bluuebunny/crossref_metadata_2025 huggingface dataset:
PtenRegulates Retinal Amacrine Cell Number by Modulating Akt, Tgfβ, and Erk Signaling
Authors: Tachibana Nobuhiko , Cantrup Robert , Dixit Rajiv , Touahri Yacine , Kaushik Gaurav , Zinyk Dawn , Daftarian Narsis , Biernaskie Jeff , McFarlane Sarah , Schuurmans Carol
Published: September 2016

All tissues are genetically programmed to acquire an optimal size that is defined by total cell number and individual cellular dimensions. The retina contains stereotyped proportions of one glial and six neuronal cell types that are generated in overlapping waves. How multipotent retinal progenitors know when to switch from making one cell type to the next so that appropriate numbers of each cell type are generated is poorly understood. Pten is a phosphatase that controls progenitor cell proliferation and differentiation in several lineages. Here, using a conditional loss-of-function strategy, we found thatPtenregulates retinal cell division and is required to produce the full complement of rod photoreceptors and amacrine cells in mouse. We focused on amacrine cell number control, identifying three downstream Pten effector pathways. First, phosphoinositide 3-kinase/Akt signaling is hyperactivated inPtenconditional knock-out (cKO) retinas, and misexpression of constitutively active Akt (Akt-CA) in retinal explants phenocopies the reduction in amacrine cell production observed inPtencKOs. Second, Akt-CA activates Tgfβ signaling in retinal explants, which is a negative feedback pathway for amacrine cell production. Accordingly, Tgfβ signaling is elevated inPtencKO retinas, and epistatic analyses placed Pten downstream of TgfβRII in amacrine cell number control. Finally,Ptenregulates Raf/Mek/Erk signaling levels to promote the differentiation of all amacrine cell subtypes, which are each reduced in number inPtencKOs.Ptenis thus a positive regulator of amacrine cell production, acting via multiple downstream pathways, highlighting its diverse actions as a mediator of cell number control.

SIGNIFICANCE STATEMENTDespite the importance of size for optimal organ function, how individual cell types are generated in correct proportions is poorly understood. There are several ways to control cell number, including readouts of organ function (e.g., secreted hormones reach functional levels when enough cells are made) or counting of cell divisions or cell number. The latter applies to the retina, where cell number is regulated by negative feedback signals, which arrest differentiation of particular cell types at threshold levels. Herein, we show thatPtenis a critical regulator of amacrine cell number in the retina, acting via multiple downstream pathways. Our studies provide molecular insights into howPTENloss in humans may lead to uncontrolled cell division in several pathological conditions.
A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse
Authors: Yamawaki Naoki , Radulovic Jelena , Shepherd Gordon M.G.
Published: September 2016

Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections onto M2 pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2–6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control.

SIGNIFICANCE STATEMENTCorticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we show that a posterior part of secondary motor cortex receives corticocortical axons from the rostral retrosplenial cortex (RSC) and these form monosynaptic excitatory connections onto a wide spectrum of excitatory projection neurons in this area. Our results define a cellular basis for direct communication from RSC to this medial frontal area, suggesting a direct link from dorsal hippocampal networks involved in spatial cognition and navigation (the “map”) to sensorimotor networks involved the control of movement (the “motor”).
Maternal Rest/Nrsf Regulates Zebrafish Behavior throughsnap25a/b
Authors: Moravec Cara E. , Samuel John , Weng Wei , Wood Ian C. , Sirotkin Howard I.
Published: September 2016

During embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs throughout its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural-specific genes during early development. Here we show that in zebrafish, maternally suppliedrestregulates expression of target genes during larval development and has lifelong impacts on behavior. Larvae deprived of maternalrestare hyperactive and show atypical spatial preferences. Adult male fish deprived of maternalrestpresent with atypical spatial preferences in a novel environment assay. Transcriptome sequencing revealed 158 genes that are repressed by maternalrestin blastula stage embryos. Furthermore, we found that maternalrestis required for target gene repression until at least 6 dpf. Importantly, disruption of the RE1 sites in eithersnap25aorsnap25bresulted in behaviors that recapitulate the hyperactivity phenotype caused by absence of maternalrest. Both maternalrestmutants andsnap25aRE1 site mutants have altered primary motor neuron architecture that may account for the enhanced locomotor activity. These results demonstrate that maternalrestrepressessnap25a/bto modulate larval behavior and that early Rest activity has lifelong behavioral impacts.

