bluuebunny/crossref_metadata_2025 huggingface dataset:
von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy
Authors: Lillicrap David
Published: September 2013

von Willebrand disease (VWD) is the most common autosomally inherited bleeding disorder. The disease represents a range of quantitative and qualitative pathologies of the adhesive glycoprotein von Willebrand factor (VWF). The pathogenic mechanisms responsible for the type 2 qualitative variants of VWF are now well characterized, with most mutations representing missense substitutions influencing VWF multimer structure and interactions with platelet GPIbα and collagen and with factor VIII. The molecular pathology of type 3 VWD has been similarly well characterized, with an array of different mutation types producing either a null phenotype or the production of VWF that is not secreted. In contrast, the pathogenetic mechanisms responsible for type 1 VWD remain only partially resolved. In the hemostasis laboratory, the measurement of VWF:Ag and VWF:RCo are key components in the diagnostic algorithm for VWD, although the introduction of direct GPIbα-binding assays may become the functional assay of choice. Molecular genetic testing can provide additional benefit, but its utility is currently limited to type 2 and 3 VWD. The treatment of bleeding in VWD involves the use of desmopressin and plasma-derived VWF concentrates and a variety of adjunctive agents. Finally, a new recombinant VWF concentrate has just completed clinical trial evaluation and has demonstrated excellent hemostatic efficacy and safety.
Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI
Authors: Copelan Edward A. , Hamilton Betty K. , Avalos Belinda , Ahn Kwang Woo , Bolwell Brian J. , Zhu Xiaochun , Aljurf Mahmoud , van Besien Koen , Bredeson Christopher , Cahn Jean-Yves , Costa Luciano J. , de Lima Marcos , Gale Robert Peter , Hale Gregory A. , Halter Joerg , Hamadani Mehdi , Inamoto Yoshihiro , Kamble Rammurti T. , Litzow Mark R. , Loren Alison W. , Marks David I. , Olavarria Eduardo , Roy Vivek , Sabloff Mitchell , Savani Bipin N. , Seftel Matthew , Schouten Harry C. , Ustun Celalettin , Waller Edmund K. , Weisdorf Daniel J. , Wirk Baldeep , Horowitz Mary M. , Arora Mukta , Szer Jeff , Cortes Jorge , Kalaycio Matt E. , Maziarz Richard T. , Saber Wael
Published: September 2013

Key Points

In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.
Comparison of RefSeq protein-coding regions in human and vertebrate genomes
Authors: Fong Jessica H , Murphy Terence D , Pruitt Kim D
Published: September 2013

Background

Advances in high-throughput sequencing technology have yielded a large number of publicly available vertebrate genomes, many of which are selected for inclusion in NCBI’s RefSeq project and subsequently processed by NCBI’s eukaryotic annotation pipeline. Genome annotation results are affected by differences in available support evidence and may be impacted by annotation pipeline software changes over time. The RefSeq project has not previously assessed annotation trends across organisms or over time. To address this deficiency, we have developed a comparative protocol which integrates analysis of annotated protein-coding regions across a data set of vertebrate orthologs in genomic sequence coordinates, protein sequences, and protein features.

Results

We assessed an ortholog dataset that includes 34 annotated vertebrate RefSeq genomes including human. We confirm that RefSeq protein-coding gene annotations in mammals exhibit considerable similarity. Over 50% of the orthologous protein-coding genes in 20 organisms are supported at the level of splicing conservation with at least three selected reference genomes. Approximately 7,500 ortholog sets include at least half of the analyzed organisms, show highly similar sequence and conserved splicing, and may serve as a minimal set of mammalian “core proteins” for initial assessment of new mammalian genomes. Additionally, 80% of the proteins analyzed pass a suite of tests to detect proteins that lack splicing conservation and have unusual sequence or domain annotation. We use these tests to define an annotation quality metric that is based directly on the annotated proteins thus operates independently of other quality metrics such as availability of transcripts or assembly quality measures. Results are available on the RefSeq FTP site [http://ftp.ncbi.nlm.nih.gov/refseq/supplemental/ProtCore/SM1.txt].

Conclusions

Our multi-factored analysis demonstrates a high level of consistency in RefSeq protein representation among vertebrates. We find that the majority of the RefSeq vertebrate proteins for which we have calculated orthology are good as measured by these metrics. The process flow described provides specific information on the scope and degree of conservation for the analyzed protein sequences and annotations and will be used to enrich the quality of RefSeq records by identifying targets for further improvement in the computational annotation pipeline, and by flagging specific genes for manual curation.
Delivering enhanced cardiovascular (Hypertension) disease care through private health facilities in Pakistan
Authors: Khan Muhammad Amir , Javed Wajiha , Ahmed Maqsood , Walley John , Khan Haroon Jahangir
Published: September 2013

Background

Cardiovascular diseases (CVDs) are one of the leading causes of death and disability in the world. Over 80% of CVD deaths take place in low-and middle-income countries. One-third of the population aged above 40 years suffers from Hypertension (HTN) and this is largely unreported as there is no registry for CVDs. No guidelines are available for use in health care facilities, especially private health facilities where practice among GPs varies considerably. We aim to conduct a Cluster Randomized Controlled trial delivering a quality HTN-CVD care package at strengthened private health facilities as compared to current practice at private health facilities.

