bluuebunny/crossref_metadata_2025 huggingface dataset:
Some considerations in the reconstruction of lead levels using laser ablation: lessons from the design stage of dendrochemistry study, St.John's, Canada
Authors: Danek Małgorzata , Bell Trevor , Laroque Colin P.
Published: January 2016

Study of soils in St. John’s, Canada showed elevated Pb levels representing a potential ex-posure risk for young children. Old trees growing in the city present a potential annually-resolved record of Pb levels over past centuries that provides important temporal and spatial dimensions to Pb exposure risk assessment. This paper reports the results of our analytical tests to develop a fast, relia-ble and cost-efficient method using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for measuring Pb concentration in annual tree rings from available tree species. Our tests focused on approaches to sample preparation as they affect the laser ablation process, the relative merits of the ablation sampling method, and the response of our available tree species, which have contrasting wood structures, to laser ablation. The range of annual Pb concentrations (ppm) measured for each of the study species were as follows: spruce (0.18–6.42); elm (0.12–7.91); and horse chestnut (0.40–14.09). Our results demonstrate that the cutting procedure for preparing tree cores produced the most consistent Pb concentrations of the three methods, although they each displayed problematic anomalies. The selection of the best laser ablation technique appears to be highly dependent on study species and goals. In general, spot analysis permits detailed and targeted studies of tree-ring struc-tures, but requires careful sampling attention for species with complex wood anatomy. The line scan method is ideal for reconstructing annually resolved element concentrations from trees and to some degree mitigates the complicating issue of intra-ring variability. Horse chestnut was determined to be the best of the available tree species because it exhibited a good response to laser ablation and pro-duced the lowest intra-ring variations in Pb concentration.
Intelligent Systems for Stabilizing Mode-Locked Lasers and Frequency Combs: Machine Learning and Equation-Free Control Paradigms for Self-Tuning Optics
Authors: Kutz J. Nathan , Brunton Steven L.
Published: January 2016

We demonstrate that a software architecture using innovations in machine learning
and adaptive control provides an ideal integration platform for self-tuning
optics. For mode-locked lasers, commercially available optical telecom
components can be integrated with servocontrollers to enact a training and
execution software module capable of self-tuning the laser cavity even in the
presence of mechanical and/or environmental perturbations, thus potentially
stabilizing a frequency comb. The algorithm training stage uses an exhaustive
search of parameter space to discover best regions of performance for one or
more objective functions of interest. The execution stage first uses a sparse
sensing procedure to recognize the parameter space before quickly moving to the
near optimal solution and maintaining it using the extremum seeking control
protocol. The method is robust and equationfree, thus requiring no detailed or
quantitatively accurate model of the physics. It can also be executed on a broad
range of problems provided only that suitable objective functions can be found
and experimentally measured.
Novel droplet near-field transducer for heat-assisted magnetic recording
Authors: Gosciniak Jacek , Mooney Marcus , Gubbins Mark , Corbett Brian
Published: January 2016

Two main ingredients of plasmonics are surface plasmon polaritons (SPP) and
localized surface plasmon resonances (LSPR) as they provide a high degree of
concentration of electromagnetic fields in the vicinity of metal surfaces, which
is well beyond that allowed by the diffraction limit of optics. Those properties
have been used in the new technique of heat assisted magnetic recording (HAMR)
to overcome an existing limit of conventional magnetic recording by utilizing a
near-field transducer (NFT). The NFT designs are based on excitation of surface
plasmons on a metal structure, which re-radiate with a subdiffraction limited
light spot confined in the near field. In this paper, we propose a novel
“droplet”-shaped NFT, which takes full advantage of a recenltly proposed
Mach–Zehnder Interferometer (MZI), a coupling arrangement that allows optimal
coupling of light to the transducer. The droplet design ensures better impedance
match with the recording media and, consequently, better coupling of power. The
droplet design results in very high enhancement of the electric field and allows
the confinement of light in a spot size much smaller than the present stateof-
the-art lollipop transducer.
Crystal structure of (2,5-dihydroxyphenyl)-(4-methoxyphenyl)methanone, C14H12O4
Authors: Benites Julio , Valderrama Jaime A. , Ríos David , Cárdenas Alejandro , Brito Iván
Published: January 2016

C14H12O4, orthorhombic, Pca21 (no. 29), a = 22.6015(12) Å, b = 7.1344(4) Å, c = 7.3789(4) Å, V = 1189.83(11) Å3, Z = 4, R
gt
(F) = 0.065, wR
ref
(F
2
) = 0.186, T = 298 K.
Crystal structure of (E)-2,4-dibromo-6-(((2-nitrophenyl)imino)methyl)phenol, C13H8Br2N2O3
Authors: Hong Yong , Huang Dushu , Liu Wei , Zhang Yinghong
Published: January 2016

C13H8Br2N2O3, monoclinic, P21/c (no. 14), a = 12.794(3) Å, b = 7.2041(15) Å, c = 14.862(3) Å, β = 93.355(5)°, V = 1367.5(5) Å3, Z = 4, R
gt
(F) = 0.0398, wR
ref
(F
2
) = 0.0938, T = 293 K.
Levofloxacin loaded gelrite-cellulose polymer based sustained ocular drug delivery: formulation, optimization and biological study
Authors: Aslam Mohammed , Imam Syed Sarim , Aqil Mohammed , Sultana Yasmin , Ali Asgar
Published: January 2016

