bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions Between SNAP-25 and Synaptotagmin-1 Are Involved in Vesicle Priming, Clamping Spontaneous and Stimulating Evoked Neurotransmission
Authors: Schupp Melanie , Malsam Jörg , Ruiter Marvin , Scheutzow Andrea , Wierda Keimpe D.B. , Söllner Thomas H. , Sørensen Jakob B.
Published: November 2016

Whether interactions between synaptotagmin-1 (syt-1) and the soluble NSF attachment protein receptors (SNAREs) are required during neurotransmission is debated. We examined five SNAP-25 mutations designed to interfere with syt-1 interactions. One mutation, D51/E52/E55A, targeted negative charges within region II of the primary interface (Zhou et al., 2015); two mutations targeted region I (D166A and D166/E170A) and one mutation targeted both (D51/E52/E55/D166A). The final mutation (D186/D193A) targeted C-terminal residues not expected to interact with syt-1. Anin vitroassay showed that the region I, region II, and region I+II (D51/E52/E55/D166A) mutants markedly reduced the attachment between syt-1 and t-SNARE-carrying vesicles in the absence of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. In the presence of PI(4,5)P2, vesicle attachment was unaffected by mutation. When expressed inSnap-25-null mouse autaptic neurons, region I mutations reduced the size of the readily releasable pool of vesicles, whereas the region II mutation reduced vesicular release probability. Combining both in the D51/E52/E55/D166A mutation abrogated evoked release. These data point to a division of labor between region I (vesicle priming) and region II (evoked release). Spontaneous release was disinhibited by region I mutations and found to correlate with defective complexin (Cpx) clamping in anin vitrofusion assay, pointing to an interdependent role of synaptotagmin and Cpx in release clamping. Mutation in region II (D51/E52/E55A) also unclamped release, but this effect could be overcome by synaptotagmin overexpression, arguing against an obligatory role in clamping. We conclude that three synaptic release functions of syt-1, vesicle priming, spontaneous release clamping, and evoked release triggering, depend on direct SNARE complex interaction.

SIGNIFICANCE STATEMENTThe function of synaptotagmin-1 (syt-1):soluble NSF attachment protein receptor (SNARE) interactions during neurotransmission remains unclear. We mutated SNAP-25 within the recently identified region I and region II of the primary synaptotagmin:SNARE interface. Usingin vitroassays and rescue experiments in autaptic neurons, we show that interactions within region II of the primary interface are necessary for synchronized calcium-triggered release, whereas region I is involved in vesicle priming. Spontaneous release was disinhibited by region I mutation and found to correlate with defective complexin (Cpx) clampingin vitro, pointing to an interdependent role of synaptotagmin and Cpx in release clamping. Therefore, vesicle priming, clamping spontaneous release, and eliciting evoked release are three different functions of syt-1 that involve different interaction modes with the SNARE complex.
Blocking the Interaction between EphB2 and ADDLs by a Small Peptide Rescues Impaired Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer's Disease
Authors: Shi Xiao-Dong , Sun Kai , Hu Rui , Liu Xiao-Ya , Hu Qiu-Mei , Sun Xiao-Yu , Yao Bin , Sun Nan , Hao Jing-Ru , Wei Pan , Han Yuan , Gao Can
Published: November 2016

Soluble amyloid-β (Aβ) oligomers, also known as Aβ-derived diffusible ligands (ADDLs), are thought to be the key pathogenic factor in Alzheimer's disease (AD), but there is still no effective treatment for preventing or reversing the progression of the disease. Targeting NMDA receptor trafficking and regulation is a new strategy for early treatment of AD. Aβ oligomers have been found to bind to the fibronectin (FN) type III repeat domain of EphB2 to trigger EphB2 degradation, thereby impairing the normal functioning of NMDA receptors and resulting in cognitive deficits. Here, we identified for the first time the interaction sites of the EphB2 FN domain with ADDLs by applying the peptide array method to design and synthesize four candidate peptides (Pep21, Pep25, Pep32, and Pep63) that might be able to block the EphB2–ADDL interaction. Among them, Pep63 was found to be the most effective at inhibiting the binding between EphB2 and ADDLs. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2- and GluN2B-containing NMDA receptors from the neuronal surface in cultured hippocampal neurons, but also improved impaired memory deficits in APPswe/PS1dE9 (APP/PS1) transgenic mice and the phosphorylation and surface expression of GluN2B-containing NMDA receptors in cultures. Together, these results suggest that blocking the EphB2–ADDL interaction by small interfering peptides may be a promising strategy for AD treatment.

SIGNIFICANCE STATEMENTAlzheimer's disease (AD) is an age-dependent neurodegenerative disorder and amyloid β-derived diffusible ligands (ADDLs) play a key role in triggering the early cognitive deficits that constitute AD. ADDLs may bind EphB2 and alter NMDA receptor trafficking and synaptic plasticity. Here, we identified the interaction sites of the EphB2 FN domain with ADDLs for the first time to develop a small (10 aa) peptide (Pep63) capable of blocking the EphB2–ADDL interaction. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2 and GluN2B-containing NMDA receptors from the neuronal surface in cultured hippocampal neurons, but also improved impaired memory deficits in APPswe/PS1dE9 (APP/PS1) transgenic mice. Our results suggest that blocking the EphB2–ADDL interaction with Pep63 may be a promising strategy for AD treatment.
Considering Sex as a Biological Variable Will Be Valuable for Neuroscience Research
Authors: Shansky Rebecca M. , Woolley Catherine S.
Published: November 2016

