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Biology subjects

Salim, H.

Publications and source records attributed to Salim, H..

4 recordsLinked to original sources

Intracellular Delivery of Peptides and Proteins with an Engineered Membrane Translocation Domain

Antibodies and other protein therapeutics have revolutionized medicine, but their application is largely limited to extracellular targets. The lack of efficient intracellular delivery methods remains a major bottleneck. Here, we engineered a family of small ([~]90 amino acids), metabolically stable membrane translocation domains (MTDs) by modifying the loop sequences of a human fibronectin type III (FN3) domain. The most potent variant, MTD4, is highly cell-permeable and can be recombinantly fused to the N- or C-terminus of any peptide or protein, serving as a versatile "plug-and-play" vehicle. We demonstrate that MTD4 fusions efficiently deliver a wide variety of functional peptides and proteins into the cytosol and nucleus of eukaryotic cells, both in vitro and in vivo. Following systemic administration, MTD4 fusion proteins exhibit broad biodistribution and homogenous tissue penetration in mice. Importantly, MTD4 is effective at low nanomolar (nM) concentrations, making it a promising platform for addressing a vast range of intracellular and previously "undruggable" targets.

bioengineering↗

Novel regional specific voltage-gated sodium channel (vgsc) mutations underlying pyrethroid resistance in Aedes albopictus (Skuse) from Northern Peninsular Malaysia

BackgroundControlling Aedes mosquitoes remains as a primary means through the application of synthetic insecticides in Malaysia, but its efficacy is undermined by the evolution of resistance. Aedes albopictus as one of the dominant and competent arboviral vectors has an elusive insecticide resistance status in different geographical regions of Northern Peninsular Malaysia. This underscores the importance of assessing the diverse types of insecticides used and their association with target-site resistance mechanism in this species, which forms the basis of the present study. MethodsWHO-bioassays were performed on Ae. albopictus larvae and adults from four localities (Penang and Perlis), towards 0.034 ppm temephos, 0.25% permethrin, 0.03% deltamethrin, 0.25% primiphos methyl and 0.1% propoxur. The partial voltage-gated sodium channel (vgsc) gene domain (DIIS6, DIIIS6, and DIVS6) of pyrethroid-exposed samples were subsequently genotyped through direct sequencing for any diagnostic single-nucleotide mutations, together with genetic variations and haplotype networks analysis. The predicted protein structures for the mutated regions and their binding affinities to pyrethroids were also evaluated using in-silico docking. Results and discussionsVarying degrees of resistance were observed in all Penang and Perlis strains to all tested insecticides. Moreover, the detection of the F1534L mutation and newly discovered non-synonymous mutations (A1022S/P, E1041K, P1585R, and F1695L) suggest the progression of resistance alleles dissemination in other strains. The analysis of genetic variations, resistance allele distribution patterns, and haplotype networks showed evidence for multiple origins of these mutations. Data also revealed the discovered mutations affect the affinity of vgsc-binding proteins to pyrethroids. ConclusionThis study highlights the genotype-phenotype associations in Ae. albopictus and their genetic links to pyrethroid resistance, offering insights to strengthen vector control strategies in Malaysia. Author summaryIn Malaysia, as in many other countries, dengue epidemic control primarily relies on managing the main vector, Ae. albopictus through commercially available insecticide applications. Vector control strategies have been extensively implemented by local health authorities, often without comprehensive information on insecticide resistance mechanisms in vector populations that could pose a major drawback of insecticide used. In an effort to assess the susceptibility status of Ae. albopictus populations, and determine the most effective insecticide for reducing Malaysian vector populations from different geographical settings, we conducted bioassays towards pyrethroid, organophosphate, and carbamate insecticide classes. Altogether, molecular-based assays were incorporated with phenotypic assay to elucidate the mechanisms modulating insecticide resistance and to unravel their genetic dynamics. Such screening offers detailed insights into specific mechanisms involved in conferring resistance for distinct adopted insecticides. This evidence aims to guide local health authorities in developing vector control strategies and exploring alternative solutions.

evolutionary biology↗

16S rRNA Amplicon Sequencing of Bagworm Metisa plana Walker (Lepidoptera: Psychidae)

The bagworm Metisa plana is one of the major pests in the oil palm plantation in Malaysia, with infestation that results in huge economical loss. Currently, the exact cause of the infestation is still undetermined. Studying the bacterial community of M. plana could provide insight on the problem as the bacteria associated with insects often provide numerous benefits to the insect itself. Using 16S rRNA amplicon sequencing, the study was conducted to compare the composition of the bacterial communities of two larval stages (early instar stage and late instar stage) from outbreak area, as well as comparing the late instar stage larvae from non-outbreak and outbreak areas. Generally, the bacterial community was dominated by Proteobacteria and Actinobacteria phyla while the Enterobacteriaceae was found to be the dominant family. When comparing between the early and late instar stage, Proteobacteria phylum was found to be more abundant in the late instar stage (82.36%) than in the early instar stage (82.28%). At the family level, the Enterobacteriaceae was slightly more abundant in late instar stage (75.46%) than in early instar stage (75.29%). The instar stage was observed to have no significant impact on the bacterial variability and showed similar bacterial community structure. When comparing between the non-outbreak area and outbreak, Proteobacteria was significantly more abundant in the outbreak area (82.02%) than in the non-outbreak area (20.57%). However, Actinobacteria was significantly more abundant in the non-outbreak area (76.29%) than in the outbreak area (14.16%). At the family level, Enterobacteriaceae was more abundant in outbreak area (75.41%) than in non-outbreak area (11.67%). Microbacteriaceae was observed to be more abundant in the non-outbreak area (70.87%) than in the outbreak area (12.47%). Although the result showed no significant difference in bacterial variability between different areas, it the bacterial community structure was significantly different.

microbiology↗

Diet composition of introduced Barn Owls (Tyto alba javanica) in urban area in comparison with agriculture settings

This study investigated the diet of introduced barn owls (Tyto alba javanica, Gmelin) in the urban area of the Main Campus of Universiti Sains Malaysia, Penang, Malaysia, based on collected regurgitated pellets. We also compared the diet of introduced urban barn owls with the diet of barn owls from two agricultural areas, i.e. oil palm plantations and rice fields. Pellet analysis of barn owls introduced in the urban area showed that commensal Norway rats, Rattus norvegicus, made up the highest proportion of the diet (65.37% prey biomass) while common shrews, Suncus murinus were the second highest consumed prey (30.12% prey biomass). Common plantain squirrel, Callosciurus notatus, made up 4.45% of the diet while insects were taken in a relatively small amount (0.046% prey biomass). Introduced barn owls showed a preference for medium-sized prey, i.e. 40 to 120g (52.96% biomass and 38.71% total). In agricultural areas, Rattus argentiventer predominated the diet of barn owls (98.24% prey biomass) in rice fields while Malayan wood rats, Rattus tiomanicus, were the most consumed prey in oil palm plantations (99.5% prey biomass). Food niche breadth value was highest for barn owls introduced in an urban area with a value of 2.90, and 1.06 in rice fields and 1.22 in oil palm plantations. Our analysis reiterates the prey preference of barn owls in various landscapes for small mammals. Our results also indicate the suitability of utilizing barn owls as a biological control not only in agricultural areas, but also as a biological control agent for commensal rodent pests in urban areas.

ecology↗