bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of Gephyrin in Zebrafish Mauthner Cells Governs Glycine Receptor Clustering and Behavioral Desensitization to Sound
Authors: Ogino Kazutoyo , Yamada Kenta , Nishioka Tomoki , Oda Yoichi , Kaibuchi Kozo , Hirata Hiromi 
Published: September 2019

The process by which future behavioral responses are shaped by past experiences is one of the central questions in neuroscience. To gain insight into this process at the molecular and cellular levels, we have applied zebrafish larvae to explore behavioral desensitization to sound. A sudden loud noise often evokes a defensive response known as the acoustic startle response (ASR), which is triggered by firing Mauthner cells in teleosts and amphibians. The probability of evoking ASR by suprathreshold sound is reduced after exposure to repetitive auditory stimuli insufficient in amplitude to evoke the ASR (subthreshold). Although it has been suggested that the potentiation of inhibitory glycinergic inputs into Mauthner cell is involved in this desensitization of the ASR, the molecular basis for the potentiation of glycinergic transmission has been unclear. Through thein vivomonitoring of fluorescently-tagged glycine receptors (GlyRs), we here showed that behavioral desensitization to sound in zebrafish is governed by GlyR clustering in Mauthner cells. We further revealed that CaMKII-dependent phosphorylation of the scaffolding protein gephyrin at serine 325 promoted the synaptic accumulation of GlyR on Mauthner neurons through the enhancement of the gephyrin-GlyR binding, which was indispensable for and could induce desensitization of the ASR. Our study demonstrates an essential molecular and cellular basis of sound-induced receptor dynamics and thus of behavioral desensitization to sound.SIGNIFICANCE STATEMENTBehavioral desensitization in the acoustic startle response of fish is known to involve the potentiation of inhibitory glycinergic input to the Mauthner cell, which is a command neuron for the acoustic startle response. However, the molecular and cellular basis for this potentiation has been unknown. Here we show that an increase in glycine receptor (GlyR) clustering at synaptic sites on zebrafish Mauthner cells is indispensable for and could induce desensitization. Furthermore, we demonstrate that CaMKII-mediated phosphorylation of the scaffolding protein gephyrin promotes GlyR clustering by increasing the binding between the β-loop of GlyRs and gephyrin. Thus, the phosphorylation of gephyrin is a key event which accounts for the potentiation of inhibitory glycinergic inputs observed during sound-evoked behavioral desensitization.
Peningkatan Aktivitas dan Hasil Belajar Siswa SMA Pada Dimensi Tiga Melalui Model Pembelajaran PBL Berbantuan Alat Peraga
Authors: Anwar Khoirul , Jurotun Jurotun 
Published: September 2019

Penelitian ini dilatar belakangi hasil belajar siswa yang belum mencapai kriteria ketuntasan minimal yang telah ditetapkan. Di samping itu, model pembelajaran yang diterapkan monoton, sehingga aktivitas siswa rendah. Penelitian ini bertujuan untuk mengetahui aktivitas dan hasil belajar siswa pada materi dimensi tiga akibat pembelajaran yang menggunakan model pembelajaran PBL berbantuan alat peraga sederhana berbahan limbah sedotan. Penelitian ini merupakan penelitian tindakan kelas dengan tiga siklus. Subyek penelitian ini siswa kelas XII IPA-1 SMA Negeri 1 Dempet Demak semester gasal tahun pelajaran 2017/2018. Pengambilan data dalam penelitian ini menggunakan teknik observasi dan angket yang selanjutnya dianalisis sebagai data kualitatif, serta penilaian hasil ulangan blok dianalisis sebagai data kuantitatif. Hasil penelitian menunjukkan bahwa model pembelajaran PBL berbantuan alat peraga sederhana berbahan limbah sedotan dapat meningkatkan hasil belajar siswa dengan rata – rata mencapai 75,44 dengan jumlah siswa yang tuntas mencapai 86,84%, dapat meningkatkan aktivitas siswa menjadi 3,68 (sangat aktif). Respon siswa terhadap model pembelajaran yang telah diterapkan adalah sangat positif (80,99%). Oleh karena itu, model pembelajaran PBL berbantuan alat peraga sederhana berbahan limbah sedotan dapat diterapkan pada pembelajaran matematika, khususnya dimensi tiga .This research is based on the learning result of students who have not met the minimum completeness criteria that have been determined, besides that, learning model that is applied monotonically so that student activity is low. This study aims to determine the activity of student learning result in the three dimensional material due to PBL learning models assisted with simple teaching aids made from straws. This research is a classroom action research with three cycles. The subject of this research is XII IPA-1 of SMAN 1 Dempet of the odd semester in 2017/2018. Taking data in this research used observation and questionnare techniques which are then analyzed as qualitative data and the result of block test are analyzed as quantitative data the result of the study showed that the PBL learning models assisted with sample teaching aids made from straws can improve student learning results by an average of 75,44 with the number of students who completed 86,84% can improve student activity to 3,68 (very active). Student response to the learning model that has been applied is very positive (80,99%). Therefore, PBL learning models assisted with simple teaching aids made from straws can be applied to mathematic learning, especially the three dimensions.
Global attracting solutions to Hilfer fractional differential inclusions of Sobolev type with noninstantaneous impulses and nonlocal conditions
Authors: Wang JinRong , Ibrahim Ahmed Gamal Gamal , O’Regan Donal 
Published: September 2019

