Single-photon microscopy to study biomolecular condensates.

Biomolecular condensates serve as membrane-less compartments within cells, concentrating proteins and nucleic acids to facilitate precise spatial and temporal orchestration of various biological processes. The diversity of these processes and the substantial variability in condensate characteristics present a formidable challenge for quantifying their molecular dynamics, surpassing the capabilities of conventional microscopy. Here, we show that our single-photon microscope provides a comprehensive live-cell spectroscopy and imaging framework for investigating biomolecular condensation.

The long noncoding RNA nHOTAIRM1 is necessary for differentiation and activity of iPSC-derived spinal motor neurons.

The mammalian nervous system is made up of an extraordinary array of diverse cells that form intricate functional connections. The programs underlying cell lineage specification, identity and function of the neuronal subtypes are managed by regulatory proteins and RNAs, which coordinate the succession of steps in a stereotyped temporal order. In the central nervous system (CNS), motor neurons (MNs) are responsible for controlling essential functions such as movement, breathing, and swallowing by integrating signal transmission from the cortex, brainstem, and spinal cord (SC) towards peripheral muscles.

Modeling Myotonic Dystrophy Type 2 Using .

Myotonic dystrophy 2 (DM2) is a genetic multi-systemic disease primarily affecting skeletal muscle. It is caused by CCTGn expansion in intron 1 of the gene, which encodes a zinc finger protein. DM2 disease has been successfully modeled in allowing the identification and validation of new pathogenic mechanisms and potential therapeutic strategies.

Yeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy.

is an essential yeast gene encoding a component of different LSM complexes involved in the regulation of mRNA splicing, stability, and translation. In previous papers, we reported that the expression in of the gene lacking the C-terminal Q/N-rich domain in an null strain () restored cell viability. Nevertheless, in this transformed strain, we observed some phenotypes that are typical markers of regulated cell death, reactive oxygen species (ROS), and oxidated RNA accumulation.

The effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders in 140 214 UK Biobank participants.

Rare genetic diseases affect millions, and identifying causal DNA variants is essential for patient care. Therefore, it is imperative to estimate the effect of each independent variant and improve their pathogenicity classification. Our study of 140 214 unrelated UK Biobank (UKB) participants found that each of them carries a median of 7 variants previously reported as pathogenic or likely pathogenic.

Specific patterns of neural activity in the hippocampus after massed or distributed spatial training.

Training with long inter-session intervals, termed distributed training, has long been known to be superior to training with short intervals, termed massed training. In the present study we compared c-Fos expression after massed and distributed training protocols in the Morris water maze to outline possible differences in the learning-induced pattern of neural activation in the dorsal CA1 in the two training conditions. The results demonstrate that training and time lags between learning opportunities had an impact on the pattern of neuronal activity in the dorsal CA1.

Enhanced fluorescence detection of miRNA by means of Bloch surface wave-based biochips.

We report on the use of biochips based on one-dimensional photonic crystals sustaining Bloch surface waves to specifically detect target miRNA that is characteristic of hemorrhagic stroke (miR-16-5p) at low concentration in a buffer solution. The biochips were functionalized with streptavidin and ssDNA oligonucleotides to enable miRNA detection. To discriminate the target miRNA from a non-specific control (miR-101a-3p), we made use of an optical platform developed to work both in label-free and fluorescence detection modes.

in the critically ill: complex infections get complicated.

is increasingly associated with various epidemics, representing a serious concern due to the broad level of antimicrobial resistance and clinical manifestations. During the last decades, has emerged as a major pathogen in vulnerable and critically ill patients. Bacteremia, pneumonia, urinary tract, and skin and soft tissue infections are the most common presentations of , with attributable mortality rates approaching 35%.

An aqueous olive leaf extract (OLE) ameliorates parameters of oxidative stress associated with lipid accumulation and induces lipophagy in human hepatic cells.

