bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Inactivation and Pharmacological Blockade of Sigma-1 Receptors Prevent Paclitaxel-Induced Sensory-Nerve Mitochondrial Abnormalities and Neuropathic Pain in Mice
Authors: Nieto Francisco R , Cendán Cruz M , Cañizares Francisco J , Cubero María A , Vela José M , Fernández-Segura Eduardo , Baeyens José M
Published: February 2014

Background:

Paclitaxel, a widely-used antineoplastic drug, produces a painful peripheral neuropathy that in rodents is associated with peripheral-nerve mitochondrial alterations. The sigma-1 receptor (σ1R) is a ligand-regulated molecular chaperone involved in mitochondrial calcium homeostasis and pain hypersensitivity. This receptor plays a key role in paclitaxel-induced neuropathic pain, but it is not known whether it also modulates mitochondrial abnormalities. In this study, we used a mouse model of paclitaxel-induced neuropathic pain to test the involvement of the σ1R in the mitochondrial abnormalities associated with paclitaxel, by using genetic (σ1R knockout mice) and pharmacologica (σ1R antagonist) approaches.

Results:

Paclitaxel administration to wild-type (WT) mice produced cold- and mechanical-allodynia, and an increase in the frequency of swollen and vacuolated mitochondria in myelinated A-fibers, but not in C-fibers, of the saphenous nerve. Behavioral and mitochondrial alterations were marked at 10 days after paclitaxel-administration and had resolved at day 28. In contrast, paclitaxel treatment did not induce allodynia or mitochondrial abnormalities in σ1R knockout mice. Moreover, the prophylactic treatment of WT mice with BD-1063 also prevented the neuropathic pain and mitochondrial abnormalities induced by paclitaxel.

Conclusions:

These results suggest that activation of the σ1R is necessary for development of the sensory nerve mitochondrial damage and neuropathic pain produced by paclitaxel. Therefore, σ1R antagonists might have therapeutic value for the prevention of paclitaxel-induced neuropathy.
Hydrology and public health: linking human leptospirosis and local hydrological dynamics in Trinidad, West Indies
Authors: Vega-Corredor Maria Cecilia , Opadeyi Jacob
Published: February 2014

Background

Human leptospirosis is currently one of the most widespread bacterial zoonoses and is the only epidemic-prone infection that can be transmitted directly from contaminated water. Transmission in humans is caused by direct or indirect contact with contaminated water, soil or infected urine, blood or tissue of carrier animals. Initial symptoms are similar with those suffered during influenza, dengue or viral hepatitis. As the disease progresses, internal organs can be compromised causing severe hemorrhages, organ failure and, potentially, death. Human leptospirosis is a growing global public health problem although, in endemic areas, it is considered a neglected disease. Hydrological factors, including rainfall and floods, have been frequently related to human leptospirosis. In the Caribbean, leptospirosis is endemic and it is a disease under surveillance. Based on confirmed cases, in Trinidad & Tobago the average annual incidence of human leptospirosis ranges between 1.78 to 1.84 cases per 100,000 population.

Methods

In this paper, we used Geographical Information System (GIS) analysis and Geographically Weighted Poisson Regression (GWPR) for the development of ecological models, to assess the spatial variability in the relationships between local hydrological factors and human leptospirosis occurrence at the community level on the island of Trinidad. Five explanatory covariates were developed for the analysis: rainfall, river drainage density, proportion of soil with free drainage, proportion of soil with imperfect/impeded drainage, and a topographic wetness index.

Results

The GWPR model presented an improvement (AICc = 392.46; deviance = 583.36) over the Global regression model (AICc = 595.52; deviance = 381.78), indicating spatial variability in the relationship of human leptospirosis and hydrological factors. Pseudo t-values of rainfall, imperfect/impeded drainage soil and the topographic wetness index showed high values (|t| >1.96) indicating that local relationships with leptospirosis occurrence may be significant.

Conclusion

Results suggest that rainfall, imperfect/impeded drainage soil and topographic wetness index influence the local dynamics of human leptospirosis.
Lateral light transfer ensures efficient resource distribution in symbiont-bearing corals
Authors: Wangpraseurt Daniel , Larkum Anthony W. D. , Franklin Jim , Szabó Milán , Ralph Peter J. , Kühl Michael
Published: February 2014

Coral tissue optics has received very little attention in the past, although the interaction between tissue and light is central to our basic understanding of coral physiology. Here we used fibre-optic and electrochemical microsensors along with variable chlorophyll fluorescence imaging to directly measure lateral light propagation within living coral tissues. Our results show that corals can transfer light laterally within their tissues to a distance of ~2 cm. Such light transport stimulates O2 evolution and photosystem II operating efficiency in areas >0.5–1 cm away from direct illumination. Light is scattered strongly in both coral tissue and skeleton, leading to photon trapping and lateral redistribution within the tissue. Lateral light transfer in coral tissue is a new mechanism by which light is redistributed over the coral colony and we argue that tissue optical properties are one of the key factors in explaining the high photosynthetic efficiency of corals.
GR-communications in St. Petersburg Mass Media Discourse
Authors: Быков  , Bykov Ilya
Published: February 2014

