bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of infiltrating peripheral myeloid cells in the brains of mouse models of lysosomal storage disorders
Authors: Cho Soo Min , Vardi Ayelet , Platt Nicolas , Futerman Anthony H. 
Published: June 2018

AbstractApproximately 70 lysosomal storage diseases are currently known, resulting from mutations in genes encoding lysosomal enzymes and membrane proteins. Defects in lysosomal enzymes that hydrolyze sphingolipids have been relatively well studied. Gaucher disease is caused by the loss of activity of glucocerebrosidase, leading to accumulation of glucosylceramide. Gaucher disease exhibits a number of subtypes, with types 2 and 3 showing significant neuropathology. Sandhoff disease results from the defective activity of β‐hexosaminidase, leading to accumulation of ganglioside GM2. Niemann‐Pick type C disease is primarily caused by the loss of activity of the lysosomal membrane protein, NPC1, leading to storage of cholesterol and sphingosine. All three disorders display significant neuropathology, accompanied by neuroinflammation. It is commonly assumed that neuroinflammation is the result of infiltration of monocyte‐derived macrophages into the brain; for instance, cells resembling lipid‐engorged macrophages (‘Gaucher cells’) have been observed in the brain of Gaucher disease patients. We now review the evidence that inflammatory macrophages are recruited into the brain in these diseases and then go on to provide some experimental data that, at least in the three mouse models tested, monocyte‐derived macrophages do not appear to infiltrate the brain. Resident microglia, which are phenotypically distinct from infiltrating macrophages, are the only myeloid population present in significant numbers within the brain parenchyma in these authentic mouse models, even during the late symptomatic stages of disease when there is substantial neuroinflammation.Open science badgesThis article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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This article is part of the Special Issue “Lysosomal Storage Disorders”.
Cyclophilin D regulates neuronal activity‐induced filopodiagenesis by fine‐tuning dendritic mitochondrial calcium dynamics
Authors: Sui Shaomei , Tian Jing , Gauba Esha , Wang Qi , Guo Lan , Du Heng 
Published: June 2018

AbstractRecent studies have highlighted the role of mitochondria in dendritic protrusion growth and plasticity. However, the detailed mechanisms that mitochondria regulate dendritic filopodia morphogenesis remain elusive. Cyclophilin D (CypD, gene name: Ppif) controls the opening of mitochondrial permeability transition pore. Although the pathological relevance of CypD has been intensively investigated, little is known about its physiological function in neurons. Here, we have found that genetic depletion of or pharmaceutical inhibition of CypD blunts the outgrowth of dendritic filopodia in response to KCl‐stimulated neuronal depolarization. Further cell biological studies suggest that such inhibitory effect of CypD loss‐of‐function is closely associated with compromised flexibility of dendritic mitochondrial calcium regulation during neuronal depolarization, as well as the resultant changes in intradendritic calcium homeostasis, calcium signaling activation, dendritic mitochondrial motility and redistribution. Interestingly, loss of CypD attenuates oxidative stress‐induced mitochondrial calcium perturbations and dendritic protrusion injury. Therefore, our study has revealed the physiological function of CypD in dendritic plasticity by acting as a fine‐tuner of mitochondrial calcium homeostasis. Moreover, CypD plays distinct roles in neuronal physiology and pathology.
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Cover Image for this issue: doi: 10.1111/jnc.14189.
Melatonin expression in periodontitis and obesity: An experimental in‐vivo investigation
Authors: Virto L. , Haugen H. J. , Fernández‐Mateos P. , Cano P. , González J. , Jiménez‐Ortega V. , Esquifino A. I. , Sanz M. 
Published: June 2018