SIGNIFICANCE STATEMENTMaternal factors deposited in the oocyte have well-established roles during embryonic development. We show that, in zebrafish, maternalrest(RE1-silencing transcription factor) regulates expression of target genes during larval development and has lifelong impacts on behavior. The Rest transcriptional repressor interacts with chromatin-modifying complexes to limit transcription of neural genes. We identify several synaptic genes that are repressed by maternal Rest and demonstrate thatsnap25a/bare key targets of maternalrestthat modulate larval locomotor activity. These results reveal that zygoticrestis unable to compensate for deficits in maternally supplied rest and uncovers novel temporal requirements for Rest activity, which has implications for the broad roles of Rest-mediated repression during neural development and in disease states.
Resolving Behavioral Output via Chemogenetic Designer Receptors Exclusively Activated by Designer Drugs
Authors: Burnett C. Joseph , Krashes Michael J.
Published: September 2016

Designer receptors exclusively activated by designer drugs (DREADDs) have proven to be highly effective neuromodulatory tools for the investigation of neural circuits underlying behavioral outputs. They exhibit a number of advantages: they rely on cell-specific manipulations through canonical intracellular signaling pathways, they are easy and cost-effective to implement in a laboratory setting, and they are easily scalable for single-region or full-brain manipulations. On the other hand, DREADDs rely on ligand–G-protein-coupled receptor interactions, leading to coarse temporal dynamics. In this review we will provide a brief overview of DREADDs, their implementation, and the advantages and disadvantages of their use in animal systems. We also will provide numerous examples of their use across a broad variety of biomedical research fields.
Anti-Inflammatory Modulation of Microglia via CD163-Targeted Glucocorticoids Protects Dopaminergic Neurons in the 6-OHDA Parkinson's Disease Model
Authors: Tentillier Noemie , Etzerodt Anders , Olesen Mads N. , Rizalar F. Sila , Jacobsen Jan , Bender Dirk , Moestrup Søren K. , Romero-Ramos Marina
Published: September 2016

Increasing evidence supports a decisive role for inflammation in the neurodegenerative process of Parkinson's disease (PD). The immune response in PD seems to involve, not only microglia, but also other immune cells infiltrated into the brain. Indeed, we observed here the infiltration of macrophages, specifically CD163+ macrophages, into the area of neurodegeneration in the 6-hydroxydopamine (6-OHDA) PD model. Therefore, we investigated the therapeutic potential of the infiltrated CD163+ macrophages to modulate local microglia in the brain to achieve neuroprotection. To do so, we designed liposomes targeted for the CD163 receptor to deliver dexamethasone (Dexa) into the CD163+ macrophages in the 6-OHDA PD model. Our data show that a fraction of the CD163-targeted liposomes were carried into the brain after peripheral intravenous injection. The 6-OHDA-lesioned rats that received repeated intravenous CD163-targeted liposomes with Dexa for 3 weeks exhibited better motor performance than the control groups and had minimal glucocorticoid-driven side effects. Furthermore, these animals showed better survival of dopaminergic neurons in substantia nigra and an increased number of microglia expressing major histocompatibility complex II. Therefore, rats receiving CD163-targeted liposomes with Dexa were partially protected against 6-OHDA-induced dopaminergic neurodegeneration, which correlated with a distinctive microglia response. Altogether, our data support the use of macrophages for the modulation of brain neurodegeneration and specifically highlight the potential of CD163-targeted liposomes as a therapeutic tool in PD.

SIGNIFICANCE STATEMENTThe immune response now evident in the progression of Parkinson's disease comprises both local microglia and other immune cells. We provide evidence that CD163+ macrophages can be a target to modulate brain immune response to achieve neuroprotection in the 6-hydroxydopamine model. To do so, we targeted the CD163+ population, which to a low but significant extent infiltrated in the neurodegenerating area of the brain. Specially designed liposomes targeted for the CD163 receptor were loaded with glucocorticoids and injected peripherally to modify the infiltrated CD163 cells toward an anti-inflammatory profile. This modification of the CD163 population resulted in a distinctive microglial response that correlated with decreased dopaminergic cell death and better motor performance.
Reactivation of Rate Remapping in CA3
Authors: Schwindel C. Daniela , Navratilova Zaneta , Ali Karim , Tatsuno Masami , McNaughton Bruce L.
Published: September 2016

The hippocampus is thought to contribute to episodic memory by creating, storing, and reactivating patterns that are unique to each experience, including different experiences that happen at the same location. Hippocampus can combine spatial and contextual/episodic information using a dual coding scheme known as “global” and “rate” remapping. Global remapping selects which set of neurons can activate at a given location. Rate remapping readjusts the firing rates of this set depending on current experience, thus expressing experience-unique patterns at each location. But can the experience-unique component be retrieved spontaneously? Whereas reactivation of recent, spatially selective patterns in hippocampus is well established, it is never perfect, raising the issue of whether the experiential component might be absent. This question is key to the hypothesis that hippocampus can assist memory consolidation by reactivating and broadcasting experience-specific “index codes” to neocortex. In CA3, global remapping exhibits attractor-like dynamics, whereas rate remapping apparently does not, leading to the hypothesis that only the former can be retrieved associatively and casting doubt on the general consolidation hypothesis. Therefore, we studied whether the rate component is reactivated spontaneously during sleep. We conducted neural ensemble recordings from CA3 while rats ran on a circular track in different directions (in different sessions) and while they slept. It was shown previously that the two directions of running result in strong rate remapping. During sleep, the most recent rate distribution was reactivated preferentially. Therefore, CA3 can retrieve patterns spontaneously that are unique to both the location and the content of recent experience.

