Machine learning and artificial intelligence: Enabling the clinical translation of atomic force microscopy-based biomarkers for cancer diagnosis.

The influence of biomechanics on cell function has become increasingly defined over recent years. Biomechanical changes are known to affect oncogenesis; however, these effects are not yet fully understood. Atomic force microscopy (AFM) is the gold standard method for measuring tissue mechanics on the micro- or nano-scale.

Retinoic acid receptor β modulates mechanosensing and invasion in pancreatic cancer cells via myosin light chain 2.

Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness and high metastatic rate. Retinoids, compounds derived from vitamin A, have a history of clinical use in cancer for their anti-proliferative and differentiation effects, and more recently have been explored as anti-stromal therapies in PDAC for their ability to induce mechanical quiescence in cancer associated fibroblasts. Here, we demonstrate that retinoic acid receptor β (RAR-β) transcriptionally represses myosin light chain 2 (MLC-2) expression in pancreatic cancer cells.

Modulation of sirtuins during monolayer chondrocyte culture influences cartilage regeneration upon transfer to a 3D culture environment.

This study examined the role of sirtuins in the regenerative potential of articular chondrocytes. Sirtuins (SIRT1-7) play a key role in regulating cartilage homeostasis. By inhibiting pro-inflammatory pathways responsible for cartilage degradation and promoting the expression of key matrix components, sirtuins have the potential to drive a favourable balance between anabolic and catabolic processes critical to regenerative medicine.

Covariation of Pluripotency Markers and Biomechanical Properties in Mouse Embryonic Stem Cells.

Pluripotent cells are subject to much interest as a source of differentiated cellular material for research models, regenerative medical therapies and novel applications such as lab-cultured meat. Greater understanding of the pluripotent state and control over its differentiation is therefore desirable. The role of biomechanical properties in directing cell fate and cell behavior has been increasingly well described in recent years.

A Biomimetic High Throughput Model of Cancer Cell Spheroid Dissemination onto Aligned Fibrillar Collagen.

Cell dissemination during tumor development is a characteristic of cancer metastasis. Dissemination from three-dimensional spheroid models on extracellular matrices designed to mimic tissue-specific physiological microenvironments may allow us to better elucidate the mechanism behind cancer metastasis and the response to therapeutic agents. The orientation of fibrillar collagen plays a key role in cellular processes and mediates metastasis through contact-guidance.

Micromirror Total Internal Reflection Microscopy for High-Performance Single Particle Tracking at Interfaces.

Single particle tracking has found broad applications in the life and physical sciences, enabling the observation and characterization of nano- and microscopic motion. Fluorescence-based approaches are ideally suited for high-background environments, such as tracking lipids or proteins in or on cells, due to superior background rejection. Scattering-based detection is preferable when localization precision and imaging speed are paramount due to the in principle infinite photon budget.

Pancreatic Ductal Adenocarcinoma: Relating Biomechanics and Prognosis.

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and carries a dismal prognosis. Resectable patients are treated predominantly with surgery while borderline resectable patients may receive neoadjuvant treatment (NAT) to downstage their disease prior to possible resection. PDAC tissue is stiffer than healthy pancreas, and tissue stiffness is associated with cancer progression.

Corrigendum: Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models.

[This corrects the article DOI: 10.3389/fbioe.2020.

Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models.

Organ-on-chip (OOC) systems recapitulate key biological processes and responses exhibited by cells, tissues, and organs . Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury.

Attachment and antibiotic response of early-stage biofilms studied using resonant hyperspectral imaging.

Many bacterial species readily develop biofilms that act as a protective matrix against external challenge, e.g., from antimicrobial treatment.

G Protein-Coupled Estrogen Receptor Regulates Actin Cytoskeleton Dynamics to Impair Cell Polarization.

Mechanical forces regulate cell functions through multiple pathways. G protein-coupled estrogen receptor (GPER) is a seven-transmembrane receptor that is ubiquitously expressed across tissues and mediates the acute cellular response to estrogens. Here, we demonstrate an unidentified role of GPER as a cellular mechanoregulator.

Simulating the evolutionary trajectories of metabolic pathways for insect symbionts in the genus .

Insect-bacterial symbioses are ubiquitous, but there is still much to uncover about how these relationships establish, persist and evolve. The tsetse endosymbiont displays intriguing metabolic adaptations to its microenvironment, but the process by which this relationship evolved remains to be elucidated. The recent chance discovery of the free-living species of the genus , , provides a serendipitous starting point from which to investigate the evolution of this symbiosis.

GPER Activation Inhibits Cancer Cell Mechanotransduction and Basement Membrane Invasion via RhoA.

