bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Synapse Development byVgatDeletion from ErbB4-Positive Interneurons
Authors: Lin Thiri W. , Tan Zhibing , Barik Arnab , Yin Dong-Min , Brudvik Egil , Wang Hongsheng , Xiong Wen-Cheng , Mei Lin 
Published: February 2018

GABA signaling has been implicated in neural development; however,in vivogenetic evidence is missing because mutant mice lacking GABA activity die prematurely. Here, we studied synapse development by ablating vesicular GABA transporter (Vgat) in ErbB4+interneurons. We show that inhibitory axo–somatic synapses onto pyramidal neurons vary from one cortical layer to another; however, inhibitory synapses on axon initial segments (AISs) were similar across layers. Conversely, parvalbumin-positive (PV+)/ErbB4+interneurons and PV-only interneurons receive a higher number of inhibitory synapses from PV+ErbB4+interneurons compared with ErbB4-only interneurons.Vgatdeletion from ErbB4+interneurons reduced axo–somatic or axo–axonic synapses from PV+ErbB4+interneurons onto excitatory neurons. This effect was associated with corresponding changes in neurotransmission. However, theVgatmutation seemed to have little effect on inhibitory synapses onto PV+and/or ErbB4+interneurons. Interestingly, perineuronal nets, extracellular matrix structures implicated in maturation, survival, protection, and plasticity of PV+interneurons, were increased in the cortex of ErbB4-Vgat−/−mice. No apparent difference was observed between males and females. These results demonstrate thatVgatof ErbB4+interneurons is essential for the development of inhibitory synapses onto excitatory neurons and suggest a role of GABA in circuit assembly.SIGNIFICANCE STATEMENTGABA has been implicated in neural development, butin vivogenetic evidence is missing because mutant mice lacking GABA die prematurely. Here, we ablatedVgatin ErbB4+interneurons in an inducible manner. We provide evidence that the formation of inhibitory and excitatory synapses onto excitatory neurons requiresVgatin interneurons. In particular, inhibitory axo–somatic and axo–axonic synapses are more vulnerable. Our results suggest a role of GABA in circuit assembly.
A Missense Mutation A384P Associated with Human Hyperekplexia Reveals a Desensitization Site of Glycine Receptors
Authors: Wang Chen-Hung , Hernandez Ciria C. , Wu Junyi , Zhou Ning , Hsu Hsin-Yu , Shen Mei-Lin , Wang Yi-Ching , Macdonald Robert L. , Wu Dong Chuan 
Published: February 2018

Hyperekplexia, an inherited neuronal disorder characterized by exaggerated startle responses with unexpected sensory stimuli, is caused by dysfunction of glycinergic inhibitory transmission. From analysis of newly identified human hyperekplexia mutations in the glycine receptor (GlyR) α1 subunit, we found that an alanine-to-proline missense mutation (A384P) resulted in substantially higher desensitization level and lower agonist sensitivity of homomeric α1 GlyRs when expressed in HEK cells. The incorporation of the β subunit fully reversed the reduction in agonist sensitivity and partially reversed the desensitization of α1A384P. The heteromeric α1A384Pβ GlyRs showed enhanced desensitization but unchanged agonist-induced maximum responses, surface expression, main channel conductance, and voltage dependence compared with that of the wild-type α1β (α1WTβ) GlyRs. Coexpression of the R392H and A384P mutant α1 subunits, which mimic the expression of the compound heterozygous mutation in a hyperekplexia patient, resulted in channel properties similar to those with α1A384Psubunit expression alone. In comparison, another human hyperekplexia mutation α1P250T, which was previously reported to enhance desensitization, caused a strong reduction in maximum currents in addition to the altered desensitization. These results were further confirmed by overexpression of α1P250Tor α1A384Psubunits in cultured neurons isolated from SD rats of either sex. Moreover, the IPSC-like responses of cells expressing α1A384Pβ induced by repeated glycine pulses showed a stronger frequency-dependent reduction than those expressing α1WTβ. Together, our findings demonstrate that A384 is associated with the desensitization site of the α1 subunit and its proline mutation produced enhanced desensitization of GlyRs, which contributes to the pathogenesis of human hyperekplexia.SIGNIFICANCE STATEMENTHuman startle disease is caused by impaired synaptic inhibition in the brainstem and spinal cord, which is due to either direct loss of GlyR channel function or reduced number of synaptic GlyRs. Considering that fast decay kinetics of GlyR-mediated inhibitory synaptic responses, the question was raised whether altered desensitization of GlyRs will cause dysfunction of glycine transmission and disease phenotypes. Here, we found that the α1 subunit mutation A384P, identified from startle disease patients, results in enhanced desensitization and leads to rapidly decreasing responses in the mutant GlyRs when they are activated repeatedly by the synaptic-like simulation. These observations suggest that the enhanced desensitization of postsynaptic GlyRs could be the primary pathogenic mechanism of human startle disease.
Auditory Input Shapes Tonotopic Differentiation of Kv1.1 Expression in Avian Cochlear Nucleus during Late Development
Authors: Akter Nargis , Adachi Ryota , Kato Akitoshi , Fukaya Ryota , Kuba Hiroshi 
Published: February 2018

