bluuebunny/crossref_metadata_2025_split huggingface dataset:
Error-Induced Blindness: Error Detection Leads to Impaired Sensory Processing and Lower Accuracy at Short Response–Stimulus Intervals
Authors: Buzzell George A. , Beatty Paul J. , Paquette Natalie A. , Roberts Daniel M. , McDonald Craig G. 
Published: February 2017

Empirical evidence indicates that detecting one's own mistakes can serve as a signal to improve task performance. However, little work has focused on how task constraints, such as the response–stimulus interval (RSI), influence post-error adjustments. In the present study, event-related potential (ERP) and behavioral measures were used to investigate the time course of error-related processing while humans performed a difficult visual discrimination task. We found that error commission resulted in a marked reduction in both task performance and sensory processing on the following trial when RSIs were short, but that such impairments were not detectable at longer RSIs. Critically, diminished sensory processing at short RSIs, indexed by the stimulus-evoked P1 component, was predicted by an ERP measure of error processing, the Pe component. A control analysis ruled out a general lapse in attention or mind wandering as being predictive of subsequent reductions in sensory processing; instead, the data suggest that error detection causes an attentional bottleneck, which can diminish sensory processing on subsequent trials that occur in short succession. The findings demonstrate that the neural system dedicated to monitoring and improving behavior can, paradoxically, at times be the source of performance failures.SIGNIFICANCE STATEMENTThe performance-monitoring system is a network of brain regions dedicated to monitoring behavior to adjust task performance when necessary. Previous research has demonstrated that activation of the performance monitoring system following incorrect decisions serves to improve future task performance. However, the present study provides evidence that, when perceptual decisions must be made rapidly (within approximately half a second of each other), activation of the performance-monitoring system is predictive of impaired task-related attention on the subsequent trial. The data illustrate that the cognitive demands imposed by error processing can interfere with, rather than enhance, task-related attention when subsequent decisions need to be made quickly.
Different CaV1.3 Channel Isoforms Control Distinct Components of the Synaptic Vesicle Cycle in Auditory Inner Hair Cells
Authors: Vincent Philippe F.Y. , Bouleau Yohan , Charpentier Gilles , Emptoz Alice , Safieddine Saaid , Petit Christine , Dulon Didier 
Published: February 2017

The mechanisms orchestrating transient and sustained exocytosis in auditory inner hair cells (IHCs) remain largely unknown. These exocytotic responses are believed to mobilize sequentially a readily releasable pool of vesicles (RRP) underneath the synaptic ribbons and a slowly releasable pool of vesicles (SRP) at farther distance from them. They are both governed by Cav1.3 channels and require otoferlin as Ca2+sensor, but whether they use the same Cav1.3 isoforms is still unknown. Using whole-cell patch-clamp recordings in posthearing mice, we show that only a proportion (∼25%) of the total Ca2+current in IHCs displaying fast inactivation and resistance to 20 μmnifedipine, al-type Ca2+channel blocker, is sufficient to trigger RRP but not SRP exocytosis. This Ca2+current is likely conducted by short C-terminal isoforms of Cav1.3 channels, notably Cav1.342Aand Cav1.343S, because their mRNA is highly expressed in wild-type IHCs but poorly expressed inOtof−/−IHCs, the latter having Ca2+currents with considerably reduced inactivation. Nifedipine-resistant RRP exocytosis was poorly affected by 5 mmintracellular EGTA, suggesting that the Cav1.3 short isoforms are closely associated with the release site at the synaptic ribbons. Conversely, our results suggest that Cav1.3 long isoforms, which carry ∼75% of the total IHC Ca2+current with slow inactivation and confer high sensitivity to nifedipine and to internal EGTA, are essentially involved in recruiting SRP vesicles. Intracellular Ca2+imaging showed that Cav1.3 long isoforms support a deep intracellular diffusion of Ca2+.SIGNIFICANCE STATEMENTAuditory inner hair cells (IHCs) encode sounds into nerve impulses through fast and indefatigable Ca2+-dependent exocytosis at their ribbon synapses. We show that this synaptic process involves long and short C-terminal isoforms of the Cav1.3 Ca2+channel that differ in the kinetics of their Ca2+-dependent inactivation and their relative sensitivity to thel-type Ca2+channel blocker nifedipine. The short C-terminal isoforms, having fast inactivation and low sensitivity to nifedipine, mainly control the fast fusion of the readily releasable pool (RRP); that is, they encode the phasic exocytotic component. The long isoforms, with slow inactivation and great sensitivity to nifedipine, mainly regulate the vesicular replenishment of the RRP; that is, the sustained or tonic exocytosis.
Astrocytic Orosomucoid-2 Modulates Microglial Activation and Neuroinflammation
Authors: Jo Myungjin , Kim Jong-Heon , Song Gyun Jee , Seo Minchul , Hwang Eun Mi , Suk Kyoungho 
Published: February 2017