Methods/Design

A pragmatic cluster randomized trial, with qualitative and economic studies, will be conducted in Sargodha district of Punjab, Pakistan, from January 2012 to December 2016. At least 912 hypertensives will be registered in the two arms, six clusters per arm. The proposed cluster randomized controlled trial will evaluate the effects of delivering quality HTN-CVD care, through enabled private health care facilities, to achieve better case registration, adherence and hypertension control also blood glucose and serum cholesterol control. The trial will be conducted through the doctors and paramedics at private health facilities. Main outcomes are mean difference in Systolic blood pressure among the two arms. Secondary outcomes are mean change in total serum cholesterol levels and mean change in glycaemic control achieved in the adult hypertensive patients. Individual and Cluster level analysis will be done according to intention-to-treat.

Discussion

Due to the high burden of disease where 1 in 3 individuals aged above 45 suffers from hypertension, topped with the fact that there is a dearth of a set of available, standardised guidelines for management, the disease is constantly on a hike in Pakistan. The government has made no effort to issue a set of guidelines adapted specifically for our population and this becomes more of a problem when managing CVD in urban population through private practitioners whose practices vary widely.If our set of context sensitive guidelines show an effectiveness in the proposed intervention districts it will be replicated in other such settings.

Trial registration

Current Controlled Trials ISRCTN34381594
Cancer-testis gene expression is associated with the methylenetetrahydrofolate reductase 677 C>T polymorphism in non-small cell lung carcinoma
Authors: Senses Kerem M , Gonen Mithat , Barutcu Ahmet R , Kalaylioglu Zeynep , Isbilen Murat , Konu Ozlen , Chen Yao T , Altorki Nasser K , Gure Ali O
Published: September 2013

Background

Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels of SAH and Homocysteine levels, and altered levels of DNA methylation. We, therefore, asked whether the five most commonly occurring polymorphisms in four of the enzymes in the 1-carbon pathway associated with CT gene expression status in patients with NSCLC.

Methods

Fifty patients among a cohort of 763 with NSCLC were selected based on CT gene expression status and typed for five polymorphisms in four genes known to affect SAM generation by allele specific q-PCR and RFLP.

Results

We identified a significant association between CT gene expression and the MTHFR 677 CC genotype, as well as the C allele of the SNP, in this cohort of patients. Multivariate analysis revealed that the genotype and allele strongly associate with CT gene expression, independent of potential confounders.

Conclusions

Although CT gene expression is associated with DNA demethylation, in NSCLC, our data suggests this is unlikely to be the result of decreased MTHFR function.
Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections
Authors: Sherry Leighann , Millhouse Emma , Lappin David F , Murray Colin , Culshaw Shauna , Nile Christopher J , Ramage Gordon
Published: September 2013

Background

A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.

Methods

Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.

Results

CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.

Conclusions

Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.
In vitro antibacterial activity of Tabernaemontana alternifolia (Roxb) stem bark aqueous extracts against clinical isolates of methicillin resistant Staphylococcus aureus
Authors: Marathe Nachiket P , Rasane Mandar H , Kumar Himanshu , Patwardhan Ankur A , Shouche Yogesh S , Diwanay Sham S
Published: September 2013

Background

The rise of antibiotic resistance among methicillin resistant Staphylococcus aureus (MRSA), have caused concerns for the treatment of MRSA infections. Hence, search for an alternative therapy for these infections is inevitable. Folk Indian medicine refers to the use of leaf and stem bark powder of Tabernaemontana alternifolia (Roxb) in treatment of skin infections, but no scientific report establishes its antibacterial activity.

Methods

Direct aqueous extracts and sequential aqueous extracts of the stem bark of T. alternifolia (using petroleum ether and ethyl acetate as other solvents) were prepared by soxhlet extraction. The antibiotic sensitivity profiles of the clinical isolates were determined against 18 antibiotics using disc diffusion method. The isolates were identified by 16S rRNA gene sequencing. The methicillin resistance among S. aureus (MRSA) was confirmed by PCR amplification of mecA gene. The disc diffusion method was used to determine the antibacterial activity of the extracts. The micro-dilution method was used to determine the minimum inhibitory concentration (MIC) of the extract against the test organism. To further evaluate the therapeutic potential of the extract, cell cytotoxicity was checked on Vero cells by MTT assay. Chemical profiling of the extract was done by HPTLC method.

Results

The aqueous extracts of T. alternifolia stem bark exhibited antibacterial activity against Gram-positive microorganisms, particularly against clinical isolates of MRSA and vancomycin resistant S. aureus (VRSA). The minimum inhibitory concentration (MIC) of extract against the isolates ranged from 600–800 μg/ml. The extract did not exhibit cytotoxic activity against Vero cells even at the concentration of 4 mg/ml. The chemical profiling revealed presence of alkaloids, flavonoids, coumarins, saponins and steroids. Petroleum ether and ethyl acetate extracts did not exhibit antibacterial activity.

