bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptotoxicity in Alzheimer's Disease Involved a Dysregulation of Actin Cytoskeleton Dynamics through Cofilin 1 Phosphorylation
Authors: Rush Travis , Martinez-Hernandez Jose , Dollmeyer Marc , Frandemiche Marie Lise , Borel Eve , Boisseau Sylvie , Jacquier-Sarlin Muriel , Buisson Alain 
Published: October 2018

Amyloid-β (Aβ) drives the synaptic impairment and dendritic spine loss characteristic of Alzheimer's disease (AD), but how Aβ affects the actin cytoskeleton remains unknown and contentious. The actin-binding protein, cofilin-1 (cof1), is a major regulator of actin dynamics in dendritic spines, and is subject to phospho-regulation by multiple pathways, including the Rho-associated protein kinase (ROCK) pathway. While cof1 is implicated as a driver of the synaptotoxicity characteristic of the early phases of AD pathophysiology, questions remain about the molecular mechanisms involved. Cofilin-actin rods are observed in neurons exposed to Aβ oligomers (Aβo) and in tissue from AD patients, and others have described an increased cofilin phosphorylation (p-cof1) in AD patients. Here, we report elevated p-cof1 of the postsynaptic enriched fraction of synaptosomes from cortical samples of male APP/PS1 mice and human AD cases of either sex. In primary cortical neurons, Aβo induced rapid actin stabilization and increased p-cof1 in the postsynaptic compartment of excitatory synapses within 30 min. Fluorescence recovery after photobleaching of actin-GFP and calcium imaging in live neurons expressing active or inactive cof1 mutants suggest that cof1 phosphorylation is necessary and sufficient for Aβo-induced synaptic impairment via actin stabilization before the reported formation of cofilin-actin rods. Moreover, the clinically available and well-tolerated ROCK inhibitor, fasudil, prevented Aβo-induced actin stabilization, synaptic impairment, and synaptic loss by blocking cofilin phosphorylation. Aβo also blocked the LTP-induced insertion of the AMPAR subunit, GluA1, at the postsynaptic density, in a fasudil-sensitive manner. These data support an important role for ROCKs and cofilin in mediating Aβ-induced synaptic impairment.SIGNIFICANCE STATEMENTWe report that amyloid-β oligomers rapidly induce aberrant stabilization of F-actin within dendritic spines, which impairs synaptic strength and plasticity. Activation of the Rho-associated protein kinase (ROCK) pathway results in phosphorylation of cof1 and is sufficient to mediate Aβo-induced actin stabilization synaptic impairment and synaptic loss. Further, the ROCK inhibitor, fasudil, prevents cofilin phosphorylation, acute synaptic disruption, and synaptotoxicity in primary cortical neurons. Together, the herein presented data provide strong support for further study of the ROCK pathway as a therapeutic target for the cognitive decline and synaptotoxicity in Alzheimer's disease.
Two Novel Candidate Genes for Insulin Secretion Identified by Comparative Genomics of Multiple Backcross Mouse Populations
Authors: Schallschmidt Tanja , Lebek Sandra , Altenhofen Delsi , Damen Mareike , Schulte Yvonne , Knebel Birgit , Herwig Ralf , Rasche Axel , Stermann Torben , Kamitz Anne , Hallahan Nicole , Jähnert Markus , Vogel Heike , Schürmann Annette , Chadt Alexandra , Al-Hasani Hadi 
Published: October 2018

