bluuebunny/crossref_metadata_2025 huggingface dataset:
Avaliação neuropsicológica de condutores idosos: Relações entre resultados em testes cognitivos, desempenho de condução automóvel e acidentes
Authors: Ferreira Inês Saraiva , Simões Mário R.
Published: January 2015

O exame de condutores idosos com recurso a testes neuropsicológicos representa uma área de investigação actual no cenário do envelhecimento demográfico. O objectivo do presente texto é identificar um conjunto de testes com valor preditivo em relação a medidas de condução automóvel, que permitam a sinalização de condutores idosos com maior risco de acidente ou de reprovação em provas de condução. Desconhecida a existência de investigações em Portugal, apresentamos uma revisão de estudos empíricos realizados noutros países. Os trabalhos recenseados evidenciam a utilidade dos testes neuropsicológicos para avaliar funções cognitivas necessárias para conduzir em segurança, nomeadamente funções executivas, visuo-espaciais, visuo-perceptivas e a atenção visual. São necessárias novas investigações orientadas para o desenvolvimento de uma bateria de avaliação neuropsicológica para condutores idosos, que contribuam para uma maior precisão e validade preditiva dos métodos de exame psicológico de condutores neste grupo etário.
Uma medida de auto-eficácia percebida em contextos sociais e académicos
Authors: Teixeira Maria Odília
Published: January 2015

Os trabalhos de validação da versão portuguesa da Escala Multidimensional de Auto-eficácia Percebida (EMAP) têm sido desenvolvidos desde 2005, em amostras de estudantes dos ensinos básico, secundário e superior. Do conjunto dos resultados, salientam-se os indicadores da precisão e da validade da medida, nomeadamente quanto à consistência interna, à dimensionalidade e ao significado dos resultados nos domínios da aprendizagem e do comportamento vocacional.
Demyelination Causes Adult CNS Progenitors to Revert to an Immature State and Express Immune Cues That Support Their Migration
Authors: Moyon Sarah , Dubessy Anne Laure , Aigrot Marie Stephane , Trotter Matthew , Huang Jeffrey K. , Dauphinot Luce , Potier Marie Claude , Kerninon Christophe , Melik Parsadaniantz Stephane , Franklin Robin J. M. , Lubetzki Catherine
Published: January 2015

The declining efficiency of myelin regeneration in individuals with multiple sclerosis has stimulated a search for ways by which it might be therapeutically enhanced. Here we have used gene expression profiling on purified murine oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the adult CNS, to obtain a comprehensive picture of how they become activated after demyelination and how this enables them to contribute to remyelination. We find that adult OPCs have a transcriptome more similar to that of oligodendrocytes than to neonatal OPCs, but revert to a neonatal-like transcriptome when activated. Part of the activation response involves increased expression of two genes of the innate immune system,IL1β andCCL2, which enhance the mobilization of OPCs. Our results add a new dimension to the role of the innate immune system in CNS regeneration, revealing how OPCs themselves contribute to the postinjury inflammatory milieu by producing cytokines that directly enhance their repopulation of areas of demyelination and hence their ability to contribute to remyelination.
Distinct Midbrain and Habenula Pathways Are Involved in Processing Aversive Events in Humans
Authors: Hennigan Kelly , D'Ardenne Kimberlee , McClure Samuel M.
Published: January 2015

Emerging evidence implicates the midbrain dopamine system and its interactions with the lateral habenula in processing aversive information and learning to avoid negative outcomes. We examined neural responses to unexpected, aversive events using methods specialized for imaging the midbrain and habenula in humans. Robust activation to aversive relative to neutral events was observed in the habenula and two regions within the ventral midbrain: one located within the ventral tegmental area (VTA) and the other in the substantia nigra (SN). Aversive processing increased functional connectivity between the VTA and the habenula, putamen, and medial prefrontal cortex, whereas the SN exhibited a different pattern of functional connectivity. Our findings provide evidence for a network comprising the VTA and SN, the habenula, and mesocorticolimbic structures that supports processing aversive events in humans.
Caveolin-1 in the Anterior Cingulate Cortex Modulates Chronic Neuropathic Pain via Regulation of NMDA Receptor 2B Subunit
Authors: Yang Jun-Xia , Hua Lu , Li Yan-Qiang , Jiang Yan-Yu , Han Dong , Liu He , Tang Qian-Qian , Yang Xiao-Na , Yin Cui , Hao Ling-Yun , Yu Le , Wu Peng , Shao Cui-Jie , Ding Hai-Lei , Zhang Yong-Mei , Cao Jun-Li
Published: January 2015

