To divide or differentiate? : nestin-mediated regulation of Cdk5 in cell fate decisions

The molecular functions of the non-cell cycle-related Cyclin-dependent kinase 5 (Cdk5) have been of primary interest within the neuroscience field, but novel undertakings are constantly emerging for the kinase in tissue homeostasis, as well as in diseases such as diabetes and cancer. Although Cdk5 activation is predominantly regulated by specific non-cyclin activator protein binding, additional mechanisms have proved to orchestrate Cdk5 signaling in cells. For example, the interaction between the intermediate filament protein nestin and Cdk5 has been proposed to determine cellular fate during neuronal apoptosis through nestin-dependent adjustment of the sensitive balance and turnover of Cdk5 activators. While nestin constitutes a crucial regulatory scaffold for appropriate Cdk5 activation in apoptosis, Cdk5 itself phosphorylates nestin with the consequence of filament reorganization in both neuronal progenitors and differentiating muscle cells. Interestingly, the two proteins are often found coexpressed in various tissues and cell types, proposing that nestin-mediated scaffolding of Cdk5 and its activators may be applicable to other tissue systems as well. In the literature, the molecular functions of nestin have remained in the shade, as it is mostly exploited as a marker protein for progenitor cells. In light of these studies, the aim of this thesis was to assess the importance of the nestin scaffold in regulation of Cdk5 actions in cell fate decisions. This thesis can be subdivided into two major projects: one that studied the nature of the Cdk5-nestin interplay in muscle, and one that assessed their role in prostate cancer. During differentiation of a myoblast cell line, the filament formation properties of nestin was found to be crucial in directing Cdk5 activity, with direct consequences on the process of differentiation. Also the genetic knockout of nestin was found to influence Cdk5 activity, although differentiation per se was not affected. Instead, the genetic ablation of nestin had broad consequences on muscle homeostasis and regeneration. While the nestin-mediated regulation of Cdk5 in muscle was found to act in multiple ways, the connection remained more elusive in cancer models. Cdk5 was, however, established as a significant determinant of prostate cancer proliferation; a behavior uncharacteristic for this differentiation-associated kinase. Through complex and simultaneous regulation of two major prostate cancer pathways, Cdk5 was placed upstream of both Akt kinase and the androgen receptor. Its action on proliferation was nonetheless mainly exerted through the Akt signaling pathway in various cancer models. In summary, this thesis contributed to the knowledge of Cdk5 regulation and functions in two atypical settings; proliferation (in a cancer framework) and muscle differentiation, which is a poorly understood model system in the Cdk5 field. This balance between proliferation and differentiation implemented by Cdk5 is ultimately regulated (where present) by the dynamics of the cytoskeletal nestin scaffold.

Qualidade sensorial de vinhos tintos finos do Rio Grande do Sul comparados aos importados da Argentina e Chile

Avaliou-se a percepção da qualidade intrínseca dos vinhos finos tintos elaborados no Rio Grande do Sul em comparação com seus principais concorrentes da Argentina e Chile. A análise sensorial foi realizada por 31 consumidores da classe de maior poder aquisitivo de Porto Alegre. O teste de aceitação propôs escalas hedônicas para avaliar os atributos sensoriais dos produtos. A análise estatística valeu-se de ANOVA e teste de Tukey. Os resultados demonstraram que a qualidade intrínseca dos vinhos brasileiros não representa um fator restritivo à competitividade do setor que pode ser alavancada com o desenvolvimento de estratégias de marketing consistentes.