Conclusion

Our results offer a scientific basis for the traditional use of T. alternifolia in the treatment of skin infections, showing that the plant extract has an enormous potential as a prospective alternative therapy against MRSA skin infections. The present study lays the basis for future studies, to validate the possible use of T. alternifolia as a candidate in the treatment of MRSA infections.
GIS-aided planning of insecticide spraying to control dengue transmission
Authors: Chu Hone-Jay , Chan Ta-Chien , Jao Fang-Ju
Published: September 2013

Background

The purpose of this paper is to integrate a multi-objective integer programming formulation and geographic information system (GIS) into dynamically planning the insecticide spraying area for preventing the transmission of dengue fever.

Methods

The optimal spraying area to combat dengue infections is calculated by the multi-objective integer programming model using the dengue epidemic in 2007 in Tainan City of southern Taiwan and is compared with the areas actually sprayed by the local health department. The dynamic epidemic indicators (i.e. frequency, intensity and duration) that identify major temporal characteristics of the dynamic process of an epidemic are all incorporated into the model.

Results

The results indicate that the model can design the spraying area effectively when the trade-off between the coverage of dengue epidemics risk and area compactness is considered.

Conclusions

The model provides an alternative way to obtain a cost-effective spraying area in controlling future dengue epidemics. The proposed model in this study will be beneficial for strategically allocating dengue control resources.
Genetic variance in Nitric Oxide Synthase and Endothelin Genes among children with and without Endothelial Dysfunction
Authors: Chatsuriyawong Siriporn , Gozal David , Kheirandish-Gozal Leila , Bhattacharjee Rakesh , Khalyfa Ahamed A , Wang Yang , Hakonarson Hakon , Keating Brendan , Sukhumsirichart Wasana , Khalyfa Abdelnaby
Published: September 2013

Background

The presence of endothelial dysfunction (ED) constitutes an early risk factor for cardiovascular disease (CVD) in children. Nitric oxide (NO) and endothelin (EDN) are generated in endothelial cells and are critical regulators of vascular function, with ED resulting from an imbalance between these two molecules. We hypothesized that genetic variants in NO synthase and EDN isoforms and its receptors (EDNRA and EDNRB) may account for a proportion of the risk for ED in developing children.

Methods

Consecutive children (ages 5–10 years) were prospectively recruited from the community. Time to peak post-occlusive reperfusion (Tmax) was considered as the indicator of either normal endothelial function (NEF; Tmax < 45 sec) or ED (Tmax ≥ 45 sec). Lipid profiles, high sensitivity C-reactive protein (hsCRP), fasting glucose and insulin were assayed using ELISA. Genomic DNA from peripheral blood was extracted and genotyped for NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), EDNRA (27 SNPs), and EDNRB (23 SNPs) using a custom SNPs array. Linkage disequilibrium was analyzed using Haploview version 4.2 software.

Results

The relative frequencies of SNPs were evaluated in 122 children, 84 with NEF and 38 with ED. The frequencies of NOS1 (11 SNPs), and EDN1 (2 SNPs) were differentially distributed between NEF vs. ED, and no significant differences emerged for all other genes. Significant SNPs for NOS1 and EDN1 SNPs were further validated with RT-PCR.

Conclusions

Genetic variants in the NOS1 and EDN1 genes appear to account for important components of the variance in endothelial function, particularly when concurrent risk factors such as obesity exist. Thus, analysis of genotype-phenotype interactions in children at risk for ED will be critical for more accurate formulation of categorical CVD risk estimates.
Evidence for the interaction of the human metapneumovirus G and F proteins during virus-like particle formation
Authors: Loo Liat Hui , Jumat Muhammad Raihan , Fu Yi , Ayi Teck Choon , Wong Pui San , Tee Nancy WS , Tan Boon Huan , Sugrue Richard J
Published: September 2013

Background

Human metapneumovirus (HMPV) is now a major cause of lower respiratory infection in children. Although primary isolation of HMPV has been achieved in several different cell lines, the low level of virus replication and the subsequent recovery of low levels of infectious HMPV have hampered biochemical studies on the virus. These experimental methodologies usually require higher levels of biological material that can be achieved following HMPV infection. In this study we demonstrate that expression of the HMPV F, G and M proteins in mammalian cells leads to HMPV virus-like particles (VLP) formation. This experimental strategy will serve as a model system to allow the process of HMPV virus assembly to be examined.

Methods

The HMPV F, G and M proteins were expressed in mammalian cell lines. Protein cross-linking studies, sucrose gradient centrifugation and in situ imaging was used to examine interactions between the virus proteins. VLP formation was examined using sucrose density gradient centrifugation and electron microscopy analysis.

Results

Analysis of cells co-expressing the F, G and M proteins demonstrated that these proteins interacted. Furthermore, in cells co-expression the three HMPV proteins the formation VLPs was observed. Image analysis revealed the VLPs had a similar morphology to the filamentous virus morphology that we observed on HMPV-infected cells. The capacity of each protein to initiate VLP formation was examined using a VLP formation assay. Individual expression of each virus protein showed that the G protein was able to form VLPs in the absence of the other virus proteins. Furthermore, co-expression of the G protein with either the M or F proteins facilitated their incorporation into the VLP fraction.