In the present work, levofloxacin in situ gel formulation was developed using gelrite as a gelling agent in combination with hydroxy propyl methyl cellulose. The developed formulations were evaluated for physicochemical parameters, in vitro release, ex vivo transcorneal study, sterility testing, antimicrobial efficacy, ocular irritation study, histopathological and stability evaluation. The in vitro drug release study showed the extended drug release up to 12 h, and the best fit kinetic model was found to be Peppas model (R
2=0.9654), suggesting a Fickian diffusion process. The developed formulations showed optimized physicochemical results for all parameters. The optimized formulation showed therapeutically efficacious antimicrobial activity. Hens egg test-chorioallantoin membrane assay (HET-CAM) showed a mean score of 0.33 up to 24 h, which indicated the non-irritant property of the developed formulation. This non-irritant and stable in situ gel formulation of levofloxacin was found to be promising and safe for use as ocular delivery. The degradation rate constant and shelf life of developed optimized formulation (F14) were found to be low (1.213×10-4 at 25°C) and 2.14 years, respectively. This renders them favorable for ocular use as they would gel once in contact with the tear fluid, thus reducing nasolacrimal drainage, but would thin upon shearing, preventing ocular irritation and therefore induced lacrimation.
Effects of fiber surface modification on the friction coefficient of luffa fiber/polyester composites under dry sliding condition
Authors: Kalusuraman G. , Siva I. , Jappes J.T. Winowlin , Kumar S. Anand
Published: January 2016

In this study, the fiber extracted from the fruit of a luffa plant was used as a reinforcement to an unsaturated polyester resin matrix under two different fiber conditions. The untreated and alkali-treated fibers were impregnated and pressed to produce laminates. Composites were made with an optimal compression pressure of 5 MPa for 12 h of curing at room temperature. Ejected samples were cut according to the dimensions specified by the ASTM test specifications. To investigate the effects of fiber surface treatment on the frictional behavior of the produced composites under dry sliding wear conditions, wear test was conducted in a pin-on-disc equipment as per ASTM G99 at varying sliding velocities. In addition, hardness and un-notched impact strengths were measured and discussed. Results showed that the change in fiber surface morphology significantly changed the coefficient of friction of the composites. Moreover, the sliding distance had a prominent influence in increasing the friction between the composite and the counter face.
Improved fluorimetric measurement of uranium uptake and distribution in spring wheat (Triticum aestivum L.)
Authors: Borcia Cătălin , Popa Karin , Cecal Alexandru , Murariu Manuela
Published: January 2016

Uranium uptake and (radio)toxicity was tested on spring wheat (Triticum aestivum L.) in a laboratory study using differently
concentrated uranium nitrate solutions. Within these experiments, two analytical assays of uranium were comparatively tested: a fast
and improved fluorimetric assay and the classical colorimetric (U(IV)–arsenazo(III) complexation) one. During the germination, the
wheat seeds and plantlets supported well the uranium solutions of treatment within the entire concentration range
(1E-4–5E-3 M). Uranium proved to be non (radio)toxic to wheat as compared with other natural and anthropogenic
radiocations, probably because its uptake by spring wheat during the germination is low. Indeed, only a small fraction of uranium
administered was located within the roots, whereas the uranium content of the stems was negligible. A high correlation between the
results obtained by two analytical methods was found. However, the fluorimetric assay proved to be more reliable and fast, and
accurate.
The mental time travel continuum: on the architecture, capacity, versatility and extension of the mental bridge into the past and future
Authors: Breeden Prescott , Dere Dorothea , Zlomuzica Armin , Dere Ekrem
Published: January 2016

Mental time travel (MTT) is the ability to remember past events and to anticipate or imagine events in the future. MTT globally serves to optimize decision-making processes, improve problem-solving capabilities and prepare for future needs. MTT is also essential in providing our concept of self, which includes knowledge of our personality, our strengths and weaknesses, as well as our preferences and aversions. We will give an overview in which ways the capacity of animals to perform MTT is different from humans. Based on the existing literature, we conclude that MTT might represent a quantitative rather than qualitative entity with a continuum of MTT capacities in both humans and nonhuman animals. Given its high complexity, MTT requires a large processing capacity in order to integrate multimodal stimuli during the reconstruction of past and/or future events. We suggest that these operations depend on a highly specialized working memory subsystem, ‘the MTT platform’, which might represent a necessary additional component in the multi-component working memory model by Alan Baddeley.
Research on trajectory planning of non-developable surface for automated tape placement processing of composite
Authors: Liu Lin , Xiao Jun , Li Yong
Published: January 2016

Tape placement manufacturing process, as one of the automated forming technologies for composite material, not only substantially improves the productivity of composite component and reduces the cost of production significantly but also raises the reliability and stability of composite structure. Automated tape placement technology is mainly applied for manufacturing the fuselage and wing panel of airplane characterized by small curvature and large size. For these kinds of structural components with a non-developable surface, trajectory planning by “natural path” method could reduce the internal stress and improve the quality of composite products to a certain extent but not be optimized by quantitative characterization. On the basis of preliminary work, the theoretical model of “unnatural degree” (UD) is introduced in the first step, which could characterize the tensile and shear strain of the laying tape quantitatively. Secondly, by adjusting the iterative step and laying direction to diminish the UD, local stress could be softened in order to optimize the laying track. Ultimately, the simulation model of the non-developable surface is established under the Matlab software environment, and the “variable step-angle” algorithm is adopted to verify the adjustment effect of the tape-laying track.
Uniform entropy vs topological entropy
Authors: Dikranjan Dikran , Kunzi Hans-Peter A.
Published: January 2016