Tonotopic differentiation is fundamental for signal processing in the auditory system. However, when and how this differentiation arises remain elusive. We addressed this issue using electrophysiology and immunohistochemistry in nucleus magnocellularis of chickens of both sexes, which is known to differ in the expression of Kv1.1 channels depending on characteristic frequency (CF). Just after hearing onset (embryonic day 12–14), Kv1 current gradually increased to a slightly larger extent in neurons with higher CF, causing a tonotopic difference of Kv1 current before hatch. However, after hatch, a much larger increase of Kv1 current occurred, particularly in higher-CF neurons, due to an augmentation of Kv1.1 expression at the plasma membrane. This later change in expression led to the large tonotopic difference of Kv1 current characteristic of mature animals. Attenuation of auditory input by inducing conductive or sensorineural hearing loss around hatch suppressed the differentiation in a level-dependent manner. Moreover, elevation of auditory input during embryonic periods could not reproduce the differentiation, suggesting that the capacity of neurons to drive Kv1.1 expression via auditory input develops in a cell-specific manner, thus underlying the frequency-specific expression of the channel within the nucleus. The results indicated that the tonotopic differentiation of Kv1.1 in nucleus magnocellularis is partially determined before hatch, but largely driven by afferent input after hatch. Our results highlight the importance of neuronal capacity for sound to drive ion channel expression as well as the level of auditory experience in the frequency tuning of brainstem auditory circuits.SIGNIFICANCE STATEMENTTuning-frequency-specific expression of ion channels is a prerequisite for auditory system function, but its underlying mechanisms remain unclear. Here, we revealed in avian cochlear nucleus that the expression of Kv1.1 became more dependent on auditory input at a late period of maturation in neurons tuned to higher-frequency sound, leading to frequency-specific Kv1.1 expression. Attenuation of auditory input during this period suppressed the differentiation in a level-dependent manner, whereas elevation of input in earlier periods could not reproduce the differentiation. Thus, the capacity of neurons to drive Kv1.1 expression via auditory input develops in a cell-specific manner and directs differentiation, highlighting the importance of neuronal character as well as the level of input in the frequency tuning of auditory circuits.
Noise-Induced Dysregulation ofQuakingRNA Binding Proteins Contributes to Auditory Nerve Demyelination and Hearing Loss
Authors: Panganiban Clarisse H. , Barth Jeremy L. , Darbelli Lama , Xing Yazhi , Zhang Jianning , Li Hui , Noble Kenyaria V. , Liu Ting , Brown LaShardai N. , Schulte Bradley A. , Richard Stéphane , Lang Hainan 
Published: February 2018

Noise exposure causes auditory nerve (AN) degeneration and hearing deficiency, though the proximal biological consequences are not entirely understood. Most AN fibers and spiral ganglion neurons are ensheathed by myelinating glia that provide insulation and ensure rapid transmission of nerve impulses from the cochlea to the brain. Here we show that noise exposure administered to mice of either sex rapidly affects myelinating glial cells, causing molecular and cellular consequences that precede nerve degeneration. This response is characterized by demyelination, inflammation, and widespread expression changes in myelin-related genes, including the RNA splicing regulatorQuaking(QKI) and numerous QKI target genes. Analysis of mice deficient in QKI revealed that QKI production in cochlear glial cells is essential for proper myelination of spiral ganglion neurons and AN fibers, and for normal hearing. Our findings implicate QKI dysregulation as a critical early component in the noise response, influencing cochlear glia function that leads to AN demyelination and, ultimately, to hearing deficiency.SIGNIFICANCE STATEMENTAuditory glia cells ensheath a majority of spiral ganglion neurons with myelin, protect auditory neurons, and allow for fast conduction of electrical impulses along the auditory nerve. Here we show that noise exposure causes glial dysfunction leading to myelin abnormality and altered expression of numerous genes in the auditory nerve, including QKI, a gene implicated in regulating myelination. Study of a conditional mouse model that specifically depleted QKI in glia showed that QKI deficiency alone was sufficient to elicit myelin-related abnormality and auditory functional declines. These results establish QKI as a key molecular target in the noise response and a causative agent in hearing loss.
C8ORF37 Is Required for Photoreceptor Outer Segment Disc Morphogenesis by Maintaining Outer Segment Membrane Protein Homeostasis
Authors: Sharif Ali S. , Yu Dongmei , Loertscher Stuart , Austin Richard , Nguyen Kevin , Mathur Pranav D. , Clark Anna M. , Zou Junhuang , Lobanova Ekaterina S. , Arshavsky Vadim Y. , Yang Jun 
Published: February 2018