Conclusion

Co-expression of the F, G and M proteins leads to the formation of VLPs, and that incorporation of the F and M proteins into VLPs is facilitated by their interaction with the G protein. Our data suggests that the G protein plays a central role in VLP formation, and further suggests that the G protein may also play a role in the recruitment of the F and M proteins to sites of virus particle formation during HMPV infection.
Noise propagation through extracellular signaling leads to fluctuations in gene expression
Authors: Tabbaa Omar P , Nudelman German , Sealfon Stuart C , Hayot Fernand , Jayaprakash Ciriyam
Published: September 2013

Background

Cell-to-cell variability in mRNA and proteins has been observed in many biological systems, including the human innate immune response to viral infection. Most of these studies have focused on variability that arises from (a) intrinsic stochastic fluctuations in gene expression and (b) extrinsic sources (e.g. fluctuations in transcription factors). The main focus of our study is the effect of extracellular signaling on enhancing intrinsic stochastic fluctuations. As a new source of noise, the communication between cells with fluctuating numbers of components has received little attention. We use agent-based modeling to study this contribution to noise in a system of human dendritic cells responding to viral infection.

Results

Our results, validated by single-cell experiments, show that in the transient state cell-to-cell variability in an interferon-stimulated gene (DDX58) arises from the interplay between the spatial randomness of the cellular sources of the interferon and the temporal stochasticity of its own production. The numerical simulations give insight into the time scales on which autocrine and paracrine signaling act in a heterogeneous population of dendritic cells upon viral infection. We study the effect of different factors that influence the magnitude of the cell-to-cell-variability of the induced gene, including the cell density, multiplicity of infection, and the time scale over which the cellular sources begin producing the cytokine.

Conclusions

We propose a mechanism of noise propagation through extracellular communication and establish conditions under which the mechanism is operative. The cellular stochasticity of gene induction, which we investigate, is not limited to the specific interferon-induced gene we have studied; a broad distribution of copy numbers across cells is to be expected for other interferon-stimulated genes. This can lead to functional consequences for the system-level response to a viral challenge.
European Community Legislation and Actions
Authors: Delfino Rossella
Published: September 2013

NB:

This section presents a series of non legislative actions and legislative acts directly or indirectly linked to contract law, which were adopted at European level between mid-April and mid July 2013.
Two-Dimensional Representation of Action and Arm-Use Sequences in the Presupplementary and Supplementary Motor Areas
Authors: Nakajima Toshi , Hosaka Ryosuke , Tsuda Ichiro , Tanji Jun , Mushiake Hajime
Published: September 2013

The medial frontal cortex has been thought to be crucially involved in temporal structuring of behavior in monkeys and humans. We examined neuronal activity in the supplementary and presupplementary motor areas of monkeys to investigate how the nervous system deals with the coding of 16 motor sequences resulting from multiple actions involving bilateral use of the arms. We first found in both areas that this behavioral demand resulted in attribute-based representation of individual motor acts, reflecting functional (action) or anatomical (right/left arm) attributes. Actions were frequently represented according to a body-axis-centered reference frame (supination or pronation) regardless of the arm to be used. Moreover, behavioral sequences were primarily represented with respect to the action- or arm-use sequence rather than the sequence of individual movements. We propose that the two-dimensional attribute-based sequence representation provides a robust and efficient means of processing multiple behavioral sequences.
Sulcal Depth-Position Profile Is a Genetically Mediated Neuroscientific Trait: Description and Characterization in the Central Sulcus
Authors: McKay D. Reese , Kochunov Peter , Cykowski Matthew D. , Kent Jack W. , Laird Angela R. , Lancaster Jack L. , Blangero John , Glahn David C. , Fox Peter T.
Published: September 2013

Genetic and environmental influences on brain morphology were assessed in an extended-pedigree design by extracting depth-position profiles (DPP) of the central sulcus (CS). T1-weighted magnetic resonance images were used to measure CS length and depth in 467 human subjects from 35 extended families. Three primary forms of DPPs were observed. The most prevalent form, present in 70% of subjects, was bimodal, with peaks near hand and mouth regions. Trimodal and unimodal configurations accounted for 15 and 8%, respectively. Genetic control accounted for 56 and 66% of between-subject variance in average CS depth and length, respectively, and was not significantly influenced by environmental factors. Genetic control over CS depth ranged from 1 to 50% across the DPP. Areas of peak heritability occurred at locations corresponding to hand and mouth areas. Left and right analogous CS depth measurements were strongly pleiotropic. Shared genetic influence lessened as the distance between depth measurements was increased. We argue that DPPs are powerful phenotypes that should inform genetic influence of more complex brain regions and contribute to gene discovery efforts.
Presynaptic Control of Corticostriatal Synapses by Endogenous GABA
Authors: Logie Christopher , Bagetta Vincenza , Bracci Enrico
Published: September 2013

