A novel 65 kDa RNA-binding protein in squid presynaptic terminals

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Neuroscience 166 (2010): 73-83, doi:10.1016/j.neuroscience.2009.12.005.A polyclonal antibody (C4), raised against the head domain of chicken myosin Va, reacted strongly towards a 65 kDa polypeptide (p65) on western blots of extracts from squid optic lobes but did not recognize the heavy chain of squid myosin V. This peptide was not recognized by other myosin Va antibodies, nor by an antibody specific for squid myosin V. In an attempt to identify it, p65 was purified from optic lobes of Loligo plei by cationic exchange and reverse phase chromatography. Several peptide sequences were obtained by mass spectroscopy from p65 cut from SDS-PAGE gels. BLAST analysis and partial matching with ESTs from a Loligo pealei data bank indicated that p65 contains consensus signatures for the hnRNP A/B family of RNA-binding proteins. Centrifugation of post mitochondrial extracts from optic lobes on sucrose gradients after treatment with RNase gave biochemical evidence that p65 associates with cytoplasmic RNP complexes in an RNA-dependent manner. Immunohistochemistry and immunofluorescence studies using the C4 antibody showed partial co-labeling with an antibody against squid synaptotagmin in bands within the outer plexiform layer of the optic lobes and at the presynaptic zone of the stellate ganglion. Also, punctate labeling by the C4 antibody was observed within isolated optic lobe synaptosomes. The data indicate that p65 is a novel RNA-binding protein located to the presynaptic terminal within squid neurons and may have a role in synaptic localization of RNA and its translation or processing.REL, JCR and JEM received financial support from the Fundação de Amparo à Pesquisa do Estado de Sao Paulo (FAPESP), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da FMRP-USP (FAEPA). JAD received financial support from the RI-INBRE Program Grant #P20RR016457 from the Nation Center for Research Resources, NIH, Bethesda, MD. DTPL, LC, SBFT, EJRV and MMAB were recipients of research fellowships from FAPESP and CNPq. REL and JEM received Productivityin- Research fellowships from CNPq

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Defining, quantifying, and reporting intensity, dose, and dosage of neurorehabilitative interventions focusing on motor outcomes

Introduction Determining the minimal amount of therapy needed for positive neurorehabilitative outcomes is important for optimizing active treatment interventions to improve motor outcomes. However, there are various challenges when quantifying these relationships: first, several consensuses on the definition and usage of the terms intensity, dose, and dosage of motor interventions have been proposed, but there seems to be no agreement, and the terms are still used inconsistently. Second, randomized controlled trials frequently underreport items relevant to determining the intensity, dose, and dosage of the interventions. Third, there is no universal measure to quantify therapy intensity accurately. This "perspectives" paper aims to increase awareness of these topics among neurorehabilitation specialists.Defining, quantifying, and reporting We searched the literature for definitions of intensity, dose, and dosage and adapted the ones we considered the most appropriate to fit the needs of neurorehabilitative interventions. Furthermore, we suggest refining the template for intervention description and replication (TIDieR) to enhance the reporting of randomized controlled trials. Finally, we performed a systematic literature search to provide a list of intensity measures and complemented these with some novel candidate measures.Discussion The proposed definitions of intensity, dose, and dosage could improve the communication between neurorehabilitation specialists and the reporting of dose and dosage in interventional studies. Quantifying intensity is necessary to improve our understanding of the minimal intensity, dose, and dosage of therapy needed to improve motor outcomes in neurorehabilitation. We consider the lack of appropriate intensity measures a significant gap in knowledge requiring future research.ISSN:2673-686

Correlación entre las lesiones desmielinizantes y el deterioro de las funciones ejecutivas en una muestra de pacientes mexicanos con esclerosis múltiple

