bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase of Spontaneous Slow Oscillations during Sleep Influences Memory-Related Processing of Auditory Cues
Authors: Batterink Laura J. , Creery Jessica D. , Paller Ken A. 
Published: January 2016

Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned arbitrary spatial locations for objects that were each paired with a characteristic sound (eg, cat–meow). Then, during SWS periods of an afternoon nap, one-half of the sounds were presented at low intensity. When object location memory was subsequently tested, recall accuracy was significantly better for those objects cued during sleep. We report here for the first time that this memory benefit was predicted by slow-wave phase at the time of stimulation. For cued objects, location memories were categorized according to amount of forgetting from pre- to post-nap. Conditions of high versus low forgetting corresponded to stimulation timing at different slow-oscillation phases, suggesting that learning-related stimuli were more likely to be processed and trigger memory reactivation when they occurred at the optimal phase of a slow oscillation. These findings provide insight into mechanisms of memory reactivation during sleep, supporting the idea that reactivation is most likely during cortical upstates.SIGNIFICANCE STATEMENTSlow-wave sleep (SWS) is characterized by synchronized neural activity alternating between active upstates and quiet downstates. The slow-oscillation upstates are thought to provide a window of opportunity for memory consolidation, particularly conducive to cortical plasticity. Recent evidence shows that sensory cues associated with previous learning can be delivered subtly during SWS to selectively enhance memory consolidation. Our results demonstrate that this behavioral benefit is predicted by slow-oscillation phase at stimulus presentation time. Cues associated with high versus low forgetting based on analysis of subsequent recall performance were delivered at opposite slow-oscillation phases. These results provide evidence of an optimal slow-oscillation phase for memory consolidation during sleep, supporting the idea that memory processing occurs preferentially during cortical upstates.
Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons
Authors: Kruse Martin , Vivas Oscar , Traynor-Kaplan Alexis , Hille Bertil 
Published: January 2016

In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons.SIGNIFICANCE STATEMENTPhosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons.
Genetic Demonstration of a Role for Stathmin in Adult Hippocampal Neurogenesis, Spinogenesis, and NMDA Receptor-Dependent Memory
Authors: Martel Guillaume , Uchida Shusaku , Hevi Charles , Chévere-Torres Itzamarie , Fuentes Ileana , Park Young Jin , Hafeez Hannah , Yamagata Hirotaka , Watanabe Yoshifumi , Shumyatsky Gleb P. 
Published: January 2016

Neurogenesis and memory formation are essential features of the dentate gyrus (DG) area of the hippocampus, but to what extent the mechanisms responsible for both processes overlap remains poorly understood. Stathmin protein, whose tubulin-binding and microtubule-destabilizing activity is negatively regulated by its phosphorylation, is prominently expressed in the DG. We show here that stathmin is involved in neurogenesis, spinogenesis, and memory formation in the DG.tTA/tetO-regulated bitransgenic mice, expressing the unphosphorylatable constitutively activeStathmin4Amutant (Stat4A), exhibit impaired adult hippocampal neurogenesis and reduced spine density in the DG granule neurons. AlthoughStat4Amice display deficient NMDA receptor-dependent memory in contextual discrimination learning, which is dependent on hippocampal neurogenesis, their NMDA receptor-independent memory is normal. Confirming NMDA receptor involvement in the memory deficits,Stat4Amutant mice have a decrease in the level of synaptic NMDA receptors and a reduction in learning-dependent CREB-mediated gene transcription. The deficits in neurogenesis, spinogenesis, and memory inStat4Amice are not present in mice in whichtTA/tetO-dependent transgene transcription is blocked by doxycycline through their life. The memory deficits are also rescued within 3 d by intrahippocampal infusion of doxycycline, further indicating a role for stathmin expressed in the DG in contextual memory. Our findings therefore point to stathmin and microtubules as a mechanistic link between neurogenesis, spinogenesis, and NMDA receptor-dependent memory formation in the DG.SIGNIFICANCE STATEMENTIn the present study, we aimed to clarify the role of stathmin in neuronal and behavioral functions. We characterized the neurogenic, behavioral, and molecular consequences of the gain-of-function stathmin mutation using a bitransgenic mouse expressing a constitutively active form of stathmin. We found that stathmin plays an important role in adult hippocampal neurogenesis and spinogenesis. In addition, stathmin mutation led to impaired NMDA receptor-dependent and neurogenesis-associated memory and did not affect NMDA receptor-independent memory. Moreover, biochemical analysis suggested that stathmin regulates the synaptic transport of NMDA receptors, which in turn influence CREB-mediated gene transcription machinery. Overall, these data suggest that stathmin is an important molecule for neurogenesis, spinogenesis, and NMDA receptor-dependent learning and memory.
Conformational Changes in Transmembrane Domain 4 of Presenilin 1 Are Associated with Altered Amyloid-β 42 Production
Authors: Tominaga Aya , Cai Tetsuo , Takagi-Niidome Shizuka , Iwatsubo Takeshi , Tomita Taisuke 
Published: January 2016

