Slingshot

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a significant public health problem characterized by persistent airflow limitation. Despite previous research into the pathogenesis of COPD, a comprehensive understanding of the cell-type-specific mechanisms in COPD remains lacking. Recent studies have implicated Rab GTPases in regulating chronic immune response and inflammation via multiple pathways. In this study, the molecular regulating mechanism of RAB32 in COPD was investigated by multiple bioinformatics mining and experimental verification...

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive manifestation of nonalcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite the growing knowledge of NASH and HCC, the association between the two conditions remains to be fully explored. Bioinformatics has emerged as a valuable approach for identifying disease-specific feature genes, enabling advancements in disease prediction, prevention, and personalized treatment strategies...

Conflict between humans and black bears (Ursus americanus) occurs throughout North America with increasing public demand to replace lethal management with non-lethal methods, such as aversive conditioning (AC). AC aims to teach animals to associate negative stimuli with humans or their infrastructure. We sought to test the efficacy of AC using radio-collared black bears in Whistler, British Columbia, by monitoring individuals and assigning those in conflict with people to control or treatment groups. We measured wariness using overt reaction distance, displacement distance, and reaction to researchers before, during and after executing 3-5-day AC programs that consisted of launching projectiles at bears in the treatment group...

OBJECTIVE: The gain of function (GOF) CTNNB1 mutations (CTNNB1 GOF ) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1 GOF HCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC. DESIGN: RNA sequencing was performed to identify the key downstream genes of CTNNB1 GOF associated with immune escape. An in vitro coculture system, murine subcutaneous or orthotopic models, spontaneously tumourigenic models in conditional gene-knock-out mice and flow cytometry were used to explore the biological function of matrix metallopeptidase 9 (MMP9) in tumour progression and immune escape...

Transient electron dynamics near the interface of counterstreaming plasmas at the onset of a relativistic collisionless shock (RCS) is investigated using particle-in-cell simulations. We identify a slingshotlike injection process induced by the drifting electric field sustained by the flowing focus of backward-moving electrons, which is distinct from the well-known stochastic acceleration. The flowing focus signifies the plasma kinetic transition from a preturbulent laminar motion to a chaotic turbulence. We find a characteristic correlation between the electron dynamics in the slingshot acceleration and the photon emission features...

Growing evidence underscores the circadian rhythm's essential function in liver stability and disease. Its disruption is progressively linked with metabolic issues, oncogene triggers, and heightened cancer susceptibility. Research points to slingshot protein phosphatase 1 (SSH1), a modulator of cofilin-1 (CFL-1), as instrumental in the reformation of the actin cytoskeleton, thereby impacting the invasiveness of various cancer types. Yet, the dynamics of SSH1's influence on liver cell stemness and circadian activity remain unclear...

Oxidative damage in the brain is one of the earliest drivers of pathology in Alzheimer's disease (AD) and related dementias, both preceding and exacerbating clinical symptoms. In response to oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) is normally activated to protect the brain from oxidative damage. However, Nrf2-mediated defense against oxidative stress declines in AD, rendering the brain increasingly vulnerable to oxidative damage. Although this phenomenon has long been recognized, its mechanistic basis has been a mystery...

Stretching elastomer bands to accumulate strain energy, for a sudden projectile launching, has been an old hunting skill that will continue to find new applications in miniaturized worlds. In this work, we explore the use of highly resilient and geometry-tailored ultrathin crystalline silicon nanowires (SiNWs) as elastic medium to fabricate the first, and the smallest, mechanical slingshot. These NW-morphed slingshots were first grown on planar surface, with desired layout, and then mounted upon standing pillar frames, with a unique self-hooking structure that allows for a facile and reliable assembly, loading and shooting maneuvers of microsphere payloads...

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of skin biology, but its utility is restricted by the requirement of fresh samples, inadequate dissociation-induced cell loss or death, and activation during tissue digestion. Single-nucleus RNA sequencing (snRNA-seq) can use frozen, hard-to-dissociate materials, which might be a promising method to circumvent the limitations of scRNA-seq for the skin tissue. OBJECTIVE: To profile skin cells using snRNA-seq in parallel with scRNA-seq...

AIMS: Systemic inflammation occurs commonly during many human disease settings and increases vascular permeability, leading to organ failure and lethal outcomes. Lipocalin 10 (Lcn10), a poorly characterized member of the lipocalin family, is remarkably altered in the cardiovascular system of human patients with inflammatory conditions. Nonetheless, whether Lcn10 regulates inflammation-induced endothelial permeability remains unknown. METHODS AND RESULTS: Systemic inflammation models were induced using mice by injection of endotoxin LPS or cecal ligation and puncture (CLP) surgery...

Intracerebral hemorrhage (ICH) is a significant health concern associated with high mortality. Cofilin plays a crucial role in stress conditions, but its signaling following ICH in a longitudinal study is yet to be ascertained. In the present study, we examined the cofilin expression in human ICH autopsy brains. Then, the spatiotemporal cofilin signaling, microglia activation, and neurobehavioral outcomes were investigated in a mouse model of ICH. Human autopsy brain sections from ICH patients showed increased intracellular cofilin localization within microglia in the perihematomal area, possibly associated with microglial activation and morphological changes...

