Depicting the cellular complexity of pancreatic adenocarcinoma by Imaging Mass Cytometry: focus on cancer-associated fibroblasts.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) represents the complexity of interaction between cancer and cells of the tumor microenvironment (TME). Immune cells affect tumor cell behavior, thus driving cancer progression. Cancer-associated fibroblasts (CAFs) are responsible of the desmoplastic and fibrotic reaction by regulating deposition and remodeling of extracellular matrix (ECM).

Multiplexed Imaging Mass Cytometry Analysis in Preclinical Models of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. PDAC is characterized by a complex tumor microenvironment (TME), that plays a pivotal role in disease progression and resistance to therapy. Investigating the spatial distribution and interaction of TME cells with the tumor is the basis for understanding the mechanisms underlying disease progression and represents a current challenge in PDAC research.

Integrating AI-Powered Digital Pathology and Imaging Mass Cytometry Identifies Key Classifiers of Tumor Cells, Stroma, and Immune Cells in Non-Small Cell Lung Cancer.

Unlabelled: Artificial intelligence (AI)-powered approaches are becoming increasingly used as histopathologic tools to extract subvisual features and improve diagnostic workflows. On the other hand, hi-plex approaches are widely adopted to analyze the immune ecosystem in tumor specimens. Here, we aimed at combining AI-aided histopathology and imaging mass cytometry (IMC) to analyze the ecosystem of non-small cell lung cancer (NSCLC).

A Multilayered Imaging and Microfluidics Approach for Evaluating the Effect of Fibrinolysis in Biofilm Formation.

The recognition of microbe and extracellular matrix (ECM) is a recurring theme in the humoral innate immune system. Fluid-phase molecules of innate immunity share regulatory roles in ECM. On the other hand, ECM elements have immunological functions.

Interrogating colorectal cancer metastasis to liver: a search for clinically viable compounds and mechanistic insights in colorectal cancer Patient Derived Organoids.

Background: Approximately 20-50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a major prognostic determinant. Here, we have interrogated a heterogeneous set of primary colorectal cancer (CRC), liver CRC metastases and adjacent liver tissue to identify molecular determinants of the colon to liver spreading. Screening Food and Drug Administration (FDA) approved drugs for their ability to interfere with an identified colon to liver metastasis signature may help filling an unmet therapeutic need.

Quantitative analysis of disease-related metabolic dysregulation of human microbiota.

The metabolic activity of all the micro-organism composing the human microbiome interacts with the host metabolism contributing to human health and disease in a way that is not fully understood. Here, we introduce STELLA, a computational method to derive the spectrum of metabolites associated with the microbiome of an individual. STELLA integrates known information on metabolic pathways associated with each bacterial species and extracts from these the list of metabolic products of each singular reaction by means of automatic text analysis.

Nuclear Biophysical Changes during Human Melanoma Plasticity.

Tumor plasticity is an emerging property of tumor cells which allows them to change their phenotype in dependence on the environment. The epithelial-mesenchymal transition plays a crucial role in helping cells acquire a more aggressive phenotype when they are in the mesenchymal state. Herein, we investigated the biophysical changes occurring during phenotypic switching in human melanoma cells, considering the blebbiness of the nuclei, their stiffness, and the involvement of polycombs with lamins.

TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase.

Tumor microenvironments are often characterized by an increase in oxidative stress levels. We studied the response to oxidative stimulation in human primary (IGR39) or metastatic (IGR37) cell lines obtained from the same patient, performing patch-clamp recordings, intracellular calcium ([Ca]) imaging, and RT-qPCR gene expression analysis. In IGR39 cells, chloramine-T (Chl-T) activated large K currents (KROS) that were partially sensitive to tetraethylammonium (TEA).

Role of body temperature variations in bat immune response to viral infections.

The ability of bats to coexist with viruses without being harmed is an interesting issue that is still under investigation. Here we use a mathematical model to show that the pattern of body temperature variations observed in bats between day and night is responsible for their ability to keep viruses in check. From the dynamical systems point of view, our model displays an intriguing quasi-periodic behaviour that might be relevant in making the system robust by avoiding viral escape due to perturbations in the body temperature cycle.

Synergistic effects of contaminants in Lombardy waters.

Quantifying synergistic environmental effects in water contamination is still an open issue. Here, we have analyzed geolocalized data of pollutants recorded in 2018 in surface and groundwater of Lombardy, one of the areas with the highest agricultural production rates, not only in Italy, but also in Europe. Both herbicides and insecticides are present at concentration levels above the legal limit, mainly in surface waters.

A Model-Driven Quantitative Analysis of Retrotransposon Distributions in the Human Genome.

Retrotransposons, DNA sequences capable of creating copies of themselves, compose about half of the human genome and played a central role in the evolution of mammals. Their current position in the host genome is the result of the retrotranscription process and of the following host genome evolution. We apply a model from statistical physics to show that the genomic distribution of the two most populated classes of retrotransposons in human deviates from random placement, and that this deviation increases with time.

