bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-Permeable Peptide Targeting the Nrf2–Keap1 Interaction: A Potential Novel Therapy for Global Cerebral Ischemia
Authors: Tu Jingyi , Zhang Xi , Zhu Ying , Dai Yongxin , Li Ning , Yang Fang , Zhang Quanguang , Brann Darrell W. , Wang Ruimin 
Published: November 2015

The current study examined efficacy of a small Tat (trans-activator of transcription)-conjugated peptide activator of the Nrf2 (nuclear factor-E2-related factor-2) antioxidant/cell-defense pathway as a potential injury-specific, novel neuroprotectant against global cerebral ischemia (GCI). A competitive peptide, DEETGE-CAL-Tat, was designed to facilitate Nrf2 activation by disrupting interaction of Nrf2 with Keap1 (kelch-like ECH-associated protein 1), a protein that sequesters Nrf2 in the cytoplasm and thereby inactivates it. The DEETGE-CAL-Tat peptide contained the critical sequence DEETGE for the Nrf2–Keap1 interaction, the cell transduction domain of the HIV-Tat protein, and the cleavage sequence of calpain, which is sensitive to Ca2+increase and allows injury-specific activation of Nrf2. Using an animal model of GCI, we demonstrated that pretreatment with the DEETGE-CAL-Tat peptide markedly decreased Nrf2 interaction with Keap1 in the rat hippocampal CA1 region after GCI, and enhanced Nrf2 nuclear translocation and DNA binding. The DEETGE-CAL-Tat peptide also induced Nrf2 antioxidant/cytoprotective target genes, reduced oxidative stress, and induced strong neuroprotection and marked preservation of hippocampal-dependent cognitive function after GCI. These effects were specific as control peptides lacked neuroprotective ability. Intriguingly, the DEETGE-CAL-Tat peptide effects were also injury specific, as it had no effect upon neuronal survival or cognitive performance in sham nonischemic animals. Of significant interest, peripheral, postischemia administration of the DEETGE-CAL-Tat peptide from days 1–9 after GCI also induced robust neuroprotection and strongly preserved hippocampal-dependent cognitive function. Based on its robust neuroprotective and cognitive-preserving effects, and its unique injury-specific activation properties, the DEETGE-CAL-Tat peptide represents a novel, and potentially promising new therapeutic modality for the treatment of GCI.SIGNIFICANCE STATEMENTThe current study demonstrates that DEETGE-CAL-Tat, a novel peptide activator of a key antioxidant gene transcription pathway in the hippocampus after global cerebral ischemia, can exert robust neuroprotection and preservation of cognitive function. A unique feature of the peptide is that its beneficial effects are injury specific. This feature is attractive as it targets drug activation specifically in the site of injury, and likely would lead to a reduction of undesirable side effects if translatable to the clinic. Due to its injury-specific activation, robust neuroprotection, and cognitive-preserving effects, this novel peptide may represent a much-needed therapeutic advance that could have efficacy in the treatment of global cerebral ischemia.
microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain
Authors: Kim Jaekwang , Yoon Hyejin , Horie Takahiro , Burchett Jack M. , Restivo Jessica L. , Rotllan Noemi , Ramírez Cristina M. , Verghese Philip B. , Ihara Masafumi , Hoe Hyang-Sook , Esau Christine , Fernández-Hernando Carlos , Holtzman David M. , Cirrito John R. , Ono Koh , Kim Jungsu 
Published: November 2015

Dysregulation of amyloid-β (Aβ) metabolism is critical for Alzheimer's disease (AD) pathogenesis. Mounting evidence suggests that apolipoprotein E (ApoE) is involved in Aβ metabolism. ATP-binding cassette transporter A1 (ABCA1) is a key regulator of ApoE lipidation, which affects Aβ levels. Therefore, identifying regulatory mechanisms of ABCA1 expression in the brain may provide new therapeutic targets for AD. Here, we demonstrate that microRNA-33 (miR-33) regulates ABCA1 and Aβ levels in the brain. Overexpression of miR-33 impaired cellular cholesterol efflux and dramatically increased extracellular Aβ levels by promoting Aβ secretion and impairing Aβ clearance in neural cells. In contrast, genetic deletion ofmir-33in mice dramatically increased ABCA1 levels and ApoE lipidation, but it decreased endogenous Aβ levels in cortex. Most importantly, pharmacological inhibition of miR-33 via antisense oligonucleotide specifically in the brain markedly decreased Aβ levels in cortex ofAPP/PS1mice, representing a potential therapeutic strategy for AD.SIGNIFICANCE STATEMENTBrain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to Aβ metabolism and Alzheimer's disease (AD). Brain lipid metabolism is largely separated from the periphery due to blood–brain barrier and different repertoire of lipoproteins. Therefore, identifying the novel regulatory mechanism of brain lipid metabolism may provide a new therapeutic strategy for AD. Although there have been studies on brain lipid metabolism, its regulation, in particular by microRNAs, is relatively unknown. Here, we demonstrate that inhibition of microRNA-33 increases lipidation of brain ApoE and reduces Aβ levels by inducing ABCA1. We provide a unique approach for AD therapeutics to increase ApoE lipidation and reduce Aβ levels via pharmacological inhibition of microRNAin vivo.
Irregular Speech Rate Dissociates Auditory Cortical Entrainment, Evoked Responses, and Frontal Alpha
Authors: Kayser Stephanie J. , Ince Robin A.A. , Gross Joachim , Kayser Christoph 
Published: November 2015