The recently implemented National Institutes of Health policy requiring that grant applicants consider sex as a biological variable in the design of basic and preclinical animal research studies has prompted considerable discussion within the neuroscience community. Here, we present reasons to be optimistic that this new policy will be valuable for neuroscience, and we suggest some ways for neuroscientists to think about incorporating sex as a variable in their research.
Low Somatic Sodium Conductance Enhances Action Potential Precision in Time-Coding Auditory Neurons
Authors: Yang Yang , Ramamurthy Bina , Neef Andreas , Xu-Friedman Matthew A.
Published: November 2016

Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear howgNainfluences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs. BCs play a central role in both relaying and refining precise timing information from the auditory nerve, whereas SCs discard precise timing information and encode the envelope of sound amplitude. Nucleated-patch recording at near-physiological temperature indicated that the Na current density was 62% lower in BCs, and the voltage dependence ofgNainactivation was 13 mV hyperpolarized compared with SCs. We endowed BCs with SC-likegNausing two-electrode dynamic clamp and found that synaptic activity at physiologically relevant rates elicited APs with significantly lower probability, through increased activation of delayed rectifier channels. In addition, for two near-simultaneous synaptic inputs, the window of coincidence detection widened significantly with increasinggNa, indicating that refinement of temporal information by BCs is degraded bygNa. Thus, reduced somaticgNaappears to be an adaption for enhancing fidelity and precision in time-coding neurons.

SIGNIFICANCE STATEMENTProper hearing depends on analyzing temporal aspects of sounds with high precision. Auditory neurons that specialize in precise temporal information have a suite of unusual intrinsic properties, including nonovershooting action potentials and few sodium channels in the soma. However, it was not clear how low sodium channel availability in the soma influenced the temporal precision of action potentials initiated in the axon initial segment. We studied this using dynamic clamp to mimic sodium channels in the soma, which yielded normal, overshooting action potentials. Increasing somatic sodium conductance had major negative consequences: synaptic activity evoked action potentials with lower fidelity, and the precision of coincidence detection was degraded. Thus, low somatic sodium channel availability appears to enhance fidelity and temporal precision.
Attenuation of Responses to Self-Generated Sounds in Auditory Cortical Neurons
Authors: Rummell Brian P. , Klee Jan L. , Sigurdsson Torfi
Published: November 2016

Many of the sounds that we perceive are caused by our own actions, for example when speaking or moving, and must be distinguished from sounds caused by external events. Studies using macroscopic measurements of brain activity in human subjects have consistently shown that responses to self-generated sounds are attenuated in amplitude. However, the underlying manifestation of this phenomenon at the cellular level is not well understood. To address this, we recorded the activity of neurons in the auditory cortex of mice in response to sounds generated by their own behavior. We found that the responses of auditory cortical neurons to these self-generated sounds were consistently attenuated, compared with the same sounds generated independently of the animals' behavior. This effect was observed in both putative pyramidal neurons and in interneurons and was stronger in lower layers of auditory cortex. Downstream of the auditory cortex, we found that responses of hippocampal neurons to self-generated sounds were almost entirely suppressed. Responses to self-generated optogenetic stimulation of auditory thalamocortical terminals were also attenuated, suggesting a cortical contribution to this effect. Further analyses revealed that the attenuation of self-generated sounds was not simply due to the nonspecific effects of movement or behavioral state on auditory responsiveness. However, the strength of attenuation depended on the degree to which self-generated sounds were expected to occur, in a cell-type-specific manner. Together, these results reveal the cellular basis underlying attenuated responses to self-generated sounds and suggest that predictive processes contribute to this effect.

SIGNIFICANCE STATEMENTDistinguishing self-generated from externally generated sensory input poses a fundamental problem for behaving organisms. Our study in mice shows for the first time that responses of auditory cortical neurons are attenuated to sounds generated manually by the animals' own behavior. This effect is distinct from the nonspecific effect of behavioral activity on auditory responsiveness that has previously been reported and its magnitude is modulated by the probability with which self-generated sounds occur, suggesting an underlying predictive process. We also reveal how this effect varies across cell types and cortical layers. These findings lay a foundation for studying impairments in the processing of self-generated sounds, which are observed in psychiatric illness, in animal disease models.
A Biophysical Model for Cytotoxic Cell Swelling
Authors: Dijkstra Koen , Hofmeijer Jeannette , van Gils Stephan A. , van Putten Michel J.A.M.
Published: November 2016

We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in conditions of low energy supply, as observed in cerebral ischemia. Our model contains Hodgkin—Huxley-type ion currents, a recently discovered voltage-gated chloride flux through the ion exchanger SLC26A11, active KCC2-mediated chloride extrusion, and ATP-dependent pumps. The model predicts changes in ion gradients and cell swelling during ischemia of various severity or channel blockage with realistic timescales. We theoretically substantiate experimental observations of chloride influx generating cytotoxic edema, while sodium entry alone does not. We show a tipping point of Na+/K+-ATPase functioning, where below cell volume rapidly increases as a function of the remaining pump activity, and a Gibbs–Donnan-like equilibrium state is reached. This precludes a return to physiological conditions even when pump strength returns to baseline. However, when voltage-gated sodium channels are temporarily blocked, cell volume and membrane potential normalize, yielding a potential therapeutic strategy.