Orosomucoid (ORM) is an acute-phase protein that belongs to the immunocalin subfamily, a group of small-molecule-binding proteins with immunomodulatory functions. Little is known about the role of ORM proteins in the CNS. The aim of the present study was to investigate the brain expression of ORM and its role in neuroinflammation. Expression of Orm2, but not Orm1 or Orm3, was highly induced in the mouse brain after systemic injection of lipopolysaccharide (LPS). Plasma levels of ORM2 were also significantly higher in patients with cognitive impairment than in normal subjects. RT-PCR, Western blot, and immunofluorescence analyses revealed that astrocytes are the major cellular sources of ORM2 in the inflamed mouse brain. Recombinant ORM2 protein treatment decreased microglial production of proinflammatory mediators and reduced microglia-mediated neurotoxicityin vitro. LPS-induced microglial activation, proinflammatory cytokines in hippocampus, and neuroinflammation-associated cognitive deficits also decreased as a result of intracerebroventricular injection of recombinant ORM2 proteinin vivo. Moreover, lentiviral shRNA-mediated Orm2 knockdown enhanced LPS-induced proinflammatory cytokine gene expression and microglial activation in the hippocampus. Mechanistically, ORM2 inhibited C-C chemokine ligand 4 (CCL4)-induced microglial migration and activation by blocking the interaction of CCL4 with C-C chemokine receptor type 5. Together, the results from our cultured glial cells, mouse neuroinflammation model, and patient studies suggest that ORM2 is a novel mediator of astrocyte–microglial interaction. We also report that ORM2 exerts anti-inflammatory effects by modulating microglial activation and migration during brain inflammation. ORM2 can be exploited therapeutically for the treatment of neuroinflammatory diseases.SIGNIFICANCE STATEMENTNeural cell interactions are important for brain physiology and pathology. Particularly, the interaction between non-neuronal cells plays a central role in regulating brain inflammation, which is closely linked to many brain disorders. Here, we newly identified orosomucoid-2 (ORM2) as an endogenous protein that mediates such non-neuronal glial cell interactions. Based on the critical role of astrocyte-derived ORM2 in modulating microglia-mediated neuroinflammation, ORM2 can be exploited for the diagnosis, prevention, or treatment of devastating brain disorders that have a strong neuroinflammatory component, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis.
Goal-Directed and Habit-Like Modulations of Stimulus Processing during Reinforcement Learning
Authors: Luque David , Beesley Tom , Morris Richard W. , Jack Bradley N. , Griffiths Oren , Whitford Thomas J. , Le Pelley Mike E. 
Published: February 2017

Recent research has shown that perceptual processing of stimuli previously associated with high-value rewards is automatically prioritized even when rewards are no longer available. It has been hypothesized that such reward-related modulation of stimulus salience is conceptually similar to an “attentional habit.” Recording event-related potentials in humans during a reinforcement learning task, we show strong evidence in favor of this hypothesis. Resistance to outcome devaluation (the defining feature of a habit) was shown by the stimulus-locked P1 component, reflecting activity in the extrastriate visual cortex. Analysis at longer latencies revealed a positive component (corresponding to the P3b, from 550–700 ms) sensitive to outcome devaluation. Therefore, distinct spatiotemporal patterns of brain activity were observed corresponding to habitual and goal-directed processes. These results demonstrate that reinforcement learning engages both attentional habits and goal-directed processes in parallel. Consequences for brain and computational models of reinforcement learning are discussed.SIGNIFICANCE STATEMENTThe human attentional network adapts to detect stimuli that predict important rewards. A recent hypothesis suggests that the visual cortex automatically prioritizes reward-related stimuli, driven by cached representations of reward value; that is, stimulus–response habits. Alternatively, the neural system may track the current value of the predicted outcome. Our results demonstrate for the first time that visual cortex activity is increased for reward-related stimuli even when the rewarding event is temporarily devalued. In contrast, longer-latency brain activity was specifically sensitive to transient changes in reward value. Therefore, we show that both habit-like attention and goal-directed processes occur in the same learning episode at different latencies. This result has important consequences for computational models of reinforcement learning.
Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache
Authors: Schain Aaron J. , Melo-Carrillo Agustin , Strassman Andrew M. , Burstein Rami 
Published: February 2017

