bluuebunny/crossref_metadata_2025 huggingface dataset:
SPARC Regulates Microgliosis and Functional Recovery following Cortical Ischemia
Authors: Lloyd-Burton Samantha M. , York Elisa M. , Anwar Mohammad A. , Vincent Adele J. , Roskams A. Jane
Published: March 2013

Secreted protein acidic rich in cysteine (SPARC) is a matricellular protein that modulates the activity of growth factors, cytokines, and extracellular matrix to play multiple roles in tissue development and repair, such as cellular adhesion, migration, and proliferation. Throughout the CNS, SPARC is highly localized in mature ramified microglia, but its role in microglia—in development or during response to disease or injury—is not understood. In the postnatal brain, immature amoeboid myeloid precursors only induce SPARC expression after they cease proliferation and migration, and transform into mature, ramified resting microglia. SPARC null/CX3CR1-GFP reporter mice reveal that SPARC regulates the distribution and branching of mature microglia, with significant differences between cortical gray and white matter in both controls and SPARC nulls. Following ischemic and excitotoxic lesion, reactive, hypertrophic microglia rapidly downregulate and release SPARC at the lesion, concomitant with reactive, hypertrophic perilesion astrocytes upregulating SPARC. After photothrombotic stroke in the forelimb sensorimotor cortex, SPARC nulls demonstrate enhanced microgliosis in and around the lesion site, which accompanies significantly enhanced functional recovery by 32 d after lesion. Microglia from SPARC nulls also intrinsically proliferate at a greater ratein vitro—an enhanced effect that can be rescued by the addition of exogenous SPARC. SPARC is thus a novel regulator of microglial proliferation and structure, and, in addition to regulating glioma progression, may play an important role in differently regulating the gray and white matter microglial responses to CNS lesion—and modulating behavioral recovery—after injury.
Plasticity of Hypothalamic Dopamine Neurons during Lactation Results in Dissociation of Electrical Activity and Release
Authors: Romanò Nicola , Yip Siew H. , Hodson David J. , Guillou Anne , Parnaudeau Sébastien , Kirk Siobhan , Tronche François , Bonnefont Xavier , Le Tissier Paul , Bunn Stephen J. , Grattan Dave R. , Mollard Patrice , Martin Agnès O.
Published: March 2013

Tuberoinfundibular dopamine (TIDA) neurons are the central regulators of prolactin (PRL) secretion. Their extensive functional plasticity allows a change from low PRL secretion in the non-pregnant state to the condition of hyperprolactinemia that characterizes lactation. To allow this rise in PRL, TIDA neurons are thought to become unresponsive to PRL at lactation and functionally silenced. Here we show that, contrary to expectations, the electrical properties of the system were not modified during lactation and that the neurons remained electrically responsive to a PRL stimulus, with PRL inducing an acute increase in their firing rate during lactation that was identical to that seen in non-pregnant mice. Furthermore, we show a long-term organization of TIDA neuron electrical activity with an harmonization of their firing rates, which remains intact during lactation. However, PRL-induced secretion of dopamine (DA) at the median eminence was strongly blunted during lactation, at least in part attributable to lack of phosphorylation of tyrosine hydroxylase, the key enzyme involved in DA synthesis. We therefore conclude that lactation, rather than involving electrical silencing of TIDA neurons, represents a condition of decoupling between electrical activity at the cell body and DA secretion at the median eminence.
Noddy, a Mouse Harboring a Missense Mutation in Protocadherin-15, Reveals the Impact of Disrupting a Critical Interaction Site between Tip-Link Cadherins in Inner Ear Hair Cells
Authors: Geng Ruishuang , Sotomayor Marcos , Kinder Kimberly J. , Gopal Suhasini R. , Gerka-Stuyt John , Chen Daniel H.-C. , Hardisty-Hughes Rachel E. , Ball Greg , Parker Andy , Gaudet Rachelle , Furness David , Brown Steve D. , Corey David P. , Alagramam Kumar N.
Published: March 2013

In hair cells of the inner ear, sound or head movement increases tension in fine filaments termed tip links, which in turn convey force to mechanosensitive ion channels to open them. Tip links are formed by a tetramer of two cadherin proteins: protocadherin 15 (PCDH15) and cadherin 23 (CDH23), which have 11 and 27 extracellular cadherin (EC) repeats, respectively. Mutations in either protein cause inner ear disorders in mice and humans. We showed recently that these two cadherins bind tip-to-tip in a “handshake” mode that involves the EC1 and EC2 repeats of both proteins. However, a paucity of appropriate animal models has slowed our understanding both of the interaction and of how mutations of residues within the predicted interface compromise tip link integrity. Here, we presentnoddy, a new mouse model for hereditary deafness. Identified in a forward genetic screen,noddyhomozygotes lack inner ear function. Mapping and sequencing showed thatnoddymutant mice harbor an isoleucine-to-asparagine (I108N) mutation in the EC1 repeat of PCDH15. Residue I108 interacts with CDH23 EC2 in the handshake and its mutation impairs the interactionin vitro. Thenoddymutation allowed us to determine the consequences of blocking the handshakein vivo: tip link formation and bundle morphology are disrupted, and mechanotransduction channels fail to remain open at rest. These results offer new insights into the interaction between PCDH15 and CDH23 and help explain the etiology of human deafness linked to mutations in the tip-link interface.
Spinal Efference Copy Signaling and Gaze Stabilization during Locomotion in JuvenileXenopusFrogs
Authors: von Uckermann Géraldine , Le Ray Didier , Combes Denis , Straka Hans , Simmers John
Published: March 2013

