The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and fibroblasts in fibrotic lung disease.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available treatment options. Recently, the involvement of purinergic receptor subtypes in the pathogenesis of different lung diseases has been demonstrated. Here we investigated the role of the purinergic receptor subtype P2Y2 in the context of fibrotic lung diseases.

Direct fluorescence detection of VirE2 secretion by Agrobacterium tumefaciens.

VirE2 is a ssDNA binding protein essential for virulence in Agrobacterium tumefaciens. A tetracysteine mutant (VirE2-TC) was prepared for in vitro and in vivo fluorescence imaging based on the ReAsH reagent. VirE2-TC was found to be biochemically active as it binds both ssDNA and the acidic secretion chaperone VirE1.

Prion-like characteristics of the bacterial protein Microcin E492.

Microcin E492 (Mcc) is a pore-forming bacteriotoxin. Mcc activity is inhibited at the stationary phase by formation of amyloid-like aggregates in the culture. Here we report that, in a similar manner as prions, Mcc naturally exists as two conformers: a β-sheet-rich, protease-resistant, aggregated, inactive form (Mcc), and a soluble, protease-sensitive, active form (Mcc).

Spontaneous Intracranial Hypotension Presenting as a "Pseudo-Chiari 1.

Spontaneous intracranial hypotension (SIH) is classified as a decrease in cerebrospinal fluid (CSF) pressure secondary to a CSF leakage and consequent descent of the brain into the foramen magnum. Diagnosing SIH can be difficult due to its overlapping findings with Arnold-Chiari type 1 Malformation (CM1) where the cerebellar tonsils herniate into the foramen magnum. The similarity of both conditions calls for a more reliable imaging technique to localize the CSF leak which could narrow the differential diagnosis and aid in choosing the correct treatment.

An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump.

Bacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics from the cell. In Gram-negative bacteria, some of these pumps form multi-protein assemblies that span the cell envelope. Here, we report the near-atomic resolution cryoEM structures of the AcrAB-TolC multidrug efflux pump in resting and drug transport states, revealing a quaternary structural switch that allosterically couples and synchronizes initial ligand binding with channel opening.

Traumatic Cervical Nerve Root Avulsion with Pseudomeningocele Formation.

Cervical nerve root avulsion is a well-documented result of motor vehicle collision (MVC), especially when occurring at high velocities. These avulsions are commonly traction injuries of nerve roots that may be accompanied by a tear in the meninges through the vertebral foramina with associated collections of cerebrospinal fluid (CSF), thereby resulting in a pseudomeningocele. We present a case of a 19-year-old male who experienced an MVC and was brought to the emergency department (ED) with right arm paralysis and other injuries.

IRE1 signaling exacerbates Alzheimer's disease pathogenesis.

Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress.

The Endoplasmic Reticulum Chaperone GRP78/BiP Modulates Prion Propagation in vitro and in vivo.

Prion diseases are fatal neurodegenerative disorders affecting several mammalian species, characterized by the accumulation of the misfolded form of the prion protein, which is followed by the induction of endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR). GRP78, also called BiP, is a master regulator of the UPR, reducing ER stress levels and apoptosis due to an enhancement of the cellular folding capacity. Here, we studied the role of GRP78 in prion diseases using several in vivo and in vitro approaches.

Association between Use of Prophylactic Indomethacin and the Risk for Bronchopulmonary Dysplasia in Extremely Preterm Infants.

Objective: To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) in a recent, large cohort of extremely preterm infants.

Study Design: Retrospective cohort study using prospectively collected data for infants with gestational ages < 29 weeks or birth weights of 401-1000 g born between 2008 and 2012 at participating hospitals of the National Institute of Child Health and Human Development Neonatal Research Network. Infants treated with indomethacin in the first 24 hours of life were compared with those who were not.

Retrospective analysis of the treatment of melasma lesions exhibiting increased vascularity with the 595-nm pulsed dye laser combined with the 1927-nm fractional low-powered diode laser.

Background: Melasma presents a significant challenge to laser surgeons. Aggressive treatments often result in rebound melasma or post-inflammatory pigmentary alteration. Recent reports suggest melasma pathogenesis may have a vascular component.

Perylene Diimide as a Precise Graphene-like Superoxide Dismutase Mimetic.

