Role of versican V0/V1 and CD44 in the regulation of human melanoma cell behaviour

Versican is a hyaluronan-binding, large extracellular matrix chondroitin sulfate proteoglycan whose expression is increased in malignant melanoma. Binding to hyaluronan allows versican to indirectly interact with the hyaluronan cell surface receptor CD44. The aim of this work was to study the effect of silencing the large versican isoforms (V0 and V1) and CD44 in the SK-mel-131 human melanoma cell line. Versican V0/V1 or CD44 silencing caused a decrease in cell proliferation and migration, both in wound healing assays and in Transwell chambers. Versican V0/V1 silencing also caused an increased adhesion to type I collagen, laminin and fibronectin. These results support the proposed role of versican as a proliferative, anti-adhesive and pro-migratory molecule. On the other hand, CD44 silencing caused a decrease in cell adhesion to vitronectin, fibronectin and hyaluronan. CD44 silencing inhibited the binding of a FITC-hyaluronan complex to the cell surface and its internalization into the cytoplasm. Our results indicate that both versican and CD44 play an important role regulating the behavior of malignant melanoma cells.

Expression of toll-like receptors by human muscle cells in vitro and in vivo:TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release and up-regulation of NKG2D-ligands

The particular microenvironment of the skeletal muscle can be the site of complex immune reactions. Toll-like receptors (TLRs) mediate inflammatory stimuli from pathogens and endogenous danger signals and link the innate and adaptive immune system. We investigated innate immune responses in human muscle. Analyzing TLR1-9 mRNA in cultured myoblasts and rhabdomyosarcoma cells, we found constitutive expression of TLR3. The TLR3 ligand Poly (I:C), a synthetic analog of dsRNA, and IFN-gamma increased TLR3 levels. TLR3 was mainly localized intracellularly and regulated at the protein level. Poly (I:C) challenge 1) activated nuclear factor-kappaB (NF-kappaB), 2) increased IL-8 release, and 3) up-regulated NKG2D ligands and NK-cell-mediated lysis of muscle cells. We examined muscle biopsy specimens of 6 HIV patients with inclusion body myositis/polymyositis (IBM/PM), 7 cases of sporadic IBM and 9 nonmyopathic controls for TLR3 expression. TLR3 mRNA levels were elevated in biopsy specimens from patients with IBM and HIV-myopathies. Muscle fibers in inflammatory myopathies expressed TLR3 in close proximity of infiltrating mononuclear cells. Taken together, our study suggests an important role of TLR3 in the immunobiology of muscle, and has substantial implications for the understanding of the pathogenesis of inflammatory myopathies or therapeutic interventions like vaccinations or gene transfer.

The Development of TASTER, a Cognitive Training Game Using Human-Centered Design, Tailored for Children with Global and Specific Cognitive Impairments

Children with Prader-Willi syndrome often exhibit challenging behavior in response to changes to routine. This phenomenon has been linked to a deficit in task switching ability which has been observed in children with the syndrome. TASTER is a cognitive training game which is being designed with input from a group of children with Prader- Willi syndrome, which aims to train task switching ability and thus reduce associated challenging behavior.

Human-directed gazing behaviour in puppies and adult dogs, Canis lupus familiaris

Recent evidence indicates that dogs' sociocognitive abilities and behaviour in a test situation are shaped by both genetic factors and life experiences. We used the 'unsolvable task' paradigm to investigate the effect of breed and age/experience on the use of human-directed gazing behaviour. Following a genetic classification based on recent genome analyses, dogs were allocated to three breed groups, namely Primitive, Hunting/Herding and Molossoid. Furthermore, we tested dogs at 2 months, 4.5. months and as adults. The test consisted of three solvable trials in which dogs could obtain food by manipulating a plastic container followed by an unsolvable trial in which obtaining the food became impossible. The dogs' behaviour towards the apparatus and the people present was analysed. At 2 months no breed group differences emerged and although human-directed gazing behaviour was observed in approximately half of the pups, it occurred for brief periods, suggesting that the aptitude to use human-directed gazing as a request for obtaining help probably develops at a later date when dogs have had more experience with human communication. Breed group differences, however, did emerge strongly in adult dogs and, although less pronounced, also in 4.5-month-old subjects, with dogs in the Hunting/Herding group showing significantly more human-directed gazing behaviour than dogs in the other two breed groups. These results suggest that, although the domestication process may have shaped the dog's human-directed communicative abilities, the later selection for specific types of work might also have had a significant impact on their emergence. © 2011 The Association for the Study of Animal Behaviour.

Ethics in sexual behavior assessment and support for people with intellectual disability

Sexuality is an issue of equality, rights, and ethics, especially when it comes to the sexuality of people with intellectual and developmental disabilities. This paper offers a discussion of ethics related to the assessment and intervention supports of sexual behavior in people with intellectual and developmental disabilities. A brief history of sexuality and disability is presented. Issues of sexual abuse of people with intellectual and developmental disabilities and the laws related to sterilization, pornography, sexual rights, and consent are explored. Finally, specific ethical concerns related to intervention by behavior analysts in the realm of sexual behavior are examined.

Evaluation of the human factor in the scheduling of smart appliances in smart grids

Recently there has been an increase of interest in implementing a new set of home appliances, known as Smart Appliances that integrate Information Technologies, the Internet of Things and the ability of communicating with other devices. While Smart Appliances are characterized as an important milestone on the path to the Smart Grid, by being able to automatically schedule their loads according to a tariff or reflecting the power that is generated using renewable sources, there is not a clear understanding on the impact that the behavior of such devices will have in the comfort levels of users, when they shift their working periods to earlier, or later than, a preset time. Given these considerations, in this work we analyse the results of an assessment survey carried out to a group of Home Appliance users regarding their habits when dealing with these machines and the subjective impact in quality caused by either finishing its programs before or after the time limit set by the user. The results of this work are expected to be used as input for the evaluation of load scheduling algorithms running in energy management systems. © 2014 Springer International Publishing.

