Methylation Silencing of ULK2, an Autophagy Gene, Is Essential for Astrocyte Transformation and Tumor Growth

Glioblastoma (GBM) is the most aggressive type of brain tumor and shows very poor prognosis. Here, using genome-wide methylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct classes of biological processes. One of the hypermethylated genes in GBM, ULK2, an upstream autophagy inducer, was found to be down-regulated in GBM. Promoter hypermethylation of ULK2 was confirmed by bisulfite sequencing. GBM and glioma cell lines had low levels of ULK2 transcripts, which could be reversed upon methylation inhibitor treatment. ULK2 promoter methylation and transcript levels showed significant negative correlation. Ectopic overexpression of ULK2-induced autophagy, which further enhanced upon nutrient starvation or temozolomide chemotherapy. ULK2 also inhibited the growth of glioma cells, which required autophagy induction as kinase mutant of ULK2 failed to induce autophagy and inhibit growth. Furthermore, ULK2 induced autophagy and inhibited growth in Ras-transformed immortalized Baby Mouse Kidney (iBMK) ATG5(+/+) but not in autophagy-deficient ATG5(-/-) cells. Growth inhibition due to ULK2 induced high levels of autophagy under starvation or chemotherapy utilized apoptotic cell death but not at low levels of autophagy. Growth inhibition by ULK2 also appears to involve catalase degradation and reactive oxygen species generation. ULK2 overexpression inhibited anchorage independent growth, inhibited astrocyte transformation in vitro and tumor growth in vivo. Of all autophagy genes, we found ULK2 and its homologue ULK1 were only down-regulated in all grades of glioma. Thus these results altogether suggest that inhibition of autophagy by ULK1/2 down-regulation is essential for glioma development.

Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions

Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

DLTS analysis of amphoteric interface defects in high-TiO2 MOS structures prepared by sol-gel spin-coating

High-kappa TiO2 thin films have been fabricated from a facile, combined sol-gel spin - coating technique on p and n type silicon substrate. XRD and Raman studies headed the existence of anatase phase of TiO2 with a small grain size of 18 nm. The refractive index `n' quantified from ellipsometry is 2.41. AFM studies suggest a high quality, pore free films with a fairly small surface roughness of 6 angstrom. The presence of Ti in its tetravalent state is confirmed by XPS analysis. The defect parameters observed at the interface of Si/TiO2 were studied by capacitance - voltage (C - V) and deep level transient spectroscopy (DLTS). The flat - band voltage (V-FB) and the density of slow interface states estimated are -0.9, -0.44 V and 5.24x10(10), 1.03x10(11) cm(-2); for the NMOS and PMOS capacitors, respectively. The activation energies, interface state densities and capture cross -sections measured by DLTS are E-V + 0.30, E-C - 0.21 eV; 8.73x10(11), 6.41x10(11) eV(-1) cm(-2) and 5.8x10(-23), 8.11x10(-23) cm(2) for the NMOS and PMOS structures, respectively. A low value of interface state density in both P-and N-MOS structures makes it a suitable alternate dielectric layer for CMOS applications. And also very low value of capture cross section for both the carriers due to the amphoteric nature of defect indicates that the traps are not aggressive recombination centers and possibly can not contribute to the device operation to a large extent. (C) 2015 Author(s).

The relationship of SIF between plate and plane fracture problems and the effect of the plate thickness on SIF

In the present paper, it is shown that the zero series eigenfunctions of Reissner plate cracks/notches fracture problems are analogous to the eigenfunctions of anti-plane and in-plane. The singularity in the double series expression of plate problems only arises in zero series parts. In view of the relationship with eigen-values of anti-plane and in-plane problem, the solution of eigen-values for Reissner plates consists of two parts: anti-plane problem and in-plane problem. As a result the corresponding eigen-values or the corresponding eigen-value solving programs with respect to the anti-plane and in-plane problems can be employed and many aggressive SIF computed methods of plane problems can be employed in the plate. Based on those, the approximate relationship of SIFs between the plate and the plane fracture problems is figured out, and the effect relationship of the plate thickness on SIF is given.