Problems of modern GR-communications are considered in this paper

through the example of St. Petersburg mass media. In the last few years

in St. Petersburg is occuring something what might be called a birth of GRprofessionals’

regional community, which has been culminated by creation

of GR-Club at St. Petersburg State University in autumn 2013. However, as

shown by results of a content analysis study, the mass media had a negative

image of public relations, government relations and lobbying as types

of communication activities.
Argumentation Representatives in German Scientific Text
Authors: Кремер  , Kremer Inessa
Published: February 2014

The paper deals with the study related to linguistic representation of argumentation in German scientific text. The structure of argumentation in scientific reviews from German journals «Lebende Sprachen», «Muttersprache», «Zeitschrift fr Phonetik, Sprachwissenschaft und Kommunikationsforschung », «Zielsprache Deutsch», which are the objects of study, has been presented in this paper. Argumentation in a scientific critical text is not just a logical procedure but also a kind of activity performed by a reviewer. Argumentation demonstrates an evaluative reasoning, where reasonable and emotional evaluations are expressed in a variety of ways and at the same time they have standard norms. It should be call information sharing, verification, evaluation and persuasion as main components of argumentation process, where the persuasion is a dominant component in the scientific text interpretation.
Indistinct Comparison of Texts by Modified Method of q-grams
Authors: Ельцова  , Eltsova M. , Гашков  , Gashkov Alexander
Published: February 2014

The paper is devoted to indistinct comparison of texts by means of q-grams and Bloom’s-filter on a material of official, art and scientific texts in Russian. The suggested method allows assess texts’ similarity approximately.
Socially engaged art practice and character education: Understanding others through visual art
Authors: Hyungsook Kim
Published: February 2014

This article examines to what extent socially engaged art practice encourages students by promoting creativity, a sense of citizen responsibility, critical thinking, reflection, an interest in social justice, and consideration of people living in the local community, and ultimately contributing significantly to character education. In community-based art education, which enables the building of character, learners overcome the limitations of knowledge-oriented education to understand others, thus adding more meaning to their lives and helping them cultivate democratic citizenship so that they may serve society. This article discusses a key feature of socially engaged art practice through a case study by focusing on the service learning of an alternative school for North Korean adolescent refugees. The theoretical roots of socially engaged art practice and service learning for developing democratic citizenship are examined. The case of art education at alternative schools for North Korean adolescent refugees is discussed through the lens of community-based art education. North Korean adolescent refugees and South Korean graduate school students taught and were taught through reciprocal participation in service learning.
Kindergarten and school as a learning environment for art
Authors: Nevanen Saila , Juvonen Antti , Ruismäki Heikki
Published: February 2014

This article focuses on kindergartens and schools as art educational environments. They were explored from three points of view: the physical environment, the social environment and the pedagogical environment created by the thinking and activities of teachers and artists. A multidimensional evaluation is used to analyse the data. (Interviews of artists and teachers (n=18), final reports (n=9), follow-up material from an art project in Helsinki beginning in 2000.) The project targeted children in kindergarten (3–6 years old) and in the first grades in school (7-9 years old) and included visual art, environmental art, literary art, drama, circus and architectural elements. School, kindergarten and the immediate surroundings offered an opportunity for a diversified cooperative achievement. The children proved to be skilful and significant members of society in carrying out their art projects.
Los matrimonios mixtos en España ¿espacios de construcción intercultural?
Authors: Albert Guardiola María Carmen , Masanet Ripoll Erika
Published: February 2014

El objetivo del artículo es plantear el contexto teórico de las características que envuelven el fenómeno de las familias multiculturales, es decir, aquellas familias en las que el origen étnico o la primera nacionalidad de uno de los miembros de la pareja no es la española (también llamadas parejas o matrimonios mixtos). Se trata de analizar las consecuencias que se derivan de la diversidad cultural, más allá de la cuantificación del hecho migratorio y presentar la metodología del estudio financiado por el Ministerio de Educación y Ciencia.
Estimation of forest biomass by means of genetic algorithm-based optimization of airborne laser scanning and digital aerial photograph features
Authors: Tuominen Sakari , Haapanen Reija
Published: February 2014

Information on forest biomass is required for several purposes, including estimation of forest bioenergy resources and forest carbon stocks. Airborne laser scanning is today considered the most accurate remote sensing method for forest inventory. The three-dimensional nature of laser scanning data enables estimation of the volumes of the tree canopies. The dimensions of the tree canopies show high correlation with the amount of forest biomass. Optical aerial photographs are often used to complement laser data, for improved distinction between tree species. The paper reports on a study testing the estimation of forest biomass variables in two study areas in Southern Finland. The biomass variables were derived on the basis of tree-level field measurements, with biomass models used for pine, spruce, and birch. The sample-plot-level biomass components were derived on the basis of tree-level data and used as reference data for airborne-laser- and aerialâphotograph-based estimation. Results were slightly better for total biomass (RMSE 22.5% and 23.6% for the two study areas) than total volume (RMSE: 23.4% and 26.1%). Species-specific estimation errors were large in general but varied between the study areas, because of differences in their forest structures.
An assessment of three variance estimators for the k-nearest neighbour technique
Authors: Magnussen Steen
Published: February 2014