In swimmingXenopus laevistadpoles, gaze stabilization is achieved by efference copies of spinal locomotory CPG output that produce rhythmic extraocular motor activity appropriate for minimizing motion-derived visual disturbances. During metamorphosis,Xenopusswitches its locomotory mechanism from larval tail-based undulatory movements to bilaterally synchronous hindlimb kick propulsion in the adult. The change in locomotory mode leads to body motion dynamics that no longer require conjugate left–right eye rotations for effective retinal image stabilization. Usingin vivokinematic analyses,in vitroelectrophysiological recordings and specific CNS lesions, we have investigated spino-extraocular motor coupling in the juvenile frog and the underlying neural pathways to understand how gaze control processes are altered in accordance with the animal's change in body plan and locomotor strategy. Recordings of extraocular and limb motor nerves during spontaneous “fictive” swimming in isolated CNS preparations revealed that there is indeed a corresponding change in spinal efference copy control of extraocular motor output. In contrast to fictive larval swimming where alternating bursts occur in bilateral antagonistic horizontal extraocular nerves, during adult fictive limb-kicking, these motor nerves are synchronously active in accordance with the production of convergent eye movements during the linear head accelerations resulting from forward propulsion. Correspondingly, the neural pathways mediating spino-extraocular coupling have switched from contralateral to strictly ipsilateral ascending influences that ensure a coactivation of bilateral extraocular motoneurons with synchronous left–right limb extensions. Thus, adaptive developmental plasticity during metamorphosis enables spinal CPG-driven extraocular motor activity to match the changing requirements for eye movement control during self-motion.
Cortical–Amygdalar Circuit Dysfunction in a Genetic Mouse Model of Serotonin Deficiency
Authors: Dzirasa Kafui , Kumar Sunil , Sachs Benjamin D. , Caron Marc G. , Nicolelis Miguel A. L.
Published: March 2013

Although the majority of first-line antidepressants increase brain serotonin and rare polymorphisms in tryptophan hydroxlase-2 (Tph2), the rate-limiting enzyme in the brain serotonin synthesis pathway, have been identified in cohorts of subjects with major depressive disorder, the circuit level alterations that results from serotonergic hypofunction remain poorly understood. Here we use chronic multicircuit neurophysiological recordings to characterize functional interactions across cortical and limbic circuits in mice engineered to express a human loss-of-function depression alleleTph2-(R441H) [Tph2 knockin (Tph2KI)]. Our results show that Tph2KI mice exhibit increased intra-network synchrony within medial prefrontal cortex (mPFC) and basal amygdala (AMY) and increased inter-network synchrony between these two brain networks. Moreover, we demonstrate that chronic treatment with fluoxetine reverses several of the circuit alterations observed within Tph2KI mice. Together, our findings establish a functional link between functional hyposerotonergia and altered mPFC–AMY network dynamics.
Calpain-2-Mediated PTEN Degradation Contributes to BDNF-Induced Stimulation of Dendritic Protein Synthesis
Authors: Briz Victor , Hsu Yu-Tien , Li Yi , Lee Erin , Bi Xiaoning , Baudry Michel
Published: March 2013

Memory consolidation has been suggested to be protein synthesis dependent. Previous data indicate that BDNF-induced dendritic protein synthesis is a key event in memory formation through activation of the mammalian target of rapamycin (mTOR) pathway. BDNF also activates calpain, a calcium-dependent cysteine protease, which has been shown to play a critical role in learning and memory. This study was therefore directed at testing the hypothesis that calpain activity is required for BDNF-stimulated local protein synthesis, and at identifying the underlying molecular mechanism. In rat hippocampal slices, cortical synaptoneurosomes, and cultured neurons, BDNF-induced mTOR pathway activation and protein translation were blocked by calpain inhibition. BDNF treatment rapidly reduced levels of hamartin and tuberin, negative regulators of mTOR, in a calpain-dependent manner. Treatment of brain homogenates with purified calpain-1 and calpain-2 truncated both proteins. BDNF treatment increased phosphorylation of both Akt and ERK, but only the effect on Akt was blocked by calpain inhibition. Levels of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a phosphatase that inactivates Akt, were decreased following BDNF treatment, and calpain inhibition reversed this effect. Calpain-2, but not calpain-1, treatment of brain homogenates resulted in PTEN degradation. In cultured cortical neurons, knockdown of calpain-2, but not calpain-1, by small interfering RNA completely suppressed the effect of BDNF on mTOR activation. Our results reveal a critical role for calpain-2 in BDNF-induced mTOR signaling and dendritic protein synthesis via PTEN, hamartin, and tuberin degradation. This mechanism therefore provides a link between proteolysis and protein synthesis that might contribute to synaptic plasticity.
Pituitary Adenylate Cyclase 1 Receptor Internalization and Endosomal Signaling Mediate the Pituitary Adenylate Cyclase Activating Polypeptide-Induced Increase in Guinea Pig Cardiac Neuron Excitability
Authors: Merriam Laura A. , Baran Caitlin N. , Girard Beatrice M. , Hardwick Jean C. , May Victor , Parsons Rodney L.
Published: March 2013