Autorregulación emocional y actitudes ante situaciones de agravio

Este trabajo trata acerca de la evaluación de la influencia de la autorregulación emocional (control de los impulsos y control en situaciones adversas) sobre las actitudes ante situaciones de agravio. La muestra comprendió a 287 adolescentes, de ambos sexos, 114 varones y 173 mujeres, de 15 a 17 años de edad, residentes en la ciudad de Paraná. Los instrumentos utilizados fueron el Cuestionario de Actitudes ante Situaciones de Agravio y el Inventario de Cociente Emocional (Eq-i). Los resultados obtenidos nos muestran que existe una relación negativa entre el control de los impulsos y el control en situaciones adversas, y las actitudes agresivas de venganza, rencor y hostilidad.

Una mirada universitaria sobre la anencefalia

Resumen: Un niño con anencefalia, debido a su innegable condición humana, merece ser tratado con respeto y dignidad, como cualquier otro hombre. Por su severa patología y su corta expectativa de vida, es una criatura frágil e indefensa a la que hay que cuidar, y no por ello aplicar tratamiento, hasta que devenga su inevitable muerte. La futilidad de cualquier medida agresiva sustenta la necesidad de proporcionarle calor y cuidados básicos, sin incurrir en tratamientos desproporcionados. Al mismo tiempo, resulta fundamental informar, acompañar y brindar apoyo médico y psicológico a toda la familia, en especial a la madre, para poder superar la muerte del niño. Por último, es preciso establecer que el pronóstico ominoso de una criatura anencefálica jamás justifica el aborto. A partir del estudio de la bibliografía argentina sobre el tema, y desde la perspectiva de un estudiante de medicina, se analizan los textos publicados, añadiendo algunos comentarios éticos actuales sobre los problemas de la anencefalia.

Royalty Licensing

Published as an article in: Economics Letters, 2010, vol. 107, issue 2, pages 284-287.

Two-part tariff licensing mechanisms

Most of the patent licensing agreements that are observed include royalties, in particular per-unit or ad valorem royalties. This paper shows that in a differ entiated duopoly that competes á la Cournot the optimal contract for an internal patentee always includes a positive royalty. Moreover, we show that the patentee would prefer to use ad valorem royalties rather than per-unit royalties when goods are complements or when they are substitutes and the degree of differentiation is suffciently low. The reason is that by including an ad valorem royalty in the licensing contract the patentee can commit strategically to be more (less) aggressive when goods are complements (substitutes) since his licensing revenues become increasing with the price of output of his rival. As a result, licensing may hurt consumers although it always increases social welfare.

Effect of Cattail (Typha domingensis) Extracts, Leachates, and Selected Phenolic Compounds on Rates of Oxygen Production by Salvinia (Salvinia minima)

Salvinia (Salvinia minima Willd.) is a water fern found in Florida waters, usually associated with Lemna and other small free-floating species. Due to its buoyancy and mat-forming abilities, it is spread by moving waters. In 1994, salvinia was reported to be present in 247 water bodies in the state (out of 451 surveyed public waters, Schardt 1997). It is a small, rapidly growing species that can become a nuisance due to its explosive growth rates and its ability to shade underwater life (Oliver 1993). Any efforts toward management of salvinia populations must consider that, in reasonable amounts, its presence is desirable since it plays an important role in the overall ecosystem balance. New management alternatives need to be explored besides the conventional herbicide treatments; for example, it has been shown that the growth of S. molesta can be inhibited by extracts of the tropical weed parthenium (Parthenium hysterophorus) and its purified toxin parthenin (Pande 1994, 1996). We believe that cattail, Typha spp. may be a candidate for control of S. minima infestations. Cattail is an aggressive aquatic plant, and has the ability to expand over areas that weren't previously occupied by other species (Gallardo et al. 1998a and references cited there). In South Florida, T. domingensis is a natural component of the Everglades ecosystem, but in many cases it has become the dominant marsh species, outcompeting other native plants. In Florida public waters, this cattail species is the most dominant emergent species of aquatic plants (Schardt 1997). Several factors enable it to accomplish opportunistic expansion, including size, growth habits, adaptability to changes in the surroundings, and the release of compounds that can prevent the growth and development of other species. We have been concerned in the past with the inhibitory effects of the T. domingensis extracts, and the phenolic compounds mentioned before, towards the growth and propagation of S. minima (Gallardo et al. 1998b). This investigation deals with the impact of cattail materials on the rates of oxygen production of salvinia, as determined through a series of Warburg experiments (Martin et al. 1987, Prindle and Martin 1996).

Prevención de la agresividad y la violencia en el deporte en edad escolar: Un estudio de revisión.

