Synergistic action of human RNaseH2 and the RNA helicase-nuclease DDX3X in processing R-loops.

R-loops are three-stranded RNA-DNA hybrid structures that play important regulatory roles, but excessive or deregulated R-loops formation can trigger DNA damage and genome instability. Digestion of R-loops is mainly relying on the action of two specialized ribonucleases: RNaseH1 and RNaseH2. RNaseH2 is the main enzyme carrying out the removal of misincorporated rNMPs during DNA replication or repair, through the Ribonucleotide Excision Repair (RER) pathway.

The Feulgen reaction: from pink-magenta to rainbow fluorescent at the Maffo Vialli's School of Histochemistry.

For over a century, Palazzo Botta (Palace Botta) has housed the University of Pavia's Biomedical Institutes. Illustrious scientists have conducted research and taught at this Palace, making significant contributions to the advancement of natural, biological, and medical science. Among them, Camillo Golgi received the Nobel Prize for discovering the so-called "black reaction.

Developmental and Nutritional Dynamics of Malpighian Tubule Autofluorescence in the Asian Tiger Mosquito .

Malpighian tubules (MTs) are arthropod excretory organs crucial for the osmoregulation, detoxification and excretion of xenobiotics and metabolic wastes, which include tryptophan degradation products along the kynurenine (KYN) pathway. Specifically, the toxic intermediate 3-hydroxy kynurenine (3-HK) is metabolized through transamination to xanthurenic acid or in the synthesis of ommochrome pigments. Early investigations in larval fat bodies revealed an intracellular autofluorescence (AF) that depended on tryptophan administration.

Impact of heat and cold shock on epigenetics and chromatin structure.

Cells are continuously exposed to various sources of insults, among which temperature variations are extremely common. Epigenetic mechanisms, critical players in gene expression regulation, undergo alterations due to these stressors, potentially leading to health issues. Despite the significance of DNA methylation and histone modifications in gene expression regulation, their changes following heat and cold shock in human cells remain poorly understood.

Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs.

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10-15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells.

Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA.

The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np alone was able to induce significant changes in the proteome of human cells. The cellular RNA helicase DDX1 was among the proteins whose levels were increased by Np expression.

Colorectal cancer patient-derived organoids and cell lines harboring ATRX and/or DAXX mutations lack Alternative Lengthening of Telomeres (ALT).

Telomere maintenance is necessary to maintain cancer cell unlimited viability. However, the mechanisms maintaining telomere length in colorectal cancer (CRC) have not been extensively investigated. Telomere maintenance mechanisms (TMM) include the re-expression of telomerase or alternative lengthening of telomeres (ALT).

Hydrogen Sulfide (HS): As a Potent Modulator and Therapeutic Prodrug in Cancer.

Hydrogen sulfide (HS) is an endogenous gaseous molecule present in all living organisms that has been traditionally studied for its toxicity. Interestingly, increased understanding of HS effects in organ physiology has recently shown its relevance as a signalling molecule, with potentially important implications in variety of clinical disorders, including cancer. HS is primarily produced in mammalian cells under various enzymatic pathways are target of intense research biological mechanisms, and therapeutic effects of HS.

GABA and GABA Receptors Mediate GABA-Induced Intracellular Ca Signals in Human Brain Microvascular Endothelial Cells.

Numerous studies recently showed that the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), can stimulate cerebral angiogenesis and promote neurovascular coupling by activating the ionotropic GABA receptors on cerebrovascular endothelial cells, whereas the endothelial role of the metabotropic GABA receptors is still unknown. Preliminary evidence showed that GABA receptor stimulation can induce an increase in endothelial Ca levels, but the underlying signaling pathway remains to be fully unraveled. In the present investigation, we found that GABA evoked a biphasic elevation in [Ca] that was initiated by inositol-1,4,5-trisphosphate- and nicotinic acid adenine dinucleotide phosphate-dependent Ca release from neutral and acidic Ca stores, respectively, and sustained by store-operated Ca entry.

Truncating Variants in in Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

Background And Objective: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease characterized by adult-onset and slowly progressive sensory neuropathy, cerebellar dysfunction, and vestibular impairment. In most cases, the disease is caused by biallelic (AAGGG) repeat expansions in the second intron of the replication factor complex subunit 1 (). However, a small number of cases with typical CANVAS do not carry the common biallelic repeat expansion.

