bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Cell Detection of Secreted Aβ and sAPPα from Human IPSC-Derived Neurons and Astrocytes
Authors: Liao Mei-Chen , Muratore Christina R. , Gierahn Todd M. , Sullivan Sarah E. , Srikanth Priya , De Jager Philip L. , Love J. Christopher , Young-Pearse Tracy L. 
Published: February 2016

Secreted factors play a central role in normal and pathological processes in every tissue in the body. The brain is composed of a highly complex milieu of different cell types and few methods exist that can identify which individual cells in a complex mixture are secreting specific analytes. By identifying which cells are responsible, we can better understand neural physiology and pathophysiology, more readily identify the underlying pathways responsible for analyte production, and ultimately use this information to guide the development of novel therapeutic strategies that target the cell types of relevance. We present here a method for detecting analytes secreted from single human induced pluripotent stem cell (iPSC)-derived neural cells and have applied the method to measure amyloid β (Aβ) and soluble amyloid precursor protein-alpha (sAPPα), analytes central to Alzheimer's disease pathogenesis. Through these studies, we have uncovered the dynamic range of secretion profiles of these analytes from single iPSC-derived neuronal and glial cells and have molecularly characterized subpopulations of these cells through immunostaining and gene expression analyses. In examining Aβ and sAPPα secretion from single cells, we were able to identify previously unappreciated complexities in the biology of APP cleavage that could not otherwise have been found by studying averaged responses over pools of cells. This technique can be readily adapted to the detection of other analytes secreted by neural cells, which would have the potential to open new perspectives into human CNS development and dysfunction.SIGNIFICANCE STATEMENTWe have established a technology that, for the first time, detects secreted analytes from single human neurons and astrocytes. We examine secretion of the Alzheimer's disease-relevant factors amyloid β (Aβ) and soluble amyloid precursor protein-alpha (sAPPα) and present novel findings that could not have been observed without a single-cell analytical platform. First, we identify a previously unappreciated subpopulation that secretes high levels of Aβ in the absence of detectable sAPPα. Further, we show that multiple cell types secrete high levels of Aβ and sAPPα, but cells expressing GABAergic neuronal markers are overrepresented. Finally, we show that astrocytes are competent to secrete high levels of Aβ and therefore may be a significant contributor to Aβ accumulation in the brain.
Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1
Authors: Rodrigues Elizabeth M. , Scudder Samantha L. , Goo Marisa S. , Patrick Gentry N. 
Published: February 2016

Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (Aβ). Specifically, it has been shown that Aβ decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Aβ-induced synaptic dysfunction in cultured rat neurons. We find that Aβ promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Aβ-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Aβ.SIGNIFICANCE STATEMENTSynaptic changes in Alzheimer's disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Aβ. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-1's established role in homeostatic synaptic scaling. This is the first demonstration of Aβ-mediated control of a ubiquitin ligase to regulate surface AMPAR expression.
Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats
Authors: Lauterborn Julie C. , Palmer Linda C. , Jia Yousheng , Pham Danielle T. , Hou Bowen , Wang Weisheng , Trieu Brian H. , Cox Conor D. , Kantorovich Svetlana , Gall Christine M. , Lynch Gary 
Published: February 2016

Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior.SIGNIFICANCE STATEMENTBrain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be mostly reversed by long-term, oral administration of a positive allosteric modulator of AMPA-type glutamate receptors. Dendritic recovery was accompanied by improvements to both synaptic plasticity and the encoding of long-term memory of a novel, complex environment. Because the short half-life compound had no evident negative effects, the results suggest a plausible strategy for treating age-related neuronal deterioration.
Color-Biased Regions of the Ventral Visual Pathway Lie between Face- and Place-Selective Regions in Humans, as in Macaques
Authors: Lafer-Sousa Rosa , Conway Bevil R. , Kanwisher Nancy G. 
Published: February 2016