We discuss the connection between the topological entropy and the uniform entropy and answer several open questions from [10, 15]. We also correct several erroneous statements given in [10, 18] without proof.
Numerical Investigation of Transient Flow in a Prototype Centrifugal Pump during Startup Period
Authors: Zhang Yu-Liang , Zhu Zu-Chao , Dou Hua-Shu , Cui Bao-Ling , Li Yi , Zhou Zhao-Zhong
Published: January 2016

Transient performance of pumps during transient operating periods, such as startup and stopping, has drawn more and more attentions recently due to the growing engineering needs. During the startup period of a pump, the performance parameters such as the flow rate and head would vary significantly in a broad range. Therefore, it is very difficult to accurately specify the unsteady boundary conditions for a pump alone to solve the transient flow in the absence of experimental results. The closed-loop pipe system including a centrifugal pump is built to accomplish the self-coupling calculation. The three-dimensional unsteady incompressible viscous flow inside the passage of the pump during startup period is numerically simulated using the dynamic mesh method. Simulation results show that there are tiny fluctuations in the flow rate even under stable operating conditions and this can be attributed to influence of the rotor–stator interaction. At the very beginning of the startup, the rising speed of the flow rate is lower than that of the rotational speed. It is also found that it is not suitable to predict the transient performance of pumps using the calculation method of quasi-steady flow, especially at the earlier period of the startup.
Evaluation of astrocytoma cell proliferation using diffusion-weighted imaging: correlation with expression of proliferating cell nuclear antigen
Authors: Zhang Kai , Li Chuanfu , Liu Ying , Li Li , Meng Xiangshui , Feng Dechao , Ma Xiangxing
Published: January 2016

The purpose of this study was to analyze if there is a significant correlation between the results of diffusionweighted
imaging (DWI) and the expression of proliferating cell nuclear antigen (PCNA) in astrocytomas. The
DWI scans of 19 different-grade astrocytomas were obtained on a 3 T magnetic resonance scanner. The average
regional apparent diffusion coefficients (ADC) were measured. The positive expression of PCNA was determined
immunohistochemically by using streptavidin-peroxidase complex staining, and was quantified by calculating its
calibrated opacity density (COD) using an image analysis system. The average regional ADC and PCNA COD of low
grade and high grade astrocytomas were compared. Correlations between regional ADC and PCNA COD were
analyzed. The average regional ADC of high grade astrocytomas was significantly (t = 10.169, P = 0.000) less (0.687
± 0.225 x 10-3 mm2/s) than that of low grade astrocytomas (1.572 ± 0.333 x 10-3 mm2/s). The PCNA COD (0.343 ±
0.052) of high grade astrocytomas was significantly (t=-7.858, P=0.000) greater than that (0.194 ± 0.012) of low
grade astrocytomas. There were strong negative correlations between regional ADC and PCNA COD (r = -0.801,
P = 0.000). The results demonstrated that DWI is helpful in evaluating cell proliferation and preoperatively grading
astrocytomas by measuring regional ADC.
Investigations of the EPR Parameters and Local Lattice Structure for the Rhombic Cu2+ Centre in TZSH Crystal
Authors: Li Chao-Ying , Liu Shi-Fei , Fu Jin-Xian
Published: January 2016

The electron paramagnetic resonance (EPR) parameters [i.e. g factors g

i
(i=x, y, z) and hyperfine structure constants A

i
] and the local lattice structure for the Cu2+ centre in Tl2Zn(SO4)2·6H2O (TZSH) crystal were theoretically investigated by utilising the perturbation formulae of these parameters for a 3d9 ion under rhombically elongated octahedra. In the calculations, the admixture of d orbitals in the ground state and the ligand orbital and spin-orbit coupling interactions are taken into account based on the cluster approach. The theoretical EPR parameters show good agreement with the observed values, and the Cu2+–H2O bond lengths are obtained as follows: R

x
≈1.98 Å, R

y
≈2.09 Å, R

z
≈2.32 Å. The results are discussed.
First Principle Investigation of (Bi2O3)
n
Clusters With n = 6 − 9
Authors: Geudtner Gerald , Calaminici Patrizia , Köster Andreas M.
Published: January 2016

Ground state and low lying isomer structures of (Bi2O3)
n
clusters with
n = 6 − 9 were determined by first-principle calculations. These calculations were performed
with the LCGTO-ADFT method as implemented in the deMon2k program. Initial structures from
Born–Oppenheimer molecular dynamics trajectories were selected as starting points for local
geometry optimizations. The optimized structures where identified as minimum structures by
frequency analysis. Furthermore, the structural relation between the clusters is
presented. This work shows for the (Bi2O3)8 cluster a higher stability then
for the other clusters.
Structure of Glassy Ag–Ge–Se by Neutron Diffraction with Isotope Substitution
Authors: Zeidler Anita , Salmon Philip Stephen , Piarristeguy Andrea , Pradel Annie , Fischer Henry Edward
Published: January 2016

