bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Staphylococcus pseudintermedius isolated from diseased dogs in Lithuania
Authors: Ruzauskas M. , Couto N. , Pavilonis A. , Klimiene I. , Siugzdiniene R. , Virgailis M. , Vaskeviciute L. , Anskiene L. , Pomba C.
Published: April 2016

The aim of this study was to characterize Staphylococcus pseudintermedius for its antimicrobial resistance and virulence factors with a special focus on methicillin-resistant (MRSP) strains isolated from sick dogs in Lithuania. Clinically sick adult dogs suffering from infections (n=214) and bitches with reproductive disorders (n=36) from kennels were selected for the study. Samples (n=192) from the 250 tested (76.8%) dogs were positive for Staphylococcus spp. Molecular profiling using the species-specific nuc gene identified 51 isolates as S. pseudintermedius (26.6% from a total number of isolated staphylococci) of which 15 isolates were identified as MRSP. Ten MRSP isolates were isolated from bitches with reproductive disorders from two large breeding kennels. Data on susceptibility of S. pseudintermedius to different antimicrobials revealed that all isolates were susceptible to vancomycin, daptomycin and linezolid. Two isolates (3.9%) were resistant to rifampicin. A high resistance was seen towards penicillin G (94.1%), tetracycline (64.7%) and macrolides (68.7%). Resistance to fluoroquinolones ranged from 25.5% (gatifloxacin) to 31.4% (ciprofloxacin). The most prevalent genes encoding resistance included blaZ, aac(6’)-Ie-aph(2’’)-Ia, mecA, and tet(M). The Luk-I gene encoding a leukotoxin was detected in 29% of the isolates, whereas the siet gene encoding exfoliative toxin was detected in 69% of the S. pseudintermedius isolates. This report of MRSP in companion animals represents a major challenge for veterinarians in terms of antibiotic therapy and is a concern for both animal and public health.
The irp2 and fyuA genes in High Pathogenicity Islands are involved in the pathogenesis of infections caused by avian pathogenic Escherichia coli (APEC)
Authors: Tu Jian , Xue Ting , Qi Kezong , Shao Ying , Huang Boyan , Wang Xueyan , Zhou Xiuhong
Published: April 2016

Avian pathogenic Escherichia coli (APEC) is a major bacterial infectious disease that may lead to local or systemic infections in chickens with clinical manifestations. The irp2-fyuA gene cluster has been confirmed to be the main genes involved in the synthesis of HPI. The objective of this study was to determine the influence of the irp2 and fyuA genes in the high pathogenicity island (HPI) of avian pathogenic Escherichia coli (APEC) on its pathogenicity by knocking out these genes. The ΔAE17 (lacking irp2) and ΔΔAE17 (lacking irp2 and fyuA) strains of APEC were constructed. The ΔAE17 and ΔΔAE17 strains showed significantly impaired capacity to adhere onto DF-1 cells. The LD50 results indicated that the virulence of the ΔAE17 and ΔΔAE17 strains was decreased in comparison with that of the AE17 strain. We concluded that the knock-out of the core HPI genes weakened APEC adhesion onto DF-1 cells, inhibited transcription of virulence genes, and reduced pathogenicity in chicks. The effects of genetic deletion of irp2 and fyuA on APEC were more severe than those produced by deletion of irp2 only, indicating that irp2 and fyuA co-regulate APEC pathogenicity.
An effect of mammary gland infection caused by Streptococcus uberis on composition and physicochemical changes of cows’ milk
Authors: Pecka-Kiełb E. , Vasil M. , Zachwieja A. , Zawadzki W. , Elečko J. , Zigo F. , Illek J. , Farkašová Z.
Published: April 2016

An effect of mammary gland infection caused by Streptococcus uberis on the changes in cows’ milk composition and its physicochemical properties was examined. The study was conducted in the herd of Slovak Pied breed cattle (with a share of HF blood), in 2nd and 3rd lactation, after 4th month of milking. Milk samples were collected from a quarter milking. The samples were subjected to microbiological analysis, basic milk composition, total bacteria count, somatic cell count and physicochemical properties were examined. Also analyses of protein fractions share and fatty acids profile were conducted. An effect of bacterial infection of the mammary gland bring an increase (P<0.01) in somatic cell count was observed in this study. Milk samples contaminated with S. uberis were characterized by higher (P<0.05) total bacteria count and total protein compared to milk samples collected from non-infected mammary gland. The level of κ-casein was significantly (P<0.05) decreased in cows with subclinical mastitis caused by S. uberis. Significant (P<0.05) reduction in the share of C13:0 acid, and an increased level of C18:0, C18:1n7t and CLA were observed in milk contaminated with S. uberis compared to healthy cows’ milk.