Beyond Sperm and Male Accessory Gland Proteins: Exploring Insect Reproductive Metabolomes.

Insect seminal fluid, the non-sperm component of the ejaculate, comprises a variegated set of molecules, including, but not limited to, lipids, proteins, carbohydrates, salts, hormones, nucleic acids, and vitamins. The identity and functional role of seminal fluid proteins (SFPs) have been widely investigated, in multiple species. However, most of the other small molecules in insect ejaculates remain uncharacterized.

Viviparity and habitat restrictions may influence the evolution of male reproductive genes in tsetse fly (Glossina) species.

Background: Glossina species (tsetse flies), the sole vectors of African trypanosomes, maintained along their long evolutionary history a unique reproductive strategy, adenotrophic viviparity. Viviparity reduces their reproductive rate and, as such, imposes strong selective pressures on males for reproductive success. These species live in sub-Saharan Africa, where the distributions of the main sub-genera Fusca, Morsitans, and Palpalis are restricted to forest, savannah, and riverine habitats, respectively.

Selective Binding and Redox-Activity on Parallel G-Quadruplexes by Pegylated Naphthalene Diimide-Copper Complexes.

G-quadruplexes (G4s) are higher-order supramolecular structures, biologically important in the regulation of many key processes. Among all, the recent discoveries relating to RNA-G4s, including their potential involvement as antiviral targets against COVID-19, have triggered the ever-increasing need to develop selective molecules able to interact with parallel G4s. Naphthalene diimides (NDIs) are widely exploited as G4 ligands, being able to induce and strongly stabilize these structures.

High Flexibility of RNaseH2 Catalytic Activity with Respect to Non-Canonical DNA Structures.

Ribonucleotides misincorporated in the human genome are the most abundant DNA lesions. The 2'-hydroxyl group makes them prone to spontaneous hydrolysis, potentially resulting in strand breaks. Moreover, their presence may decrease the rate of DNA replication causing replicative fork stalling and collapse.

The polyphenol/saponin-rich Rhus tripartita extract has an apoptotic effect on THP-1 cells through the PI3K/AKT/mTOR signaling pathway.

Background: Hyperactivation of mechanistic target of rapamycin (mTOR) signaling pathway is involved in the regulation of cellular growth, proliferation, and more in general, is a common phenomenon in most types of cancers. Thus, natural substances targeting this pathway can be of great therapeutic potential in supporting the treatment of tumor patients. Rhus tripartita (Ucria) Grande is a plant growing in desertic areas which is traditionally used for the treatment of several diseases in Tunisia.

Tephritid Fruit Fly Semiochemicals: Current Knowledge and Future Perspectives.

The Dipteran family Tephritidae (true fruit flies) comprises more than 5000 species classified in 500 genera distributed worldwide. Tephritidae include devastating agricultural pests and highly invasive species whose spread is currently facilitated by globalization, international trade and human mobility. The ability to identify and exploit a wide range of host plants for oviposition, as well as effective and diversified reproductive strategies, are among the key features supporting tephritid biological success.

A Role for Human DNA Polymerase λ in Alternative Lengthening of Telomeres.

Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol λ) in ALT cells represses ALT activity and induces telomeric stress. In addition, replication stress in the absence of Pol λ, strongly affects the survival of ALT cells.

Electrophysiological Responses of the Mediterranean Fruit Fly, Ceratitis capitata, to the Cera Trap® Lure: Exploring Released Antennally-Active Compounds.

The Mediterranean fruit fly (medfly), Ceratitis capitata, is a worldwide pest of agriculture able to use olfactory cues to locate habitat, food sources, mates and oviposition sites. The sensitivity of medfly olfaction has been exploited to develop olfactory-based attractants that are currently important tools for detection, control and eradication of its populations. Among these is Cera Trap (BIOIBERICA, S.

Host DDX Helicases as Possible SARS-CoV-2 Proviral Factors: A Structural Overview of Their Hijacking Through Multiple Viral Proteins.

As intracellular parasites, viruses hijack the host cell metabolic machinery for their replication. Among other cellular proteins, the DEAD-box (DDX) RNA helicases have been shown to be hijacked by coronaviruses and to participate in essential DDX-mediated viral replication steps. Human DDX RNA helicases play essential roles in a broad array of biological processes and serve multiple roles at the virus-host interface.