Cinética de la transferencia de masa durante la deshidratación osmótica de yacón (Smallanthus sonchifolius)

El yacón (Smallanthus sonchifolius) es un tubérculo andino de vida útil muy corta bajo condiciones ambientales. Los objetivos de este trabajo fueron determinar: 1) la cinética de deshidratación osmótica de yacón, utilizando sacarosa como soluto; 2) el ajuste de la ecuación de Peleg a los datos experimentales; y 3) el coeficiente de difusión usando la ecuación de Hawkes y Flink. La fruta se peló y cortó en placas de 3 x 3 x 0,3 cm. Se la deshidrató osmóticamente con solución de sacarosa al 40% (p/p), hasta aw = 0,97. El proceso se realizó a temperatura de 25 °C y con agitación continua (105 rpm). Se determinó la pérdida de peso de las muestras, la ganancia de sólidos y la retención de agua. Los parámetros obtenidos para el ajuste de pérdida de agua y ganancia de sólidos son respectivamente: k1: 8,2 0,1 y k2: 0,53 ± 0,06; k1: 234 ± 8 y k2: 2,6 ± 0,5. La mayor transferencia de masa, tanto de agua como de soluto, ocurre durante los primeros 60 a 90 minutos de proceso, lográndose una ganancia media de sólidos de 9,5 [g.100 g-1 MF] y una pérdida de agua de 68,8 [g.100 g-1MF]. Se puede asegurar que es posible aplicar satisfactoriamente el proceso de deshidratación osmótica en yacón como pre tratamiento de conservación.

Secagem de bananas prata e d'água por convecção forçada

Estudou-se a influência de variáveis como cultivar, formato (cilindro e disco), branqueamento e condições do ar aquecido (temperatura: 50 e 70 ºC e velocidade: 0,14 e 0,42 m/s) sobre o comportamento de secagem convectiva de bananas com uso de modelagem matemática. As bananas foram desidratadas em secador de bandejas e pesada em intervalos pré-determinados. O modelo exponencial foi bem ajustado às curvas de secagem (R²: 0,98-0,99), mostrando que os fatores mais influentes sobre a taxa de secagem foram a temperatura, a velocidade do ar e o branqueamento. De acordo com as constantes cinéticas apresentadas pelo modelo recomenda-se a secagem de banana, em qualquer dos formatos estudados, nas seguintes condições: para banana-prata, uso de branqueamento e secagem a 50 ºC/0,42 m/s; e para banana-d'água, sem uso de branqueamento e secagem a 70 ºC/0,42 m/s.

Evaluation of the efficacy of commercial sanitizers against adhered and planktonic cells of Listeria monocytogenes and Salmonella spp.

Antimicrobial activities of two commercial disinfectants, alone or combined with heat, against three Salmonella strains and three Listeria monocytogenes strains were studied. The efficacy of disinfectants against planktonic bacteria and bacteria attached to three food contact industrial surfaces (stainless steel, polytetraflourethylene, and rubber) was investigated. The tests were conducted using the sanitizer (quaternary ammonium compounds, and alquyldiethylenediamineglycine and di-alquyldiamineethylglycine) concentrations recommended by the manufacturers, and concentrations twice and four times higher than those values. The recommended concentrations were not effective to kill bacteria, especially when they were attached to surfaces. Concentrations of disinfectants twice and four times higher than those recommended were needed to fully eliminate planktonic bacteria. These same sanitizer concentrations were not sufficient to remove attached bacteria. To remove them from the surfaces, a treatment with recommended concentrations in combination with heat was needed. Our results indicate that these two pathogenic bacteria could survive common sanitation programs used in the food industry.

Relationship between the price of fish and its quality attributes: a study within a community at the University of São Paulo, Brazil

The aim of this study was to evaluate the associations between the products' market price and attributes related to fish purchase and consumption within a university community in Brazil. A structured questionnaire consisting of a five-point Likert scale was used. It was previously tested and made available to the university community via the Internet. The sample comprised 1966 voluntaries including university students and faculty and staff members. A descriptive analysis of data was performed using Spearman's correlation analysis. The results showed that the majority of the respondents (56%) consume fish at home; some consume fish at restaurants (39%), and 5% at family or friends' houses, reinforcing the idea that variables such as culture and reference groups are fundamental determinants of purchase and consumption behavior. It was identified a significant (p < 0.001) and very strong correlation between the attributes price and nutritional value (r = 0.92); price and availability at the usual places of purchase (r = 0.92); price and packaging (r = 0.92); price and brand name (r = 0.91); and price and of the Federal Inspection stamp (r = 0.91) and a low positive correlation (p < 0.001) between the price variable and the initiative for fish traceability (r = 0.16). This study demonstrated that the price of fish is associated with the quality of the product and the attributes related to it such as packaging, nutritional value, and availability of the product in the market.

