bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Endocytic Scaffolding Protein together with Synapsin Regulates Synaptic Vesicle Clustering in theDrosophilaNeuromuscular Junction
Authors: Winther Åsa M.E. , Vorontsova Olga , Rees Kathryn A. , Näreoja Tuomas , Sopova Elena , Jiao Wei , Shupliakov Oleg 
Published: November 2015

Many endocytic proteins accumulate in the reserve pool of synaptic vesicles (SVs) in synapses and relocalize to the endocytic periactive zone during neurotransmitter release. Currently little is known about their functions outside the periactive zone. Here we show that in theDrosophilaneuromuscular junction (NMJ), the endocytic scaffolding protein Dap160 colocalizes during the SV cycle and forms a functional complex with the SV-associated phosphoprotein synapsin, previously implicated in SV clustering. This direct interaction is strongly enhanced under phosphorylation-promoting conditions and is essential for proper localization of synapsin at NMJs. In adap160rescue mutant lacking the interaction between Dap160 and synapsin, perturbed reclustering of SVs during synaptic activity is observed. Our data indicate that in addition to the function in endocytosis, Dap160 is a component of a network of protein–protein interactions that serves for clustering of SVs in conjunction with synapsin. During the SV cycle, Dap160 interacts with synapsin dispersed from SVs and helps direct synapsin back to vesicles. The proteins function in synergy to achieve efficient clustering of SVs in the reserve pool.SIGNIFICANCE STATEMENTWe provide the first evidence for the function of the SH3 domain interaction in synaptic vesicle (SV) organization at the synaptic active zone. UsingDrosophilaneuromuscular junction as a model synapse, we describe the molecular mechanism that enables the protein implicated in SV clustering, synapsin, to return to the pool of vesicles during neurotransmitter release. We also identify the endocytic scaffolding complex that includes Dap160 as a regulator of the events linking exocytosis and endocytosis in synapses.
Brain Connectivity Associated with Muscle Synergies in Humans
Authors: Rana Manku , Yani Moheb S. , Asavasopon Skulpan , Fisher Beth E. , Kutch Jason J. 
Published: November 2015

The human brain is believed to simplify the control of the large number of muscles in the body by flexibly combining muscle coordination patterns, termed muscle synergies. However, the neural connectivity allowing the human brain to access and coordinate muscle synergies to accomplish functional tasks remains unknown. Here, we use a surprising pair of synergists in humans, the flexor hallucis longus (FHL, a toe flexor) and the anal sphincter, as a model that we show to be well suited in elucidating the neural connectivity underlying muscle synergy control. First, using electromyographic recordings, we demonstrate that voluntary FHL contraction is associated with synergistic anal sphincter contraction, but voluntary anal sphincter contraction occurs without FHL contraction. Second, using fMRI, we show that two important medial wall motor cortical regions emerge in relation to these tasks: one located more posteriorly that preferentially activates during voluntary FHL contraction and one located more anteriorly that activates during both voluntary FHL contraction as well as voluntary anal sphincter contraction. Third, using transcranial magnetic stimulation, we demonstrate that the anterior region is more likely to generate anal sphincter contraction than FHL contraction. Finally, using a repository resting-state fMRI dataset, we demonstrate that the anterior and posterior motor cortical regions have significantly different functional connectivity with distinct and distant brain regions. We conclude that specific motor cortical regions in humans provide access to different muscle synergies, which may allow distinct brain networks to coordinate muscle synergies during functional tasks.SIGNIFICANCE STATEMENTHow the human nervous system coordinates activity in a large number of muscles is a fundamental question. The brain and spinal cord are believed to simplify the control of muscles by grouping them into functional units called muscle synergies. Motor cortex is involved in activating muscle synergies; however, the motor cortical connections that regulate muscle synergy activation are unknown. Here, we studied pelvic floor muscle synergies to elucidate these connections in humans. Our experiments confirmed that distinct motor cortical regions activate different muscle synergies. These regions have different connectivity to distinct brain networks. Our results are an important step forward in understanding the cortical control of human muscles synergies, and may also have important clinical implications for understanding movement dysfunction.
A Variable Oscillator Underlies the Measurement of Time Intervals in the Rostral Medial Prefrontal Cortex during Classical Eyeblink Conditioning in Rabbits
Authors: Caro-Martín C. Rocío , Leal-Campanario Rocío , Sánchez-Campusano Raudel , Delgado-García José M. , Gruart Agnès 
Published: November 2015

