bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parkinson's disease: acid‐glucocerebrosidase activity and alpha‐synuclein clearance
Authors: Blanz Judith , Saftig Paul 
Published: February 2016

AbstractThe role of mutations in the gene GBA1 encoding the lysosomal hydrolase β‐glucocerebrosidase for the development of synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, was only very recently uncovered. The knowledge obtained from the study of carriers or patients suffering from Gaucher disease (a common lysosomal storage disorder because of GBA1 mutations) is of particular importance for understanding the role of the enzyme and its catabolic pathway in the development of synucleinopathies. Decreased activity of β‐glucocerebrosidase leads to lysosomal dysfunction and the accumulation of its substrate glucosylceramide and related lipid derivatives. Glucosylceramide is suggested to stabilize toxic oligomeric forms of α‐synuclein that negatively influence the activity of β‐glucocerebrosidase and to partially block export of newly synthesized β‐glucocerebrosidase from the endoplasmic reticulum to late endocytic compartments, amplifying the pathological effects of α‐synuclein and ultimately resulting in neuronal cell death. This pathogenic molecular feedback loop and most likely other factors (such as impaired endoplasmic reticulum‐associated degradation, activation of the unfolded protein response and dysregulation of calcium homeostasis induced by misfolded GC mutants) are involved in shifting the cellular homeostasis from monomeric α‐synuclein towards oligomeric neurotoxic and aggregated forms, which contribute to Parkinson's disease progression. From a therapeutic point of view, strategies aiming to increase either the expression, stability or delivery of the β‐glucocerebrosidase to lysosomes are likely to decrease the α‐synuclein burden and may be useful for an in depth evaluation at the organismal level.
image
Lysosomes are critical for protein and lipid homeostasis. Recent research revealed that dysfunction of this organelle contributes to the development of neurodegenerative diseases such as Parkinson's disease (PD). Mutations in the lysosomal hydrolase β‐glucocerebrosidase (GBA1) are a major risk factor for the development of PD and the molecular events linked to the reduced activity of GBA1 and the pathological accumulation of lipids and α‐synuclein are just at the beginning to be understood. New therapeutic concepts in regards to how to increase the expression, stability, or delivery of β‐glucocerebrosidase to lysosomes are currently developed.This article is part of a special issue on Parkinson disease.
Walking the tightrope: proteostasis and neurodegenerative disease
Authors: Yerbury Justin J. , Ooi Lezanne , Dillin Andrew , Saunders Darren N. , Hatters Danny M. , Beart Philip M. , Cashman Neil R. , Wilson Mark R. , Ecroyd Heath 
Published: February 2016

AbstractA characteristic of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), is the aggregation of specific proteins into protein inclusions and/or plaques in degenerating brains. While much of the aggregated protein consists of disease specific proteins, such as amyloid‐β, α‐synuclein, or superoxide dismutase1 (SOD1), many other proteins are known to aggregate in these disorders. Although the role of protein aggregates in the pathogenesis of neurodegenerative diseases remains unknown, the ubiquitous association of misfolded and aggregated proteins indicates that significant dysfunction in protein homeostasis (proteostasis) occurs in these diseases. Proteostasis is the concept that the integrity of the proteome is in fine balance and requires proteins in a specific conformation, concentration, and location to be functional. In this review, we discuss the role of specific mechanisms, both inside and outside cells, which maintain proteostasis, including molecular chaperones, protein degradation pathways, and the active formation of inclusions, in neurodegenerative diseases associated with protein aggregation.
imageA characteristic of many neurodegenerative diseases is the aggregation of specific proteins, which alone provides strong evidence that protein homeostasis is disrupted in these disease states. Proteostasis is the maintenance of the proteome in the correct conformation, concentration, and location by functional pathways such as molecular chaperones and protein degradation machinery. Here, we discuss the potential roles of quality control pathways, both inside and outside cells, in the loss of proteostasis during aging and disease.
Nurses as Leaders in Disaster Preparedness and Response—A Call to Action
Authors: Veenema Tener Goodwin , Griffin Anne , Gable Alicia R. , MacIntyre Linda , Simons RADM Nadine , Couig Mary Pat , Walsh John J. , Lavin Roberta Proffitt , Dobalian Aram , Larson Elaine 
Published: February 2016