The structure of glassy Ag0.077Ge0.212Se0.711, which
lies at y = 0.077 on the
Ag
y
(Ge0.23Se0.77)1−y
tie-line,
was investigated by using the method of neutron diffraction with
silver isotope substitution. Two glass transition temperatures were
found from a characterisation of the material using modulated
differential scanning calorimetry, which indicates a mixed phase
material. The diffraction method provides site-specific information on
the Ag coordination environment, and gives an average of
3.5(1) Ag–Se nearest-neighbours with a bond distance
of 2.65(1) Å together with 0.9(1)
Ag–Ag next nearest-neighbours at a distance of
2.9(2) Å. The incorporation of silver does not
appear to have a marked effect on the coordination number of Se
to other matrix (Ge or Se) atoms, which supports the
notion that Ag forms dative bonds with Se lone-pair
electrons. A model is given for predicting the change in the Se
to matrix atom coordination number when a monovalent metal such as
Ag is added to a Se rich Ge–Se base
glass.
In VivoMRI Mapping of Brain Iron Deposition across the Adult Lifespan
Authors: Acosta-Cabronero Julio , Betts Matthew J. , Cardenas-Blanco Arturo , Yang Shan , Nestor Peter J.
Published: January 2016

Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map,in vivofor the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)—a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort ofN= 116 healthy adults (20–79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM–age associations were identified in several deep-brain nuclei—chiefly the striatum and midbrain—and across motor, premotor, posterior insular, superior prefrontal, and cerebellar cortices. The validity of QSM as a suitablein vivoimaging technique with which to monitor iron dysregulation in the human brain was demonstrated by confirming age-related increases in several subcortical nuclei that are known to accumulate iron with age. The study indicated that, in addition to these structures, there is a predilection for iron accumulation in the frontal lobes, which when combined with the subcortical findings, suggests that iron accumulation with age predominantly affects brain regions concerned with motor/output functions.

SIGNIFICANCE STATEMENTThis study used a whole-brain imaging approach known as quantitative susceptibility mapping (QSM) to provide a novel insight into iron accumulation in the brain across the adult lifespan. Validity of the method was demonstrated by showing concordance with ROI analysis and prior knowledge of iron accumulation in subcortical nuclei. We discovered that, beyond these regions, there is extensive involvement of the frontal lobes that has been missed by past ROI analyses. Broadly speaking, therefore, the motor system selectively accumulates iron with age. The results offer insights into the aging process, but also offer a new approach to studying the role of iron dysregulation in the evolution of age-related neurodegenerative diseases.
Dynamic Changes in Striatal mGluR1 But Not mGluR5 during Pathological Progression of Parkinson's Disease in Human Alpha-SynucleinA53TTransgenic Rats: A Multi-PET Imaging Study
Authors: Yamasaki Tomoteru , Fujinaga Masayuki , Kawamura Kazunori , Furutsuka Kenji , Nengaki Nobuki , Shimoda Yoko , Shiomi Satoshi , Takei Makoto , Hashimoto Hiroki , Yui Joji , Wakizaka Hidekatsu , Hatori Akiko , Xie Lin , Kumata Katsushi , Zhang Ming-Rong
Published: January 2016

Parkinson's disease (PD) is a prevalent degenerative disorder affecting the CNS that is primarily characterized by resting tremor and movement deficits. Group I metabotropic glutamate receptor subtypes 1 and 5 (mGluR1 and mGluR5, respectively) are important targets for investigation in several CNS disorders. In the present study, we investigated thein vivoroles of mGluR1 and mGluR5 in chronic PD pathology by performing longitudinal positron emission tomography (PET) imaging inA53Ttransgenic (A53T-Tg) rats expressing an abnormal human α-synuclein (ASN) gene.A53T-Tgrats showed a dramatic decline in general motor activities with age, along with abnormal ASN aggregation and striatal neuron degeneration. In longitudinal PET imaging, striatal nondisplaceable binding potential (BPND) values for [11C]ITDM (N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[11C]methylbenzamide), a selective PET ligand for mGluR1, temporarily increased before PD symptom onset and dramatically decreased afterward with age. However, striatal BPNDvalues for (E)-[11C]ABP688 [3-(6-methylpyridin-2-ylethynyl)-cyclohex-2-enone-(E)-O-[11C]methyloxime], a specific PET ligand for mGluR5, remained constant during experimental terms. The dynamic changes in striatal mGluR1 BPNDvalues also showed a high correlation in pathological decreases in general motor activities. Furthermore, declines in mGluR1 BPNDvalues were correlated with decreases in BPNDvalues for [18F]FE-PE2I [(E)-N-(3-iodoprop-2E-enyl)-2β-carbo-[18F]fluoroethoxy-3β-(4-methylphenyl) nortropane], a specific PET ligand for the dopamine transporter, a biomarker for dopaminergic neurons. In conclusion, our results have demonstrated for the first time that dynamic changes occur in mGluR1, but not mGluR5, that accompany pathological progression in a PD animal model.