A jackknife (JK), a bootstrap (BOOT), and an empirical difference estimator (EDE) of totals and variance were assessed in simulated sampling from three artificial but realistic complex multivariate populations (Nâ=â8000 elements) organized in clusters of four elements. Intra-cluster correlations of the target variables (Y) varied from 0.03 to 0.26. Time-saving implementations of JK and BOOT are detailed. In simple random sampling (SRS), bias in totals was â¤ 0.4% for the two largest sample sizes (nâ=â200, 300), but slightly larger for nâ=â50, and 100. In cluster sampling (CLU) bias was typically 0.1% higher and more variable. The lowest overall bias was in EDE. In both SRS and CLU, JK estimates of standard error were slightly (3%) too high, while the bootstrap estimates in both SRS and CLU were too low (8%). Estimates of error suggested a trend in EDE toward an overestimation with increasing sample size. Calculated 95% confidence intervals achieved a coverage that in most cases was fairly close (Â±â2%) to the nominal level. For estimation of a population total the EDE estimator appears to be slightly better than the JK estimator.
Comparing the efficiency of drum and disc chippers
Authors: Spinelli Raffaele , Cavallo Eugenio , Eliasson Lars , Facello Alessio
Published: February 2014

The study compared the effect of chipper type on productivity, power demand, fuel consumption and product quality. Tests were conducted on two commercial chipper models, a disc and a drum chipper. Both chippers had the same diameter capacity, were applied to the same tractor and fed with the same feedstock types. Fifteen replications were conducted per machine and for each of four different feedstock types, reaching a total of 120 tests. The disc chipper had a higher energy efficiency and used 19% less fuel per unit product, possibly due to its simpler design, integrating comminuting and discharge system in one synergic device. In contrast, the drum chipper was 8% more productive, since it cut with the same energy all along the length of its knives. The drum chipper produced smaller chips, with a higher incidence of fines. Feedstock type had a strong effect on productivity, energy efficiency and product quality. The effect of feedstock type was mainly related to piece size, and may be stronger than the effect of chipper type. Further studies should determine the effect of blade wear on the relative performance of the two chipper types.
Tree biomass and soil carbon stocks in indigenous forests in comparison to plantations of exotic species in the Taita Hills of Kenya
Authors: Omoro Loice , Starr Mike , Pellikka Petri
Published: February 2014

Carbon (C) densities of the tree biomass and soil (0â50 cm) in indigenous forest and plantations of eucalyptus, cypress and pine in the Taita Hills, Kenya were determined and compared. The cypress and pine plantations were about 30-years-old and eucalyptus plantations about 50-years-old. Biomass C densities were estimated from breast height diameter and wood density using allometric functions developed for tropical species and an assumed C content of 50%. Belowground biomass C densities were estimated using root:shoot biomass ratios. Soil organic C (SOC) densities were calculated from measured organic carbon contents (0â20 and 20â50 cm layers) and modelled bulk density values. Mean total biomass C and SOC densities for indigenous forest were greater than those of the plantations, and the difference was significant (pâ<â0.05) in the cases of cypress and pine biomass and pine SOC. The correlation between biomass C and SOC densities was nearly significant in the case of indigenous forest, but negative. Biomass C densities were not significantly correlated with mean annual precipitation, mean annual temperature or potential evapotranspiration, but pine biomass C densities were significantly correlated to actual evapotranspiration. SOC densities were more strongly correlated to mean annual precipitation than biomass C densities, but only significantly so in the case of pine. Neither biomass C nor SOC densities were correlated to plant available water capacity of the soil. Indigenous forest SOC densities were significantly correlated to soil clay contents, but negatively. Indigenous forests sequester more C in biomass and soil than do 30 to 50-year-old plantations of exotics, but it remains unclear if this is an intrinsic difference between indigenous forest and plantations of exotics or because of insufficient time for SOC levels in plantations to recover after clearance of original indigenous forest.
Evaluation of the double normal distribution for tree diameter distribution modeling
Authors: Zasada Michał
Published: February 2014

The double normal distribution consists of two normal distributions truncated at their means and then combined in such a way, that points of truncation now become the overall distribution mode. So far, parameters of the double normal distribution have been estimated exclusively using the method of moments. This study evaluates the maximum likelihood method for the estimation of the double normal distribution parameters in Scots pine stands in Poland, and compares it to the results of the method of moments and the two-parameter Weibull distribution fitted using the maximum likelihood method and the method of moments. Presented results show that it is not recommended to use the maximum likelihood method of parameter fitting with Nelder-Mead and quasi-Newton optimization algorithms for the double normal distribution for small samples. However, it can be used for large samples, giving the fit comparable to the two-parameter Weibull distribution and providing parameters having sound practical and biological meaning. In the case of smaller samples for the double normal distribution it is recommended to apply the maximum likelihood method with the alternative simulated annealing optimization algorithm, use the method of moments or substitute the described distribution with more the flexible and robust Weibull distribution. For the smaller samples, the method of moments was superior to the maximum likelihood method.
Estimating coarse roots biomass in young silver birch stands on post-agricultural lands in central Poland
Authors: Bijak Szymon , Zasada Michał , Bronisz Agnieszka , Bronisz Karol , Czajkowski Maciej , Ludwisiak Łukasz , Tomusiak Robert , Wojtan Rafał
Published: February 2014