The entrainment of slow rhythmic auditory cortical activity to the temporal regularities in speech is considered to be a central mechanism underlying auditory perception. Previous work has shown that entrainment is reduced when the quality of the acoustic input is degraded, but has also linked rhythmic activity at similar time scales to the encoding of temporal expectations. To understand these bottom-up and top-down contributions to rhythmic entrainment, we manipulated the temporal predictive structure of speech by parametrically altering the distribution of pauses between syllables or words, thereby rendering the local speech rate irregular while preserving intelligibility and the envelope fluctuations of the acoustic signal. Recording EEG activity in human participants, we found that this manipulation did not alter neural processes reflecting the encoding of individual sound transients, such as evoked potentials. However, the manipulation significantly reduced the fidelity of auditory delta (but not theta) band entrainment to the speech envelope. It also reduced left frontal alpha power and this alpha reduction was predictive of the reduced delta entrainment across participants. Our results show that rhythmic auditory entrainment in delta and theta bands reflect functionally distinct processes. Furthermore, they reveal that delta entrainment is under top-down control and likely reflects prefrontal processes that are sensitive to acoustical regularities rather than the bottom-up encoding of acoustic features.SIGNIFICANCE STATEMENTThe entrainment of rhythmic auditory cortical activity to the speech envelope is considered to be critical for hearing. Previous work has proposed divergent views in which entrainment reflects either early evoked responses related to sound encoding or high-level processes related to expectation or cognitive selection. Using a manipulation of speech rate, we dissociated auditory entrainment at different time scales. Specifically, our results suggest that delta entrainment is controlled by frontal alpha mechanisms and thus support the notion that rhythmic auditory cortical entrainment is shaped by top-down mechanisms.
Human Auditory Cortex Neurochemistry Reflects the Presence and Severity of Tinnitus
Authors: Sedley William , Parikh Jehill , Edden Richard A.E. , Tait Valerie , Blamire Andrew , Griffiths Timothy D. 
Published: November 2015

It is not known why tinnitus occurs in some cases of hearing damage but not others. Abnormalities of excitation–inhibition balance could influence whether tinnitus develops and its severity if it does. Animal models of hearing damage, which also produce tinnitus based on behavioral evidence, have identified abnormalities of GABAergic inhibition, both cortically and subcortically. However, the precise relationships of GABA inhibitory changes to tinnitus itself, as opposed to other consequences of hearing damage, remain uncertain. Here, we used magnetic resonance spectroscopy to non-invasively quantify GABA in the left (LAC) and right (RAC) auditory cortices of a group of 14 patients with lateralized tinnitus (eight left ear) and 14 controls matched for age, sex, and hearing. We also explored the potential relationships with other brain metabolites (i.e., choline,N-acetylaspartate, and creatine). The presence of tinnitus was associated with a reduction in auditory cortex GABA concentration. Regardless of tinnitus laterality,post hoctesting indicated reductions that were significant in RAC and nonsignificant in LAC. Tinnitus severity and hearing loss were correlated positively with RAC choline but not GABA. We discuss the results in the context of current models of tinnitus and methodological constraints.SIGNIFICANCE STATEMENTPermanently affecting one in seven adults, tinnitus lacks both widely effective treatments and adequate understanding of its brain mechanisms. Existing animal models represent tinnitus that may not be distinguishable from homeostatic responses to the auditory insults used to induce it. Human studies can be well controlled in this regard but are usually not (with few even matching control subjects for hearing loss) and are limited in scope as a result of relying solely on non-invasive recording techniques. Here, we exploit recent advances in non-invasive spectroscopic techniques to establish, in a human study tightly controlled for hearing loss and hyperacusis, that tinnitus is associated with a significant reduction in auditory cortex GABA concentration, which has implications for understanding and treatment of the condition.
Memory Meets Control in Hippocampal and Striatal Binding of Stimuli, Responses, and Attentional Control States
Authors: Jiang Jiefeng , Brashier Nadia M. , Egner Tobias 
Published: November 2015

