bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTORC1 activation in B cells confers impairment of marginal zone microarchitecture by exaggerating cathepsin activity
Authors: Meena Naresh Kumar , Pattanayak Shakti Prasad , Ben‐Nun Yael , Benhamron Sandrine , Kumar Saran , Merquiol Emmanuelle , Hövelmeyer Nadine , Blum Galia , Tirosh Boaz 
Published: August 2018

SummaryMammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and lymphocyte proliferation. It is inhibited by the tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2. Deletion of either gene results in robust activation of mTORC1. Mature B cells reside in the spleen at two major anatomical locations, the marginal zone (MZ) and follicles. The MZ constitutes the first line of humoral response against blood‐borne pathogens and undergoes atrophy in chronic inflammation. In previous work, we showed that mice deleted for TSC1 in their B cells (TSC1BKO) have almost no MZ B cells, whereas follicular B cells are minimally affected. To explore potential underlying mechanisms for MZ B‐cell loss, we have analysed the spleen MZ architecture of TSC1BKO mice and found it to be severely impaired. Examination of lymphotoxins (LTα and LTβ) and lymphotoxin receptor (LTβR) expression indicated that LTβR levels in spleen stroma were reduced by TSC1 deletion in the B cells. Furthermore, LTα transcripts in B cells were reduced. Because LTβR is sensitive to proteolysis, we analysed cathepsin activity in TSC1BKO. A higher cathepsin activity, particularly of cathepsin B, was observed, which was reduced by mTORC1 inhibition with rapamycin in vivo. Remarkably, in vivo administration of a pan‐cathepsin inhibitor restored LTβR expression, LTα mRNA levels and the MZ architecture. Our data identify a novel connection, although not elucidated at the molecular level, between mTORC1 and cathepsin activity in a manner relevant to MZ dynamics.
Eu‐substitution‐induced commensurate phase with enhanced ferroelectric property in Ba4(EuxLa1−x)2Fe2Nb8O30 multiferroics
Authors: Hong Jiang Sheng , Huang Yu Hui , Wu Yong Jun , Fu Mao Sen , Li Juan , Liu Xiao Qiang 
Published: August 2018

AbstractEffects of Eu‐substitution on the crystal structure, dielectric, ferroelectric, and magnetic properties have been systematically studied for Ba4(EuxLa1−x)2Fe2Nb8O30 (x = 0, 0.3, 0.5, 0.7, 0.9, 0.95, 1) tungsten bronze ceramics. The tetragonal bronze structure is confirmed in all compositions. With the increase of x, Ba4(EuxLa1−x)2Fe2Nb8O30 ceramics transform from paraelectric to ferroelectric. The compositions of x = 0.9, 0.95, and 1 show first‐order ferroelectric phase transitions above room temperature (391 K for x = 0.9, 404 K for x = 0.95, and 425 K for x = 1). The ferroelectric behavior is associated with a commensurate octahedral tilting, which is caused by large A2‐A1 ionic‐radius difference. Magnetic hysteresis loops for all compositions at room temperature have been obtained, which could be ascribed to both the secondary phase and tungsten bronze structure per se. It is confirmed that the radius difference between A2 and A1 cations plays a critical role on the structure, dielectric, and ferroelectric characteristics.
Laser‐induced coloration of ceramic tiles covered with magnetron sputtered precursor layers
Authors: Rico Víctor J. , Lahoz Ruth , Rey‐García Francisco , de Francisco Isabel , Gil‐Rostra Jorge , Espinós Juan Pedro , de la Fuente Germán F. , González‐Elipe Agustín R. 
Published: August 2018

AbstractThis paper reports a new methodology for the coloring of glazed ceramic tiles consisting of the near infrared pulsed laser processing of copper containing oxide coatings prepared by magnetron sputtering. As a second approach, the employ for the same purpose of a novel laser furnace technique is also described. Changing the laser parameters and using the laser furnace to treat the tiles at high temperature during irradiation has resulted in a wide color palette. The optical characterization of the modified tiles by UV‐Vis spectroscopy has been complemented with their microstructural and compositional analysis by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Time Of Flight Secondary Ion Mass Spectrometry (TOF‐SIMS). The chemical composition of the surface was obtained by X‐ray Photoemission Spectroscopy (XPS) and its structure determined by X?ray diffraction (XRD). The chemical resistance was characterized by several tests following the norm ISO 10545‐13. Color changes have been attributed to surface microstructural and chemical transformations that have been accounted for by simple models involving different ablation, melting, diffusion, and segregation/agglomeration phenomena depending on the laser treatments employed.
Employee‐friendly practices, product market competition and firm value
Authors: Chang Saeyoung , Jo Hoje 
Published: August 2018