Background and ObjectiveMelatonin deficiency has been associated with obesity and systemic inflammation. This study aims to evaluate whether melatonin could interfere with the mechanisms of co‐morbidity linking obesity and periodontitis.Material and MethodsTwenty‐eight male Wistar rats were randomly divided in 4 groups: control group (Con) (fed with standard diet); high‐fat diet group (HFD) (fed with a diet containing 35.2% fat); Con group with induced periodontitis (Con‐Perio) and HFD group with induced periodontitis (HFD‐Perio). To induce periodontitis, the method of oral gavages with Porphyromonas gingivalis ATCC W83K1 and Fusobacterium nucleatum DMSZ 20482 was used. Circulating melatonin levels were analyzed by multiplex immunoassays. Periodontitis was assessed by alveolar bone loss (micro‐computed tomography and histology) and by surrogate inflammatory outcomes (periodontal pocket depth, modified gingival index and plaque dental index).ResultsPlasma melatonin levels were significantly decreased (P < .05) in the obese rats with periodontitis when compared with controls or with either obese or periodontitis rats. Alveolar bone loss increased 27.71% (2.28 µm) in HFD‐Perio group compared with the Con group. The histological analysis showed marked periodontal tissue destruction with osteoclast activity, particularly in the HFD‐Perio group. A significant negative correlation (P < .05) was found between periodontal pocket depth, modified gingival index and circulating melatonin levels.ConclusionObese and periodontitis demonstrated significantly lower melatonin concentrations when compared with controls, but in obese rats with periodontitis these concentrations were even significantly lower when compared with either periodontitis or obese rats. These results may indicate that melatonin deficiency could be a key mechanism explaining the co‐morbidity effect in the association between obesity and periodontitis.
Microbiota and Dose Response: Evolving Paradigm of Health Triangle
Authors: Coleman Margaret , Elkins Christopher , Gutting Bradford , Mongodin Emmanuel , Solano‐Aguilar Gloria , Walls Isabel 
Published: June 2018

AbstractSRA Dose‐Response and Microbial Risk Analysis Specialty Groups jointly sponsored symposia that addressed the intersections between the “microbiome revolution” and dose response. Invited speakers presented on innovations and advances in gut and nasal microbiota (normal microbial communities) in the first decade after the Human Microbiome Project began. The microbiota and their metabolites are now known to influence health and disease directly and indirectly, through modulation of innate and adaptive immune systems and barrier function. Disruption of healthy microbiota is often associated with changes in abundance and diversity of core microbial species (dysbiosis), caused by stressors including antibiotics, chemotherapy, and disease. Nucleic‐acid‐based metagenomic methods demonstrated that the dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, probiotics, and prebiotics were considered in human and animal models (in vivo and in vitro). Discussion included approaches for design of future microbial dose–response studies to account for the presence of the indigenous microbiota that provide normal colonization resistance, and the absence of the protective microbiota in dysbiosis. As NextGen risk analysis methodology advances with the “microbiome revolution,” a proposed new framework, the Health Triangle, may replace the old paradigm based on the Disease Triangle (focused on host, pathogen, and environment) and germophobia. Collaborative experimental designs are needed for testing hypotheses about causality in dose–response relationships for pathogens present in our environments that clearly compete in complex ecosystems with thousands of bacterial species dominating the healthy superorganism.
Self‐harm by Sharp Foreign Body Ingestion
Authors: Robertson Alexander R. 
Published: June 2018

ObjectiveIngestion of sharp foreign bodies is a less frequently encountered method of selfharm. This study aims to follow up patients presenting with foreign body (FB) ingestion requiring urgent endoscopic intervention under general anaesthetic in theatre, characterise each patient and establish whether admission or removal of the FB promotes further self‐harm.MethodEleven adult patients, totalling 38 presentations over a 28‐month period were identified. Each was followed up from an initial presentation requiring endoscopy.Result9/11 (81.9%) where transferred either from prison or psychiatric care with an extensive history of multimodal and usually violent self‐harm. Of these 8/9 (88.9%) had a formal psychiatric diagnosis linked to their previous self‐harm. Objects retrieved included pens, razor blades, cutlery, wiring, batteries, a metal screw and a TV aerial. The median time between presentations with self‐harm was 11 days. Those discharged from the emergency department re‐presented after a median of 7.5 days. This was longer, at 14 days, if admitted to hospital; with those having endoscopic procedures re‐presenting after a median of 11 days.ConclusionsInpatient endoscopic removal of the FB was not associated with an earlier presentation with further self‐harm when compared with discharge straight form A+E, but was frequently repeated, often in a characterised manner.
LITTLELEAF (LL) encodes a WD40 repeat domain‐containing protein associated with organ size variation in cucumber
Authors: Yang Luming , Liu Hanqiang , Zhao Jianyu , Pan Yupeng , Cheng Siyuan , Lietzow Calvin D. , Wen Changlong , Zhang Xiaolan , Weng Yiqun 
Published: June 2018