AbstractPurposeTo develop a vision for the future of disaster nursing, identify barriers and facilitators to achieving the vision, and develop recommendations for nursing practice, education, policy, and research.Design and MethodsA series of semistructured conference calls were conducted with 14 national subject matter experts to generate relevant concepts regarding national nursing workforce preparedness. An invitational daylong workshop hosted by the Veterans Emergency Management Evaluation Center, U.S. Department of Veterans Affairs, was held in December 2014 to expand and refine these concepts. Workshop participants included 70 nurses, emergency managers, and a broad range of public health professionals. Conference call notes and audiotapes of the workshop were transcribed and thematic analysis conducted to outline a vision for the future of nursing in disaster preparedness and response, and to articulate an agenda for nursing practice, education, policy, and research to achieve that vision.FindingsThe group developed a vision for the future of disaster nursing, and identified current barriers and opportunities to advance professional disaster nursing. A broad array of recommendations for nursing practice, education, policy, and research, as well as implementation challenges, are summarized in this article.ConclusionsThis project represents an important step toward enhancing nurses’ roles as leaders, educators, responders, policymakers, and researchers in disaster preparedness and response. Nurses and the health and human service organizations that employ them are encouraged to engage in an expansive national dialogue regarding how to best incorporate the vision and recommendations into their individual lives and the organizations for which they work.Clinical RelevanceNurses comprise the largest healthcare workforce, and opportunities exist to strengthen disaster readiness, enhance national surge capacity, and build community resiliency to disasters.
Tenoumer impact crater, Mauritania: Impact melt genesis from a lithologically diverse target
Authors: Schultze Dina Simona , Jourdan Fred , Hecht Lutz , Reimold Wolf Uwe , Schmitt Ralf‐Thomas 
Published: February 2016

AbstractImpact melt rocks from the 1.9 km diameter, simple bowl‐shaped Tenoumer impact crater in Mauritania have been analyzed chemically and petrologically. They are heterogeneous and can be subdivided into three types based on melt matrix color, occurrence of lithic clast components, amount of vesiculation (melt degassing), different proportions of carbonate melt mingled into silicate melt, and bulk rock chemical composition. These heterogeneities have two main causes (1) due to the small size of the impact crater, there was probably no coherent melt pool where a homogeneous mixture of melts, derived from different target lithologies, could be created; and (2) melt rock heterogeneity occurring at the thin section scale is due to fast cooling during and after the dynamic ejection and emplacement process. The overall period of crystal growth from these diverse melts was extremely short, which provides a further indication that complete chemical equilibration of the phases could not be achieved in such short time. Melt mixing processes involved in the generation of impact melts are, thus, recorded in nonequilibrium growth features. Variable mixing processes between chemically different melt phases and the formation of hybrid melts can be observed even at millimeter scales. Due to extreme cooling rates, different mixing and mingling stages are preserved in the varied parageneses of matrix minerals and in the mineral chemistry of microlites. 40Ar39Ar step‐heating chronology on specimens from three melt rock samples yielded five concordant inverse isochron ages. The inverse isochron plots show that minute amounts of inherited 40Ar* are present in the system. We calculated a weighted mean age of 1.57 ± 0.14 Ma for these new results. This preferred age represents a refinement from the previous range of 21 ka to 2.5 Ma ages based on K/Ar and fission track dating.
Silencing of the tomato phosphatidylinositol‐phospholipase C2 (SlPLC2) reduces plant susceptibility to Botrytis cinerea
Authors: Gonorazky Gabriela , Guzzo María Carla , Abd‐El‐Haliem Ahmed M. , Joosten Matthieu H.A.J. , Laxalt Ana María 
Published: February 2016