Chronic pain is still a basic science and clinical challenge. Unraveling of the neurobiological mechanisms involved in chronic pain will offer novel targets for the development of therapeutic strategies. It is well known that central sensitization in the anterior cingulate cortex (ACC) plays a critical role in initiation, development, and maintenance of chronic pain. However, the underlying mechanisms still remain elusive. Here, we reported that caveolin-1 (Cav-1), a scaffolding protein in membrane rafts, was persistently upregulated and activated in the ACC neurons after chronic constriction injury (CCI) in mice. Knockdown or blocking of Cav-1 in the contralateral ACC to the injury side reversed CCI-induced pain behavioral and neuronal sensitization and overexpression of Cav-1 in the ipsilateral ACC-induced pain behavior in the unaffected hindpaw. Furthermore, we found that Cav-1 directly binding with NMDA receptor 2B subunit (NR2B) and promotion of NR2B surface levels in the ACC contributed to modulation of chronic neuropathic pain. Disrupting the interaction of Cav-1 and NR2B through microinjection of a short peptide derived from the C-terminal of NR2B into the ACC exhibited a significant anti-nociception effect associated with decrease of surface NR2B expression. Moreover, Cav-1 increased intracellular Ca2+concentration and activated the ERK/CREB signaling pathway in an NR2B-dependent manner in the ACC. Our findings implicate that Cav-1 in the ACC neurons modulates chronic neuropathic pain via regulation of NR2B and subsequent activation of ERK/CREB signaling, suggesting a possible caveolin-mediated process would participate in neuronal transmission pathways implicated in pain modulation.
Spatial and Temporal Characteristics of Error-Related Activity in the Human Brain
Authors: Neta Maital , Miezin Francis M. , Nelson Steven M. , Dubis Joseph W. , Dosenbach Nico U.F. , Schlaggar Bradley L. , Petersen Steven E.
Published: January 2015

A number of studies have focused on the role of specific brain regions, such as the dorsal anterior cingulate cortex during trials on which participants make errors, whereas others have implicated a host of more widely distributed regions in the human brain. Previous work has proposed that there are multiple cognitive control networks, raising the question of whether error-related activity can be found in each of these networks. Thus, to examine error-related activity broadly, we conducted a meta-analysis consisting of 12 tasks that included both error and correct trials. These tasks varied by stimulus input (visual, auditory), response output (button press, speech), stimulus category (words, pictures), and task type (e.g., recognition memory, mental rotation). We identified 41 brain regions that showed a differential fMRI BOLD response to error and correct trials across a majority of tasks. These regions displayed three unique response profiles: (1) fast, (2) prolonged, and (3) a delayed response to errors, as well as a more canonical response to correct trials. These regions were found mostly in several control networks, each network predominantly displaying one response profile. The one exception to this “one network, one response profile” observation is the frontoparietal network, which showed prolonged response profiles (all in the right hemisphere), and fast profiles (all but one in the left hemisphere). We suggest that, in the place of a single localized error mechanism, these findings point to a large-scale set of error-related regions across multiple systems that likely subserve different functions.
Saccade Planning Evokes Topographically Specific Activity in the Dorsal and Ventral Streams
Authors: Saber Golbarg T. , Pestilli Franco , Curtis Clayton E.
Published: January 2015

Saccade planning may invoke spatially-specific feedback signals that bias early visual activity in favor of top-down goals. We tested this hypothesis by measuring cortical activity at the early stages of the dorsal and ventral visual processing streams. Human subjects maintained saccade plans to (prosaccade) or away (antisaccade) from a spatial location over long memory-delays. Results show that cortical activity persists in early visual cortex at the retinotopic location of upcoming saccade goals. Topographically specific activity persists as early as V1, and activity increases along both dorsal (V3A/B, IPS0) and ventral (hV4, VO1) visual areas. Importantly, activity persists when saccade goals are available only via working memory and when visual targets and saccade goals are spatially disassociated. We conclude that top-down signals elicit retinotopically specific activity in visual cortex both in the dorsal and ventral streams. Such activity may underlie mechanisms that prioritize locations of task-relevant objects.
Itk Signals Promote Neuroinflammation by Regulating CD4+T-Cell Activation and Trafficking
Authors: Kannan Arun K. , Kim Do-Geun , August Avery , Bynoe Margaret S.
Published: January 2015

Here we demonstrate that interleukin-2-inducible T-cell kinase (Itk) signaling in cluster of differentiation 4-positive (CD4+) T cells promotes experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). We show thatItk−/−mice exhibit reduced disease severity, and transfer ofItk−/−CD4+T cells into T cell-deficient recipients results in lower disease severity. We observed a significant reduction of CD4+T cells in the CNS ofItk−/−mice or recipients ofItk−/−CD4+T cells during EAE, which is consistent with attenuated disease.Itk−/−CD4+T cells exhibit defective response to myelin antigen stimulation attributable to displacement of filamentous actin from the CD4+coreceptor. This results in inadequate transmigration ofItk−/−CD4+T cells into the CNS and across brain endothelial barriersin vitro. Finally,Itk−/−CD4+T cells show significant reduction in production of T-helper 1 (Th1) and Th17 cytokines and exhibit skewed T effector/T regulatory cell ratios. These results indicate that signaling by Itk promotes autoimmunity and CNS inflammation, suggesting that it may be a viable target for treatment of MS.
Overexpression of the Type 1 Adenylyl Cyclase in the Forebrain Leads to Deficits of Behavioral Inhibition
Authors: Chen Xuanmao , Cao Hong , Saraf Amit , Zweifel Larry S. , Storm Daniel R.
Published: January 2015