After G-protein-coupled receptor activation and signaling at the plasma membrane, the receptor complex is often rapidly internalized via endocytic vesicles for trafficking into various intracellular compartments and pathways. The formation of signaling endosomes is recognized as a mechanism that produces sustained intracellular signals that may be distinct from those generated at the cell surface for cellular responses including growth, differentiation, and survival. Pituitary adenylate cyclase activating polypeptide (PACAP;Adcyap1) is a potent neurotransmitter/neurotrophic peptide and mediates its diverse cellular functions in part through internalization of its cognate G-protein-coupled PAC1 receptor (PAC1R;Adcyap1r1). In the present study, we examined whether PAC1R endocytosis participates in the regulation of neuronal excitability. Although PACAP increased excitability in 90% of guinea pig cardiac neurons, pretreatment with Pitstop 2 or dynasore to inhibit clathrin and dynamin I/II, respectively, suppressed the PACAP effect. Subsequent addition of inhibitor after the PACAP-induced increase in excitability developed gradually attenuated excitability with no changes in action potential properties. Likewise, the PACAP-induced increase in excitability was markedly decreased at ambient temperature. Receptor trafficking studies with GFP-PAC1 cell lines demonstrated the efficacy of Pitstop 2, dynasore, and low temperatures at suppressing PAC1R endocytosis. In contrast, brefeldin A pretreatments to disrupt Golgi vesicle trafficking did not blunt the PACAP effect, and PACAP/PAC1R signaling still increased neuronal cAMP production even with endocytic blockade. Our results demonstrate that PACAP/PAC1R complex endocytosis is a key step for the PACAP modulation of cardiac neuron excitability.
Behavioral and Structural Responses to Chronic Cocaine Require a Feedforward Loop Involving ΔFosB and Calcium/Calmodulin-Dependent Protein Kinase II in the Nucleus Accumbens Shell
Authors: Robison Alfred J. , Vialou Vincent , Mazei-Robison Michelle , Feng Jian , Kourrich Saïd , Collins Miles , Wee Sunmee , Koob George , Turecki Gustavo , Neve Rachael , Thomas Mark , Nestler Eric J.
Published: March 2013

The transcription factor ΔFosB and the brain-enriched calcium/calmodulin-dependent protein kinase II (CaMKIIα) are induced in the nucleus accumbens (NAc) by chronic exposure to cocaine or other psychostimulant drugs of abuse, in which the two proteins mediate sensitized drug responses. Although ΔFosB and CaMKIIα both regulate AMPA glutamate receptor expression and function in NAc, dendritic spine formation on NAc medium spiny neurons (MSNs), and locomotor sensitization to cocaine, no direct link between these molecules has to date been explored. Here, we demonstrate that ΔFosB is phosphorylated by CaMKIIα at the protein-stabilizing Ser27 and that CaMKII is required for the cocaine-mediated accumulation of ΔFosB in rat NAc. Conversely, we show that ΔFosB is both necessary and sufficient for cocaine induction of CaMKIIα gene expressionin vivo, an effect selective for D1-type MSNs in the NAc shell subregion. Furthermore, induction of dendritic spines on NAc MSNs and increased behavioral responsiveness to cocaine after NAc overexpression of ΔFosB are both CaMKII dependent. Importantly, we demonstrate for the first time induction of ΔFosB and CaMKII in the NAc of human cocaine addicts, suggesting possible targets for future therapeutic intervention. These data establish that ΔFosB and CaMKII engage in a cell-type- and brain-region-specific positive feedforward loop as a key mechanism for regulating the reward circuitry of the brain in response to chronic cocaine.
Differential Control of Opioid Antinociception to Thermal Stimuli in a Knock-In Mouse Expressing Regulator of G-Protein Signaling-Insensitive GαoProtein
Authors: Lamberts Jennifer T. , Smith Chelsea E. , Li Ming-Hua , Ingram Susan L. , Neubig Richard R. , Traynor John R.
Published: March 2013

Regulator of G-protein signaling (RGS) proteins classically function as negative modulators of G-protein-coupled receptor signaling.In vitro, RGS proteins have been shown to inhibit signaling by agonists at the μ-opioid receptor, including morphine. The goal of the present study was to evaluate the contribution of endogenous RGS proteins to the antinociceptive effects of morphine and other opioid agonists. To do this, a knock-in mouse that expresses an RGS-insensitive (RGSi) mutant Gαoprotein, GαoG184S(GαoRGSi), was evaluated for morphine or methadone antinociception in response to noxious thermal stimuli. Mice expressing GαoRGSi subunits exhibited a naltrexone-sensitive enhancement of baseline latency in both the hot-plate and warm-water tail-withdrawal tests. In the hot-plate test, a measure of supraspinal nociception, morphine antinociception was increased, and this was associated with an increased ability of opioids to inhibit presynaptic GABA neurotransmission in the periaqueductal gray. In contrast, antinociception produced by either morphine or methadone was reduced in the tail-withdrawal test, a measure of spinal nociception. In whole-brain and spinal cord homogenates from mice expressing GαoRGSi subunits, there was a small loss of Gαoexpression and an accompanying decrease in basal G-protein activity. Our results strongly support a role for RGS proteins as negative regulators of opioid supraspinal antinociception and also reveal a potential novel function of RGS proteins as positive regulators of opioid spinal antinociceptive pathways.
Inhibition of a SNARE-Sensitive Pathway in Astrocytes Attenuates Damage following Stroke
Authors: Hines Dustin J. , Haydon Philip G.
Published: March 2013

