bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuning the Brake While Raising the Stake: Network Dynamics during Sequential Decision-Making
Authors: Meder David , Haagensen Brian Numelin , Hulme Oliver , Morville Tobias , Gelskov Sofie , Herz Damian Marc , Diomsina Beata , Christensen Mark Schram , Madsen Kristoffer Hougaard , Siebner Hartwig Roman 
Published: May 2016

When gathering valued goods, risk and reward are often coupled and escalate over time, for instance, during foraging, trading, or gambling. This escalating frame requires agents to continuously balance expectations of reward against those of risk. To address how the human brain dynamically computes these tradeoffs, we performed whole-brain fMRI while healthy young individuals engaged in a sequential gambling task. Participants were repeatedly confronted with the option to continue with throwing a die to accumulate monetary reward under escalating risk, or the alternative option to stop to bank the current balance. Within each gambling round, the accumulation of gains gradually increased reaction times for “continue” choices, indicating growing uncertainty in the decision to continue. Neural activity evoked by “continue” choices was associated with growing activity and connectivity of a cortico-subcortical “braking” network that positively scaled with the accumulated gains, including pre-supplementary motor area (pre-SMA), inferior frontal gyrus, caudate, and subthalamic nucleus (STN). The influence of the STN on continue-evoked activity in the pre-SMA was predicted by interindividual differences in risk-aversion attitudes expressed during the gambling task. Furthermore, activity in dorsal anterior cingulate cortex (ACC) reflected individual choice tendencies by showing increased activation when subjects made nondefault “continue” choices despite an increasing tendency to stop, but ACC activity did not change in proportion with subjective choice uncertainty. Together, the results implicate a key role of dorsal ACC, pre-SMA, inferior frontal gyrus, and STN in computing the trade-off between escalating reward and risk in sequential decision-making.SIGNIFICANCE STATEMENTUsing a paradigm where subjects experienced increasing potential rewards coupled with increasing risk, this study addressed two unresolved questions in the field of decision-making: First, we investigated an “inhibitory” network of regions that has so far been investigated with externally cued action inhibition. In this study, we show that the dynamics in this network under increasingly risky decisions are predictive of subjects' risk attitudes. Second, we contribute to a currently ongoing debate about the anterior cingulate cortex's role in sequential foraging decisions by showing that its activity is related to making nondefault choices rather than to choice uncertainty.
A Respiration-Coupled Rhythm in the Rat Hippocampus Independent of Theta and Slow Oscillations
Authors: Lockmann André L. V. , Laplagne Diego A. , Leão Richardson N. , Tort Adriano B. L. 
Published: May 2016

During slow-wave sleep and deep anesthesia, the rat hippocampus displays a slow oscillation (SO) that follows “up-and-down” state transitions in the neocortex. There has been recent debate as to whether this local field potential (LFP) rhythm reflects internal processing or entrains with respiratory inputs. To solve this issue, here we have concomitantly recorded respiration along with hippocampal, neocortical, and olfactory bulb (OB) LFPs in rats anesthetized with urethane. During the course of anesthesia, LFPs transitioned between activity states characterized by the emergence of different oscillations. By jointly analyzing multisite LFPs and respiratory cycles, we could distinguish three types of low-frequency hippocampal oscillations: (1) SO, which coupled to neocortical up-and-down transitions; (2) theta, which phase-reversed across hippocampal layers and was largest at the fissure; and (3) a low-frequency rhythm with largest amplitude in the dentate gyrus, which coupled to respiration-entrained oscillations in OB and to respiration itself. In contrast, neither theta nor SO coupled to respiration. The hippocampal respiration-coupled rhythm and SO had frequency <1.5 Hz, whereas theta tended to be faster (>3 Hz). Tracheotomy abolished hippocampal respiration-coupled rhythm, which was restored by rhythmic delivery of air puffs into the nasal cavity. These results solve the apparent contradictions among previous studies by demonstrating that the rat hippocampus produces multiple types of low-frequency oscillations. Because they synchronize with different brain circuits, however, we postulate that each activity pattern plays a unique role in information processing.SIGNIFICANCE STATEMENTThe rat hippocampus exhibits a large-amplitude slow oscillation (<1.5 Hz) during deep sleep and anesthesia. It is currently debated whether this rhythm reflects internal processing with the neocortex or entrainment by external inputs from rhythmic nasal respiration, which has similar frequency. Here we reconcile previous studies by showing that the hippocampus can actually produce two low-frequency rhythms at nearby frequencies: one that indeed couples to respiration and another that is coupled to the neocortex. We further show that the respiration-coupled rhythm differs from theta oscillations. The results support a role for brain oscillations in connecting distant brain regions, and posit the respiratory cycle as an important reference for neuronal communication between olfactory and memory networks.
The Cerebral Network of Parkinson's Tremor: An Effective Connectivity fMRI Study
Authors: Dirkx Michiel F. , den Ouden Hanneke , Aarts Esther , Timmer Monique , Bloem Bastiaan R. , Toni Ivan , Helmich Rick C. 
Published: May 2016