Abstract
To identify novel disease genes for type 2 diabetes (T2D) we generated two backcross populations of obese and diabetes-susceptible New Zealand Obese (NZO/HI) mice with the two lean mouse strains 129P2/OlaHsd and C3HeB/FeJ. Subsequent whole-genome linkage scans revealed 30 novel quantitative trait loci (QTL) for T2D-associated traits. The strongest association with blood glucose [12 cM, logarithm of the odds (LOD) 13.3] and plasma insulin (17 cM, LOD 4.8) was detected on proximal chromosome 7 (designated Nbg7p, NZO blood glucose on proximal chromosome 7) exclusively in the NZOxC3H crossbreeding, suggesting that the causal gene is contributed by the C3H genome. Introgression of the critical C3H fragment into the genetic NZO background by generating recombinant congenic strains and metabolic phenotyping validated the phenotype. For the detection of candidate genes in the critical region (30–46 Mb), we used a combined approach of haplotype and gene expression analysis to search for C3H-specific gene variants in the pancreatic islets, which appeared to be the most likely target tissue for the QTL. Two genes, Atp4a and Pop4, fulfilled the criteria from our candidate gene approaches. The knockdown of both genes in MIN6 cells led to decreased glucose-stimulated insulin secretion, indicating a regulatory role of both genes in insulin secretion, thereby possibly contributing to the phenotype linked to Nbg7p. In conclusion, our combined- and comparative-cross analysis approach has successfully led to the identification of two novel diabetes susceptibility candidate genes, and thus has been proven to be a valuable tool for the discovery of novel disease genes.
Performing Parentage Analysis in the Presence of Inbreeding and Null Alleles
Authors: Huang Kang , Mi Rui , Dunn Derek W , Wang Tongcheng , Li Baoguo 
Published: October 2018

Abstract
Parentage analysis is an important method that is used widely in zoological and ecological studies. Current mathematical models of parentage analyses usually assume that a population has a uniform genetic structure and that mating is panmictic. In a natural population, the geographic or social structure of a population, and/or nonrandom mating, usually leads to a genetic structure and results in genotypic frequencies deviating from those expected under the Hardy-Weinberg equilibrium (HWE). In addition, in the presence of null alleles, an observed genotype represents one of several possible true genotypes. The true father of a given offspring may thus be erroneously excluded in parentage analyses, or may have a low or negative LOD score. Here, we present a new mathematical model to estimate parentage that includes simultaneously the effects of inbreeding, null alleles, and negative amplification. The influences of these three factors on previous model are evaluated by Monte-Carlo simulations and empirical data, and the performance of our new model is compared under controlled conditions. We found that, for both simulated and empirical data, our new model outperformed other methods in many situations. We make available our methods in a new, free software package entitled parentage. This can be downloaded via http://github.com/huangkang1987/parentage.
Neurodevelopmental Consequences of Preterm Isolated Cerebellar Hemorrhage: A Systematic Review
Authors: Hortensius Lisa M. , Dijkshoorn Aicha B.C. , Ecury-Goossen Ginette M. , Steggerda Sylke J. , Hoebeek Freek E. , Benders Manon J.N.L. , Dudink Jeroen 
Published: October 2018

CONTEXT:
The effect of neonatal cerebellar hemorrhage on neurodevelopmental outcome (NDO) in the absence of supratentorial injury is still largely unknown.

OBJECTIVE:
To evaluate the influence of isolated neonatal cerebellar hemorrhage on cognitive, motor, language, and behavioral NDOs and assess the effect of location and size on outcome.

DATA SOURCES:
Embase, Medline, and Scopus were searched from inception to September 30, 2017.

STUDY SELECTION:
Studies in which a diagnosis of isolated cerebellar hemorrhage was reported in preterm infants (&lt;32 weeks’ gestation) with a standardized NDO at ≥12 months of age were included.

DATA EXTRACTION:
Patient characteristics, location, and size of bleeding and NDO (defined as severe [yes or no] on the basis of given cutoff points) in 4 domains were extracted.

RESULTS:
Of the 1519 studies identified, 8 were included in final analyses. Of infants with isolated cerebellar hemorrhage, 128 were described (cumulative incidence: 2.3%). The incidence of severe delay in cognition, motor, language, and behavioral development was 38%, 39%, 41%, and 38%, respectively. The overall incidence of severe neurodevelopmental delay in ≥1 domain ranged from 43% to 75% and was most seen in infants with vermis involvement (87%–93%) and with large bleeds (46%–82%).