The invasive properties of cancer cells are intimately linked to their mechanical phenotype, which can be regulated by intracellular biochemical signalling. Cell contractility, induced by mechanotransduction of a stiff fibrotic matrix, and the epithelial-mesenchymal transition (EMT) promote invasion. Metastasis involves cells pushing through the basement membrane into the stroma-both of which are altered in composition with cancer progression.

Large-scale urban underground hydro-thermal modelling - A case study of the Royal Borough of Kensington and Chelsea, London.

The shallow subsurface of dense cities is increasingly exploited for various purposes due to the significant rise in urban populations. Past research has shown that underground activities have a significant impact on local subsurface temperatures. However, the resulting spatial variability of ground temperature elevations on a city-scale is not well understood due to the lack of sufficient information and modelling complexity at such large scales.

An in vitro investigation of the inflammatory response to the strain amplitudes which occur during high frequency oscillation ventilation and conventional mechanical ventilation.

Children randomised in the neonatal period to high frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) in the United Kingdom Oscillation study (UKOS) had superior lung function at 11 to 14 years of age. During HFOV, much smaller tidal volumes, but a higher mean airway distending pressure is delivered, hence, a possible explanation for a volume dependent effect on long term lung function could be an increase in inflammation in response to higher tidal volumes and strains. We tested that hypothesis by assessing interleukin-6 (IL-6) and -8 (IL-8) release from A549 alveolar analogue cells following biaxial mechanical strain applied at 0.

Multiparameter antibiotic resistance detection based on hydrodynamic trapping of individual E. coli.

There is an urgent need to develop novel methods for assessing the response of bacteria to antibiotics in a timely manner. Antibiotics are traditionally assessed via their effect on bacteria in a culture medium, which takes 24-48 h and exploits only a single parameter, i.e.

A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Metabolism, and Host Diet.

The tsetse fly is the insect vector for the parasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium, The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model of metabolism. The model enabled the design and experimental verification of a defined medium that supports growth This has been used subsequently to analyze aspects of metabolism, revealing multiple unique adaptations of the symbiont to its environment.

Tamoxifen mechanically deactivates hepatic stellate cells via the G protein-coupled estrogen receptor.

Tamoxifen has been used for many years to target estrogen receptor signalling in breast cancer cells. Tamoxifen is also an agonist of the G protein-coupled estrogen receptor (GPER), a GPCR ubiquitously expressed in tissues that mediates the acute response to estrogens. Here we report that tamoxifen promotes mechanical quiescence in hepatic stellate cells (HSCs), stromal fibroblast-like cells whose activation triggers and perpetuates liver fibrosis in hepatocellular carcinomas.

GPER is a mechanoregulator of pancreatic stellate cells and the tumor microenvironment.

The mechanical properties of the tumor microenvironment are emerging as attractive targets for the development of therapies. Tamoxifen, an agonist of the G protein-coupled estrogen receptor (GPER), is widely used to treat estrogen-positive breast cancer. Here, we show that tamoxifen mechanically reprograms the tumor microenvironment through a newly identified GPER-mediated mechanism.

Tamoxifen mechanically reprograms the tumor microenvironment via HIF-1A and reduces cancer cell survival.

The tumor microenvironment is fundamental to cancer progression, and the influence of its mechanical properties is increasingly being appreciated. Tamoxifen has been used for many years to treat estrogen-positive breast cancer. Here we report that tamoxifen regulates the level and activity of collagen cross-linking and degradative enzymes, and hence the organization of the extracellular matrix, via a mechanism involving both the G protein-coupled estrogen receptor (GPER) and hypoxia-inducible factor-1 alpha (HIF-1A).

Retinoic Acid Receptor-β Is Downregulated in Hepatocellular Carcinoma and Cirrhosis and Its Expression Inhibits Myosin-Driven Activation and Durotaxis in Hepatic Stellate Cells.

Hepatic stellate cells (HSCs) are essential perisinusoidal cells in both healthy and diseased liver. HSCs modulate extracellular matrix (ECM) homeostasis when quiescent, but in liver fibrosis, HSCs become activated and promote excess deposition of ECM molecules and tissue stiffening via force generation and mechanosensing. In hepatocellular carcinoma (HCC), activated HSCs infiltrate the stroma and migrate to the tumor core to facilitate paracrine signaling with cancer cells.

Is photography-based taxonomy really inadequate, unnecessary, and potentially harmful for biological sciences? A reply to Ceríaco et al. (2016).

An opinion piece was recently published in this journal which, remarkably, is less than one page in length, but has 493 authors (signatories) and has gained over 15 thousand reads on ResearchGate in a very short time. Ceríaco et al. (2016) argue for a blanket ban to be imposed on the uncommon practice of basing new species descriptions in zoology on photographic evidence only of the animal.