Fat embolism syndrome in Duchenne muscular dystrophy: Report on a novel case and systematic literature review.

We report a non-ambulatory 13-year-old boy with Duchenne muscular dystrophy who experienced severe acute respiratory distress syndrome and cerebral fat embolism following elective soft tissue surgery. Post-surgery radiological examination revealed bilateral femoral fractures and marked osteopenia that were believed to have caused disseminated pulmonary and cerebral fat embolism. The patient had never been on glucocorticoid treatment.

Is the future female for turtles? Climate change and wetland configuration predict sex ratios of a freshwater species.

Climate change and land-use change are leading drivers of biodiversity decline, affecting demographic parameters that are important for population persistence. For example, scientists have speculated for decades that climate change may skew adult sex ratios in taxa that express temperature-dependent sex determination (TSD), but limited evidence exists that this phenomenon is occurring in natural settings. For species that are vulnerable to anthropogenic land-use practices, differential mortality among sexes may also skew sex ratios.

Connected While Distant: Networking CUREs Across Classrooms to Create Community and Empower Students.

Connections, collaborations, and community are key to the success of individual scientists as well as transformative scientific advances. Intentionally building these components into science, technology, engineering and mathematics (STEM) education can better prepare future generations of researchers. Course-based undergraduate research experiences (CUREs) are a new, fast-growing teaching practice in STEM that expand opportunities for undergraduate students to gain research skills.

P2Y receptors mediate nucleotide-induced EGFR phosphorylation and stimulate proliferation and tumorigenesis of head and neck squamous cell carcinoma cell lines.

Objectives: To assess functional expression of the P2Y nucleotide receptor (P2YR) in head and neck squamous cell carcinoma (HNSCC) cell lines and define its role in nucleotide-induced epidermal growth factor receptor (EGFR) transactivation. The use of anti-EGFR therapeutics to treat HNSCC is hindered by intrinsic and acquired drug resistance. Defining novel pathways that modulate EGFR signaling could identify additional targets to treat HNSCC.

Purinergic signaling in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by three major histopathological markers: amyloid-β (Aβ) plaques, neurofibrillary tangles and gliosis in the central nervous system (CNS). It is now accepted that neuroinflammatory events in the CNS play a crucial role in the development of AD. This review focuses on neuroinflammatory signaling mediated by purinergic receptors (P1 adenosine receptors, P2X ATP-gated ion channels and G protein-coupled P2Y nucleotide receptors) and how therapeutic modulation of purinergic signaling influences disease progression in AD patients and animal models of AD.

Adaptive population divergence and directional gene flow across steep elevational gradients in a climate-sensitive mammal.

The ecological effects of climate change have been shown in most major taxonomic groups; however, the evolutionary consequences are less well-documented. Adaptation to new climatic conditions offers a potential long-term mechanism for species to maintain viability in rapidly changing environments, but mammalian examples remain scarce. The American pika (Ochotona princeps) has been impacted by recent climate-associated extirpations and range-wide reductions in population sizes, establishing it as a sentinel mammalian species for climate change.

P2Y R deletion ameliorates sialadenitis in IL-14α-transgenic mice.

Objective: Interleukin-14α-transgenic (IL-14αTG) mice develop an autoimmune exocrinopathy with characteristics similar to Sjögren's syndrome, including sialadenitis and hyposalivation. The P2Y receptor (P2Y R) for extracellular ATP and UTP is upregulated during salivary gland inflammation (i.e.

Low-affinity binding in to P2YR mediates force-dependent integrin activation during hantavirus infection.

Pathogenic hantaviruses bind to the plexin-semaphorin-integrin (PSI) domain of inactive, β integrins. Previous studies have implicated a cognate interaction between the bent conformation β/β integrins and an arginine-glycine-aspartic acid (RGD) sequence in the first extracellular loop of P2YR. With single-molecule atomic force microscopy, we show a specific interaction between an atomic force microscopy tip decorated with recombinant αβ integrins and (RGD)P2YR expressed on cell membranes.

P2X7 receptor antagonism prevents IL-1β release from salivary epithelial cells and reduces inflammation in a mouse model of autoimmune exocrinopathy.

Salivary gland inflammation is a hallmark of Sjögren's syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated nonselective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1β and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome.