The existence of color-processing regions in the human ventral visual pathway (VVP) has long been known from patient and imaging studies, but their location in the cortex relative to other regions, their selectivity for color compared with other properties (shape and object category), and their relationship to color-processing regions found in nonhuman primates remain unclear. We addressed these questions by scanning 13 subjects with fMRI while they viewed two versions of movie clips (colored, achromatic) of five different object classes (faces, scenes, bodies, objects, scrambled objects). We identified regions in each subject that were selective for color, faces, places, and object shape, and measured responses within these regions to the 10 conditions in independently acquired data. We report two key findings. First, the three previously reported color-biased regions (located within a band running posterior–anterior along the VVP, present in most of our subjects) were sandwiched between face-selective cortex and place-selective cortex, forming parallel bands of face, color, and place selectivity that tracked the fusiform gyrus/collateral sulcus. Second, the posterior color-biased regions showed little or no selectivity for object shape or for particular stimulus categories and showed no interaction of color preference with stimulus category, suggesting that they code color independently of shape or stimulus category; moreover, the shape-biased lateral occipital region showed no significant color bias. These observations mirror results in macaque inferior temporal cortex (Lafer-Sousa and Conway, 2013), and taken together, these results suggest a homology in which the entire tripartite face/color/place system of primates migrated onto the ventral surface in humans over the course of evolution.SIGNIFICANCE STATEMENTHere we report that color-biased cortex is sandwiched between face-selective and place-selective cortex on the bottom surface of the brain in humans. This face/color/place organization mirrors that seen on the lateral surface of the temporal lobe in macaques, suggesting that the entire tripartite system is homologous between species. This result validates the use of macaques as a model for human vision, making possible more powerful investigations into the connectivity, precise neural codes, and development of this part of the brain. In addition, we find substantial segregation of color from shape selectivity in posterior regions, as observed in macaques, indicating a considerable dissociation of the processing of shape and color in both species.
Orexin Neurons Respond Differentially to Auditory Cues Associated with Appetitive versus Aversive Outcomes
Authors: Hassani Oum Kaltoum , Krause Matthew R. , Mainville Lynda , Cordova Christopher A. , Jones Barbara E. 
Published: February 2016

Orexin (Orx) neurons are known to be involved in the promotion and maintenance of waking because they discharge in association with cortical activation and muscle tone during waking and because, in their absence, waking with muscle tone cannot be maintained and narcolepsy with cataplexy ensues. Whether Orx neurons discharge during waking in association with particular conditions, notably with appetitive versus aversive stimuli or positive versus negative emotions, is debated and considered important in understanding their role in supporting particular waking behaviors. Here, we used the technique of juxtacellular recording and labeling in head-fixed rats to characterize the discharge of Orx neurons during the performance of an associative discrimination task with auditory cues for appetitive versus aversive outcomes. Of 57 active, recorded, and neurobiotin-labeled neurons in the lateral hypothalamus, 11 were immunohistochemically identified as Orx-positive (Orx+), whereas none were identified as melanin-concentrating hormone-positive. Orx+neurons discharged at significantly higher rates during the tone associated with sucrose than during the tone associated with quinine delivered upon licking. They also discharged at high rates after the tone associated with sucrose. Across periods and outcomes, their discharge was positively correlated with EEG gamma activity and EMG activity, which is indicative of cortical activation and behavioral arousal. These results suggest that Orx neurons discharge in a manner characteristic of reward neurons yet also characteristic of arousal neurons. Accordingly, the Orx neurons may respond to and participate in reward processes while modulating cortical activity and muscle tone to promote and maintain arousal along with learned adaptive behavioral responses.SIGNIFICANCE STATEMENTOrexin neurons play a critical role in promoting and maintaining a waking state because, in their absence, narcolepsy with cataplexy ensues. Known to discharge during waking and not during sleep, they have also been proposed to be selectively active during appetitive behaviors. Here, we recorded and labeled neurons in rats to determine the discharge of immunohistochemically identified orexin neurons during performance of an associative discrimination task. Orexin neurons responded differentially to auditory cues associated with appetitive sucrose versus aversive quinine, indicating that they behave like reward neurons. However, correlated discharge with cortical and muscle activity indicates that they also behave like arousal neurons and can thus promote cortical activation with behavioral arousal and muscle tone during adaptive waking behaviors.
LA IDEA DE CIENCIA EN MIGUEL ANTONIO CARO
Authors: Tovar Leonardo 
Published: February 2016