SIGNIFICANCE STATEMENTCytotoxic edema most commonly results from energy shortage, such as in cerebral ischemia, and refers to the swelling of brain cells due to the entry of water from the extracellular space. We show that the principle of electroneutrality explains why chloride influx is essential for the development of cytotoxic edema. With the help of a biophysical model of a single neuron, we show that a tipping point of the energy supply exists, below which the cell volume rapidly increases. We simulate realistic time courses to and reveal critical components of neuronal swelling in conditions of low energy supply. Furthermore, we show that, after transient blockade of the energy supply, cytotoxic edema may be reversed by temporary blockade of Na+channels.
Multivariate Brain Prediction of Heart Rate and Skin Conductance Responses to Social Threat
Authors: Eisenbarth Hedwig , Chang Luke J. , Wager Tor D.
Published: November 2016

Psychosocial stressors induce autonomic nervous system (ANS) responses in multiple body systems that are linked to health risks. Much work has focused on the common effects of stress, but ANS responses in different body systems are dissociable and may result from distinct patterns of cortical–subcortical interactions. Here, we used machine learning to develop multivariate patterns of fMRI activity predictive of heart rate (HR) and skin conductance level (SCL) responses during social threat in humans (N= 18). Overall, brain patterns predicted both HR and SCL in cross-validated analyses successfully (rHR= 0.54,rSCL= 0.58, bothp< 0.0001). These patterns partly reflected central stress mechanisms common to both responses because each pattern predicted the other signal to some degree (rHR→SCL= 0.21 andrSCL→HR= 0.22, bothp< 0.01), but they were largely physiological response specific. Both patterns included positive predictive weights in dorsal anterior cingulate and cerebellum and negative weights in ventromedial PFC and local pattern similarity analyses within these regions suggested that they encode common central stress mechanisms. However, the predictive maps and searchlight analysis suggested that the patterns predictive of HR and SCL were substantially different across most of the brain, including significant differences in ventromedial PFC, insula, lateral PFC, pre-SMA, and dmPFC. Overall, the results indicate that specific patterns of cerebral activity track threat-induced autonomic responses in specific body systems. Physiological measures of threat are not interchangeable, but rather reflect specific interactions among brain systems.

SIGNIFICANCE STATEMENTWe show that threat-induced increases in heart rate and skin conductance share some common representations in the brain, located mainly in the vmPFC, temporal and parahippocampal cortices, thalamus, and brainstem. However, despite these similarities, the brain patterns that predict these two autonomic responses are largely distinct. This evidence for largely output-measure-specific regulation of autonomic responses argues against a common system hypothesis and provides evidence that different autonomic measures reflect distinct, measurable patterns of cortical–subcortical interactions.
Failure to launch: aberrant cumulus gene expression during oocyte in vitro maturation
Authors: Brown Hannah M , Dunning Kylie R , Sutton-McDowall Melanie , Gilchrist Robert B , Thompson Jeremy G , Russell Darryl L
Published: November 2016

In vitro maturation (IVM) offers significant benefits for human infertility treatment and animal breeding, but this potential is yet to be fully realised due to reduced oocyte developmental competence in comparison with in vivo matured oocytes. Cumulus cells occupy an essential position in determining oocyte developmental competence. Here we have examined the areas of deficient gene expression, as determined within microarrays primarily from cumulus cells of mouse COCs, but also other species, between in vivo matured and in vitro matured oocytes. By retrospectively analysing the literature, directed by focussing on downregulated genes, we provide an insight as to why the in vitro cumulus cells fail to support full oocyte potential and dissect molecular pathways that have important roles in oocyte competence. We conclude that the roles of epidermal growth factor signalling, the expanded extracellular matrix, cumulus cell metabolism and the immune system are critical deficiencies in cumulus cells of IVM COCs.
Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration
Authors: Grassmann Felix , Heid Iris M , Weber Bernhard H F ,   International AMD Genomics Consortium (IAMDGC)
Published: November 2016

Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 1.0 × 10−773 and 6.7 × 10−5. This now allows prioritization of the gene of interest for subsequent functional studies.
RASopathies Are Associated With Delayed Puberty; Are They Associated With Precocious Puberty Too?
Authors: van der Kaay Daniëlle C.M. , Levine Bat-Sheva , Doyle Daniel , Mendoza-Londono Roberto , Palmert Mark R.
Published: November 2016

RASopathies, such as Noonan, Costello, and cardio-facio-cutaneous syndromes, are developmental disorders caused by mutations in rat sarcoma–mitogen-activated protein kinase pathway genes. Mutations that cause Noonan syndrome have been associated with delayed puberty. Here we report 4 patients with either Costello or cardio-facio-cutaneous syndrome who developed precocious puberty, suggesting complex regulation of the hypothalamic–pituitary–gonadal axis and the timing of puberty by the rat sarcoma–mitogen-activated protein kinase pathway. Additional study of the timing of puberty among patients with RASopathies is warranted to ascertain the incidence of delayed and precocious puberty in these conditions and to examine genotype–phenotype correlations, which may provide insight into pathways that regulate the timing of puberty.
Inhaled Corticosteroids for Bronchopulmonary Dysplasia: A Meta-analysis
Authors: Shinwell Eric S. , Portnov Igor , Meerpohl Joerg J. , Karen Tanja , Bassler Dirk
Published: November 2016

CONTEXT:

Bronchopulmonary dysplasia (BPD) in preterm infants remains a major health burden despite many therapeutic interventions. Inhaled corticosteroids (IC) may be a safe and effective therapy.