Biotechnological richness of the northeastern semi-arid region: antioxidant activity of casein hydrolysates from Moxotó goat milk (Capra hircus Linnaeus, 1758) obtained by papain action

This study aimed to identify antioxidant peptides from caprine casein hydrolysates by papain application using MALDI-TOF mass spectrometer, and a 2² full factorial design, with 4 axial points, in order to evaluate kinetic parameters (time and pH) effects on the degree of hydrolysis as well as the antioxidant activity of Moxotó goat milk casein peptides. Degree of hydrolysis was determined by total and soluble protein ratio in casein. Antioxidant activity was measured by ABTS method with 2, 2-cation-azinobis (3-ethylbenzothiazoline-6-sulfonic acid). TROLOX was used as standard. Peptide pattern and sequence of antioxidant amino acids were obtained using MALDI-TOF/MS. The highest degree of hydrolysis (28.5%) and antioxidant activity (2329.6 mmol.L TROLOX. mg- 1 peptide) were observed in the permeate. NENLL, NPWDQVK and LLYQEPVLGPV peptides, detected in the permeate, were pointed as the responsible for antioxidant activity, suggesting their potential application as food supplement and pharmaceutical products.

Designing and validating the methodology for the Internet assessment of fish consumption at a university setting

Assessing fish consumption is complex and involves several factors; however, the use of questionnaires in surveys and the use of the Internet as tool to collect data have been considered promising approaches. Therefore, the objective of this research was to design a data collection technique using a questionnaire to assess fish consumption by making it available on a specific home page on the Internet. A bibliographical survey or review was carried out to identify the features of the instrument, and therefore pre-tests were conducted with previous instruments, followed by the Focus Group technique. Specialists then performed an analysis and conducted an online pre-test. Multivariate data analysis was applied using the SmartPLS software. The results indicate that 1.966 participants belonging to the University of São Paulo (USP) community participated in the test, and after the exclusion of some variables, a statistically significant results were obtained. The final constructs comprised consumption, quality, and general characteristics. The instrument consisted of behavioral statements in a 5-point Likert scale and multiple-choice questions. The Cronbach's alpha reliability coefficient was 0.66 for general characteristics, 0.98 for quality, and 0.91 for consumption, which indicate good reliability of the instrument. In conclusion, the results proved that the Internet assessment is efficient. The instrument of analysis allowed us to better understand the process of buying and consuming fish in the country, and it can be used as base for further research.

Fennougristi löytää kielen aarteita päivittäin

Haastateltana Julia Kuprina, joka työskentelee Koneen Säätiön apurahan turvin projektitutkijana Avointa kieliteknologiaa uralilaisille vähemmistökielille (AKU) -projektissa Helsingin yliopiston Nykykielten laitoksen ja Tromssan yliopiston Giellateknon yhteistyönä.

Biomarcadores da injúria renal aguda

A creatinina continua a ser o padrão laboratorial para diagnóstico da injúria renal aguda (IRA). Esforços para prevenção da nefrotoxicidade foram prejudicados pelo atraso no diagnóstico da IRA por critérios utilizando somente a creatinina como marcador, havendo, por isso, grande interesse em identificar mais precocemente biomarcadores confiáveis. Além disso, o tratamento precoce da IRA pode ser correlacionado com um melhor prognóstico e a identificação de biomarcadores para um diagnóstico precoce pode melhorar a eficácia de estratégia terapêutica. Portanto, torna-se imperativo encontrar biomarcadores que possam estratificar corretamente o grau de lesão renal e o risco de desenvolver doença renal crônica (DRC). Aqui, nós revisamos as principais características dos emergentes biomarcadores em nefrologia.