γ-Secretase is an intramembrane-cleaving protease that produces amyloid-β peptide 42 (Aβ42), which is the toxic and aggregation-prone species of Aβ that causes Alzheimer's disease. Here, we used the substituted cysteine accessibility method to analyze the structure of transmembrane domains (TMDs) 4 and 5 of human presenilin 1 (PS1), a catalytic subunit of γ-secretase. We revealed that TMD4 and TMD5 face the intramembranous hydrophilic milieu together with TMD1, TMD6, TMD7, and TMD9 of PS1 to form the catalytic pore structure. Notably, we found a correlation in the distance between the cytosolic sides of TMD4/TMD7 and Aβ42production levels, suggesting that allosteric conformational changes of the cytosolic side of TMD4 affect Aβ42-generating γ-secretase activity. Our results provide new insights into the relationship between the structure and activity of human PS1.SIGNIFICANCE STATEMENTModulation of γ-secretase activity to reduce toxic amyloid-β peptide species is one plausible therapeutic approaches for Alzheimer's disease. However, precise mechanistic information of γ-secretase still remains unclear. Here we identified the conformational changes in transmembrane domains of presenilin 1 that affect the proteolytic activity of the γ-secretase. Our results highlight the importance of understanding the structural dynamics of presenilin 1 in drug development against Alzheimer's disease.
TFEB and TFE3 are novel components of the integrated stress response
Authors: Martina José A , Diab Heba I , Brady Owen A , Puertollano Rosa 
Published: January 2016

AbstractTo reestablish homeostasis and mitigate stress, cells must activate a series of adaptive intracellular signaling pathways. The participation of the transcription factors TFEB and TFE3 in cellular adaptation to starvation is well established. Here, we show that TFEB and TFE3 also play an important role in the cellular response to ER stress. Treatment with ER stressors causes translocation of TFEB and TFE3 to the nucleus in a process that is dependent on PERK and calcineurin but not on mTORC1. Activated TFEB and TFE3 enhance cellular response to stress by inducing direct transcriptional upregulation of ATF4 and other UPR genes. Under conditions of prolonged ER stress, TFEB and TFE3 contribute to cell death, thus revealing an unexpected role for these proteins in controlling cell fate. This work evidences a broader role of TFEB and TFE3 in the cellular response to stress than previously anticipated and reveals an integrated cooperation between different cellular stress pathways.
Parenting a child with haemophilia while living in a non-metropolitan area
Authors: Little Trudi , Strodl Esben , Brown Simon , Mooney Tara 
Published: January 2016

Abstract
The experience of living in a non-metropolitan area and parenting a child with haemophilia is relatively unknown. Using Interpretive Phenomenological Analysis (IPA), the following study explored the experiences of seven parents, from which four themes emerged: ‘bearing the brunt of diagnosis’ captures the impact of the diagnosis; ‘if you can’t help me, who can?’ reveals experiences with the health system; ‘tackling the challenge of treatment’ encompasses difficulties in adhering to the treatment regime; ‘I need you to understand’ reflects desires for others support and understanding. These themes should be considered when developing support systems and interventions for parents living in non-metropolitan areas.
How the classification of von Willebrand Disease can guide therapy
Authors: Laffan Michael A 
Published: January 2016

Abstract
In a recent editorial published in Haemophilia, Millar asks ‘Why and how do we classify von Willebrand disease?’ [1]. This may seem like a philosophical question, but two case reports in this edition of The Journal of Haemophilia Practice illustrate good practical answers to both parts of the question.
As línguas românicas do/no Magrebe: percurso histórico e presença contemporânea
Authors: Olmo Francisco Javier Calvo del 
Published: January 2016