Individual-based analysis of hair corticosterone reveals factors influencing chronic stress in the American pika.

Glucocorticoids are often measured in wildlife to assess physiological responses to environmental or ecological stress. Hair, blood, saliva, or fecal samples are generally used depending on the timescale of the stress response being investigated and species-specific considerations. Here, we report the first use of hair samples to measure long-term corticosterone levels in the climate-sensitive American pika ().

P2Y receptor modulates shear stress-induced cell alignment and actin stress fibers in human umbilical vein endothelial cells.

Endothelial cells release ATP in response to fluid shear stress, which activates purinergic (P2) receptor-mediated signaling molecules including endothelial nitric oxide (eNOS), a regulator of vascular tone. While P2 receptor-mediated signaling in the vasculature is well studied, the role of P2Y receptors in shear stress-associated endothelial cell alignment, cytoskeletal alterations, and wound repair remains ill defined. To address these aspects, human umbilical vein endothelial cell (HUVEC) monolayers were cultured on gelatin-coated dishes and subjected to a shear stress of 1 Pa.

Maternal signature whistle use aids mother-calf reunions in a bottlenose dolphin, Tursiops truncatus.

Individual vocal signatures play an important role in parent-offspring recognition in many animals. One species that uses signature calls to accurately facilitate individual recognition is the bottlenose dolphin. Female dolphins and their calves will use their highly individualised signature whistles to identify and maintain contact with one another.

Purinergic receptors as potential therapeutic targets in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive loss of memory and cognitive ability and is a serious cause of mortality. Many of the pathological characteristics associated with AD are revealed post-mortem, including amyloid-β plaque deposition, neurofibrillary tangles containing hyperphosphorylated tau proteins and neuronal loss in the hippocampus and cortex. Although several genetic mutations and risk factors have been associated with the disease, the causes remain poorly understood.

Increased Expression of TGF-β Signaling Components in a Mouse Model of Fibrosis Induced by Submandibular Gland Duct Ligation.

Transforming growth factor-β (TGF-β) is a multi-functional cytokine with a well-described role in the regulation of tissue fibrosis and regeneration in the liver, kidney and lung. Submandibular gland (SMG) duct ligation and subsequent deligation in rodents is a classical model for studying salivary gland damage and regeneration. While previous studies suggest that TGF-β may contribute to salivary gland fibrosis, the expression of TGF-β signaling components has not been investigated in relation to mouse SMG duct ligation-induced fibrosis and regeneration following ductal deligation.

The P2Y Receptor Interacts with VE-Cadherin and VEGF Receptor-2 to Regulate Rac1 Activity in Endothelial Cells.

Vascular endothelial cadherin (VE-cadherin) mediates homophylic adhesion between endothelial cells and is an important regulator of angiogenesis, blood vessel permeability and leukocyte trafficking. Rac1, a member of the Rho family of GTPases, controls VE-cadherin adhesion by acting downstream of several growth factors, including angiopoietin-1 and vascular endothelial growth factor (VEGF). Here we show that UTP-induced activation of the G protein-coupled P2Y nucleotide receptor (P2YR) in human coronary artery endothelial cells (HCAECs) activated Rac1 and caused a transient complex to form between P2YR, VE-cadherin and VEGF receptor-2 (VEGFR-2).

P2Y receptors in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia, affecting more than 10% of people over the age of 65. Age is the greatest risk factor for AD, although a combination of genetic, lifestyle and environmental factors also contribute to disease development. Common features of AD are the formation of plaques composed of beta-amyloid peptides (Aβ) and neuronal death in brain regions involved in learning and memory.

Determinants of pika population density vs. occupancy in the Southern Rocky Mountains.

Species distributions are responding rapidly to global change. While correlative studies of local extinction have been vital to understanding the ecological impacts of global change, more mechanistic lines of inquiry are needed for enhanced forecasting. The current study assesses whether the predictors of local extinction also explain population density for a species apparently impacted by climate change.

P2Y2 nucleotide receptor activation enhances the aggregation and self-organization of dispersed salivary epithelial cells.

Hyposalivation resulting from salivary gland dysfunction leads to poor oral health and greatly reduces the quality of life of patients. Current treatments for hyposalivation are limited. However, regenerative medicine to replace dysfunctional salivary glands represents a revolutionary approach.