The type 1 adenylyl cyclase (AC1) is an activity-dependent, calcium-stimulated adenylyl cyclase expressed in the nervous system that is implicated in memory formation. We examined the locomotor activity, and impulsive and social behaviors of AC1+ mice, a transgenic mouse strain overexpressing AC1 in the forebrain. Here we report that AC1+ mice exhibit hyperactive behaviors and demonstrate increased impulsivity and reduced sociability. In contrast, AC1 and AC8 double knock-out mice are hypoactive, and exhibit increased sociability and reduced impulsivity. Interestingly, the hyperactivity of AC1+ mice can be corrected by valproate, a mood-stabilizing drug. These data indicate that increased expression of AC1 in the forebrain leads to deficits in behavioral inhibition.
Chromatin Landscape Defined by Repressive Histone Methylation during Oligodendrocyte Differentiation
Authors: Liu Jia , Magri Laura , Zhang Fan , Marsh Nidaa O. , Albrecht Stefanie , Huynh Jimmy L. , Kaur Jasbir , Kuhlmann Tanja , Zhang Weijia , Slesinger Paul A. , Casaccia Patrizia
Published: January 2015

In many cell types, differentiation requires an interplay between extrinsic signals and transcriptional changes mediated by repressive and activating histone modifications. Oligodendrocyte progenitors (OPCs) are electrically responsive cells receiving synaptic input. The differentiation of these cells into myelinating oligodendrocytes is characterized by temporal waves of gene repression followed by activation of myelin genes and progressive decline of electrical responsiveness. In this study, we used chromatin isolated from rat OPCs and immature oligodendrocytes, to characterize the genome-wide distribution of the repressive histone marks, H3K9me3 and H3K27me3, during differentiation. Although both marks were present at the OPC stage, only H3K9me3 marks (but not H3K27me3) were found to be increased during differentiation, at genes related to neuronal lineage and regulation of membrane excitability. Consistent with these findings, the levels and activity of H3K9 methyltransferases (H3K9 HMT), but not H3K27 HMT, increased more prominently upon exposure to oligodendrocyte differentiating stimuli and were detected in stage-specific repressive protein complexes containing the transcription factors SOX10 or YY1. Silencing H3K9 HMT, but not H3K27 HMT, impaired oligodendrocyte differentiation and functionally altered the response of oligodendrocytes to electrical stimulation. Together, these results identify repressive H3K9 methylation as critical for gene repression during oligodendrocyte differentiation.
Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats
Authors: Achterberg E.J. Marijke , van Kerkhof Linda W.M. , Damsteegt Ruth , Trezza Viviana , Vanderschuren Louk J.M.J.
Published: January 2015

Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD.
Combinatorial Mutagenesis of the Voltage-Sensing Domain Enables the Optical Resolution of Action Potentials Firing at 60 Hz by a Genetically Encoded Fluorescent Sensor of Membrane Potential
Authors: Piao Hong Hua , Rajakumar Dhanarajan , Kang Bok Eum , Kim Eun Ha , Baker Bradley J.
Published: January 2015

ArcLight is a genetically encoded fluorescent voltage sensor using the voltage-sensing domain of the voltage-sensing phosphatase fromCiona intestinalisthat gives a large but slow-responding optical signal in response to changes in membrane potential (Jin et al., 2012). Fluorescent voltage sensors using the voltage-sensing domain from other species give faster yet weaker optical signals (Baker et al., 2012; Han et al., 2013). Sequence alignment of voltage-sensing phosphatases from different species revealed conserved polar and charged residues at 7 aa intervals in the S1–S3 transmembrane segments of the voltage-sensing domain, suggesting potential coil–coil interactions. The contribution of these residues to the voltage-induced optical signal was tested using a cassette mutagenesis screen by flanking each transmembrane segment with unique restriction sites to allow for the testing of individual mutations in each transmembrane segment, as well as combinations in all four transmembrane segments. Addition of a counter charge in S2 improved the kinetics of the optical response. A double mutation in the S4 domain dramatically reduced the slow component of the optical signal seen in ArcLight. Combining that double S4 mutant with the mutation in the S2 domain yielded a probe with kinetics <10 ms. Optimization of the linker sequence between S4 and the fluorescent protein resulted in a new ArcLight-derived probe, Bongwoori, capable of resolving action potentials in a hippocampal neuron firing at 60 Hz. Additional manipulation of the voltage-sensing domain could potentially lead to fluorescent sensors capable of optically resolving neuronal inhibition and subthreshold synaptic activity.
Bridging the Gap between Perceptual and Cognitive Perspectives on Absolute Pitch
Authors: Elmer Stefan , Rogenmoser Lars , Kühnis Jürg , Jäncke Lutz
Published: January 2015