Este artigo propõe-se reunir e examinar elementos que permitam traçar o percurso histórico das línguas românicas no Magrebe. Desde uma abordagem interdisciplinar, apresentam-se as comunidades latinizadas durante a dominação romana, os contatos linguísticos que produziram a Língua Franca mediterrânea no período medieval, as minorias de mouriscos e sefardim procedentes da Península Ibérica estabelecidas no norte da África nos séculos XIV e XV, o processo da colonização francesa nos séc. XIX e XX e o mosaico linguístico das últimas décadas, após a independência. Dessa forma, identificam-se os componentes linguísticos latinos e românicos, cindidos e descontínuos, constitutivos do Magrebe enquanto espaço geográfico, cultural e humano. This paper aims to gather and examine some elements to draw the historical course of the Romance languages in the Maghreb. It employs an interdisciplinary approach to present the Latinized communities during Roman domination, language contacts that produced the Mediterranean Lingua Franca during Middle Age, Moorish and Sephardic minorities settled in fifteenth and sixteenth centuries, the process of French colonization in nineteenth and twentieth centuries and the linguistic mosaic of last decades, after national independences. This itinerary permits to pinpoint a linguistic Latin-Romance component, fragmented and discontinuous, constitutive of the Maghreb as a geographic, cultural and human space.
Uma análise de relativas livres em posição de sujeito e efeitos de compatibilidade no português brasileiro
Authors: Medeiros Júnior Paulo 
Published: January 2016

Entende-se que relativas livres sejam sujeitas ao que se chama efeito de compatibilidade, que prevê que a categoria/Caso do sintagma-wh integrando essa sentença precisa ser compatível com os requerimentos do predicador da matriz. Alguns estudos como os de Suñer (1983, 1984) e Harbert (1983) propõem que relativas livres em posição de sujeito estão livres dos efeitos de compatibilidade em línguas pro-Drop. Os dados do PB parecem contradizer essa ideia; mesmo em posição de sujeito, relativas livres precisam “combinar”. Os dados avaliados neste paper, por seu comportamento sintático e semântico, são interpretados não como relativas livres em posição de sujeito, e sim como perguntas indiretas em posição de tópico. A proposta final é a de que o PB é uma língua de 100% de matching. Free relatives are supposed to be affected by the so-called matching effects, according to which the category/Case of the Wh-element integrating this sentence must match the requirements of the matrix predicate. Some works, as the ones by Suñer (1983, 1984) and Harbert (1983), have proposed that subject free relatives are free from matching effects in pro-Drop languages. Brazilian Portuguese data seem though to contradict this idea; even in subject position, free relatives must match. Focused data are interpreted in this paper (considering their syntactic and semantic behavior) not as subject free relatives, but as topicalized indirect questions. The conclusion is: Brazilian Portuguese is a 100% matching language.
Desarrollo del entorno personal de aprendizaje para tutoría e investigación en niveles educativos superiores
Authors: Dzib Goodin Alma , Castevich John , Hogan Dolores Luna , Sanders Linda , Slovec Kathleen , Yelizarov Daniel 
Published: January 2016

<p>El concepto de entorno personal se refiere a los sistemas que facilitan a los aprendices a tomar control de manera autónoma sus aprendizajes. Esto incluye apoyos para determinar sus propias metas, comprensión de contenidos y de los procesos implicados en el proceso de aprendizaje. Usualmente el mayor impulso se ofrece en torno a las nuevas tecnologías, ya que se supone que el alumno es capaz de interactuar de manera efectiva con los lenguajes y entornos tecnológicos, pues más jóvenes las generaciones, más conocimiento tienen del uso y manejo de la información en medios digitales.</p><p>Partir de este supuesto, y suponer que el alumno es capaz por si mismo de encontrar su propio camino, lleva a mucha frustración, especialmente cuando se considera como factor clave las diferencias culturales.</p><p>El presente trabajo busca reconocer que existen diferencias culturales en el manejo de herramientas que se considerar usuales como las redes sociales para desarrollar propuestas académicas que permitan apoyar el aprendizaje de los estudiantes y se encuentra que existen factores que pueden potencialmente beneficiar o entorpecer el desarrollo académico de los estudiantes si estas no son consideradas en los programas educativos.</p><p>Reconocer dichas diferencias es clave para trabajar en programas de apoyo a los estudiantes, pues una vez que éstos reconocen sus potencialidades y son capaces de generar las estrategias adecuadas a los requerimientos de las nuevas tecnologías, serán más eficientes en su aprendizaje.</p>
Wrong-Site Surgery in Orthopaedics: Prevalence, Risk Factors, and Strategies for Prevention
Authors: Santiesteban Lauren , Hutzler Lorraine , Bosco Joseph A. , Robb William 
Published: January 2016

