Balancing limited resources in actin network competition.

In cells, multiple actin networks coexist in a dynamic manner. These networks compete for a common pool of actin monomers and actin-binding proteins. Interestingly, all of these networks manage to coexist despite the strong competition for resources.

Weight Trends After Spinal Cord Stimulation Therapy for Chronic Pain.

Objectives: Spinal cord stimulation (SCS) therapy is an effective treatment for chronic pain, particularly in conditions such as postlaminectomy syndrome and complex regional pain syndrome (CRPS). Rare case reports described significant weight loss in patients who underwent dorsal column SCS therapy for chronic pain. Recently, neuromodulation for obesity has become a novel field for research.

Galvanotactic directionality of cell groups depends on group size.

Motile cells migrate directionally in the electric field in a process known as galvanotaxis, important and under-investigated phenomenon in wound healing and development. We previously reported that individual fish keratocyte cells migrate to the cathode in electric fields, that inhibition of PI3 kinase reverses single cells to the anode, and that large cohesive groups of either unperturbed or PI3K-inhibited cells migrate to the cathode. Here we find that small uninhibited cell groups move to the cathode, while small groups of PI3K-inhibited cells move to the anode.

Gut epithelial electrical cues drive differential localization of enterobacteria.

Salmonella translocate to the gut epithelium via microfold cells lining the follicle-associated epithelium (FAE). How Salmonella localize to the FAE is not well characterized. Here we use live imaging and competitive assays between wild-type and chemotaxis-deficient mutants to show that Salmonella enterica serotype Typhimurium (S.

Cell cycle-dependent centrosome clustering precedes proplatelet formation.

Platelet-producing megakaryocytes (MKs) primarily reside in the bone marrow, where they duplicate their DNA content with each cell cycle resulting in polyploid cells with an intricate demarcation membrane system. While key elements of the cytoskeletal reorganizations during proplatelet formation have been identified, what initiates the release of platelets into vessel sinusoids remains largely elusive. Using a cell cycle indicator, we observed a unique phenomenon, during which amplified centrosomes in MKs underwent clustering following mitosis, closely followed by proplatelet formation, which exclusively occurred in G of interphase.

Focal adhesions are controlled by microtubules through local contractility regulation.

Microtubules regulate cell polarity and migration via local activation of focal adhesion turnover, but the mechanism of this process is insufficiently understood. Molecular complexes containing KANK family proteins connect microtubules with talin, the major component of focal adhesions. Here, local optogenetic activation of KANK1-mediated microtubule/talin linkage promoted microtubule targeting to an individual focal adhesion and subsequent withdrawal, resulting in focal adhesion centripetal sliding and rapid disassembly.

Comparison of Dentatorubrothalamic Tractography Methods Based on the Anatomy of the Rubral Wing.

Background And Objectives: Precise localization of the dentatorubrothalamic (DRT) tract can facilitate anatomic targeting in MRI-guided high-intensity focused ultrasound (HIFU) thalamotomy and thalamic deep brain stimulation for tremor. The anatomic segment of DRT fibers adjacent to the ventral intermediate nucleus of the thalamus (VIM), referred to as the rubral wing (RW), may be directly visualized on the fast gray matter acquisition T1 inversion recovery. We compared reproducibility, lesion overlap, and clinical outcomes when reconstructing the DRT tract using a novel anatomically defined RW region of interest, DRT-RW, to an existing tractography method based on the posterior subthalamic area region of interest (DRT-PSA).

Helical motors and formins synergize to compact chiral filopodial bundles: A theoretical perspective.

Chiral actin bundles have been shown to play an important role in cell dynamics, but our understanding of the molecular mechanisms which combine to generate chirality remains incomplete. To address this, we numerically simulate a crosslinked filopodial bundle under the actions of helical myosin motors and/or formins and examine the collective buckling and twisting of the actin bundle. We first show that a number of proposed mechanisms to buckle polymerizing actin bundles without motor activity fail under biologically-realistic parameters.

Friction patterns guide actin network contraction.

The shape of cells is the outcome of the balance of inner forces produced by the actomyosin network and the resistive forces produced by cell adhesion to their environment. The specific contributions of contractile, anchoring and friction forces to network deformation rate and orientation are difficult to disentangle in living cells where they influence each other. Here, we reconstituted contractile actomyosin networks in vitro to study specifically the role of the friction forces between the network and its anchoring substrate.

Electric field-guided collective motility initiation of large epidermal cell groups.

Recent research has elucidated mechanochemical pathways of single cell polarization, but much less is known about collective motility initiation in adhesive cell groups. We used galvanotactic assays of zebrafish keratocyte cell groups, pharmacological perturbations, electric field switches, particle imaging velocimetry, and cell tracking to show that large cell groups initiate motility in minutes toward the cathode. Interestingly, while PI3K-inhibited single cells are biased toward the anode, inhibiting PI3K does not affect the cathode-directed cell group migration.