<p>El artículo analiza la concepción de Miguel Antonio Caro en torno a la ciencia. En el primer apartado se reseñan las críticas del pensador bogotano contra la filosofía positivista, que en sus tres versiones (el positivismo de Comte, el evolucionismo biológico de Darwin y el evolucionismo social de Spencer) pretende poner las hipótesis científicas por encima de las verdades de la religión. A continuación, se expone la doctrina católica del autor en torno al verdadero saber científico, que en coincidencia con Meléndez Pelayo, Caro estima necesariamente afín a la fe. Para concluir, se discute la visión reaccionaria de Caro sobre la ciencia moderna, ya que ésta ha estado en la base de la mentalidad anticientífica de la educación en Colombia.</p>
The Dissection of Expression Quantitative Trait Locus Hotspots
Authors: Tian Jianan , Keller Mark P , Broman Aimee Teo , Kendziorski Christina , Yandell Brian S , Attie Alan D , Broman Karl W 
Published: February 2016

AbstractStudies of the genetic loci that contribute to variation in gene expression frequently identify loci with broad effects on gene expression: expression quantitative trait locus hotspots. We describe a set of exploratory graphical methods as well as a formal likelihood-based test for assessing whether a given hotspot is due to one or multiple polymorphisms. We first look at the pattern of effects of the locus on the expression traits that map to the locus: the direction of the effects and the degree of dominance. A second technique is to focus on the individuals that exhibit no recombination event in the region, apply dimensionality reduction (e.g., with linear discriminant analysis), and compare the phenotype distribution in the nonrecombinant individuals to that in the recombinant individuals: if the recombinant individuals display a different expression pattern than the nonrecombinant individuals, this indicates the presence of multiple causal polymorphisms. In the formal likelihood-based test, we compare a two-locus model, with each expression trait affected by one or the other locus, to a single-locus model. We apply our methods to a large mouse intercross with gene expression microarray data on six tissues.
¿Es necesario profundizar en la relación entre docente de matemáticas y la formación de las actitudes y creencias hacia la disciplina?
Authors: Gamboa-Araya Ronny 
Published: February 2016

La problemática asociada con la enseñanza y aprendizaje de las matemáticas ha sido una preocupación recurrente en varios países. El dominio afectivo del alumnado, dentro de este contexto, ha surgido como un elemento relevante que permite explicar algunos aspectos sobre ella. Desde esta perspectiva, surge la necesidad de profundizar en la influencia que el personal docente posee en el dominio afectivo de sus estudiantes, pues lo que hace en el aula podría ayudar a afianzar o modificar las actitudes y creencias del estudiantado. El objetivo de este artículo es señalar aspectos relacionados con el domino afectivo en matemáticas que poseen influencia en la enseñanza y aprendizaje de la disciplina y la necesidad de abordarlos desde la percepción del profesorado. El propósito es que, desde su labor diaria, modifique su quehacer e incentive un cambio de imagen de la materia. Para ello se presentan los resultados de distintas investigaciones que evidencian el papel del dominio afectivo, la influencia del personal docente y la necesidad realizar mayor investigación sobre el papel del profesorado.
Complete Influenza Vaccination Trends for Children Six to Twenty-Three Months
Authors: Santibanez Tammy A. , Grohskopf Lisa A. , Zhai Yusheng , Kahn Katherine E. 
Published: February 2016

OBJECTIVE:
Prevention of influenza among infants and young children is a public health priority because of their high risk for influenza-related complications. Depending on a child’s age and previous influenza vaccination history, they are recommended to receive either 1 dose or 2 doses of influenza vaccine to be considered fully vaccinated against influenza for the season. We compared estimates of full (complete) influenza vaccination coverage of children 6 to 23 months across 10 consecutive influenza seasons (2002–2012), by race/ethnicity, age group, and by number of doses required to be fully vaccinated given child’s vaccination history.

METHODS:
National Immunization Survey data were used to estimate full influenza vaccination status among children 6 to 23 months on the basis of provider report. Estimates were computed by using Kaplan-Meier survival analysis methods.

RESULTS:
Full influenza vaccination coverage among children 6 to 23 months increased from 4.8% in the 2002–2003 influenza season to 44.7% in the 2011–2012 season. In all 10 influenza seasons studied, non-Hispanic black children and Hispanic children had lower full influenza vaccination coverage than non-Hispanic white children. For all 10 influenza seasons, full influenza vaccination coverage was higher among children requiring only 1 dose compared with those requiring 2 doses.