Functioning of the glymphatic system, a network of paravascular tunnels through which cortical interstitial solutes are cleared from the brain, has recently been linked to sleep and traumatic brain injury, both of which can affect the progression of migraine. This led us to investigate the connection between migraine and the glymphatic system. Taking advantage of a novelin vivomethod we developed using two-photon microscopy to visualize the paravascular space (PVS) in naive uninjected mice, we show that a single wave of cortical spreading depression (CSD), an animal model of migraine aura, induces a rapid and nearly complete closure of the PVS around surface as well as penetrating cortical arteries and veins lasting several minutes, and gradually recovering over 30 min. A temporal mismatch between the constriction or dilation of the blood vessel lumen and the closure of the PVS suggests that this closure is not likely to result from changes in vessel diameter. We also show that CSD impairs glymphatic flow, as indicated by the reduced rate at which intraparenchymally injected dye was cleared from the cortex to the PVS. This is the first observation of a PVS closure in connection with an abnormal cortical event that underlies a neurological disorder. More specifically, the findings demonstrate a link between the glymphatic system and migraine, and suggest a novel mechanism for regulation of glymphatic flow.SIGNIFICANCE STATEMENTImpairment of brain solute clearance through the recently described glymphatic system has been linked with traumatic brain injury, prolonged wakefulness, and aging. This paper shows that cortical spreading depression, the neural correlate of migraine aura, closes the paravascular space and impairs glymphatic flow. This closure holds the potential to define a novel mechanism for regulation of glymphatic flow. It also implicates the glymphatic system in the altered cortical and endothelial functioning of the migraine brain.
Unresponsive Choline Transporter as a Trait Neuromarker and a Causal Mediator of Bottom-Up Attentional Biases
Authors: Koshy Cherian Ajeesh , Kucinski Aaron , Pitchers Kyle , Yegla Brittney , Parikh Vinay , Kim Youngsoo , Valuskova Paulina , Gurnani Sarika , Lindsley Craig W. , Blakely Randy D. , Sarter Martin 
Published: February 2017

Some rats [sign-trackers (STs)] are prone to attribute incentive salience to reward cues, which can manifest as a propensity to approach and contact pavlovian cues, and for addiction-like behavior. STs also exhibit poor attentional performance, relative to goal-trackers (GTs), which is associated with attenuated acetylcholine (ACh) levels in prefrontal cortex (Paolone et al., 2013). Here, we demonstrate a cellular mechanism, linked to ACh synthesis, that accounts for attenuated cholinergic capacity in STs. First, we found that electrical stimulation of the basal forebrain increased cortical choline transporter (CHT)-mediated choline transport in GTs, paralleled by a redistribution of CHTs to the synaptic plasma membrane. Neither increases in choline uptake nor translocation of CHTs occurred in STs. Second, and consistent with uptake/translocation alterations, STs demonstrated a reduced ability to support cortical ACh releasein vivocompared with GTs after reverse-dialysis to elevate extracellular potassium levels. Third, rats were significantly more likely to develop sign-tracking behavior if treated systemically before pavlovian conditioned approach training with the CHT inhibitor VU6001221. Consistent with its proposed mechanisms, administration of VU6001221 attenuated potassium-evoked ACh levels in prefrontal cortex measured within vivomicrodialysis. We propose that loss of CHT-dependent activation of cortical cholinergic activity in STs degrades top-down executive control over behavior, producing a bias for bottom-up or stimulus-driven attention. Such an attentional bias contributes to nonadaptive reward processing and thus identifies a novel mechanism that can support psychopathology, including addiction.SIGNIFICANCE STATEMENTThe vulnerability for addiction-like behavior has been associated with psychological traits, such as the propensity to attribute incentive salience to reward cues that is modeled in rats by sign-tracking behavior. Sign-trackers tend to approach and contact cues associated with reward, whereas their counterparts, the goal-trackers, have a preference for approaching the location of the reward. Here, we show that the capacity of presynaptic cholinergic synapses to respond to stimulation by elevating presynaptic choline uptake and releasing acetylcholine is attenuated in sign-trackers. Furthermore, pharmacological inhibition of choline transport induced sign-tracking behavior. Our findings suggest that reduced levels of cholinergic neuromodulation can mediate an attentional bias toward reward-related cues, thereby allowing such cues to exert relatively greater control over behavior.
LINGO-1 Regulates Oligodendrocyte Differentiation through the Cytoplasmic Gelsolin Signaling Pathway
Authors: Shao Zhaohui , Lee Xinhua , Huang Guanrong , Sheng Guoqing , Henderson Christopher E. , Louvard Daniel , Sohn Jiho , Pepinsky Blake , Mi Sha 
Published: February 2017