C8ORF37is a causative gene for three different clinical forms of incurable retinal degeneration. However, the completely unknown function ofC8ORF37limits our understanding of the pathogenicity ofC8ORF37mutations. Here, we performed a comprehensive phenotypic characterization of aC8orf37KO mouse line, generated using CRISPR/Cas9 technology. BothC8orf37KO male and female mice exhibited progressive and simultaneous degeneration of rod and cone photoreceptors but no non-ocular phenotypes. The major ultrastructural feature ofC8orf37KO photoreceptors was massive disorganization of the outer segment (OS) membrane discs starting from the onset of disc morphogenesis during development. At the molecular level, the amounts of multiple OS-specific membrane proteins, including proteins involved in membrane disc organization, were reduced, although these proteins were targeted normally to the OS. Considering the distribution of C8ORF37 throughout the photoreceptor cell body, the normal structure of the KO photoreceptor connecting cilium, and the absence of defects in other ciliary organs of the KO mice, our findings do not support the previous notion that C8ORF37 was a ciliary protein. Because C8ORF37 is absent in the photoreceptor OS, C8ORF37 may participate in the secretory pathway of OS membrane proteins in the photoreceptor cell body and thus maintain the homeostasis of these proteins. This study established a valid animal model for future therapeutic studies ofC8ORF37-associated retinal degeneration. This study also shed new light on the role of C8ORF37 in photoreceptors and on the pathogenic mechanism underlying retinal degeneration caused byC8ORF37mutations.SIGNIFICANCE STATEMENTInherited retinal degeneration is a group of incurable conditions with poorly understood underlying molecular mechanisms. We investigatedC8ORF37, a causative gene for three retinal degenerative conditions: retinitis pigmentosa, cone–rod dystrophy, and Bardet–Biedl syndrome.C8ORF37encodes a protein with no known functional domains and thus its biological function is unpredictable. We knocked out theC8ORF37ortholog in mice, which resulted in a retinal phenotype similar to that observed in patients. We further demonstrated that C8ORF37 is required for photoreceptor outer segment disc formation and alignment, a process that is critical for photoreceptor function and survival. This study advances our understanding of the pathogenesis of retinal degeneration and establishes a valuable mouse model for future therapeutic development.
Cardiac magnetic resonance imaging of myocardial mass and fibrosis in primary aldosteronism
Authors: Grytaas Marianne Aa , Sellevåg Kjersti , Thordarson Hrafnkell B , Husebye Eystein S , Løvås Kristian , Larsen Terje H 
Published: February 2018

Background
Primary aldosteronism (PA) is associated with increased cardiovascular morbidity, presumably due to left ventricular (LV) hypertrophy and fibrosis. However, the degree of fibrosis has not been extensively studied. Cardiac magnetic resonance imaging (CMR) contrast enhancement and novel sensitive T1 mapping to estimate increased extracellular volume (ECV) are available to measure the extent of fibrosis.

Objectives
To assess LV mass and fibrosis before and after treatment of PA using CMR with contrast enhancement and T1 mapping.

Methods
Fifteen patients with newly diagnosed PA (PA1) and 24 age- and sex-matched healthy subjects (HS) were studied by CMR with contrast enhancement. Repeated imaging with a new scanner with T1 mapping was performed in 14 of the PA1 and 20 of the HS median 18 months after specific PA treatment and in additional 16 newly diagnosed PA patients (PA2).

Results
PA1 had higher baseline LV mass index than HS (69 (53–91) vs 51 (40–72) g/m2; P < 0.001), which decreased significantly after treatment (58 (40–86) g/m2; P < 0.001 vs baseline), more with adrenalectomy (n = 8; −9 g/m2; P = 0.003) than with medical treatment (n = 6; −5 g/m2; P = 0.075). No baseline difference was found in contrast enhancement between PA1 and HS. T1 mapping showed no increase in ECV as a myocardial fibrosis marker in PA. Moreover, ECV was lower in the untreated PA2 than HS 10 min post-contrast, and in both PA groups compared with HS 20 min post-contrast.

