👤 Tahir Maqbool

For a long time, noncoding RNAs (ncRNAs) were considered irrelevant fragments of the genome, dismissed as genetic noise. However, recent breakthroughs have unveiled their crucial Role in regulating gene expression, influencing fundamental biological processes such as chromatin remodeling, epigenetic modifications, and cellular communication. Among them, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have drawn considerable attention due to their strong association with neurodegenerative disorders and cardiovascular diseases (CVDs). Despite their apparent differences, these conditions share molecular regulatory networks that ncRNAs help orchestrate. LncRNAs, like ANRIL and MEG3, play a Role in vascular integrity and cardiac fibrosis, while MIAT and MALAT1 are implicated in heart failure and ischemic injury. In Alzheimer's disease, BACE1-AS and BC200 contribute to the buildup of amyloid plaques and tau protein tangles, worsening cognitive decline. The ability of ncRNAs to act as molecular sponges-binding to miRNAs and modulating gene expression-demonstrates their intricate Role in disease progression. With advances in sequencing technologies and computational biology, ncRNAs are emerging as promising biomarkers and therapeutic targets. New approaches, including CRISPR-based gene editing and RNA therapeutics, present exciting possibilities for intervention. However, challenges such as stability, precise delivery, and potential side effects must be addressed before these treatments can be translated into clinical practice. This chapter delves into the expanding field of ncRNA research, highlighting its potential to reshape the future of precision medicine and targeted therapies. Show less

The MAPK/ERK pathway plays a critical role in the regulation of milk production by controlling cellular processes such as proliferation, differentiation and survival, which are essential for lactogenesis and mammary gland function. Bubalus bubalis (Water buffalo), known for its unique physiological and ecological characteristics, serves as an ideal model to explore the evolutionary and molecular roles of MAPK/ERK pathway genes. This study presents the first comprehensive computational analysis of MAPK/ERK genes in B. bubalis, identifying 21 key genes involved in the pathway. Phylogenetic analysis clustered these genes into 13 distinct clades, such as MST1, GRB2, RAS, ETS1, JUN and FOS, and revealed close evolutionary relationships with Bos taurus and Camelus bactrianus. Structural characterization identified 10 conserved motifs, including essential domains like protein kinase, ETS and RAS, reflecting their functional significance. Gene structure analysis revealed substantial variation in exon-intron patterns, while synteny analysis confirmed collinearity with human orthologs, indicating genomic conservation. Physicochemical analysis highlighted a broad range of molecular weights and isoelectric points, with most proteins classified as hydrophilic and thermostable. Gene duplication and selection analyses revealed seven segmentally duplicated gene pairs, with the JUN-ETS1 and DUSP6-MST1 pairs showing evidence of positive selection, suggesting functional divergence. These findings establish a foundational understanding of MAPK/ERK pathway genes in B. bubalis and provide valuable insights into potential targets for genetic improvement, selective breeding and sustainable dairy management strategies aimed at enhancing milk production and quality. Show less

Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored. We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes. During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort. Show less

Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive loss of cognitive functions like thinking, memory, reasoning, behavioral abilities, and social skills thus affecting the ability of a person to perform normal daily functions independently. There is no definitive cure for this disease, and treatment options available for the management of the disease are not very effective as well. Based on histopathology, AD is characterized by the accumulation of insoluble deposits of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although several molecular events contribute to the formation of these insoluble deposits, the aberrant post-translational modifications (PTMs) of AD-related proteins (like APP, Aβ, tau, and BACE1) are also known to be involved in the onset and progression of this disease. However, early diagnosis of the disease as well as the development of effective therapeutic approaches is impeded by lack of proper clinical biomarkers. In this review, we summarized the current status and clinical relevance of biomarkers from cerebrospinal fluid (CSF), blood and extracellular vesicles involved in onset and progression of AD. Moreover, we highlight the effects of several PTMs on the AD-related proteins, and provide an insight how these modifications impact the structure and function of proteins leading to AD pathology. Finally, for disease-modifying therapeutics, novel approaches, and targets are discussed for the successful treatment and management of AD. Show less

Mammalian-wide interspersed repeats (MIRs) are retrotransposed elements of mammalian genomes. Here, we report the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N20) CCTCTCTG in the core region of MIRs. ZNF768 binding is preferentially associated with euchromatin and promoter regions of genes. Binding was observed for genes expressed in a cell type-specific manner in human B cell line Raji and osteosarcoma U2OS cells. Mass spectrometric analysis revealed binding of ZNF768 to Elongator components Elp1, Elp2 and Elp3 and other nuclear factors. The N-terminus of ZNF768 contains a heptad repeat array structurally related to the C-terminal domain (CTD) of RNA polymerase II. This array evolved in placental animals but not marsupials and monotreme species, displays species-specific length variations, and possibly fulfills CTD related functions in gene regulation. We propose that the evolution of MIRs and ZNF768 has extended the repertoire of gene regulatory mechanisms in mammals and that ZNF768 binding is associated with cell type-specific gene expression. Show less