OBJECTIVE:

To assess the safety and efficacy of IC for prevention or treatment of BPD or death in preterm infants.

DATA SOURCES:

PubMed, the Cochrane Library, Embase, and CINAHL from their inception until November 2015 together with other relevant sources.

STUDY SELECTION:

Randomized controlled trials of ICs versus placebo for either prevention or treatment of BPD.

DATA EXTRACTION:

This meta-analysis used a random-effects model with assessment of quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

RESULTS:

Thirty-eight trials were identified, and 16 met inclusion criteria. ICs were associated with a significant reduction in death or BPD at 36 weeks’ postmenstrual age (risk ratio [RR] = 0.86, 95% confidence interval [CI] 0.75 to 0.99, I2 = 0%, P = .03; 6 trials, n = 1285). BPD was significantly reduced (RR = 0.77, 95% CI 0.65 to 0.91, I2 = 0%, 7 trials, n = 1168), although there was no effect on death (RR = 0.97, 95% CI 0.42 to 2.2, I2 = 50%, 7 trials, n = 1270). No difference was found for death or BPD at 28 days’ postnatal age. The use of systemic steroids was significantly reduced in treated infants (13 trials, n = 1537, RR = 0.87, 95% CI 0.76 to 0.98 I2 = 3%,). No significant differences were found in neonatal morbidities and other adverse events.

LIMITATIONS:

Long-term follow-up data are awaited from a recent large randomized controlled trial.

CONCLUSIONS:

Very preterm infants appear to benefit from ICs with reduced risk for BPD and no effect on death, other morbidities, or adverse events. Data on long-term respiratory, growth, and developmental outcomes are eagerly awaited.
Dissolved oxygen modelling using artificial neural network: a case of River Nzoia, Lake Victoria basin, Kenya
Authors: Edwin Kimutai Kanda , Emmanuel Chessum Kipkorir , Job Rotich Kosgei
Published: November 2016

River Nzoia in Kenya, due to its role in transporting industrial and municipal wastes in addition to agricultural runoff to Lake Victoria, is vulnerable to pollution. Dissolved oxygen is one of the most important indicators of water pollution. Artificial neural network (ANN) has gained popularity in water quality forecasting. This study aimed at assessing the ability of ANN to predict dissolved oxygen using four input variables of temperature, turbidity, pH and electrical conductivity. Multilayer perceptron network architecture was used in this study. The data consisted of 113 monthly values for the input variables and output variable from 2009–2013 which were split into training and testing datasets. The results obtained during training and testing were satisfactory with R2 varying from 0.79 to 0.94 and RMSE values ranging from 0.34 to 0.64 mg/l which imply that ANN can be used as a monitoring tool in the prediction of dissolved oxygen for River Nzoia considering the non-correlational relationship of the input and output variables. The dissolved oxygen values follow seasonal trend with low values during dry periods.
PENGOPERASIAN ALAT TANGKAP TUGUK BILIS (STOW NETS) DI SUNGAI MUSI BAGIAN HILIR
Authors: Gautama Sidarta
Published: November 2016

Kegiatan penangkapan ikan di Sumatera Selatan dilakukan oleh masyarakat di sepanjang Daerah Aliran Sungai (DAS) Musi dengan tingkat intensitas, jumlah,dan keragaman alat tangkap yang bervariasi sesuai dengan lokasi dan musim. Jumlah jenis alat tangkap yang beroperasi di DAS Musi bagian hilir mencapai11 jenis (Husnah et. al., 2003), salah satu diantaranya adalah tuguk layang atau biasa juga disebut tuguk bilis (stow nets).
Floristic characteristics of alien invasive seed plant species in China
Authors: WANG CONGYAN , LIU JUN , XIAO HONGGUANG , ZHOU JIAWEI , DU DAOLIN
Published: November 2016

ABSTRACT This study aims to determine the floristic characteristics of alien invasive seed plant species (AISPS) in China. There are a total of five hundred and thirteen AISPS, belonging to seventy families and two hundred and eighty-three genera. Seventy families were classified into nine areal types at the family level, and "Cosmopolitan" and "Pantropic" are the two main types. Two hundred and eighty-three genera were classified into twelve areal types at the genus level, and "Pantropic", "Trop. Asia & Amer. disjuncted", and "Cosmopolitan" are the three main types. These results reveal a certain degree of diversity among AISPS in China. The floristic characteristics at the family level exhibit strong pantropic characteristics. Two possible reasons for this are as follows. Firstly, southeastern China is heavily invaded by alien invasive plant species and this region has a mild climate. Secondly, southeastern China is more disturbed by human activities than other regions in China. The floristic characteristics at the genus level display strong pantropic but with abundant temperate characteristics. This may be due to that China across five climatic zones and the ecosystems in which the most alien invasive plant species occur have the same or similar climate with their natural habitat.
POSTHARVEST OF IRRADIATED TAHITI LIME FRUITS
Authors: SILVA SIMONE RODRIGUES DA , BEZERRA DÉBORA NANCY FERNANDES , BASSAN MEIRE MENEZES , CANTUARIAS-AVILÉS TATIANA , ARTHUR VALTER
Published: November 2016