SIGNIFICANCE STATEMENTThe hippocampus is required for memory of events and their spatial contexts. The primary correlate of hippocampal activity is location in space, but multiple memories can occur in the same location. To be useful for distinguishing these memories, the hippocampus must be able, not only to express, but also to retrieve both spatial and nonspatial information about events. Whether it can retrieve nonspatial information has been challenged recently. We exposed rats to two different experiences (running in different directions) in the same locations and showed that even the nonspatial components of hippocampal cell firing are reactivated spontaneously during sleep, supporting the conclusion that both types of information about a recent experience can be retrieved.
Increasing the GluN2A/GluN2B Ratio in Neurons of the Mouse Basal and Lateral Amygdala Inhibits the Modification of an Existing Fear Memory Trace
Authors: Holehonnur Roopashri , Phensy Aarron J. , Kim Lily J. , Milivojevic Milica , Vuong Dat , Daison Delvin K. , Alex Saira , Tiner Michael , Jones Lauren E. , Kroener Sven , Ploski Jonathan E.
Published: September 2016

Reconsolidation updating is a form of memory modification in which an existing memory can become destabilized upon retrieval and subsequently be modified via protein-synthesis-dependent reconsolidation. However, not all memories appear to destabilize upon retrieval and thus are not modifiable via reconsolidation updating approaches and the neurobiological basis for this remains poorly understood. Here, we report that auditory fear memories created with 10 tone–shock pairings are resistant to retrieval-dependent memory destabilization and are associated with an increase in the synaptic GluN2A/GluN2B ratio in neurons of the basal and lateral amygdala (BLA) compared with weaker fear memories created via one or three tone–shock pairings. To increase the GluN2A/GluN2B ratio after learning, we generated a line of mice that expresses an inducible and doxycycline-dependent GFP-GluN2A transgene specifically in α-CaMKII-positive neurons. Our findings indicate that increasing the GluN2A/GluN2B ratio in BLA α-CaMKII-positive neurons after a weak fear memory has consolidated inhibits retrieval-dependent memory destabilization and modification of the fear memory trace. This was associated with a reduction in retrieval-dependent AMPA receptor trafficking, as evidenced by a reduction in retrieval-dependent phosphorylation of GluR1 at serine-845. In addition, we determined that increasing the GluN2A/GluN2B ratio before fear learning significantly impaired long term memory consolidation, whereas short-term memory remained unaltered. An increase in the GluN2A/GluN2B ratio after fear learning had no influence on fear extinction or expression. Our results underscore the importance of NMDAR subunit composition for memory destabilization and suggest a mechanism for why some memories are resistant to modification.

SIGNIFICANCE STATEMENTMemory modification using reconsolidation updating is being examined as one of the potential treatment approaches for attenuating maladaptive memories associated with emotional disorders. However, studies have shown that, whereas weak memories can be modified using reconsolidation updating, strong memories can be resistant to this approach. Therefore, treatments targeting the reconsolidation process are unlikely to be clinically effective unless methods are devised to enhance retrieval-dependent memory destabilization. Currently, little is known about the cellular and molecular events that influence the induction of reconsolidation updating. Here, we determined that an increase in the GluN2A/GluN2B ratio interferes with retrieval-dependent memory destabilization and inhibits the initiation of reconsolidation updating.
Glial Cell Calcium Signaling Mediates Capillary Regulation of Blood Flow in the Retina
Authors: Biesecker Kyle R. , Srienc Anja I. , Shimoda Angela M. , Agarwal Amit , Bergles Dwight E. , Kofuji Paulo , Newman Eric A.
Published: September 2016

The brain is critically dependent on the regulation of blood flow to nourish active neurons. One widely held hypothesis of blood flow regulation holds that active neurons stimulate Ca2+increases in glial cells, triggering glial release of vasodilating agents. This hypothesis has been challenged, as arteriole dilation can occur in the absence of glial Ca2+signaling. We address this controversy by imaging glial Ca2+signaling and vessel dilation in the mouse retina. We find that sensory stimulation results in Ca2+increases in the glial endfeet contacting capillaries, but not arterioles, and that capillary dilations often follow spontaneous Ca2+signaling. In IP3R2−/−mice, where glial Ca2+signaling is reduced, light-evoked capillary, but not arteriole, dilation is abolished. The results show that, independent of arterioles, capillaries actively dilate and regulate blood flow. Furthermore, the results demonstrate that glial Ca2+signaling regulates capillary but not arteriole blood flow.