It should be concluded that S. uberis causes the increase in total bacteria count, SCC and the decrease in κ-casein level, which significantly affects deterioration of technological quality of cows’ milk.
Genistein causes germ cell reduction in the genital ridges of Japanese quail Coturnix japonica embryo
Authors: Intarapat S. , Sailasuta A. , Satayalai O.
Published: April 2016

Genistein (GEN), an isoflavonoid phytoestrogen, is one of the potent estrogenic compounds derived from plants that can cause disrupting effects on sex organ development in non-mammalian and mammalian species. The present study revealed effect of genistein on germ cell number in the genital ridges during gonadogenesis. Genistein (16 and 24 μg/g egg) was injected into the egg yolk prior to incubation. Effect of genistein on quail-primordial germ cells (PGCs) number was examined by counting the number of Wisteria floribunda (WFA)-positive cells localized in both left and right genital ridges compared with the control group. Both concentrations of genistein resulted in significant decrease of PGC number compared with the control group. Percentages of the sterility rate of the embryo treated with 16 and 24 μg of genistein/g egg were 19% and 23%, respectively. These results provide evidence that genistein may be a germ cell toxicant causing sterility later in life of adult birds. This is the first report on the effect of genistein on PGC number in the genital ridges of the avian embryo.
The mechanisms of complement activation in normal bovine serum and normal horse serum against Yersinia enterocolitica O:9 strains with different outer membrane proteins content
Authors: Miętka K. , Brzostek K. , Guz-Regner K. , Bugla-Płoskońska G.
Published: April 2016

Yersinia enterocolitica is a common zoonotic pathogen and facultative intracellular bacterium which can survive within blood cells. Cattle and horses are considered a reservoir of Y. enterocolitica which often causes several serious syndromes associated with yersiniosis such as abortions, premature births or infertility. The aim of our investigation was to determine the vitality of Y. enterocolitica O:9 strains (Ye9) in bovine and horse sera (NBS and NHrS) and explain the role of outer membrane proteins (OMPs) in serum resistance of these bacteria. Our previous studies demonstrated moderate human serum (NHS) resistance of the wild type Ye9 strain, whereas mutants lacking YadA, Ail or OmpC remained sensitive to the bactericidal activity of NHS. The present study showed that the wild type of Ye9 strain was resistant to the bactericidal activity of both NHrS and NBS, while Ye9 mutants lacking the YadA, Ail and OmpC proteins were sensitive to NHrS and NBS as well as to NHS. The mechanisms of complement activation against Ye9 strains lacking Ail and YadA were distinguished, i.e. activation of the classical/lectin pathways decisive in the bactericidal mechanism of complement activation of NBS, parallel activation of the classical/lectin and alternative pathways of NHrS. In this research the mechanism of independent activation of the classical/lectin or the alternative pathway of NBS and NHrS against Ye9 lacking OmpC porin was also established. The results indicate that serum resistance of Ye9 is multifactorial, in which extracellular structures, i.e. outer membrane proteins (OMPs) such as Ail, OmpC or YadA, play the main role.
Monitoring of Yersinia enterocolitica strains from free-living animals using different methods
Authors: Syczyło K. , Platt-Samoraj A. , Bancerz-Kisiel A. , Szczerba-Turek A. , Lipczyńska K. , Jabłoński A. , Procajło Z. , Szweda W.
Published: April 2016

The aim of the study was to monitor Y. enterocolitica strains from free-living animals captured during 2011-2014 hunting seasons in Poland using warm (ITC) and cold (PSB) enrichment and molecular examination. Over 1600 samples have been cultured. After ITC/PSB enrichment 237 strains presenting features characteristic for Y. enterocolitica were isolated. Molecular examination using multiplex PCR revealed 140 isolates from PSB and 78 from ITC. The concentration of pathogenic Yersinia in asymptomatic carriers is low and the PCR detection should be preceded by bacteriological examination.
In situ formation of copper nanoparticles in a p(NIPAM-VAA-AAm) terpolymer microgel that retains the swelling behavior of microgels
Authors: Khan Khakemin , Shaikh Ahson Jabbar , Siddiq Mohammad , Sherazi Tauqir A. , Nawaz Mohsan
Published: April 2016

Copper nanoparticles (CuNPs) are formed inside a microgel assembly by an in situ reduction method, confirmed by changes observed in the absorption spectra of CuNPs at different pH values. The presence of CuNPs has been also confirmed by X-ray diffraction (XRD) studies. The terpolymer microgel p(N-isopropylacrylamide-vinyl acetic acid-acrylamide) (p[NIPAM-VAA-AAm]), which is reported for the first time, was synthesized by free radical emulsion polymerization of a temperature-sensitive NIPAM monomer, pH sensitive VAA monomer and a hydrophilic AAm monomer. The effect of temperature below and above the pKa of VAA and the effect of pH at 20°C in the absence and presence of CuNPs on the hydrodynamic radius of microgel was studied. Size of microgel particles is a function of temperature due to the presence of NIPAM, and a function of pH due to the presence of VAA. The presence of CuNPs has little or no effect on the size of microgels by varying pH, which allows these gels to retain their properties with added benefits of CuNPs for possible drug delivery applications.
Design of OFDM-Based Radio Communication Systems for Coast-to-Sea and Coast-to-Air Propagation Environments
Authors: Gajewski Sławomir
Published: April 2016

In the paper the study of radio communication system design process for systems based on OFDM transmission is considered. The signal propagation model for 1.4 GHz frequency band is discussed, and the study of signal propagation characteristics, important from the point of view of OFDM system design, is presented. The methodology of OFDM interface design is proposed and some characteristics of the OFDM-based radio communication system are analysed.
The Use of Satellite Data in the Operational 3D Coupled Ecosystem Model of the Baltic Sea (3D Cembs)
Authors: Nowicki Artur , Janecki Maciej , Darecki Mirosław , Piotrowski Piotr , Dzierzbicka-Głowacka Lidia
Published: April 2016

The objective of this paper is to present an automatic monitoring system for the 3D CEMBS model in the operational version. This predictive, eco hydrodynamic model is used as a tool to control the conditions and bio productivity of the Baltic sea environment and to forecast physical and ecological changes in the studied basin. Satellite-measured data assimilation is used to constrain the model and achieve higher accuracy of its results.