Conclusion
Specific treatment rapidly reduced LV mass in PA. Increased myocardial fibrosis was not found and may not represent a common clinical problem.
Multivariate Analysis of the Cotton Seed Ionome Reveals a Shared Genetic Architecture
Authors: Pauli Duke , Ziegler Greg , Ren Min , Jenks Matthew A , Hunsaker Douglas J , Zhang Min , Baxter Ivan , Gore Michael A 
Published: February 2018

AbstractTo mitigate the effects of heat and drought stress, a better understanding of the genetic control of physiological responses to these environmental conditions is needed. To this end, we evaluated an upland cotton (Gossypium hirsutum L.) mapping population under water-limited and well-watered conditions in a hot, arid environment. The elemental concentrations (ionome) of seed samples from the population were profiled in addition to those of soil samples taken from throughout the field site to better model environmental variation. The elements profiled in seeds exhibited moderate to high heritabilities, as well as strong phenotypic and genotypic correlations between elements that were not altered by the imposed irrigation regimes. Quantitative trait loci (QTL) mapping results from a Bayesian classification method identified multiple genomic regions where QTL for individual elements colocalized, suggesting that genetic control of the ionome is highly interrelated. To more fully explore this genetic architecture, multivariate QTL mapping was implemented among groups of biochemically related elements. This analysis revealed both additional and pleiotropic QTL responsible for coordinated control of phenotypic variation for elemental accumulation. Machine learning algorithms that utilized only ionomic data predicted the irrigation regime under which genotypes were evaluated with very high accuracy. Taken together, these results demonstrate the extent to which the seed ionome is genetically interrelated and predictive of plant physiological responses to adverse environmental conditions.
Farklı oranlarda CrC partikül takviyesi kullanılarak toz metalürjisi yöntemiyle üretilmiş Cu matrisli kompozit malzemelerin mikroyapı ve mekanik özelliklerinin incelenmesi
Authors: UZUN Mahir , MÜNİS Mehmet Mehdi , USCA Üsame Ali 
Published: February 2018

Bu çalışmada, toz metalürjisi (T/M) yöntemi
kullanılarak farklı oranlarda CrC partikülleri, Cu matrisi içerisinde
kullanılarak Cu matrisli kompozit malzeme üretimi amaçlanmıştır. Bu amaçla Saf
Cu tozu içerisine CrC partikülleri ağırlıkça %5, %10, %15 ve %20 olmak üzere farklı oranlarda
katılmıştır. Hazırlanan karşımlar 450 MPa basınç altında şekillendirilmiştir.
Şekillendirilen parçalar 950 0C’de 60 dakika boyunca
sinterlenmiştir. Sinterleme işleminin başarısı yoğunluğun ve SEM görüntülerinin
incelenmesi ile değerlendirilmiştir. Üretilen kompozit malzemelerin mikroyapı
ve mekanik özellikleri incelenmiştir. Mikroskop incelemeleri taramalı elektron
mikroskobu (SEM) kullanılarak yapılmıştır. Yapılan SEM incelenmesinde, eş
eksenli tanelerden oluşan Cu matrisi içerisinde CrC fazının dengeli dağıldığı
gözlenmiştir. Yapılan sertlik ölçümlerinde, CrC oranı arttıkça buna bağlı
olarak sertliğin arttığı gözlenmiştir.
Field experimental data for crop modeling of wheat growth response to nitrogen fertilizer, elevated CO2, water stress, and high temperature
Authors: Kassie Belay T. , Kimball Bruce A. , Jamieson Peter D. , Bowden J. W. , Sayre Ken D. , Groot J. J. , Pinter Paul J. , LaMorte Robert L. , Hunsaker Douglas J. , Wall Gerard W. , Leavitt Steven W. , White Jeffrey W. , Asseng Senthold 
Published: February 2018