Absolute pitch (AP) refers to the rare ability to identify the chroma of a tone or to produce a specific pitch without reference to keyality (e.g., G or C). Previously, AP has been proposed to rely on the distinctive functional-anatomical architecture of the left auditory-related cortex (ARC), this specific trait possibly enabling an optimized early “categorical perception”. In contrast, currently prevailing models of AP postulate that cognitive rather than perceptual processes, namely “pitch labeling” mechanisms, more likely constitute the bearing skeleton of AP. This associative memory component has previously been proposed to be dependent, among other mechanisms, on the recruitment of the left dorsolateral prefrontal cortex (DLPFC) as well as on the integrity of the left arcuate fasciculus, a fiber bundle linking the posterior supratemporal plane with the DLPFC. Here, we attempted to integrate these two apparently conflicting perspectives on AP, namely early “categorical perception” and “pitch labeling”. We used electroencephalography and evaluated resting-state intracranial functional connectivity between the left ARC and DLPFC in a sample of musicians with and without AP. Results demonstrate significantly increased left-hemispheric theta phase synchronization in AP compared with non-AP musicians. Within the AP group, this specific electrophysiological marker was predictive of absolute-hearing behavior and explained ∼30% of variance. Thus, we propose that in AP subjects the tonal inputs and the corresponding mnemonic representations are tightly coupled in such a manner that the distinctive electrophysiological signature of AP can saliently be detected in only 3 min of resting-state measurements.
cJun and CREB2 in the Postsynaptic Neuron Contribute to Persistent Long-Term Facilitation at a Behaviorally Relevant Synapse
Authors: Hu Jiang-Yuan , Levine Amir , Sung Ying-Ju , Schacher Samuel
Published: January 2015

Basic region leucine zipper (bZIP) transcription factors regulate gene expression critical for long-term synaptic plasticity or neuronal excitability contributing to learning and memory. At sensorimotor synapses ofAplysia, changes in activation or expression of CREB1 and CREB2 in sensory neurons are required for long-term synaptic plasticity. However, it is unknown whether concomitant stimulus-induced changes in expression and activation of bZIP transcription factors in the postsynaptic motor neuron also contribute to persistent long-term facilitation (P-LTF). We overexpressed various forms of CREB1, CREB2, or cJun in the postsynaptic motor neuron L7 in cell culture to examine whether these factors contribute to P-LTF. P-LTF is evoked by 2 consecutive days of 5-HT applications (2 5-HT), while a transient form of LTF is produced by 1 day of 5-HT applications (1 5-HT). Significant increases in the expression of both cJun and CREB2 mRNA in L7 accompany P-LTF. Overexpressing each bZIP factor in L7 did not alter basal synapse strength, while coexpressing cJun and CREB2 in L7 evoked persistent increases in basal synapse strength. In contrast, overexpressing cJun and CREB2 in sensory neurons evoked persistent decreases in basal synapse strength. Overexpressing wild-type cJun or CREB2, but not CREB1, in L7 can replace the second day of 5-HT applications in producing P-LTF. Reducing cJun activity in L7 blocked P-LTF evoked by 2 5-HT. These results suggest that expression and activation of different bZIP factors in both presynaptic and postsynaptic neurons contribute to persistent change in synapse strength including stimulus-dependent long-term synaptic plasticity.
Diversity of Glutamatergic Synaptic Strength in Lateral Prefrontal versus Primary Visual Cortices in the Rhesus Monkey
Authors: Medalla Maria , Luebke Jennifer I.
Published: January 2015

Understanding commonalities and differences in glutamatergic synaptic signaling is essential for understanding cortical functional diversity, especially in the highly complex primate brain. Previously, we have shown that spontaneous EPSCs differed markedly in layer 3 pyramidal neurons of two specialized cortical areas in the rhesus monkey, the high-order lateral prefrontal cortex (LPFC) and the primary visual cortex (V1). Here, we used patch-clamp recordings and confocal and electron microscopy to determine whether these distinct synaptic responses are due to differences in firing rates of presynaptic neurons and/or in the features of presynaptic or postsynaptic entities. As with spontaneous EPSCs, TTX-insensitive (action potential-independent) miniature EPSCs exhibited significantly higher frequency, greater amplitude, and slower kinetics in LPFC compared with V1 neurons. Consistent with these physiological differences, LPFC neurons possessed higher densities of spines, and the mean width of large spines was greater compared with those on V1 neurons. Axospinous synapses in layers 2–3 of LPFC had larger postsynaptic density surface areas and a higher proportion of large perforated synapses compared with V1. Axonal boutons in LPFC were also larger in volume and contained ∼1.6× more vesicles than did those in V1. Further, LPFC had a higher density of AMPA GluR2 receptor labeling than V1. The properties of spines and synaptic currents of individual layer 3 pyramidal neurons measured here were significantly correlated, consistent with the idea that significantly more frequent and larger synaptic currents are likely due to more numerous, larger, and more powerful synapses in LPFC compared with V1.
Mapping the Stability of Human Brain Asymmetry across Five Sex-Chromosome Aneuploidies
Authors: Lin Amy , Clasen Liv , Lee Nancy Raitano , Wallace Gregory L. , Lalonde Francois , Blumenthal Jonathan , Giedd Jay N. , Raznahan Armin
Published: January 2015

The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n= 28), XXY (n= 58), XYY (n= 26), XXYY (n= 20), and XXXXY (n= 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.
Gene Dosage in the Dysbindin Schizophrenia Susceptibility Network Differentially Affect Synaptic Function and Plasticity
Authors: Mullin Ariana P. , Sadanandappa Madhumala K. , Ma Wenpei , Dickman Dion K. , VijayRaghavan Krishnaswamy , Ramaswami Mani , Sanyal Subhabrata , Faundez Victor
Published: January 2015