In this paper, we establish the existence of decay mild solutions on an unbounded interval of nonlocal fractional semilinear differential inclusions with noninstantaneous impulses and involving the Hilfer derivative. Our argument uses fixed point theorems, semigroup theory, multi-functions and a measure of noncompactness on the space of piecewise weighted continuous functions defined on an unbounded interval. An example is provided to illustrate our results.
Identification of Acer2 as a First Susceptibility Gene for Lithium-Induced Nephrogenic Diabetes Insipidus in Mice
Authors: de Groot Theun , Ebert Lena K. , Christensen Birgitte Mønster , Andralojc Karolina , Cheval Lydie , Doucet Alain , Mao Cungui , Baumgarten Ruben , Low Benjamin E. , Sandhoff Roger , Wiles Michael V. , Deen Peter M.T. , Korstanje Ron 
Published: September 2019

Significance Statement
Lithium causes nephrogenic diabetes insipidus and hypercalcemia in 20% and 10% of patients, respectively, and may lead to metabolic acidosis. To determine the potential role of genetic predisposition in these adverse effects, the authors fed mice from 29 genetically different inbred strains a normal or a lithium-supplemented diet. Some strains developed adverse effects, whereas others did not. Genome-wide association studies revealed eight loci containing different candidate genes that were associated with development of lithium-induced nephrogenic diabetes insipidus. Of these, Acer2 is specifically expressed in the collecting duct; mice lacking Acer2 were more likely to develop lithium-induced nephrogenic diabetes insipidus. These findings demonstrate the importance of genetic variation in susceptibility for lithium-induced adverse effects in mice, and the genes identified may facilitate subsequent identification of human susceptibility genes.

Background
Lithium, mainstay treatment for bipolar disorder, causes nephrogenic diabetes insipidus and hypercalcemia in about 20% and 10% of patients, respectively, and may lead to acidosis. These adverse effects develop in only a subset of patients treated with lithium, suggesting genetic factors play a role.

Methods
To identify susceptibility genes for lithium-induced adverse effects, we performed a genome-wide association study in mice, which develop such effects faster than humans. On day 8 and 10 after assigning female mice from 29 different inbred strains to normal chow or lithium diet (40 mmol/kg), we housed the animals for 48 hours in metabolic cages for urine collection. We also collected blood samples.

Results
In 17 strains, lithium treatment significantly elevated urine production, whereas the other 12 strains were not affected. Increased urine production strongly correlated with lower urine osmolality and elevated water intake. Lithium caused acidosis only in one mouse strain, whereas hypercalcemia was found in four strains. Lithium effects on blood pH or ionized calcium did not correlate with effects on urine production. Using genome-wide association analyses, we identified eight gene-containing loci, including a locus containing Acer2, which encodes a ceramidase and is specifically expressed in the collecting duct. Knockout of Acer2 led to increased susceptibility for lithium-induced diabetes insipidus development.