LIMITATIONS:
Different neurodevelopmental scales lead to data heterogeneity, and reporting of data on a group level limited possibilities for an outcome description on an individual level.

CONCLUSIONS:
Of infants with isolated cerebellar hemorrhage, 43% to 75% were severely delayed in cognition, motor, language, and/or behavioral development, with the highest incidence with vermis involvement and with large bleeds.
A contrastive overlook at Asian literature in the Americas: two examples
Authors: Suárez José I. 
Published: October 2018

This paper will critically explore and compare East Asian perspectives and adaptation modes in the Americas as well as self-perception within the realm of “the Other” through two novels: Yawara! A Travessia Nihondin-Brasil (Yawara! The Nihondin-Brazil Journey 2006) by Júlio Miyazawa, a Nipo-Brazilian (Nisei), and Yellow on the Outside, Shame on the Inside: Asian Culture Revealed by the Sino-American Anson Chi (Web published). ***Um olhar contrastivo sobre a literatura asiática nas Américas: dois exemplos***O presente artigo explora e compara criticamente as perspectivas do Leste Asiático e seus modos de adaptação nas Américas, bem como a autopercepção no âmbito do “Outro” em dois romances: Yawara! A travessia Nihondin-Brasil (2006), de Júlio Miyazawa, um nipo-brasileiro (nissei), e Yellow on the Outside, Shame on the Inside: Asian Culture Revealed (Amarelo por fora, vergonha por dentro: cultura asiática revelada), do sino-americano Anson Chi (publicado na Web).Palavras-chave: Nissei; Emigração; Outro; Cultura asiática.
Memory and the written testimony: the actresses of the public theatre in Calcutta in the 19th & 20th century
Authors: Gooptu Sarvani 
Published: October 2018

Modern theatrical performances in Bengali language in Calcutta, the capital of British colonial rule, thrived from the mid-nineteenth century though they did not include women performers till 1874. The story of the early actresses is difficult to trace due to a lack of evidence in contemporary sources. So though a researcher is vaguely aware of their significance and contribution to Indian theatre, they have remained shadowy figures – nameless except for those few who have left a written testimony of their lives and activities. It is my intention through the study of this primary material and the scattered references to these legendary actresses in vernacular journals and memoirs, to recreate the stories of some of these divas and draw a connection between testimony and lasting memory. ***Memória e testemunho escrito: as atrizes do teatro público em Calcutá nos séculos XIX e XX***As representações teatrais modernas na língua bengali em Calcutá, a capital do governo colonial britânico, prosperaram a partir de meados do século XIX, embora não incluíssem mulheres até 1874. É difícil traçar a história das primeiras atrizes devido à falta de evidências em fontes contemporâneas. Dessa forma, embora o pesquisador tenha uma vaga consciência de sua contribuição e importância para o teatro indiano, elas permaneceram obscuras – anônimas, com exceção daquelas que deixaram um testemunho escrito de suas vidas e atividades. Por meio do estudo desse material primário e das referências esparsas a essas lendárias atrizes em diários e memórias na língua vernácula, pretendo recriar as histórias de algumas dessas divas e estabelecer uma conexão entre testemunho e memória duradouraPalavras-chave: Atrizes; Teatro bengali; Párias sociais; Representação e produção criativa; Memória e testemunho escrito.
Einsatz von Bisphosphonaten beim Pferd – eine Literaturübersicht
Authors: Düsterdieck-Zellmer Katja 
Published: October 2018