A strong body of research has defined the role of excitotoxic glutamate in animal models of brain ischemia and stroke; however, clinical trials of glutamate receptor antagonists have demonstrated their limited capacity to prevent brain damage following ischemia. We propose that astrocyte–neuron signaling represents an important modulatory target that may be useful in mediating damage following stroke. To assess the impact of astrocyte signaling on damage following stroke, we have used the astrocyte-specific dominant-negative SNARE mouse model (dnSNARE). Recent findings have shown that the astrocytic SNARE signaling pathway can affect neuronal excitability by regulating the surface expression of NMDA receptors. Using focal photothrombosis via the Rose Bengal method, as well as excitotoxic NMDA lesions, we show that dnSNARE animals exhibited a sparing of damaged tissue quantified using Nissl and NeuN staining. At the same time point, animals were also tested in behavioral tasks that probe the functional integrity of stroke- or lesion-damaged motor and somatosensory areas. We found that dnSNARE mice performed significantly better than littermate controls on rung walk and adhesive dot removal tasks following lesion. Together, our results demonstrate the important role of astrocytic signaling under ischemic conditions. Drugs targeting astrocyte signaling have a potential benefit for the outcome of stroke in human patients by limiting the spread of damage.
Rate of convergence of the density estimation of regression residual
Authors: Györfi László , Walk Harro
Published: March 2013

Consider the regression problem with a response variable Y and with a d-dimensional feature vector X. For the regression function m(x) = E{Y|X = x}, this paper investigates methods for estimating the density of the residual Y − m(X) from independent and identically distributed data. If the density is twice differentiable and has compact support then we bound the rate of convergence of the kernel density estimate. It turns out that for d ≤ 3 and for partitioning regression estimates, the regression estimation error has no influence on the rate of convergence of the density estimate.
Giant uterine leiomyoma causing acute symptoms
Authors: Máté Szabolcs , Szatmári Erzsébet , Sipos Norbert , Széll János , Szánthó András , Rigó Jr. János
Published: March 2013

The case history of a 71-year-old woman with acute dyspnoea caused by a giant leiomyoma and severe acute anemia due to intratumoral hemorrhage is presented. Urgent operation was performed, and a 13.5 kg pendular tumor was removed. The cornerstones of the differential diagnoses and therapy of giant abdominal tumors is discussed. Orv. Hetil., 2013, 154, 387–390.
Compliance with clinical trial registration and reporting guidelines by Latin American and Caribbean journals
Authors: Reveiz Ludovic , Villanueva Eleana , Iko Chimaraoke , Simera Iveta
Published: March 2013

The objective of this study was to determine to what extent Latin American and Caribbean biomedical journals have endorsed and complied with clinical trial registration and reporting guidelines. A search of randomized clinical trials was carried out using the LILACS database. The randomized clinical trials identified through the search were assessed to determine whether trial registration and CONSORT guidance was mentioned. Information regarding endorsement of the ICMJE, trial registration and other reporting guidelines was extracted from the online instructions for authors of the journals included in the study. The search identified 477 references. We assessed a random sample of 240 titles of which 101 were randomized clinical trials published in 56 journals. Trial registration was reported in 19.8% of the randomized clinical trials, 6.9% were prospectively registered and 3% mentioned CONSORT. The ICMJE was mentioned by 68% of the journals and 36% of journals required trial registration. Fewer journals provided advice on reporting guidelines: CONSORT (13%), PRISMA (1.8%), STROBE (1.8%), and the EQUATOR network (3.6%). Wider endorsement of trial registration and adherence to reporting guidelines is necessary in clinical trials conducted in Latin America and the Caribbean.
Sífilis materna e congênita: ainda um desafio
Authors: Magalhães Daniela Mendes dos Santos , Kawaguchi Inês Aparecida Laudares , Dias Adriano , Calderon Iracema de Mattos Paranhos
Published: March 2013

Este estudo descritivo coletou informações sociodemográficas, obstétricas e relacionadas ao diagnóstico e tratamento da gestante/puérpera e parceiro das 67 gestantes/puérperas notificadas no Sistema Nacional de Agravos de Notificação, usuárias de maternidades públicas do Distrito Federal, Brasil, entre 2009 e 2010. As informações do acompanhamento clínico e laboratorial recebido pela criança vieram do prontuário médico hospitalar, fichas de notificação compulsória e Cartão da Criança. Das gestantes, 41,8% foram adequadamente tratadas, o principal motivo para a inadequação foi a ausência (83,6%) ou inadequação do tratamento do parceiro (88,1%). Mais de um terço necessitou de novo tratamento na maternidade por falta de documentação terapêutica no pré-natal. Dos recém-nascidos com sífilis congênita, 48% fizeram estudo radiográfico, 42% passaram por punção liquórica e 36% deles não receberam qualquer tipo de intervenção. Nota-se, assim, que a qualidade do pré-natal recebido pela gestante não é suficiente para garantir o controle da sífilis congênita e o alcance da meta de incidência da doença.
Decomposição da diferença da expectativa de vida de Minas Gerais em relação ao Rio de Janeiro e São Paulo, Brasil
Authors: Chiavegatto Filho Alexandre Dias Porto , Laurenti Ruy
Published: March 2013