ABSTRACT This study aimed to evaluate the postharvest quality evolution of gamma-irradiated ‘Tahiti’ limes. Shiny, olivegreen fruits with coarse skin (56 cm equatorial diameter) harvested in commercial orchars and processed in commercial packing house line were used. In a preliminary assay, fruits harvested in April 2011 were exposed to a gamma radiation range from 0 to 750 Gy. The 250 and 750 Gy doses negatively affected skin quality and pulp of exposed fruits. For this reason, new assays were carried out using lower doses to irradiate fruits harvested in July 2011 (off-season) and January 2012 (regular harvest period). Fruit harvested in both periods were selected and exposed to radiation doses of 0, 50, 100, 150, and 200 Gy. All irradiations occurred at a rate of 0.46 Gy/h. After fruit irradiation, physical and chemical analyses were performed along a 20-day storage period at room temperature (24 ± 1ºC and 80 ± 5% RH). Irradiation of fruits harvested in July 2011 and January 2012 and treated with doses of up to 200 Gy did not affect the ascorbic acid content, but doses > 100 Gy caused skin yellowing of fruits harvested on both periods. Gamma radiation at doses = 50 Gy reduced the total soluble solids content in off-season fruits. Exposure of fruits harvested in the main harvest period to radiation doses = 150 Gy increased weight loss. Irradiation of ‘Tahiti’ limes at doses between 50 Gy and 700 Gy did not preserve postharvest quality during storage at room temperature.
Um Estudo Comparativo Entre Coeficientes de Difusão Verticais na Simulação da Dispersão de Poluentes em uma Camada Limite Convectiva
Authors: Leite Maria de Fatima Silva , Moreira Davidson Martins
Published: November 2016

Resumo Este trabalho apresenta um estudo comparativo entre diferentes coeficientes de difusão verticais aplicados em um modelo de dispersão para determinação da concentração de poluentes atmosféricos em uma camada limite convectiva. O modelo de dispersão é uma solução semi-analítica da equação de difusão-advecção tridimensional e estacionária, sendo que os resultados das simulações foram confrontados com dados experimentais da literatura. As melhores performances foram obtidas com o coeficiente de difusão proveniente da teoria estatística de Taylor e propriedades espectrais. Entretanto, resultados menos satisfatórios foram obtidos com a parametrização Asymmetric Convective Model version 2 (ACM2), muito usada como uma das opções para camada limite atmosférica no modelo de mesoescala Weather Research and Forecasting (WRF).
ESTUDO EM CLUSTERS TECNOLÓGICOS IBERO AMERICANOS
Authors: Toledo Fabio Lamartine Barbosa , Mafioletti Keller , Amal Mohamed , Hoeltgebaum Marianne
Published: November 2016

RESUMO O presente artigo analisa o índice de especialização e sua relação com inovação, internacionalização e a qualificação. Limitando-se a alguns setores inseridos nos clusters tecnológicos das regiões de Florianópolis/SC, Recife/PE, Região do Porto/Portugal e Região da Cataluña/Espanha, buscou-se verificar como o desenvolvimento da inovação (patentes submetidas), a internacionalização (volume de exportação) e a qualificação (mestres e doutores) nestas regiões relaciona-se com o índice de especialização das mesmas. Utilizou-se neste estudo um recorte longitudinal, no qual a evolução do índice de especialização foi analisado ao longo de um período de quatro anos e confrontado com os indicadores: qualificação, internacionalização e inovação. Foram formuladas três hipóteses, as quais foram testadas por meio do tratamento dos dados obtidos nas regiões dos quatro clusters pesquisados.
NO JOGO DO MERCADO: O CASO DE UMA STARTUP GAÚCHA
Authors: Schreiber Dusan , Pinheiro Cristiano Max Pereira , Branco Marsal Ávila Alves , Antonello Cláudia Simone , Land Deise
Published: November 2016

RESUMO O empreendedorismo tem recebido estímulo na maioria dos países por sua relevância econômica e social, em virtude de seu potencial de gerar emprego e renda. Mais recentemente, com o surgimento e a consolidação dos segmentos econômicos que representam a indústria criativa, o apoio tornou-se mais visível e evidente. A principal característica destas atividades consiste no valor agregado a partir do uso intensivo de competências técnicas e artísticas, baseadas no talento individual, dependente mais de inteligência, aptidão, habilidades e capacidades específicas individuais e coletivas, do que de investimento em bens de capital. A criação e o desenvolvimento de jogos digitais é considerado um dos setores mais representativos e promissores da indústria criativa, no entanto o correspondente mercado, apesar de recente, é complexo. Ele não exige apenas competência técnica específica, sendo requerida também capacidade de coordenação e de desenvolvimento relacional com potenciais parceiros para viabilizar economicamente o lançamento do jogo no mercado. O caso de ensino aqui apresentado é verídico e evidencia alguns dos desafios com os quais os empreendedores deste segmento econômico se deparam. O caso oferece importantes contribuições tanto para gestores como para potenciais empreendedores, bem como oportuniza elementos para promover discussões em aulas nas disciplinas de empreendedorismo, marketing, estratégia e gestão de pessoas.
Cardiovascular risk factors associated with frailty syndrome among hospitalized elderly people: a cross-sectional study
Authors: Tavares Darlene Mara dos Santos , Colamego Camila Gigante , Pegorari Maycon Sousa , Ferreira Pollyana Cristina dos Santos , Dias Flávia Aparecida , Bolina Alisson Fernandes
Published: November 2016