The human brain encodes experience in an integrative fashion by binding together the various features of an event (i.e., stimuli and responses) into memory “event files.” A subsequent reoccurrence of an event feature can then cue the retrieval of the memory file to “prime” cognition and action. Intriguingly, recent behavioral studies indicate that, in addition to linking concrete stimulus and response features, event coding may also incorporate more abstract, “internal” event features such as attentional control states. In the present study, we used fMRI in healthy human volunteers to determine the neural mechanisms supporting this type of holistic event binding. Specifically, we combined fMRI with a task protocol that dissociated the expression of event feature-binding effects pertaining to concrete stimulus and response features, stimulus categories, and attentional control demands. Using multivariate neural pattern classification, we show that the hippocampus and putamen integrate event attributes across all of these levels in conjunction with other regions representing concrete-feature-selective (primarily visual cortex), category-selective (posterior frontal cortex), and control demand-selective (insula, caudate, anterior cingulate, and parietal cortex) event information. Together, these results suggest that the hippocampus and putamen are involved in binding together holistic event memories that link physical stimulus and response characteristics with internal representations of stimulus categories and attentional control states. These bindings then presumably afford shortcuts to adaptive information processing and response selection in the face of recurring events.SIGNIFICANCE STATEMENTMemory binds together the different features of our experience, such as an observed stimulus and concurrent motor responses, into so-called event files. Recent behavioral studies suggest that the observer's internal attentional state might also become integrated into the event memory. Here, we used fMRI to determine the brain areas responsible for binding together event information pertaining to concrete stimulus and response features, stimulus categories, and internal attentional control states. We found that neural signals in the hippocampus and putamen contained information about all of these event attributes and could predict behavioral priming effects stemming from these features. Therefore, medial temporal lobe and dorsal striatum structures appear to be involved in binding internal control states to event memories.
REST Regulates Non–Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin II
Authors: Kim Hyung Joon , Denli Ahmet M. , Wright Rebecca , Baul Tithi D. , Clemenson Gregory D. , Morcos Ari S. , Zhao Chunmei , Schafer Simon T. , Gage Fred H. , Kagalwala Mohamedi N. 
Published: November 2015

RE-1 silencing transcription factor (REST), a master negative regulator of neuronal differentiation, controls neurogenesis by preventing the differentiation of neural stem cells. Here we focused on the role of REST in the early steps of differentiation and maturation of adult hippocampal progenitors (AHPs). REST knockdown promoted differentiation and affected the maturation of rat AHPs. Surprisingly, REST knockdown cells enhanced the differentiation of neighboring wild-type AHPs, suggesting that REST may play a non–cell-autonomous role. Gene expression analysis identified Secretogranin II (Scg2) as the major secreted REST target responsible for the non–cell-autonomous phenotype. Loss-of-function ofScg2inhibited differentiationin vitro, and exogenous SCG2 partially rescued this phenotype. Knockdown of REST in neural progenitors in mice led to precocious maturation into neurons at the expense of mushroom spinesin vivo. In summary, we found that, in addition to its cell-autonomous function, REST regulates differentiation and maturation of AHPs non–cell-autonomously via SCG2.SIGNIFICANCE STATEMENTOur results reveal that REST regulates differentiation and maturation of neural progenitor cellsin vitroby orchestrating both cell-intrinsic and non–cell-autonomous factors and thatScg2is a major secretory target of REST with a differentiation-enhancing activity in a paracrine manner.In vivo, REST depletion causes accelerated differentiation of newborn neurons at the expense of spine defects, suggesting a potential role for REST in the timing of the maturation of granule neurons.
Antisense Transcription of Retrotransposons in Drosophila: An Origin of Endogenous Small Interfering RNA Precursors
Authors: Russo Joseph , Harrington Andrew W , Steiniger Mindy 
Published: November 2015