Fatty liver is a disease characterized by a buildup of lipids in the liver, often resulting from excessive consumption of high-fat-containing foods. Fatty liver can degenerate, over time, into more severe forms of liver diseases, especially when oxidative stress occurs. Olive leaf extract (OLE) is a reliable source of polyphenols with antioxidant and hypolipidemic properties that have been successfully used in medicine, cosmetics, and pharmaceutical products.

In Vitro Probiotic Properties and In Vivo Anti-Ageing Effects of PFA2018AU Strain Isolated from Carrots on .

Lactic acid bacteria (LAB) share and provide several beneficial effects on human health, such as the release of bioactive metabolites, pathogen competition, and immune stimulation. The two major reservoirs of probiotic microorganisms are the human gastro-intestinal tract and fermented dairy products. However, other sources, such as plant-based foods, represent important alternatives thanks to their large distribution and nutritive value.

H3 Lysine 4 Methylation Is Required for Full Activation of Genes Involved in α-Ketoglutarate Availability in the Nucleus of Yeast Cells after Diauxic Shift.

We show that in the metabolic diauxic shift is associated with a H3 lysine 4 tri-methylation (H3K4me3) increase which involves a significant fraction of transcriptionally induced genes which are required for the metabolic changes, suggesting a role for histone methylation in their transcriptional regulation. We show that histone H3K4me3 around the start site correlates with transcriptional induction in some of these genes. Among the methylation-induced genes are and , which regulate the nuclear availability of α-ketoglutarate, which, as a cofactor for Jhd2 demethylase, regulates H3K4 tri-methylation.

Light Stress in Yeasts: Signaling and Responses in Creatures of the Night.

Living organisms on the surface biosphere are periodically yet consistently exposed to light. The adaptive or protective evolution caused by this source of energy has led to the biological systems present in a large variety of organisms, including fungi. Among fungi, yeasts have developed essential protective responses against the deleterious effects of light.

Preparation of Hydrogel Composites Using a Sustainable Approach for In Situ Silver Nanoparticles Formation.

The recognized antibacterial properties of silver nanoparticles (AgNPs) characterize them as attractive nanomaterials for developing new bioactive materials less prone to the development of antibiotic resistance. In this work, we developed new composites based on self-assembling Fmoc-Phe3 peptide hydrogels impregnated with in situ prepared AgNPs. Different methodologies, from traditional to innovative and eco-sustainable, were compared.

The Chromatin Landscape around DNA Double-Strand Breaks in Yeast and Its Influence on DNA Repair Pathway Choice.

DNA double-strand breaks (DSBs) are harmful DNA lesions, which elicit catastrophic consequences for genome stability if not properly repaired. DSBs can be repaired by either non-homologous end joining (NHEJ) or homologous recombination (HR). The choice between these two pathways depends on which proteins bind to the DSB ends and how their action is regulated.

AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation.

The AurkA kinase is a well-known mitotic regulator, frequently overexpressed in tumors. The microtubule-binding protein TPX2 controls AurkA activity, localization, and stability in mitosis. Non-mitotic roles of AurkA are emerging, and increased nuclear localization in interphase has been correlated with AurkA oncogenic potential.

Loss of ATP2C1 function promotes trafficking and degradation of NOTCH1: Implications for Hailey-Hailey disease.

Hailey-Hailey disease (HHD) is a rare autosomal dominantly inherited disorder caused by mutations in the ATP2C1 gene that encodes an adenosine triphosphate (ATP)-powered calcium channel pump. HHD is characterized by impaired epidermal cell-to-cell adhesion and defective keratinocyte growth/differentiation. The mechanism by which mutant ATP2C1 causes HHD is unknown and current treatments for affected individuals do not address the underlying defects and are ineffective.

A truncated and catalytically inactive isoform of KDM5B histone demethylase accumulates in breast cancer cells and regulates H3K4 tri-methylation and gene expression.