We were interested in determining whether rostral medial prefrontal cortex (rmPFC) neurons participate in the measurement of conditioned stimulus–unconditioned stimulus (CS-US) time intervals during classical eyeblink conditioning. Rabbits were conditioned with a delay paradigm consisting of a tone as CS. The CS started 50, 250, 500, 1000, or 2000 ms before and coterminated with an air puff (100 ms) directed at the cornea as the US. Eyelid movements were recorded with the magnetic search coil technique and the EMG activity of the orbicularis oculi muscle. Firing activities of rmPFC neurons were recorded across conditioning sessions. Reflex and conditioned eyelid responses presented a dominant oscillatory frequency of ≈12 Hz. The firing rate of each recorded neuron presented a single peak of activity with a frequency dependent on the CS-US interval (i.e., ≈12 Hz for 250 ms, ≈6 Hz for 500 ms, and≈3 Hz for 1000 ms). Interestingly, rmPFC neurons presented their dominant firing peaks at three precise times evenly distributed with respect to CS start and also depending on the duration of the CS-US interval (only for intervals of 250, 500, and 1000 ms). No significant neural responses were recorded at very short (50 ms) or long (2000 ms) CS-US intervals. rmPFC neurons seem not to encode the oscillatory properties characterizing conditioned eyelid responses in rabbits, but are probably involved in the determination of CS-US intervals of an intermediate range (250–1000 ms). We propose that a variable oscillator underlies the generation of working memories in rabbits.SIGNIFICANCE STATEMENTThe way in which brains generate working memories (those used for the transient processing and storage of newly acquired information) is still an intriguing question. Here, we report that the firing activities of neurons located in the rostromedial prefrontal cortex recorded in alert behaving rabbits are controlled by a dynamic oscillator. This oscillator generated firing frequencies in a variable band of 3–12 Hz depending on the conditioned stimulus–unconditioned stimulus intervals (1 s, 500 ms, 250 ms) selected for classical eyeblink conditioning of behaving rabbits. Shorter (50 ms) and longer (2 s) intervals failed to activate the oscillator and prevented the acquisition of conditioned eyelid responses. This is an unexpected mechanism to generate sustained firing activities in neural circuits generating working memories.
VPS26A–SNX27 Interaction-Dependent mGluR5 Recycling in Dorsal Horn Neurons Mediates Neuropathic Pain in Rats
Authors: Lin Tzer-Bin , Lai Cheng-Yuan , Hsieh Ming-Chun , Wang Hsueh-Hsiao , Cheng Jen-Kun , Chau Yat-Pang , Chen Gin-Den , Peng Hsien-Yu 
Published: November 2015

Retromer, which crucially contributes to endosomal sorting machinery through the retrieval and recycling of signaling receptors away from degradation, has been identified as a critical element for glutamatergic-receptor-dependent neural plasticity at excitatory synapses. We observed it accompanied by behavioral allodynia; neuropathic injury time-dependently enhanced VPS26A and SNX27 expression; VPS26A–SNX27 coprecipitation; and VPS26A-positive, SNX27-positive, and VPS26A–SNX27 double-labeled immunoreactivity in the dorsal horn of Sprague Dawley rats that were all sufficiently ameliorated through the focal knock-down of spinal VPS26A expression. Although the knock-down of spinal SNX27 expression exhibited similar effects, spinal nerve ligation (SNL)-enhanced VPS26A expression remained unaffected. Moreover, SNL also increased membrane-bound and total mGluR5 abundance, VPS26A-bound SNX27 and mGluR5 and mGluR5-bound VPS26A and SNX27 coprecipitation, and mGluR5-positive and VPS26A/SNX27/mGluR5 triple-labeled immunoreactivity in the dorsal horn, and these effects were all attenuated through the focal knock-down of spinal VPS26A and SNX27 expression. Although administration with MPEP adequately ameliorated SNL-associated allodynia, mGluR5 expression, and membrane insertion, SNL-enhanced VPS26A and SNX27 expression were unaffected. Together, these results suggested a role of spinal VPS26A–SNX27-dependent mGluR5 recycling in the development of neuropathic pain. This is the first study that links retromer-associated sorting machinery with the spinal plasticity underlying pain hypersensitivity and proposes the possible pathophysiological relevance of endocytic recycling in pain pathophysiology through the modification of glutamatergic mGluR5 recycling.SIGNIFICANCE STATEMENTVPS26A–SNX27-dependent mGluR5 recycling plays a role in the development of neuropathic pain. The regulation of the VPS26A–SNX27 interaction that modifies mGluR5 trafficking and expression in the dorsal horn provides a novel therapeutic strategy for pain relief.
Endothelial CD36 Contributes to Postischemic Brain Injury by Promoting Neutrophil Activation via CSF3
Authors: Garcia-Bonilla Lidia , Racchumi Gianfranco , Murphy Michelle , Anrather Josef , Iadecola Costantino 
Published: November 2015