Here we show that the active portion of a graphitic nanoparticle can be mimicked by a perylene diimide (PDI) to explain the otherwise elusive biological and electrocatalytic activity of the nanoparticle construct. Development of molecular analogues that mimic the antioxidant properties of oxidized graphenes, in this case the poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs), will afford important insights into the highly efficient activity of PEG-HCCs and their graphitic analogues. PEGylated perylene diimides (PEG-PDI) serve as well-defined molecular analogues of PEG-HCCs and oxidized graphenes in general, and their antioxidant and superoxide dismutase-like (SOD-like) properties were studied.

Challenges in Laboratory Detection of Unusual Substance Abuse: Issues with Magic Mushroom, Peyote Cactus, Khat, and Solvent Abuse.

Drug abuse is a worldwide problem. Although commonly abused drugs can be identified during routine urine drug testing, less commonly abused drugs may escape detection. These less commonly abused drugs not only include some designer drugs such as synthetic cannabinoid but also include abuse of psychedelic magic mushroom (active ingredients: psilocybin and psilocin), peyote cactus (active ingredient: mescaline), and khat plants (active ingredient: cathinone).

Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding.

Numerous epidemiological studies have shown a significantly higher risk for development of Alzheimer's disease (AD) in patients affected by type 2 diabetes (T2D), but the molecular mechanism responsible for this association is presently unknown. Both diseases are considered protein misfolding disorders associated with the accumulation of protein aggregates; amyloid-beta (Aβ) and tau in the brain during AD, and islet amyloid polypeptide (IAPP) in pancreatic islets in T2D. Formation and accumulation of these proteins follows a seeding-nucleation model, where a misfolded aggregate or 'seed' promotes the rapid misfolding and aggregation of the native protein.

Increased susceptibility to Aβ toxicity in neuronal cultures derived from familial Alzheimer's disease (PSEN1-A246E) induced pluripotent stem cells.

Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients.

Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease.

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrP) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply.

The superior regenerative potential of muscle-derived stem cells for articular cartilage repair is attributed to high cell survival and chondrogenic potential.

Three populations of muscle-derived cells (PP1, PP3, and PP6) were isolated from mouse skeletal muscle using modified preplate technique and retrovirally transduced with BMP4/GFP.  , the PP1 cells (fibroblasts) proliferated significantly slower than the PP3 (myoblasts) and PP6 cells (muscle-derived stem cells); the PP1 and PP6 cells showed a superior rate of survival compared with PP3 cells under oxidative stress; and the PP6 cells showed significantly superior chondrogenic capabilities than PP1 and PP3 cells. , the PP6 cells promoted superior cartilage regeneration compared with the other muscle-derived cell populations.

Paraprotein-Related Kidney Disease: Attack of the Killer M Proteins.

Paraproteins are monoclonal Igs or their components (light or heavy chains) that are produced by a clonal population of mature B cells, most commonly plasma cells. These paraproteins or monoclonal proteins are secreted into the blood and subsequently filtered by the glomerulus before entering into urine, where they can cause various types of kidney disease, including both glomerular and tubulointerstitial injuries. Furthermore, a monoclonal protein that causes a specific glomerular or tubulointerstitial lesion in a human can reproducibly cause the same pathology when injected into an animal, supporting unique paraprotein characteristics.

A Nonoperative Approach for Neurosurgical Management of a Sylvian Fissure Dermoid Cyst.

The nonoperative management of sylvian fissure dermoid/epidermoid cysts presents a risk that is difficult to quantify. With rupture, potentially fatal complications such as chemical meningitis, hydrocephalus, fever, seizure, or meningeal irritation may occur. In this paper, we present an asymptomatic case of such a cyst with imaging evidence of prior rupture, and we review the literature for the likelihood of future complications.

Delaying aging in Caenorhabditis elegans with protein aggregation inhibitors.

Recent evidence suggests that during aging there is widespread accumulation of aggregated insoluble proteins, even in the absence of pathological conditions. Pharmacological manipulation of protein aggregation might be helpful to unveil the involvement of protein aggregates during aging, as well as to develop novel strategies to delay aging. Here we investigated the effect of known protein aggregation inhibitors on the lifespan and health-span of Caenorhabditis elegans.