Ao contrário de outros países, comparações entre regiões brasileiras ainda são pouco realizadas. Minas Gerais, Rio de Janeiro e São Paulo têm boa cobertura do registro de óbitos e semelhanças geográficas, o que permite identificar oportunidades de intervenção em saúde. Por outro lado, existem importantes diferenças socioeconômicas, consistentemente piores em Minas Gerais. Foi realizada uma decomposição da diferença da expectativa de vida de Minas Gerais em relação ao Rio de Janeiro e São Paulo para 1996, 2000 e 2010, utilizando a metodologia de Arriaga. Minas Gerais apresentou maior expectativa de vida em relação aos outros dois estados durante todo o período, tanto para homens quanto para mulheres. O grupo etário dos idosos e as doenças crônicas foram as mais importantes para explicar essa diferença, especialmente neoplasias e doenças isquêmicas do coração. Diferenças no estilo de vida e prática de atividade física (melhores em Minas Gerais do que em relação ao Rio de Janeiro e São Paulo) podem ajudar a explicar a inconsistência entre os níveis socioeconômicos e a situação de saúde.
Evaluation of RC and SFRC exterior beam–column joint under cyclic loading for reduction in lateral reinforcement of the joint region
Authors: Patel Priti A. , Desai Atul K. , Desai Jatin A.
Published: March 2013

The integrity of a reinforced concrete structure should be safe and stable under lateral loads, especially those structures that depend on the behaviour of the beam–column joint. The ductility capacity of structural elements has a key role to play in seismic design. The ability of the structure to sustain levels of inelastic deformation under lateral loads, implicit in ductility values, is dependent on the material and detailing used. For the ductile behaviour of beam–column joints, a considerable amount of lateral reinforcement is necessary. An experimental investigation is presented on the use of steel fibre reinforced concrete (SFRC) to provide ductility in a beam–column joint even after the increase in hoop spacing of lateral ties. Six one-third scale exterior beam–column joints were tested under reverse cyclic loading. The SFRC beam–column joint contained volume fraction of 1·5% steel fibre for all variable hoop spacing. The results were compared and evaluated with respect to strength, displacement ductility, energy dissipation, specific damping capacity and stiffness. Experimental results reveal that a SFRC beam–column joint performs satisfactorily and improved joint behaviour is indicated. The results also indicate that a reduction in the number of lateral ties in the beam–column joint by the appropriate use of SFRC can be an alternative solution for avoiding conjunction of reinforcement.
The Test of Time: Art Encyclopedias and the Formation of the Canon of 17Th-Century Painters in the Low Countries
Authors: Vermeylen Filip , van Dijck Maarten , de Laet Veerle
Published: March 2013

This article deals with the process of canon formation for Flemish and Dutch painters from the 17th century onwards. We examine how the essential art-historical treatises and art encyclopedias since Houbraken's Grote Schouburgh der Nederlandsche Konstschilders en Schilderessen ranked and evaluated the leading painters, based on the attention given to them in these volumes. Using standardized z-scores, we map the relative importance the selected artists received in these publications over the 3 centuries. In doing so, we emphasize the path-dependency and the dimension of time in explaining the endurance of certain artists in the long run. From our research it emanates that the canon of Netherlandish painters is much more volatile than previously assumed.
Interested Experts, Confused Novices: Art Expertise and the Knowledge Emotions
Authors: Silvia Paul J.
Published: March 2013

Experts and novices differ in how they experience and understand art, and expertise in the arts moderates a wide range of aesthetic processes. The present research examined the role of expertise in the experience of interest and confusion, two knowledge emotions, particularly whether expertise moderated the cognitive appraisals that bring about the emotions. A sample of 174 people viewed and rated a series of abstract images taken from small-press publications. Expertise was measured with the aesthetic fluency scale (Smith & Smith, 2006), and multivariate multilevel models were used to estimate the effects of expertise and appraisals. As expected, people high in expertise found the images significantly more interesting and less confusing. The main effects of appraisals on interest and confusion replicated past work, and expertise interacted with most of the appraisals—the cognitive foundations of interest and confusion have different weights for experts and novices.
Slova s dvojnymi udarenijami (prosodicesko-intonacionnaja interpretacija teksta poemy "Luc Mikrokozma" Petra Negosa)
Authors: Marojevic Radmilo
Published: March 2013

V nastojascej stat'e rassmatrivaetsja prosodiceskaja i intonacionnaja
struktura stiha poemy ?Luc mikrokozma? Petra Negosa, v castnosti: udarenija
(metriceskie i nemetriceskie, glavnye i pobocnye). V stat'e vvoditsja i
obosnovyvaetsja ponjatie sloznogo foneticeskogo slova, sostojascego iz odnogo
glavnogo foneticeskogo slova i odnogo ili bolee pobocnyh foneticeskih slov. V
monograficeskom issledovanii, sostavnoj cast'ju kotorogo javljaetsja
nastojascaja stat'ja, rassmatrivajutsja voprosy lingvisticeskoj i
stihovedceskoj interpretacii pobocnyh udarenij v serbskom i russkom jazykah,
a imenno: a) mesto pobocnyh udarenij v prosodiceskoj sisteme issleduemyh
jazykov i b) metriceskaja i ritmiceskaja funkcija pobocnyh udarenij v
serbskom i russkom fol'klore i hudozestvennoj literature.
On nouns functioning as prepositions
Authors: Dragicevic Rajna
Published: March 2013

