Ca-dependent vesicular and non-vesicular lipid transfer controls hypoosmotic plasma membrane expansion.

Robust coordination of surface and volume changes is critical for cell integrity. Few studies have elucidated the plasma membrane (PM) remodeling events during cell surface and volume alteration, especially regarding PM sensing and its subsequent rearrangements. Here, using fission yeast protoplasts, we reveal a Ca-dependent mechanism for membrane addition that ensures PM integrity and allows its expansion during acute hypoosmotic cell swelling.

Cdc42 mobility and membrane flows regulate fission yeast cell shape and survival.

Polarized exocytosis induced by local Cdc42 GTPase activity results in membrane flows that deplete low-mobility membrane-associated proteins. A reaction-diffusion particle model comprising Cdc42 positive feedback activation, hydrolysis by GTPase-activating proteins (GAPs), and flow-induced displacement by exo/endocytosis shows that flow-induced depletion of low mobility GAPs promotes polarization. We modified Cdc42 mobility in Schizosaccharomyces pombe by replacing its prenylation site with 1, 2 or 3 repeats of the Rit C-terminal membrane-binding domain (ritC), yielding alleles with progressively lower mobility and increased flow-coupling.

Myosin-I synergizes with Arp2/3 complex to enhance the pushing forces of branched actin networks.

Class I myosins (myosin-Is) colocalize with Arp2/3 complex-nucleated actin networks at sites of membrane protrusion and invagination, but the mechanisms by which myosin-I motor activity coordinates with branched actin assembly to generate force are unknown. We mimicked the interplay of these proteins using the "comet tail" bead motility assay, where branched actin networks are nucleated by the Arp2/3 complex on the surface of beads coated with myosin-I and nucleation-promoting factor. We observed that myosin-I increased bead movement efficiency by thinning actin networks without affecting growth rates.

Myosin-I Synergizes with Arp2/3 Complex to Enhance Pushing Forces of Branched Actin Networks.

Myosin-Is colocalize with Arp2/3 complex-nucleated actin networks at sites of membrane protrusion and invagination, but the mechanisms by which myosin-I motor activity coordinates with branched actin assembly to generate force are unknown. We mimicked the interplay of these proteins using the "comet tail" bead motility assay, where branched actin networks are nucleated by Arp2/3 complex on the surface of beads coated with myosin-I and the WCA domain of N-WASP. We observed that myosin-I increased bead movement efficiency by thinning actin networks without affecting growth rates.

Nivolumab-Induced Lichen Planopilaris: Case Report and Literature Review of Hair Disorders Associated with Targeted Oncological Therapies.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapies. Their mechanism promotes a cytotoxic T-cell activation against the tumor cells, but as a consequence, immune-mediated toxicities are increasingly being identified. Cutaneous immune-mediated adverse events (AE) occur in 32% of patients, with possible higher grade AEs seen with anti-programmed cell death protein 1, such as nivolumab.

Force transmission by retrograde actin flow-induced dynamic molecular stretching of Talin.

Force transmission at integrin-based adhesions is important for cell migration and mechanosensing. Talin is an essential focal adhesion (FA) protein that links F-actin to integrins. F-actin constantly moves on FAs, yet how Talin simultaneously maintains the connection to F-actin and transmits forces to integrins remains unclear.

Force transmission by retrograde actin flow-induced dynamic molecular stretching of Talin.

Force transmission at integrin-based adhesions is important for cell migration and mechanosensing. Talin is an essential focal adhesion (FA) protein that links F-actin to integrins. F-actin constantly moves on FAs, yet how Talin simultaneously maintains the connection to F-actin and transmits forces to integrins remains unclear.

Cdc42 mobility and membrane flows regulate fission yeast cell shape and survival.

Local Cdc42 GTPase activation promotes polarized exocytosis, resulting in membrane flows that deplete low-mobility membrane-associated proteins from the growth region. To investigate the self-organizing properties of the Cdc42 secretion-polarization system under membrane flow, we developed a reaction-diffusion particle model. The model includes positive feedback activation of Cdc42, hydrolysis by GTPase-activating proteins (GAPs), and flow-induced displacement by exo/endocytosis.

Compressive forces stabilize microtubules in living cells.

Microtubules are cytoskeleton components with unique mechanical and dynamic properties. They are rigid polymers that alternate phases of growth and shrinkage. Nonetheless, the cells can display a subset of stable microtubules, but it is unclear whether microtubule dynamics and mechanical properties are related.

Global pattern in hunger and educational opportunity: a multilevel analysis of child hunger and TIMSS mathematics achievement.

In low-income countries, there exists a common concern about the effect of hunger and food insecurity on educational outcomes. However, income inequalities, economic slowdown, conflict, and climate change have raised those concerns globally. Yet, little is known about how widespread the problem of hunger in schools is worldwide.

Motion-robust, blood-suppressed, reduced-distortion diffusion MRI of the liver.

Purpose: To evaluate feasibility and reproducibility of liver diffusion-weighted (DW) MRI using cardiac-motion-robust, blood-suppressed, reduced-distortion techniques.

Methods: DW-MRI data were acquired at 3T in an anatomically accurate liver phantom including controlled pulsatile motion, in eight healthy volunteers and four patients with known or suspected liver metastases. Standard monopolar and motion-robust (M1-nulled, and M1-optimized) DW gradient waveforms were each acquired with single-shot echo-planar imaging (ssEPI) and multishot EPI (msEPI).

Multistage Testing in Heterogeneous Populations: Some Design and Implementation Considerations.