Corticostriatal terminals have presynaptic GABABreceptors that limit glutamate release, but how these receptors are activated by endogenous GABA released by different types of striatal neurons is still unknown. To address this issue, we used single and paired whole-cell recordings combined with stimulation of corticostriatal fibers in rats and mice. In the presence of opioid, GABAA, and NK1 receptor antagonists, antidromic stimulation of a population of striatal projection neurons caused suppression of subsequently evoked EPSPs in projection neurons. These effects were larger at intervals of 500 ms than 1 or 2 s, and were fully blocked by the selective GABABreceptor antagonist CGP 52432. Bursts of spikes in individual projection neurons were not able to inhibit evoked EPSPs. Similarly, spikes in fast spiking interneurons and low-threshold spike interneurons failed to elicit detectable effects mediated by GABABreceptors. Conversely, spikes in individual neurogliaform interneurons suppressed evoked EPSPs, and these effects were blocked by CGP 52432. These results provide the first demonstration of how GABABreceptors are activated by endogenous GABA released by striatal neuronal types.
Decrease of Gray Matter Volume in the Midbrain is Associated with Treatment Response in Medication-Overuse Headache: Possible Influence of Orbitofrontal Cortex
Authors: Riederer Franz , Gantenbein Andreas R. , Marti Marvin , Luechinger Roger , Kollias Spyridon , Sándor Peter S.
Published: September 2013

Patients with chronic daily headache and overuse of analgesics, triptans, or other acute headache compounds, are considered to suffer from medication-overuse headache (MOH). This implies that medication overuse is the cause of headache chronification. It remains a key question why only two-thirds of patients with chronic migraine-like headache and overuse of pain medication improve after detoxification, whereas the remainder continue to have chronic headache. In the present longitudinal MRI study, we used voxel-based morphometry to investigate gray matter changes related to medication withdrawal in a group of humans with MOH. As a main result, we found that only patients with significant clinical improvement showed a significant decrease of previously increased gray matter in the midbrain including periaqueductal gray matter and nucleus cuneiformis, whereas patients without improvement did not. Patients without treatment response had less gray matter in the orbitofrontal cortex. Another striking result is the correlation of treatment response with the amount of orbitofrontal gray matter. Thus, we demonstrate adaptive gray matter changes within the pain modulatory system in patients with MOH who responded to detoxification, probably reflecting neuronal plasticity. Decreased gray matter in the orbitofrontal cortex at baseline may be predictive of poor response to treatment.
Activity-Dependent Regulation of the K/Cl Transporter KCC2 Membrane Diffusion, Clustering, and Function in Hippocampal Neurons
Authors: Chamma Ingrid , Heubl Martin , Chevy Quentin , Renner Marianne , Moutkine Imane , Eugène Emmanuel , Poncer Jean Christophe , Lévi Sabine
Published: September 2013

The neuronal K/Cl transporter KCC2 exports chloride ions and thereby influences the efficacy and polarity of GABA signaling in the brain. KCC2 is also critical for dendritic spine morphogenesis and the maintenance of glutamatergic transmission in cortical neurons. Because KCC2 plays a pivotal role in the function of central synapses, it is of particular importance to understand the cellular and molecular mechanisms underlying its regulation. Here, we studied the impact of membrane diffusion and clustering on KCC2 function. KCC2 forms clusters in the vicinity of both excitatory and inhibitory synapses. Using quantum-dot-based single-particle tracking on rat primary hippocampal neurons, we show that KCC2 is slowed down and confined at excitatory and inhibitory synapses compared with extrasynaptic regions. However, KCC2 escapes inhibitory synapses faster than excitatory synapses, reflecting stronger molecular constraints at the latter. Interfering with KCC2–actin interactions or inhibiting F-actin polymerization releases diffusion constraints on KCC2 at excitatory but not inhibitory synapses. Thus, F-actin constrains KCC2 diffusion at excitatory synapses, whereas KCC2 is confined at inhibitory synapses by a distinct mechanism. Finally, increased neuronal activity rapidly increases the diffusion coefficient and decreases the dwell time of KCC2 at excitatory synapses. This effect involves NMDAR activation, Ca2+influx, KCC2 S940 dephosphorylation and calpain protease cleavage of KCC2 and is accompanied by reduced KCC2 clustering and ion transport function. Thus, activity-dependent regulation of KCC2 lateral diffusion and clustering allows for a rapid regulation of chloride homeostasis in neurons.
The nature of parts of speech
Authors: Lehmann Christian
Published: September 2013

Parts of speech have both semantic and structural aspects. The two sets of features are essentially incommensurate, since the semantic features derive from the functions of language in communication and cognition, while the structural features are essentially based in the combinatorial potential of signs in a text. Consequently, the two sets of features are largely independent of each other.Their combination in a language yields sets of parts of speech whose systematicity is largely language-internal. To the extent that there is a functional motivation for parts of speech, three restrictions must be made: 1) It is not, in the first place, a cognitive, but rather a communicative motivation. 2) The functional motivation of word classes is not direct, but mediated by semantic and syntactic categories of higher order. 3) Only the primary word classes (verb and noun) are motivated in this way. The secondary classes (adjectives, adverbs etc.) and the minor word classes (pronouns, subordinators etc.) increasingly have a systeminternal structural rather than a universal functional motivation. Given these heterogeneous functions and constraints, there is no uniform nature to all parts of speech.
Estimativa de atributos do solo por meio de espectrorradiometria difusa
Authors: Cezar Everson , Nanni Marcos Rafael , Demattê José Alexandre M. , Chicati Marcelo Luiz , Oliveira Roney Berti de
Published: September 2013