SummaryThe tomato [Solanum lycopersicum (Sl)] phosphatidylinositol‐phospholipase C (PI‐PLC) gene family is composed of six members, named SlPLC1 to SlPLC6, differentially regulated on pathogen attack. We have previously shown that the fungal elicitor xylanase induces a raise of SlPLC2 and SlPLC5 transcripts and that SlPLC2, but not SlPLC5, is required for xylanase‐induced expression of defense‐related genes. In this work we studied the role of SlPLC2 in the interaction between tomato and the necrotrophic fungus Botrytis cinerea. Inoculation of tomato leaves with B. cinerea increases SlPLC2 transcript levels. We knocked‐down the expression of SlPLC2 by virus‐induced gene silencing and plant defense responses were analyzed upon B. cinerea inoculation. SlPLC2 silenced plants developed smaller necrotic lesions concomitantly with less proliferation of the fungus. Silencing of SlPLC2 resulted as well in a reduced production of reactive oxygen species. Upon B. cinerea inoculation, transcript levels of the salicylic acid (SA)‐defense pathway marker gene SlPR1a were diminished in SlPLC2 silenced plants compared to non‐silenced infected plants, while transcripts of the jasmonic acid (JA)‐defense gene markers Proteinase Inhibitor I and II (SlPI‐I and SlPI‐II) were increased. This implies that SlPLC2 participates in plant susceptibility to B. cinerea.
Application of cosmetic nail varnish does not affect the antifungal efficacy of amorolfine 5% nail lacquer in the treatment of distal subungual toenail onychomycosis: results of a randomised active‐controlled study and in vitro assays
Authors: Sigurgeirsson B. , Ghannoum M. A. , Osman‐Ponchet H. , Kerrouche N. , Sidou F. 
Published: February 2016

SummaryAs onychomycosis is unsightly, this study clinically evaluated whether the antifungal efficacy of amorolfine 5% nail lacquer (NL) was affected by a masking, natural‐coloured, cosmetic nail varnish applied 24 h later; in vitro investigations were also performed. Subjects with mild‐to‐moderate distal subungual toenail onychomycosis were randomised to receive amorolfine 5% NL once weekly with or without cosmetic nail varnish applied 24 h later. After 12‐week treatment, antifungal activity of affected toenail clippings was assessed by measurement of zones of inhibition (ZOIs) on Trichophyton mentagrophytes seeded agar plates. Mean diameters were 53.5 mm for the amorolfine 5% NL‐alone group (n = 23) and 53.6 mm for amorolfine 5% NL plus cosmetic nail varnish group (n = 25). Also, mycological cultures of subungual debris at week 12 were negative for all subjects in both groups. Most subjects (88%) reported that cosmetic nail varnish masked their infected toenails. Additionally, cadaver human nails coated in vitro with or without cosmetic nail varnish 10 min or 24 h post amorolfine NL application all gave ZOIs on Trichophyton rubrum agar plates representing potent antifungal activity. In conclusion, cosmetic nail varnish applied post amorolfine had no effect on the subungual antifungal activity of amorolfine 5% NL or its penetration through toenails.
Immunolocalization of AMPA receptor subunits within the enteric nervous system of the mouse colon and the effect of their activation on spontaneous colonic contractions
Authors: Seifi M. , Swinny J. D. 
Published: February 2016

