Biology subjects

Tabassum, N.

Publications and source records attributed to Tabassum, N..

3 recordsLinked to original sources

bioRxiv2020

Homeodomain protein 1 is an essential regulator of gene expression during sexual differentiation of malaria parasites

Transmission of Plasmodium falciparum and other malaria parasites requires their differentiation from asexual blood stages into gametocytes, the non-replicative sexual stage necessary for transmission to the mosquito vector. This transition involves changes in gene expression and chromatin reorganization that result in the activation and silencing of stage-specific genes. However, the genomes of malaria parasites have been noted for their dearth of transcriptional and chromatin regulators and the molecular mediators of these changes remain largely unknown. We recently identified HomeoDomain Protein 1 (HDP1) as a DNA-binding protein that enhances the expression of key genes that are critical for early sexual differentiation. The discovery of a homeodomain-like DNA-binding protein marks a new class of transcriptional regulator in malaria parasites outside of the better-characterized ApiAP2 family. In this study, we show that HDP1 facilitates the necessary upregulation of inner membrane complex components during early gametocytogenesis that gives P. falciparum gametocytes they characteristic shape and is required for gametocyte maturation and parasite transmission.

microbiology↗

bioRxiv2020

Mutational landscapes of normal breast during age and pregnancy determine cancer risk

The accumulation of somatic mutations in the healthy breast throughout life and pregnancy is poorly understood1-10. Similarly, the mutational landscape of both epithelial and stromal components of the mammary gland has not been investigated. Both are relevant for breast cancer (BC), as the interplay between age, pregnancy, and cancer risk has not been fully characterized11. We describe whole genome sequencing analysis of epithelial and stromal compartments from the normal breast. We show that, in a similar way to other normal organs, the mutational burden of the mammary nulliparous epithelium significantly increases with age. In a nulliparous status, mutated clones are maintained at a consistently small size throughout the life of the individual; however, at parity, pre-existent clones significantly increase in size with age. Both epithelial and stromal compartments of the healthy breast contain pre-existing known cancer mutations, albeit at low rate, indicative of subsequent positive selection for mutations in tissue-specific driver genes. In line with this, both compartments also present gene enrichment in preferentially mutated cancer pathways. Our results show that mutational landscapes differ between the parous and nulliparous epithelium and suggest an explanation for both differential breast cancer risk and development of pregnancy-associated BC (PABC).

genetics↗

bioRxiv2020

In Silico Analysis of Effect of non-synonymous SNPs associated with Permanent Neonatal Diabetes Mellitus on Stability and Structure of Human Insulin

MotivationProteins are the building-blocks of life. However with the deluge of data on protein sequences and their association with diseases, it is imperative to use computational tools to aid experimental analysis. Determination of the impact of disease-causing SNPs on proteins structure is crucial in discovering how a disease affects the functions on a fundamental level and thereafter, determining potential drug targets. ResultsSNPs associated with the genetic disease permanent neonatal diabetus mellitus (PNDM) were studied to determine their impact on human insulin. Out of 16 missense variants, eight were predicted to be deleterious. 6 of the SNPs resulted in high structural differences (RMSD > 0.9, H bonds > 35). Stability changes were also determined.

bioinformatics↗