Infiltration of tumor spheroids by activated immune cells.

Recent years have seen a tremendous growth of interest in understanding the role that the adaptive immune system could play in interdicting tumor progression. In this context, it has been shown that the density of adaptive immune cells inside a solid tumor serves as a favorable prognostic marker across different types of cancer. The exact mechanisms underlying the degree of immune cell infiltration is largely unknown.

Effects of Physiological and Pathological Urea Concentrations on Human Microvascular Endothelial Cells.

Urea is the uremic toxin accumulating with the highest concentration in the plasma of chronic kidney disease (CKD) patients, not being completely cleared by dialysis. Urea accumulation is reported to exert direct and indirect side effects on the gastrointestinal tract, kidneys, adipocytes, and cardiovascular system (CVS), although its pathogenicity is still questioned since studies evaluating its side effects lack homogeneity. Here, we investigated the effects of physiological and pathological urea concentrations on a human endothelial cell line from the microcirculation (Human Microvascular Endothelial Cells-1, HMEC-1).

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.

FLIM-FRET Investigation of Heterogeneous Huntingtin Aggregation in HeLa Cells.

Fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) technique is a novel tool to study protein-protein interaction combining FRET detection, lifetime measurements, and high-resolution imaging. This chapter describes a FLIM-FRET protocol for the detection and quantification of heterogeneous huntingtin aggregates in HeLa cells co-transfected with huntingtin variants containing polyglutamine tracts of different lengths.

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.

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.

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.

Metamaterial architecture from a self-shaping carnivorous plant.

As meticulously observed and recorded by Darwin, the leaves of the carnivorous plant L. slowly fold around insects trapped on their sticky surface in order to ensure their digestion. While the biochemical signaling driving leaf closure has been associated with plant growth hormones, how mechanical forces actuate the process is still unknown.

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.

From jamming to collective cell migration through a boundary induced transition.

Cell monolayers provide an interesting example of active matter, exhibiting a phase transition from flowing to jammed states as they age. Here we report experiments and numerical simulations illustrating how a jammed cellular layer rapidly reverts to a flowing state after a wound. Quantitative comparison between experiments and simulations shows that cells change their self-propulsion and alignment strength so that the system crosses a phase transition line, which we characterize by finite-size scaling in an active particle model.

Preferential myofibroblast differentiation of cardiac mesenchymal progenitor cells in the presence of atrial fibrillation.

Atrial fibrillation (AF) is characterized by electrical, contractile, and structural remodeling mediated by interstitial fibrosis. It has been shown that human cardiac mesenchymal progenitor cells (CMPCs) can be differentiated into endothelial, smooth muscle, and fibroblast cells. Here, we have investigated, for the first time, the contribution of CMPCs in the fibrotic process occurring in AF.

Cholesterol impairment contributes to neuroserpin aggregation.

Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer's and Parkinson's diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins.