Biology subjects

Perera, N.

Publications and source records attributed to Perera, N..

5 recordsLinked to original sources

bioRxiv2026

X-Chromosomal STR-based analysis of genetic diversity, structure, and phylogeny in the Sri Lankan Vedda population

The Vedda people are regarded as the direct descendants of Sri Lanka's Mesolithic hunter-gatherers and represent one of South Asia's oldest surviving indigenous populations. X-chromosomal short tandem repeat (X-STR) analysis provides a powerful framework to examine their genetic distinctiveness, as the X chromosome exhibits sex-biased biparental inheritance and greater sensitivity to demographic and evolutionary forces compared to autosomal markers. However, no X-STR-based genetic investigations have yet been conducted on this population. In the present study, we successfully genotyped 50 unrelated Veddas individuals using a recently developed 16 X-STR multiplex PCR system optimized for Sri Lankan populations. Our analyses revealed a statistically significant genetic differentiation (2.43%) between the Veddas and the principal local ethnic groups; Sinhalese, Sri Lankan Tamils, Indian Tamils, and Moors exceeding previous estimates based on autosomal STR markers. Comparative analysis with 32 global populations positioned the Veddas as a genetically distinct and isolated group, separated from clusters representing South Asians, Europeans, Middle Easterners, and other indigenous populations such as Australian Aboriginals, Bhil Indians, and Kedayans, emphasizing their unique genetic heritage. Reduced allelic (115) and haplotype (62) counts, alongside significant linkage disequilibrium detected among eight pairs of X-STR loci, reflect the influence of genetic drift within this small, endogamous, and historically isolated population. These findings highlight the evolutionary and demographic distinctiveness of the Veddas and provide essential baseline data for future population genomic studies. Furthermore, the demonstrated high discriminatory power of the 16 X-STR loci supports their continued application in population genetics and anthropological research within this unique community.

genetics↗

bioRxiv2026

The Colonic Mucus Layer is Thinner and is Associated with Goblet Cell Hyperplasia in the db/db Mouse Model of Type 2 Diabetes

Background & AimsDiabetes mellitus has been associated with both intestinal barrier dysfunction and peripheral neuropathy leading to increased risk of infection. The mucus layer forms a physical barrier against pathogens and is a critical component of the intestinal barrier that may be impaired in diabetes. This study aimed to assess how diabetes impacts goblet cells (GCs), mucus layer integrity, and innervation in the colon. MethodsFluorescence microscopy was used to investigate GCs, the mucus layer, and innervation in the colon of db/db mice. Custom open-access image analysis pipelines were developed to quantify GC numbers, location and content, mucus thickness, bacterial colonization, and innervation density in intestinal tissue sections. We also treated mice with the clinically used glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide to assess its capacity to reverse pathological changes to GCs and the mucus layer in a model of established type 2 diabetes (T2DM). ResultsThe mucus layer was significantly thinner in the colon of db/db mice with established diabetes and bacteria more readily colonized the epithelium and crypts. Intercrypt GC numbers were significantly reduced in db/db mice. However, there were significantly more GCs per crypt, and crypts were elongated in the db/db colon. Innervation was reduced in the mucosa and external muscle of the colon, consistent with diabetic neuropathic changes. Liraglutide treatment increased the size of GCs but had no effect on GC numbers, mucus thickness, or innervation in this model of established T2DM. ConclusionsMucus barrier dysfunction and GC hyperplasia is evident in the db/db colon. Increased microbial penetrability through the mucus layer suggests potential implications for the increased risk of gastrointestinal infection in diabetes.

physiology↗

bioRxiv2026

A 3D Tumor-on-a-chip Platform to Identify Drugs that Block Breast Cancer Cell Intravasation