Diversos avanços têm sido conquistados no campo da espectrorradiometria difusa, nas últimas décadas. Na área agrícola, a busca por métodos de quantificação de atributos físicos e químicos do ambiente de produção, com base na reflectância do solo, tem sido pesquisada constantemente. O objetivo deste trabalho foi avaliar a possibilidade de estimar os teores de silte, areia, argila, soma de bases, matéria orgânica e ferro total em amostras de solo, a partir de sua energia refletida. As amostras foram coletadas em uma área de 2.500 ha, localizada na região noroeste paranaense, composta por solos das classes Latossolo Vermelho, Nitossolo Vermelho, Argissolo Vermelho, Cambissolo Háplico e Neossolo Quartzarênico. As profundidades de amostragem foram de 0-0,2 e 0,2-0,8 m. Os pontos amostrados foram escolhidos com base em um grid: de 500 x 500 m, que recobriu toda a área de trabalho, totalizando, dessa forma, 100 pontos para o horizonte superficial e 100 pontos para o subsuperficial. As leituras espectrais foram obtidas em laboratório pelo sensor FieldSpec 3 JR. na faixa de 350 a 2.500 nm. As curvas espectrais das amostras foram separadas em bandas e alturas, que se relacionaram com cada atributo por meio de regressão linear múltipla. A espectrorradiometria difusa evidenciou-se mais eficiente na estimação de areia, argila, soma de bases e ferro total e menos eficiente na estimação da matéria orgânica e do silte, em ambos os horizontes. Os resultados após a validação dos modelos indicam que a espectrorradiometria difusa é ferramenta promissora, que pode ser utilizada na determinação de atributos do solo.
Compaction of an Oxisol and chemical composition of palisadegrass
Authors: Sousa Neto Eurico Lucas de , Pierangeli Maria Aparecida Pereira , Lal Rattan
Published: September 2013

Compaction is an important problem in soils under pastoral land use, and can make livestock systems unsustainable. The objective of this research was to study the impact of soil compaction on yield and quality of palisade (UROCHLOA BRIZANTHA cv. Marandu). The experiment was conducted on an Oxisol in the State of Mato Grosso, Brazil. Treatments consisted of four levels of soil compaction: no compaction (NC), slight compaction (SC), medium compaction (MC) and high compaction (HC). The following soil properties were evaluated (layers 0-0.05 and 0.05-0.10 m): aggregate size distribution, bulk density (BD), macroporosity, microporosity, total porosity (TP), relative compaction (RC), and the characteristics of crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and dry matter yield (DMY) of the forage. Highly compacted soil had high BD and RC, and low TP (0-0.05 m). Both DMY and CP were affected by HC, and both were strongly related to BD. Higher DMY (6.96 Mg ha-1) and CP (7.8 %) were observed in the MC treatment (BD 1.57 Mg m-3 and RC 0.91 Mg m-3, in 0-0.05 m). A high BD of 1.57 Mg m-3 (0-0.05 m) did not inhibit plant growth. The N concentration in the palisade biomass differed significantly among compaction treatments, and was 8.72, 11.20, 12.48 and 10.98 g kg-1 in NC, SC, MC and HC treatments, respectively. Increase in DMY and CP at the MC level may be attributed to more absorption of N in this coarse-textured soil.
Extractants to assess zinc phytoavailability in mineral fertilizer and industrial by-products
Authors: Souza Camila Prado Cenciani de , Abreu Cleide Aparecida de , Andrade Cristiano Alberto de , Abreu Mônica Ferreira de
Published: September 2013

Efficient analytical methods for the quantification of plant-available Zn contained in mineral fertilizers and industrial by-products are fundamental for the control and marketing of these inputs. In this sense, there are some doubts on the part of the scientific community as well as of the fertilizer production sector, whether the extractor requested by the government (Normative Instruction No. 28, called 2nd extractor), which is citric acid 2 % (2 % CA) (Brasil, 2007b), is effective in predicting the plant availability of Zn via mineral fertilizers and about the agronomic significance of the required minimal solubility of 60 % compared to the total content (HCl) (Brasil, 2007a). The purpose of this study was to evaluate the alternative extractors DTPA, EDTA, neutral ammonium citrate (NAC), buffer solution pH 6.0, 10 % HCl, 10 % sulfuric acid, 1 % acetic acid, water, and hot water to quantify the contents of Zn available for maize and compare them with indices of agronomic efficiency of fertilizers and industrial by-products when applied to dystrophic Clayey Red Latosol and Dystrophic Alic Red Yellow Latosol with medium texture. The rate of Zn applied to the soil was 5 mg kg-1, using the sources zinc sulfate, commercial granular zinc, ash and galvanic sludge, ash and two brass slags. Most Zn was extracted from the sources by DTPA, 10 % HCl, NAC, 1% acetic acid, and 10 % sulfuric acid. Recovery by the extractors 2 % CA, EDTA, water, and hot water was low. The agronomic efficiency index was found to be high when using galvanic sludge (238 %) and commercial granular zinc (142 %) and lower with brass slag I and II (67 and 27 %, respectively). The sources galvanizing ash and brass ash showed solubility lower than 60 % in 2 % CA, despite agronomic efficiency indices of 78 and 125 %, respectively. The low agronomic efficiency index of industrial by-products such as brass slag I and galvanizing ash can be compensated by higher doses, provided there is no restriction, as well as for all other sources, in terms of contaminant levels of arsenic, cadmium, chromium, lead, and mercury as required by law (Normative Instruction No 27/2006). The implementation of 2nd extractor 2 % CA and the requirement of minimum solubility for industrial by-products could restrict the use of alternative sources as potential Zn sources for plants.
Nutrient extraction and exportation by common bean cultivars under different fertilization levels: I - macronutrients
Authors: Soratto Rogério Peres , Fernandes Adalton Mazetti , Santos Letícia Andriani dos , Job André Luiz Gomes
Published: September 2013