3D CEMBS is a version of the Community Earth System Model, adapted for the Baltic Sea. It consists of coupled ocean and ice models, working in active mode together with the ecosystem module. Atmospheric forecast from the UM model (Interdisciplinary Centre for Mathematical and Computational Modelling of the Warsaw University) are used as a forcing fields feed through atmospheric data model. In addition, river inflow of freshwater and nutrient deposition from 71 main rivers is processed by land model. At present, satellite data from AQUA MODIS, processed by the SatBałtyk project Operational System are used for the assimilation of sea surface temperature and chlorophyll a concentration. In the operational mode, 48-hour forecasts are produced at six-hour intervals, providing a wide range of hydrodynamic and biochemical parameters.
Motion Prediction of Catamaran with a Semisubmersible Bow in Wave
Authors: Sun Hanbing , Jing Fengmei , Jiang Yi , Zou Jin , Zhuang Jiayuan , Ma Weijia
Published: April 2016

Compared with standard vessels, a slender catamaran with a semi-submerged bow (SSB) demonstrates superior seakeeping performance. To predict the motion of an SSB catamaran, computational fluid dynamics methods are adopted in this study and results are validated through small-scale model tests. The pitch, heave, and vertical acceleration are calculated at various wavelengths and speeds. Based on the overset grid and motion region methods, this study obtains the motion responses of an SSB catamaran in regular head waves. The results of the numerical studies are validated with the experimental data and show that the overset grid method is more accurate in predicting the motion of an SSB catamaran; the errors can be controlled within 20%. The movement data in regular waves shows that at a constant speed, the motion response initially increases and then decreases with increasing wavelength. This motion response peak is due to the encountering frequency being close to the natural frequency. Under identical sea conditions, the motion response increases with the increasing Froude number. The motion prediction results, that derive from a short-term irregular sea state, show that there is an optimal speed range that can effectively reduce the amplitude of motion.
Effective Method for Determining Environmental Loads on Supporting Structures for Offshore Wind Turbines
Authors: Dymarski Paweł , Ciba Ewelina , Marcinkowski Tomasz
Published: April 2016

This paper presents a description of an effective method for determining loads due to waves and current acting on the supporting structures of the offshore wind turbines. This method is dedicated to the structures consisting of the cylindrical or conical elements as well as (truncates) pyramids of polygon with a large number of sides (8 or more). The presented computational method is based on the Morison equation, which was originally developed only for cylindrically shaped structures. The new algorithm shown here uses the coefficients of inertia and drag forces that were calculated for non-cylindrical shapes. The analysed structure consists of segments which are truncated pyramids on the basis of a hex decagon. The inertia coefficients, CM, and drag coefficients, CD, were determined using RANSE-CFD calculations. The CFD simulations were performed for a specific range of variation of the period, and for a certain range of amplitudes of the velocity. In addition, the analysis of influence of the surface roughness on the inertia and drag coefficients was performed. In the next step, the computations of sea wave, current and wind load on supporting structure for the fifty-year storm were carried out. The simulations were performed in the time domain and as a result the function of forces distribution along the construction elements was obtained. The most unfavourable distribution of forces will be used, to analyse the strength of the structure, as the design load.
Gibbs Sampling Segmentation of Parallel Dependency Trees for Tree-Based Machine Translation
Authors: Mareček David , Žabokrtský Zdeněk
Published: April 2016

We present a work in progress aimed at extracting translation pairs of source and target dependency treelets to be used in a dependency-based machine translation system. We introduce a novel unsupervised method for parallel tree segmentation based on Gibbs sampling. Using the data from a Czech-English parallel treebank, we show that the procedure converges to a dictionary containing reasonably sized treelets; in some cases, the segmentation seems to have interesting linguistic interpretations.
A Minimally Supervised Approach for Synonym Extraction with Word Embeddings
Authors: Leeuwenberg Artuur , Vela Mihaela , Dehdari Jon , van Genabith Josef
Published: April 2016

In this paper we present a novel approach to minimally supervised synonym extraction. The approach is based on the word embeddings and aims at presenting a method for synonym extraction that is extensible to various languages.

We report experiments with word vectors trained by using both the continuous bag-of-words model (CBoW) and the skip-gram model (SG) investigating the effects of different settings with respect to the contextual window size, the number of dimensions and the type of word vectors. We analyze the word categories that are (cosine) similar in the vector space, showing that cosine similarity on its own is a bad indicator to determine if two words are synonymous. In this context, we propose a new measure, relative cosine similarity, for calculating similarity relative to other cosine-similar words in the corpus. We show that calculating similarity relative to other words boosts the precision of the extraction. We also experiment with combining similarity scores from differently-trained vectors and explore the advantages of using a part-of-speech tagger as a way of introducing some light supervision, thus aiding extraction.