CONCLUSIONS:
Less than half of children 6 to 23 months in the United States, and an even a smaller percentage of Hispanic and non-Hispanic black children, are fully vaccinated against influenza. More implementation of evidence-based strategies that increase the percentage of children who are fully vaccinated is needed.
Kalmyk and Khalkha Ethnographica in Gábor Bálint of Szentkatolna’s manuscripts (1871–1873)
Authors: Birtalan Ágnes 
Published: February 2016

The Hungarian (Székely) Gábor Bálint of Szentkatolna (1844–1913) was one of the first researchers of Kalmyk and Khalkha vernacular language, folklore and ethnography. His valuable records are written in a very accurate transcription and include the specimens of Kalmyk and Khalkha spoken languages, folklore material and ethnographic narratives, and a comparative grammar of western and eastern Mongolian languages. Bálint’s manuscripts had not been released until recent years when Ágnes Birtalan published his Comparative Grammar in 2009 and the Kalmyk corpus with a comprehensive analysis in 2011.
The present article aims to give an introduction to Bálint’s ethnographic materials recorded among the Kalmyks (1871–1872) and Khalkhas (1873). Despite the similar economic and cultural milieu the two ethnic groups lived in, there is considerable difference between the Kalmyk and Khalkha text corpora. Besides presenting and systematising Bálint’s ethnographic material, I shall try to clarify the reason why this significant divergence emerges between the two text corpora. Specimens of a particular phase of the wedding ceremony are represented as examples from both text corpora.
A Mixed Methods Study of Pre-­service Teachers’ Attitudes toward LGBTQ Themed Literature
Authors: Malo-Juvera Victor 
Published: February 2016

<p>While many of studies provide valuable insights into teachers’ attitudes toward LGBTQ curricula, more research is needed that examines pre-service teachers’ attitudes toward LGBTQ themed texts. The results from the type of research reported on in this article could assist teacher preparation programs to develop coursework intended to increase the willingness of pre-service teachers to use LGBTQ themed young adult literature in the classroom. </p>
Supporting Parents with Mental Health Support in the NICU
Authors: Discenza Deborah 
Published: February 2016

AbstractParents of premature babies are at high risk for postpartum depression and Posttraumatic stress disorder and need a lot of mental health support. Enter Parijat Deshpande, a mother who gave birth to her son in the 24th week and has a background in psychology and is now a health and wellness counselor. Parijat has a strong focus on perinatal wellness and helping parents of a preemie reduce their stress and increase the parent–child bond.
Cash Balance Pension Plans: Good News or Bad News?
Authors: Rao Arundhati , Higgins Leslee , Taylor Sandra 
Published: February 2016

<span>Modification of defined benefit plans and conversion of defined contribution plans into Cash Balance Pension Plans (CBPs) has attracted a lot of attention recently. A comparison of the three plans and an examination of 10 companies reveal a significant financial incentive in favor of CBPs. The “good news” for a younger employee is level accrual of benefits and plan portability, and for stockholders, a smaller impact on net income. CBPs bear “bad news” for older and/or less mobile employees and the stockholders when the plan assets perform poorly. </span>
The Jock Tax Contest: Professional Athletes Vs. The States - Background And Current Developments
Authors: Ekmekjian Elizabeth C. , Wilkerson James C. , Bing Robert W. 
Published: February 2016

Opening day of the Major League Baseball‟s 2<span>002 season fell on April 1 of that year. After the National Anthem was sung, the crowd applauded as the New York Mets took the field, and the umpire yelled, “play ball.” The State of New York also cheered. Why? New York, like a number of other states and localities, imposes an income tax on athletes that visit its borders. So, when Tex- as Rangers shortstop, Alex Rodriguez, the highest paid baseball player during the 2002 season with a salary of $22 million, played 4 regular season games in the Big Apple, he incurred a tax liability of approximately $34,250. This state income taxation of nonresident professional athletes is commonly referred to as “the jock tax.” This paper introduces the reader to the jock tax beginning with a brief explanation of state income taxes, continuing with a discussion of its complexi- ties and historical/current issues faced by athletes, teams and the states through implementation of the tax. The paper concludes with the broader implications of a state or local taxing jurisdiction's powers to tax its nonresident visitors. </span>