Study analyses coarse (d>2 mm of diameter) roots biomass dynamics in young succession stands of silver birch ( Roth) growing on abandoned farmlands in central Poland. Research material based on 181 sample trees, which were gathered in 20 pure silver birch stands in 5 locations. The age of the trees varied from 1 to 16 years. Coarse roots biomass of the investigated trees ranged from 0.7 to 4305.5 g/tree (422.6 g/tree on average) showing great variability (coefficient of variation equals 185%). A clear dependence of belowground biomass on the age and size of a tree was observed. Root-to-shoot ratio values vary from 0.1 to 1.0 with evidence of a tendency to decrease with increasing age, diameter at the breast height and height of analysed trees. An allometric equation was elaborated for the estimation of belowground biomass based on height or diameter at breast height of young silver birches. The suitability of this formula should be considered for the estimation of biomass accumulation and carbon sequestration by young successional silver birch stands growing on abandoned agricultural lands.Betula pendula
Comparative Study of Energy Harvesting from ZnO Nanorods Using Different Flexible Substrates
Authors: Hussain Mushtaque , Abbasi Mazhar Ali , Khan Azam , Nur Omer , Willander Magnus
Published: February 2014

The step toward the fabrication of nanodevices with low cost and improved performance is of high demand; therefore, in the present study, different flexible substrates like common paper, textile fabric, plastic and aluminum foil have been utilized to harvest electrical energy. ZnO nanorods (NRs) were grown by using low-temperature aqueous chemical growth method. The obtained ZnO NRs were highly dense, well aligned, uniformly distributed over the substrates and exhibited good crystal quality. The structural study was carried out by using X-ray powder diffraction and scanning electron microscopy. The piezoelectric properties of ZnO NRs were investigated by the help of an atomic force microscope using contact mode. The measurements of generated piezoelectricity were around 16.2 mV, 23.2 mV, 38.5 mV and 43.3 mV for common paper, textile fabric, plastic and aluminum foil, respectively. This investigation is an important step in order to study the effect of different substrates influencing the magnitude of the output voltage under identical growth and measurement conditions. We expect that this study will help identify the most suitable flexible substrate for harvesting energy. It also offers a promising alternative powering source for the next generation nanodevices using non-conventional substrates like aluminum foil. Moreover, the use of aluminum foil as flexible and low cost substrate may pave the way to develop devices in different fields including energy harvesting.
Central CRTH2, a Second Prostaglandin D2Receptor, Mediates Emotional Impairment in the Lipopolysaccharide and Tumor-Induced Sickness Behavior Model
Authors: Haba Ryota , Shintani Norihito , Onaka Yusuke , Kanoh Takuya , Wang Hyper , Takenaga Risa , Hayata Atsuko , Hirai Hiroyuki , Nagata Kin-ya , Nakamura Masataka , Kasai Atsushi , Hashimoto Ryota , Nagayasu Kazuki , Nakazawa Takanobu , Hashimoto Hitoshi , Baba Akemichi
Published: February 2014

Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) is a second prostaglandin D2receptor involved in mediating the allergic response; however, its central function is not yet known. Here, we demonstrate that central CRTH2 mediates emotional impairment. Lipopolysaccharide (LPS)-induced decreases in social interaction and novel exploratory behavior were observed in wild-type (CRTH2+/+) mice but not CRTH2-deficient (CRTH2−/−) mice, but both genotypes showed hypolocomotion and anorexia following LPS injection. Tumor (colon 26) inoculation, a more pathologically relevant model, induced decreases in social interaction and novel exploratory behavior in CRTH2+/+, but not CRTH2−/−mice. In addition, the CRTH2 antagonists including clinically available ramatroban reversed impaired social interaction and novel exploratory behavior after either LPS or tumor inoculation in CRTH2+/+mice. Finally, LPS-induced c-Fos expression in the hypothalamic paraventricular nucleus (PVN) and central amygdala (CeA) was selectively abolished in CRTH2−/−mice. These results show that CRTH2 participates in LPS-induced emotional changes and activation in the PVN and CeA. Our study provides the first evidence that central CRTH2 regulates specific emotional behaviors, and that CRTH2 antagonism has potential as a therapeutic target for behavioral symptoms associated with tumors and infectious diseases.
Dissociation between Neural Signatures of Stimulus and Choice in Population Activity of Human V1 during Perceptual Decision-Making
Authors: Choe Kyoung Whan , Blake Randolph , Lee Sang-Hun
Published: February 2014