Abnormal vital signs are common after bowel resection and do not predict anastomotic leak.

Background: Anastomotic leak is a serious complication of gastrointestinal surgery. Abnormal vital signs are often cited in retrospective peer review and medicolegal settings as evidence of negligence in the failure to make an early diagnosis. We aimed to profile the postoperative courses of patients who undergo intestinal anastomosis and determine how reliably abnormal vital signs predict anastomotic leaks.

Loss of P2Y₂ nucleotide receptors enhances early pathology in the TgCRND8 mouse model of Alzheimer's disease.

Neuroinflammation is a prominent feature in Alzheimer's disease (AD) and activation of the brain's innate immune system, particularly microglia, has been postulated to both retard and accelerate AD progression. Recent studies indicate that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is an important regulator of innate immunity by assisting in the recruitment of monocytes to injured tissue, neutrophils to bacterial infections and eosinophils to allergen-infected lungs. In this study, we investigated the role of the P2Y2R in progression of an AD-like phenotype in the TgCRND8 mouse model that expresses Swedish and Indiana mutations in amyloid precursor protein (APP).

Up-regulation and activation of the P2Y(2) nucleotide receptor mediate neurite extension in IL-1β-treated mouse primary cortical neurons.

The pro-inflammatory cytokine interleukin-1β (IL-1β), whose levels are elevated in the brain in Alzheimer's and other neurodegenerative diseases, has been shown to have both detrimental and beneficial effects on disease progression. In this article, we demonstrate that incubation of mouse primary cortical neurons (mPCNs) with IL-1β increases the expression of the P2Y2 nucleotide receptor (P2Y2R) and that activation of the up-regulated receptor with UTP, a relatively selective agonist of the P2Y2R, increases neurite outgrowth. Consistent with the accepted role of cofilin in the regulation of neurite extension, results indicate that incubation of IL-1β-treated mPCNs with UTP increases the phosphorylation of cofilin, a response absent in PCNs isolated from P2Y2R(-/-) mice.

Coupling of P2Y receptors to G proteins and other signaling pathways.

P2Y receptors are G protein-coupled receptors (GPCRs) that are activated by adenine and uridine nucleotides and nucleotide sugars. There are eight subtypes of P2Y receptors (P2Y, P2Y, P2Y, P2Y, P2Y, P2Y, P2Y, and P2Y), which activate intracellular signaling cascades to regulate a variety of cellular processes, including proliferation, differentiation, phagocytosis, secretion, nociception, cell adhesion, and cell migration. These signaling cascades operate mainly by the sequential activation or deactivation of heterotrimeric and monomeric G proteins, phospholipases, adenylyl and guanylyl cyclases, protein kinases, and phosphodiesterases.

P2Y receptors in the mammalian nervous system: pharmacology, ligands and therapeutic potential.

P2Y receptors for extracellular nucleotides are coupled to activation of a variety of G proteins and stimulate diverse intracellular signaling pathways that regulate functions of cell types that comprise the central nervous system (CNS). There are 8 different subtypes of P2Y receptor expressed in cells of the CNS that are activated by a select group of nucleotide agonists. Here, the agonist selectivity of these 8 P2Y receptor subtypes is reviewed with an emphasis on synthetic agonists with high potency and resistance to degradation by extracellular nucleotidases that have potential applications as therapeutic agents.

P2X7 receptor activation induces inflammatory responses in salivary gland epithelium.

Inflammation of the salivary gland is a well-documented aspect of salivary gland dysfunction that occurs in Sjogren's syndrome (SS), an autoimmune disease, and in γ-radiation-induced injury during treatment of head and neck cancers. Extracellular nucleotides have gained recognition as key modulators of inflammation through activation of cell surface ionotropic and metabotropic receptors, although the contribution of extracellular nucleotides to salivary gland inflammation is not well understood. In vitro studies using submandibular gland (SMG) cell aggregates isolated from wild-type C57BL/6 mice indicate that treatment with ATP or the high affinity P2X7R agonist 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) induces membrane blebbing and enhances caspase activity, responses that were absent in SMG cell aggregates isolated from mice lacking the P2X7R (P2X7R(-/-)).