Targeting TDP-43 Proteinopathy in hiPSC-Derived Mutated hNPCs with Mitoxantrone Drugs and miRNAs.

TDP-43 mutation-driven Amyotrophic Lateral Sclerosis (ALS) motor neuron disease is one of the most prominent forms (approximately 97%) in cases of sporadic ALS. Dysfunctional autophagy and lysosomal function are the prime mechanisms behind ALS. Mitoxantrone (Mito), a synthetic doxorubicin analog, is an inhibitor of DNA and RNA synthesis/repair via intercalating with nitrogenous bases and inhibiting topoisomerase II.

HiCForecast: dynamic network optical flow estimation algorithm for spatiotemporal Hi-C data forecasting.

Motivation: The exploration of the 3D organization of DNA within the nucleus in relation to various stages of cellular development has led to experiments generating spatiotemporal Hi-C data. However, there is limited spatiotemporal Hi-C data for many organisms, impeding the study of 3D genome dynamics. To overcome this limitation and advance our understanding of genome organization, it is crucial to develop methods for forecasting Hi-C data at future time points from existing timeseries Hi-C data.

A constitutive heterochromatic region shapes genome organization and impacts gene expression in Neurospora crassa.

Background: Organization of the eukaryotic genome is essential for proper function, including gene expression. In metazoans, chromatin loops and Topologically Associated Domains (TADs) organize genes into transcription factories, while chromosomes occupy nuclear territories in which silent heterochromatin is compartmentalized at the nuclear periphery and active euchromatin localizes to the nucleus center. A similar hierarchical organization occurs in the fungus Neurospora crassa where its seven chromosomes form a Rabl conformation typified by heterochromatic centromeres and telomeres independently clustering at the nuclear membrane, while interspersed heterochromatic loci aggregate across Megabases of linear genomic distance to loop chromatin in TAD-like structures.

A Constitutive Heterochromatic Region Shapes Genome Organization and Impacts Gene Expression in .

Background: Organization of the eukaryotic genome is essential for proper function, including gene expression. In metazoans, chromatin loops and Topologically Associated Domains (TADs) organize genes into transcription factories, while chromosomes occupy nuclear territories in which silent heterochromatin is compartmentalized at the nuclear periphery and active euchromatin localizes to the nucleus center. A similar hierarchical organization occurs in the fungus where its seven chromosomes form a Rabl conformation typified by heterochromatic centromeres and telomeres independently clustering at the nuclear membrane, while interspersed heterochromatic loci aggregate across Megabases of linear genomic distance to loop chromatin in TAD-like structures.

HCMV miR-UL70-3p downregulates the rapamycin-induced autophagy by targeting the autophagy-related protein 9A (ATG9A).

Human cytomegalovirus (HCMV) is a representative that establishes persistent infections in humans, and exhibits high seropositivity rates in adults. It has co-evolved with its human host and employs various strategies to evade antiviral mechanisms by utilizing a significant portion of its genome. HCMV-encoded proteins and miRNAs have been implicated in regulating these mechanisms, enabling viral survival within the human body.

Proteome architecture of human-induced pluripotent stem cell-derived three-dimensional organoids as a tool for early diagnosis of neuronal disorders.

Background And Objectives: Induced pluripotent stem cells (iPSCs) derived three-dimensional (3D) model for rare neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) is emerging as a novel alternative to human diseased tissue to explore the disease etiology and potential drug discovery. In the interest of the same, we have generated a TDP-43-mutated human iPSCs (hiPSCs) derived 3D organoid model of ALS disease. The high-resolution mass spectrometry (MS)-based proteomic approach is used to explore the differential mechanism under disease conditions and the suitability of a 3D model to study the disease.

Hcmv-miR-UL148D regulates the staurosporine-induced apoptosis by targeting the Endoplasmic Reticulum to Nucleus signaling 1(ERN1).

The propensity of viruses to co-opt host cellular machinery by reprogramming the host's RNA-interference machinery has been a major focus of research, however, regulation of host defense mechanisms by virus-encoded miRNA, is an additional regulatory realm gaining momentum in the arena of host-viral interactions. The Human Cytomegalovirus (HCMV) miRNAs, regulate many cellular pathways alone or in concordance with HCMV proteins, thereby paving a conducive environment for successful infection in the human host. We show that HCMV miRNA, hcmv-miR-UL148D inhibits staurosporine-induced apoptosis in HEK293T cells.

Ameliorative effect of fluvoxamine against colon carcinogenesis via COX-2 blockade with oxidative and metabolic stress reduction at the cellular, molecular and metabolic levels.

Fluvoxamine's (FLX's) anticancer potential was investigated in pre-clinical research utilizing a DMH-induced colorectal cancer (CRC) rat model. qRT-PCR and immunoblotting validated the mechanistic investigation. The CRC condition was induced in response to COX-2 and IL-6, however, following FLX therapy, the condition returned to normal.

Human Cytomegalovirus miR-UL70-3p Downregulates the HO-Induced Apoptosis by Targeting the Modulator of Apoptosis-1 (MOAP1).

Human Cytomegalovirus (HCMV) is a prototypic , causing persistent infections in humans. There are medications that are used to treat the symptoms; however, there is no cure yet. Thus, understanding the molecular mechanisms of HCMV replication and its persistence may reveal new prevention strategies.

Role of HCMV miR-UL70-3p and miR-UL148D in overcoming the cellular apoptosis.

The studies into the pathophysiology of viral miRNAs are still in infancy; the interspecies regulation at the miRNA level fuels the spark of the investigation into the repertoire of virus-host interactions. Reports pertaining to the viral miRNAs role in modulating/evading the host immune response are surging up; we initiated this in silico study to speculate the role of human cytomegalovirus (HCMV)-encoded miRNAs on human antiviral mechanisms such as apoptosis and autophagy. The results indicate that both the above mechanisms were targeted by the HCMV miRNAs, located in the unique long region of the HCMV genome.