SummaryPlants employ tight genetic control to integrate intrinsic growth signals and environmental cues to enable organs to grow to a defined size. Many genes contributing to cell proliferation and/or cell expansion, and consequently organ size control, have been identified, but the regulatory pathways are poorly understood. Here we have characterized a cucumber littleleaf (ll) mutant which exhibits smaller organ sizes but more lateral branches than the wild type. The small organ size in ll was due to a reduction of both cell number and cell size. Quantitative trait locus (QTL) analyses revealed co‐localization of major‐effect QTLs for fruit size, fruit and seed weight, as well as number of lateral branches, with the LL locus indicating pleiotropic effects of the ll mutation. We demonstrate that LL is an ortholog of Arabidopsis STERILE APETALA (SAP) encoding a WD40 repeat domain‐containing protein; the mutant protein differed from the wild type by a single amino acid substitution (W264G) in the second WD40 repeat. W264 was conserved in 34 vascular plant genomes examined. Phylogenetic analysis suggested that LL originated before the emergence of flowering plants but was lost in the grass genome lineage. The function of LL in organ size control was confirmed by its overexpression in transgenic cucumbers and ectopic expression in Arabidopsis. Transcriptome profiling in LL and ll bulks revealed a complex regulatory network for LL‐mediated organ size variation that involves several known organ size regulators and associated pathways. The data support LL as an important player in organ size control and lateral branch development in cucumber.
Chemical quenching of singlet oxygen by plastoquinols and their oxidation products in Arabidopsis
Authors: Ferretti Ursula , Ciura Joanna , Ksas Brigitte , Rác Marek , Sedlářová Michaela , Kruk Jerzy , Havaux Michel , Pospíšil Pavel 
Published: June 2018

SummaryPrenylquinols (tocochromanols and plastoquinols) serve as efficient physical and chemical quenchers of singlet oxygen (1O2) formed during high light stress in higher plants. Although quenching of 1O2 by prenylquinols has been previously studied, direct evidence for chemical quenching of 1O2 by plastoquinols and their oxidation products is limited in vivo. In the present study, the role of plastoquinol‐9 (PQH2‐9) in chemical quenching of 1O2 was studied in Arabidopsis thaliana lines overexpressing the SOLANESYL DIPHOSPHATE SYNTHASE 1 gene (SPS1oex) involved in PQH2‐9 and plastochromanol‐8 biosynthesis. In this work, direct evidence for chemical quenching of 1O2 by plastoquinols and their oxidation products is presented, which is obtained by microscopic techniques in vivo. Chemical quenching of 1O2 was associated with consumption of PQH2‐9 and formation of its various oxidized forms. Oxidation of PQH2‐9 by 1O2 leads to plastoquinone‐9 (PQ‐9), which is subsequently oxidized to hydroxyplastoquinone‐9 [PQ(OH)‐9]. We provide here evidence that oxidation of PQ(OH)‐9 by 1O2 results in the formation of trihydroxyplastoquinone‐9 [PQ(OH)3‐9]. It is concluded here that PQH2‐9 serves as an efficient 1O2 chemical quencher in Arabidopsis, and PQ(OH)3‐9 can be considered as a natural product of 1O2 reaction with PQ(OH)‐9. The understanding of the mechanisms underlying 1O2 chemical quenching provides information on the role of plastoquinols and their oxidation products in the response of plants to photooxidative stress.
Vascular endothelial growth factor as early biomarker for hypoxia in Oreochromis niloticus
Authors: Hamdy Soha M. , Shaban Amany M. , Mahmoud Amany A. , Gad Nahed S. , Ibrahim Wael A. 
Published: June 2018