Parkinson's resting tremor has been linked to pathophysiological changes both in the basal ganglia and in a cerebello-thalamo-cortical motor loop, but the role of those circuits in initiating and maintaining tremor remains unclear. Here, we test whether and how the cerebello-thalamo-cortical loop is driven into a tremor-related state by virtue of its connectivity with the basal ganglia. An internal replication design on two independent cohorts of tremor-dominant Parkinson patients sampled brain activity and tremor with concurrent EMG-fMRI. Using dynamic causal modeling, we tested: (1) whether activity at the onset of tremor episodes drives tremulous network activity through the basal ganglia or the cerebello-thalamo-cortical loop and (2) whether the basal ganglia influence the cerebello-thalamo-cortical loop through connectivity with the cerebellum or motor cortex. We compared five physiologically plausible circuits, model families in which transient activity at the onset of tremor episodes (assessed using EMG) drove network activity through the internal globus pallidus (GPi), external globus pallidus, motor cortex, thalamus, or cerebellum. In each family, we compared two models in which the basal ganglia and cerebello-thalamo-cortical loop were connected through the cerebellum or motor cortex. In both cohorts, cerebral activity associated with changes in tremor amplitude (using peripheral EMG measures as a proxy for tremor-related neuronal activity) drove network activity through the GPi, which effectively influenced the cerebello-thalamo-cortical loop through the motor cortex. We conclude that cerebral activity related to Parkinson's tremor first arises in the GPi and is then propagated to the cerebello-thalamo-cortical circuit.SIGNIFICANCE STATEMENTParkinson's resting tremor has been linked to pathophysiological changes both in the basal ganglia and in a cerebello-thalamo-cortical motor loop, but the role of those circuits in initiating and maintaining tremor remains unclear. Using dynamic causal modeling of concurrently collected EMG-fMRI data in two cohorts of Parkinson's patients, we showed that cerebral activity associated with changes in tremor amplitude drives network activity through the basal ganglia. Furthermore, the basal ganglia effectively influenced the cerebello-thalamo-cortical circuit through the motor cortex (but not the cerebellum). Our findings suggest that Parkinson's tremor-related activity first arises in the basal ganglia and is then propagated to the cerebello-thalamo-cortical circuit.
Caveolin-1 Is Critical for Lymphocyte Trafficking into Central Nervous System during Experimental Autoimmune Encephalomyelitis
Authors: Wu Hao , Deng Ruixia , Chen Xingmiao , Wong Waiman Connie , Chen Hansen , Gao Lei , Nie Yichu , Wu Wutian , Shen Jiangang 
Published: May 2016

Multiple sclerosis (MS) is a progressive autoimmune disease of the CNS with its underlying mechanisms not fully understood. In the present study, we tested the hypothesis that caveolin-1, a major membrane scaffolding protein, plays a critical role in the pathogenesis of experimental autoimmune encephalomyelitis, a laboratory murine model of MS. We found increased expression of caveolin-1 in serum and spinal cord tissues in association with disease incidence and severity in wild-type mice with active encephalomyelitis. After immunization, Cav-1 knock-out mice showed remarkable disease resistance with decreased incidence and clinical symptoms. Furthermore, Cav-1 knock-out mice had alleviated encephalitogenic T cells trafficking into the CNS with decreased expressions of adhesion molecules ICAM-1 and VCAM-1 within the lesions. In agreement within vivostudies,in vitroknockdown of caveolin-1 compromised the upregulation of ICAM-1 in endothelial cells, leading to the amelioration of the transendothelial migration of pathogenic TH1 and TH17 cells. Together, those results indicate that caveolin-1 serves as an active modulator of CNS-directed lymphocyte trafficking and could be a therapeutic target for neuroinflammatory diseases, such as multiple sclerosis.SIGNIFICANCE STATEMENTThe hallmark feature of neuroinflammatory diseases is the massive infiltrations of encephalitogenic leukocytes into the CNS parenchyma, a process that remains largely unclear. Our study demonstrates the critical contribution of caveolin-1 to encephalomyelitis pathogenesis and CNS-directed lymphocyte trafficking by modulation of adhesion molecules ICAM-1 and VCAM-1, highlighting the pathological involvement of caveolin-1 in neuroinflammatory diseases.
Neural Activity-Dependent Regulation of Radial Glial Filopodial Motility Is Mediated by Glial cGMP-Dependent Protein Kinase 1 and Contributes to Synapse Maturation in the Developing Visual System
Authors: Sild Mari , Van Horn Marion R. , Schohl Anne , Jia Dantong , Ruthazer Edward S. 
Published: May 2016

