Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS.

Rapamycin improves satellite cells' autophagy and muscle regeneration during hypercapnia.

Both CO2 retention, or hypercapnia, and skeletal muscle dysfunction predict higher mortality in critically ill patients. Mechanistically, muscle injury and reduced myogenesis contribute to critical illness myopathy, and while hypercapnia causes muscle wasting, no research has been conducted on hypercapnia-driven dysfunctional myogenesis in vivo. Autophagy flux regulates myogenesis by supporting skeletal muscle stem cell - satellite cell - activation, and previous data suggest that hypercapnia inhibits autophagy.

Correction: Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae.

Although in humans, the brain fails to heal after an injury, young zebrafish are able to restore tissue structural integrity in less than 24 h, thanks to the mechanical action of microglia.

A randomized study of cryoablation of intercostal nerves in patients undergoing minimally invasive thoracic surgery.

Objectives: Minimally invasive thoracic surgery can cause significant pain, and optimizing pain control after surgery is highly desirable. We examined pain control after intercostal nerve block with or without cryoablation of the intercostal nerves.

Methods: This was a randomized study (NCT05348447) of adults scheduled for a minimally invasive thoracic procedure.

Aging, brain-derived neurotrophic factor, and allergen-induced pulmonary responses in mice.

Asthma in the elderly is being recognized as more severe, resistant to standard therapies, and having greater morbidity. Therefore, it comes important to understand the impact of aging-associated airway structure and function changes towards pathogenesis of asthma in the elderly. Here, airway smooth muscle plays important roles in airway hyperreactivity and structural remodeling.

Biofunctionalized gelatin hydrogels support development and maturation of iPSC-derived cortical organoids.

Human neural organoid models have become an important tool for studying neurobiology. However, improving the representativeness of neural cell populations in such organoids remains a major effort. In this work, we compared Matrigel, a commercially available matrix, to a neural cadherin (N-cadherin) peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids.

Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae.

Wound closure after brain injury is crucial for tissue restoration but remains poorly understood at the tissue level. We investigated this process using in vivo observations of larval zebrafish brain injury. Our findings show that wound closure occurs within the first 24 h through global tissue contraction, as evidenced by live-imaging and drug inhibition studies.

Effects of glial-derived neurotrophic factor on remodeling and mitochondrial function in human airway smooth muscle cells.

Airway smooth muscle (ASM) cells play important roles in airway remodeling of asthma. Our previous studies show that in vivo administration of glial-derived neurotrophic factor (GDNF) in mice induces thickening and collagen deposition in bronchial airways, whereas chelation of GDNF by GFRα1-Fc attenuates airway remodeling in the context of allergen exposure. To determine whether GDNF has direct effects on ASM, in this study, we examined GDNF in ASM cells from normal versus asthmatic humans.

Rule breakers achieve successful shoulder balance: unraveling the myth of upper instrumented vertebrae selection criteria.

Purpose: This study compared shoulder balance outcomes in "rule breakers" (RB) vs. "rule followers" (RF) based on commonly utilized upper instrumented vertebrae (UIV) selection guidelines.

Methods: Adolescent idiopathic scoliosis (AIS) patients (Lenke 1-4) who underwent posterior spine fusion (PSF) with minimum 2-year follow-up had radiographic measurement of shoulder balance including first rib angle (FRA), T1 tilt, coracoid process height difference (CPHD), and clavicle angle (CA) at preop, postop, 6-month, 1-year, and 2-year timepoints.

Improved Composite Hydrogel for Bioengineered Tracheal Graft Demonstrates Effective Early Angiogenesis.

: Collagen-agarose hydrogel blends currently used in tracheal graft bioengineering contain relatively high concentrations of collagen to withstand mechanical stresses associated with native trachea function (e.g., breathing).

Piezo channels modulate human lung fibroblast function.

Bronchial airways and lung parenchyma undergo both static and dynamic stretch in response to normal breathing as well as in the context of insults such as mechanical ventilation (MV) or in diseases such as asthma and chronic obstructive pulmonary disease (COPD) which lead to airway remodeling involving increased extracellular matrix (ECM) production. Here, the role of fibroblasts is critical, but the relationship between stretch- and fibroblast-induced ECM remodeling under these conditions is not well-explored. Piezo (PZ) channels play a role in mechanotransduction in many cell and organ systems, but their role in mechanical stretch-induced airway remodeling is not known.

Succinate dehydrogenase-complex II regulates skeletal muscle cellular respiration and contractility but not muscle mass in genetically induced pulmonary emphysema.

Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema and are independently associated with higher mortality. If reduced cellular respiration contributes to muscle atrophy in that setting remains unknown. Using a mouse with genetically induced pulmonary emphysema that recapitulates muscle dysfunction, we found that reduced activity of succinate dehydrogenase (SDH) is a hallmark of its myopathic changes.

Blood DNA methylation in post-acute sequelae of COVID-19 (PASC): a prospective cohort study.

Background: DNA methylation integrates environmental signals with transcriptional programs. COVID-19 infection induces changes in the host methylome. While post-acute sequelae of COVID-19 (PASC) is a long-term complication of acute illness, its association with DNA methylation is unknown.

Sex differences in sociodemographic, clinical, and laboratory variables in childhood asthma: A birth cohort study.

Background: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sexdifferences in pediatric asthma cohorts.

Objective: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort.

Effects of Low-Level Light Therapy on Resting-State Connectivity Following Moderate Traumatic Brain Injury: Secondary Analyses of a Double-blinded Placebo-controlled Study.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases.

Endoplasmic reticulum stress-induced senescence in human lung fibroblasts.

Loss of proteostasis and cellular senescence have been previously established as characteristics of aging; however, their interaction in the context of lung aging and potential contributions to aging-associated lung remodeling remains understudied. In this study, we aimed to characterize endoplasmic reticulum (ER) stress response, cellular senescence, and their interaction in relation to extracellular matrix (ECM) production in lung fibroblasts from young (25-45 yr) and old (>60 yr) humans. Fibroblasts from young and old patients without significant preexisting lung disease were exposed to vehicle, MG132, etoposide, or salubrinal.

Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor-Proximal Proteins with Immunological Functions.

The BCR allows for Ag-driven B cell activation and subsequent Ag endocytosis, processing, and presentation to recruit T cell help. Core drivers of BCR signaling and endocytosis are motifs within the receptor's cytoplasmic tail (primarily CD79). However, BCR function can be tuned by other proximal cellular elements, such as CD20 and membrane lipid microdomains.

Multidisciplinary evidence-based tools for improving consistency of care and neonatal nutrition.

Background: Extrauterine growth restriction from inadequate nutrition remains a significant morbidity in very low birth weight infants. Participants in the California Perinatal Quality Care Collaborative Quality Improvement Collaborative, Grow, Babies, Grow! developed or refined tools to improve nutrition and reduce practice variation.

Method: Five Neonatal Intensive Care Units describe the development and implementation of nutrition tools.

Lowest instrumented vertebrae in early onset scoliosis: is there a role for a more selective approach?

Purpose: This purpose of this study was to assess the impact of patient and implant characteristics on LIV selection in ambulatory children with EOS and to assess the relationship between the touched vertebrae (TV), the last substantially touched vertebrae (LSTV), the stable vertebrae (SV), the sagittal stable vertebrae (SSV), and the LIV.

Methods: A multicenter pediatric spine database was queried for patients ages 2-10 years treated by growth friendly instrumentation with at least 2-year follow up. The relationship between the LIV and preoperative spinal height, curve magnitude, and implant type were assessed.