Reconocimiento-NoComercial-SinObraDerivada 3.0 España (CC BY-NC-ND 3.0 ES)

Protocolo de prevención de partidos de riesgo: una experiencia aplicada para la prevención de la violencia en el fútbol base

[EN] This study presents an applied experience which takes part of a program on prevention of the violence in soccer in school age. The aim was the acquisition of the commitment of the trainers involved in matches considered as non sportive, in the fulfillment of sportive behavior guidelines. To achieve this aim, a meeting was carried out by the trainers of the equipments that led violent incidents in the first round of the league, with the presidents of these equipments, with representatives of the local football Federation and with representatives of the Committee of referees. From this meeting it was intended: 1) to reduce the probability of aggressive and violent incidents; 2) to promote a relation of cooperation between the entities of the teams that led non sportive incidents, and the referee group; and 3) Make the sports context be a protector to prevent non sportive behaviors. The results of this study reflect that the participation had a positive effect in the improvement of the sportsmanship in the return football matches of the league.

Decarbonising urban transportation

18 p.

How resources control aggression in Drosophila

How animals use sensory information to weigh the risks vs. benefits of behavioral decisions remains poorly understood. Inter-male aggression is triggered when animals perceive both the presence of an appetitive resource, such as food or females, and of competing conspecific males. How such signals are detected and integrated to control the decision to fight is not clear. Here we use the vinegar fly, Drosophila melanogaster, to investigate the manner in which food and females promotes aggression.

In the first chapter, we explore how food controls aggression. As in many other species, food promotes aggression in flies, but it is not clear whether food increases aggression per se, or whether aggression is a secondary consequence of increased social interactions caused by aggregation of flies on food. Furthermore, nothing is known about how animals evaluate the quality and quantity of food in the context of competition. We show that food promotes aggression independently of any effect to increase the frequency of contact between males. Food increases aggression but not courtship between males, suggesting that the effect of food on aggression is specific. Next, we show that flies tune the level of aggression according to absolute amount of food rather than other parameters, such as area or concentration of food. Sucrose, a sugar molecule present in many fruits, is sufficient to promote aggression, and detection of sugar via gustatory receptor neurons is necessary for food-promoted aggression. Furthermore, we show that while food is necessary for aggression, too much food decreases aggression. Finally, we show that flies exhibit strategies consistent with a territorial strategy. These data suggest that flies use sweet-sensing gustatory information to guide their decision to fight over a limited quantity of a food resource.

Following up on the findings of the first chapter, we asked how the presence of a conspecific female resource promotes male-male aggression. In the absence of food, group-housed male flies, who normally do not fight even in the presence of food, fight in the presence of females. Unlike food, the presence of females strongly influences proximity between flies. Nevertheless, as group-housed flies do not fight even when they are in small chambers, it is unlikely that the presence of female indirectly increases aggression by first increasing proximity. Unlike food, the presence of females also leads to large increases in locomotion and in male-female courtship behaviors, suggesting that females may influence aggression as well as general arousal. Female cuticular hydrocarbons are required for this effect, as females that do not produce CH pheromones are unable to promote male-male aggression. In particular, 7,11-HD––a female-specific cuticular hydrocarbon pheromone critical for male-female courtship––is sufficient to mediate this effect when it is perfumed onto pheromone-deficient females or males. Recent studies showed that ppk23⁺ GRNs label two population of GRNs, one of which detects male cuticular hydrocarbons and another labeled by ppk23 and ppk25, which detects female cuticular hydrocarbons. I show that in particular, both of these GRNs control aggression, presumably via detection of female or male pheromones. To further investigate the ways in which these two classes of GRNs control aggression, I developed new genetic tools to independently test the male- and female-sensing GRNs. I show that ppk25-LexA and ppk25-GAL80 faithfully recapitulate the expression pattern of ppk25-GAL4 and label a subset of ppk23⁺ GRNs. These tools can be used in future studies to dissect the respective functions of male-sensing and female-sensing GRNs in male social behaviors.

Finally, in the last chapter, I discuss quantitative approaches to describe how varying quantities of food and females could control the level of aggression. Flies show an inverse-U shaped aggressive response to varying quantities of food and a flat aggressive response to varying quantities of females. I show how two simple game theoretic models, “prisoner’s dilemma” and “coordination game” could be used to describe the level of aggression we observe. These results suggest that flies may use strategic decision-making, using simple comparisons of costs and benefits.

