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It has long been proposed that the cell cycle is regulated by physical forces at the cell–cell and cell–extracellular matrix (ECM) interfaces 1 – 12 . However, the evolution of these forces during the cycle has never been measured in a tissue, and whether this evolution affects cell cycle progression is unknown. Here, we quantified cell–cell tension and cell–ECM traction throughout the complete cycle of a large cell population in a growing epithelium. These measurements unveil temporal mechanical patterns that span the entire cell cycle and regulate its duration, the G1–S transition and mitotic rounding. Cells subjected to higher intercellular tension exhibit a higher probability to transition from G1 to S, as well as shorter G1 and S–G2–M phases. Moreover, we show that tension and mechanical energy are better predictors of the duration of G1 than measured geometric properties. Tension increases during the cell cycle but decreases 3 hours before mitosis. Using optogenetic control of contractility, we show that this tension drop favours mitotic rounding. Our results establish that cell cycle progression is regulated cooperatively by forces between the dividing cell and its neighbours. Monitoring growing epithelial cells through the cell cycle, Uroz et al. find that cell–cell tension and cell–matrix traction forces differ across the cell cycle and affect cell cycle duration, the G1–S transition and mitotic rounding.

Dynamics of epithelial tissues determine key processes in development, tissue healing and cancer invasion. These processes are critically influenced by cell–cell adhesion forces. However, the identity of the proteins that resist and transmit forces at cell–cell junctions remains unclear, and how these proteins control tissue dynamics is largely unknown. Here we provide a systematic study of the interplay between cell–cell adhesion proteins, intercellular forces and epithelial tissue dynamics. We show that collective cellular responses to selective perturbations of the intercellular adhesome conform to three mechanical phenotypes. These phenotypes are controlled by different molecular modules and characterized by distinct relationships between cellular kinematics and intercellular forces. We show that these forces and their rates can be predicted by the concentrations of cadherins and catenins. Unexpectedly, we identified different mechanical roles for P-cadherin and E-cadherin; whereas P-cadherin predicts levels of intercellular force, E-cadherin predicts the rate at which intercellular force builds up. Trepat and colleagues conduct a systematic analysis of how key cell–cell adhesion molecules affect intercellular forces and epithelial monolayer dynamics.

Despite the increasing popularity of doctoral education, many students do not complete their studies, and very little information is available about them. Understanding why some students consider that they do not want to, or cannot, continue with their studies is essential to reduce dropout rates and to improve the overall quality of doctoral programmes. This study focuses on the motives students give for considering dropping out of their doctoral degree. Participants were 724 social sciences doctoral students from 56 Spanish universities, who responded to a questionnaire containing doctoral degree conditions questions and an open-ended question on motives for dropping out. Results showed that a third of the sample, mainly the youngest, female and part time students, stated that they had intended to drop out. The most frequent motives for considering dropping out were difficulties in achieving a balance between work, personal life and doctoral studies and problems with socialization. Overall, results offer a complex picture that has implications for the design of doctoral programmes, such as the conditions and demands of part-time doctoral studies or the implementation of educational proposals that facilitate students' academic and personal integration into the scientific community in order to prevent the development of a culture of institutional neglect.

•Organic forms of magnesium are more bioavailable than inorganic forms.•Magnesium citrate's percentage of absorption is dose dependent.•The tissue distribution of magnesium depends on the form administered.•All magnesium supplements can maintain physiological levels in healthy people. The market for food supplements is booming thanks to their increased consumption. European regulations include different ways in which vitamins and minerals are administered, without making it clear to the consumer whether one formulation has advantages over the other. The aim of this review was to compare the bioavailability of different forms of magnesium and analyze the differences between them. Based on a PICO (population, intervention, comparison, outcome) research question, a search strategy was established for magnesium bioavailability studies comparing different forms in the PubMed, Cochrane, Web of Science, and Scopus databases. We found 433 studies, out of which 14 were finally selected. Inorganic formulations appear to be less bioavailable than organic ones, and the percentage of absorption is dose dependent. All magnesium dietary supplements can maintain physiological levels in healthy people without prior deficit, although this cannot be assured in older people or those with illnesses or previous subphysiological levels.

Network analysis is currently used in a myriad of contexts, from identifying potential drug targets to predicting the spread of epidemics and designing vaccination strategies and from finding friends to uncovering criminal activity. Despite the promise of the network approach, the reliability of network data is a source of great concern in all fields where complex networks are studied. Here, we present a general mathematical and computational framework to deal with the problem of data reliability in complex networks. In particular, we are able to reliably identify both missing and spurious interactions in noisy network observations. Remarkably, our approach also enables us to obtain, from those noisy observations, network reconstructions that yield estimates of the true network properties that are more accurate than those provided by the observations themselves. Our approach has the potential to guide experiments, to better characterize network data sets, and to drive new discoveries.