AbstractAquatic pollution is a serious problem causing fish hypoxia. This study is conducted to assess the effects of environmental pollutants entering Lake Qaroun using vascular endothelial growth factor (VEGF) biomarker on Oreochromis niloticus. Water and fish samples were collected from contaminated sites to be compared with a reference relatively unpolluted site. Water physicochemical parameters, the oxidative stress biomarkers and histological studies of liver and gills were determined. Highly significant differences in water quality parameters were observed. Fish sampled from contaminated sites showed highly significant changes in oxidative stress and hypoxia‐related biomarkers compared to the reference site. These changes were accompanied by the existence of histological damages in liver and gill tissues. Moreover, there were differences in the banding pattern of fish serum proteins from the same sites. These results provide evidence that stress biomarkers and VEGF are useful for the assessment of hypoxia in aquatic environments influenced by multiple pollution sources.
Train Energy and Dynamics Simulator (TEDS) Revenue Service Validation
Authors: Stewart Monique F. , Andersen David R. , Booth Graydon F. , Buel Tanner , Singh Som P. 
Published: June 2018

The Train Energy and Dynamics Simulator (TEDS) is state-of-the-art simulation software, developed by the Federal Railroad Administration (FRA), to study train operation safety and performance as affected by a wide variety of rolling stock, track, train handling and operating configurations. As part of developing TEDS, existing and published data on braking, draft systems and train performance were used for initial validation of TEDS.
This paper describes two revenue service tests conducted to further validate TEDS. The first test was on a loaded unit train, while the second test was on a mixed train with empty and loaded cars and included distributed power in which the remote brake valve was cut in. Collected test data included throttle position, train speed, locomotive power, brake system pressures and coupler forces. Several events from these tests, representing typical train operating scenarios, were selected for comparison with TEDS predicted results. The TEDS predictions matched the measured test data for all of the scenarios simulated, further validating the performance of the software and offering additional assurance on the use of TEDS for simulating performance and safety critical train dynamic behavior.
Improving Collision Post Crashworthiness of Legacy Locomotives
Authors: Gordon Jeff , Swamy Srini , Cakdi Sabri , Radovich Matthew , Prabhakaran Anand , Singh Som P. 
Published: June 2018

Modern freight locomotives are built to crashworthiness standards that are defined in Subpart D of Code of Federal Regulations (CFR) Part 229 and Association of American Railroads (AAR) S-580 standards [1, 2]. The first freight locomotive crashworthiness standard, AAR S-580, was released in 1989 and became effective as of August 1990 [3]. Locomotives that were manufactured before the 1990, so-called “legacy”, lack the crew protection offered by the modern “crashworthy” locomotives [4]. While legacy locomotives, such as narrow-nose designs that were manufactured before 1990s, are generally relegated to non-lead locomotive service in Class I railroads, these units are sometimes used in mainline service. Even though the number of narrow-nose locomotives has declined, there remains a risk of injuries and fatalities for the crew for the next several years.
The scope of this study is the following;
• The assessment of injuries and fatalities from collisions involving legacy locomotives,
• The crashworthiness evaluation of collision posts for a sample legacy (narrow-nose, legacy) locomotive assembled in the 1960s and rebuilt in 2001,
• Analysis of alternative collision post designs to meet and exceed the collision post requirements in the 2001 version of AAR S-580.
Transient Stability of Rotary Frequency Converter Fed Low Frequency Railway Grids: The Impact of Different Grid Impedances and Different Converter Station Configurations
Authors: Laury John , Abrahamsson Lars , Bollen Math 
Published: June 2018