MicroRNA-222 Regulates Melanoma Plasticity.

Melanoma is one of the most aggressive and highly resistant tumors. Cell plasticity in melanoma is one of the main culprits behind its metastatic capabilities. The detailed molecular mechanisms controlling melanoma plasticity are still not completely understood.

Comparative analysis of metabolic and transcriptomic features of .

Some species have a longer lifespan than others, but usually lifespan is correlated with typical body weight. Here, we study the lifetime evolution of the metabolic behaviour of , a killifish with an extremely short lifespan with respect to other fishes, even when taking into account rescaling by body weight. Comparison of the gene expression patterns of with those of zebrafish and mouse () shows that a broad set of metabolic genes and pathways are affected in during ageing in a way that is consistent with a global deregulation of chromatin.

Unjamming of active rotators.

Active particle assemblies can exhibit a wide range of interesting dynamical phases depending on internal parameters such as density, adhesion strength or self-propulsion. Active self-rotations are rarely studied in this context, although they can be relevant for active matter systems, as we illustrate by analyzing the motion of Chlamydomonas reinhardtii algae under different experimental conditions. Inspired by this example, we simulate the dynamics of a system of interacting active disks endowed with active torques and self-propulsive forces.

Chromatin and Cytoskeletal Tethering Determine Nuclear Morphology in Progerin-Expressing Cells.

The nuclear morphology of eukaryotic cells is determined by the interplay between the lamina forming the nuclear skeleton, the chromatin inside the nucleus, and the coupling with the cytoskeleton. Nuclear alterations are often associated with pathological conditions as in Hutchinson-Gilford progeria syndrome, in which a mutation in the lamin A gene yields an altered form of the protein, named progerin, and an aberrant nuclear shape. Here, we introduce an inducible cellular model of Hutchinson-Gilford progeria syndrome in HeLa cells in which increased progerin expression leads to alterations in the coupling of the lamin shell with cytoskeletal or chromatin tethers as well as with polycomb group proteins.

Cross-Talk Between circRNAs and mRNAs Modulates MiRNA-mediated Circuits and Affects Melanoma Plasticity.

CircularRNAs (circRNAs) are non-coding RNAs which compete for microRNA (miRNA) binding, influencing the abundance and stability of other RNA species. Herein we have investigated the effect of circRNAs on the mir200-ZEB1 feedback loop in relationship with the aggressiveness of human melanoma cells. We first compared the level of expression of key factors in the mir200-ZEB1 feedback loop in primary human melanoma cells compared with their matching metastatic one and found a correlation between the aggressiveness of the cells and the level of expression of ZEB1 and SNAI1.

Molecular mechanisms of heterogeneous oligomerization of huntingtin proteins.

There is still no successful strategy to treat Huntington's disease, an inherited autosomal disorder associated with the aggregation of mutated forms of the huntingtin protein containing polyglutamine tracts with more than 36 repeats. Recent experimental evidence is challenging the conventional view of the disease by revealing transcellular transfer of mutated huntingtin proteins which are able to seed oligomers involving wild type forms of the protein. Here we decipher the molecular mechanism of this unconventional heterogeneous oligomerization by performing discrete molecular dynamics simulations.

Sulforaphane Cannot Protect Human Fibroblasts From Repeated, Short and Sublethal Treatments with Hydrogen Peroxide.

A delicate balance of reactive oxygen species (ROS) exists inside the cell: when the mechanisms that control the level of ROS fail, the cell is in an oxidative stress state, a condition that can accelerate aging processes. To contrast the pro-aging effect of ROS, the supplementation of antioxidants has been recently proposed. Sulforaphane (SFN) is an isothiocyanate isolated from Brassica plants that has been shown to modulate many critical factors inside the cells helping to counteract aging processes.

Impact of the cross-talk between circular and messenger RNAs on cell regulation.

Circular RNAs (circRNA) are non-coding RNAs characterized by a closed-loop structure providing increased stability and enhancing their ability to compete with messenger RNAs (mRNA) for microRNA (miRNA) binding. An important open question is if circRNA plays a physiological role in the cells regulating critical cellular functions. We address this question with a combination of theoretical modeling and experimental analysis.

Regeneration in distantly related species: common strategies and pathways.

While almost all animals are able to at least partially replace some lost parts, regeneration abilities vary considerably across species. Here we study gene expression patterns in distantly related species to investigate conserved regeneration strategies. To this end, we collect from the literature transcriptomic data obtained during the regeneration of three species ( and ), and compare them with gene expression during regeneration in vertebrates and mammals.

Speed of evolution in large asexual populations with diminishing returns.

The adaptive evolution of large asexual populations is generally characterized by competition between clones carrying different beneficial mutations. Interference slows down the adaptation speed and makes the theoretical description of the dynamics more complex with respect to the successional occurrence and fixation of beneficial mutations typical of small populations. A simplified modeling framework considering multiple beneficial mutations with equal and constant fitness advantage is known to capture some of the essential features of laboratory evolution experiments.