Differentiation and maturation of oligodendrocyte progenitor cells (OPCs) involve the assembly and disassembly of actin microfilaments. However, how actin dynamics are regulated during this process remains poorly understood. Leucine-rich repeat and Ig-like domain-containing Nogo receptor interacting protein 1 (LINGO-1) is a negative regulator of OPC differentiation. We discovered that anti-LINGO-1 antibody-promoted OPC differentiation was accompanied by upregulation of cytoplasmic gelsolin (cGSN), an abundant actin-severing protein involved in the depolymerization of actin filaments. Treating rat OPCs with cGSN siRNA reduced OPC differentiation, whereas overexpression of cGSN promoted OPC differentiationin vitroand remyelinationin vivo. Furthermore, coexpression of cGSN and LINGO-1 blocked the inhibitory effect of LINGO-1. Our study demonstrates that cGSN works downstream of LINGO-1 signaling pathway, which enhances actin dynamics and is essential for OPC morphogenesis and differentiation. This finding may lead to novel therapeutic approaches for the treatment of demyelinating diseases such as multiple sclerosis (MS).SIGNIFICANCE STATEMENTMyelin loss and subsequent axon degeneration contributes to a variety of neurological diseases, such as multiple sclerosis (MS). Understanding the regulation of myelination by oligodendrocytes is therefore critical for developing therapies for the treatment of MS. We previously demonstrated that leucine-rich repeat and Ig-like domain-containing Nogo receptor interacting protein 1 (LINGO-1) is a negative regulator of oligodendrocyte differentiation and that anti-LINGO-1 promotes remyelination in preclinical animal models for MS and in a phase II acute optic neuritis clinical trial (RENEW). The mechanism by which LINGO-1 regulates oligodendrocyte differentiation is unknown. Here, we demonstrate that LINGO-1 regulates oligodendrocyte differentiation and maturation through the cytoplasmic gelsolin signaling pathway, providing new drug targets for the treatment of demyelination diseases.
Mobile Introns Shape the Genetic Diversity of Their Host Genes
Authors: Repar Jelena , Warnecke Tobias 
Published: February 2017

AbstractSelf-splicing introns populate several highly conserved protein-coding genes in fungal and plant mitochondria. In fungi, many of these introns have...Self-splicing introns populate several highly conserved protein-coding genes in fungal and plant mitochondria. In fungi, many of these introns have retained their ability to spread to intron-free target sites, often assisted by intron-encoded endonucleases that initiate the homing process. Here, leveraging population genomic data from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Lachancea kluyveri, we expose nonrandom patterns of genetic diversity in exons that border self-splicing introns. In particular, we show that, in all three species, the density of single nucleotide polymorphisms increases as one approaches a mobile intron. Through multiple lines of evidence, we rule out relaxed purifying selection as the cause of uneven nucleotide diversity. Instead, our findings implicate intron mobility as a direct driver of host gene diversity. We discuss two mechanistic scenarios that are consistent with the data: either endonuclease activity and subsequent error-prone repair have left a mutational footprint on the insertion environment of mobile introns or nonrandom patterns of genetic diversity are caused by exonic coconversion, which occurs when introns spread to empty target sites via homologous recombination. Importantly, however, we show that exonic coconversion can only explain diversity gradients near intron–exon boundaries if the conversion template comes from outside the population. In other words, there must be pervasive and ongoing horizontal gene transfer of self-splicing introns into extant fungal populations.
Prevalence of tuberculosis among health care workers in tuberculosis specialized hospitals in China
Authors: Du Jian , Pang Yu , Ma Yan , Mi Fengling , Liu Yuhong , Li Liang 
Published: February 2017

Abstract

Objectives
Tuberculosis (TB) specialized hospitals are playing an increasingly important role in the diagnosis and treatment of patients with TB in China. This study aimed to investigate the prevalence of TB among health care workers (HCWs) in TB specialized hospitals in China.