A central challenge in international large-scale assessments is adequately measuring dozens of highly heterogeneous populations, many of which are low performers. To that end, multistage adaptive testing offers one possibility for better assessing across the achievement continuum. This study examines the way that several multistage test design and implementation choices can impact measurement performance in this setting.

Prevalence of wound complications following Mohs micrographic surgery (MMS): a cross-sectional study of 1000 patients undergoing MMS and wound repair in a UK teaching hospital.

Background: Mohs micrographic surgery (MMS) for nonmelanoma skin cancer is often quoted as having an excellent safety profile.

Aim: To determine the complication rate of patients undergoing MMS in a large UK Mohs unit and subdivide complication rates into mild/intermediate and major, and to identify potential risk factors necessitating a clinical intervention.

Methods: This was a single-centre, cross-sectional study of 1000 consecutive cases of MMS performed with in-house repair.

Discrete mechanical model of lamellipodial actin network implements molecular clutch mechanism and generates arcs and microspikes.

Mechanical forces, actin filament turnover, and adhesion to the extracellular environment regulate lamellipodial protrusions. Computational and mathematical models at the continuum level have been used to investigate the molecular clutch mechanism, calculating the stress profile through the lamellipodium and around focal adhesions. However, the forces and deformations of individual actin filaments have not been considered while interactions between actin networks and actin bundles is not easily accounted with such methods.

Cell patterning by secretion-induced plasma membrane flows.

Cells self-organize using reaction-diffusion and fluid-flow principles. Whether bulk membrane flows contribute to cell patterning has not been established. Here, using mathematical modeling, optogenetics, and synthetic probes, we show that polarized exocytosis causes lateral membrane flows away from regions of membrane insertion.

Characterization and correction of cardiovascular motion artifacts in diffusion-weighted imaging of the pancreas.

Purpose: To assess the effects of cardiovascular-induced motion on conventional DWI of the pancreas and to evaluate motion-robust DWI methods in a motion phantom and healthy volunteers.

Methods: 3T DWI was acquired using standard monopolar and motion-compensated gradient waveforms, including in an anatomically accurate pancreas phantom with controllable compressive motion and healthy volunteers (n = 8, 10). In volunteers, highly controlled single-slice DWI using breath-holding and cardiac gating and whole-pancreas respiratory-triggered DWI were acquired.

Enhancement of cerebrovascular 4D flow MRI velocity fields using machine learning and computational fluid dynamics simulation data.

Blood flow metrics obtained with four-dimensional (4D) flow phase contrast (PC) magnetic resonance imaging (MRI) can be of great value in clinical and experimental cerebrovascular analysis. However, limitations in both quantitative and qualitative analyses can result from errors inherent to PC MRI. One method that excels in creating low-error, physics-based, velocity fields is computational fluid dynamics (CFD).

Assessment of sex differences in ventricular-vascular coupling of left ventricular and aortic flow derived from 4D flow MRI in healthy, young adults.

To gain further insight into male-female differences in cardiovascular conditions it is important to understand sex differences in healthy populations. A previous study from our group of 39 healthy young volunteers (20-35 years) paradoxically found that men had greater left ventricular (LV) kinetic energy (KE) but women had greater LV vorticity. We reanalyzed cardiac four-dimensional flow MRI data from 20 of the original subjects (10 male and 10 female) to quantify aortic flow in addition to LV flow.

A pilot study of bladder voiding with real-time MRI and computational fluid dynamics.

Lower urinary track symptoms (LUTS) affect many older adults. Multi-channel urodynamic studies provide information about bladder pressure and urinary flow but offer little insight into changes in bladder anatomy and detrusor muscle function. Here we present a novel method for real time MRI during bladder voiding.

Intracranial vascular flow oscillations in Alzheimer's disease from 4D flow MRI.

Recent modeling and experimental evidence suggests clearance of soluble metabolites from the brain can be driven by low frequency flow oscillations (LFOs) through the intramural periarterial drainage (IPAD) pathway. This study investigates the use of 4D flow MRI to derive LFOs from arterial and venous measures of blood flow. 3D radial 4D flow MRI data were acquired on a 3.

Fission Yeast Polarization: Modeling Cdc42 Oscillations, Symmetry Breaking, and Zones of Activation and Inhibition.

Cells polarize for growth, motion, or mating through regulation of membrane-bound small GTPases between active GTP-bound and inactive GDP-bound forms. Activators (GEFs, GTP exchange factors) and inhibitors (GAPs, GTPase activating proteins) provide positive and negative feedbacks. We show that a reaction-diffusion model on a curved surface accounts for key features of polarization of model organism fission yeast.

Inhibition of Shh Signaling through MAPK Activation Controls Chemotherapy-Induced Alopecia.

Chemotherapy-induced hair loss (alopecia) (CIA) remains a major unsolved problem in clinical oncology. CIA is often considered to be a consequence of the antimitotic and apoptosis-promoting properties of chemotherapy drugs acting on rapidly proliferating hair matrix keratinocytes. Here, we show that in a mouse model of CIA, the downregulation of Shh signaling in the hair matrix is a critical early event.

Sex Differences in Cardiac Flow Dynamics of Healthy Volunteers.

Purpose: The purpose of this study was to further understand the relationship between cardiac function and flow, on the basis of sex, by quantifying cardiac flow characteristics and relating them to cardiac muscle performance in young adults.

Materials And Methods: In this cross-sectional study, cardiac four-dimensional flow (4D flow) magnetic resonance imaging (MRI) and two-dimensional cine MRI were performed on 20 male and 19 female volunteers aged 20-35. Velocity-based metrics of flow, kinetic energy, vorticity, and efficiency indices were quantified, as well as cardiac strain metrics.