ABSTRACT CONTEXT AND OBJECTIVE: Identification of frailty syndrome and its relationship with cardiovascular risk factors among hospitalized elderly people is important, since this may contribute towards broadening of knowledge regarding this association within tertiary-level services. This study aimed to evaluate the cardiovascular risk factors associated with frailty syndrome among hospitalized elderly people. DESIGN AND SETTING: Observational cross-sectional study in a public teaching hospital. METHODS: The participants were elderly patients admitted to clinical and surgical wards. The cardiovascular risk factors assessed were: body mass index (BMI), waist circumference, systemic arterial hypertension (SAH), blood glucose, total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides. To identify frailty syndrome, the method proposed by Fried was used. The data were analyzed through descriptive statistics, chi-square test (P < 0.10) and multinomial logistic regression (P < 0.05). RESULTS: A total of 205 individuals were evaluated. It was found that 26.3% (n = 54) of the elderly people were frail, 51.7% (n = 106) were pre-frail and 22% (n = 45) were non-frail. The preliminary bivariate analysis (P < 0.10) for the regression model showed that frailty was associated with BMI (P = 0.016), LDL cholesterol (P = 0.028) and triglycerides (P = 0.093). However, in the final multivariate model, only overweight remained associated with the pre-frail condition (odds ratio, OR = 0.44; 95% confidence interval, CI = 0.20-0.98; P = 0.045). CONCLUSION: States of frailty were highly present in the hospital environment. The pre-frail condition was inversely associated with overweight.
Prevalence of knee arthroplasty in the state of São Paulo between 2003 and 2010
Authors: Carvalho Rogério Teixeira de , Canté Jonny Chaves Lima , Lima Juliana Hoss Silva , Tavares Luiz Alberto Barbosa , Takano Marcelo Itiro , Tavares Fernando Gomes
Published: November 2016

ABSTRACT CONTEXT AND OBJECTIVE: The volume of knee arthroplasty procedures has increased over the last decade. The aim of this study was to estimate the frequency of these procedures performed within the public healthcare system of the state of São Paulo between 2003 and 2010. DESIGN AND SETTING: Cross-sectional study conducted in the state of São Paulo by researchers at Hospital do Servidor Público do Estado de São Paulo. METHODS: A sample of 10,952 patients (7,891 females and 3,061 males) who underwent primary total knee arthroplasty (TKA) and revision of total knee arthroplasty (RTKA) in the state of São Paulo between 2003 and 2010 was evaluated. The patients were cataloged using the public healthcare service's TABNET software. All of the patients presented primary osteoarthritis of the knee. The variables of gender, number of primary TKA procedures and number of RTKA procedures were evaluated. RESULTS: A total of 10,952 TKA procedures were performed (annual average of 1369), of which 9,271 (85%) were TKA and 1,681 (15%), RTKA. Of the TKA procedures, 72% were carried out on females (P < 0.0001), while 70% of the RTKA procedures were on females (P < 0.0001). The average ratio of TKA to RTKA was 5.5:1 (P < 0.0001); the ratios in 2003 and 2010 were 9.0:1 and 4.4:1 (P < 0.0001), respectively. CONCLUSION: The number and frequency of TKA and RTKA procedures increased in the state of São Paulo between 2003 and 2010. This increase was relatively greater in RTKA than in TKA and was predominantly in female patients.
O imbróglio de Raízes: notas sobre a fortuna crítica da obra de Sérgio Buarque de Holanda
Authors: Vainfas Ronaldo
Published: November 2016

Resumo O artigo analisa as condições de produção e recepção da obra inaugural de Sérgio Buarque de Holanda, Raízes do Brasil, considerando a crítica historiográfica sobre o autor. Nesse sentido, comenta a controvérsia sobre as edições de Raízes; analisa a "teoria da América" que inspirou o livro de 1936; reflete sobre a presença da filosofia e da historiografia alemã, bem como da francesa, na produção de Sérgio. Por fim, à guisa de conclusão, analisa a polêmica em torno do pensamento político de Sérgio ao longo do século XX.
Validação para a língua portuguesa do Educational Practices Questionnaire (Student Version)
Authors: Almeida Rodrigo Guimarães dos Santos , Mazzo Alessandra , Martins José Carlos Amado , Souza-Junior Valtuir Duarte de , Mendes Isabel Amélia Costa
Published: November 2016

Resumo Objetivo Traduzir e validar para língua portuguesa o Educational Practices Questionnaire (Student Version). Métodos Estudo do tipo metodológico, de tradução e validação de instrumento. Para o processo de validação criou-se o evento: III Workshop Brasil – Portugal: Atendimento ao Paciente Crítico. Resultados Participaram da pesquisa 103 enfermeiros. Os testes psicométricos (validade e fidelidade da escala, o padrão de correlação entre as variáveis, o teste de adequação amostral e o teste de esfericidade) apresentaram resultados satisfatórios. Os agrupamentos encontrados na análise fatorial não apresentaram coerência com a literatura estudada. Assim, optou-se em seguir a divisão estabelecida pelos autores originais. Conclusão A escala foi denominada: Questionário de Práticas Educativas. Os achados demonstraram boas propriedades psicométricas e um adequado potencial de uso, todavia futuras pesquisas se fazem necessárias para consolidação desse questionário, bem como a expansão de sua dimensionalidade.
Tempos de acesso a serviços de saúde face ao infarto do miocárdio
Authors: Mendes Andreia Santos , Reis Virgínia Ramos dos Santos Souza , Santos Carlos Antonio de Souza Teles , Mussi Fernanda Carneiro
Published: November 2016