We perform both intrinsic and extrinsic evaluation on our final system: intrinsic evaluation is carried out manually by two human evaluators and we use the output of our system in a machine translation task for extrinsic evaluation, showing that the extracted synonyms improve the evaluation metric.
3. Developing by Drawing Creativity of Children Activities
Authors: Ceauşu Felicia
Published: April 2016

The potential creativity elements can be expressivity, flexibility, fluency, brain sensibility as well as the qualities of the analyzers and temperamental characteristics which have an important role in triggering, developing and manifesting creativity. Here we must also take into account the relationship of the subject with the environment and educational factors. For the child, creativity has certain time limits that are determined by a multitude of factors such as: adaptation to new changes, will, creative type cognitive type, the feeling of duty and responsibility, ideal, surrounding atmosphere. In the current paperwork, we aimed to elevate the development level of creativity by plastic arts and we remarked that, in those plastic art activities where the basic method was the play, the efficient organization of the activities of plastic arts. The child is an active subject of knowledge who absorbs with lust the information proposed by the educator, he/she must be ready to receive more and more knowledge. The main task of the adults is to create optimal conditions of discovery and achievement of his/her creative possibilities and to take into consideration the individuality of each child.
In-Situ Characterization of Isotropic and Transversely Isotropic Elastic Properties Using Ultrasonic Wave Velocities
Authors: Pant S. , Laliberte J. , Martinez M. , Rocha B.
Published: April 2016

In this paper, a one-sided, in situ method based on the time of flight measurement of ultrasonic waves was described. The primary application of this technique was to non-destructively measure the stiffness properties of isotropic and transversely isotropic materials. The method consists of generating and receiving quasi-longitudinal and quasi-shear waves at different through-thickness propagation angles. First, analytical equations were provided to calculate the ultrasonic wave velocities. Then, an inverse method based on non-linear least square technique was used to calculate the stiffness constants using the ultrasonic wave velocities. Sensitivity analysis was performed by randomly perturbing the velocity data, thus observing the effects of perturbations on the calculated stiffness constants. An improved algorithm was proposed and tested to reduce the effects of random errors. Based on the sensitivity analysis, minimum number of angles required to inversely calculate the stiffness constants were suggested for isotropic and transversely isotropic material. The method was experimentally verified on an isotropic 7050-T7451 aluminum with two different thicknesses and a transversely isotropic composite laminate fabricated using 24 plies of CYCOM 977-2 12 k HTA unidirectional carbon fiber reinforced polymer (CFRP) prepregs. The results demonstrated that this technique is able to accurately measure the material properties of isotropic material. As for the transversely isotropic material, this method was able to accurately measure the material properties if the experimental errors can be reduced to less than 1 %.
Quasi-Static, Cyclic Fatigue and Fracture Behavior of Alloy Steel for Structural Applications: Influence of Orientation
Authors: Gowda S. , Hotz C. , Manigandan K. , Srivatsan T. S. , Patnaik A. , Payer J.
Published: April 2016

In this paper, the results of a study aimed at understanding the extrinsic influence of test specimen orientation, with respect to a wrought alloy-steel plate, on the stress-controlled cyclic fatigue properties and fracture behavior of a structural steel is highlighted. The alloy steel chosen was ASTM A572 grade 50. Samples of this alloy steel, prepared from both the longitudinal and transverse orientations, were cyclically deformed over a range of maximum stress and the corresponding number of cycles to failure (NF) was recorded. The influence of test specimen orientation and intrinsic microstructural effects on cyclic fatigue life and fracture behavior are presented and discussed. Overall, the macroscopic fracture mode was essentially identical regardless of orientation of the test specimen with respect to the wrought plate. The microscopic mechanisms governing cyclic deformation, fatigue life, and final fracture behavior are presented in light of the mutually interactive influences of magnitude of applied stress, intrinsic microstructural effects, orientation of test specimen, and deformation characteristics of the key microstructural constituents.
Physiological Properties of Neurons in Bat Entorhinal Cortex Exhibit an Inverse Gradient along the Dorsal–Ventral Axis Compared to Entorhinal Neurons in Rat
Authors: Heys James G. , Shay Christopher F. , MacLeod Katrina M. , Witter Menno P. , Moss Cynthia F. , Hasselmo Michael E.
Published: April 2016

Medial entorhinal cortex (MEC) grid cells exhibit firing fields spread across the environment on the vertices of a regular tessellating triangular grid. In rodents, the size of the firing fields and the spacing between the firing fields are topographically organized such that grid cells located more ventrally in MEC exhibit larger grid fields and larger grid-field spacing compared with grid cells located more dorsally. Previous experiments in brain slices from rodents have shown that several intrinsic cellular electrophysiological properties of stellate cells in layer II of MEC change systematically in neurons positioned along the dorsal–ventral axis of MEC, suggesting that these intrinsic cellular properties might control grid-field spacing. In the bat, grid cells in MEC display a functional topography in terms of grid-field spacing, similar to what has been reported in rodents. However, it is unclear whether neurons in bat MEC exhibit similar gradients of cellular physiological properties, which may serve as a conserved mechanism underlying grid-field spacing in mammals. To test whether entorhinal cortex (EC) neurons in rats and bats exhibit similar electrophysiological gradients, we performed whole-cell patch recordings along the dorsal–ventral axis of EC in bats. Surprisingly, our data demonstrate that the sag response properties and the resonance properties recorded in layer II neurons of entorhinal cortex in the Egyptian fruit bat demonstrate an inverse relationship along the dorsal–ventral axis compared with the rat.