AbstractIn this paper, we examine whether employee‐friendly practices are associated with product market competition, and whether firm value is related to employee‐friendly practices and product market competition. Using a large sample of US firms, we find positive and significant associations between employee friendliness and product market competition, and between firm value and employee friendliness when product market competition is high, consistent with the value creation theory. Both positive relations hold when we account for corporate governance. In addition, using the list of Fortune's ‘100 Best Companies to Work For’ as an alternative measure of employee‐friendly policies, we find firms in more competitive industries are more likely to treat their workers favourably. Furthermore, we find that the market reaction is more positive when firms in more competitive industries are selected for the Fortune list.
Is “chronic kidney disease” a disease?
Authors: Smart Benjamin T.H. , Stevens Richard J. , Verbakel Jan Y. 
Published: August 2018

AbstractSeveral philosophers of medicine have attempted to answer the question “what is disease?” In current clinical practice, an umbrella term “chronic kidney disease” (CKD) encompasses a wide range of kidney health states from commonly prevalent subclinical, asymptomatic disease to rare end‐stage renal disease requiring transplant or dialysis to support life. Differences in severity are currently expressed using a “stage” system, whereby stage 1 is the least severe, and stage 5 the most. Early stage CKD in older patients is normal, of little concern, and does not require treatment. However, studies have shown that many patients find being informed of their CKD distressing, even in its early stages. Using existing analyses of disease in the philosophy literature, we argue that the most prevalent diagnoses of CKD are not, in fact, diseases. We conclude that, in many diagnosed cases of CKD, diagnosing a patient with a “disease” is not only redundant, but unhelpful.
Acyclovir inhibits Cyprinid herpesvirus 3 multiplication in vitro
Authors: Troszok Agnieszka , Kolek Ludmiła , Szczygieł Joanna , Wawrzeczko Joanna , Borzym Ewa , Reichert Michał , Kamińska Teresa , Ostrowski Tomasz , Jurecka Patrycja , Adamek Mikołaj , Rakus Krzysztof , Irnazarow Ilgiz 
Published: August 2018

AbstractCyprinid herpesvirus 3 (CyHV‐3), also known as koi herpesvirus (KHV), is an aetiological agent of a virulent and lethal disease in common and koi carp. In this study, we examined in vitro the anti‐CyHV‐3 activity of acyclovir (ACV), nucleoside analogue commonly used against human herpesviruses, as well as acyclovir monophospate (ACV‐MP). The cytotoxicity of theACVand theACV‐MPfor two common carp cell lines,CCB(Common carp brain) andKF1 (Koi carp fin 1), was determined by means ofMTTand crystal violet assays. In subsequent studies, the concentration of 66.67 μM was applied. TheACVand theACV‐MP(66.67 μM) inhibited a cytopathic effect (CPE) induced by the CyHV‐3 virus in theCCB(ACVby 66%,ACV‐MPby 58%) and theKF1 (ACVby 25%,ACV‐MPby 37%). The viral load measured by the means of TaqManqPCRwas reduced in a range of 67%–93% depending on the analogue, the cell line and the time of incubation. The expression of viral genes (ORF149,ORF3,ORF134 andORF78) inCCBcells infected with the CyHV‐3 was strongly downregulated within the range of 78%–91%. In summary, both theACVand theACV‐MPcan inhibit CyHV‐3 replication in vitro.
First examination of the Lough Neagh European eel (Anguilla anguilla) population for eel virus European, eel virus European X and Anguillid Herpesvirus‐1 infection by employing novel molecular techniques
Authors: McConville James , Fringuelli Elena , Evans Derek , Savage Paul 
Published: August 2018