➢ The incidence of wrong-site surgery in orthopaedics is unknown. This is due to a lack of data regarding the exact numbers of surgical procedures performed and a lack of a uniform mandatory error reporting infrastructure.➢ Twenty-one percent of hand surgeons, 50% of spinal surgeons, and 8.3% of knee surgeons surveyed have reported performing at least one wrong-site surgery during their career.➢ Every orthopaedic surgeon, no matter his or her orthopaedic subspecialty, is at risk for completing a wrong-site surgery during his or her career. Prevention of wrong-site surgery should remain a priority for the orthopaedic community.➢ Surgeon leadership, commitment, and vigilance are critical to improve patient safety by ensuring that validated safety processes are used in all orthopaedic settings including effective surgical team communication, checklists, and routine collection and analysis of quality and safety data.
Lithofacies Classification of Thin-Layered Turbidite Reservoirs Through the Integration of Core Data and Dielectric-Dispersion Log Measurements
Authors: Pirrone M.. , Battigelli A.. , Ruvo L.. 
Published: January 2016

SummaryDistal turbidites consist of thin laminations (inch scale), usually ranging from fine sand to clay-rich deposits and may represent major hydrocarbon reservoirs: Conventionally, they are studied by means of a log-based binary modeling that discriminates productive and nonproductive layers. Nevertheless, the binary model represents a major drawback when dealing with laminations in the silt-grain-size range, because their allotment to either end member can be extremely problematic.This paper deals with a novel, probabilistic, lithological facies-classification approach that integrates core data and a high-resolution dielectric-dispersion wireline log: Its 1-in. vertical resolution and a related fit-for-purpose petrophysical model make the log tool's response suitable to describe the lithological heterogeneity of these reservoirs.The approach is presented by means of a study performed on the cored section of a well drilled into a laminated gas-bearing Pleistocene reservoir in the Adriatic Basin. A core-based classification was first carried out with sedimentological descriptions, mineralogical analyses, cation-exchange-capacity (CEC) measurements, routine and special core analyses, and a statistical investigation of grain-size distributions: This allowed the identification of four lithofacies ranging from hemipelagite to coarse silt. Next, a log-based classification was carried out with a multivariate statistical numerical technique integrated in a Bayesian framework run on the dielectric-dispersion model curves. The outputs are the probability of log-facies, the most-probable facies scenario, and the associated uncertainty by means of entropy computation. In the end, a four-facies log-based classification was obtained that matches the core-based classification with an overall agreement in excess of 93%.Compared with the conventional methodology, the presented approach shows the added value of identifying intermediate lithologies, thus leading to a more-accurate quantification of the thickness of the potentially hydrocarbon-bearing net reservoir.
An Integrated Work Flow for a Comprehensive Evaluation of Thin, Silty Hydrocarbon-Reservoir Sequences
Authors: Chu Wei-Chun , Steckhan Jan 
Published: January 2016

Summary
A robust work flow is established to identify low-resistivity pay (LRP) in thinly laminated sands with silty and/or shaly layers. The work flow integrates data from gas-while-drilling, conventional logging, and nuclear-magnetic-resonance (NMR) logging for picking intervals for further examination with a wireline formation tester (WFT). A mini-drill-stem test (DST) is performed by means of a WFT equipped with either a single probe (SP) or a dual packer (DP) to determine the fluid type and productivity of each individual level.
Two field examples are presented to compare well performance predicted by the microscale mini-DSTs with macroscale production tests. In both cases, the traditional DST is eliminated from the drilling/completion program. The final verification consists of comparing contributions of individual levels derived from the mini-DSTs with production logs.
In the first case, mini-DSTs are able to provide the fluid type and individual-level transmissibility (kh/μ) for eight out of 13 distinct levels. A cost-effective approach of running mini-DSTs by means of a WFT equipped with a single probe is demonstrated to investigate multiple levels in the thin-hydrocarbon reservoir sequence. Guidelines are provided as to when a WFT with a DP is to be deployed to perform a mini-DST in a laminated formation.
In the second case, the same work flow was applied to derive the fluid type and transmissibility for two wells consisting of more than 30 distinct levels in the same field. After integrating mini-DST results from the two wells 750 m apart, a framework is constructed to establish both vertical and lateral heterogeneities of thinly laminated reservoirs. The integration helps visualize the multiple-layer reservoir.
Our examples confirm that mini-DSTs effectively define individual-layer producibilities in multiple-layered reservoirs. The benefits are illustrated through case histories that demonstrate our ability to manage expectations of well performance in thin hydrocarbon-reservoir sequences.