Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels.

Pancreatic stellate cells (PSCs) are primarily responsible for producing the stiff tumor tissue in pancreatic ductal adenocarcinoma (PDAC). Thereby, PSCs generate a stiffness gradient between the healthy pancreas and the tumor. This gradient induces durotaxis, a form of directional cell migration driven by differential stiffness. The molecular sensors behind durotaxis are still unclear. To investigate the role of mechanosensitive ion channels in PSC durotaxis, we established a two-dimensional stiffness gradient mimicking PDAC. Using pharmacological and genetic methods, we investigated the role of the ion channels Piezo1, TRPC1, and TRPV4 in PSC durotaxis. We found that PSC migration towards a stiffer substrate is diminished by altering Piezo1 activity. Moreover, disrupting TRPC1 along with TRPV4 abolishes PSC durotaxis even when Piezo1 is functional. Hence, PSC durotaxis is optimal with an intermediary level of mechanosensitive channel activity, which we simulated using a numerically discretized mathematical model. Our findings suggest that mechanosensitive ion channels, particularly Piezo1, detect the mechanical microenvironment to guide PSC migration.

Midterm outcomes of a short-cemented bipolar radial head arthroplasty, in a cohort of 56 cases with minimum 2-years follow-up.

BACKGROUND: Radial head prostheses are used in comminuted radial head fractures for elbow stabilisation when reduction and internal fixation is not possible. Several implant designs exist, but no large series exist about a short-cemented and bipolar implant. HYPOTHESIS: The hypothesis was that this prosthesis design shows good clinical, functional, and radiological results, with acceptable rate of complications. STUDY DESIGN: This retrospective study included the prostheses with bipolar design and short-cemented stem (Evolutive™), with a minimum 2-years follow-up. MATERIALS AND METHODS: All prosthesis implanted in our Traumatology Center were included, with minimum 2-years follow-up. The evaluation consisted of a clinical and functional evaluation, associated with an independent radiographic assessment. All complications were listed, as long as rate and reasons for implant removal. RESULTS: Fifty-six implants were studied with a mean follow-up of 64.9months (24 to 119). Fifty-three cases were acute injuries with 16% isolated radial head fractures and 76% complex elbow injury such as ulno-humeral, radio-ulnar or longitudinal forearm instability. Fifty (89%) implants were still in place at last follow-up. The main reason for implant removal was during arthrolysis procedure. Ranges of motion were: 126° in flexion, 9° of extension loss, 76° of pronation and 79° of supination. Mean Mayo Elbow Performance Index was 84.1 with 72% of excellent or good results, and the median quick-DASH was rated 18.2. Radiographic evaluation found 12% significant ulno-humeral arthtitis, 64% capitellar osteopenia and 12% loosening. We recorded 5% of implant-related complications. DISCUSSION: The short-cemented stem bipolar radial head prosthesis presents clinical and functional results similar to other radial head prosthesis with low incidence of elbow arthritis, when treating both isolated radial head fracture or complexes elbow injury. This implant should therefore be valid for treating comminuted radial head fractures in all types of traumatological injuries. LEVEL OF EVIDENCE: IV; Retrospective cohort study.

Interactions between Fermi polarons in monolayer WS2.

Interactions between quasiparticles are of fundamental importance and ultimately determine the macroscopic properties of quantum matter. A famous example is the phenomenon of superconductivity, which arises from attractive electron-electron interactions that are mediated by phonons or even other more exotic fluctuations in the material. Here we introduce mobile exciton impurities into a two-dimensional electron gas and investigate the interactions between the resulting Fermi polaron quasiparticles. We employ multi-dimensional coherent spectroscopy on monolayer WS2, which provides an ideal platform for determining the nature of polaron-polaron interactions due to the underlying trion fine structure and the valley specific optical selection rules. At low electron doping densities, we find that the dominant interactions are between polaron states that are dressed by the same Fermi sea. In the absence of bound polaron pairs (bipolarons), we show using a minimal microscopic model that these interactions originate from a phase-space filling effect, where excitons compete for the same electrons. We furthermore reveal the existence of a bipolaron bound state with remarkably large binding energy, involving excitons in different valleys cooperatively bound to the same electron. Our work lays the foundation for probing and understanding strong electron correlation effects in two-dimensional layered structures such as moiré superlattices.

WITHDRAWN: Midterm outcomes of a short cemented bipolar radial head arthroplasty, in a cohort of 56 cases with minimum 2-years follow-up.

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Graded titin cleavage progressively reduces tension and uncovers the source of A-band stability in contracting muscle.

The giant muscle protein titin is a major contributor to passive force; however, its role in active force generation is unresolved. Here, we use a novel titin-cleavage (TC) mouse model that allows specific and rapid cutting of elastic titin to quantify how titin-based forces define myocyte ultrastructure and mechanics. We show that under mechanical strain, as TC doubles from heterozygous to homozygous TC muscles, Z-disks become increasingly out of register while passive and active forces are reduced. Interactions of elastic titin with sarcomeric actin filaments are revealed. Strikingly, when titin-cleaved muscles contract, myosin-containing A-bands become split and adjacent myosin filaments move in opposite directions while also shedding myosins. This establishes intact titin filaments as critical force-transmission networks, buffering the forces observed by myosin filaments during contraction. To perform this function, elastic titin must change stiffness or extensible length, unveiling its fundamental role as an activation-dependent spring in contracting muscle.

Signatures of spatially correlated noise and non-secular effects in two-dimensional electronic spectroscopy.

We investigate how correlated fluctuations affect oscillatory features in rephasing and non-rephasing two-dimensional (2D) electronic spectra of a model dimer system. Based on a beating map analysis, we show that non-secular environmental couplings induced by uncorrelated fluctuations lead to oscillations centered at both cross- and diagonal-peaks in rephasing spectra as well as in non-rephasing spectra. Using an analytical approach, we provide a quantitative description of the non-secular effects in terms of the Feynman diagrams and show that the environment-induced mixing of different inter-excitonic coherences leads to oscillations in the rephasing diagonal-peaks and non-rephasing cross-peaks. We demonstrate that as correlations in the noise increase, the lifetime of oscillatory 2D signals is enhanced at rephasing cross-peaks and non-rephasing diagonal-peaks, while the other non-secular oscillatory signals are suppressed. We discuss that the asymmetry of 2D lineshapes in the beating map provides information on the degree of correlations in environmental fluctuations. Finally we investigate how the oscillatory features in 2D spectra are affected by inhomogeneous broadening.

Bloch-Redfield equations for modeling light-harvesting complexes.

We challenge the misconception that Bloch-Redfield equations are a less powerful tool than phenomenological Lindblad equations for modeling exciton transport in photosynthetic complexes. This view predominantly originates from an indiscriminate use of the secular approximation. We provide a detailed description of how to model both coherent oscillations and several types of noise, giving explicit examples. All issues with non-positivity are overcome by a consistent straightforward physical noise model. Herein also lies the strength of the Bloch-Redfield approach because it facilitates the analysis of noise-effects by linking them back to physical parameters of the noise environment. This includes temporal and spatial correlations and the strength and type of interaction between the noise and the system of interest. Finally, we analyze a prototypical dimer system as well as a 7-site Fenna-Matthews-Olson complex in regards to spatial correlation length of the noise, noise strength, temperature, and their connection to the transfer time and transfer probability.