SIGNIFICANCE STATEMENTWe show that a Ca2+-dependent glial cell signaling mechanism is responsible for regulating capillary but not arteriole diameter. This finding resolves a long-standing controversy regarding the role of glial cells in regulating blood flow, demonstrating that glial Ca2+signaling is both necessary and sufficient to dilate capillaries. While the relative contributions of capillaries and arterioles to blood flow regulation remain unclear, elucidating the mechanisms that regulate capillary blood flow may ultimately lead to the development of therapies for treating diseases where blood flow regulation is disrupted, including Alzheimer's disease, stroke, and diabetic retinopathy. This finding may also aid in revealing the underlying neuronal activity that generates BOLD fMRI signals.
Diphtheria Toxin-Induced Cell Death Triggers Wnt-Dependent Hair Cell Regeneration in Neonatal Mice
Authors: Hu Lingxiang , Lu Jingrong , Chiang Hao , Wu Hao , Edge Albert S. B. , Shi Fuxin
Published: September 2016

Cochlear hair cells (HCs), the sensory cells that respond to sound, do not regenerate after damage in adult mammals, and their loss is a major cause of deafness. Here we show that HC regeneration in newborn mouse ears occurred spontaneously when the original cells were ablated by treatment with diphtheria toxin (DT) in ears that had been engineered to overexpress the DT receptor, but was not detectable when HCs were ablatedin vivoby the aminoglycoside antibiotic neomycin. A variety of Wnts (Wnt1, Wnt2, Wnt2b, Wnt4, Wnt5a, Wnt7b, Wnt9a, Wnt9b, and Wnt11) and Wnt pathway component Krm2 were upregulated after DT damage. Nuclear β-catenin was upregulated in HCs and supporting cells of the DT-damaged cochlea. Pharmacological inhibition of Wnt decreased spontaneous regeneration, confirming a role of Wnt signaling in HC regeneration. Inhibition of Notch signaling further potentiated supporting cell proliferation and HC differentiation that occurred spontaneously. The absence of new HCs in the neomycin ears was correlated to less robust Wnt pathway activation, but the ears subjected to neomycin treatment nonetheless showed increased cell division and HC differentiation after subsequent forced upregulation of β-catenin. These studies suggest, first, that Wnt signaling plays a key role in regeneration, and, second, that the outcome of a regenerative response to damage in the newborn cochlea is determined by reaching a threshold level of Wnt signaling rather than its complete absence or presence.

SIGNIFICANCE STATEMENTSensory HCs of the inner ear do not regenerate in the adult, and their loss is a major cause of deafness. We found that HCs regenerated spontaneously in the newborn mouse after diphtheria toxin (DT)-induced, but not neomycin-induced, HC death. Regeneration depended on activation of Wnt signaling, and regeneration in DT-treated ears correlated to a higher level of Wnt activation than occurred in nonregenerating neomycin-treated ears. This is significant because insufficient regeneration caused by a failure to reach a threshold level of signaling, if true in the adult, has the potential to be exploited for development of clinical approaches for the treatment of deafness caused by HC loss.
Perception and Processing of Faces in the Human Brain Is Tuned to Typical Feature Locations
Authors: de Haas Benjamin , Schwarzkopf D. Samuel , Alvarez Ivan , Lawson Rebecca P. , Henriksson Linda , Kriegeskorte Nikolaus , Rees Geraint
Published: September 2016

Faces are salient social stimuli whose features attract a stereotypical pattern of fixations. The implications of this gaze behavior for perception and brain activity are largely unknown. Here, we characterize and quantify a retinotopic bias implied by typical gaze behavior toward faces, which leads to eyes and mouth appearing most often in the upper and lower visual field, respectively. We found that the adult human visual system is tuned to these contingencies. In two recognition experiments, recognition performance for isolated face parts was better when they were presented at typical, rather than reversed, visual field locations. The recognition cost of reversed locations was equal to ∼60% of that for whole face inversion in the same sample. Similarly, an fMRI experiment showed that patterns of activity evoked by eye and mouth stimuli in the right inferior occipital gyrus could be separated with significantly higher accuracy when these features were presented at typical, rather than reversed, visual field locations. Our findings demonstrate that human face perception is determined not only by the local position of features within a face context, but by whether features appear at the typical retinotopic location given normal gaze behavior. Such location sensitivity may reflect fine-tuning of category-specific visual processing to retinal input statistics. Our findings further suggest that retinotopic heterogeneity might play a role for face inversion effects and for the understanding of conditions affecting gaze behavior toward faces, such as autism spectrum disorders and congenital prosopagnosia.