Primary visual cortex (V1) forms the initial cortical representation of objects and events in our visual environment, and it distributes information about that representation to higher cortical areas within the visual hierarchy. Decades of work have established tight linkages between neural activity occurring in V1 and features comprising the retinal image, but it remains debatable how that activity relates to perceptual decisions. An actively debated question is the extent to which V1 responses determine, on a trial-by-trial basis, perceptual choices made by observers. By inspecting the population activity of V1 from human observers engaged in a difficult visual discrimination task, we tested one essential prediction of the deterministic view: choice-related activity, if it exists in V1, and stimulus-related activity should occur in the same neural ensemble of neurons at the same time. Our findings do not support this prediction: while cortical activity signifying the variability in choice behavior was indeed found in V1, that activity was dissociated from activity representing stimulus differences relevant to the task, being advanced in time and carried by a different neural ensemble. The spatiotemporal dynamics of population responses suggest that short-term priors, perhaps formed in higher cortical areas involved in perceptual inference, act to modulate V1 activity prior to stimulus onset without modifying subsequent activity that actually represents stimulus features within V1.
Representation of the Material Properties of Objects in the Visual Cortex of Nonhuman Primates
Authors: Goda Naokazu , Tachibana Atsumichi , Okazawa Gouki , Komatsu Hidehiko
Published: February 2014

Information about the material from which objects are made provide rich and useful clues that enable us to categorize and identify those objects, know their state (e.g., ripeness of fruits), and properly act on them. However, despite its importance, little is known about the neural processes that underlie material perception in nonhuman primates. Here we conducted an fMRI experiment in awake macaque monkeys to explore how information about various real-world materials is represented in the visual areas of monkeys, how these neural representations correlate with perceptual material properties, and how they correspond to those in human visual areas that have been studied previously. Using a machine-learning technique, the representation in each visual area was read out from multivoxel patterns of regional activity elicited in response to images of nine real-world material categories (metal, wood, fur, etc.). The congruence of the neural representations with either a measure of low-level image properties, such as spatial frequency content, or with the visuotactile properties of materials, such as roughness, hardness, and warmness, were tested. We show that monkey V1 shares a common representation with human early visual areas reflecting low-level image properties. By contrast, monkey V4 and the posterior inferior temporal cortex represent the visuotactile properties of material, as in human ventral higher visual areas, although there were some interspecies differences in the representational structures. We suggest that, in monkeys, V4 and the posterior inferior temporal cortex are important stages for constructing information about the material properties of objects from their low-level image features.
Feature-Selective Attention in Healthy Old Age: A Selective Decline in Selective Attention?
Authors: Quigley Cliodhna , Müller Matthias M.
Published: February 2014

Deficient selection against irrelevant information has been proposed to underlie age-related cognitive decline. We recently reported evidence for maintained early sensory selection when older and younger adults used spatial selective attention to perform a challenging task. Here we explored age-related differences when spatial selection is not possible and feature-selective attention must be deployed. We additionally compared the integrity of feedforward processing by exploiting the well established phenomenon of suppression of visual cortical responses attributable to interstimulus competition. Electroencephalogram was measured while older and younger human adults responded to brief occurrences of coherent motion in an attended stimulus composed of randomly moving, orientation-defined, flickering bars. Attention was directed to horizontal or vertical bars by a pretrial cue, after which two orthogonally oriented, overlapping stimuli or a single stimulus were presented. Horizontal and vertical bars flickered at different frequencies and thereby elicited separable steady-state visual-evoked potentials, which were used to examine the effect of feature-based selection and the competitive influence of a second stimulus on ongoing visual processing. Age differences were found in feature-selective attentional modulation of visual responses: older adults did not show consistent modulation of magnitude or phase. In contrast, the suppressive effect of a second stimulus was robust and comparable in magnitude across age groups, suggesting that bottom-up processing of the current stimuli is essentially unchanged in healthy old age. Thus, it seems that visual processing per se is unchanged, but top-down attentional control is compromised in older adults when space cannot be used to guide selection.
Cortical Correlates of Human Motion Perception Biases
Authors: Vintch Brett , Gardner Justin L.
Published: February 2014

Human sensory perception is not a faithful reproduction of the sensory environment. For example, at low contrast, objects appear to move slower and flicker faster than veridical. Although these biases have been observed robustly, their neural underpinning is unknown, thus suggesting a possible disconnect of the well established link between motion perception and cortical responses. We used functional imaging to examine the encoding of speed in the human cortex at the scale of neuronal populations and asked where and how these biases are encoded. Decoding, voxel population, and forward-encoding analyses revealed biases toward slow speeds and high temporal frequencies at low contrast in the earliest visual cortical regions, matching perception. These findings thus offer a resolution to the disconnect between cortical responses and motion perception in humans. Moreover, biases in speed perception are considered a leading example of Bayesian inference because they can be interpreted as a prior for slow speeds. Therefore, our data suggest that perceptual priors of this sort can be encoded by neural populations in the same early cortical areas that provide sensory evidence.
The Synaptic Targeting of mGluR1 by Its Carboxyl-Terminal Domain Is Crucial for Cerebellar Function
Authors: Ohtani Yoshiaki , Miyata Mariko , Hashimoto Kouichi , Tabata Toshihide , Kishimoto Yasushi , Fukaya Masahiro , Kase Daisuke , Kassai Hidetoshi , Nakao Kazuki , Hirata Tatsumi , Watanabe Masahiko , Kano Masanobu , Aiba Atsu
Published: February 2014