Conclusions
We demonstrate that genome-wide association studies in mice can be used successfully to identify susceptibility genes for development of lithium-induced adverse effects. We identified Acer2 as a first susceptibility gene for lithium-induced diabetes insipidus in mice.
О «непутевых черничках» и «птичках небесных»: парадокс монастырской тотальности
Authors: Медведева Ксения Сергеевна 
Published: September 2019

В статье рассматривается специфика устройства современных православных монастырей в России. В частности, анализируются дихотомия «мир – монастырь» и разделение внешнего и внутреннего порядка. Для анализа использованы материалы, находящиеся в открытом доступе (вебсайты церковных организаций), а также полевые материалы, собранные автором в ходе включенного наблюдения и неструктурированных интервью с 2012 по 2016 гг. в женских православных монастырях. Автор делает вывод о том, что несмотря на дихотомию «мир – монастырь», которая проходит как в реальном, так и в виртуальном пространстве, современные российские монастыри скорее не «убежища от мира», как полагал Эрвин Гоффман, а прибежища для него. Дихотомия «мир – монастырь» поддерживается пространственной организацией монастыря, его писаными и негласными правилами, которые, впрочем, могут нарушаться с обеих сторон. Монастырский порядок регулируется внешними и внутренними механизмами. К внешним инструментам можно отнести церковные документы, с которыми насельники обычно знакомы плохо, правила и нормы поведения, усваиваемые в процессе социализации в монастыре. Знание устава предполагает не знакомство с конкретным текстом, а скорее успешную социализацию, усвоение принятых в данном сообществе норм и правил поведения, которые могут быть не зафиксированы в письменных документах. Кроме этого, внешне монастырская жизнь регулируется особым распорядком, который может различаться в разных обителях, но служит одной цели – при внешнем однообразии создать условия для внутренней жизни. Внешние механизмы поддержания порядка необходимы, но недостаточны: порядок в том числе зависит от главного в монастыре – «внут­ренней жизни», самодисциплины самих насельников и реализации ими своей свободы. Кажущаяся несвобода в виде внешней регуляции, которую обеспечивает монастырь, парадоксальным образом конституирует свободу внутренней жизни его насельников. Особые условия и акцент на внутренней жизни являются парадоксом монастырской тотальности и отличают монастырь от других тотальных институтов.
Breve panorama da judicialização da saúde no Brasil e os reflexos dos julgamentos dos recursos repetitivos pelos Tribunais Superiores
Authors: Ribeiro Catarina de Sá Guimarães , Wanderley Queiroz Cristina Câmara 
Published: September 2019

Objectives: in view of the new parameters established in the recent judgments of repetitive appeals that are representative of controversies in health demands by the Brazilian Supreme Court, the study analyzed the decision-making profile of the lower courts based on this fact. Methods: the judgments handed down by the Pernambuco Judiciary were analyzed after the publication of the respective minutes of judgment in the electronic Justice Gazette, the initial landmark of the obligation to observe the established theses, according to the rule of §11, art. 1.035 of the Code of Civil Procedure. Results: the results showed shy changes in the way health demands were resolved, with attachment to old ways of deciding, without deepening the necessary multidisciplinary discussion that the issue requires. Discussion and conclusions: the results obtained may contribute to alert to the need to resolve the judicialization of health rationally and in line with the binding theses defined by the Superior Courts.
The Degree of Overjet and Anterior Traumatic Dental Injury in the Mixed Dentition: A Single-Center Experience
Authors: Munro Monica , Ackerman Marc B 
Published: September 2019

Objective. The objective of this retrospective chart review study was twofold. The first was to determine whether there is a correlation between the degree of overjet and the type of anterior traumatic dental injury (ATDI) in the mixed dentition. The second was to assess whether the decision to not treat young patients with prominent upper front teeth for trauma prevention resulted in a greater number of ATDI's in patients of record from a single-center. Study Design. The authors conducted a retrospective chart review of patients presenting to the Boston Children's Hospital (BCH) Emergency Department with an ATDI in the mixed dentition between October 2011 and March 2016.Results. Patients with an overjet less than or equal to 4 millimeters experienced all types of ATDI with greater frequency than those patients with an overjet greater than 4 mm.Conclusions. Our experience at BCH described in this study has led us to believe that a patient's risk of suffering an ATDI has more to do with the type of activities they participate in rather than the degree of their overjet.
Legal Basis for the Creation of a System for Preventing Gene Doping and Countering Genetic Modification in Sport
Authors: Shevchenko O. A. , Vorontsov D. I. 
Published: September 2019