SIGNIFICANCE STATEMENTFaces attract our attention and trigger stereotypical patterns of visual fixations, concentrating on inner features, like eyes and mouth. Here we show that the visual system represents face features better when they are shown at retinal positions where they typically fall during natural vision. When facial features were shown at typical (rather than reversed) visual field locations, they were discriminated better by humans and could be decoded with higher accuracy from brain activity patterns in the right occipital face area. This suggests that brain representations of face features do not cover the visual field uniformly. It may help us understand the well-known face-inversion effect and conditions affecting gaze behavior toward faces, such as prosopagnosia and autism spectrum disorders.
Parsing the Behavioral and Brain Mechanisms of Third-Party Punishment
Authors: Ginther Matthew R. , Bonnie Richard J. , Hoffman Morris B. , Shen Francis X. , Simons Kenneth W. , Jones Owen D. , Marois René
Published: September 2016

The evolved capacity for third-party punishment is considered crucial to the emergence and maintenance of elaborate human social organization and is central to the modern provision of fairness and justice within society. Although it is well established that the mental state of the offender and the severity of the harm he caused are the two primary predictors of punishment decisions, the precise cognitive and brain mechanisms by which these distinct components are evaluated and integrated into a punishment decision are poorly understood. Using fMRI, here we implement a novel experimental design to functionally dissociate the mechanisms underlying evaluation, integration, and decision that were conflated in previous studies of third-party punishment. Behaviorally, the punishment decision is primarily defined by a superadditive interaction between harm and mental state, with subjects weighing the interaction factor more than the single factors of harm and mental state. On a neural level, evaluation of harms engaged brain areas associated with affective and somatosensory processing, whereas mental state evaluation primarily recruited circuitry involved in mentalization. Harm and mental state evaluations are integrated in medial prefrontal and posterior cingulate structures, with the amygdala acting as a pivotal hub of the interaction between harm and mental state. This integrated information is used by the right dorsolateral prefrontal cortex at the time of the decision to assign an appropriate punishment through a distributed coding system. Together, these findings provide a blueprint of the brain mechanisms by which neutral third parties render punishment decisions.

SIGNIFICANCE STATEMENTPunishment undergirds large-scale cooperation and helps dispense criminal justice. Yet it is currently unknown precisely how people assess the mental states of offenders, evaluate the harms they caused, and integrate those two components into a single punishment decision. Using a new design, we isolated these three processes, identifying the distinct brain systems and activities that enable each. Additional findings suggest that the amygdala plays a crucial role in mediating the interaction of mental state and harm information, whereas the dorsolateral prefrontal cortex plays a crucial, final-stage role, both in integrating mental state and harm information and in selecting a suitable punishment amount. These findings deepen our understanding of how punishment decisions are made, which may someday help to improve them.
Analysis, Performance, and Tension Perception of an Unmeasured Prelude for Harpsichord
Authors: Goodchild Meghan , Gingras Bruno , McAdams Stephen
Published: September 2016

This study focuses on the relationships between music analysis, performance, and tension perception. Part 1 examines harpsichordists’ analyses and performances of an unmeasured prelude—a semi-improvisatory genre open to interpretive freedom. Twelve harpsichordists performed the Prélude non mesuré No. 7 by Louis Couperin on a harpsichord equipped with a MIDI console and submitted a formal analysis. Using a curve-fitting approach, we investigated the correspondence between analyzed segmentations and group-final lengthening. We found that harpsichordists also employed “group-final anticipation,” involving deceleration before, and acceleration through, analyzed boundaries. In Part 2, three listener groups (harpsichordists, musicians, and nonmusicians) continuously rated tension for 12 performances. In contrast to measured music, local tension peaks, rather than troughs, occurred at boundaries featuring group-final lengthening. Associations were found between global tempo and tension ratings, with significant differences among the three listener groups. Performers expressed the large-scale structure through the amount of tempo variability, which was also reflected in tension rating variability.
Motor and Audiovisual Learning Consolidate Auditory Memory of Tonally Ambiguous Melodies
Authors: Schiavio Andrea , Timmers Renee
Published: September 2016

The present study investigated the role of motor and audiovisual learning in the memorization of four tonally ambiguous melodies for piano. A total of one hundred and twenty participants divided into three groups — pianists, other musicians (i.e., not pianists), and nonmusicians — learned the melodies through either playing them on a keyboard (playing condition), through performing the melodies on a piano without auditory feedback (silent playing condition), through watching a video with a performer playing the melodies (seeing condition), or through listening to them (control condition). Participants were exposed to each melody four times during the learning phase (in additional to hearing it once during a familiarization phase). This exposure consisted of an alternation between hearing the melody and engaging with the melody in the way determined by the learning condition. Participants in the control group only received the auditory aspect of the learning phase and listened to each melody twice. Memory of the melodies was tested after a 10-minute break. Our results indicate a benefit of motor learning for all groups of participants, suggesting that active sensorimotor experience plays a key role in musical skill acquisition.
Language Priming by Music and Speech
Authors: Jungers Melissa K. , Hupp Julie M. , Dickerson Sara D.
Published: September 2016