The scavenger receptor CD36 is a critical factor initiating ischemic brain injury, but the cell type(s) expressing CD36 and responsible for its harmful effects remain unknown. Using bone marrow (BM) chimeras subjected to transient middle cerebral artery occlusion, we found that CD36−/−mice transplanted with wild-type (WT) BM (WT→CD36−/−) have smaller infarcts (−67%), comparable with those of mice lacking CD36 both in brain and hematogenous cells (CD36−/−→CD36−/−; − 72%). Conversely, WT mice receiving CD36−/−BM (CD36−/−→WT) have infarcts similar to WT→WT mice, suggesting that CD36 in the host brain (i.e., in microglia and endothelial cells), and not in hematogenous cells is involved in the damage. As anticipated, postischemic neutrophil infiltration in CD36−/−→CD36−/−mice was attenuated. Surprisingly, however, in WT→CD36−/−mice, in which infarcts were small, neutrophil infiltration was large and similar to that of CD36−/−→WT mice, in which infarcts were not reduced. Postischemic neutrophil free radical production was attenuated in WT→CD36−/−mice compared with CD36−/−→WT mice, whereas expression of the neutrophil activator colony-stimulating factor 3 (CSF3) was suppressed in CD36−/−cerebral endothelial cells, but not microglia. In CD36−/−cerebral endothelial cultures exposed to extracts from stroke brains, the upregulation of CSF3, but not neutrophil attractant chemokines, was suppressed. Intracerebroventricular administration of CSF3, 24 h after stroke, reconstituted neutrophil radical production and increased infarct volume in WT→CD36−/−mice. The findings identify endothelial cells as a key player in the deleterious effects of CD36 in stroke, and unveil a novel role of endothelial CD36 in enabling neutrophil neurotoxicity through CSF3.SIGNIFICANCE STATEMENTIschemic stroke is a leading cause of death and disability worldwide with limited therapeutic options. The inflammatory response initiated by cerebral ischemia-reperfusion contributes to ischemic brain injury and is a potential therapeutic target. Here we report that CD36, an innate immunity receptor involved in the initiation of postischemic inflammation, is a previously unrecognized regulator of neutrophil cytotoxicity. The effect is mediated by endothelial CD36 via upregulation of the neutrophil activator CSF3 in cerebral endothelial cells. Therefore, approaches to modulate cerebral endothelial CD36 signaling or to neutralize CSF3 may provide novel therapeutic opportunities to ameliorate postischemic inflammatory injury.
Reduction of trabecular and cortical volumetric bone mineral density at the proximal femur in patients with acromegaly
Authors: Valassi Elena , Crespo Iris , Malouf Jorge , Llauger Jaume , Aulinas Anna , Marín Ana Maria , Biagetti Betina , Webb Susan M 
Published: November 2015

ObjectiveData on dual energy absorptiometry (DXA)-measured bone mineral density (BMD) at the level of the total hip (TH) and femoral neck (FN) in patients with acromegaly (ACRO) are conflicting. Increase in bone size associated with ACRO may limit the reliability of DXA. Our objective is to evaluate trabecular and cortical volumetric BMD (vBMD) across the proximal femur in ACRO patients.DesignCross sectional study in a clinical research center.PatientsThirty-five ACRO patients (19 males; mean age, 48±7 years; BMI, 27.5±4.4 kg/m2; 17 with active disease) and 35 age, gender, and BMI-matched controls.ResultsvBMD was assessed by quantitative computed tomography at the level of the TH, FN, trochanter (TR), and intertrochanteric (IT). Trabecular vBMD was lower in both total and active ACRO as compared with controls (P<0.01). Cortical vBMD was lower in ACRO patients (active and controlled) vs controls at both TH and TR sites (P<0.05). These findings were confirmed when only eugonadal patients were analyzed. Both total cross sectional area (CSA) and average cortical thickness (ACT) were greater in ACRO patients vs controls (P<0.05). An inverse association between disease duration and trabecular vBMD at TH (r=−0.42, P=0.023) and IT (r=−0.41, P=0.026) was also found.ConclusionBoth cortical and trabecular vBMD are reduced at the proximal femur in ACRO patients, regardless of gender, gonadal status, and disease activity. Disease duration is negatively associated with trabecular vBMD at the TH and IT.
Divergent Residues Within Histone H3 Dictate a Unique Chromatin Structure in Saccharomyces cerevisiae
Authors: McBurney Kristina L , Leung Andrew , Choi Jennifer K , Martin Benjamin J E , Irwin Nicholas A T , Bartke Till , Nelson Christopher J , Howe LeAnn J 
Published: November 2015