ZusammenfassungTiludronsäure bzw. Clodronsäure führt bei einigen Pferden mit Podotrochlosesyndrom zur Linderung der Lahmheit. Der Therapieeffekt tritt meist 2–6 Monate nach Gabe des Medikaments ein. Bei Pferden ohne Verbesserung der Lahmheit kann eine Folgebehandlung doch noch die Lahmheit verringern. Pferde mit einer Erkrankungsdauer von weniger als 6 Monaten haben eine bessere Chance auf Behandlungserfolg. Bisphosphonate (BP) können Nierenschäden hervorrufen, weshalb es sich empfiehlt, die Nierenfunktion vor und nach der Behandlung zu untersuchen. Pferde mit Nierenschäden sollten nicht mit BP behandelt werden, weil diese Substanzen eine weitere Beeinträchtigung der Nierenfunktion verursachen können. Deshalb sollen BP auch nicht zusammen mit nichtsteroidalen Antiphlogistika oder anderen nephrotoxischen Medikamenten verabreicht werden. Eine der häufigsten Nebenwirkungen nach BP-Applikation ist Kolik. Eine konservative Behandlung mit Führen im Schritt reicht meist aus. Falls eine medikamentöse Behandlung nötig wird, sollte diese mit N-Butylscopolamin, Xylazin, Detomidin oder Butorphanol (möglicherweise auch in Kombinationen) erfolgen. Die Verabreichung nichtsteroidaler Antiphlogistika wird nicht empfohlen. Bei Auftreten von Muskelfaszikulationen sollten die Plasmaelektrolytwerte bestimmt werden. Die Verabreichungsweise von BP-Produkten sollte den Empfehlungen der Herstellerfirmen folgen. Lokale Applikationen wie intraartikuläre Injektionen oder Verabreichung per Stauungsinfusion an den distalen Gliedmaßen sind möglicherweise schädlich und zurzeit nicht zu empfehlen.
Feldstudie zum freien Abferkeln im Kaltstall
Authors: Erhard Michael , Kickstein Janina , Bergmann Shana , Klein Sandrina , Patzkéwitsch Dorian 
Published: October 2018

Zusammenfassung
Ziel dieser Feldstudie war, in einem nach den BIO-AUSTRIA-Produktionsrichtlinien wirtschaftenden ökologischen Ferkelerzeugerbetrieb von Sommer 2015 bis Sommer 2017 das vorhandene freie Abferkel-system hinsichtlich der Praxistauglichkeit zu überprüfen, vor allem aber die Ferkelverluste und deren Ursachen zu erfassen. Die sogenannte „Ethobox” (HAKA, Josef Häufele GmbH & Co. KG, Erbach-Dellmensingen, Deutschland) war in zwei Kaltställen mit Ausläufen installiert. Material und Methoden: Die Reproduktionsrate wurde routinemäßig über Stallkarten erfasst. Ferkelverluste wurden in erdrückte Ferkel oder sonstige Verluste eingeteilt und der Zeitpunkt des Verlusts vermerkt. Ergebnisse: Die Datenerfassung erstreckte sich auf 490 Würfe (Sau: Deutsches Edelschwein x Deutsche Landrasse; Eber: Pietrain/Pietrain x Duroc; durchschnittliche Wurfnummer: 2,5 ± 1,3; durchschnittliche Anzahl lebend geborener Ferkel: 10,5 ± 2,8; durchschnittliche Anzahl tot geborener Ferkel: 0,8 ± 1,7). Im Mittel wurden 0,72 Ferkel pro Wurf erdrückt. Die sonstigen Ferkelverluste lagen bei 0,58 Ferkeln pro Wurf. Die Gesamtferkelverlustrate betrug 12,4 %. In der 1. Lebenswoche wurden 98,6 % der Verluste durch Erdrücken dokumentiert. Die sonstigen Verluste machten in diesem Zeitraum einen Anteil von 53,1 % aus. Schlussfolgerung und klinische Relevanz: Die Studie bestätigt, dass die 1. Lebenswoche als “kritische Lebensphase” der Ferkel in Bezug auf Erdrückungsverluste anzusehen ist. Nach den Resultaten hat sich die untersuchte freie Abferkelbucht für den Betrieb als praxistauglich erwiesen. Vor allem die niedrige Anzahl lebend geborener Ferkel dürfte in Bezug auf die vergleichsweise geringen Ferkelverluste eine wesentliche Rolle spielen.
Intradermale versus intramuskuläre Impfstoffapplikation bei Saugferkeln
Authors: Göller Manuel , Fels Michaela , Gerdts Wiebke-Rebekka , Kemper Nicole 
Published: October 2018