The paper is devoted to the study of the key factors underlying the building of a balanced system of legal norms aimed at preventing gene doping and countering the spread of genetic modifications of athletes. The paper explores the goals of countering doping as such and focuses on the dangers and potential harm to the sports of such a relatively new threat as gene doping. The authors discuss approaches to understanding gene therapy, as well as the prospects of embedding resistance to gene doping in existing legal mechanisms, including the possibility of using the mechanism of therapeutic exceptions (TUE). The current approaches to the definition of the essence of doping are studied and it is determined why gene therapy has a significant risk of being recognized as such. The risks and threats to the sphere of sport caused by the ongoing development of genetic technologies and the spread of their application are outlined. The possible consequences of the use of the results of genetic research, as well as the use of gene therapy, which may affect the field of sports, are discussed. The authors study issues of responsibility for the use of gene doping, subjects against which appropriate sanctions can be imposed, as well as the issue of the application of state coercion to individual subjects, without which the use of gene doping would be impossible. At the same time, the paper formulates the problems that need to be solved in the short term to ensure the preventive nature of the fight against gene doping in sport, and identifies the questions that society must answer to form a system of countering gene doping.
A prospective study of gestational trophoblastic disease profile with special reference to mortality and pregnancy outcome after successful management of the same
Authors: Bhattacharya Abantika , Panja Tanmay Kanti , Bhattacharya Amiya , Baur Baijayanti , Madhwani Kishore P. 
Published: September 2019

Background: Gestational trophoblastic disease (GTD) is a group of rare tumors that involve abnormal growth of cells inside a woman's uterus. GTD does not develop from cells of the uterus like cervical cancer or endometrial (uterine lining) cancer do. Instead, these tumors start in the cells that would normally develop into the placenta during pregnancy. GTD is unique because the maternal lesions arise from the fetal tissue as a molar pregnancy. All forms of GTD can be treated. In most cases the treatment produces a complete cure. The study was conducted to assess the various presenting features of GTD and factors associated with it.Methods: It was an observational hospital based prospective epidemiological study. Complete enumeration technique was followed and a total of 305 female patients were included in the sample. A pre-designed and pre-tested interview schedule was used to record different information and detailed history.Results: Of the 305 patients studied, 67.2% were diagnosed with H. mole, 23% patients were diagnosed with gestational trophoblastic tumor, among them 4.9% had choriocarcinoma. Majority were primigravida and of blood group O type. Pregnancy outcome after successful management of GTD were 63.3% had full term pregnancy, 20% cases had repeat molar pregnancy, 10% had spontaneous abortion while 6.7% (2/30) had pre term delivery.Conclusions: Gestational trophoblastic disease is seen most commonly in reproductive age group. If it is not diagnosed on time it can be fatal. This is a highly curable tumor even in the presence of distant metastasis.
DIAGNOSING ESL LEARNERS’ VOCABULARY KNOWLEDGE THROUGH MEMORY STRATEGIES
Authors: B R Aravind , V Dr. Rajasekaran 
Published: September 2019