The colligative properties of ATP and catecholamines demonstrated in vitro are thought to be responsible for the extraordinary accumulation of solutes inside chromaffin cell secretory vesicles, although this has yet to be demonstrated in living cells. Because functional cells cannot be deprived of ATP, we have knocked down the expression of the vesicular nucleotide carrier, the VNUT, to show that a reduction in vesicular ATP is accompanied by a drastic fall in the quantal release of catecholamines. This phenomenon is particularly evident in newly synthesized vesicles, which we show are the first to be released. Surprisingly, we find that inhibiting VNUT expression also reduces the frequency of exocytosis, whereas the overexpression of VNUT drastically increases the quantal size of exocytotic events. To our knowledge, our data provide the first demonstration that ATP, in addition to serving as an energy source and purinergic transmitter, is an essential element in the concentration of catecholamines in secretory vesicles. In this way, cells can use ATP to accumulate neurotransmitters and other secreted substances at high concentrations, supporting quantal transmission.

Can we help predict the future impact of researchers using early-career factors? We analyze early-career factors of the world’s 100 most prominent researchers across 8 scientific fields and identify four key drivers in researchers’ initial career: working at a top 25 ranked university, publishing a paper in a top 5 ranked journal, publishing most papers in top quartile (high-impact) journals and co-authoring with other prominent researchers in their field. We find that over 95% of prominent researchers across multiple fields had at least one of these four features in the first 5 years of their career. We find that the most prominent scientists who had an early career advantage in terms of citations and h-index are more likely to have had all four features, and that this advantage persists throughout their career after 10, 15 and 20 years. Our findings show that these few early-career factors help predict researchers’ impact later in their careers. Our research thus points to the need to enhance fairness and career mobility among scientists who have not had a jump start early on.

Triple-Negative Breast Cancer (TNBC) presents a significant challenge due to its aggressiveness and lack of targeted therapies. Understanding the interaction between TNBC cells and the extracellular matrix (ECM) in three-dimensional (3D) culture systems is vital for developing accurate in vitro models. This study explores the impact of electrospinning setup orientation, solvent selection, and polymer composition on scaffold design and TNBC cell culture. Various polystyrene (PS) and poly-ε-caprolactone (PCL) combinations were electrospun using different solvent combinations (dichloromethane/dimethylformamide (DCM/DMF), tetrahydrofuran/dimethylformamide (THF/DMF), chloroform/dichloromethane (Chl/DCM) and acetone) and setup orientations (vertical, horizontal). Scaffolds were characterized using Scanning Electron Microscopy (SEM) to assess fiber diameter and pore size. Cell proliferation and morphology were analyzed through MTT assay, SEM and Confocal Laser Scanning Microscopy (CLSM). Pore area and fiber diameter were influenced by solvent combination (THF/DMF < DCM/DMF < acetone < Chl/DCM) and orientation setup (horizontal < vertical). Sterilization assay revealed that 1-hour immersion in 70% ethanol followed by 30 min ultra-violet (UV) light exposure achieved sterilization with minimal scaffold degradation. High proliferation with no significant reduction compared to monolayer culture was found in some scaffolds and variability in cell morphology between scaffolds was also detected. Results highlight the critical role of scaffold printing parameters for 3D TNBC cell culture. Electrospun PS/PCL 40/60 scaffolds dissolved in DCM/DMF are promising in vitro models, providing a valuable tool for cancer research.

[Abstract] Background: The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury. Method: Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis. Main results: Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables. Conclusions: Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

Recent advancements in brain stimulation and nanomedicine have ushered in a new era of therapeutic interventions for psychiatric and neurodegenerative disorders. This review explores the cutting-edge innovations in brain stimulation techniques, including their applications in alleviating symptoms of main neurodegenerative disorders and addiction. Deep Brain Stimulation (DBS) is an FDA-approved treatment for specific neurodegenerative disorders, including Parkinson’s Disease (PD), and is currently under evaluation for other conditions, such as Alzheimer’s Disease. This technique has facilitated significant advancements in understanding brain electrical circuitry by enabling targeted brain stimulation and providing insights into neural network function and dysfunction. In reviewing DBS studies, this review places particular emphasis on the underlying main neurotransmitter modifications and their specific brain area location, particularly focusing on the dopaminergic system, which plays a critical role in these conditions. Furthermore, this review delves into the groundbreaking developments in nanomedicine, highlighting how nanotechnology can be utilized to target aberrant signaling in neurodegenerative diseases, with a specific focus on the dopaminergic system. The discussion extends to emerging technologies such as magnetoelectric nanoparticles (MENPs), which represent a novel intersection between nanoformulation and brain stimulation approaches. These innovative technologies offer promising avenues for enhancing the precision and effectiveness of treatments by enabling the non-invasive, targeted delivery of therapeutic agents as well as on-site, on-demand stimulation. By integrating insights from recent research and technological advances, this review aims to provide a comprehensive understanding of how brain stimulation and nanomedicine can be synergistically applied to address complex neuropsychiatric and neurodegenerative disorders, paving the way for future therapeutic strategies.