Neurodevelopmental disorders arise from single or multiple gene defects. However, the way multiple loci interact to modify phenotypic outcomes remains poorly understood. Here, we studied phenotypes associated with mutations in the schizophrenia susceptibility genedysbindin(dysb), in isolation or in combination with null alleles in thedysbnetwork componentBlos1. In humans, theBlos1orthologBloc1s1encodes a polypeptide that assembles, with dysbindin, into the octameric BLOC-1 complex. We biochemically confirmed BLOC-1 presence inDrosophilaneurons, and measured synaptic output and complex adaptive behavior in response to BLOC-1 perturbation. Homozygous loss-of-function alleles ofdysb,Blos1, or compound heterozygotes of these alleles impaired neurotransmitter release, synapse morphology, and homeostatic plasticity at the larval neuromuscular junction, and impaired olfactory habituation. This multiparameter assessment indicated that phenotypes were differentially sensitive to genetic dosages of loss-of-function BLOC-1 alleles. Our findings suggest that modification of a second genetic locus in a defined neurodevelopmental regulatory network does not follow a strict additive genetic inheritance, but rather, precise stoichiometry within the network determines phenotypic outcomes.
Gene Expression Analyses Identify Narp Contribution in the Development of l-DOPA-Induced Dyskinesia
Authors: Charbonnier-Beaupel Fanny , Malerbi Marion , Alcacer Cristina , Tahiri Khadija , Carpentier Wassila , Wang Chuansong , During Matthew , Xu Desheng , Worley Paul F. , Girault Jean-Antoine , Hervé Denis , Corvol Jean-Christophe
Published: January 2015

In Parkinson's disease, long-term dopamine replacement therapy is complicated by the appearance ofl-DOPA-induced dyskinesia (LID). One major hypothesis is that LID results from an aberrant transcriptional program in striatal neurons induced byl-DOPA and triggered by the activation of ERK. To identify these genes, we performed transcriptome analyses in the striatum in 6-hydroxydopamine-lesioned mice. A time course analysis (0–6 h after treatment withl-DOPA) identified an acute signature of 709 genes, among which genes involved in protein phosphatase activity were overrepresented, suggesting a negative feedback on ERK activation byl-DOPA.l-DOPA-dependent deregulation of 28 genes was blocked by pretreatment with SL327, an inhibitor of ERK activation, and 26 genes were found differentially expressed between highly and weakly dyskinetic animals after treatment withl-DOPA. The intersection list identified five genes:FosB,Th,Nptx2,Nedd4l, andCcrn4l. Nptx2encodes neuronal pentraxin II (or neuronal activity-regulated pentraxin, Narp), which is involved in the clustering of glutamate receptors. We confirmed increasedNptx2expression afterl-DOPA and its blockade by SL327 using quantitative RT-PCR in independent experiments. Using an escalatingl-DOPA dose protocol, LID severity was decreased in Narp knock-out mice compared with their wild-type littermates or after overexpression of a dominant-negative form of Narp in the striatum. In conclusion, we have identified a molecular signature induced byl-DOPA in the dopamine-denervated striatum that is dependent on ERK and associated with LID. Here, we demonstrate the implication of one of these genes,Nptx2, in the development of LID.
Lack of glucagon receptor signaling and its implications beyond glucose homeostasis
Authors: Charron Maureen J , Vuguin Patricia M
Published: January 2015

Glucagon action is transduced by a G protein-coupled receptor located in liver, kidney, intestinal smooth muscle, brain, adipose tissue, heart, pancreatic β-cells, and placenta. Genetically modified animal models have provided important clues about the role of glucagon and its receptor (Gcgr) beyond glucose control. The PubMed database was searched for articles published between 1995 and 2014 using the key terms glucagon, glucagon receptor, signaling, and animal models. Lack of Gcgr signaling has been associated with: i) hypoglycemic pregnancies, altered placentation, poor fetal growth, and increased fetal–neonatal death; ii) pancreatic glucagon cell hyperplasia and hyperglucagonemia; iii) altered body composition, energy state, and protection from diet-induced obesity; iv) impaired hepatocyte survival; v) altered glucose, lipid, and hormonal milieu; vi) altered metabolic response to prolonged fasting and exercise; vii) reduced gastric emptying and increased intestinal length; viii) altered retinal function; and ix) prevention of the development of diabetes in insulin-deficient mice. Similar phenotypic findings were observed in the hepatocyte-specific deletion ofGcgr. Glucagon action has been involved in the modulation of sweet taste responsiveness, inotropic and chronotropic effects in the heart, satiety, glomerular filtration rate, secretion of insulin, cortisol, ghrelin, GH, glucagon, and somatostatin, and hypothalamic signaling to suppress hepatic glucose production. Glucagon (α) cells under certain conditions can transdifferentiate into insulin (β) cells. These findings suggest that glucagon signaling plays an important role in multiple organs. Thus, treatment options designed to block Gcgr activation in diabetics may have implications beyond glucose homeostasis.
Drosophila Oocytes as a Model for Understanding Meiosis: An Educational Primer to Accompany “Corolla Is a Novel Protein That Contributes to the Architecture of the Synaptonemal Complex of Drosophila”
Authors: Ables Elizabeth T
Published: January 2015