Methods
We conducted a crosssectional survey to collect longitudinal information on the number of HCWs and patients with TB from HCWs among 203 TB hospitals in China.

Results
Overall, these 186 TB cases accounted for the incidence of 985 per 100,000 population. The prevalence ratios among medical professionals (PR = 2.40) and laboratory technicians (PR = 2.17) were significantly higher than other hospital staff (PR = 1.04). In addition, general hospitals with TB clinics had the highest prevalence ratio of TB (PR = 5.15), while designated TB hospitals had the lowest prevalence ratio (PR = 1.48).

Conclusion
Our findings demonstrated that HCWs are suffering from an increased risk of infection with TB in China, and medical professionals (physicians and nurses) and general hospitals with TB clinics have the highest prevalence ratio of TB.
Minimally Important Differences in Patient or Proxy-Reported Outcome Studies Relevant to Children: A Systematic Review
Authors: Ebrahim Shanil , Vercammen Kelsey , Sivanand Arunima , Guyatt Gordon H. , Carrasco-Labra Alonso , Fernandes Ricardo M. , Crawford Mark W. , Nesrallah Gihad , Johnston Bradley C. 
Published: February 2017

CONTEXT:
No study has characterized and appraised all anchor-based minimally important differences (MIDs) associated with patient-reported outcome (PRO) instruments in pediatric studies.

OBJECTIVE:
To complete a comprehensive systematic survey and appraisal of published anchor-based MIDs associated with PRO instruments used in children.

DATA SOURCES:
Medline, Embase, and PsycINFO (1989 to February 11, 2015).

STUDY SELECTION:
Studies reporting empirical ascertainment of anchor-based MIDs among PROs used in pediatric care.

DATA EXTRACTION:
All pertinent data items related to the characteristics of PRO instruments, anchors, and MIDs.

RESULTS:
Of 4179 unique citations, 30 studies (including 32 cohorts) proved eligible and reported on 28 unique PROs (8 generic, 13 disease-specific, 5 symptoms-specific, 2 function-specific), with 9 (32%) classified as patient-reported, 11 (39%) proxy-reported, and 8 (29%) both patient- and proxy-reported. Of the 30 studies, we rated 14 (44%) as providing highly credible estimates of the MID. Most cohorts (n = 20, 62%) recorded patients’ direct response to the target PRO and the use of an independent standard of comparison (n = 25, 78%). Most, however, failed to effectively report measurement properties of the anchor (n = 24, 75%).

LIMITATIONS:
We have not yet addressed the measurement properties of instrument to measure credibility; our search was restricted to 3 electronic sources, and we used a single data abstractor.

CONCLUSIONS:
Our study found 28 PROs that have been developed for children, with fewer than half providing credible estimates. Clinicians, clinical trialists, systematic reviewers, and guideline developers seeking to effectively summarize and interpret results of studies addressing PROs in child health are likely to find our comprehensive compendium of MIDs of use, both in providing best estimates of MIDs and identifying credible estimates.
Politização da criminalidade e vulnerabilidade social: entre os paradigmase da justiça criminal e da seletividade penal
Authors: Tourinho Luciano De Oliveira Souza , Sotero Ana Paula Da Silva , Lima Mariana Gomes , Nonato João Leles 
Published: February 2017

O contexto contemporâneo reforça a existência de um processo de politização da justiça, resultando no abandono do caráter jurisdicionalpelos atores judiciais, que passam a perseguir objetivos políticos, a partir da substituição dos critérios relativos ao âmbito legal por paradigmas de oportunidade. Dessa forma, o processo penal, em sua concretude, direciona-se às classes sociais mais vulneráveis, numa relação de seletividade por vulnerabilidade, implicação negativa da relação entre disponibilidade de recursos materiais ou simbólicos e o acesso às múltiplas oportunidades. O poder político é exercido, como regra, por indivíduos que integram classes dominantes da sociedade: são os interesses desta que costumam ser contemplados, gerando prejuízos às camadas sociais menos favorecidas. A presente construção teórica objetiva explorar a relação entre política e seu exercício arbitrário, a partir da criminalização de condutas de grupos selecionados, resultando da revisão de literatura atinente às temáticas abordadas, com utilização do método dialético e uma abordagem crítica.