This paper analyzes semantic transformations of nouns functioning as
prepositions. The semantic characteristics of prepositions are discussed, and
Belic? concept of adverbial origin and meaning of prepositions is reviewed.
Contrary to usual perception that prepositions have mere grammatical meaning,
it is concluded in this paper that they also have lexical meaning, like
adverbs. Cognitive linguistics has so far dealt with lexical meanings of
prepositions, and it is up to contemporary semantics to further explore and
evolve this approach. Based on this fact that prepositions have lexical
meaning, it is argued that nouns functioning as prepositions retain that
lexical attribute though with different semantic value, rather than it adopts
grammatical characteristics. It is concluded that semantic meaning of those
nouns used as prepositions could be broken into two segments: adverbial
(place) and nominal (partitive). The nouns which upon occasions may function
as prepositions in Serbian language as a rule denote place and they always
are used with genitive case (mostly partitive), and as a consequence they
often have partitive meaning. In the sentences with nouns functioning as
prepositions, the act expressed encompasses the part of the localizator or it
is performed on its bounds, or near it. Which meaning would prevail depends
on the noun, or verb, or noun in genitive case. A noun and its related
preposition are treated as two lexemes in Serbian descriptive dictionaries,
independent but close in meanings, since the preposition originated from a
noun in a process defined by Irena Grickat as grammar polysemy, i.e. a
polysemy with the grammatical result. In some grammar books identical forms
of a preposition and nominative and accusative noun forms are defined as
homophoria, and those prepositions and nouns are called homophores. Since
homophoria is a type of homonymy, and homonymy excludes semantic relation
between lexemes, the term homophoria had to be discarded. It is suggested in
this paper that only few nouns in Serbian language can function as
prepositions due to fact that only those few have possibility to combine
semantically high-productive spaciality with partitivity (rarely
possessiveness), as a result of their obligatory usage with partitive
(sometimes, possessive) genitive. The usage of nouns as prepositions in
Serbian language is slowly going out because their semantics is imprecise,
and in certain circumstances difficult to differentiate, which means that the
process of transformation of nouns into prepositions was not complete. Thus,
more frequent today are compound prepositions formed by a real preposition
and a noun (navrh, uvrh, podno). Their semantics is more distinctive and more
precise due to real preposition as constituents.
Sovremennaja serbskaja jazykovaja situacija (s tocki zrenija vzaimootnosenija mezdu standartnym i razgovornym jazykami)
Authors: Likomanova Iskra
Published: March 2013

V stat'e s tocki zrenija tradicionoj PLS s nekotoroj sovremennoj
modifikacii ee postulatov otnositel'no slavjanskih literaturnyh jazykov
rassmatrivaetsja sovremennaja jazykovaja situacija v serbskom jazykovom
prostranstve (JaP), tipologiceski sravnivaja ee s drugimi slavjanskimi
jazykami. Osnovnaja ideja raboty v sosuscestvovanii vseh raznovidnostej
nacional'nogo jazyka na protjazenii danogo JaP, na kotoroe skladyvaetsja kak
standartnyj literaturnyj jazyk, tak i vse drugie, v t.c. ustnye idiomy:
dialektnaja rec', povsednevnaja rec', razgovornaja rec', idiolekty nositelej
jazyka. Vvedeno i ?ksplicirovano ponjatie ?otstojanija? mezdu dvumja
osnovnymi normami nacional'nogo jazyka - literaturnoj i kollokvial'noj,
kotorye dlja serbskogo (vprocem i dlja bolgarskogo) otlicaetsja bol'soj
blizost'ju A+ i A-, t.e. fokusov norm. ?to utverzdenie provoditsja s ucetom
genezisa norm, s ucetom ih vysokoj stepen'ju variancii i segodnja i s
ucetom aktual'nogo vzaimodejstvija mezdu nimi. Na sociolingvisticeskie
ponjatija bifokal'nosti norm skladyvaetsja i rjad politiceskih ponjatij kak
oficial'nye i regional'nye men'sinstvennye jazyki, kotorye toze vhodjat v
kartinu JaP, nahodjas' v kommunikativnom prostranstve nacii. Vvidu
dinamiceskih ekstra- i intralingvisticeskih processov, novyh sposobov
sovremennoj komunikacii v sovremennom serbskom jazyke-angloamerikanizacii,
perenosa terminologiceskoj, razgovornoj leksiki iz ustnuju rec' v
pis'mennuju, standartnuju - esce bol'se suzaetsja rasstojanie mezdu dvumja
osnovnymi raznovidnostjami serbskogo jazyka. V etom plane zasluzivaet osoboe
vnimanie teoreticeskoe i prakticeskoe opisanie ne tol'ko norm standartnogo
jazyka, no i opisanie zivoj kollokvial'noj normy, kotoraja dlja serbskogo
jazyka predstavljaet osobuju slavjanskuju specifiku - v tipologiceskom plane.
Exenatide-Induced Reduction in Energy Intake Is Associated With Increase in Hypothalamic Connectivity
Authors: Schlögl Haiko , Kabisch Stefan , Horstmann Annette , Lohmann Gabriele , Müller Karsten , Lepsien Jöran , Busse-Voigt Franziska , Kratzsch Jürgen , Pleger Burkhard , Villringer Arno , Stumvoll Michael
Published: March 2013

OBJECTIVE

Glucagon-like peptide-1 receptor agonists such as exenatide are known to influence neural activity in the hypothalamus of animals and to reduce energy intake. In humans, however, significant weight loss has been observed in only a subgroup of patients. Why only some individuals respond with weight loss and others do not remains unclear. In this functional magnetic resonance imaging (fMRI) study, we investigated differences in hypothalamic connectivity between “responders” (reduction in energy intake after exenatide infusion) and “nonresponders.”