SUMMARY Achieving a thorough understanding of the events and ramifications of meiosis is a common learning objective for undergraduate introductory biology, genetics, and cell biology courses. Meiosis is also one of the most challenging cellular processes for students to conceptualize. Connecting textbook descriptions of meiosis to current research in the field of genetics in a problem-based learning format may aid students’ understanding of this important biological concept. This primer seeks to assist students and instructors by providing an introductory framework upon which to integrate discussions of current meiosis research into traditional genetics or cell biology curriculum.

Related article in GENETICS: Collins, K. et al., 2014 Corolla Is a Novel Protein That Contributes to the Architecture of the Synaptonemal Complex of Drosophila. Genetics 198:219–228.
Recent and Massive Expansion of the Mating-Type-Specific Region in the Smut Fungus Microbotryum
Authors: Whittle Carrie A , Votintseva Antonina , Ridout Kate , Filatov Dmitry A
Published: January 2015

The presence of large genomic regions with suppressed recombination (SR) is a key shared property of some sex- and mating-type determining (mat) chromosomes identified to date in animals, plants, and fungi. Why such regions form and how they evolve remain central questions in evolutionary genetics. The smut fungus Microbotryum lychnis-dioicae is a basidiomycete fungus in which dimorphic mat chromosomes have been reported, but the size, age, and evolutionary dynamics of the SR region remains unresolved. To identify the SR region in M. lychnis-dioicae and to study its evolution, we sequenced 12 genomes (6 per mating type) of this species and identified the genomic contigs that show fixed sequence differences between the mating types. We report that the SR region spans more than half of the mat chromosome (>2.3 Mbp) and that it is of very recent origin (∼2 × 106 years) as the average sequence divergence between mating types was only 2% in the SR region. This contrasts with a much higher divergence in and around the mating-type determining pheromone receptor locus in the SR, suggesting a recent and massive expansion of the SR region. Our results comprise the first reported case of recent massive SR expansion documented in a basidiomycete fungus.
Composition and diversity of the Chironomidae in subtropical streams: effects of environmental predictors and temporal analysis
Authors: Restello Rozane Maria , Biasi Cristiane , Moraes Pedro Felipe Moutinho Bernardo de , Gabriel Gabriella , Hepp Luiz Ubiratan
Published: January 2015

AIMS: The aims of this study were (i) to evaluate the spatial and temporal distribution of chironomids in subtropical streams and (ii) to investigate the importance of environmental predictors in the distribution of this group. METHODS: Samples were collected in four annual seasons between 2010 and 2011, in 10 streams located in an agricultural matrix in southern Brazil, using a Surber sampler. Organisms were identified to the genus level. Some environmental variables were analysed in the sampling sites of the Chironomidae. The variations in abundance and diversity were compared by Analysis of Variance, whereas the community composition was analysed using Multivariate Analysis of Variance. A Redundance Analysis was used to evaluate the effect of environmental variables on the chironomid community. RESULTS: 7,349 individuals were identified, belonging to three subfamilies (Chironominae, Tanypodinae and Orthocladiinae) and 57 genera. The abundance and richness of the Chironomidae were similar between sites and seasons. However, the composition varied spatially and temporally (p < 0.001). Water temperature, total organic carbon, total nitrogen and carbon:nitrogen ratio were variables that influenced the chironomid community. The genera Thienemanniela, Pentaneura, Paratanytarsus, Parapentaneura, Parametriocnemus, Hudsonimyia, Labrundinea and Larsia were present in summer, whereas Parakiefferiella, Paramerina, Metriocnemus were indicators for winter. CONCLUSIONS: The spatial distribution of chironomids was directly related to the environmental conditions of the sampling sites. The temporal variation in the community followed a pattern in relation to water temperature. The variables physical and chemical operate as environmental filters and thereby alter the chironomid community.
Structure and composition of the benthic macroinvertebrate community on wetland and irrigated rice cultivation
Authors: Juruá Karen Tavares , Pagel Isadora Adamoli , Tavares Vitor Emanuel , Sosinski Lilian Terezinha Winckler
Published: January 2015

Wetlands are environmentally and economically important ecosystems. The irrigated rice crops are considered artificial wetlands, because they offer food and refuge to different aquatic communities. The benthic macroinvertebrates are used to study environmental quality. The knowledge from the organisms which inhabit the natural and artificial wetlands can help to verify less harmful management practices in the agroecosystems. AIM: The aim of this research was to analyze and compare the benthic macroinvertebrate community from a wetland and an experimental kind of rice cultivation. METHODS: It was used dip nets 1 mm mesh every 15 days, with six repetitions in each place, from January to March 2010. After washing and screening them in the laboratory, the organisms were identified using stereoscope microscope and identification keys, and classified according to their functional trophic group. RESULTS: The whole organisms collected were 33,293 specimens. It was found 34 taxa, being 26 founded in the rice crops and 31 on the wetland. The natural wetland shows greater abundance, being responsible for 90.47% from the total abundance in this study. In the rice crop the abundance and the richness increased in the course of collection. However, it did not reach the values founded in the wetlands during the cultivation period. The most found groups in the two environmental were Belostomatidae and Planorbidae, while Hyalellidae and Elmidae were found only in the wetland, being a stress indicator in the wetland. CONCLUSIONS: The community structure including abundance, richness and composition was statistical different between wetlands and rice cultivation.
Chemical change of leaves during breakdown affects associated invertebrates in a subtropical stream
Authors: Tonin Alan Mosele , Restello Rozane Maria , Hepp Luiz Ubiratan
Published: January 2015

