK-886, that disrupts tau oligomers and reduces tau-induced cell cytotoxicity with nanomolar potency. Using SPR and an advanced single-molecule FRET technique, we show that MK-886 directly binds to tau and specifically perturbs the folding of tau monomer in the proline-rich and microtubule-binding regions. Furthermore, we show that MK-886 accelerates the tau aggregation lag phase using a thioflavin-T assay, implying that the compound stabilizes a non-toxic, on-pathway oligomer. The technology described here should generalize to the study and targeting of conformational ensembles within the aggregation pathways of most intrinsically disordered proteins.

neuroscience↗