Abstract
Histones are among the most conserved proteins known, but organismal differences do exist. In this study, we examined the contribution that divergent amino acids within histone H3 make to cell growth and chromatin structure in Saccharomyces cerevisiae. We show that, while amino acids that define histone H3.3 are dispensable for yeast growth, substitution of residues within the histone H3 α3 helix with human counterparts results in a severe growth defect. Mutations within this domain also result in altered nucleosome positioning, both in vivo and in vitro, which is accompanied by increased preference for nucleosome-favoring sequences. These results suggest that divergent amino acids within the histone H3 α3 helix play organismal roles in defining chromatin structure.
Uterustumore bei älteren Miniaturschweinen – Diagnostik und Therapie
Authors: Nickoll I. , Kauffold J. , Puff C. , Waldmann K.-H. , von Altrock A. , Höltig D. 
Published: November 2015

ZusammenfassungMiniaturschweine (Minipigs) gehören immer häufiger zu den Patienten der Kleintierpraxis. Da sie in der Regel ein deutlich höheres Lebensalter erreichen als Schweine in der Nutztierhaltung, treten bei ihnen Alterserkrankungen auf, die bei konventionell gehaltenen Schweinen keine Rolle spielen. Hierzu gehören neoplastische Veränderungen des Uterus. Die beiden präsentierten Fallbeispiele beschreiben ein uterines Adenokarzinom sowie ein Leiomyom bei zwei Minipigsauen. Diskutiert werden Optionen und Grenzen der Diagnostik (unspezifische klinische Symptomatik, Röntgen, Ultraschall und Computertomographie), die Gefahr der Verwechslung mit häufiger vorkommenden differenzialdiagnostisch zu berücksichtigenden Erkrankungen (Obstipation, Zystitis, Endometritis) in der Schweinemedizin sowie die Therapie bei Verdacht auf Vorliegen eines Uterustumors im Rahmen der gesetzlichen Möglichkeiten.
2014 -2016 Editorial Board and Note from the Editors
Authors: Hanna Eriny , Belenzada Jelena 
Published: November 2015

A Note from the Editors

We are delighted to welcome you to Volume 10 of the Vanderbilt Undergraduate Research Journal (VURJ), a selection of some of the finest research conducted within the undergraduate community at Vanderbilt University. In the decade since its inception, VURJ has featured over 100 articles in the sciences, humanities, and social sciences.
After a brief hiatus in 2014, VURJ came back stronger than ever, boasting our most diverse and selective issue yet. With 73 submissions from students at all four of Vanderbilt’s undergraduate schools, 19 outstanding articles were selected for publication. All submitted manuscripts underwent a rigorous multi-step review process, including two to three rounds of readings by trained peer reviewers, and final selection for publication by VURJ’s team of associate editors. In this issue, you will learn about and explore a diverse selection of topics from arts in trauma therapy to the resurrection of extinct species, an exciting assortment that provides a small glimpse into Vanderbilt’s thriving and dynamic academic community.
We encourage you to engage further with this community by contributing some of your own work to our next issue, or by applying to join our team of editors.
Happy reading and best wishes,
Jelena Belenzada
Editor in Chief, 2014-2015

Eriny Hanna
Editor at Large, 2014-2015
Risk Assessments for Invasive Plants: A Midwestern U.S. Comparison
Authors: Buerger Amanda , Howe Katherine , Jacquart Ellen , Chandler Monika , Culley Theresa , Evans Christopher , Kearns Kelly , Schutzki Robert , Riper Laura Van 
Published: November 2015