RESEARCH DESIGN AND METHODS

We performed a randomized, double-blinded, placebo-controlled, cross-over fMRI study with intravenous administration of exenatide in obese male volunteers. During brain scanning with continuous exenatide or placebo administration, participants rated food and nonfood images. After each scanning session, energy intake was measured using an ad libitum buffet. Functional hypothalamic connectivity was assessed by eigenvector centrality mapping, a measure of connectedness throughout the brain.

RESULTS

Responders showed significantly higher connectedness of the hypothalamus, which was specific for the food pictures condition, in the exenatide condition compared with placebo. Nonresponders did not show any significant exenatide-induced changes in hypothalamic connectedness.

CONCLUSIONS

Our results demonstrate a central hypothalamic effect of peripherally administered exenatide that occurred only in the group that showed an exenatide-dependent anorexigenic effect. These findings indicate that the hypothalamic response seems to be the crucial factor for the effect of exenatide on energy intake.
The olfactory system in Alzheimer’s disease: Pathology, pathophysiology and pathway for therapy
Authors: Kovács Tibor
Published: March 2013

Olfaction is frequently mentioned as a “neglected sense”, although the olfactory system has several interesting and unique anatomical and physiological features. Olfactory involvement is present in several degenerative disorders, especially in Alzheimer’s disease (AD). The peripheral and central parts of the olfactory system are damaged even in the early stages of AD, manifesting in profound olfactory deficits. Besides the early pathology, the olfactory system may be involved in the pathogenesis of AD by providing a route of entry for pathological agents still unknown. In contrast to this olfactory vector hypothesis, the olfactory system can be used to deliver therapeutic agents in AD, such as nerve growth factor and insulin, by decreasing the side-effects of the therapy or providing a non-invasive method of delivery.
Antisense oligonucleotide mediated therapy of spinal muscular atrophy
Authors: Sivanesan Senthilkumar , Howell Matthew , DiDonato Christine , Singh Ravindra
Published: March 2013

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. SMA results from deletions or mutations of survival motor neuron 1 (SMN1), an essential gene. SMN2, a nearly identical copy, can compensate for SMN1 loss if SMN2 exon 7 skipping is prevented. Among the many cis-elements involved in the splicing regulation of SMN exon 7, intronic splicing silencer N1 (ISS-N1) has emerged as the most effective target for an antisense oligonucleotide (ASO)-mediated splicing correction of SMN2 exon 7. Blocking of ISS-N1 by an ASO has been shown to fully restore SMN2 exon 7 inclusion in SMA patient cells as well as in vivo. Here we review how ISS-N1 targeting ASOs that use different chemistries respond differently in the various SMA mouse models. We also compare other ASO-based strategies for therapeutic splicing correction in SMA. Given that substantial progress on ASO-based strategies to promote SMN2 exon 7 inclusion in SMA has been made, and that similar approaches in a growing number of genetic diseases are possible, this report has wide implications.
The Drift of Modern Fiction
Authors: Edgar Pelham
Published: March 2013

Two tendencies are constant in every form of literature, as indeed they are constant in every manifestation of human activity. We may regard them, therefore, as laws of life operating universally, it is true, but reflected most discernibly in the sensitive medium of the expressive arts. And it is by these tendencies of retrogression and progression that we must seek to measure the advance of fiction, which if not the greatest is incontestably the most flexible of literary forms.
Energy and Action
Authors: Eve
Published: March 2013

It is necessary from time to time either to coin a new word to convey a new meaning, or to use an old word to serve a fresh purpose or idea. The precise meaning given to “energy” by Rankine is now well appreciated, with the further qualification that it may be either due to motion (kinetic), or due to position or shape (potential). All moving masses—air, rivers, projectiles and fly-wheels—have this capacity to do work in virtue of their motion, and the modern term kinetic energy replaces the historically interesting “vis viva”—the living force! The vis viva of a moving body was measured by its mass (or weight) multiplied by the square of its velocity, and kinetic energy is one-half of this quantity. There is nothing mystical about the one-half, it is merely a matter of mathematical convenience. It makes not much difference whether a man buys wine by the pint or by the quart, unless it makes a difference in the amount that he consumes.
The Iceberg—Poem
Authors: Roberts Charles
Published: March 2013

A poem.
Homeric Technique
Authors: Owen
Published: March 2013

There have appeared in recent years a number of books on Homer which encourage the hope that the spirit of Homeric criticism is undergoing a change. It is not that the controversy is settled, or that the Unitarians have won, but the realization seems to be creeping in that after all the Homeric Question has very little to do with the poems. Mr. Bowra puts the case thus: “Both sides have begun to agree on the opinion that, whatever the authorship of the Iliad may be, it is still in some sense a work of art and has undergone some formative influence from a single poet. This poet may have composed the whole poem or he may have transformed independent poems into a unity, but in either case the poem may, and indeed must, be considered as a single work of art.” And Professor Woodhouse more pointedly: “Nothing can alter the fact that the Odyssey stands in the world just as it is, and not otherwise. The function of criticism, here at any rate, is not to teach the poet a better way, but to endeavour to realize at full value just what he has chosen to give, in the way in which he chose to give it.”
Goethe's Place in the History of Science
Authors: Brett
Published: March 2013