AIMS: Our objective was assess the effects of leaf chemical change during breakdown on the associated invertebrates. METHODS: We evaluate the chemical composition of leaves (of two tree species; Sebastiania brasiliensis and Campomanesia xanthocarpa) and the density of invertebrates during leaf breakdown (on four incubation times; 3, 7, 14 and 22 days) in a subtropical stream. Linear multiple regression analysis were performed to evaluate the relationship between invertebrate density and changes in leaf chemical during breakdown. RESULTS: Density of invertebrates was related to the chemical composition of leaves. There was a positive correlation of K (β = 3.48) and a negative of C:N (β = -0.34), polyphenols (β = -0.16), Ca (β = -2.98) and Mg (β = -2.58) with the total density of invertebrates. Density of invertebrates on leaves reached 38 ± 9 and 192 ± 31 individuals g-1 leaf DM during the first 3 and 7 days of incubation, had decreased by the 14th day (117 ± 18) and then increased after 22 days (270 ± 41). CONCLUSIONS: We conclude that changes in the chemistry of decomposing leaves affect invertebrate colonization process. This conclusion reinforce the importance of understand the dynamic of energy and nutrients and its association with the biological communities of tropical riparian ecosystems.
Short-term physiological responses to copper stress in Salvinia auriculata Aubl.
Authors: Bizzo Andresa Lana Thomé , Intorne Aline Chaves , Gomes Pollyana Honório , Suzuki Marina Satika , Esteves Bruno dos Santos
Published: January 2015

AIM: To evaluate, in a short-time exposure, the physiological responses of Salvinia auriculata Aubl. under different concentrations of Cu. METHODS: The plants were exposed to treatments with 0.01, 0.1, 1 and 10 mM of Cu in a period of 2 days. Then development variables of S. auriculata (weight, photosynthetic pigments, and soluble carbohydrate), lipid peroxidation (malondialdehyde, aldehydes, and electrolyte leakage) and production of antioxidants (anthocyanins, carotenoids, flavonoids, and proline) were evaluated. RESULTS: It was observed fresh weight reductions in concentrations above 1 mM of Cu. Chlorophyll a decreased with the increase of Cu concentrations unlike chlorophyll b. The ratio chlorophyll a / chlorophyll b was changed due to the degradation of photosynthetic pigments. The reductions of carotenoids were more pronounced than that of total chlorophyll. The values of electrolyte leakage ranged from 14 to 82 % and lipid peroxidation from 7 to 46 nmol.g-1. Flavonoids and soluble carbohydrates showed reductions with the increase of Cu concentration. Anthocyanins, phenolic compounds, and proline when subjected to 0.1 mM of Cu had increased, suggesting adaptability of plant stress caused directly by metal and reactive oxygen species. In higher concentrations, degradation and/or direct modifications of these molecules possibly occurred. CONCLUSIONS: The data suggest that S. auriculata is provided with an efficient mechanism against stress caused by Cu in the concentration of 0.1 mM. As for higher concentrations (1 and 10 mM), despite its role as micronutrients, Cu was toxic to the plant due to the redox behavior of this metal, which leads to the exacerbated formation of reactive oxygen species, inducing to severe damage such as biological membrane degradation and protein denaturation.
Determining the high variability of pCO2 and pO2 in the littoral zone of a subtropical coastal lake
Authors: Tonetta Denise , Fontes Maria Luiza Schmitz , Petrucio Mauricio Mello
Published: January 2015

The aquatic metabolism comprises production and mineralization of organic matter through biological processes, such as primary production and respiration that can be estimated by gases concentration in the water column. AIM: The study aimed to assess the temporal variability of pCO2 and pO2 in the littoral zone of a subtropical coastal lake. Our hypotheses are i) high variability in meteorological conditions, such as temperature and light, drive the high variability in pCO2 and pO2, and ii) the lake is permanently heterotrophic due to the low phosphorus concentration. METHODS: We estimated pCO2 from pH-alkalinity method, and pO2 from dissolved oxygen concentration and water temperature measured in free-water during 24 hours in the autumn, winter, spring and summer. RESULTS: Our findings showed that limnological variables had low temporal variability, while the meteorological variables and pCO2 presented a high coefficient of variation, which is representative of each climatic season. In autumn and winter, it was recorded that the lake was supersaturated in CO2 relative to the atmosphere, while in spring and summer CO2 concentration was below the concentration found in the atmosphere. Over 24 hours, pCO2 also showed high variability, with autumn presenting higher concentration during the night when compared to daytime. Water temperature and chlorophyll a were negatively correlated with pCO2, while pO2 was positively correlated with wind and light. CONCLUSION: Agreeing with our first hypothesis, pCO2 showed an expressive temporal variation in a subtropical lake associated to the high variability in meteorological conditions. On the other hand, our second hypothesis was not confirmed, since Peri Lake exported CO2 to the atmosphere in some periods and in others, CO2 was removed from the atmosphere.
Composition and species richness phytoplankton in a subtropical floodplain lake: a long-term study
Authors: Bortolini Jascieli Carla , Bovo-Scomparin Vânia Mara , Paula Aline Caroline Magro de , Moresco Geovani Arnhold , Reis Larissa Mozini , Jati Susicley , Rodrigues Luzia Cleide
Published: January 2015