SIGNIFICANCE STATEMENTSynaptic signaling by glutamate, the principal excitatory neurotransmitter in the brain, is modulated by group I metabotropic glutamate receptors, including the mGluR1 and mGluR5 subtypes. In the brain, mGluR1 and mGluR5 have distinct functional roles and regional distributions. Their roles in brain pathology, however, are not well characterized. Using longitudinal PET imaging in a chronic rat model of PD, we demonstrated that expression of mGluR1, but not mGluR5, dynamically changed in the striatum accompanying pathological PD progression. These findings imply that monitoring mGluR1in vivomay provide beneficial information to further understand central nervous system disorders.
The Matrix Proteins Hasp and Hig Exhibit Segregated Distribution within Synaptic Clefts and Play Distinct Roles in Synaptogenesis
Authors: Nakayama Minoru , Suzuki Emiko , Tsunoda Shin-ichi , Hama Chihiro
Published: January 2016

The synaptic cleft is the space through which neurotransmitters convey neural information between two synaptic terminals. This space is presumably filled with extracellular matrix molecules involved in synaptic function or differentiation. However, little is known about the identities of the matrix components, and it remains unclear how these molecules organize the matrix in synaptic clefts. In this study, we identified Hasp, aDrosophilasecretory protein containing CCP and WAP domains. Molecular genetic analysis revealed that Hasp diffuses extracellularly and is predominantly captured at synaptic clefts of cholinergic synapses. Furthermore, Hasp regulates levels of DLG and the nAChR subunits Dα6 and Dα7 at postsynaptic terminals. Hasp is required for trapping of another matrix protein, Hig, which is also secreted and diffused in the brain, at synaptic clefts of cholinergic synapses; however, Hig is dispensable for localization of Hasp at synaptic clefts. In addition, in the brains of triple mutants for the nAChR subunits Dα5, Dα6, and Dα7, the level of Hig, but not Hasp, was markedly reduced in synaptic regions, indicating that these nAChR subunits are required to anchor Hig to synaptic clefts. High-resolution microscopy revealed that Hasp and Hig exhibit segregated distribution within individual synaptic clefts, reflecting their differing roles in synaptogenesis. These data provide insight into how Hasp and Hig construct the synaptic cleft matrix and regulate the differentiation of cholinergic synapses, and also illuminate a previously unidentified architecture within synaptic clefts.

SIGNIFICANCE STATEMENTThe synapse has been extensively studied because it is essential for neurotransmission. By contrast, the space between the synaptic terminals, the synaptic cleft, is still an undeveloped research area despite its ubiquity in synapses. In fruit fly brains, we obtained evidence that the matrix protein Hasp and the previously identified Hig, both of which are secreted extracellularly, localize predominantly to synaptic clefts of cholinergic synapses, and modulate the levels of nAChR subunits on postsynaptic membranes. However, Hasp and Hig play differential roles in matrix formation and exhibit segregated distribution within synaptic clefts. These results reveal the molecular mechanisms of synaptic matrix construction and illuminate a molecular architecture within synaptic clefts previously unrevealed in any animal species.
Spontaneous Fluctuations in the Flexible Control of Covert Attention
Authors: Sali Anthony W. , Courtney Susan M. , Yantis Steven
Published: January 2016

Spontaneous fluctuations in cognitive flexibility are characterized by moment-to-moment changes in the efficacy of control over attentional shifts. We used fMRI to investigate the neural correlates in humans of spontaneous fluctuations in readiness to covertly shift attention between two peripheral rapid serial visual presentation streams. Target detection response time (RT) after a shift or hold of covert spatial attention served as a behavioral index of fluctuations in attentional flexibility. In particular, the cost associated with shifting attention compared with holding attention varied as a function of pretrial brain activity in key regions of the default mode network (DMN), but not the dorsal attention network. High pretrial activity within the DMN was associated with a greater increase in shift trial RT relative to hold trial RT, revealing that these areas are associated with a state of attentional stability. Conversely, high pretrial activity within bilateral anterior insula and the presupplementary motor area/supplementary motor area was associated with a greater decrease in shift trial RT relative to hold trial RT, reflecting increased flexibility. Our results importantly clarify the roles of the precuneus, medial prefrontal cortex, and lateral parietal cortex, indicating that reduced activity may not simply indicate greater task engagement, but also, specifically, a readiness to update the focus of attention. Investigation of the neural correlates of spontaneous changes in attentional flexibility may contribute to our understanding of disorders of cognitive control as well as healthy variability in the control of spatial attention.

SIGNIFICANCE STATEMENTIndividuals regularly experience fluctuations in preparatory cognitive control that affect performance in everyday life. For example, individuals are able to more quickly initiate a spatial shift of attention at some moments than at others. The current study revealed that pretrial brain activity in specific cortical regions predicted trial-by-trial changes in participants' abilities to flexibly shift the focus of attention. Intrinsically generated fluctuations in brain activity within several key default mode network regions, as well as within the anterior insula and presupplementary/supplementary motor areas, carried behavioral consequences for preparatory attentional control beyond lapses of attentional engagement. Our results are the first to link intrinsic variation in pretrial brain activity to moment-by-moment changes in preparatory attentional control over spatial selection.
Seizure-Induced Sympathoexcitation Is Caused by Activation of Glutamatergic Receptors in RVLM That Also Causes Proarrhythmogenic Changes Mediated by PACAP and Microglia in Rats
Authors: Bhandare Amol M. , Kapoor Komal , Pilowsky Paul M. , Farnham Melissa M.J.
Published: January 2016