Radial glia in the developing optic tectum extend highly dynamic filopodial protrusions within the tectal neuropil, the motility of which has previously been shown to be sensitive to neural activity and nitric oxide (NO) release. Usingin vivotwo-photon microscopy, we performed time-lapse imaging of radial glial cells and measured filopodial motility in the intact albinoXenopus laevistadpole. Application of MK801 to block neuronal NMDA receptor (NMDAR) currents confirmed a significant reduction in radial glial filopodial motility. This reduction did not occur in glial cells expressing a dominant-negative form of cGMP-dependent protein kinase 1 (PKG1), and was prevented by elevation of cGMP levels with the phosphodiesterase type 5 inhibitor sildenafil. These results suggest that neuronal NMDAR activation results in the release of NO, which in turn modulates PKG1 activation in glial cells to control filopodial motility. We further showed that interfering with the function of the small GTPases Rac1 or RhoA, known to be regulated by PKG1 phosphorylation, decreased motility or eliminated filopodial processes respectively. These manipulations led to profound defects in excitatory synaptic development and maturation of neighboring neurons.SIGNIFICANCE STATEMENTRadial glia in the developing brain extend motile filopodia from their primary stalk. Neuronal NMDA receptor activity controls glial motility through intercellular activation of cGMP-dependent protein kinase 1 (PKG1) signaling in glial cells. Manipulating PKG1, Rac1, or RhoA signaling in radial gliain vivoto eliminate glial filopodia or impair glial motility profoundly impacted synaptogenesis and circuit maturation.
Photosensitization in Porphyrias and Photodynamic Therapy Involves TRPA1 and TRPV1
Authors: Babes Alexandru , Sauer Susanne K. , Moparthi Lavanya , Kichko Tatjana I. , Neacsu Cristian , Namer Barbara , Filipovic Milos , Zygmunt Peter M. , Reeh Peter W. , Fischer Michael J. M. 
Published: May 2016

Photosensitization, an exaggerated sensitivity to harmless light, occurs genetically in rare diseases, such as porphyrias, and in photodynamic therapy where short-term toxicity is intended. A common feature is the experience of pain from bright light. In human subjects, skin exposure to 405 nm light induced moderate pain, which was intensified by pretreatment with aminolevulinic acid. In heterologous expression systems and cultured sensory neurons, exposure to blue light activated TRPA1 and, to a lesser extent, TRPV1 channels in the absence of additional photosensitization. Pretreatment with aminolevulinic acid or with protoporphyrin IX dramatically increased the light sensitivity of both TRPA1 and TRPV1 via generation of reactive oxygen species. Artificial lipid bilayers equipped with purified human TRPA1 showed substantial single-channel activity only in the presence of protoporphyrin IX and blue light. Photosensitivity and photosensitization could be demonstrated in freshly isolated mouse tissues and led to TRP channel-dependent release of proinflammatory neuropeptides upon illumination. With antagonists in clinical development, these findings may help to alleviate pain during photodynamic therapy and also allow for disease modification in porphyria patients.SIGNIFICANCE STATEMENTCutaneous porphyria patients suffer from burning pain upon exposure to sunlight and other patients undergoing photodynamic therapy experience similar pain, which can limit the therapeutic efforts. This study elucidates the underlying molecular transduction mechanism and identifies potential targets of therapy. Ultraviolet and blue light generates singlet oxygen, which oxidizes and activates the ion channels TRPA1 and TRPV1. The disease and the therapeutic options could be reproduced in models ranging from isolated ion channels to human subjects, applying protoporphyrin IX or its precursor aminolevulinic acid. There is an unmet medical need, and our results suggest a therapeutic use of the pertinent antagonists in clinical development.
Corticothalamic Axons Are Essential for Retinal Ganglion Cell Axon Targeting to the Mouse Dorsal Lateral Geniculate Nucleus
Authors: Shanks James A. , Ito Shinya , Schaevitz Laura , Yamada Jena , Chen Bin , Litke Alan , Feldheim David A. 
Published: May 2016