Resumo Objetivo Analisar os tempos relacionados ao acesso de homens e mulheres com infarto do miocárdio a hospitais referência em cardiologia e a correlação entre eles. Métodos Pesquisa transversal, com 100 pessoas com infarto entrevistadas em hospitais referência em cardiologia. Dados analisados por estatística descritiva e inferencial, adotando-se significância estatística. Resultados Os tempos foram elevados (decisão para atendimento, chegada ao primeiro serviço de saúde, permanência na rede de atenção e admissão em hospitais referência em cardiologia), exceto o de transporte, sobretudo para mulheres. Houve maior contribuição do tempo de decisão na composição do tempo de chegada ao primeiro serviço de saúde e do tempo de permanência na rede na composição do tempo de chegada aos hospitais referência em cardiologia. Conclusão A longa espera por atenção especializada reflete a falta de estrutura dos serviços de saúde, e o tempo de decisão elevado reflete a falta do não reconhecimento do infarto pelos participantes.
Sofrimento moral em enfermeiros dos departamentos de fiscalização do Brasil
Authors: Silveira Luciana Ramos , Ramos Flávia Regina Souza , Schneider Dulcinéia Ghizoni , Vargas Mara Ambrosina de Oliveira , Barlem Edison Luiz Devos
Published: November 2016

Resumo Objetivo Identificar a frequência e a intensidade das causas de sofrimento moral vivenciado por enfermeiros nos departamentos de fiscalização do Brasil. Métodos Estudo transversal realizado com 28 profissionais de competência gerencial e 113 profissionais de competência fiscalizatória. A amostra foi intencional e não probabilística. Os dados foram obtidos por meio de questionário e submetidos à análise descritiva e bivariada. Resultados Os participantes revelaram causas do sofrimento moral em dois momentos: Primeiro associado ao processo de fiscalização lento por parte das instituições fiscalizadas e Corens; e insuficiência de recursos humanos. Segundo associado aos problemas éticos; condições de trabalho; e qualidade da assistência de enfermagem. Conclusão Refletir sobre as causas do sofrimento moral neste cenário é reconhecer a necessidade de algumas mudanças que devem acontecer na base que sustenta os preceitos éticos e condutas morais da profissão, para assim fortalecer a categoria.
The duration of pubertal growth peak among three skeletal classes
Authors: Jeelani Waqar ,   The Aga Khan University Hospital,  Pakistan, Fida Mubassar , Shaikh Attiya ,   The Aga Khan University Hospital,  Pakistan,   Aga Khan University Hospital,  Pakistan
Published: November 2016

ABSTRACT Introduction: Pubertal growth peak is closely associated with a rapid increase in mandibular length and offers a wide range of therapeutic modifiability. Objective: The aim of the present study was to determine and compare the mean ages of onset and duration of pubertal growth peak among three skeletal classes. Methods: A retrospective cross-sectional study was conducted using lateral cephalograms of 230 subjects with growth potential (110 males, 120 females). Subjects were categorized into three classes (Class I = 81, Class II = 82, Class III = 67), according to the sagittal relationship established between the maxilla and the mandible. The cervical vertebral maturation stage was recorded by means of Baccetti's method. The mean ages at CS3 and CS4 and the CS3-CS4 age interval were compared between boys and girls and among three skeletal classes. Results: Pubertal growth peak occurred on average four months earlier in girls than boys (p = 0.050). The average duration of pubertal growth peak was 11 months in Class I, seven months in Class II and 17 months in Class III subjects. Interclass differences were highly significant (Cohen's d > 0.08). However, no significant difference was found in the timing of pubertal growth peak onset among three skeletal classes (p = 0.126 in boys, p = 0.262 in girls). Conclusions: Girls enter pubertal growth peak on average four months earlier than boys. Moreover, the duration of pubertal growth peak is on average four months shorter in Class II and six months longer in Class III subjects as compared to Class I subjects.
The Inflection Point of the Speed-Density Relation and the Social Force Model
Authors: Kretz Tobias , Lohmiller Jochen , Schlaich Johannes
Published: November 2016

It has been argued that the speed-density diagram of pedestrian movement has an inflection point. This inflection point was found empirically in investigations of closed-loop single-file pedestrian movement.The reduced complexity of single-file movement does not only allow a higher precision for the evaluation of empirical data, but it also significantly simplifies analytical considerations. This is especially true if one assumes homogeneous conditions, i.e. neglects temporal variations (consider time averages, neglect stop-and-go waves), individual differences of pedestrians (all simulated pedestrians have identical parameters) and investigates only steady-state (not the initial phase). As will be shown in this contribution one then can make a transition from the microscopic to a continuous and macroscopic perspective.Building on that it will be shown that certain (common) variants of the Social Force Model (SFM) do not produce an inflection point in the speed-density diagram if – assuming periodic boundary conditions – infinitely many pedestrians contribute to the force computed for one pedestrian. It will furthermore be shown that if – in said 1d movement situation – one only considers nearest neighbors for the computation of the inter-pedestrian forces the Social Force Model in the continuous description results in the so called Kladek formula for the speed-density relation. Since the Kladek formula exhibits the desired inflection point this observation is used as a motivation for an extension of the Social Force Model which allows to transform the continuous description of the SFM continuously to the Kladek formula and which also exhibits the inflection point in the speed density relation. It will be shown then, that this extended SFM yields astonishingly similar speed density relations as the original SFM when only a fixed limited number of (nearest) pedestrians are considered in the computation of the inter-pedestrian force.Finally it will be discussed, if also the description of the speed-density diagram for (motorized, four-wheel) vehicular and/or bicycle traffic could benefit from these measures.
Compound heterozygous LDLR variant in severely affected familial hypercholesterolemia patient.
Authors: Al-Allaf Faisal A , Alashwal Abdullah , Abduljaleel Zainularifeen , Taher Mohiuddin M , Bouazzaoui Abdellatif , Abalkhail Hala , Al-Allaf Ahmad F , Athar Mohammad
Published: November 2016