Purpose of the study: The present study diagnoses the vocabulary knowledge employed by ESL learners’ through memory strategies. Schmiit’s (1990) Taxonomy of Vocabulary Learning Strategies (VLS) questionnaire was adopted and administered to 93 ESL learners. In order to get authenticities about the ESL learners’ memory strategies with vocabulary learning, semi-structured interviews were also conducted with 30 participants who completed the questionnaire. The result exposed the subsequent array of memory strategies used by ESL learners from the most frequent to the least frequent strategies, particularly findings revealed that ‘Use new word in sentences’, ‘Study word with a pictorial representation of its Meaning’, ‘Connect word to a personal experience’ are most popular whereas ‘Use scales for gradable adjectives’, ‘Relating word to unrelated items (Peg method)’ were least used memory strategies.
Methodology: Schmitt’s Vocabulary Learning Strategies Questionnaire (VLSQ) (1997) was favored to diagnose the vocabulary knowledge through memory strategies of 93 ESL learners. Initially the responses were collected through Google Forms. Additionally, 30 ESL learners were randomly selected for interviews in accordance to reassure participants’ comprehension of the subject matters.
Main Findings: The study finds effective result among 93 ESL learners in acquiring vocabulary knowledge while using memory strategies with the assistance of technological modalities. It also listed the most frequent and least frequent use of memory strategies in Schmitt’s Vocabulary Learning Strategies Questionnaire (VLSQ) (1997).
Applications of this study: The present study is conducted in English Language Laboratory, where ESL learners’ can be benefitted and the learners can use these memory strategies while learning a new vocabulary when encountering a word.
Novelty/Originality of this study: The existing technological modalities will assist the learners to correlate more effectively. Subject and language experts in the field can design the instructional materials and tools to assist ESL learners to improve vocabulary knowledge through memory strategies.
Small intestinal damage associated with the use of nonsteroidal anti-inflammatory drugs
Authors: Karateev A. E. , Moroz E. V. , Kryukov E. V. 
Published: September 2019

The use of nonsteroidal anti-inflammatory drugs (NSAID), even if short-term, may be associated to small intestinal complications, such as erosions, ulcers and chronic mucosal inflammation. Video capsule endoscopy allows for identification of such lesions in 20 to 55% of the patients who have taken nonselective NSAID for 2 to 4 weeks. The pathophysiology of NSAID-induced enteropathy is related to a reduced reparative potential of the mucosa and abnormalities of the microbial balance in the small intestine. In real world practice, NSAID enteropathy is commonly asymptomatic, and its manifestations, such as bleeding, perforation and ileus, are quite rare (about 0.3 episodes per 100 patient-years). The main manifestation of NSAID enteropathy is chronic iron deficient anemia. The use of rebamipide, sulfasalazine, mesalazine, and rifaximin has been discussed in the treatment of NSAID enteropathy, whereas its prevention implies preferential administration of coxibs, the use of rebamipide and probiotics.
De incertidumbre no se muere. Un desafío no resuelto sobre verdad y conocimiento = Uncertainty does not kill. An open challenge about truth and knowledge
Authors: Marchese Elena 
Published: September 2019

Resumen: La idea de certeza absoluta, típica del primer realismo alético, ha encontrado en la ley un hábitat ideal en el que se ha enraizado profundamente. La insostenibilidad epistemológica de esta noción, y el daño que ha causado a la reflexión jurídica, han sido denunciados de manera clara: tanto por Luigi Ferrajoli, como por la dogmática iusfilosófica que ha seguido sus ideas (los llamados «teóricos del hecho»). En este trabajo intento, por una parte, analizar la labor de estos teóricos, aportando elementos de reflexión sobre el tema de la verdad y del conocimiento judicial; por otra parte, también intento mostrar que la «rehabilitación» del realismo alético, en el ámbito jurídico, subsiste todavía como un problema abierto y lleno de interés para la reflexión filosófica. Traducción de Jorge Baquerizo. Palabras clave: verdad, conocimiento procesal, teóricos del hecho, Ferrajoli, realismo y antirealismo alético.Abstract: The idea of absolute certainty -typical of the first alethic realism- found an ideal habitat in Law and it rooted deeply into it. The epistemological unsustainability of this notion and the harms it caused to the legal debate were denounced clearly by Luigi Ferrajoli and the following scholars (i.e. the «fact-theorists»). This paper is aimed, on the one hand, at assessing the work of these jurists and provide food for thought on the topics of truth and procedural knowledge; on the other hand, it tries to show that the problem of the «rehabilitation» of alethic realism in the legal field still remains open and full of interest for the philosophical reflection. Keywords: truth, judicial knowledge, fact-theorists, Ferrajoli, alethic realism and anti-realism.