Zusammenfassung
Ziel dieser Studie war, eine intradermale Impfmethode gegen Mycoplasma hyopneumoniae bei Saugferkeln im Hinblick auf Hautreaktionen, Leistungsparameter und arbeitstechnische Gesichtspunkte mit einer konventionell durchgeführten intramuskulären Impfung wissenschaftlich zu vergleichen und mögliche Konsequenzen für das Wohlbefinden der Tiere abzuleiten. Material und Methoden: Unter Feldbedingungen wurden insgesamt 672 Saugferkel aus drei Durchgängen geimpft, davon 338 intradermal und 334 intramuskulär. Neben einer umfassenden Bonitur wurde die lokale Hautreaktion an der Impfstelle bonitiert, indem die Größe der Schwellung (Scoring 0–5) sowie die Rötung und Krustenbildung (Scoring 0–3) benotet wurden. Die Ferkel wurden am Tag vor der Impfung und 8 Tage später einzeln gewogen. Ferner erfolgten eine Messung und Dokumentation der für die jeweilige Impfung benötigten Zeit. Ergebnisse: Am 1. Tag nach der Impfung zeigten 71,3 % der intramuskulär geimpften Ferkel und 2,7 % der intradermal geimpften Ferkel keine Schwellung an der Impfstelle. Diese Unterschiede nivellierten sich mit zunehmendem zeitlichem Abstand zur Impfung. Die tägliche Gewichtszunahme der Ferkel differierte zwischen der intradermal (248 g) und der intramuskulär (258 g) geimpften Gruppe nicht signifikant. Die intradermale Impfung benötigte pro Ferkel im Schnitt 11 Sekunden, die intramuskuläre Impfung 17 Sekunden. Schlussfolgerungen und klinische Relevanz: In dieser ersten Studie konnten keine nachteiligen Effekte der intradermalen Impfung auf Leistungsparameter und keine länger anhaltenden Hautreaktionen bei Saugferkeln nachgewiesen werden. An den Hautreaktionen zeigte sich sehr gut die bei der intradermalen Impfung gewünschte Immunantwort an der Impfstelle, die nach 7 Tagen aber nicht mehr offensichtlich war. Darüber hinaus stellte sich der arbeitstechnische Vorteil der intradermalen Impfung klar heraus. Um letztendlich mögliche Vorteile hinsichtlich der Auswirkungen auf das Wohlbefinden von Saugferkeln zu evaluieren, sind weitere Analysen anhand von Videobeobachtungen erforderlich.
METHODOLOGY OF DETERMINING THE PARAMETERS OF TRACTION ELECTRIC MOTOR FAILURES WHEN OPERATING TROLLEYBUSES
Authors: Pavlenko T. P. , Shavkun V. M. , Scurihin V. I. , Lukashova N. P. 
Published: October 2018