AbstractSeveral states in the Midwestern United States are using risk assessment to determine the invasiveness of introduced plant species, and each assessment process is different. This may lead to differences in results for the same species between states, creating concern about credibility by those using the assessments. In this study, risk assessments for six Midwestern states were compared, examining format, content, and assessment committee membership. Case studies were conducted for four species for which at least five of the six states in the study completed a risk assessment; results were compared in the context of general differences in assessment content and those specific to each species. Furthermore, 14 species for which only four of the six states completed assessments were briefly examined for outcome differences only, and possible reasons for these inconsistencies. Overall, differences in assessments did not result in incompatible conclusions for the species compared, suggesting that unique assessments in each state can provide consistent and credible results. We propose that these Midwestern states share species resources with each other to further improve consistency between the assessments.
La USMC y su influencia sobre la industria del calzado de Estados Unidos, Latinoamérica y Europa en la primera mitad del siglo XX. ¿Un monopolio eficiente?
Authors: Miranda José A. 
Published: November 2015

<span style="font-family: Times New Roman; font-size: small;"> </span><p>Este artículo analiza la estrategia de la United Shoe Machinery Company, empresa que dominó el mercado mundial de maquinaria para calzado en la primera mitad del siglo XX, su penetración en Latinoamérica y en el resto del mundo y los procesos judiciales antimonopolio que sufrió en Estados Unidos. A pesar de su posición de práctico monopolio, la empresa tuvo un desempeño eficiente que impulsó la innovación tecnológica y la modernización de la industria del calzado en muchos países.</p><p class="MsoNormal" style="margin: 0cm 0cm 6pt;"> </p><span style="font-family: Times New Roman; font-size: small;"> </span>
KAMAR MANDI SEBAGAI TEMPAT BERSUCI (THAHARAH)
Authors: Sedayu Agung 
Published: November 2015

Keeping cleanliness and holiness is the duty for all moslems. To perform these religious duties, every time and everywhere, we must keep and support hard on the holiness of the physic and psychic value aspects. Most cleaning activities have been done in toilet and the other similar places. The Main tool to clean is water; therefore toilet is always having water having the image as a wet place. Toilet is one of the arranged rooms in building and assumed to be added room that is not so important. In fact, it has a very vital and important function. Inside of the toilet we have the erudition and philosophy which must be done, like praying before and after entering this room, and also some other rules to follow when we are in it. Cleaning the psychic is started at cleaning the body, and cleaning the psychic is supported by cleanliness of our environment including toilet as a part of the house. Therefore, before designing it, all of the moslem architects must concern and focus on the erudition and philosophy of Islamic fiqih containing about the effort to be clean and holy. Design results should reflect Islamic values, and the toilet having Islamic characteristics, especially having strength points on cleanliness and holiness. This paper is to discuss about toilet design from the perspective of fiqih values on cleanliness and holiness. The objectives are to give more information and knowledge about toilet design principles having Islamic values based on fiqih law references on cleanliness and holiness.<br /><br />Keywords: Toilet, Place To Clean<br /><br />
Pengaruh Islam terhadap Perkembangan Budaya Jawa: tembang Macapat
Authors: Mulyono Asmaun Sahlan, 
Published: November 2015

<div class="WordSection1"><p>Islam came to Indonesia since the seventh century AD has a major influence on the transformation of the local culture. From cultures that were previously heavily influenced by Hinduism is primarily based on two major books from India, the Ramayana and the Mahabharata to the new culture that is influenced by Islamic values. One form of cultural transformation in the field of Javanese literature is the birth of the tembang macapat (song of macapat). Tembang macapat is a form of transformation from Javanese literature of the form kakawin literary dan kidung (ancient Javanese song) became a form of Java new song (gending). During its development, macapat song contains a lot of Islamic values so utilized by teachers, preachers, religious scholars and Ulama’ to the means of education and transformation of Islamic values.</p> <p> </p> <p>Islam datang ke Indonesia sejak abad ke tujuh Masehi memiliki pengaruh besar terhadap transformasi budaya setempat. Dari kebudayaan yang sebelumnya banyak dipengaruhi oleh agama Hindu terutama didasarkan pada dua karya besar dari India yaitu Ramayana dan Mahabharata menuju kepada kebudayaan baru yang dipengaruhi oleh nilai-nilai Islam. Salah satu bentuk transformasi kebudayaan dalam bidang sastra Jawa adalah lahirnya tembang macapat. Tembang macapat merupakan bentuk transformasi sastra Jawa dari bentuk kakawin dan kidung menjadi sastra puisi yang berupa lagu/gending. Dalam perkembangannya, tembang macapat banyak mengandung nilai-nilai Islam sehingga dimanfaatkan oleh para guru, mubaligh, kyai maupun ulama’ untuk sarana pendidikan dan dakwah nilai-nilai Islam.</p> <p> </p></div>