Abstract
Movement of transposons causes insertions, deletions, and chromosomal rearrangements potentially leading to premature lethality in Drosophila melanogaster. To repress these elements and combat genomic instability, eukaryotes have evolved several small RNA-mediated defense mechanisms. Specifically, in Drosophila somatic cells, endogenous small interfering (esi)RNAs suppress retrotransposon mobility. EsiRNAs are produced by Dicer-2 processing of double-stranded RNA precursors, yet the origins of these precursors are unknown. We show that most transposon families are transcribed in both the sense (S) and antisense (AS) direction in Dmel-2 cells. LTR retrotransposons Dm297, mdg1, and blood, and non-LTR retrotransposons juan and jockey transcripts, are generated from intraelement transcription start sites with canonical RNA polymerase II promoters. We also determined that retrotransposon antisense transcripts are less polyadenylated than sense. RNA-seq and small RNA-seq revealed that Dicer-2 RNA interference (RNAi) depletion causes a decrease in the number of esiRNAs mapping to retrotransposons and an increase in expression of both S and AS retrotransposon transcripts. These data support a model in which double-stranded RNA precursors are derived from convergent transcription and processed by Dicer-2 into esiRNAs that silence both sense and antisense retrotransposon transcripts. Reduction of sense retrotransposon transcripts potentially lowers element-specific protein levels to prevent transposition. This mechanism preserves genomic integrity and is especially important for Drosophila fitness because mobile genetic elements are highly active.
Lista con anotaciones de las Angiospermas de la Reserva Biológica Alberto Brenes (microcuencas de lo Ríos San Lorenzo y San Lorencito),Costa Rica
Authors: Gómez-Laurito Jorge , Ortiz Rodolfo 
Published: November 2015

<div class="page" title="Page 1"><div class="layoutArea"><div class="column"><p><span>La Reserva Biológica Alberto Brenes está localizada al noroeste de Costa Rica, en la vertiente Caribe, con elevaciones que van de 800 a 1500 m. Esta área está expuesta a altas precipitaciones durante todo el año (4500 mm) con pocas lluvias de febrero a abril. Con temperaturas moderadas debido a la ele- vación, la cobertura de nubes y la alta precipitación dan como resultado un bosque tropical húmedo de pre- montano, que también se puede ubicar como un bosque nuboso de transición entre el bosque nuboso de montano, que se halla en elevaciones más altas, y el bosque tropical húmedo de elevaciones más bajas. Así, por su ámbito altitudinal intermedio, los bosques de la Reserva Biológica A. M. Brenes poseen una diversi- dad notable de especies que pertenecen a zonas bajas y altas de Costa Rica. Se presenta aquí una lista con anotaciones de las plantas de la Reserva distribuidas en 137 familias de angiospermas, representadas por 483 géneros y 1294 especies. Las familias con mayor número de especies son Araceae (50), Gesneriaceae (52), Melastomataceae (61), Orchidaceae (208), Rubiaceae (75) y Solanaceae (37). Los géneros de mono- cotiledóneas con mayor número de especies son </span><span>Pleurothallis </span><span>(34), </span><span>Anthurium </span><span>(25) y </span><span>Maxillaria </span><span>(23). Los géneros de dicotiledóneas con mayor número de especies son </span><span>Peperomia </span><span>(33), </span><span>Piper </span><span>(23), </span><span>Miconia </span><span>(16), </span><span>Ocotea </span><span>(21) y </span><span>Psychotria </span><span>s.s. (15). Las siguientes especies fueron descritas de la Reserva A.M. Brenes como nuevas para la ciencia: </span><span>Drymonia submarginalis </span><span>(Gesneriaceae), </span><span>Ocotea gomezii</span><span>, </span><span>Ocotea morae</span><span>, </span><span>Povedadaphne quadriporata </span><span>(Lauraceae), </span><span>Marlierea mesoamericana </span><span>(Myrtaceae), </span><span>Prosthechea ortizii </span><span>(Orchidaceae, como </span><span>Encyclia ortizii</span><span>), </span><span>Coccoloba porphyrostachys</span><span>, </span><span>Coccoloba liportizii </span><span>(Polygonaceae), </span><span>Rudgea monofructus </span><span>(Rubiaceae) y </span><span>Ticodendron incognitum </span><span>(Ticodendraceae); ésta última, una familia nueva para la ciencia. </span></p></div></div></div>
¿Incrustamiento sin espacio? Situando el comercio justo en la industria florícola ecuatoriana
Authors: Lyall Angus 
Published: November 2015