Some sounds from music and language follow domain-specific syntactic rules and may be processed by distinct brain regions. However, domain-general mechanisms may explain some connections between music and language. The current study tested how rate differences in music and language perception influence the subsequent production of speech. In two experiments, participants were primed with fast or slow sentences (Experiment 1) or melodies (Experiment 2) and then produced novel picture descriptions. Participants’ rate of production was influenced by the rate of the prime, both within-domain (language-language) and cross-domain (music-language). A shared mechanism for domain-general rate processing is proposed.
Moving Music
Authors: Kohn Dafna , Eitan Zohar
Published: September 2016

We examined how children (5- and 8-year-olds) associate changes in musical parameters with bodily motion, using movement and verbal tasks. In Task 1, participants moved to short musical stimuli involving bidirectional changes in pitch, loudness, or tempo. In Task 2, participants selected motion features appropriate to the same stimuli (forced-choice verbal task). In Task 1 the distribution of movement features significantly varied for different musical parameters: pitch change associated most strongly with vertical motion, loudness change with muscular energy and vertical motion, and tempo change with speed and muscular energy. In both tasks and for both ages, directions of change in motion and musical parameters correlated, e.g., increase in loudness was associated with increasing speed, increasing muscular energy, and spatial rise. The effect of pitch direction was mediated by temporal order, suggesting that overall pitch contour, rather than local direction only, affects bodily motion. Age affected responses to pitch direction, rather than loudness or tempo change. Results suggest that children consistently correlate musical and movement features through both verbal and motion responses, presenting an intricate web of auditory-motor-cognitive mappings.
Rhythm in the Speech and Music of Jazz and Riddim Musicians
Authors: Carpenter Angela C. , Levitt Andrea G.
Published: September 2016

Previous research has demonstrated similarities in the rhythmic characteristics of the speech and instrumental music within individual languages, such as French or English, but clear differences in these rhythmic patterns between languages. A recent finding has shown a comparable result for the rhythmic patterns of the spontaneous speech and instrumental music of musicians who speak different dialects of English, such that within-dialect speech and music rhythms are more similar to one another than are across-dialect rhythms. We extend the latter finding by comparing the rhythmic characteristics of the spontaneous speech and jazz productions of jazz musicians who speak American English with those of the spontaneous speech and riddim productions of Jamaican musicians, who speak Jamaican English. We found that the speech and music rhythmic patterns were similar within each dialect but different across dialects. Though scholars have suggested a link between speech prosody and jazz in the past, this is the first study known to us to demonstrate a link between the rhythmic properties of the speech and music of jazz musicians.
Natural mutations in IFITM3 modulate post‐translational regulation and toggle antiviral specificity
Authors: Compton Alex A , Roy Nicolas , Porrot Françoise , Billet Anne , Casartelli Nicoletta , Yount Jacob S , Liang Chen , Schwartz Olivier
Published: September 2016

The interferon‐induced transmembrane (IFITM) proteins protect host cells from diverse virus infections. IFITM proteins also incorporate into HIV‐1 virions and inhibit virus fusion and cell‐to‐cell spread, with IFITM3 showing the greatest potency. Here, we report that amino‐terminal mutants of IFITM3 preventing ubiquitination and endocytosis are more abundantly incorporated into virions and exhibit enhanced inhibition of HIV‐1 fusion. An analysis of primate genomes revealed that IFITM3 is the most ancient antiviral family member of the IFITM locus and has undergone a repeated duplication in independent host lineages. Some IFITM3 genes in nonhuman primates, including those that arose following gene duplication, carry amino‐terminal mutations that modify protein localization and function. This suggests that “runaway” IFITM3 variants could be selected for altered antiviral activity. Furthermore, we show that adaptations in IFITM3 result in a trade‐off in antiviral specificity, as variants exhibiting enhanced activity against HIV‐1 poorly restrict influenza A virus. Overall, we provide the first experimental evidence that diversification of IFITM3 genes may boost the antiviral coverage of host cells and provide selective functional advantages.
The echocardiography of replacement heart valves
Authors: Chambers John B.
Published: September 2016

This is a practical description of how replacement valves are assessed using echocardiography. Normal transthoracic appearances including normal variants are described. The problem of differentiating normal function, patient–prosthesis mismatch and pathological obstruction in aortic replacement valves with high gradients is discussed. Obstruction and abnormal regurgitation is described for valves in the aortic, mitral and right-sided positions and when to use echocardiography in suspected infective endocarditis. The roles of transoesophageal and stress echocardiography are described and finally when other imaging techniques may be useful.
The effects of radiofrequency electromagnetic radiation on sperm function
Authors: Houston B J , Nixon B , King B V , De Iuliis G N , Aitken R J
Published: September 2016