Cardiovascular autonomic dysfunction in seizure is a major cause of sudden unexpected death in epilepsy. The catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) maintain sympathetic vasomotor tone and blood pressure through their direct excitatory projections to the intermediolateral (IML) cell column. Glutamate, the principal excitatory neurotransmitter in brain, is increased in seizures. Pituitary adenylate cyclase activating polypeptide (PACAP) is an excitatory neuropeptide with neuroprotective properties, whereas microglia are key players in inflammatory responses in CNS. We investigated the roles of glutamate, PACAP, and microglia on RVLM catecholaminergic neurons during the cardiovascular responses to 2 mg/kg kainic acid (KA)-induced seizures in urethane anesthetized, male Sprague Dawley rats. Microinjection of the glutamate antagonist, kynurenic acid (50 nl; 100 mM) into RVLM, blocked the seizure-induced 43.2 ± 12.6% sympathoexcitation (p≤ 0.05), and abolished the pressor responses, tachycardia, and QT interval prolongation. PACAP or microglia antagonists (50 nl) (PACAP(6–38), 15 pmol; minocycline 10 mg/ml) microinjected bilaterally into RVLM had no effect on seizure-induced sympathoexcitation, pressor responses, or tachycardia but abolished the prolongation of QT interval. The actions of PACAP or microglia on RVLM neurons do not cause sympathoexcitation, but they do elicit proarrhythmogenic changes. An immunohistochemical analysis in 2 and 10 mg/kg KA-induced seizure rats revealed that microglia surrounding catecholaminergic neurons are in a “surveillance” state with no change in the number of M2 microglia (anti-inflammatory). In conclusion, seizure-induced sympathoexcitation is caused by activation of glutamatergic receptors in RVLM that also cause proarrhythmogenic changes mediated by PACAP and microglia.

SIGNIFICANCE STATEMENTSudden unexpected death in epilepsy is a major cause of death in epilepsy. Generally, seizures are accompanied by changes in brain function leading to uncontrolled nerve activity causing high blood pressure, rapid heart rate, and abnormal heart rhythm. Nevertheless, the brain chemicals causing these cardiovascular changes are unknown. Chemicals, such as glutamate and pituitary adenylate cyclase activating polypeptide, whose expression is increased after seizures, act on specific cardiovascular nuclei in the brain and influence the activity of the heart, and blood vessels. Microglia, which manage excitation in the brain, are commonly activated after seizure and produce pro- and/or anti-inflammatory factors. Hence, we aimed to determine the effects of blocking glutamate, pituitary adenylate cyclase activating polypeptide, and microglia in the RVLM and their contribution to cardiovascular autonomic dysfunction in seizure.
Bilingual Language Control in Perception versus Action: MEG Reveals Comprehension Control Mechanisms in Anterior Cingulate Cortex and Domain-General Control of Production in Dorsolateral Prefrontal Cortex
Authors: Blanco-Elorrieta Esti , Pylkkänen Liina
Published: January 2016

For multilingual individuals, adaptive goal-directed behavior as enabled by cognitive control includes the management of two or more languages. This work used magnetoencephalography (MEG) to investigate the degree of neural overlap between language control and domain-general cognitive control both in action and perception. Highly proficient Arabic–English bilingual individuals participated in maximally parallel language-switching tasks in production and comprehension as well as in analogous tasks in which, instead of the used language, the semantic category of the comprehended/produced word changed. Our results indicated a clear dissociation of language control mechanisms in production versus comprehension. Language-switching in production recruited dorsolateral prefrontal regions bilaterally and, importantly, these regions were similarly recruited by category-switching. Conversely, effects of language-switching in comprehension were observed in the anterior cingulate cortex and were not shared by category-switching. These results suggest that bilingual individuals rely on adaptive language control strategies and that the neural involvement during language-switching could be extensively influenced by whether the switch is active (e.g., in production) or passive (e.g., in comprehension). In addition, these results support that humans require high-level cognitive control to switch languages in production, but the comprehension of language switches recruits a distinct neural circuitry. The use of MEG enabled us to obtain the first characterization of the spatiotemporal profile of these effects, establishing that switching processes begin ∼400 ms after stimulus presentation.

SIGNIFICANCE STATEMENTThis research addresses the neural mechanisms underlying multilingual individuals' ability to successfully manage two or more languages, critically targeting whether language control is uniform across linguistic domains (production and comprehension) and whether it is a subdomain of general cognitive control. The results showed that language production and comprehension rely on different networks: whereas language control in production recruited domain-general networks, the brain bases of switching during comprehension seemed language specific. Therefore, the crucial assumption of the bilingual advantage hypothesis, that there is a close relationship between language control and general cognitive control, seems to only hold during production.
Anxiety- and Depression-Like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice
Authors: Siopi Eleni , Denizet Marie , Gabellec Marie-Madeleine , de Chaumont Fabrice , Olivo-Marin Jean-Christophe , Guilloux Jean-Philippe , Lledo Pierre-Marie , Lazarini Françoise
Published: January 2016