Retinal ganglion cells (RGCs) relay information about the outside world to multiple subcortical targets within the brain. This information is either used to dictate reflexive behaviors or relayed to the visual cortex for further processing. Many subcortical visual nuclei also receive descending inputs from projection neurons in the visual cortex. Most areas receive inputs from layer 5 cortical neurons in the visual cortex but one exception is the dorsal lateral geniculate nucleus (dLGN), which receives layer 6 inputs and is also the only RGC target that sends direct projections to the cortex. Here we ask how visual system development and function changes in mice that develop without a cortex. We find that the development of a cortex is essential for RGC axons to terminate in the dLGN, but is not required for targeting RGC axons to other subcortical nuclei. RGC axons also fail to target to the dLGN in mice that specifically lack cortical layer 6 projections to the dLGN. Finally, we show that when mice develop without a cortex they can still perform a number of vision-dependent tasks.SIGNIFICANCE STATEMENTThe dorsal lateral geniculate nucleus (dLGN) is a sensory thalamic relay area that receives feedforward inputs from retinal ganglion cells (RGCs) in the retina, and feed back inputs from layer 6 neurons in the visual cortex. In this study we examined genetically manipulated mice that develop without a cortex or without cortical layer 6 axonal projections, and find that RGC axons fail to project to the dLGN. Other RGC recipient areas, such as the superior colliculus and suprachiasmatic nucleus, are targeted normally. These results provide support for a new mechanism of target selection that may be specific to the thalamus, whereby descending cortical axons provide an activity that promotes feedforward targeting of RGC axons to the dLGN.
Two-Locus Likelihoods Under Variable Population Size and Fine-Scale Recombination Rate Estimation
Authors: Kamm John A , Spence Jeffrey P , Chan Jeffrey , Song Yun S 
Published: May 2016

Abstract
Two-locus sampling probabilities have played a central role in devising an efficient composite-likelihood method for estimating fine-scale recombination rates. Due to mathematical and computational challenges, these sampling probabilities are typically computed under the unrealistic assumption of a constant population size, and simulation studies have shown that resulting recombination rate estimates can be severely biased in certain cases of historical population size changes. To alleviate this problem, we develop here new methods to compute the sampling probability for variable population size functions that are piecewise constant. Our main theoretical result, implemented in a new software package called LDpop, is a novel formula for the sampling probability that can be evaluated by numerically exponentiating a large but sparse matrix. This formula can handle moderate sample sizes (n≤50) and demographic size histories with a large number of epochs (D≥64). In addition, LDpop implements an approximate formula for the sampling probability that is reasonably accurate and scales to hundreds in sample size (n≥256). Finally, LDpop includes an importance sampler for the posterior distribution of two-locus genealogies, based on a new result for the optimal proposal distribution in the variable-size setting. Using our methods, we study how a sharp population bottleneck followed by rapid growth affects the correlation between partially linked sites. Then, through an extensive simulation study, we show that accounting for population size changes under such a demographic model leads to substantial improvements in fine-scale recombination rate estimation.
Synovial Chondromatosis
Authors: Neumann Julie A. , Garrigues Grant E. , Brigman Brian E. , Eward William C. 
Published: May 2016

➢ Synovial chondromatosis is a rare, benign condition of unknown etiology in which the synovium undergoes metaplasia leading to cartilaginous nodules that ultimately break free, mineralize, and even ossify.➢ The most commonly involved joint is the knee.➢ Patients may be asymptomatic or may present with pain, swelling, and limited range of motion.➢ Plain radiographs can be diagnostic and mineralized nodules are pathognomonic.➢ Recommended treatment involves arthroscopic or open removal of loose bodies with or without a synovectomy to prevent further articular and periarticular destruction and to relieve symptoms.
AVALIAÇÃO DOS REGISTROS DO NÚMERO DE CONSULTAS DE PRÉ-NATAL NO CARTÃO DA GESTANTE, SANITAS E SISPRENATAL
Authors: GONÇALVES LAÍSS ALMEIDA , COSTA LUDMILA CABRAL , FERREIRA VINÍCIUS LANNA , ABREU MERY SILVA 
Published: May 2016