In conclusion, male-male aggression in Drosophila is controlled by simple gustatory cues from food and females, which are detected by gustatory receptor neurons. Different quantities of resource cues lead to different levels of aggression, and flies show putative territorial behavior, suggesting that fly aggression is a highly strategic adaptive behavior. How these resource cues are integrated with male pheromone cues and give rise to this complex behavior is an interesting subject, which should keep researchers busy in the coming years.

Avaliação da eficácia da terapia fotodinâmica como adjunto ao tratamento periodontal de pacientes com periodontite agressiva

A periodontite agressiva é um processo inflamatório de origem bacteriana mediado pelo sistema imunológico do hospedeiro e é provavelmente a forma mais grave de doença periodontal, apresentando destruição das estruturas tanto de proteção quanto de suporte dentário, num período relativamente rápido, normalmente levando a perda prematura dos elementos dentários e, em alguns casos, terapia antimicrobiana adjunta é necessária em adição à terapia mecânica. O objetivo do presente ensaio clínico randomizado controlado foi avaliar o efeito clínico da terapia fotodinâmica como adjunto ao tratamento periodontal não cirúrgico no tratamento da periodontite agressiva Os seguintes parâmetros clínicos foram avaliados: índice de placa visível, sangramento à sondagem, profundidade de bolsa à sondagem, nível de inserção clínica relativo, envolvimento de furca e mobilidade. Foram selecionados dez pacientes com periodontite agressiva, os quais foram examinados no dia zero e após três meses.O desenho do estudo consistiu em um modelo de boca dividida, onde um hemiarco foi tratado com raspagem e alisamento radicular e terapia fotodinâmica (laser diodo) e o outro apenas com raspagem e alisamento radicular. Três meses após o término do tratamento, os grupos terapêuticos apresentaram resultados semelhantes para todos os parâmetros clínicos avaliados: ambas as terapias tiveram sucesso, como redução de profundidade de bolsa, ganho de nível de inserção clínica relativo, redução de índice de placa visível, redução de sangramento à sondagem, diminuição de envolvimento de furca e diminuição de mobilidade, porém sem diferenças estatisticamente significantes entre elas. Dentro das limitações do presente estudo, os resultados sugerem que a terapia fotodinâmica adjuntamente ao tratamento periodontal não cirúrgico mecânico foi tão eficaz quanto o tratamento periodontal não cirúrgico mecânico sozinho.

Perfil imunológico e microbiológico de pacientes com periodontites crônica e agressiva

O objetivo deste estudo foi determinar os níveis de interleucina-1β (IL-1 β), IL-2, IL-4, IL-8, interferon-γ (IFN-γ) e a atividade de elastase no fluido gengival (FG) de pacientes com periodontite crônica generalizada (PCG) e periodontite agressiva generalizada (PAgG), e correlacionar com indivíduos de um grupo controle com gengivite apenas. Um objetivo secundário foi analisar o perfil microbiológico subgengival destes indivíduos. Dados clínicos transversais foram obtidos de 20 pacientes com PCG, 17 pacientes com PAgG e 10 indivíduos com gengivite. Amostras de FG foram coletadas com tiras de papel e os níveis de: IL-1β, IL-2, IL-4, IL-8 e IFN-γ foram medidos, utilizando um imunoensaio do tipo multiplex (Luminex). Atividade da elastase foi avaliada por um ensaio enzimático. Amostras de placa subgengival foram analisadas através do checkerboard DNA-DNA hybridization. As diferenças de significância entre os grupos para dados imunológicos e microbiológicos foram realizadas utilizando o teste Kruskal-Wallis, ajustando para múltiplas comparações. As médias dos parâmetros clínicos e os volumes de FG foram maiores nos pacientes com PCG e PAgG comparados ao grupo gengivite. Níveis mais elevados de IL-1β e atividade de elastase foram encontrados em sítios profundos quando comparado a sítios rasos em ambos os grupos com periodontite (p <0,05). Os dados microbiológicos apresentaram níveis significativamente mais elevados das espécies do complexo vermelho em pacientes com PCG e PAgG, quando comparados aos indivíduos com gengivite (p <0,05). Não houve diferença estatisticamente significante nos níveis de biomarcadores no FG e nos níveis de espécies bacterianas subgengivais entre pacientes com PCG e pacientes com PAgG. Sendo assim, concluímos que os dados do presente estudo não mostraram diferença estatisticamente significante nos parâmetros imunológicos e microbiológicos medidos entre indivíduos com PCG e PAgG.