Goethe was aware that his age was an age of specialists who were not likely to accept as science the opinions of a poet, though they, frequently accepted as poetry the metrical compositions of scientists. For this reason he gave an account of his work in a history of his botanical studies, asserting that he had devoted himself “seriously through many years to the study of the physical and physiological phenomena of nature, observing thein with the perseverance which passion alone can give”. This is unadulterated truth, but even this candid statement has not sufficed to reconcile the average mind to a belief in the possible union of such extremes as poetry and science. The historian of literature approaches Goethe's scientific writings with some misgiving and treats them as though they needed some apology. The historian of science, if he is honest, cannot overlook Goethe; but the history of science is still an undeveloped branch of literature and is dominated by the belief that what is now superseded has very little intrinsic value. Between these two attitudes, both limited and consequently prejudiced, there is a middle path which the circumstances indicate, and the first necessity is to define the special conditions which make intelligible the synthesis of poetry and science in the personality of Goethe.
Matthew Arnold and the Elizabethans
Authors: Brown
Published: March 2013

Nothing is more peculiar in the criticism of Matthew Arnold than the rarity and the brevity of his references to his English contemporaries. “ How astonishing it would be”, exclaims Mr. T. S. Eliot “if a man like Arnold had concerned himself with the art of the novel, had compared Thackeray with Flaubert, had analysed the work of Dickens, had shown his contemporaries exactly why the author of Amos Barton is a more serious writer than Dickens, and, why the author of La Chartreuse de Parme is more serious than either” It would not be in the least astonishing: the usual way to a critical reputation, the way followed by Sainte-Beuve and by Taine and by Hazlitt, is in large part, at least, by illuminating analysis and appraisal of contemporary books. Matthew Arnold was so far from following this way that his only significant allusion to Dickens is in the course of an argument about Irish education and his only consideration of Tennyson and Clough is in a consideration of the style and metre proper to a translation of Homer. He speaks of his contemporaries only in passing, touches only upon an aspect or two of their work, leaves us in doubt of the estimate he would place upon them. Arnold's silence was no accident,—it was imposed upon him by his definition of criticism as “a disinterested endeavour to learn and propagate the best that is known and thought in the world”. “How much of current English literature” he inquires, “comes into this ‘best that is known and thought in the world’?” And he makes haste to answer: “Not very much, I fear.”
Marjorie Pickthall
Authors: Collin
Published: March 2013

Marjorie Pickthall was harassed by two or three handicaps. If she could have got rid of them she would have been the solitary great writer in Canadian literature.
Reviews
Authors: Cochrane  , Shaw  , Cunningham G. Watts , Burt
Published: March 2013

John Buchan, Memory-Hold-the-Door, reviewed by C. N. Cochrane

Etienne Gilson, Dante et la Philosophie, reviewed by J. E. Shaw

David Bidney, The Psychology and Ethics of Spinoza: A Study in the History and Logic of Ideas, reviewed by G. Watts Cunningham

R. Flenley, Essays in Canadian History, reviewed by A. L. Burt
Thematic Symbols in the Poetry of Aiken and MacLeish
Authors: Edison George
Published: March 2013

Conrad Aiken and Archibald MacLeish re-echo traditional accents in modern American poetry. In contrast to much that is mordant and contumacious in the verse of today, their work is instinct with a strangely pained and penetrating lyricism. Despite a technical modernism of phrase and mode, they reveal a profound emotional kinship with the varied utterance of other poets in every age who have been sensitive to the soft, inexorable footfall of change and whose days have been haunted by what Middleton Murry calls "the anguish of the temporal." This is not to imply that Aiken and MacLeish have remained unresponsive to the burden of their contemporaneity; nor is it to suggest that their poetry merely registers an aesthetic withdrawal, such as characterizes the dream-saturated verse of de la Mare, or the gnome-like waywardness of Yeats's early work. On the contrary, both these men have sought to communicate a complex and poignant sense of alienation which they have experienced in face of the grotesque and dreary vulgarities of modern bourgeois civilization.
The Place of Art in Plato's Ideal State
Authors: Duncan Sir Patrick
Published: March 2013

The passages in the Republic in which Plato imposes restrictions on the exercise of the artistic faculty-more especially on poets -in the ideal State, have called for much explanation and some criticism from his commentators. It has seemed difficult to reconcile Plato as we know him from his writings, richly endowed as he was with the imagination of the poet, and with a supreme gift of dramatic creation and literary expression, with the attitude towards art and literature which he makes Socrates adopt in the Republic. There, as it would seem, the only value to be found in art, or at any rate in literature and music, is in the extent to which it directly reinforces the moral code of which the ideal State is the expression. Art, in other words, must be didactic, and must not exhibit or present any situation or character from which a moral lesson cannot directly be drawn. Beyond that it is to be strictly banned.
Variations in Canadian Landscape Painting
Authors: Buchanan Donald
Published: March 2013

The first sign of a really popular interest in our more original landscape painters, the first indication that the reading public had a taste for descriptions of new trends in Canadian painting, came about two years after F. B. Housser had published his book A Canadian Art Movement(1926). The book sold slowly at first, then more rapidly and was soon being widely read. Mr Housser, who was a financial editor, had written an account in an easy, journalistic style of how Lawren Harris and A. Y. Jackson and the others in the Group of Seven, scorning the dullness of academic painting, had launched an art movement in which bright colours and decorative patterns replaced the gray skies and naturalist landscapes favoured by the Dutch and Barbizon schools. This story of the Group of Seven had many facets to attract the layman. There was romance in the life of Tom Thomson, who had been a ranger in Algonquin Park and had painted the wilderness with an intense concentration upon its bolder aspects. Also, A. Y. Jackson had expressed the gospel of nationalism; Jackson who, in letters and in an occasional public address, had insisted that Canadian painters in their work must understand that the atmosphere, the colours, the four changes of season, were different in this country from elsewhere.