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Biology subjects

Ali, M. H.

Publications and source records attributed to Ali, M. H..

4 recordsLinked to original sources

Multimodal Fusion of Circular Functional Data on High-resolution Neuroretinal Phenotypes

Progressive optic neuropathies, particularly glaucoma, represent a significant global health challenge, and the need for precise understanding of heterogeneous neurodegenerative phenotypes cannot be overstated. Here, we brought together two complementary sources of unstructured yet clinically relevant information about neuroretinal rim (NRR) thinning, a common clinical marker of such decay. These are based on a new dataset of fundus digital images and a corresponding dataset of optical coherence tomography, both collected from a large clinical cohort of healthy eyes. First, we represented them using a common data structure that imposed a high-resolution scale of 180 equally spaced and registered measurements on a 360{degrees} circular axis. We modeled the NRR measurements of each eye as circular curves and aligned these multimodal curves to obtain a fused NRR curve for each eye. Unsupervised clustering of these fused curves identified four clusters of eyes with structural heterogeneity, which were also found to have distinctive clinical covariates. Computation of functional derivatives revealed troughs in the curves of each cluster. Using circular statistics, we estimated the directional distributions of these troughs as potentially clinically relevant regions of NRR degeneration. A comparative study using landmark registration based on functional canonical correlation analysis demonstrated that our curve-alignment-based multimodal fusion is superior. Moreover, it improves the robustness of baseline NRR data obtained from fundus imaging.

bioinformatics↗

Targeted blocking of gene splicing can dysregulate intron-embedded microRNAs

ASOs (antisense oligonucleotides) are a promising therapeutic approach for suppression, induction of gene expression or the correction of aberrant splicing. Addressing whether ASOs targeting genes embedded with intronic noncoding RNAs (ncRNAs) affect the expression and function of intronic ncRNAs is of importance to the success of ASOs in clinical trials. While studying the development of the zebrafish posterior pituitary (neurohypophysis), an important neuroendocrine interface, we observed that an ASO targeting the splice site, in contrast to the one targeting the translation site of the gene slit3, disrupts neurohypophyseal axonal morphogenesis. In addition to altered slit3 splicing, we also observed an increase in the expression of slit3 and slit3 intron-embedded primary mir218a-1 transcripts. The ASO-induced phenotype was not observed when mature mir218a-1 was blocked by an ASO or in mir218a-1-/- mutants. In addition, we also found that previously reported phenotypes due to ASOs targeting the splice site of pank2 and dnm2a were partially rescued when the mature mir103 and mir199-5p embedded in their introns, respectively, were blocked by ASOs. Our observation that ASOs targeting splice sites can affect intronic microRNA expression and function warrants further validation for other classes of ncRNAs. In addition, the idiosyncratic phenotypes when using translation and splice-blocking ASOs can be potentially used as a marker to identify the role of intronic ncRNAs.

molecular biology↗

Highly multiplexed ddPCR-amplicon sequencing reveals strong Plasmodium falciparum population structure and isolated populations amenable to local elimination efforts in Zanzibar

Over the past 15 years, Zanzibar has made great strides towards malaria elimination; yet progress has stalled. Parasite genetic data of Plasmodium falciparum may inform strategies for malaria elimination by helping to identify contributory factors to parasite persistence. Here we elucidate fine-scale parasite population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. We sequenced 518 P. falciparum samples from 5 districts covering both main islands using a novel, highly multiplexed droplet digital PCR (ddPCR)-based amplicon deep sequencing method targeting 35 microhaplotypes and drug-resistance loci. Despite high genetic diversity, we observe strong fine-scale spatial and temporal structure of local parasite populations, including isolated populations on Pemba Island and genetically admixed populations on Unguja Island, providing evidence of ongoing local transmission. We observe a high proportion of highly related parasites in individuals living closer together, including between clinical index cases and the mostly asymptomatic cases surrounding them, consistent with isolation-by-distance. We identify a substantial fraction (2.9%) of related parasite pairs between Zanzibar, and mainland Tanzania and Kenya, consistent with recent importation. We identify haplotypes known to confer resistance to known antimalarials in all districts, including multidrug-resistant parasites, but most parasites remain sensitive to current first-line treatments. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and reveals actionable patterns, including isolated parasite populations, which may be prioritized for malaria elimination.

genomics↗

In Silico Investigations on Curcuminoids from Curcuma longa as Positive Regulators of Wnt/β-catenin Signaling Pathway in Wound Healing

Curcuma longa (Turmeric) is a traditionally used herb in wound healing. The efficacy of fresh Turmeric paste to heal wound has already been investigated in multiple ethnobotanical studies. Wnt/{beta}-catenin signaling pathway plays a significant role in wound healing and injury repair processes which has been evident in different in vitro studies. This study aims to analyze the potentiality of Curcuminoids (Curcumin I, Curcumin II and Curcumin III) from Curcuma longa to bind and enhance the activity of two intracellular signaling proteins-Casein Kinase-1 (CK1) and Glycogen Synthase Kinase-3{beta} (GSK3B) involved in Wnt/{beta}-catenin signaling pathway. Present study is largely based on computer-based molecular docking program which mimics the in vivo condition and works on specific algorithm to interpret the binding affinity and poses of a ligand molecule to a receptor. Curcumin I showed better affinity of binding with CK1 (-10.31 Kcal/mol binding energy) and Curcumin II showed better binding affinity (-7.55 Kcal/mol binding energy) for GSK3B. Subsequently, Drug likeness property, ADME/Toxicity profile, Pharmacological activity and Site of metabolism of the Curcuminoids were also analyzed. All of the ligand molecules showed quite similar pharmacological properties.

bioinformatics↗