SIGNIFICANCE STATEMENTAs animals navigate, neurons in medial entorhinal cortex (MEC), termed grid cells, discharge at regular spatial intervals. In bats and rats, the spacing between the firing fields of grid cells changes systematically along the dorsal–ventral axis of MEC. It has been proposed that these changes could be generated by systematic differences in the intrinsic cellular physiology of neurons distributed along the dorsal–ventral axis of MEC. The results from our study show that key intrinsic physiological properties of neurons in entorhinal cortex of the bat and rat change in the opposite direction along the dorsal–ventral axis of entorhinal cortex, suggesting that these intrinsic physiological properties cannot account in the same way across species for the change in grid-field spacing shown along the dorsal–ventral axis.
Wiring Specificity and Synaptic Diversity in the Mouse Lateral Central Amygdala
Authors: Hou Wen-Hsien , Kuo Ning , Fang Ge-Wei , Huang Hsien-Sung , Wu Kun-Pin , Zimmer Andreas , Cheng Jen-Kun , Lien Cheng-Chang
Published: April 2016

The central amygdala (CeA) nucleus, a subcortical structure composed of mostly GABA-releasing (GABAergic) neurons, controls fear expression via projections to downstream targets in the hypothalamus and brainstem. The CeA consists of the lateral (CeL) and medial (CeM) subdivisions. The CeL strongly gates information transfer to the CeM, the main output station of the amygdala, but little is known about the functional organization of local circuits in this region. Using cluster analysis, we identified two major electrophysiologically distinct CeL neuron classes in mouse amygdala slices, the early-spiking (ES) and late-spiking (LS) neurons. These two classes displayed distinct autaptic transmission. Compared with LS neurons, ES neurons had strong and depressing autapses, which enhanced spike-timing precision. With multiple patch-clamp recordings, we found that CeL neurons made chemical, but not electrical, synapses. Analysis of individual connections revealed cannabinoid type 1 receptor-mediated suppression of the ES, but not of the LS cell output synapse. More interestingly, the efficacy of the ES→LS or LS→ES synapse was ∼2-fold greater than that of the LS→LS or ES→ES synapse. When tested at 20 Hz, synapses between different neurons, but not within the same class, were markedly depressing and were more powerful to sculpt activity of postsynaptic neurons. Moreover, neurons of different classes also form synapses with higher degree of connectivity. We demonstrate that ES and LS neurons represent two functionally distinct cell classes in the CeL and interactions between presynaptic and postsynaptic neurons dictate synaptic properties between neurons.

SIGNIFICANCE STATEMENTThe central lateral amygdala (CeL) is a key node in fear circuits, but the functional organization of local circuits in this region is largely unknown. The CeL consists of mostly GABAergic inhibitory neurons with different functional and molecular features. Here, we report that the presynaptic cell class determines functional properties of autapses and cannabinoid-mediated modulation of synaptic transmission between neurons, whereas presynaptic versus postsynaptic cell classes dictate the connectivity, efficacy, and dynamics of GABAergic synapses between any two neurons. The wiring specificity and synaptic diversity have a great impact on neuronal output in amygdala inhibitory networks. Such synaptic organizing principles advance our understanding of the significance of physiologically defined neuronal phenotypes in amygdala inhibitory networks.
Sphingosine-1-Phosphate (S1P) Impacts Presynaptic Functions by Regulating Synapsin I Localization in the Presynaptic Compartment
Authors: Riganti Loredana , Antonucci Flavia , Gabrielli Martina , Prada Ilaria , Giussani Paola , Viani Paola , Valtorta Flavia , Menna Elisabetta , Matteoli Michela , Verderio Claudia
Published: April 2016

Growing evidence indicates that sphingosine-1-P (S1P) upregulates glutamate secretion in hippocampal neurons. However, the molecular mechanisms through which S1P enhances excitatory activity remain largely undefined. The aim of this study was to identify presynaptic targets of S1P action controlling exocytosis. Confocal analysis of rat hippocampal neurons showed that S1P applied at nanomolar concentration alters the distribution of Synapsin I (SynI), a presynaptic phosphoprotein that controls the availability of synaptic vesicles for exocytosis. S1P induced SynI relocation to extrasynaptic regions of mature neurons, as well as SynI dispersion from synaptic vesicle clusters present at axonal growth cones of developing neurons. S1P-induced SynI relocation occurred in a Ca2+-independent but ERK-dependent manner, likely through the activation of S1P3receptors, as it was prevented by the S1P3receptor selective antagonist CAY1044 and in neurons in which S1P3receptor was silenced. Our recent evidence indicates that microvesicles (MVs) released by microglia enhance the metabolism of endogenous sphingolipids in neurons and stimulate excitatory transmission. We therefore investigated whether MVs affect SynI distribution and whether endogenous S1P could be involved in the process. Analysis of SynI immunoreactivity showed that exposure to microglial MVs induces SynI mobilization at presynaptic sites and growth cones, whereas the use of inhibitors of sphingolipid cascade identified S1P as the sphingolipid mediating SynI redistribution. Our data represent the first demonstration that S1P induces SynI mobilization from synapses, thereby indicating the phosphoprotein as a novel target through which S1P controls exocytosis.