AbstractLough Neagh is home to the largest wild‐caught European eel (Anguilla anguilla) commercial fishery in the EU, producing 14% of the EU catch and worth £3.2 million to the local economy. Viral infections have been suggested to play a contributory role in the decline of the worldwide eel stock, but previous studies of the Lough Neagh European eel population had not observed either acute or chronic viral signs. Eel virus European (EVE), Eel virus European X (EVEX) and Anguillid herpesvirus‐1 (HVA) have been detected throughout Europe and as the Lough Neagh eel fishery is supplemented by re‐stocking of eels from France, Spain and the United Kingdom and these viral infections may be asymptomatic, it is vital that the viral pathogen prevalence in the Lough is accurately determined. This study aimed to ascertain the presence of these viruses in the Lough Neagh European eel population by employing novel molecular techniques testing specifically for the presence of EVE, EVEX and HVA. No evidence was found of HVA infection, whereas EVE and EVEX were found, albeit at a very low prevalence.
Correlates of burnout among professionals working with people with intellectual and developmental disabilities
Authors: Finkelstein A. , Bachner Y. G. , Greenberger C. , Brooks R. , Tenenbaum A. 
Published: August 2018

AbstractBackgroundAlthough burnout has been recognised as an important stress‐related problem among staff working with people with intellectual and developmental disabilities (IDD), literature on the subject is limited yet emerging. The aim of this study is twofold: (1) to evaluate the level of burnout within different professions working with IDD; (2) to examine the association between socio‐demographic, professional and organisational characteristics and burnout.MethodOne hundred ninety‐nine professionals working with people with IDD were enrolled in the study (66% response rate). Participants were recruited from several facilities that provide care for people with IDD of all ages, in the Jerusalem area and in other cities in central Israel. The anonymous questionnaires included valid and reliable measures of burnout, socio‐demographic variables, professional variables and organisational variables.ResultsParticipants' mean age was 38.3 years, and most were women. There were no significant differences in burnout levels among the different professionals. Role ambiguity, perceived overload, care‐recipient group and job involvement were significant predictors of burnout. The model explained a high percentage (46.8%) of the observed variance.ConclusionsMost of these predictors are organisational measures. These findings demonstrate that organisational variables are more significantly associated with burnout of staff working with people with IDD than the socio‐demographic factors or professional characteristics. Identifying and better understanding the specific factors associated with burnout among professionals working with IDD could facilitate unique intervention programs to reduce burnout levels in staff.
The catalytic function of the gephyrin‐binding protein IQSEC3 regulates neurotransmitter‐specific matching of pre‐ and post‐synaptic structures in primary hippocampal cultures
Authors: Früh Simon , Tyagarajan Shiva K. , Campbell Benjamin , Bosshard Giovanna , Fritschy Jean‐Marc 
Published: August 2018

AbstractIn dissociated neuronal cultures the absence of spatial and temporal cues causes the emergence of mismatched synapses, where post‐synaptic proteins of GABAergic synapses are in part apposed to glutamatergic pre‐synaptic terminals and vice versa. This mismatch offers an opportunity to study the mechanisms that regulate correct apposition of pre‐ and post‐synaptic elements. We report here that the IQ motif and Sec7 domain‐containing protein 3 (IQSEC3; BRAG3; synArfGEF) specifically regulates the mislocalization of GABAergic post‐synaptic density (PSD) proteins. Over‐expression of IQSEC3 constructs harboring mutations that ablate Sec7 domain or IQ motif function revealed that IQSEC3 catalytic activity is involved in the control of apposition between the GABAergic PSD and glutamatergic terminals. Neurons co‐expressing eGFP‐gephyrin with IQSEC3 Sec7 mutant displayed a drastically increased fraction of mismatched eGFP‐gephyrin clusters compared to other IQSEC3 constructs. Along with eGFP‐gephyrin, endogenous GABAA receptor cluster mismatching was increased by IQSEC3 Sec7 mutant over‐expression. Conversely, GFP‐PSD‐95 clusters were unaffected by over‐expression of any IQSEC3 construct. The GABAergic PSD mismatch phenotype was recapitulated by Arf6 dominant‐negative mutant over‐expression, suggesting that Arf6 activation by IQSEC3 is an essential step in this pathway. In addition, we provide biochemical evidence to confirm gephyrin/IQSEC3 interaction near the IQSEC3 IQ motif, which in turn binds calmodulin at low Ca2+ concentrations. Taken together, our findings identify a post‐synaptic protein which specifically regulates correct apposition of the GABAergic PSD to pre‐synaptic terminals.
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Amyloid oligomerization of the Parkinson's disease related protein α‐synuclein impacts on its curvature‐membrane sensitivity
Authors: Gallea José Ignacio , Ambroggio Ernesto E. , Vilcaes Aldo Alejandro , James Nicholas G. , Jameson David M. , Celej María Soledad 
Published: August 2018