Mobile phone usage has become an integral part of our lives. However, the effects of the radiofrequency electromagnetic radiation (RF-EMR) emitted by these devices on biological systems and specifically the reproductive systems are currently under active debate. A fundamental hindrance to the current debate is that there is no clear mechanism of how such non-ionising radiation influences biological systems. Therefore, we explored the documented impacts of RF-EMR on the male reproductive system and considered any common observations that could provide insights on a potential mechanism. Among a total of 27 studies investigating the effects of RF-EMR on the male reproductive system, negative consequences of exposure were reported in 21. Within these 21 studies, 11 of the 15 that investigated sperm motility reported significant declines, 7 of 7 that measured the production of reactive oxygen species (ROS) documented elevated levels and 4 of 5 studies that probed for DNA damage highlighted increased damage due to RF-EMR exposure. Associated with this, RF-EMR treatment reduced the antioxidant levels in 6 of 6 studies that discussed this phenomenon, whereas consequences of RF-EMR were successfully ameliorated with the supplementation of antioxidants in all 3 studies that carried out these experiments. In light of this, we envisage a two-step mechanism whereby RF-EMR is able to induce mitochondrial dysfunction leading to elevated ROS production. A continued focus on research, which aims to shed light on the biological effects of RF-EMR will allow us to test and assess this proposed mechanism in a variety of cell types.
A role for seminal plasma in modulating pregnancy outcomes in domestic species
Authors: Bromfield John J
Published: September 2016

Seminal plasma is a complex fluid produced by the accessory glands of the male reproductive tract. Seminal plasma acts primarily as a transport medium for sperm on its arduous journey through the male and then female reproductive tract following ejaculation. This spermatozoan expedition will hopefully result in the meeting of and resultant fertilization of an oocyte, perpetuating the genetic lineage of both sexes. Whereas seminal plasma has historically been perceived as only a transport medium providing a nutrient-rich fluid environment for sperm during this exchange of genetic material, new insights into a complex communication pathway between males and females has been unraveled in the past 30 years. This new research suggests seminal plasma as a method to promote early pregnancy success by modulating cellular and molecular adaptions of the maternal environment required to facilitate healthy, successful pregnancy outcomes. Whereas much work on this exciting new communication process has focused on mice and translation to human reproduction, here we review the current evidence in domestic species where artificial insemination in the absence of seminal plasma is routine. Improving artificial insemination in domestic species to optimize offspring health and productivity could have far-reaching impacts on agriculturally relevant species such as cattle, sheep, pigs and horses.
Perceptions of dental students on introduction of simulation-based BLS teaching in their course
Authors: Ibnerasa Shazia , de Garve Willem
Published: September 2016

This article was migrated. The article was not marked as recommended. IntroductionMedical emergencies in dental clinic can be upsetting to any practicing dentist. Cardiac arrest requiring cardiopulmonary resuscitation (CPR) is one such medical emergency which can occur in dental office. Every dental practitioner therefore should at least be able to perform the basics of CPR. The purpose of the study was to demonstrate self-perceived perceptions of change in knowledge, skills and confidence level of 3rd year dental students after introduction of simulation based basic life support (BLS) teaching. It was assumed that after simulation based BLS teaching, dental students would feel more confident in providing immediate management to a patient of cardiac arrest during dental practice.Methods3rd year dental students attending General Medicine clinical rotation received two hours simulation based BLS teaching and perceptions of students were taken on a questionnaire, based on Likert scale. Change in self-perceived perceptions of knowledge, skills and confidence of students was analyzed.ResultsAnalysis showed that simulation based teaching significantly increases the level of knowledge, skills and self-perceived confidence of students regarding BLS skills.ConclusionThe study determined the perceived effectiveness of simulation based teaching in increasing the confidence level of dental students regarding performance of BLS skills in dental office.
EFEITOS DA ORIENTAÇÃO DA ATIVIDADE FÍSICA EM PACIENTES COM OSTEOARTRITE AVANÇADA DO JOELHO
Authors: Fernandes Ricardo de Souza Campos , Nogueira Monica Paschoal
Published: September 2016

RESUMO Introdução: A osteoartrite (OA) do joelho atinge 20% da população mundial e 70% a 80% dos indivíduos com mais de 65 anos. Caracteriza-se por dor e incapacidade funcional determinada pela degeneração da cartilagem articular e do osso subcondral. Seu tratamento conservador inclui a prática de exercícios físicos. Objetivo : Determinar os efeitos da prescrição e orientação da atividade física em pacientes com OA avançada do joelho. Métodos: Foram incluídos 23 pacientes submetidos a atividade física com orientação e avaliados no momento inicial, aos três e aos seis meses, pelo sistema de pontuação EVA e WOMAC (3 domínios). Foi utilizado o modelo linear generalizado e nas situações com diferença significante entre os tempos de avaliação, foram feitas comparações múltiplas com o teste de Bonferroni, com nível de significância de cinco por cento. Resultados : Houve diferença estatisticamente significante entre as pontuações EVA e WOMAC no início do estudo e aos três e seis meses. Esses resultados foram independentes do grau de OA e de doença uni ou bilateral. Conclusão : A orientação da atividade física no tratamento de pacientes com OA avançada de joelho, melhora a função articular e deve ser considerada inclusive nos casos com indicação de artroplastia.
BURNOUT E COPING EM ATLETAS DE VOLEIBOL: UMA ANÁLISE LONGITUDINAL
Authors: Pires Daniel Alvarez , Filho Maurício Gattás Bara , Debien Paula Barreiros , Coimbra Danilo Reis , Ugrinowitsch Herbert
Published: September 2016