SIGNIFICANCE STATEMENTGrowing evidence indicates that the bioactive lipid sphingosine and its metabolite sphingosine-1-P (S1P) stimulate excitatory transmission. While it has been recently clarified that sphingosine influences directly the exocytotic machinery by activating the synaptic vesicle protein VAMP2 to form SNARE fusion complexes, the molecular mechanism by which S1P promotes neurotransmission remained largely undefined. In this study, we identify Synapsin I, a presynaptic phosphoprotein involved in the control of availability of synaptic vesicles for exocytosis, as the key target of S1P action. In addition, we provide evidence that S1P can be produced at mature axon terminals as well as at immature growth cones in response to microglia-derived signals, which may be important to stabilize nascent synapses and to restore or potentiate transmission.
α-Synuclein Mutation Inhibits Endocytosis at Mammalian Central Nerve Terminals
Authors: Xu Jianhua , Wu Xin-Sheng , Sheng Jiansong , Zhang Zhen , Yue Hai-Yuan , Sun Lixin , Sgobio Carmelo , Lin Xian , Peng Shiyong , Jin Yinghui , Gan Lin , Cai Huaibin , Wu Ling-Gang
Published: April 2016

α-Synuclein (α-syn) missense and multiplication mutations have been suggested to cause neurodegenerative diseases, including Parkinson's disease (PD) and dementia with Lewy bodies. Before causing the progressive neuronal loss, α-syn mutations impair exocytosis, which may contribute to eventual neurodegeneration. To understand how α-syn mutations impair exocytosis, we developed a mouse model that selectively expressed PD-related human α-syn A53T (h-α-synA53T) mutation at the calyx of Held terminals, where release mechanisms can be dissected with a patch-clamping technique. With capacitance measurement of endocytosis, we reported that h-α-synA53T, either expressed transgenically or dialyzed in the short term in calyces, inhibited two of the most common forms of endocytosis, the slow and rapid vesicle endocytosis at mammalian central synapses. The expression of h-α-synA53Tin calyces also inhibited vesicle replenishment to the readily releasable pool. These findings may help to understand how α-syn mutations impair neurotransmission before neurodegeneration.

SIGNIFICANCE STATEMENTα-Synuclein (α-syn) missense or multiplication mutations may cause neurodegenerative diseases, such as Parkinson's disease and dementia with Lewy bodies. The initial impact of α-syn mutations before neuronal loss is impairment of exocytosis, which may contribute to eventual neurodegeneration. The mechanism underlying impairment of exocytosis is poorly understood. Here we report that an α-syn mutant, the human α-syn A53T, inhibited two of the most commonly observed forms of endocytosis, slow and rapid endocytosis, at a mammalian central synapse. We also found that α-syn A53T inhibited vesicle replenishment to the readily releasable pool. These results may contribute to accounting for the widely observed early synaptic impairment caused by α-syn mutations in the progression toward neurodegeneration.
l-Lactate-Mediated Neuroprotection against Glutamate-Induced Excitotoxicity Requires ARALAR/AGC1
Authors: Llorente-Folch Irene , Rueda Carlos B. , Pérez-Liébana Irene , Satrústegui Jorgina , Pardo Beatriz
Published: April 2016

ARALAR/AGC1/Slc25a12, the aspartate-glutamate carrier from brain mitochondria, is the regulatory step in the malate-aspartate NADH shuttle, MAS. MAS is used to oxidize cytosolic NADH in mitochondria, a process required to maintain oxidative glucose utilization. The role of ARALAR was analyzed in two paradigms of glutamate-induced excitotoxicity in cortical neurons: glucose deprivation and acute glutamate stimulation. ARALAR deficiency did not aggravate glutamate-induced neuronal deathin vitro, although glutamate-stimulated respiration was impaired. In contrast, the presence ofl-lactate as an additional source protected against glutamate-induced neuronal death in control, but not ARALAR-deficient neurons.l-Lactate supplementation increased glutamate-stimulated respiration partially prevented the decrease in the cytosolic ATP/ADP ratio induced by glutamate and substantially diminished mitochondrial accumulation of 8-oxoguanosine, a marker of reactive oxygen species production, only in the presence, but not the absence, of ARALAR. In addition,l-lactate potentiated glutamate-induced increase in cytosolic Ca2+, in a way independent of the presence of ARALAR. Interestingly,in vivo, the loss of half-a-dose of ARALAR inaralar+/−mice enhanced kainic acid-induced seizures and neuronal damage with respect to control animals, in a model of excitotoxicity in which increasedl-lactate levels andl-lactate consumption have been previously proven. These results suggest that,in vivo, an inefficient operation of the shuttle in thearalarhemizygous mice prevents the protective role ofl-lactate on glutamate excitotoxiciy and that the entry and oxidation ofl-lactate through ARALAR-MAS pathway is required for its neuroprotective function.