AIM: Phytoplankton species diversity in floodplain lakes is influenced by different conditions imposed by the hydrosedimentological regime of the main channel. This study evaluated the predictors of composition and species richness phytoplankton in the long-term scale, in a floodplain lake directly connected to the Paraná River. We hypothesized that species richness of the floodplain lake is directly related to the degree of connectivity with the main channel. METHODS: Quarterly samplings were conducted between February 2000 and March 2013 (except in 2001 and 2003), under the water surface of the pelagic zone of the lake. Data were analyzed with Spearman correlation, PCA, DCA, ANOVA and regression analysis. RESULTS: We identified 397 taxa with high contribution of rare species (72%). Chlorophyceans and diatoms were the most frequent groups. There was a trend of increasing of diatoms and decrease of cyanobacteria. The DCA showed differences in phytoplankton composition. The highest mean richness values were found in years with high number of days under potamophase. Significant differences between years were detected for total species richness and first axis of DCA. Regression analysis indicated that the predictors of species richness were Zeu and Zmax. CONCLUSION: The species richness phytoplankton of the floodplain lake is directly related to the level of connectivity with the main channel.
Identifying and Addressing the Needs of Adolescents and Young Adults With Cancer: Summary of an Institute of Medicine Workshop
Authors: Nass Sharyl J. , Beaupin Lynda K. , Demark-Wahnefried Wendy , Fasciano Karen , Ganz Patricia A. , Hayes-Lattin Brandon , Hudson Melissa M. , Nevidjon Brenda , Oeffinger Kevin C. , Rechis Ruth , Richardson Lisa C. , Seibel Nita L. , Smith Ashley W.
Published: January 2015

Cancer is the leading disease-related cause of death in adolescents and young adults (AYAs). This population faces many short- and long-term health and psychosocial consequences of cancer diagnosis and treatment, but many programs for cancer treatment, survivorship care, and psychosocial support do not focus on the specific needs of AYA cancer patients. Recognizing this health care disparity, the National Cancer Policy Forum of the Institute of Medicine convened a public workshop to examine the needs of AYA patients with cancer. Workshop participants identified many gaps and challenges in the care of AYA cancer patients and discussed potential strategies to address these needs. Suggestions included ways to improve access to care for AYAs, to deliver cancer care that better meets the medical and psychosocial needs of AYAs, to develop educational programs for providers who care for AYA cancer survivors, and to enhance the evidence base for AYAs with cancer by facilitating participation in research.
Load-resisting mechanism to mitigate progressive collapse of flat slab structures
Authors: Qian Kai , Li Bing
Published: January 2015

For reinforced concrete flat slab structures, column failure due to unexpected extreme loading may significantly increase the moment and shear force at adjacent slab–column connections, which can trigger punching shear failure at these connections and result in progressive collapse of flat slab structures. To determine the possible load-resisting mechanisms developed in flat slab structures in resisting progressive collapse, three multi-panel flat slab substructures are tested in this study. A flat slab substructure is tested as a control specimen. The remaining two specimens are strengthened by adding drop panels or post-installed shear bolts. Punching shear failure is observed in the control specimen and the specimen with post-installed shear bolts after reaching their yield loads. However, even the control specimen without any strengthening exhibited considerable post-failure resistance and deformation capacity mainly due to sufficient integrity reinforcement, which had been installed in the bottom of the slab. Test results indicated that drop panels not only increase the flexural resistance but also raise the punching shear resistance of the connections significantly. Thus, no obvious punching shear failure is observed in the specimen with drop panels. However, post-installed shear bolts can only increase the punching shear resistance. For post-failure behaviour, this is not very effective. The test results demonstrated that flexural failure dominates the performance of test specimens, as relatively low slab reinforcement ratio but high span/thickness ratio was designed.
A ceraphronid wasp in Early Miocene amber from the Dominican Republic (Hymenoptera: Ceraphronidae)
Authors: Engel Michael S.
Published: January 2015

The first fossil of the parasitoid wasp family Ceraphronidae (Ceraphronoidea) is described and figured.  Ceraphron ceuthonymus Engel, new species, is described from Early Miocene (Burdigalian) amber from the Dominican Republic and distinguished from its close congeners.  A brief summary of the fossil record of Ceraphronoidea is provided.