AbstractThe amyloid aggregation of the presynaptic protein α‐synuclein (AS) is pathognomonic of Parkinson's disease and other neurodegenerative disorders. Physiologically, AS contributes to synaptic homeostasis by participating in vesicle maintenance, trafficking, and release. Its avidity for highly curved acidic membranes has been related to the distinct chemistry of the N‐terminal amphipathic helix adopted upon binding to appropriated lipid interfaces. Pathologically, AS populate a myriad of toxic aggregates ranging from soluble oligomers to insoluble amyloid fibrils. Different gain‐of‐toxic function mechanisms are linked to prefibrillar oligomers which are considered as the most neurotoxic species. Here, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oligomeric species, produced using a popular method based on lyophilization and rehydration, to lipid vesicles of different curvatures and compositions. We found that AS oligomerization has a profound impact on protein‐lipid interaction, altering binding affinity and/or curvature sensitivity depending on membrane composition. Our work provides novel insights into how the formation of prefibrillar intermediate species could contribute to neurodegeneration due to a loss‐of‐function mechanism.Open PracticesThis 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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The S100B story: from biomarker to active factor in neural injury
Authors: Michetti Fabrizio , D'Ambrosi Nadia , Toesca Amelia , Puglisi Maria Ausiliatrice , Serrano Alessia , Marchese Elisa , Corvino Valentina , Geloso Maria Concetta 
Published: August 2018

AbstractS100B is a Ca2+‐binding protein mainly concentrated in astrocytes. Its levels in biological fluids (cerebrospinal fluid, peripheral and cord blood, urine, saliva, amniotic fluid) are recognized as a reliable biomarker of active neural distress. Although the wide spectrum of diseases in which the protein is involved (acute brain injury, neurodegenerative diseases, congenital/perinatal disorders, psychiatric disorders) reduces its specificity, its levels remain an important aid in monitoring the trend of the disorder. Mounting evidence now points to S100B as a Damage‐Associated Molecular Pattern molecule which, when released at high concentration, through its Receptor for Advanced Glycation Endproducts, triggers tissue reaction to damage in a series of different neural disorders. This review addresses this novel scenario, presenting data indicating that S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease: acute brain injury (ischemic/hemorrhagic stroke, traumatic injury), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis), congenital/perinatal disorders (Down syndrome, spinocerebellar ataxia‐1), psychiatric disorders (schizophrenia, mood disorders), inflammatory bowel disease. In many cases, over‐expression/administration of the protein induces worsening of the disease, whereas its deletion/inactivation produces amelioration. This review points out that the pivotal role of the protein resulting from these data, opens the perspective that S100B may be regarded as a therapeutic target for these different diseases, which appear to share some common features reasonably attributable to neuroinflammation, regardless their origin.
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Improved metabolism and body composition beyond normal levels following gastric bypass surgery: a longitudinal study
Authors: Andersson D. P. , Dahlman I. , Eriksson Hogling D. , Bäckdahl J. , Toft E. , Qvisth V. , Näslund E. , Thorell A. , Rydén M. , Arner P. 
Published: August 2018