SIGNIFICANCE STATEMENTLactate now stands as a metabolite necessary for multiple functions in the brain and is an alternative energy source during excitotoxic brain injury. Here we find that the absence of a functional malate-aspartate NADH shuttle caused byaralar/AGC1 disruption causes a block in lactate utilization by neurons, which prevents the protective role of lactate on excitotoxicity, but not glutamate excitotoxicity itself. Thus, failure to use lactate is detrimental and is possibly responsible for the exacerbatedin vivoexcitotoxicity inaralar+/−mice.
cGMP-Dependent Protein Kinase Encoded byforagingRegulates Motor Axon Guidance inDrosophilaby Suppressing Lola Function
Authors: Peng Qionglin , Wang Yijin , Li Meixia , Yuan Deliang , Xu Mengbo , Li Changqing , Gong Zhefeng , Jiao Renjie , Liu Li
Published: April 2016

Correct pathfinding and target recognition of a developing axon are exquisitely regulated processes that require multiple guidance factors. Among these factors, the second messengers, cAMP and cGMP, are known to be involved in establishing the guidance cues for axon growth through different intracellular signaling pathways. However, whether and how cGMP-dependent protein kinase (PKG) regulates axon guidance remains poorly understood. Here, we show that the motor axons of intersegmental nerve b (ISNb) in theDrosophilaembryo display targeting defects during axon development in the absence offoraging(for), a gene encoding PKG.In vivotag expression revealed PKG to be present in the ventral nerve code at late embryonic stages, supporting its function in embryonic axon guidance. Mechanistic studies showed that the transcription factorlongitudinal lacking(lola) genetically interacts withfor.PKG physically associates with the LolaT isoform via the C-terminal zinc-finger-containing domain. Overexpression of PKG leads to the cytoplasmic retention of LolaT in S2 cells, suggesting a role for PKG in mediating the nucleocytoplasmic trafficking of Lola. Together, these findings reveal a novel function of PKG in regulating the establishment of neuronal connectivity by sequestering Lola in the cytoplasm.

SIGNIFICANCE STATEMENTAxon pathfinding and target recognition are important processes in the formation of specific neuronal connectivity, which rely upon precise coordinated deployment of multiple guidance factors. This paper reveals the role of cGMP-dependent protein kinase (PKG) in regulating the pathfinding and targeting of the developing axons inDrosophila. Moreover, our study indicates that PKG regulates the cytoplasmic-nuclear trafficking of the transcription factor LolaT, suggesting a mechanism of PKG in directing motor axon guidance. These findings highlight a new function of PKG in axon guidance by suppressing a transcription factor.
Rapid Adaptation Induces Persistent Biases in Population Codes for Visual Motion
Authors: Zavitz Elizabeth , Yu Hsin-Hao , Rowe Elise G. , Rosa Marcello G.P. , Price Nicholas S. C.
Published: April 2016

Each visual experience changes the neural response to subsequent stimuli. If the brain is unable to incorporate these encoding changes, the decoding, or perception, of subsequent stimuli is biased. Although the phenomenon of adaptation pervades the nervous system, its effects have been studied mainly in isolation, based on neuronal encoding changes induced by an isolated, prolonged stimulus. To understand how adaptation-induced biases arise and persist under continuous, naturalistic stimulation, we simultaneously recorded the responses of up to 61 neurons in the marmoset (Callithrix jacchus) middle temporal area to a sequence of directions that changed every 500 ms. We found that direction-specific adaptation following only 0.5 s of stimulation strongly affected encoding for up to 2 s by reducing both the gain and the spike count correlations between pairs of neurons with preferred directions close to the adapting direction. In addition, smaller changes in bandwidth and preferred direction were observed in some animals. Decoding individual trials of adaptation-affected activity in simultaneously recorded neurons predicted repulsive biases that are consistent with the direction aftereffect. Surprisingly, removing spike count correlations by trial shuffling did not impact decoding performance or bias. When adaptation had the largest effect on encoding, the decoder made the most errors. This suggests that neural and perceptual repulsion is not a mechanism to enhance perceptual performance but is instead a necessary consequence of optimizing neural encoding for the identification of a wide range of stimulus properties in diverse temporal contexts.

SIGNIFICANCE STATEMENTAlthough perception depends upon decoding the pattern of activity across a neuronal population, the encoding properties of individual neurons are unreliable: a single neuron's response to repetitions of the same stimulus is variable, and depends on both its spatial and temporal context. In this manuscript, we describe the complete cascade of adaptation-induced effects in sensory encoding and show how they predict population decoding errors consistent with perceptual biases. We measure the time course of adaptation-induced changes to the response properties of neurons in isolation, and to the correlation structure across pairs of simultaneously recorded neurons. These results provide novel insight into how and for how long adaptation affects the neural code, particularly during continuous, naturalistic vision.
Mice Can Use Second-Order, Contrast-Modulated Stimuli to Guide Visual Perception
Authors: Khastkhodaei Zeinab , Jurjut Ovidiu , Katzner Steffen , Busse Laura
Published: April 2016

Visual processing along the primate ventral stream takes place in a hierarchy of areas, characterized by an increase in both complexity of neuronal preferences and invariance to changes of low-level stimulus attributes. A basic type of invariance is form-cue invariance, where neurons have similar preferences in response to first-order stimuli, defined by changes in luminance, and global features of second-order stimuli, defined by changes in texture or contrast. Whether in mice, a now popular model system for early visual processing, visual perception can be guided by second-order stimuli is currently unknown. Here, we probed mouse visual perception and neural responses in areas V1 and LM using various types of second-order, contrast-modulated gratings with static noise carriers. These gratings differ in their spatial frequency composition and thus in their ability to invoke first-order mechanisms exploiting local luminance features. We show that mice can transfer learning of a coarse orientation discrimination task involving first-order, luminance-modulated gratings to the contrast-modulated gratings, albeit with markedly reduced discrimination performance. Consistent with these behavioral results, we demonstrate that neurons in area V1 and LM are less responsive and less selective to contrast-modulated than to luminance-modulated gratings, but respond with broadly similar preferred orientations. We conclude that mice can, at least in a rudimentary form, use second-order stimuli to guide visual perception.