AbstractBackgroundThe appropriate expression of specific neurotransmitter receptors within the cellular networks that compose the enteric nervous system (ENS) is central to the regulation of gastrointestinal (GI) functions. While the ENS expression patterns of the neurotransmitter glutamate have been well documented, the localization of its receptors on ENS neurons remains to be fully characterized. We investigated the expression patterns of glutamate receptor AMPA subunits within ENS neurons of the mouse colon and the consequences of their pharmacological activation on spontaneous colonic contractility.MethodsRT‐PCR was used to detect individual AMPA receptor (GluR 1‐4) subunit expression at the mRNA level in mouse colon tissue. Immunohistochemistry and confocal microscopy was used to localize the expression of the GluR1 and 4 subunits in colon tissue. Brain tissue was used as a positive control. Organ bath preparations were used to determine the effect of AMPA receptors activation on the force and frequency of colonic longitudinal smooth muscle spontaneous contractions.Key ResultsGluR1, 3, 4 mRNA was detected in the mouse colon. Immunoreactivity for GluR1 and 4 subunits was detected on the somatic and dendritic surfaces of subpopulations of neurochemically defined ENS neurons. The pharmacological activation of AMPA receptors increased the force but not frequency of spontaneous colonic contractions.Conclusions & InferencesMolecularly distinct AMPA receptor subtypes are differentially expressed within the neural networks of the mouse colon and have a direct role in motility. These data provide the rationale for the development of AMPA‐selective ligands for the therapeutic delivery to the GIT in motility disorders.
Radiologic Improvement After Early Medical Intervention in Localised Facial Morphea
Authors: Khan Muhammad Amjad , Shaw Lindsay , Eleftheriou Despina , Prabhakar Prab , Chong Wui K. , Glover Mary 
Published: February 2016

AbstractWe report the case of a young girl who presented with hemiparesis, seizures, and subtle features consistent with a linear form of facial morphea (en coup de sabre). She was treated with pulsed parenteral steroids and oral steroids and started on methotrexate. Magnetic resonance imaging results and neurologic problems improved after 6 months. Switching off inflammation early in the course of disease seemed to reverse some of the central nervous system changes. Assessment of children with unexplained hemiparesis and seizures should include careful examination of the face and scalp, looking for subtle signs of skin change and asymmetry. This is one of the few reported cases of neuroradiologic improvement after immunosuppressive treatment in a child with en coup de sabre.
Transplant related ocular surface disorders: Advanced techniques for ocular surface rehabilitation after ocular complications secondary to hematopoietic stem cell transplantation
Authors: Stahl Erin D. , Mahomed Faheem , Hans Amneet K. , Dalal Jignesh D. 
Published: February 2016

AbstractHSCT has been linked to the development of an assortment of ocular surface complications with the potential to lead to permanent visual impairment if left untreated or if not treated early in the course of disease. Strategies for therapy include maintenance of lubrication and tear preservation, prevention of evaporation, decreasing inflammation, and providing epithelial support. The ultimate aim of treatment is to prevent permanent ocular sequelae through prompt ophthalmology consultation and the use of advanced techniques for ocular surface rehabilitation. We describe several rehabilitation options of ocular surface complications occurring secondarily during the post‐HSCT course.
Fragile X mental retardation protein controls ion channel expression and activity
Authors: Ferron Laurent 
Published: February 2016

AbstractFragile X‐associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA‐binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage‐gated potassium channels (Kv3.1 and Kv4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium‐activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single‐channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium‐activated potassium (BK) channel; this interaction increases calcium‐dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage‐gated calcium channel, Cav2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X‐associated disorders.
image
Complete Coding Sequences of Three Toscana Virus Strains Isolated from Sandflies in France
Authors: Baklouti Amal , Leparc Goffard Isabelle , Piorkowski Geraldine , Coutard Bruno , Papageorgiou Nicolas , De Lamballerie Xavier , Charrel Rémi N. 
Published: February 2016

ABSTRACT

Toscana virus (TOSV) is an arthropod-borne virus belonging to the sandfly fever Naples virus species within the genus
Phlebovirus
. We report here the complete coding sequences of three TOSV strains belonging to lineage B and isolated from sandflies trapped in the Southeast of France between 2009 and 2013.
Direct Visualization of Ebola Virus Fusion Triggering in the Endocytic Pathway
Authors: Spence Jennifer S. , Krause Tyler B. , Mittler Eva , Jangra Rohit K. , Chandran Kartik 
Published: February 2016