The metabotropic glutamate receptor subtype 1 (mGluR1, Grm1) in cerebellar Purkinje cells (PCs) is essential for motor coordination and motor learning. At the synaptic level, mGluR1 has a critical role in long-term synaptic depression (LTD) at parallel fiber (PF)-PC synapses, and in developmental elimination of climbing fiber (CF)-PC synapses. mGluR1a, a predominant splice variant in PCs, has a long carboxyl (C)-terminal domain that interacts with Homer scaffolding proteins. Cerebellar roles of the C-terminal domain at both synaptic and behavior levels remain poorly understood. To address this question, we introduced a short variant, mGluR1b, which lacks this domain into PCs of mGluR1-knock-out (KO) mice (mGluR1b-rescue mice). In mGluR1b-rescue mice, mGluR1b showed dispersed perisynaptic distribution in PC spines. Importantly, mGluR1b-rescue mice exhibited impairments in inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+release, CF synapse elimination, LTD induction, and delay eyeblink conditioning: they showed normal transient receptor potential canonical (TRPC) currents and normal motor coordination. In contrast, PC-specific rescue of mGluR1a restored all cerebellar defects of mGluR1-KO mice. We conclude that the long C-terminal domain of mGluR1a is required for the proper perisynaptic targeting of mGluR1, IP3R-mediated Ca2+release, CF synapse elimination, LTD, and motor learning, but not for TRPC currents and motor coordination.
The Yin and Yang of Calcium Effects on Synaptic Vesicle Endocytosis
Authors: Wu Xin-Sheng , Wu Ling-Gang
Published: February 2014

A large number of studies suggest that calcium triggers and accelerates vesicle endocytosis at many synapses and non-neuronal secretory cells. However, many studies show that prolonging the duration of the stimulation train, which induces more calcium influx, slows down endocytosis; and several studies suggest that instead of triggering endocytosis, calcium actually inhibits endocytosis. Here we addressed this apparent conflict at a large nerve terminal, the calyx of Held in rat brainstem, in which recent studies suggest that transient calcium increase up to tens of micromolar concentration at the micro/nano domain triggers endocytosis. By dialyzing 0–1 μmcalcium into the calyx via a whole-cell pipette, we found that slow endocytosis was inhibited by calcium dialysis in a concentration-dependent manner. Thus, prolonged, small, and global calcium increase inhibits endocytosis, whereas transient and large calcium increase at the micro/nano domain triggers endocytosis and facilitates endocytosis. This yin and yang effect of calcium may reconcile apparent conflicts regarding whether calcium accelerates or inhibits endocytosis. Whether endocytosis is fast or slow depends on the net outcome between the yin and yang effect of calcium.
Nonlinear Dose-Dependent Impact of D1 Receptor Activation on Motor Cortex Plasticity in Humans
Authors: Fresnoza Shane , Paulus Walter , Nitsche Michael A. , Kuo Min-Fang
Published: February 2014

The neuromodulator dopamine plays an important role in synaptic plasticity. The effects are determined by receptor subtype specificity, concentration level, and the kind of neuroplasticity induced. D1-like receptors have been proposed to be involved in cognitive processes via their impact on plasticity. Cognitive studies in humans and animals revealed a dosage-dependent effect of D1-like receptor activation on task performance. In humans, D1-like receptor activation re-establishes plasticity under D2 receptor block. However, a dosage-dependent effect has not been explored so far. To determine the impact of the amount of D1-like receptor activation on neuroplasticity in humans, we combined sulpiride, a selective D2 receptor antagonist, with the dopamine precursorl-DOPA (25, 100, and 200 mg) or applied placebo medication. The impact on plasticity induced by anodal and cathodal transcranial direct current stimulation (tDCS) was compared with the impact on plasticity induced by excitatory and inhibitory paired associative stimulation (PAS) at the primary motor cortex of healthy humans. Stimulation-generated cortical excitability alterations were monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. D1-like receptor activation produced an inverted U-shaped dose–response curve on plasticity induced by both facilitatory tDCS and PAS. For excitability-diminishing tDCS and PAS, aftereffects were abolished or converted trendwise into facilitation. These data extend findings of dose-dependent inverted U-shaped effects of D1 receptor activation on neuroplasticity of the motor cortex.
Bax Interacting Factor-1 Promotes Survival and Mitochondrial Elongation in Neurons
Authors: Wang David B. , Uo Takuma , Kinoshita Chizuru , Sopher Bryce L. , Lee Rona J. , Murphy Sean P. , Kinoshita Yoshito , Garden Gwenn A. , Wang Hong-Gang , Morrison Richard S.
Published: February 2014