Field experimental data of five experiments covering a wide range of growing conditions are assembled for wheat growth and cropping systems modeling. The data include an experiment on interactive effects of elevated CO2 by water and elevated CO2 by nitrogen fertilizer application from a Free-Air Carbon Dioxide Enrichment experiment (FACE) at Arizona in USA; a nitrogen rate fertilizer experiment from three locations and two years in The Netherlands; water deficit experiments at Lincoln in New Zealand and at Cunderdin in Australia; and a temperature sensitivity experiment at Obregon in Mexico. The data consist of 65 experimental treatments with more than 1000 detailed observations, with time series of development and growth, soil water and soil nitrogen dynamics, yield and yield components, daily weather, soil characteristics, and cultivar descriptions. These data have been used in various previous agronomic and crop modeling studies. Assembled data are quality checked and supplied in Agricultural Model Inter-comparison and Improvement (AgMIP) format. Data access via DOI 10.7910/DVN/V4P6PU.
Field data set of different cropping systems for agro-ecosystem modelling from MÃ¼ncheberg, Germany
Authors: Mirschel Wilfried , Barkusky Dietmar , Kersebaum Kurt Christian , Laacke Liane , Luzi Karin , Rosner Gunhild , Wenkel Karl-Otto 
Published: February 2018

A coherent field dataset (1993-1998) for three different cropping systems (intensive, organic, extensive) under rainfed conditions on the basis of the identical crop rotation (sugar beet - winter wheat - winter barley - winter rye - catch crop) located at the Experimental Station with sandy soils (Eutric Cambisol) of the Leibniz Centre for Agricultural Landscape Research (ZALF) MÃ¼ncheberg, Germany, is described in detail. Soil and crop processes as well as meteorological parameters were intensively monitored and all agro-management actions were meticulously recorded. The dataset contains data for crop (ontogenesis, plant, tiller and ear numbers, above-ground and root biomasses, yield, carbon and nitrogen content), soil (water and nitrogen contents), weather (all essential meteorological parameters) and management (soil tillage, sowing, fertilization, harvest). Additional the data set contains the meta-information for the observations. The dataset was used within the international workshop â€œModelling Water and Nutrient Dynamics in Soil-Water Systemâ€ with the participation of 18 different models from nine countries. The dataset is available via the Open Research Data Portal at ZALF MÃ¼ncheberg and is published under DOI 10.4228/ZALF.1992.167.
Cumhuriyet Dönemi Özgün Baskıresmi İçinde Litografi (Taşbaskı) Sanatının Gelişimi
Authors: Keskin İsmail 
Published: February 2018

Litografi (taşbaskı), imgelerin ve yazıların kağıda çalışır gibi taş yüzeyine resmedilmesine olanak tanıyan bir baskıresim tekniğidir. Diğer baskı tekniklerine göre daha işlevsel yapısı, görsel etki
zenginliği ve hızlı basım olanaklarıyla icadından kısa süre sonra bütün dünyaya yayılmıştır. Fazla zaman geçmeden ülkemize, İstanbul’a da getirilmiştir. Avrupalılaşma ideallerinin başlamasıyla, Osmanlı’nın son dönemlerinde ülkemize giren teknik, halk hikayelerinin görselleştirilmesinde
önemli bir araç olmuştur. Tasvirin yasak sayılması, litografinin imkanlarında güzel yazı geleneğiyle bütünleşmiş seyirlik resimler ile yıkılmış, batılı resim anlayışının başlangıcı niteliğindeki resimler
yaygınlaşmıştır.

1800’lerin sonlarında yurt dışına eğitim için gönderilen yetenekli asker öğrenciler, Avrupa resmini öğrenip İstanbul’a döndüklerinde Türk topraklarında akademik sanat eğitimi ve baskıresmin
kurumsallaşmasına öncülük etmişlerdir.

Osman Hamdi Bey’in Kurduğu Sanayi-i Nefise Mektebi Alisi akademik sanat eğitiminin ilk
önemli kurumu olmuş, Harp Okulu’nda Hoca Ali Rıza Bey litografiyi öğreterek Türkiye’de akademik baskıresmin temellerini atmıştır. 1936’da ülkemize davet edilen Fransız sanat eğitimcisi Leo-
pold Lévy Akademi’de, litografi donanımını da bünyesinde barındıran ilk özgün baskıresim atölyesini kurmuştur. Ciddi işleyen bir litografi atölyesi ise ancak 1950’li yıllarda yürürlüğe girmiştir.

Bu araştırmada, akademik anlamda ilk sanatsal litografilerin ortaya çıkışı, İstanbul ve
Anadolu’da sanat eğitimi kurumlarında atölyelerin yaygınlaşması, 1960’lı yılların başından itibaren ivme gösteren özgün baskıresim içinde, litografinin gelişim hareketleri, öncü sanatçılar ve
sanat eğitimi kurumlarının tekniği yaşatma çabaları ele alınacaktır.&nbsp;