ABSTRACT

Ebola virus (EBOV) makes extensive and intricate use of host factors in the cellular endosomal/lysosomal pathway to release its genome into the cytoplasm and initiate infection. Following viral internalization into endosomes, host cysteine proteases cleave the EBOV fusion glycoprotein (GP) to unmask the binding site for its intracellular receptor, the cholesterol transporter Niemann-Pick C1 (NPC1). GP-NPC1 interaction is required for viral entry. Despite these and other recent discoveries, late events in EBOV entry following GP-NPC1 binding and culminating in GP-catalyzed fusion between viral and cellular lipid bilayers remain enigmatic. A mechanistic understanding of EBOV membrane fusion has been hampered by the failure of previous efforts to reconstitute fusion
in vitro
or at the cell surface. This report describes an assay to monitor initial steps directly in EBOV membrane fusion—triggering of GP and virus-cell lipid mixing—by single virions in live cells. Fusogenic triggering of GP occurs predominantly in Rab7-positive (Rab7
+
) endosomes, absolutely requires interaction between proteolytically primed GP and NPC1, and is blocked by key GP-specific neutralizing antibodies with therapeutic potential. Unexpectedly, cysteine protease inhibitors do not inhibit lipid mixing by virions bearing precleaved GP, even though they completely block cytoplasmic entry by these viruses, as shown previously. These results point to distinct cellular requirements for different steps in EBOV membrane fusion and suggest a model in which host cysteine proteases are dispensable for GP fusion triggering after NPC1 binding but are required for the formation of fusion pores that permit genome delivery.

IMPORTANCE
Ebola virus (EBOV) causes outbreaks of highly lethal disease for which no approved vaccines or treatments exist. Recent work has elucidated key molecular features of the complex EBOV entry process, including stepwise interactions with multiple host factors. However, there is a critical gap in our understanding of events that surround the final membrane fusion step which persists due to the paucity of direct and extensive investigation of EBOV fusion. Here, we report a real-time assay for EBOV glycoprotein fusion triggering and use it to define its cellular location and requirements. We also uncover an unexpected requirement for host proteases at a step after fusion triggering that may reflect their role in formation of fusion pores for genome delivery.
Adiposity and response to an obesity prevention intervention in Pakistani and Bangladeshi primary school boys and girls: a secondary analysis using the BEACHeS feasibility study
Authors: Cezard Geneviève , Bansal Narinder , Bhopal Raj , Pallan Miranda , Gill Paramjit , Barrett Timothy , Adab Peymane 
Published: February 2016

ObjectivesAs a secondary analysis of the BEACHeS study, we hypothesised there would be sex differences in Pakistani and Bangladeshi school children when examining adiposity and their response to an obesity intervention.DesignThe Birmingham healthy Eating and Active lifestyle for CHildren Study (BEACHeS) was designed as a Phase II feasibility study of a complex intervention.Setting8 primary schools with predominantly South Asian children in Birmingham, UKParticipants1090 pupils (aged 5–7 years old) from school year 1 and 2 were allocated at school level to receive an intervention. A total of 574 were enrolled in the study with consent. We focused on the 466 children of Pakistani and Bangladeshi origin (50.6% boys).InterventionDelivered between 2007 and 2009, the 1-year obesity prevention intervention targeted school and family-based dietary and physical activities.Primary and secondary outcome measures and analysisAdiposity measures including skinfold thickness were compared by sex at baseline and follow-up. Gains in adiposity measures were compared between control and intervention arms in boys and in girls. Measures were compared using two-sample t tests and Wilcoxon-Mann-Whitney rank sum tests according to normality distribution.ResultsAt baseline, girls had larger skinfold measures at all sites compared to boys although body mass index (BMI) was similar (eg, median subscapular skinfold 6.6 mm vs 5.7 mm; p<0.001). At follow-up, girls in the intervention group gained less weight and adiposity compared to respective controls (p<0.05 for weight, BMI, waist circumference, central and thigh skinfold) with a median total skinfold gain of 7.0 mm in the control group compared to 0.3 mm in the intervention group.ConclusionsOur secondary analysis suggests differences in adiposity in Pakistani and Bangladeshi girls and boys and in the effect of the intervention reducing adiposity in girls. These preliminary findings indicate that including sex differences should be examined in future trials.Trial registration numberISRCTN51016370; Post-results.