Bax-interacting factor 1 (Bif-1, also known as endophilin B1) is a multifunctional protein involved in the regulation of apoptosis, mitochondrial morphology, and autophagy. Previous studies in non-neuronal cells have shown that Bif-1 is proapoptotic and promotes mitochondrial fragmentation. However, the role of Bif-1 in postmitotic neurons has not been investigated. In contrast to non-neuronal cells, we now report that in neurons Bif-1 promotes viability and mitochondrial elongation. In mouse primary cortical neurons, Bif-1 knockdown exacerbated apoptosis induced by the DNA-damaging agent camptothecin. Neurons from Bif-1-deficient mice contained fragmented mitochondria and Bif-1 knockdown in wild-type neurons also resulted in fragmented mitochondria which were more depolarized, suggesting mitochondrial dysfunction. During ischemic stroke, Bif-1 expression was downregulated in the penumbra of wild-type mice. Consistent with Bif-1 being required for neuronal viability, Bif-1-deficient mice developed larger infarcts and an exaggerated astrogliosis response following ischemic stroke. Together, these data suggest that, in contrast to non-neuronal cells, Bif-1 is essential for the maintenance of mitochondrial morphology and function in neurons, and that loss of Bif-1 renders neurons more susceptible to apoptotic stress. These unique actions may relate to the presence of longer, neuron-specific Bif-1 isoforms, because only these forms of Bif-1 were able to rescue deficiencies caused by Bif-1 suppression. This finding not only demonstrates an unexpected role for Bif-1 in the nervous system but this work also establishes Bif-1 as a potential therapeutic target for the treatment of neurological diseases, especially degenerative disorders characterized by alterations in mitochondrial dynamics.
Fear Conditioning Potentiates Synaptic Transmission onto Long-Range Projection Neurons in the Lateral Subdivision of Central Amygdala
Authors: Penzo Mario A. , Robert Vincent , Li Bo
Published: February 2014

Recent studies indicate that the lateral subdivision of the central amygdala (CeL) is essential for fear learning. Specifically, fear conditioning induces cell-type-specific synaptic plasticity in CeL neurons that is required for the storage of fear memories. The CeL also controls fear expression by gating the activity of the medial subdivision of the central amygdala (CeM), the canonical amygdala output to areas that mediate defensive responses. In addition to the connection with CeM, the CeL sends long-range projections to innervate extra-amygdala areas. However, the long-range projection CeL neurons have not been well characterized, and their role in fear regulation is unknown. Here we show in mice that a subset of CeL neurons directly project to the midbrain periaqueductal gray (PAG) and the paraventricular nucleus of the thalamus, two brain areas implicated in defensive behavior. These long-range projection CeL neurons are predominantly somatostatin-positive (SOM+) neurons, which can directly inhibit PAG neurons, and some of which innervate both the PAG and paraventricular nucleus of the thalamus. Notably, fear conditioning potentiates excitatory synaptic transmission onto these long-range projection CeL neurons. Thus, our study identifies a subpopulation of SOM+CeL neurons that may contribute to fear learning and regulate fear expression independent of CeM.
Structure of Plasticity in Human Sensory and Motor Networks Due to Perceptual Learning
Authors: Vahdat Shahabeddin , Darainy Mohammad , Ostry David J.
Published: February 2014

As we begin to acquire a new motor skill, we face the dual challenge of determining and refining the somatosensory goals of our movements and establishing the best motor commands to achieve our ends. The two typically proceed in parallel, and accordingly it is unclear how much of skill acquisition is a reflection of changes in sensory systems and how much reflects changes in the brain's motor areas. Here we have intentionally separated perceptual and motor learning in time so that we can assess functional changes to human sensory and motor networks as a result of perceptual learning. Our subjects underwent fMRI scans of the resting brain before and after a somatosensory discrimination task. We identified changes in functional connectivity that were due to the effects of perceptual learning on movement. For this purpose, we used a neural model of the transmission of sensory signals from perceptual decision making through to motor action. We used this model in combination with a partial correlation technique to parcel out those changes in connectivity observed in motor systems that could be attributed to activity in sensory brain regions. We found that, after removing effects that are linearly correlated with somatosensory activity, perceptual learning results in changes to frontal motor areas that are related to the effects of this training on motor behavior and learning. This suggests that perceptual learning produces changes to frontal motor areas of the brain and may thus contribute directly to motor learning.
The Transcription Factors Islet and Lim3 Combinatorially Regulate Ion Channel Gene Expression
Authors: Wolfram Verena , Southall Tony D. , Günay Cengiz , Prinz Astrid A. , Brand Andrea H. , Baines Richard A.
Published: February 2014

Expression of appropriate ion channels is essential to allow developing neurons to form functional networks. Our previous studies have identified LIM-homeodomain (HD) transcription factors (TFs), expressed by developing neurons, that are specifically able to regulate ion channel gene expression. In this study, we use the technique of DNA adenine methyltransferase identification (DamID) to identify putative gene targets of four such TFs that are differentially expressed inDrosophilamotoneurons. Analysis of targets for Islet (Isl), Lim3, Hb9, and Even-skipped (Eve) identifies both ion channel genes and genes predicted to regulate aspects of dendritic and axonal morphology. Significantly, some ion channel genes are bound by more than one TF, consistent with the possibility of combinatorial regulation. One such gene isShaker(Sh), which encodes a voltage-dependent fast K+channel (Kv1.1). DamID reveals thatShis bound by both Isl and Lim3. We used body wall muscle as a test tissue because in conditions of low Ca2+, the fast K+current is carried solely by Sh channels (unlike neurons in which a second fast K+current, Shal, also contributes). Ectopic expression ofisl, but notLim3, is sufficient to reduce bothShtranscript and Sh current level. By contrast, coexpression of both TFs is additive, resulting in a significantly greater reduction in both Sh transcript and current compared withislexpression alone. These observations provide evidence for combinatorial activity of Isl and Lim3 in regulating ion channel gene expression.
Vitamin D deficiency in elderly people in Swedish nursing homes is associated with increased mortality
Authors: Samefors Maria , Östgren Carl Johan , Mölstad Sigvard , Lannering Christina , Midlöv Patrik , Tengblad Anders
Published: February 2014

Objective

Institutionalised elderly people at northern latitudes may be at elevated risk for vitamin D deficiency. In addition to osteoporosis-related disorders, vitamin D deficiency may influence several medical conditions conferring an increased mortality risk. The aim of this study was to explore the prevalence of vitamin D deficiency and its association with mortality.