The use of cultivars with a higher yield potential and the adoption of new technology have achieved high grain yields in common bean, which probably changed the demand for nutrients in this crop. However, there is almost no information about the periods of the cycle in which nutrients are most demanded at which quantities by the main cultivars. The objective of this study was to evaluate the macronutrient extraction and exportation by the common bean cultivars Pérola and IAC Alvorada, under different levels of NPK fertilization, on a dystroferric Red Nitosol, in Botucatu, São Paulo State, Brazil. The experiment was arranged in a randomized complete block (split plot) design with four replications. The plots consisted of six treatments based on a 2 x 3 factorial model, represented by two cultivars and three NPK levels (PD0 - 'Pérola' without fertilization, PD1 - 'Pérola' with 50 % of recommended fertilization, PD2 - 'Pérola' with 100 % of recommended fertilization, AD0 - 'IAC Alvorada' without fertilization, AD1 - 'IAC Alvorada' with 50 % of recommended fertilization, and AD2 - 'IAC Alvorada' with 100 % of recommended fertilization) and subplots sampled seven times during the cycle. At higher levels of NPK fertilization, the grain yield and macronutrient extraction and exportation of both cultivars were higher, but without statistical differences. Macronutrient absorption was higher in the treatments with 100 % of recommended NPK fertilization (average amounts per hectare: 140 kg N, 16.5 kg P, 120 kg K, 69 kg Ca, 17.9 kg Mg, and 16.3 kg S). Regardless of the treatment, the demand for N, P, K, Ca, and Mg was highest from 45 to 55 days after emergence (DAE), i.e., in the R7 stage (pod formation), while the highest S absorption rates were concentrated between 55 and 65 DAE. More than 70 % of P, between 58 and 69 % of N, 40 and 52 % of S, 40 and 48 % of K, and 35 and 45 % of Mg absorbed during the cycle was exported with grains, whereas less than 15 % of Ca was exported.
Mobiliário escolar francês e os projetos vanguardistas de Jean Prouvé e André Lurçat na primeira metade do século XX
Authors: Bencostta Marcus Levy
Published: September 2013

O objetivo deste artigo é investigar a história do mobiliário escolar enquanto componente de uma modernidade que tem como um dos seus focos de discussão os discursos e os projetos idealizados pelos arquitetos. Esta é a uma tentativa de tentar enxergá-los como autênticas peças de investigação que facilitam a compreensão de uma das faces da cultura material escolar. Com o presente tema coloco em cena a valorização do papel desses profissionais, muitos deles desconhecidos da historiografia da educação, que juntos com educadores e médicos pensaram caminhos possíveis para uma escola que almejava ser moderna. Assim, concentrarei minhas análises na realidade do ocidente europeu da primeira metade do século XX e o papel que desempenharam alguns arquitetos franceses como protagonistas na configuração de um mobiliário que procurava alcançar demandas que favorecessem a saúde e a aprendizagem dos alunos em sala de aula.
'Seeing through touch': the material world of visually impaired children
Authors: Grosvenor Ian , Macnab Natasha
Published: September 2013

This article examines the changing material world of the visually impaired child and the ways in which this has been viewed and understood by scholars, philosophers, educators and other commentators over time. It describes and analyses tactile encounters as they have been planned for by educators, museum curators and others, from the Age of the Enlightenment until the present day. It takes as its starting point a recent blog that appeared online in 2011, which posted images from handling sessions for the visually impaired child, organized by John Alfred Charlton Deas from Sunderland Museum, England, between 1913-1926. It traces the provenance and development of ideas around 'seeing through touch', from the embossed books and maps and the printing machines for systems such as Braille in the nineteenth century to the theoretical and pedagogical developments which began to occur at the start of the twentieth century.
Raul Lino, protagonista de uma mudança na arquitetura escolar durante a I República Portuguesa
Authors: Silva Carlos Manique da
Published: September 2013