Introduction: The actin regulatory protein, cofilin plays a key signaling role in many cells for numerous cellular responses including in proliferation, development, motility, migration, secretion and growth. In the pancreas it is important in islet insulin secretion, growth of pancreatic cancer cells and in pancreatitis. However, there are no studies on its role or activation in pancreatic acinar cells. Methods: To address this question, we studied the ability of CCK to activate cofilin in pancreatic acinar cells, AR42J cells and CCK1 -R transfected Panc-1 cells, the signaling cascades involved and its effect on enzyme secretion and MAPK activation, a key mediator of pancreatic growth...

Microglial activation and failure of the antioxidant defense mechanisms are major hallmarks in different brain injuries, particularly traumatic brain injury (TBI). Cofilin is a cytoskeleton-associated protein involved in actin binding and severing. In our previous studies, we identified the putative role of cofilin in mediating microglial activation and apoptosis in ischemic and hemorrhagic conditions. Others have highlighted the involvement of cofilin in ROS production and the resultant neuronal death; however, more studies are needed to delineate the role of cofilin in oxidative stress conditions...

Filming atomic motion within molecules is an active pursuit of molecular physics and quantum chemistry. A promising method is laser-induced Coulomb Explosion Imaging (CEI) where a laser pulse rapidly ionizes many electrons from a molecule, causing the remaining ions to undergo Coulomb repulsion. The ion momenta are used to reconstruct the molecular geometry which is tracked over time (i.e., filmed) by ionizing at an adjustable delay with respect to the start of interatomic motion. Results are distorted, however, by ultrafast motion during the ionizing pulse...

The acrosome is a membranous organelle positioned in the anterior portion of the sperm head and is essential for male fertility. Acrosome biogenesis requires the dynamic cytoskeletal shuttling of vesicles towards nascent acrosome which is regulated by a series of accessory proteins. However, much remains unknown about the molecular basis underlying this process. Here, we generated Ssh2 knock-out (KO) mice and HA-tagged Ssh2 knock-in (KI) mice to define the functions of Slingshot phosphatase 2 (SSH2) in spermatogenesis and demonstrated that as a regulator of actin remodeling, SSH2 is essential for acrosome biogenesis and male fertility...

Single-cell technologies have become valuable tools to trace dendritic cell differentiation trajectories. Here, we illustrate the workflow used for processing of mouse bone marrow for single-cell RNA sequencing and trajectory analyses, as done in Dress et al. (Nat Immunol 20:852-864, 2019). This short methodology is presented as a starting point for researchers just beginning to dive into the complex field of dendritic cell ontogeny and cellular development trajectory analyses.

Protein tyrosine phosphatases (PTPs) are involved in malignant transformation and metastasis. According to one of our previous studies, Slingshot homolog 1 (SSH1), a member of PTPs, is significantly associated with the survival of intrahepatic cholangiocarcinoma (iCCA) patients. However, the underlying mechanisms of SSH1 in iCCA remain largely elusive. Here, the expression and clinical significance of SSH1 were assessed using the iCCA patient samples. The results showed that SSH1 was dramatically up-regulated in iCCA tissues and elevated SSH1 expression was associated with worse overall survival of iCCA patients...

Experiment, theory, and simulation are employed to understand the dispersion of colloidal particles in a periodic array of oscillating harmonic traps generated by optical tweezers. In the presence of trap oscillation, a nonmonotonic and anisotropic dispersion is observed. Surprisingly, the stiffest traps produce the largest dispersion at a critical frequency, and the particles diffuse significantly faster in the direction of oscillation than those undergoing passive Stokes-Einstein-Sutherland diffusion. Theoretical predictions for the effective diffusivity of the particles as a function of trap stiffness and oscillation frequency are developed using generalized Taylor dispersion theory and Brownian dynamics simulations...

Rapid and sustained condensate droplet departure from a surface is key toward achieving high heat-transfer rates in condensation, a physical process critical to a broad range of industrial and societal applications. Despite the progress in enhancing condensation heat transfer through inducing its dropwise mode with hydrophobic materials, sophisticated surface engineering methods that can lead to further enhancement of heat transfer are still highly desirable. Here, by employing a three-dimensional, multiphase computational approach, we present an effective out-of-plane biphilic surface topography, which reveals an unexplored capillarity-driven departure mechanism of condensate droplets...

Accumulating toxic protein assemblies, including Aβ and tau, and dysfunctional mitochondria are associated with synaptic and neuronal loss in Alzheimer's disease (ad). Such accumulations are thought to be due to clearance defects in the autophagy-lysosome pathway. Mitochondrial dysfunction is evident in ad brains and animal models at multiple levels, such as mitochondrial genomic mutations, disrupted bioenergetics, deregulated mitochondrial dynamics, and impaired clearance of damaged mitochondria (mitophagy)...