Numerous clinical reports underscore the frequency of olfactory impairments in patients suffering from major depressive disorders (MDDs), yet the underlying physiopathological mechanisms remain poorly understood. We hypothesized that one key link between olfactory deficits and MDD lies in hypercortisolemia, a cardinal symptom of MDD. Corticosterone (CORT) is known to negatively correlate with hippocampal neurogenesis, yet its effects on olfactory neurogenesis and olfaction remain unknown. Here we used a rodent model of anxiety/depression-like states, which is based on chronic CORT administration and studied the effects of the antidepressant fluoxetine (FLX) on behavior, olfaction, and adult neurogenesis in the dentate gyrus (DG), olfactory bulb (OB), and the olfactory epithelium (OE). Chronic CORT had no effect on cell proliferation in the OE or on olfactory sensory neurons projecting to the OB, but induced pronounced deficits in olfactory acuity, fine discrimination of odorants and olfactory memory. These alterations were accompanied by a significant decrease in the number of adult-born neurons in both the DG and OB. Remarkably, FLX not only reversed depression-like states as expected, but also improved olfactory acuity, memory, and restored impaired adult neurogenesis. However, fine olfactory discrimination was not restored. Morphological analysis of adult-born neurons in both the DG and the OB showed that dendritic complexity was not significantly affected by CORT, but was increased by FLX. These findings demonstrate an essential role for glucocorticoids in triggering olfactory impairments in MDD and highlight a novel therapeutic effect of FLX.

SIGNIFICANCE STATEMENTIncreasing clinical reports show that major depression is characterized by pronounced olfactory deficits, yet the underlying mechanisms remain unknown. In this work, we used an endocrine model of depression to study whether hypothalamic-pituitary-adrenal axis perturbation could be sufficient to provoke olfactory impairments. We found that chronic corticosterone not only induces marked deficits in olfactory acuity, fine discrimination and olfactory memory, but also significantly decreases bulbar and hippocampal neurogenesis. Importantly, the antidepressant fluoxetine restores both adult neurogenesis and depressive states, and improves most olfactory functions. Our data reveal that impairment of hypothalamic-pituitary-adrenal axis during depression can lead to olfactory deficits and that the neurogenic effects of selective serotonin reuptake inhibitor antidepressants can successfully restore certain olfactory functions.
De NovoEmergence of Odor Category Representations in the Human Brain
Authors: Qu Lisa P. , Kahnt Thorsten , Cole Sydni M. , Gottfried Jay A.
Published: January 2016

Categorization allows organisms to efficiently extract relevant information from a diverse environment. Because of the multidimensional nature of odor space, this ability is particularly important for the olfactory system. However, categorization relies on experience, and the processes by which the human brain forms categorical representations about new odor percepts are currently unclear. Here we used olfactory psychophysics and multivariate fMRI techniques, in the context of a paired-associates learning task, to examine the emergence of novel odor category representations in the human brain. We found that learning between novel odors and visual category information induces a perceptual reorganization of those odors, in parallel with the emergence of odor category-specific ensemble patterns in perirhinal, orbitofrontal, piriform, and insular cortices. Critically, the learning-induced pattern effects in orbitofrontal and perirhinal cortex predicted the magnitude of categorical learning and perceptual plasticity. The formation ofde novocategory-specific representations in olfactory and limbic brain regions suggests that such ensemble patterns subserve the development of perceptual classes of information, and imply that these patterns are instrumental to the brain's capacity for odor categorization.

SIGNIFICANCE STATEMENTHow the human brain assigns novel odors to perceptual classes and categories is poorly understood. We combined an olfactory-visual paired-associates task with multivariate pattern-based fMRI approaches to investigate thede novoformation of odor category representations within the human brain. The identification of emergent odor category codes within the perirhinal, piriform, orbitofrontal, and insular cortices suggests that these regions can integrate multimodal sensory input to shape category-specific olfactory representations for novel odors, and may ultimately play an important role in assembling each individual's semantic knowledge base of the olfactory world.
Myocardial Infarction Causes Transient Cholinergic Transdifferentiation of Cardiac Sympathetic Nerves via gp130
Authors: Olivas Antoinette , Gardner Ryan T. , Wang Lianguo , Ripplinger Crystal M. , Woodward William R. , Habecker Beth A.
Published: January 2016

Sympathetic and parasympathetic control of the heart is a classic example of norepinephrine (NE) and acetylcholine (ACh) triggering opposing actions. Sympathetic NE increases heart rate and contractility through activation of β receptors, whereas parasympathetic ACh slows the heart through muscarinic receptors. Sympathetic neurons can undergo a developmental transition from production of NE to ACh and we provide evidence that mouse cardiac sympathetic nerves transiently produce ACh after myocardial infarction (MI). ACh levels increased in viable heart tissue 10–14 d after MI, returning to control levels at 21 d, whereas NE levels were stable. At the same time, the genes required for ACh synthesis increased in stellate ganglia, which contain most of the sympathetic neurons projecting to the heart. Immunohistochemistry 14 d after MI revealed choline acetyltransferase (ChAT) in stellate sympathetic neurons and vesicular ACh transporter immunoreactivity in tyrosine hydroxylase-positive cardiac sympathetic fibers. Finally, selective deletion of the ChAT gene from adult sympathetic neurons prevented the infarction-induced increase in cardiac ACh. Deletion of the gp130 cytokine receptor from sympathetic neurons prevented the induction of cholinergic genes after MI, suggesting that inflammatory cytokines induce the transient acquisition of a cholinergic phenotype in cardiac sympathetic neurons.Ex vivoexperiments examining the effect of NE and ACh on rabbit cardiac action potential duration revealed that ACh blunted both the NE-stimulated decrease in cardiac action potential duration and increase in myocyte calcium transients. This raises the possibility that sympathetic co-release of ACh and NE may impair adaptation to high heart rates and increase arrhythmia susceptibility.