Os diferentes Sistemas de Informações em Saúde devem fornecer informações confiáveis, pois subsidiam a organização de estratégias e políticas na área da saúde. Visando identificar a compatibilidade de dados nos indicadores de saúde relacionados à assistência ao pré-natal, decidimos avaliar os registros referentes ao número de consultas no cartão da gestante, SANITAS e no SISPRENATAL. A amostra foi composta por mulheres do município de Ipatinga que concluíram o pré-natal no período de 2011/12, que possuíam o cartão da gestante, registros no SANITAS e no SISPRENATAL. Os dados foram coletados por meio de relatórios dos sistemas e acesso direto ao cartão da gestante, coletados em unidades básicas de saúde previamente sorteadas. Sendo exportados para o epiinfo 3.5.3 e para o SPSS 15.0 para análise. Nesta pesquisa houve correlação significativa e mais elevada entre os registros contidos no cartão e no SANITAS. Não se pode observar correlação significativa entre os registros do cartão versus SISPRENATAL ou SANITAS versus SISPRENATAL, demonstrando baixa compatibilidade de dados entre eles. Palavras chaves: Pré-natal. Sistemas de informação. Compatibilidade de dados.
Evaluation of the Glutamine 27 Glutamic Acid Polymorphism in the Adrenoceptor β2 Surface Gene on Obesity and Metabolic Phenotypes in Taiwan
Authors: Hsiao Tun-Jen , Lin Eugene 
Published: May 2016

Background The single-nucleotide polymorphism (SNP), rs1042714 or glutamine 27 glutamic acid (Gln27Glu), in the adrenoceptor β2 surface ( ADRB2) gene has previously been examined for association with obesity with inconclusive results. The objective of this study was to determine whether the ADRB2 rs1042714 SNP could influence obesity and obesity-related metabolic traits in a Taiwanese population. Methods The ADRB2 rs1042714 SNP and obesity-related metabolic traits including blood pressure, total cholesterol, triglyceride, fasting glucose, waist circumference, and body mass index (BMI) were examined in 967 individuals with general health examinations. Results Our data revealed that the ADRB2 rs1042714 SNP exhibited a significant association with obesity among the subjects ( P = 0.021). Furthermore, the carriers of the GG genotype had a significantly higher BMI than those with the CC genotype (26.0 ± 5.6 vs 24.3 ± 3.8 kg/m2; P = 0.009) and those with the CG genotype (26.0 ± 5.6 vs 23.6 ± 3.3 kg/m2; P = 0.001). We also found a nominal association with systolic blood pressure ( P = 0.058) and triglyceride ( P = 0.055) levels in the ADRB2 rs1042714 SNP. Conclusions Our study indicates that the ADRB2 rs1042714 SNP may contribute to the risk of obesity and predict obesity-related metabolic traits such as BMI, triglyceride, and systolic blood pressure in Taiwanese subjects.
Neutrophil CD64 as a Diagnostic Marker of Sepsis in Neonates
Authors: Elawady Sanaa , Botros Shahira K. , Sorour Ashraf E. , Ghany Eman Abdel , Elbatran Gamal , Ali Raghdaa 
Published: May 2016

Background Sepsis in neonates hospitalized in the neonatal intensive care unit is a global problem and is a significant contributor to morbidity and mortality. Neutrophil surface CD64, the high-affinity Fc receptor, is quantitatively up-regulated during infection and sepsis. Objective Our goal in this prospective study was to measure the neutrophil CD64 in blood as an adjunct to our previously validated hematologic scoring system for detecting neonatal sepsis. Methods A prospective study enrolled newborns with documented sepsis (n = 25), clinical sepsis (n = 25), and control newborns (n = 25). C-reactive protein, neutrophil CD64, complete blood counts, and blood cultures were taken. Neutrophil CD64 was analyzed by flow cytometry. Results CD64 was significantly elevated in the groups with documented and clinical sepsis ( P < 0.001). CD64 had a sensitivity of 96%, a specificity of 100%, a positive predictive value of 96.2%, and a negative predictive value of 100% with a cutoff value of 45.8% and 46.0% in the confirmed and the clinical sepsis groups, respectively. Conclusions CD64 expression on neutrophils increases significantly in neonates with sepsis and can be considered a useful diagnostic marker for early diagnosis of neonatal infection as a single determination compared with other inflammatory markers.