Crawling, waving, inch worming, dilating, and pivoting mechanics of migrating cells: Lessons from Ken Jacobson.

Research on the locomotion of single cells on hard, flat surfaces brought insight into the mechanisms of leading-edge protrusion, spatially graded adhesion, front-rear coordination, and how intracellular and traction forces are harnessed to execute various maneuvers. Here, we highlight how, by studying a variety of cell types, shapes, and movements, Ken Jacobson and his collaborators made several discoveries that triggered the mechanistic understanding of cell motility. We then review the recent advancements and current perspectives in this field.

Recycling of the actin monomer pool limits the lifetime of network turnover.

Intracellular organization is largely mediated by actin turnover. Cellular actin networks continuously assemble and disassemble, while maintaining their overall appearance. This behavior, called "dynamic steady state," allows cells to sense and adapt to their environment.

Interrelated effects of chromosome size, mechanics, number, location-orientation and polar ejection force on the spindle accuracy: a 3D computational study.

The search-and-capture model of spindle assembly has been a guiding principle for understanding prometaphase for decades. The computational model presented allows one to address two questions: how rapidly the microtubule-kinetochore connections are made, and how accurate these connections are. In most previous numerical simulations, the model geometry was drastically simplified.

Actin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives.

Deviations from mirror symmetry in the development of bilateral organisms are common but the mechanisms of initial symmetry breaking are insufficiently understood. The actin cytoskeleton of individual cells self-organises in a chiral manner, but the molecular players involved remain essentially unidentified and the relationship between chirality of an individual cell and cell collectives is unclear. Here, we analysed self-organisation of the chiral actin cytoskeleton in individual cells on circular or elliptical patterns, and collective cell alignment in confined microcultures.

Mechanosensation: Capping actin filaments for robustness.

Actin networks adapt to resistance by becoming denser. A recent investigation shows that this mechanosensation relies on a force-sensitive mechanical ratchet of capping actin filaments to reorganize the network. This and other mechanical feedback mechanisms make actin-based protrusion amazingly robust.

F-actin bending facilitates net actomyosin contraction By inhibiting expansion with plus-end-located myosin motors.

Contraction of actomyosin networks underpins important cellular processes including motility and division. The mechanical origin of actomyosin contraction is not fully-understood. We investigate whether contraction arises on the scale of individual filaments, without needing to invoke network-scale interactions.

Dorsal Root Ganglion Stimulation as a Salvage Therapy Following Failed Spinal Cord Stimulation.

Introduction: Spinal cord stimulation (SCS) can provide long-term pain relief for various chronic pain conditions, but some patients have no relief with trial stimulation or lose efficacy over time. To "salvage" relief in patients who do not respond or have lost efficacy, alternative stimulation paradigms or anatomical targets can be considered. Dorsal root ganglion stimulation (DRG-S) has a different mechanism of action and anatomical target than SCS.

Spinal Cord Stimulation: New Waveforms and Technology.

The efficacy of spinal cord stimulation for treating chronic pain has encouraged the development of a wide variety of different technologies for stimulation. In this review, the authors first discuss how parameters of stimulation determine the stimulation waveform. They then discuss new stimulation waveforms, including high frequency and burst stimulation, and the evidence supporting their use.

CellDynaMo-stochastic reaction-diffusion-dynamics model: Application to search-and-capture process of mitotic spindle assembly.

We introduce a Stochastic Reaction-Diffusion-Dynamics Model (SRDDM) for simulations of cellular mechanochemical processes with high spatial and temporal resolution. The SRDDM is mapped into the CellDynaMo package, which couples the spatially inhomogeneous reaction-diffusion master equation to account for biochemical reactions and molecular transport within the Langevin Dynamics (LD) framework to describe dynamic mechanical processes. This computational infrastructure allows the simulation of hours of molecular machine dynamics in reasonable wall-clock time.

A broad and variable lumbosacral myotome map uncovered by foraminal nerve root stimulation.

Objective: The human myotome is fundamental to the diagnosis and treatment of neurological disorders. However, this map was largely constructed decades ago, and its breadth, variability, and reliability remain poorly described, limiting its practical use.

Methods: The authors used a novel method to reconstruct the myotome map in patients (n = 42) undergoing placement of dorsal root ganglion electrodes for the treatment of chronic pain.

Dorsal root ganglion stimulation device explantation: A multicenter pooled data analysis.

Introduction: Dorsal root ganglion stimulation (DRG-S) is a relatively new neuromodulation modality. Therefore, data on long-term device explantation rates is limited. This investigation aimed to assess DRG-S device explantation rates at long-term follow-up.