<p>En las últimas dos décadas <em>Fairtrade International</em> se ha consolidada como la certificadora de comercio justo más grande del mundo. Mucho de su crecimiento se debe a la expansión de sus prácticas desde la exclusiva certificación de cooperativas de pequeños agricultores hacia la regulación de agroindustrias y empresas no agrícolas. En contextos de trabajo asalariado, <em>Fairtrade </em>afirma mejorar las condiciones laborales y ambientales y promover el desarrollo local. Muchos investigadores elogian a <em>Fairtrade </em>por “re-incrustar” relaciones económicas en relaciones sociales y éticas. En este artículo, señalo los testimonios de trabajadores de tres florícolas ecuatorianas certificadas, quienes si bien reconocen varias de estas afirmaciones, nos permiten observar que al enmarcar <em>Fairtrade </em>como mecanismo de “re-incrustamiento” se omite el deseo de ellos de dejar la industria floricultura y re-incrustar sus relaciones económicas en las relaciones del espacio social local. Mientras Polanyi concibe el incrustamiento en relaciones histórica y geográficamente situadas, planteo que ciertos acercamientos académicos a <em>Fairtrade </em>se mal apropian de su noción del concepto para describir relaciones abstractas entre consumidores y trabajadores. Pongo este concepto en diálogo con el trabajo de Henri Lefebvre sobre el espacio social y el territorio para re-conceptualizar lo que significaría un desarrollo territorial bajo <em>Fairtrade </em>y subrayar los límites y contradicciones de este mecanismo. </p>
Conectando sures. La construcción de redes académicas entre América Latina y África
Authors: Bayle Paola Adriana 
Published: November 2015

<p style="margin: 0cm 0cm 0pt; text-align: justify; line-height: 150%;"><span style="line-height: 150%; font-family: 'Times',serif; font-size: 12pt; mso-bidi-font-family: Calibri; mso-no-proof: yes; mso-bidi-font-size: 11.0pt;" lang="ES-AR">En el presente trabajo se abordan las estrategias ejecutadas por el Consejo Latinoamericano de Ciencias Sociales (CLACSO) diseñadas para fortalecer los vínculos académicos entre las periferias del Sistema Académico Mundial (SAM). Particularmente este artículo se centra en la prehistoria del actual Programa de Cooperación Académica Sur-Sur en el que CLACSO participa activamente junto con otras instituciones. Esta política –que comenzó desde los inicios de CLACSO (finales de la década de 1960 y principios de la de 1970)– estuvo orientada inicialmente a establecer lazos con instituciones académicas africanas. Creemos que CLACSO desarrolló esta política institucional a partir de evidenciar las asimetrías del SAM, construido históricamente erigiendo centros y periferias (norte y sur), en donde estas últimas se encuentran debilitadas en sus posibilidades de producción y circulación de saberes. Iniciativas de este tipo muestran cómo es posible limitar la dominación absoluta por parte de los centros. </span></p><p style="margin: 0cm 0cm 0pt; text-align: justify; line-height: 150%;"><span style="line-height: 150%; font-family: 'Times',serif; font-size: 12pt; mso-bidi-font-family: Calibri; mso-no-proof: yes; mso-bidi-font-size: 11.0pt;" lang="ES-AR"> </span></p>
Presentación Dossier. Lecciones de América Latina sobre las dimensiones racionales, cognitivas e institucionales del cambio de políticas
Authors: Fontaine Guillaume 
Published: November 2015

<p> </p><div> <p style="margin: 0cm 0cm 0pt; text-indent: 0cm;"><span style="font-family: 'Times',serif; mso-bidi-font-family: 'Arial Unicode MS'; mso-no-proof: yes;" lang="ES-TRAD"><span style="font-size: medium;">La revisión de la literatura especializada lleva a identificar tres tipos de enfoques analíticos del cambio de políticas. Los racionalistas –con las teorías del incrementalismo, las corrientes múltiples y el equilibrio puntuado– privilegian el proceso de toma de decisión y la racionalidad (limitada) de los actores. Los cognitivistas –con el marco analítico de coaliciones promotoras, la teoría de los referenciales globales/sectoriales y la teoría crítica– hacen hincapié en las representaciones de los problemas de políticas y los discursos legitimadores de decisiones. Los neoinstitucionalistas –con las teorías de la lógica de lo adecuado, la dependencia de la trayectoria y los tres órdenes de cambio de políticas– subrayan la importancia de las instituciones formales e informales en el desenvolvimiento de las políticas públicas.</span></span></p></div>