SIGNIFICANCE STATEMENTTo extract object boundaries in natural scenes, the primate visual system does not only rely on differences in local luminance but can also take into account differences in texture or contrast. Whether the mouse, which has a much simpler visual system, can use such second-order information to guide visual perception is unknown. Here we tested mouse perception of second-order, contrast-defined stimuli and measured their neural representations in two areas of visual cortex. We find that mice can use contrast-defined stimuli to guide visual perception, although behavioral performance and neural representations were less robust than for luminance-defined stimuli. These findings shed light on basic steps of feature extraction along the mouse visual cortical hierarchy, which may ultimately lead to object recognition.
PGC-1α, glucose metabolism and type 2 diabetes mellitus
Authors: Wu Haijiang , Deng Xinna , Shi Yonghong , Su Ye , Wei Jinying , Duan Huijun
Published: April 2016

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by glucose metabolic disturbance. A number of transcription factors and coactivators are involved in this process. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important transcription coactivator regulating cellular energy metabolism. Accumulating evidence has indicated that PGC-1α is involved in the regulation of T2DM. Therefore, a better understanding of the roles of PGC-1α may shed light on more efficient therapeutic strategies. Here, we review the most recent progress on PGC-1α and discuss its regulatory network in major glucose metabolic tissues such as the liver, skeletal muscle, pancreas and kidney. The significant associations between PGC-1α polymorphisms and T2DM are also discussed in this review.
Filosofía y prensa en Colombia: el caso del Magazín Dominical de El Espectador (1980-1990). Una experiencia investigativa
Authors: Pachón Soto Damián , Cuellar Camilo
Published: April 2016

Este artículo busca dar respuesta a la siguiente pregunta: ¿sé ocupan los filósofos colombianos de las problemáticas nacionales? Para responderla se acudió al levantamiento de archivo y posterior análisis de los artículos de interés filosófico publicados en Magazín Dominical de El Espectador en 1980-1990. Se partió del supuesto de que es posible encontrar en la prensa escritos filosóficos relacionados con las coyunturas y realidades nacionales de ese convulsivo periodo.
Comparación de la eficiencia del método de optimización BFGS en C, OX y R para un modelo de regresión no lineal
Authors: Rondón Poveda Luz Marina
Published: April 2016

En este artículo se presenta una comparación de la eficiencia del método de optimización no linealBFGS cuando es aplicado usando los programas C, Ox y R. Esta comparación se realiza al evaluar el desempeño del método BFGS cuando es usado para obtener las estimativas de máxima verosimilitud de los parámetros de un  modelo de regresión no lineal con errores de distribución normal. La eficiencia del método se estudia usando algunas medidas como, por ejemplo, el número promedio de evaluaciones de la  función y de la derivada de la función requeridas para la convergencia del método.Estas medidas se obtienen usando simulación de Monte Carlo.
Uso de modelos aditivos para evaluar la variabilidad espacial y temporal en datos 3D
Authors: Rincón Rodríguez Francisco Andrés
Published: April 2016

Este articulo está dirigido a identificar la presencia de variabilidad sobre tiempo y espacio para la temperatura del agua en Santa Marta, Colombia. El proceso de modelamiento considera una aproximación a través de un modelo lineal, el uso de modelos aditivos como una alternativa para capturar patrones no lineales, evaluación de la necesidad de un efecto no paramétrico para cada una de las covariables y finalmente un diagnóstico sobre los residuales para valorar la necesidad de incluir una estructura de covarianza sobre tiempo y/o espacio.
Implementación de cartas de control en el paquete estadístico R para el monitoreo de procesos en media con datos autocorrelacionados
Authors: Gonzáles Joaquín , Zambrano Alex
Published: April 2016

Las cartas de control estadístico son gráficos que dentro del control de proceso estadístico permiten monitorear la(s) característica(s) de calidad de un proceso industrial o de servicios y son ampliamente usadas en la actualidad. Para la implementación de las cartas usuales se asume que las observaciones no presentan una estructura de autocorrelación, pero en la práctica esta condición es violada con frecuencia. La presencia de autocorrelación tiene un serio impacto sobre el incremento sustancial en la frecuencia de falsas alarmas en dichas cartas. En los últimos 20 años, varias propuestas  de cartas de control se han presentado teniendo en cuenta la estructura de autocorrelación  en los datos para su construcción. En este artículo se presenta la construcción y comparación en forma ilustrativa  de dos de dichas propuestas, una dada por AR1988 basada sobre los residuales del modelo tipo ARMA que mejor se ajuste a los datos, y la otra dada  por MONT2 basada sobre la estadística EWMA, con el objeto de que sirvan como instrumento de enseñanza y aprendizaje de este tipo de cartas, ya que paquetes  especializados en control estadístico de la calidad no tienen implementadas estas cartas. Tal es el caso del paquete estadístico  R, el cual es usado en este trabajo  para la programación  e implementación de las cartas mencionadas.