Purpose. The work is aimed to study the change in parameters of traction electric motors of trolleybuses during operation and improvement of the technical state control system, using modern diagnostic methods. Methodology. Solution of the scientific problem is based on the control of technical state and change in the parameters of traction electric motors in the process of operation. For analysis of operational factors, we used the method of mathematical statistics and probability theory. Mathematical modelling and design of experiment, multifactor regression analysis provides an assessment of the reliability of the electric traction motor elements. Physical and statistical methods provide for research and detection of patterns of influence of the factors that accelerate the wear of parts. This allows us to generate models of system reliability that take into account the influence of operational factors on the reliability. Findings. As a result of the studies we obtained quantitative characteristics of the reliability of commutator and established that the failures of traction motors make up 20% of all failures of electrical equipment. We analysed the operation conditions of traction electric motors and determined the failure distribution law N{mx,sx}, which allows assessing the progression between gradual failures. We obtained a mathematical model characterizing the object operation. A generalized equation of the failure rate of elements for traction electric motor (TEM) was found. We improved the estimation methods of reliability of TEM element base that makes it possible to determine the ETM lifetime taking into account the features of each trolleybus. We established the failure rate of commutators using physical and statistical methods. Originality. For the first time, the choice of physico-statistical methods of simulation and reliability calculation was substantiated. We determined the regularities of change in parameters of the trolleybus traction electric motor elements, which makes it possible to control the processes of their wear in the operation conditions. We developed a mathematical model for estimating the traction electric motor reliability, based on a system analysis of the probabilities of failures of subsystems to be diagnosed. Practical value. Based on the results of the study, we developed practical recommendations for rational choice of diagnostic parameters of traction motors. Their implementation at the enterprises of electric transport will increase reliability of electric motors in general up to 10%. It is proposed to use the results of the work in the educational process and in the research work of students at the Department of Electric Transport of the O.M. Beketov National University of Urban Economy in Kharkiv. The developed methodology for determination of parameters of traction electric motors when operating trolleybuses allows assessing the reliability of any type of trolleybus traction motor.
SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts
Authors: Wei Chengguo , Banu Khadija , Garzon Felipe , Basgen John M. , Philippe Nimrod , Yi Zhengzi , Liu Ruijie , Choudhuri Jui , Fribourg Miguel , Liu Tong , Cumpelik Arun , Wong Jenny , Khan Mubeen , Das Bhaskar , Keung Karen , Salem Fadi , Campbell Kirk N. , Kaufman Lewis , Cravedi Paolo , Zhang Weijia , O'Connell Philip J. , He John Cijiang , Murphy Barbara , Menon Madhav C. 
Published: October 2018

Background
We previously showed that the presence of a CKD-associated locus in SHROOM3 in a donor kidney results in increased expression of SHROOM3 (an F-actin–binding protein important for epithelial morphogenesis, via rho-kinase [ROCK] binding); this facilitates TGF-b signaling and allograft fibrosis. However, other evidence suggests Shroom3 may have a protective role in glomerular development.

Methods
We used human data, Shroom3 knockdown podocytes, and inducible shRNA-mediated knockdown mice to study the role of Shroom3 in adult glomeruli.

Results
Expression data from the Nephroseq database showed glomerular and nonglomerular SHROOM3 had opposing associations with renal function in CKD biopsy samples. In human allografts, homozygosity at rs17319721, the SHROOM3 locus linked with lower GFR, was associated with reduced albuminuria by 2 years after transplant. Although our previous data showed reduced renal fibrosis with tubular Shroom3 knockdown, this study found that glomerular but not tubular Shroom3 knockdown induced albuminuria. Electron microscopy revealed diffuse foot process effacement, and glomerular RNA-sequencing showed enrichment of tyrosine kinase signaling and podocyte actin cytoskeleton pathways in knockdown mice. Screening SHROOM3-interacting proteins identified FYN (a src-kinase) as a candidate.We confirmed the interaction of endogenous SHROOM3 with FYN in human podocytes via a critical Src homology 3–binding domain, distinct from its ROCK-binding domain. Shroom3-Fyn interaction was required in vitro and in vivo for activation of Fyn kinase and downstream nephrin phosphorylation in podocytes. SHROOM3 knockdown altered podocyte morphology, cytoskeleton, adhesion, and migration.

Conclusions
We demonstrate a novel mechanism that may explain SHROOM3’s dichotomous associations in glomerular versus nonglomerular compartments in CKD