Papel da lipocalina associada à gelatinase neutrofílica (NGAL) urinária na nefrotoxicidade da cisplatina em pacientes com câncer de cabeça e pescoço

Introdução: A injúria renal aguda (IRA) em pacientes que recebem a cisplatina é comum, portanto, a avaliação da função renal em pacientes utilizando drogas nefrotóxicas é fundamental. Objetivo: Avaliar a incidência da IRA e o papel da lipocalina associada à gelatinase neutrofílica (NGAL) na avaliação da função renal em pacientes com câncer de cabeça e pescoço (CCP) que receberam a cisplatina. Métodos: Foram avaliados prospectivamente 50 pacientes com CCP, tratados com três sessões de cisplatina. Foram coletados sangue e urina 24 horas antes da cisplatina, 24 horas após a infusão, 48 horas após cada aplicação e 35 dias após o término do tratamento (NGAL urinária, proteína C reativa, creatinina e taxa de filtração glomerular, desidrogenase lática e magnésio plasmáticos). Resultados: A IRA foi observada em 78% dos pacientes. Houve aumento na creatinina, ureia e queda na TFG após cada ciclo de cisplatina, e aumento da NGAL urinária. Foi observada associação positiva entre os níveis de NGAL e a creatinina e PCR. Evidenciou-se um aumento dos níveis de creatinina, NGAL, PCR e diminuição da TFG nos pacientes com IRA em relação aos pacientes sem IRA. Conclusão: Observamos IRA em 78% dos pacientes avaliados com CCP tratados com a cisplatina e correlação da NGAL com a creatinina e a TFG em demonstrar lesão renal. Os níveis de NGAL podem estar elevados em relação aos níveis basais, mesmo antes da utilização da cisplatina.

Mineraalien rikastusprosessin vesijalanjälki

Mineraalien rikastamiseen käytetään useita fysikaalisia ja kemiallisia menetelmiä. Prosessi sisältää malmin hienonnuksen, rikastuksen ja lopuksi vedenpoistamisen rikastelietteestä. Malmin rikastamiseen käytetään muun muassa vaahdotusta, liuotusta, magneettista rikastusta ja tiheyseroihin perustuvia rikastusmenetelmiä. Rikastuslietteestä voidaan poistaa vettä sakeuttamalla ja suodattamalla. Rikastusprosessin ympäristövaikutuksia voidaan arvioida laskemalla tuotteen vesijalanjälki, joka kertoo valmistamiseen kulutetun veden määrän. Tässä kirjallisuustyössä esiteltiin mineraalien käsittelymenetelmiä sekä prosessijätevesien puhdistusmenetelmiä. Kirjallisuuslähteiden pohjalta selvitettiin Pyhäsalmen kaivoksella valmistetun kuparianodin vesijalanjälki sekä esitettiin menetelmiä, joilla prosessiin tarvittavan raakaveden kulutusta voitaisiin vähentää. Pyhäsalmella kuparirikasteesta valmistetun kuparianodin vesijalanjälki on 240 litraa H2O ekvivalenttia tuotettua tonnia kohden. Pyhäsalmen prosessin raakaveden kulutusta voidaan vähentää lisäämällä sisäistä vedenkierrätystä. Kalsiumsulfaatin saostuminen putkiin ja pumppuihin on ilmentynyt ongelmaksi vedenkierrätyksen lisäämisessä. Kalsiumsulfaattia voidaan erottaa vedestä membraaneihin, ioninvaihtoon ja sähkökemiaan perustuvilla tekniikoilla. Vaihtoehdossa, jossa johdetaan kaikista kolmesta vaahdotuksesta saatavat rikastuslietteen ja rikastushiekan sakeutuksien ylitteet sekä suodatuksien suodosvedet samaan vedenkäsittelyyn voidaan kattaa arviolta noin 65 % koko veden tarpeesta. Raakavettä säästetään vuodessa 3,4 Mm^3 ja samalla rikastushiekka-altaiden tarvittava koko pienenee, joka vähentää ympäristöriskejä.