AbstractBackgroundThe cardiometabolic risk profile improves following bariatric surgery. However, the degree of improvement in relation to weight‐stable control subjects is unknown.ObjectivesTo study the differences in cardiometabolic risk profile between formerly obese patients following Roux‐en‐Y gastric bypass (RYGB) surgery and control subjects.MethodsSubjects undergoing RYGB and reaching a BMI <30 kg m−2 2 years postsurgery were matched with control subjects regarding age, sex and BMI. The following examinations were performed: insulin sensitivity measured by hyperinsulinaemic–euglycaemic clamp, insulin clearance, homeostatic model assessment of insulin resistance (HOMA‐IR), lipid profile, inflammatory marker levels, dual‐energy X‐ray absorptiometry and subcutaneous adipose tissue cellularity (fat cell size and number).ResultsSixty‐nine subjects undergoing RYGB were matched to a control subject. Insulin sensitivity measured by hyperinsulinaemic–euglycaemic clamp, blood pressure, inflammatory status and glucose, triglyceride and HDL cholesterol levels were comparable to values of control subjects. However, HOMA‐IR (1.0 ± 0.5 vs. 1.3 ± 0.7, P = 0.005), insulin clearance (0.38 ± 0.08 vs. 0.34 ± 0.08 μL m−2 min−1, P < 0.0001) and circulating levels of insulin (31 ± 15 vs. 37 ± 17 pmol L−1, P = 0.008), total cholesterol (4.1 ± 0.7 vs. 4.8 ± 0.9 mmol L−1, P < 0.0001) and LDL cholesterol (2.1 ± 0.6 vs. 2.9 ± 0.8 mmol L−1, P < 0.0001) were improved beyond the levels in matched control subjects. Furthermore, formerly obese subjects had higher lean and lower fat mass as well as a more benign type of adipose cellularity (hyperplasia with many small fat cells) compared to control subjects.ConclusionsSubjects who underwent RYGB and reached a postobese state demonstrated a beneficial body composition, slightly increased insulin sensitivity as indirectly measured by HOMA‐IR and higher insulin clearance, lower atherogenic lipid/lipoprotein levels and benign adipocyte morphology compared with control subjects who had never been obese. In line with previous results, our findings may in part explain why RYGB confers long‐term protection against metabolic complications.
Genes that make you fat, but keep you healthy
Authors: Loos R. J. F. , Kilpeläinen T. O. 
Published: August 2018

AbstractObesity prevalence continues to rise worldwide, posing a substantial burden on people's health. However, up to 45% of obese individuals do not suffer from cardiometabolic complications, also called the metabolically healthy obese (MHO). Concurrently, up to 30% of normal‐weight individuals demonstrate cardiometabolic risk factors that are generally observed in obese individuals, the metabolically obese normal weight (MONW). Besides lifestyle, environmental factors and demographic factors, innate biological mechanisms are known to contribute to the aetiology of the MHO and MONW phenotypes, as well. Experimental studies in animal models have shown that adipose tissue expandability, fat distribution, adipogenesis, adipose tissue vascularization, inflammation and fibrosis, and mitochondrial function are the main mechanisms that uncouple adiposity from its cardiometabolic comorbidities. We reviewed current genetic association studies to expand insights into the biology of MHO/MONW phenotypes. At least four genetic loci were identified through genome‐wide association studies for body fat percentage (BF%) of which the BF%‐increasing allele was associated with a protective effect on glycemic and lipid outcomes. For some, this association was mediated through favourable effects on body fat distribution. Other studies that characterized the genetic susceptibility of insulin resistance found that a higher susceptibility was associated with lower overall adiposity due to less fat accumulation at hips and legs, suggesting that an impaired capacity to store fat subcutaneously or a preferential storage in the intra‐abdominal cavity may be metabolically harmful. Clearly, more work remains to be done in this field, first through gene discovery and subsequently through functional follow‐up of identified genes.
Clinical Practices and Barriers to Best Practice Implementation of Psychologists Working with Adults with Intellectual Disability and Comorbid Mental Ill Health
Authors: Man Joyce , Kangas Maria , Trollor Julian , Sweller Naomi 
Published: August 2018

AbstractEvidence‐based practice (EBP) has not been well established in the area of intellectual disability (ID) and comorbid mental ill health. Some attempts in the form of policies and practice guidelines have been made. The aim of this study was to investigate assessment practices of Australian psychologists working with adults from this specialist population and explore barriers to best practice implementation. One hundred and two psychologists completed a self‐report online survey exploring barriers to EBP implementation. Sixty‐one psychologists completed questions relating to their practice including diagnostic practices, application of special considerations, and use of specialist resources. Psychologists reported many assessment practices that were in line with current national and international guidelines including utilization of specialist assessment resources, interdisciplinary collaboration, and application of reasonable adjustments to standard practice to suit the needs of individuals with dual disabilities. However, the sample also reported a number of barriers to implementing best practice recommendations such as diagnostic issues, limited access, and awareness of clinical resources and limited access to mental health services. Findings from this study have implications for best practice guidelines and policies in how mental health services for individuals with IDs and their families are delivered in Australia. This includes facilitating collaboration between health and disability services, adequate training, and access to specialist resources and access to mental health services equipped to support the needs of this specialist population.