KDM5B histone demethylase is overexpressed in many cancers and plays an ambivalent role in oncogenesis, depending on the specific context. This ambivalence could be explained by the expression of KDM5B protein isoforms with diverse functional roles, which could be present at different levels in various cancer cell lines. We show here that one of these isoforms, namely KDM5B-NTT, accumulates in breast cancer cell lines due to remarkable protein stability relative to the canonical PLU-1 isoform, which shows a much faster turnover.

Microencapsulation by a Spray Drying Approach to Produce Innovative Probiotics-Based Products Extending the Shelf-Life in Non-Refrigerated Conditions.

Recently, there has been a growing interest in producing functional foods containing encapsulated probiotic bacteria due to their positive effects on human health. According to their perceived health benefits, probiotics have been incorporated into a range of dairy products, but the current major challenge is to market new, multicomponent probiotic foods and supplements. Nevertheless, only a few products containing encapsulated probiotic cells can be found as non-refrigerated products.

Structural Characterization of Murine Phosphodiesterase 5 Isoforms and Involvement of Cysteine Residues in Supramolecular Assembly.

Phosphodiesterases (PDEs) are a superfamily of evolutionarily conserved cyclic nucleotide (cAMP/cGMP)-hydrolyzing enzymes, components of transduction pathways regulating crucial aspects of cell life. Within this family, the cGMP-dependent PDE5 is the major hydrolyzing enzyme in many mammalian tissues, where it regulates a number of cellular and tissular processes. Using as a model organism, the murine PDE5A1, A2 and A3 isoforms were successfully expressed and studied, evidencing, for the first time, a distinct role of each isoform in the control, modulation and maintenance of the cellular redox metabolism.

Cytokinins.

The extraordinary variety that characterizes the living world in terms of forms and structures is the result of natural selection that allows an organism to be in perfect harmony with its environmental niche. Once a specific shape is acquired, many different factors act together to guarantee phenotypic robustness and developmental stability of the organism. Among these factors, hormones play a key role in the regulation and coordination of growth - they control the activity of a single cell, the progression to tissue organization, the development of specific organs, ending with the development of the entire body.

WiFi Related Radiofrequency Electromagnetic Fields Promote Transposable Element Dysregulation and Genomic Instability in .

Exposure to artificial radio frequency electromagnetic fields (RF-EMFs) has greatly increased in recent years, thus promoting a growing scientific and social interest in deepening the biological impact of EMFs on living organisms. The current legislation governing the exposure to RF-EMFs is based exclusively on their thermal effects, without considering the possible non-thermal adverse health effects from long term exposure to EMFs. In this study we investigated the biological non-thermal effects of low-level indoor exposure to RF-EMFs produced by WiFi wireless technologies, using as the model system.

Milmed Yeast Alters the LPS-Induced M1 Microglia Cells to Form M2 Anti-Inflammatory Phenotype.

Microglial cells polarized towards a proinflammatory phenotype are considered the main cellular players of neuroinflammation, underlying several neurodegenerative diseases. Many studies have suggested that imbalance of the gut microbial composition is associated with an increase in the pro-inflammatory cytokines and oxidative stress that underlie chronic neuroinflammatory diseases, and perturbations to the gut microbiota were detected in neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease. The importance of gut-brain axis has been uncovered and the relevance of an appropriate microbiota balance has been highlighted.

2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in .

High levels of 2-hydroxyisobutyric acid (2-HIBA) were found in urines of patients with obesity and hepatic steatosis, suggesting a potential involvement of this metabolite in clinical conditions. The gut microbial origin of 2-HIBA was hypothesized, however its actual origin and role in biological processes are still not clear. We investigated how treatment with 2-HIBA affected the physiology of the model organism , in both standard and high-glucose diet (HGD) growth conditions, by targeted transcriptomic and metabolomic analyses, Coherent Anti-Stokes Raman Scattering (CARS) and two-photon fluorescence microscopy.