Resumen: Antecedentes: La esclerosis múltiple (EM) se caracteriza por una gran diversidad de síntomas neurológicos de entre los cuales el deterioro cognitivo recientemente ha cobrado una especial relevancia. Hasta el momento la evidencia acerca de una correlación entre las características de las lesiones y el deterioro cognitivo específico aún no es concluyente. Objetivo: Analizar si existe una correlación entre las características de las lesiones desmielinizantes y el desempeño de las funciones ejecutivas básicas en estos pacientes. Pacientes y métodos: Se incluyeron 21 pacientes adultos con puntaje de 0-5 en la escala de Kurtzke, sin exacerbaciones de la enfermedad en los 3 meses previos a la evaluación. Se les aplicaron las pruebas de Stroop y el Wisconsin Card Sorting Test (WCST). La localización de las lesiones fue determinada por resonancia magnética a través de un observador experto y cegado. Resultados: Las lesiones desmielinizantes se distribuyeron con mayor frecuencia en los lóbulos occipitales y frontales. En el Stroop se observó que a medida que se incrementa la demanda cognitiva en cada sección de la prueba, aumentan el tiempo de reacción y el número de errores. En el WCST, un 33,33% presentó un deterioro medio a moderado. No se encontró una relación entre la lesiones desmielinizantes –localización, tamaño y suma total– y los puntajes de las pruebas aplicadas. Conclusión: En la explicación del deterioro cognitivo en la EM se deben considerar no solo las lesiones desmielinizantes, sino también otros factores biológicos, psicológicos y sociales. Abstract: Background: Multiple Sclerosis (MS) is characterised by several neurological symptoms including cognitive impairment, which has recently been the subject of considerable study. At present, evidence pointing to a correlation between lesion characteristics and specific cognitive impairment is not conclusive. Objective: To investigate the presence of a correlation between the characteristics of demyelinating lesions and performance of basic executive functions in a sample of MS patients. Patients and methods: We included 21 adult patients with scores of 0 to 5 on the Kurtzke scale and no exacerbations of the disease in at least 3 months prior to the evaluation date. They completed the Stroop test and the Wisconsin Card Sorting Test (WCST). The location of the lesions was determined using magnetic resonance imaging (MRI) performed by a blinded expert in neuroimaging. Results: Demyelinating lesions were more frequently located in the frontal and occipital lobes. The Stroop test showed that as cognitive demand increased on each of the sections in the test, reaction time and number of errors increased. On the WCST, 33.33% of patients registered as having moderate cognitive impairment. No correlation could be found between demyelinating lesion characteristics (location, size, and number) and patients’ scores on the tests. Conclusion: Explanations of the causes of cognitive impairment in MS should examine a variety of biological, psychological, and social factors instead of focusing solely on demyelinating lesions. Palabras clave: Esclerosis múltiple, Deterioro cognitivo, Funciones ejecutivas, Lesiones desmielinizantes, Neuropsicología, México, Keywords: Multiple sclerosis, Cognitive impairment, Executive functions, Demyelinating lesions, Neuropsychology, Mexic

Correlation between demyelinating lesions and executive function decline in a sample of Mexican patients with multiple sclerosis