Metastasis is the leading cause of death in breast cancer patients, yet there are no drugs specifically designed to block cancer cell intravasation, an early step of the metastatic cascade that originates circulating tumour cells (CTCs). A major challenge in developing anti-intravasation drugs is the scarcity of relevant in vitro platforms suitable for predictable drug discovery. Intravasation is a fundamental step of metastasis and involves the crossing of cancer cells through an endothelial barrier to enter the blood circulation. Here we developed an intravasation-on-a-chip model with controlled extracellular matrix composition, fluid flow and shear stress, which mimics the dynamic tumour-endothelium interface. The systems allows real-time imaging of intravasation and the isolation and quantification of intravasated cancer cells. As a proof-of-concept for drug testing, we show that perfusion with the PI3K/mTOR inhibitor Dactolisib, significantly reduced intravasation without compromising endothelial cell viability. The system also provides the capability to evaluate inhibitor on-target activity via imaging analysis. This intravasation-on-a-chip model offers a powerful, scalable, and imaging-compatible platform for discovering and evaluating anti-intravasation compounds.

cancer biology↗

bioRxiv2023

Anti-dengue viral activity of Glycyrrhiza glabra roots in Vero cells

Dengue is a global public health problem but no antiviral agent exists for dengue. Plants have been the source of many pharmaceutical agents. Therefore, we explored the antiviral potential of the aqueous extracts of Glycyrrhiza glabra (GG) roots on dengue viruses. Cell cytotoxicity assay with 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide solution was used for estimating the maximum nontoxic dose (MNTD) and 50% cytotoxic concentration (CC50). Plaque reduction antiviral assay on Vero cells infected with dengue virus serotypes 1,2,3 and 4 were treated with dilutions of the MNTD of GG extract to calculate the half maximal inhibitory concentration (IC50). Selectivity index (SI) was calculated as CC50/IC50 ratio. Following bioactivity guided fractionation, MNTD, CC50, IC50 and SI values for fractions E and F were similarly obtained. Inhibition of NS1 antigen levels produced by dengue serotype-1 infected monocytes was studied in the presence and absence of GG extract after 48 hours. GG MNTD and CC50 were 166.7 {micro}g/mL and 651.9 {micro}g/mL. GG extract showed 98-100% inhibition of all four dengue serotypes at the MNTD and the IC50 values of the four serotypes ranged from 10-50 {micro}g/mL indicating moderate pan-serotype inhibitory activity. Cytotoxicity of GG against Vero cells was low (CC50 >500 {micro}g/mL). SI of GG extract for all four dengue serotypes were >10, indicating it had good potential as an antiviral agent. Fraction E and F had low to moderate inhibitory activity for all four serotypes and showed good potential as an antiviral agent only for dengue 4. This is the first report of significant anti-dengue viral activity of GG extract on all four dengue serotypes. Author SummaryDengue is a global public health problem but no antiviral agent exists for dengue. This study explores the antiviral potential of the aqueous extract of Glycyrrhiza glabra (GG) roots on dengue viruses. Virus inhibition in Vero cell lines infected with dengue virus serotypes 1-4 and treated with GG extract was demonstrated. GG extract was 98-100% inhibitory to all four serotypes and had moderate pan-serotype inhibitory activity. It had good potential as an antiviral agent with low cytotoxicity. This is the first report of significant anti-dengue viral activity of GG extract on all four dengue serotypes.

microbiology↗

bioRxiv2021

Palaeogenomic analysis of black rat (Rattus rattus) reveals multiple European introductions associated with human economic history

The distribution of the black rat (Rattus rattus) has been heavily influenced by its association with humans. The dispersal history of this non-native commensal rodent across Europe, however, remains poorly understood, and different introductions may have occurred during the Roman and medieval periods. Here, in order to reconstruct the population history of European black rats, we generated a de novo genome assembly of the black rat, 67 ancient black rat mitogenomes and 36 ancient nuclear genomes from sites spanning the 1st-17th centuries CE in Europe and North Africa. Analyses of mitochondrial DNA confirm that black rats were introduced into the Mediterranean and Europe from Southwest Asia. Genomic analyses of the ancient rats reveal a population turnover in temperate Europe between the 6th and 10th centuries CE, coincident with an archaeologically attested decline in the black rat population. The near disappearance and re-emergence of black rats in Europe may have been the result of the breakdown of the Roman Empire, the First Plague Pandemic, and/or post-Roman climatic cooling.

evolutionary biology↗