Design

The Study of Health and Drugs in the Elderly (SHADES) is a prospective cohort study among elderly people (>65 years) in 11 nursing homes in Sweden.

Methods

We analysed the levels of 25-hydroxyvitamin D3(25(OH)D3) at baseline. Vital status of the subjects was ascertained and hazard ratios (HRs) for mortality according to 25(OH)D3quartiles were calculated.

Results

We examined 333 study participants with a mean follow-up of 3 years. A total of 147 (44%) patients died within this period. Compared with the subjects in Q4 (25(OH)D3>48 nmol/l), HR (with 95% CI) for mortality was 2.02 (1.31–3.12) in Q1 (25(OH)D3<29 nmol/l) (P<0.05); 2.03 (1.32–3.14) in Q2 (25(OH)D330–37 nmol/l) (P<0.05) and 1.6 (1.03–2.48) in Q3 (25(OH)D338–47 nmol/l) (P<0.05). The mean 25(OH)D3concentration was 40.2 nmol/l (s.d. 16.0) and 80% had 25(OH)D3below 50 nmol/l. The vitamin D levels decreased from baseline to the second and third measurements.

Conclusions

Vitamin D deficiency was highly prevalent and associated with increased mortality among the elderly in Swedish nursing homes. Strategies are needed to prevent, and maybe treat, vitamin D deficiency in the elderly in nursing homes and the benefit of vitamin D supplementation should be evaluated in randomised clinical trials.
Characterisation of the biological activity of xenin-25 degradation fragment peptides
Authors: Martin Christine M A , Parthsarathy Vadivel , Pathak Varun , Gault Victor A , Flatt Peter R , Irwin Nigel
Published: February 2014

Xenin-25, a peptide co-secreted with the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), possesses promising therapeutic actions for obesity-diabetes. However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9–25, xenin 11–25, xenin 14–25 and xenin 18–25. This study has examined the biological activities of these fragment peptides.In vitrostudies using BRIN-BD11 cells demonstrated that native xenin-25 and xenin 18–25 possessed significant (P<0.05 toP<0.001) insulin-releasing actions at 5.6 and 16.7 mM glucose, respectively, but not at 1.1 mM glucose. In addition, xenin 18–25 significantly (P<0.05) potentiated the insulin-releasing action of the stable GIP mimetic (d-Ala2)GIP. In contrast, xenin 9–25, xenin 11–25 and xenin 14–25 displayed neither insulinotropic nor GIP-potentiating actions. Moreover, xenin 9–25, xenin 11–25 and xenin 14–25 significantly (P<0.05 toP<0.001) inhibited xenin-25 (10−6 M)-induced insulin releasein vitro. I.p. administration of xenin-based peptides in combination with glucose to high fat-fed mice did not significantly affect the glycaemic excursion or glucose-induced insulin release compared with controls. However, when combined with (d-Ala2)GIP, all xenin peptides significantly (P<0.01 toP<0.001) reduced the overall glycaemic excursion, albeit to a similar extent as (d-Ala2)GIP alone. Xenin-25 and xenin 18–25 also imparted a potential synergistic effect on (d-Ala2)GIP-induced insulin release in high fat-fed mice. All xenin-based peptides lacked significant satiety effects in normal mice. These data demonstrate that the C-terminally derived fragment peptide of xenin-25, xenin 18–25, exhibits significant biological actions that could have therapeutic utility for obesity-diabetes.
Differentiation of trophoblast cells from human embryonic stem cells: to be or not to be?
Authors: Roberts R Michael , Loh Kyle M , Amita Mitsuyoshi , Bernardo Andreia S , Adachi Katsuyuki , Alexenko Andrei P , Schust Danny J , Schulz Laura C , Telugu Bhanu Prakash V L , Ezashi Toshihiko , Pedersen Roger A
Published: February 2014

It is imperative to unveil the full range of differentiated cell types into which human pluripotent stem cells (hPSCs) can develop. The need is twofold: it will delimit the therapeutic utility of these stem cells and is necessary to place their position accurately in the developmental hierarchy of lineage potential. Accumulated evidence suggested that hPSC could developin vitrointo an extraembryonic lineage (trophoblast (TB)) that is typically inaccessible to pluripotent embryonic cells during embryogenesis. However, whether these differentiated cells are truly authentic TB has been challenged. In this debate, we present a case for and a case against TB differentiation from hPSCs. By analogy to other differentiation systems, our debate is broadly applicable, as it articulates higher and more challenging standards for judging whether a given cell type has been genuinely produced from hPSC differentiation.