Background: Multiple sclerosis (MS) is characterised by several neurological symptoms including cognitive impairment, which has recently been the subject of considerable study. At present, evidence pointing to a correlation between lesion characteristics and specific cognitive impairment is not conclusive. Objective: To investigate the presence of a correlation between the characteristics of demyelinating lesions and performance of basic executive functions in a sample of MS patients. Material and methods: We included 21 adult patients with scores of 0 to 5 on the Kurtzke scale and no exacerbations of the disease in at least 3 months prior to the evaluation date. They completed the Stroop test and the Wisconsin Card Sorting Test (WCST). The location of the lesions was determined using magnetic resonance imaging (MRI) performed by a blinded expert in neuroimaging. Results: Demyelinating lesions were more frequently located in the frontal and occipital lobes. The Stroop test showed that as cognitive demand increased on each of the sections in the test, reaction time and number of errors increased. On the WCST, 33.33% of patients registered as having moderate cognitive impairment. No correlation could be found between demyelinating lesion characteristics (location, size, and number) and patients’ scores on the tests. Conclusion: Explanations of the causes of cognitive impairment in MS should examine a variety of biological, psychological, and social factors instead of focusing solely on demyelinating lesions. Resumen: Antecedentes: La Esclerosis Múltiple (EM) se caracteriza por una gran diversidad de síntomas neurológicos de entre los cuales el deterioro cognitivo recientemente ha cobrado una especial relevancia. Hasta el momento la evidencia acerca de una correlación entre las características de las lesiones y el deterioro cognitivo específico aún no es concluyente. Objetivo: Analizar si existe una correlación entre las características de las lesiones desmielinizantes y el desempeño de las funciones ejecutivas básicas en estos pacientes. Pacientes y Métodos: Se incluyeron 21 pacientes adultos con puntaje de 0-5 en la escala de Kurtzke, sin exacerbaciones de la enfermedad en los 3 meses previos a la evaluación. Se les aplicaron las pruebas de Stroop, y el Wisconsin Card Sorting Test (WCST). La localización de las lesiones fue determinada por Resonancia Magnética por un observador experto y cegado Resultados: Las lesiones desmielinizantes se distribuyeron con mayor frecuencia en los lóbulos occipitales y frontales. En el Stroop se observó que, a medida que se incrementa la demanda cognitiva en cada sección de la prueba, aumentan el tiempo de reacción y el número de errores. En el WCST, un 33.33% presentó un deterioro medio a moderado. No se encontró una relación entre la lesiones desmielinizantes – localización, tamaño y suma total – y los puntajes de las pruebas aplicadas. Conclusión: En la explicación del deterioro cognitivo en la EM, se deben considerar no sólo a las lesiones desmielinizantes sino también otros factores biológicos, psicológicos y sociales. Keywords: Multiple sclerosis, Cognitive impairment, Executive functions, Demyelinating lesions, Neuropsychology, Mexico, Palabras clave: Esclerosis múltiple, Deterioro cognitivo, Funciones ejecutivas, Lesiones desmielinizantes, Neuropsicología, Méxic

Envisioning the future of transhumant pastoralism through participatory scenario planning: a case study in Spain

Transhumance is a practice of nomadic pastoralism that was once common in Mediterranean Europe. This livestock-rearing system is associated with the maintenance of cultural landscapes and the delivery of a wide range of ecosystem services. Although transhumance is still practised in Spain on a small scale, its future is highly uncertain because of socioeconomic constraints and other drivers of change. A participatory scenario-planning exercise with 68 participants, including shepherds, decision-makers, veterinarians, environmental experts, intermediaries from the wool and meat markets, and researchers, was used to envision plausible futures for transhumance and to enlighten policy-making for the maintenance of this practice along the Conquense Drove Road, one of the largest foot-based transhumant social-ecological networks still in use in Spain. Specifically, the aims were to: (1) analyse the drivers influencing the future of transhumance, (2) depict the current situation of transhumance, (3) envision future scenarios for this activity, (4) analyse ecosystem services’ trade-offs between different scenarios and their effect on human wellbeing, and (5) provide some insights for policy-making related to the maintenance of transhumance. Four plausible future scenarios were built, each showing clear trade-offs in the delivery of 19 ecosystem services, such as food, fibre, ecological connectivity, soil fertility, air quality, fire prevention, cultural identity, local ecological knowledge and cultural exchanges, as well as the different dimensions of human wellbeing. As a result of the participatory process, nine management strategies were identified for the maintenance of transhumance. Priority was given to the implementation of payment schemes for ecosystem services, the enhancement of social capital among transhumants and institutional coordination, the improvement of product marketing, and the restoration and conservation of drove roads. Finally, the implications of the current reform of the Common Agricultural Policy in the European Union for the maintenance of transhumance are discussed

Development Of A Neural Network Coupled With A Mathematical Model To Optimize The Secondary Cooling Zones In The Continuous Casting Of Steel Billets [acoplamento De Técnicas De Redes Neurais E Modelagem Matemática Da Solidificação Para Aotimização Do Resfriamento Secundário No Processo De Lingotamento Contínuo De Aços]