O objetivo do presente artigo é o de analisar um conjunto de projetos de escolas primárias desenhados pelo arquiteto Raul Lino durante a I República Portuguesa (1910-1926). O que se procura demonstrar é que os projetos em causa afirmam uma vontade de mudança relativamente a anteriores programas arquitetónicos. Em causa, nesse momento histórico, um novo olhar sobre a criança e as realidades escolares e sociais; algo que tem implicações na maneira como a escola é fisicamente concebida. Nesse sentido, a reflexão organiza-se em torno de três entradas, que enquadram um conjunto de preocupações pedagógicas e sociais muito presentes no período histórico em questão: i) bem-estar físico e mental da criança; ii) "ensino intuitivo"; e iii) imagem social do professor de instrução primária. Por outro lado, no que concerne à análise dos espaços edificados, adota-se como matriz analítica: i) a sua forma ou estrutura morfológica; ii) a sua função e as atividades que neles se realizam; e iii) as relações existentes entre os diferentes espaços e as respetivas funções.
A lousa de uso escolar: traços da história de uma tecnologia da escola moderna
Authors: Barra Valdeniza Maria Lopes da
Published: September 2013

O trabalho que segue é fruto de um estudo que se inscreve no universo da cultura material escolar, sendo a metodologia empregada a de natureza bibliográfica, com vistas a destacar a história de um suporte técnico-material de relevância das práticas escolares da escola moderna, a lousa de uso escolar. Concentra-se no espaço temporal dado pelo século XIX, por ser este o cenário que dará visibilidade ao esforço de difusão das primeiras práticas escolares de ensino. Parte da hipótese de que a relação entre material e método pode traduzir concepções de ensino, conferindo centralidade à lousa como a tecnologia que, inscrita no conjunto das práticas escolares, resultará na constituição e consolidação do modelo escolar da transmissão simultânea de ensino.
Ne pas toucher aux œuvres: o princípio da (in)tangibilidade da obra de arte no contexto de sua exibição e suas (contra)significações pedagógicas
Authors: Pereira Marcelo de Andrade
Published: September 2013

Este ensaio, de cunho filosófico e programático, discorre sobre as significações da arte no contexto de sua exibição e suas implicações pedagógicas. Por contexto de exibição compreende-se os espaços institucionais e não institucionais que abrigam e expõem a produção dita de arte, tais como: os museus e as galerias de arte. O texto discute o caráter politico e pedagógico, como também ideológico da arte e das instituições museais ao analisar as injunções dessas instituições face às suas representações sociais e ao mercado de arte. Com isso, busca demonstrar de que maneira os discursos que sacralizam a arte, o artista e o espaço de exibição das obras de arte minimizam ou mesmo restringem o acesso à experiência da e com a arte; procura problematizar os meandros de uma relação de poder estabelecida entre público e obra no âmbito de exposição. Esta investigação tem, ademais, o propósito de descortinar as "promessas benfazejas da arte e de suas instituições de exposição" que grassam no âmbito do ensino de arte, tornando-o, não raro, mecanismo de reprodução da cultura dominante. Analisa, em suma, como a esfera da arte normatiza não apenas a produção da arte, como também estabelece os critérios de seleção das obras e do público. A investigação se ampara pelas contribuições de Paul Valéry, Theodor Adorno, Pierre Bourdieu, Bruno Deloche, Roger L. Taylor, Nildo Viana e Marilia Xavier Cury.
Adaptação cultural e validação dos construtos: serviço logístico, satisfação e lealdade
Authors: Su Alexandre Fun Ghi , Sampaio Mauro
Published: September 2013

Este estudo apresenta o processo de adaptação cultural dos construtos serviço logístico, satisfação e lealdade à língua portuguesa. A adaptação cultural inclui as fases: tradução, retrotradução, revisão por comitê, pré-teste e análise de confiabilidade e validade. Os resultados mostram que há evidências de que as medidas utilizadas são confiáveis, porém foi necessário excluir 11 itens da relação de 35 itens teóricos identificados na literatura. Também há evidências de que as medidas são válidas como instrumentos de pesquisa em português pelos métodos de: análise de conteúdo; validade convergente; validade discriminante; análise fatorial exploratória; e análise fatorial confirmatória.
Diretrizes para implantação coletiva e semipresencial de sistemas certificáveis de gestão
Authors: Izeppe Fábio Roberto , Oliveira Otávio José de
Published: September 2013

Este artigo tem por objetivo sistematizar diretrizes para implantação coletiva e semipresencial, situação em que não há participação ativa de um consultor ou especialista diretamente na empresa, de sistemas certificáveis de gestão, tais como a ISO 9001, ISO 14001 e OHSAS 18001. Este artigo é de cunho teórico-conceitual e, para seu desenvolvimento, foram estudadas mais diretamente quatro experiências práticas provenientes da teoria, de implantação coletiva e semipresencial de sistemas que, em conjunto com o referencial teórico geral, forneceram subsídios para a sistematização das diretrizes. Essas diretrizes estão estruturadas com base nos seguintes itens: seleção das empresas; sensibilização; diagnóstico; planejamento; treinamentos; implementação; verificação e correção.