SIGNIFICANCE STATEMENTSympathetic neurons normally make norepinephrine (NE), which increases heart rate and the contractility of cardiac myocytes. We found that, after myocardial infarction, the sympathetic neurons innervating the heart begin to make acetylcholine (ACh), which slows heart rate and decreases contractility. Several lines of evidence confirmed that the source of ACh was sympathetic nerves rather than parasympathetic nerves that are the normal source of ACh in the heart. Global application of NE with or without ACh toex vivohearts showed that ACh partially reversed the NE-stimulated decrease in cardiac action potential duration and increase in myocyte calcium transients. That suggests that sympathetic co-release of ACh and NE may impair adaptation to high heart rates and increase arrhythmia susceptibility.
Calcium-Permeable AMPA Receptors Mediate the Induction of the Protein Kinase A-Dependent Component of Long-Term Potentiation in the Hippocampus
Authors: Park Pojeong , Sanderson Thomas M. , Amici Mascia , Choi Sun-Lim , Bortolotto Zuner A. , Zhuo Min , Kaang Bong-Kiun , Collingridge Graham L.
Published: January 2016

Two forms of NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) at hippocampal CA1 synapses can be distinguished based on their sensitivity to inhibitors of protein kinase A (PKA). The PKA-dependent form requires multiple episodes of high-frequency stimulation (HFS) or theta burst stimuli (TBS) with a spacing between episodes in the order of minutes. To investigate the mechanism by which spaced episodes induce the PKA-dependent form of LTP, we have compared, in interleaved experiments, spaced (s) and compressed (c) TBS protocols in the rat CA1 synapses. We find that LTP induced by sTBS, but not that induced by cTBS, involves the insertion of calcium-permeable (CP) AMPARs, as assessed using pharmacological and electrophysiological criteria. Furthermore, a single TBS when paired with rolipram [4-(3-(cyclopentyloxy)-4-methoxyphenyl)pyrrolidin-2-one], to activate PKA, generates an LTP that also involves the insertion of CP-AMPARs. These data demonstrate that the involvement of CP-AMPARs in LTP is critically determined by the timing of the induction trigger and is associated specifically with the PKA-dependent form of LTP.

SIGNIFICANCE STATEMENTLong-term potentiation is a family of synaptic mechanisms that are believed to be important for learning and memory. Two of the most extensively studied forms are triggered by the synaptic activation of NMDA receptors and expressed by changes in AMPA receptor function. They can be distinguished on the basis of their requirement for activation of a protein kinase, PKA. We show that the PKA-dependent form also involves the transient insertion of calcium-permeable AMPA receptors. These results have implications for relating synaptic plasticity to learning and memory and suggest a specific linkage between PKA activation and the rapid synaptic insertion of calcium-permeable AMPA receptors during long-term potentiation.
Transitions between Multiband Oscillatory Patterns Characterize Memory-Guided Perceptual Decisions in Prefrontal Circuits
Authors: Wimmer Klaus , Ramon Marc , Pasternak Tatiana , Compte Albert
Published: January 2016

Neuronal activity in the lateral prefrontal cortex (LPFC) reflects the structure and cognitive demands of memory-guided sensory discrimination tasks. However, we still do not know how neuronal activity articulates in network states involved in perceiving, remembering, and comparing sensory information during such tasks. Oscillations in local field potentials (LFPs) provide fingerprints of such network dynamics. Here, we examined LFPs recorded from LPFC of macaques while they compared the directions or the speeds of two moving random-dot patterns, S1 and S2, separated by a delay. LFP activity in the theta, beta, and gamma bands tracked consecutive components of the task. In response to motion stimuli, LFP theta and gamma power increased, and beta power decreased, but showed only weak motion selectivity. In the delay, LFP beta power modulation anticipated the onset of S2 and encoded the task-relevant S1 feature, suggesting network dynamics associated with memory maintenance. After S2 onset the difference between the current stimulus S2 and the remembered S1 was strongly reflected in broadband LFP activity, with an early sensory-related component proportional to stimulus difference and a later choice-related component reflecting the behavioral decision buildup. Our results demonstrate that individual LFP bands reflect both sensory and cognitive processes engaged independently during different stages of the task. This activation pattern suggests that during elementary cognitive tasks, the prefrontal network transitions dynamically between states and that these transitions are characterized by the conjunction of LFP rhythms rather than by single LFP bands.

SIGNIFICANCE STATEMENTNeurons in the brain communicate through electrical impulses and coordinate this activity in ensembles that pulsate rhythmically, very much like musical instruments in an orchestra. These rhythms change with “brain state,” from sleep to waking, but also signal with different oscillation frequencies rapid changes between sensory and cognitive processing. Here, we studied rhythmic electrical activity in the monkey prefrontal cortex, an area implicated in working memory, decision making, and executive control. Monkeys had to identify and remember a visual motion pattern and compare it to a second pattern. We found orderly transitions between rhythmic activity where the same frequency channels were active in all ongoing prefrontal computations. This supports prefrontal circuit dynamics that transitions rapidly between complex rhythmic patterns during structured cognitive tasks.