This work presents the insertion of an artificial intelligence technique (neural network) applied to continuous casting billet process. It was developed a neural network algorithm, which works linked to a mathematical model to determine the optimum values for the water flow rates in the secondary cooling zones. Firstly, the results obtained by the mathematical model were validated against experimental data (industrial) and a good agreement has been observed, in a second step these results were used by the neural network algorithm for determining optimum settings of water flow rates in the different sprays zones, which are conducive to the best quality of the solidified ingot. With the new set of values for flow rates, another simulation was carried out analyzing the solidification process during continuous casting in order to attain metallurgical restrictions concerning the reheating of strand surface temperature and metallurgical length.31853194Russel, S.J., Norvig, P., (1990) Artificial Intelligence: A Modern Approach, , Prentice Hall, Upper Saddle River, New JerseyBhadeshia, H.K.D.H., Neural Networks in Materials Science (1999) ISIJ International, 39 (10), pp. 966-979Kominami, H., Neural Network System for Breakout Prediction in Conditions Casting Process (1991) Nippon Steel Technical Report, (49). , AprWatanabe, T., Omura, K., Konishi, M., Watanabe, C., Furukawa, K., Mold Level Control in Continuous Casting by Neural Network Model (1999) ISIJ, 39 (10), pp. 1053-1060Zietsman, J.H., Kumar, S., Meech, J.A., Samarasekera, I.V., Brimacombe, J.K., Taper J.P.Design in Continuous Billet Casting Using Artificial Neural Networks (1998) Ironmaking and Steelmaking, 25 (6), pp. 476-483Mukherjee, A., Artificial Neural Networks for the Prediction of Mechanical Behavior of Metal Matrix Composites (1995) Acta Metallurgical, 43 (11), pp. 4083-4091. , FebSowka, E., Dikhoff, P.S., Harder, J., Munscher, F., Beirer, G., Breakout Avoidance System, BASYS, for Continuous Slab Casting (1999) Iron & Steel Engineer, pp. 30-35. , MayToledo, G.A., Lainez, J., Cirión, J.C., Model Optimization of Continuous Casting Steel Secondary Cooling (1993) Materials Science & Engineering A, 173, pp. 287-291Brimacombe, J.K., Baptista, L.A., (1980) Spray Cooling in the Continuous Casting of SteelThomas, B.G., Samarasekera, I.V., Brimacombe, J.K., Mathematical Model of the Thermal Processing of Steel Ingots: Part 1 Heat Flow Model (1987) Metallurgical Transactions, 18 B, pp. 119-130Brimacombe, J.K., Argarwal, P.K., Baptista, L.A., Hibbins, S., Prabhakar, B., Spray Cooling in the Continuous Casting of Steel (1980) Steelmaking Proceedings of the NOH-BOS Conference (ISS-AIME), pp. 109-123Santos, C.A., Spim Jr., J.A., Ierardi, M.C.F., Garcia, A., The Use of Artificial Intelligence Technique for the Optimization of Process Parameters Used in the Continuous Casting of Steel (2002) Applied Mathematical Modeling, 26 (11), pp. 1077-109

Enhancing the accuracy of rational function-based models using optimization

Rational function approximations are widely used for the modelling of frequency-dependent effects in power system components. This paper proposes to use optimization by the damped Gauss-Newton method to improve the accuracy of rational approximations calculated by three mainstream fitting techniques: Bode's asymptotic approximation, Sanathanan-Koerner iteration, and vector fitting. The optimization method is described in detail along with an outline of the numerical implementation. The proposed methodology is demonstrated for a synthetic example for the modelling of a measured reactor frequency response and for the rational fitting of the frequency-dependent parameters corresponding to a single-phase transmission line. In this example, we also present the impact of the optimization enhancement on the final time domain responses. ©2015 Elsevier B.V. All rights reserved