RESUMO Introdução: No contexto esportivo, uma das principais recomendações para o melhor entendimento sobre a síndrome de burnout e o coping é a realização de estudos longitudinais que possam descrever o processo de desenvolvimento da síndrome e as estratégias empregadas para o seu enfrentamento. Objetivos: Analisar as percepções das dimensões de burnout e as estratégias de coping durante uma temporada esportiva, e correlacionar as características temporais de burnout e das estratégias de coping. Métodos: Mediante delineamento longitudinal, foram acompanhados 15 atletas profissionais de voleibol do sexo masculino (média de idade = 24,00 ± 3,55 anos) participantes da Superliga Nacional. Para mensurar as dimensões de burnout e as estratégias de coping foram utilizadas as versões traduzidas do Athlete Burnout Questionnaire e do Athletic Coping Skills Inventory. A coleta de dados foi realizada em quatro momentos de uma temporada esportiva. O comportamento dos indicadores de burnout e coping foi verificado através do teste de Friedman, com post hoc de Wilcoxon, enquanto que o coeficiente de correlação de Spearman (rho) foi empregado para verificar as correlações entre os indicadores de burnout e de coping. Resultados: Foi observado aumento significativo da desvalorização esportiva e do índice global de burnout com o transcorrer da temporada, porém não foram encontradas diferenças significativas no emprego das estratégias de coping nos quatro momentos. Foram observadas correlações inversas e significativas entre a dimensão de burnout, senso reduzido de realização esportiva e a estratégia de coping, confiança/motivação, em todos os momentos da temporada. Conclusão: Os achados evidenciaram aumento na percepção de burnout nos atletas a partir do acúmulo de treinamentos e competições, bem como da exigência por ótimo desempenho na competição-chave. O estudo também apontou a relevância do fator motivacional no surgimento do burnout.
Results after implementation of a protocol on the incidence of urinary tract infection in an intensive care unit
Authors: Miranda Anna Letícia , Oliveira Ana Lúcia Lyrio de , Nacer Daiana Terra , Aguiar Cynthia Adalgisa Mesojedovas
Published: September 2016

ABSTRACT Objective: to compare the results of urinary tract infection incidence, by means of the rate of indwelling urethral catheter use, and to identify microorganisms in urine cultures and surveillance cultures before and after the implementation of a clinical protocol for intensive care unit patients . Method: urinary tract infection is defined as a positive urine culture > 105 CFU/mL, notified by the hospital infection control service, six months before and after the implementation of the protocol. The sample consisted of 47 patients, 28 reported before and 19 after implementation. The protocol established in the institution is based on the Ministry of Health manual to prevent healthcare-related infections; the goal is patient safety and improving the quality of health services. Results: a negative linear correlation was observed between the later months of implementation and the reduction of reported cases of urinary tract infection, using the Spearman rank order coefficient (p = 0.045), and a reduction in the number of urine culture microorganisms (p = 0.026) using the Fisher exact test. Conclusion: educational interventions with implementation protocols in health institutions favor the standardization of maintenance of the invasive devices, which may reduce colonization and subsequent infections.
Tuberculosis control in people living with HIV/AIDS
Authors: Magnabosco Gabriela Tavares , Lopes Lívia Maria , Andrade Rubia Laine de Paula , Brunello Maria Eugênia Firmino , Monroe Aline Aparecida , Villa Tereza Cristina Scatena
Published: September 2016

ABSTRACT Objective: to analyze the offering of health actions and services for the control of tuberculosis for people living with HIV/AIDS being followed up in the Specialized Care Services for HIV/AIDS in Ribeirão Preto, SP, Brazil. Method: quantitative, exploratory survey study. Participated 253 people living with HIV/AIDS followed up by this service, considering as inclusion criteria: individuals older than 18 years living in the city and not inmates. Data collection was conducted from January 2012 to May 2013 through interviews with the support of a specific instrument. Data were analyzed using indicators and a composite index. Results: the offering of services for the control of tuberculosis in people living with HIV/AIDS by municipal services was considered as intermediate, reinforcing the need for better planning for comprehensive assistance, coordination of professionals in teams and among the services network, in addition to professional training and continuing education. Conclusion: it is necessary to implement strategies that promote shared actions between TB and HIV / AIDS programs and between different services in order to strengthen the local care network, aimed at producing an individualized care, comprehensive and responsive.