Familial hypercholesterolemia (FH) is most commonly caused by mutations in the LDL receptor (LDLR), which is responsible for hepatic clearance of LDL from the blood circulation. We described a severely affected FH proband and their first-degree blood relatives; the proband was resistant to statin therapy and was managed on an LDL apheresis program. In order to find the causative genetic variant in this family, direct exon sequencing of the LDLR, APOB and PCSK9 genes was performed. We identified a compound heterozygous mutation in the proband with missense p.(W577C) and frameshift p.(G676Afs33) variants at exons 12 and 14 of the LDLR gene respectively. DNA sequencing of LDLR gene from the parents demonstrated that the missense variant was inherited from the mother and frameshift variant was inherited from the father. The frameshift variant resulted in a stop signal 33 codons downstream of the deletion, which most likely led to a truncated protein that lacks important functional domains, including the trans-membrane domain and the cytoplasmic tail domain. The missense variant is also predicted to be likely pathogenic and affect EGF-precursor homology domain of the LDLR protein. The segregation pattern of the variants was consistent with the lipid profile, suggesting a more severe FH phenotype when the variants are in the compound heterozygous state. The finding of a compound heterozygous mutation causing severe FH phenotype is important for the genotype-phenotype correlation and also enlarges the spectrum of FH-causative LDLR variants in the Arab population, including the Saudi population.
Archaisms of the french Language in Canada
Authors: Kruglyak E. E.
Published: November 2016

The article discusses archaisms in the French language of Canada. Being isolated from the French of France Canadian variant of French has undergone its development and has retained those lexical units and meanings which the French language of France has lost.
Healthy Native Community Fellowship: An Indigenous Leadership Program to Enhance Community Wellness
Authors: Rae Rebecca , Jones Marita , Handal Alexis J , Bluehorse-Anderson Marge , Frazier Shelley , Maltrud Kristine , Percy Chris , Tso Tina , Varela Frances , Wallerstein Nina
Published: November 2016

The Healthy Native Communities Fellowship (HNCF) is a grassroots evidence-based mentorship and leadership program that develops the skills and community-building capacities of leaders and community teams to improve health status through several intermediate social and cultural mechanisms: (a) strengthening social participation (also known as social capital or cohesion); (b) strengthening cultural connectedness and revitalization of cultural identity; and (c) advocating for health-enhancing policies, practices, and programs that strengthen systems of prevention and care, as well as address the structural social determinants of health. This leadership program uses a community-based participatory research (CBPR) approach and participatory evaluation to investigate how the work of local American Indian and Alaska Native leaders (fellows) and their community coalitions contributes to individual, family, and community level health outcomes.
Transformation of Sulfonamides and Tetracyclines during Anaerobic Fermentation of Liquid Manure
Authors: Spielmeyer Astrid , Stahl Franziska , Petri Madeleine S. , Zerr Walter , Brunn Hubertus , Hamscher Gerd
Published: November 2016

Liquid manure is frequently used as soil fertilizer due to its high nutrient content. It can also contain residues of pharmaceuticals, such as antibiotics, if farm animals are medicated. The anaerobic fermentation process in biogas plants is discussed as one way to reduce the input of antibiotics into the environment. Therefore, 10 worldwide‐applied sulfonamides (sulfachloropyridazine, sulfadiazine, sulfadimethoxine, sulfaguanidine, sulfamerazine, sulfamethazine, sulfamethoxazole, sulfamethoxypyridazine, sulfapyridine, and sulfathiazole) and four frequently used tetracyclines (chlortetracycline, doxycycline, oxytetracycline, and tetracycline) were investigated concerning their elimination pattern during anaerobic fermentation. Batch fermenters with autoclaved and non‐autoclaved inoculum were utilized to distinguish between biotic and abiotic elimination pathways. Overall, sulfadimethoxine, sulfamethoxypyridazine, and sulfamethoxazole showed the highest elimination, which was considerably reduced by autoclaving before inoculation. Structure elucidation via nuclear magnetic resonance and different mass spectrometry techniques revealed only minor structural modifications such as O‐demethylation and hydrogenation, which did not result in a considerably reduced antimicrobial activity. These results show that, especially, sulfonamides are more persistent than expected. Future studies should deal with the elucidation of relevant process parameters for an enhanced compound degradation.

Core Ideas

Veterinary antibiotics were incubated in both active and autoclaved inoculum.

Substance‐related elimination profiles were found for sulfonamides and tetracyclines.

Autoclaving of the inoculum reduced the elimination of the sulfonamides.

O‐Demethylation and hydrogenation led to various transformation products.

Some transformation products showed a reduced antimicrobial activity.