One method of strengthening low frequency AC railway grids is to upgrade Booster Transformer (BT) catenary systems, to Auto Transformer (AT) catenary systems. An AT catenary system has lower equivalent impedance compared to a BT system. Thus, an upgrade makes the existing converter stations electrically closer.
Converter stations may have different types of Rotary Frequency Converters (RFCs) installed in them, and it is not well explored how different RFCs behaves and interact during and after a large disturbance.
Using the Anderson-Fouad model of synchronous machines to describe the dynamics of RFCs, several case studies have been performed through numerical simulations. The studies investigate the interactions within and between converter stations constituted with different RFC types, for BT as well AT catenary systems.
The numerical studies reveal that replacing BT with AT catenary systems, results in a more oscillatory system behaviour. This is seen for example in the power oscillations between and inside converter stations, after fault clearance.
Electroacupuncture: A New Approach to Open the Blood–brain Barrier in Rats Recovering from Middle Cerebral Artery Occlusion
Authors: Zhang Jiangsong , Lin Xianming , Zhou Hui , Chen Yuanyuan , Xiao Shuangkai , Jiao Junyue , Zhao Yibin , Di Zhong 
Published: June 2018

Objective To examine for an opening effect on the blood–brain barrier (BBB) in intact rats and rats with experimental ischaemia-reperfusion (I/R) during the recovery period after various electroacupuncture (EA) treatments with different time courses, and to determine whether there is a time-dependent effect. An additional objective was to determine whether this method could induce the penetration of nerve growth factor (NGF) through the BBB. Methods A middle cerebral artery occlusion (MCAO) model was first established. We chose different stimulation time courses and observed the effects of EA treatment (100 Hz frequency; 2 mA intensity) at GV20 and GV26 on the BBB in rats recovering from MCAO 3 weeks after modelling. The rats were injected with 2% Evans blue (EB) saline. The brain water content was measured using a wet/dry weighing method. The degree of penetration of EB was detected using spectrophotometry and laser confocal microscopy. The rats were then injected with NGF, and the concentration of NGF in the brain tissues was measured using ELISA. Results The increase in the BBB permeability was most notable following the 8 min EA stimulation (P<0.05), which may be advantageous for the targeted delivery of drugs (such as NGF) into the brain. Additionally, this effect did not appear to cause brain oedema (P>0.05) in healthy or MCAO rats. Conclusions EA treatment for a certain stimulation time at GV20 and GV26 in MCAO rats can increase BBB permeability.
Left ventricular chamber dilation and filling pressure may help to categorise patients with type 2 diabetes
Authors: Zoppini Giacomo , Bergamini Corinna , Bonapace Stefano , Trombetta Maddalena , Mantovani Alessandro , Toffalini Anna , Lanzoni Laura , Bertolini Lorenzo , Zenari Luciano , Bonora Enzo , Targher Giovanni , Rossi Andrea 
Published: June 2018

BackgroundType 2 diabetes may alter cardiac structure and function. Many patients with type 2 diabetes have diastolic dysfunction with preserved ejection fraction (EF). Recently, this latter measure was criticised. Thus, this research looked at the impact of left ventricular end-diastolic volume and E/e′ ratio variations in patients with type 2 diabetes and preserved EF with the aim to recognise different clinical phenotypes.MethodsIn this cross-sectional study, we evaluated 176 men affected by type 2 diabetes with transthoracic echocardiography. All subjects have preserved EF (>50%). Patients were stratified into four groups based on the median value of both left ventricular end-diastolic volume and E/e′ ratio, and the clinical variables were registered. The independent predictors associated with the groups were analysed by a multinomial logistic regression model.ResultsDiabetes duration, age, estimated glomerular filtration rate and antihypertensive treatments were significantly different among the groups as were EF, left atrial volume index (LAVI), E/A, septum thickness and s′ mean wave. Multinomial regression analysis showed that the groups significantly differed for age, diabetes duration, EF, LAVI, septum thickness and s′ mean wave. The main result of this study was that patients with higher left ventricular volume and higher E/e′ ratio (group 2) showed the worse clinical profile.ConclusionsOur study might suggest that variations of left ventricular end-diastolic volume along with E/e′ ratio variations, even in the normal range, may allow to recognise phenotypes of patients with type 2 diabetes with worse clinical characteristics. This finding should be tested in prospective studies to assess the predictive roles of these phenotypes.