Wavelet analysis of human DNA

This paper studies the human DNA in the perspective of signal processing. Six wavelets are tested for analyzing the information content of the human DNA. By adopting real Shannon wavelet several fundamental properties of the code are revealed. A quantitative comparison of the chromosomes and visualization through multidimensional and dendograms is developed.

Effects of antihypertensive drugs in the differentiation and activation of human bone cells

O osso é um tecido metabolicamente ativo e a sua remodelação é importante para regular e manter a massa óssea. Esse processo envolve a reabsorção do material ósseo por ação dos osteoclastos e a síntese de novo material ósseo mediado pelos osteoblastos. Vários estudos têm sugerido que a pressão arterial elevada está associada a alterações no metabolismo do cálcio, o que leva ao aumento da perda de cálcio e da remoção de cálcio do osso. Embora as alterações no metabolismo ósseo sejam um efeito adverso associado a alguns fármacos antihipertensores, o conhecimento em relação a este efeito terapêutico ligado com os bloqueadores de canais de cálcio é ainda muito escasso. Uma vez que os possíveis efeitos no osso podem ser atribuídos à ação antihipertensiva dessas moléculas, ou através de um efeito direto nas atividades metabólicas ósseas, torna-se necessário esclarecer este assunto. Devido ao facto de que as alterações no metabolismo ósseo são um efeito adverso associado a alguns fármacos antihipertensores, o objetivo deste trabalho é avaliar o efeito que os bloqueadores dos canais de cálcio exercem sobre as células ósseas humanas, nomeadamente osteoclastos, osteoblastos e co-culturas de ambos os tipos celulares. Verificou-se que os efeitos dos fármacos antihipertensores variaram consoante o fármaco testado e o sistema de cultura usado. Alguns fármacos revelaram a capacidade de estimular a osteoclastogénese e a osteoblastogénese em concentrações baixas. Independentemente da identidade do fármaco, concentrações elevadas revelaram ser prejudiciais para a resposta das células ósseas. Os mecanismos intracelulares através dos quais os efeitos foram exercidos foram igualmente afetados de forma diferencial pelos diferentes fármacos. Em resumo, este trabalho demonstrou que os bloqueadores dos canais de cálcio utilizados possuem a capacidade de afetar direta- e indiretamente a resposta de células ósseas humanas, cultivadas isoladamente ou co-cultivadas. Este tipo de informação é crucial para compreender e prevenir os potenciais efeitos destes fármacos no tecido ósseo, e também para adequar e eventualmente melhorar a terapêutica antihipertensora de cada paciente.

Power Law Behavior and Self-similarity in Modern Industrial Accidents

Advances in technology have produced more and more intricate industrial systems, such as nuclear power plants, chemical centers and petroleum platforms. Such complex plants exhibit multiple interactions among smaller units and human operators, rising potentially disastrous failure, which can propagate across subsystem boundaries. This paper analyzes industrial accident data-series in the perspective of statistical physics and dynamical systems. Global data is collected from the Emergency Events Database (EM-DAT) during the time period from year 1903 up to 2012. The statistical distributions of the number of fatalities caused by industrial accidents reveal Power Law (PL) behavior. We analyze the evolution of the PL parameters over time and observe a remarkable increment in the PL exponent during the last years. PL behavior allows prediction by extrapolation over a wide range of scales. In a complementary line of thought, we compare the data using appropriate indices and use different visualization techniques to correlate and to extract relationships among industrial accident events. This study contributes to better understand the complexity of modern industrial accidents and their ruling principles.

Casualties distribution in human and natural hazards

Catastrophic events, such as wars and terrorist attacks, big tornadoes and hurricanes, huge earthquakes, tsunamis, floods, and landslides, are always accompanied by a large number of casualties. The size distribution of these casualties have separately been shown to follow approximate power law (PL) distributions. In this paper, we analyze the number of victims of catastrophic phenomena, in particular, terrorism, and find double PL behavior. This means that the data set is better approximated by two PLs instead of one. We have plotted the two PL parameters corresponding to all terrorist events occurred in every year, from 1980 to 2010. We observe an interesting pattern in the chart, where the lines, that connect each pair of points defining the double PLs, are roughly aligned to each other.

O impacto da liderança na motivação dos profissionais de hotelaria do Grande Porto: o caso de um hotel 4****

A liderança e a motivação são aspetos essenciais no alcance do sucesso das organizações. Os líderes alcançaram um papel de destaque nas organizações, quer através da tomada de decisões estratégicas, quer na motivação dos colaboradores. Os conceitos e o entendimento da liderança têm vindo a mudar no decurso do tempo. E sugere que, provavelmente, a liderança adquirirá novos significados e será alvo de novas abordagens no futuro. Porque as sociedades, as organizações e as pessoas mudam, é presumível que novas janelas de compreensão venham a ser abertas. Atendendo a que vivemos numa era de globalização, em que a tecnologia, as estratégias e a estrutura das organizações são quase uniformes, a verdadeira vantagem competitiva só poderá surgir das competências dos recursos humanos. Os líderes também alcançaram um papel de destaque nas organizações, quer através da tomada de decisões estratégicas, quer na motivação dos colaboradores, motivação esta que é o motor que potencia capacidade para que os colaboradores sejam persistentes visando alcançar os seus objetivos. Na indústria hoteleira, objeto de estudo da presente investigação, um dos desafios permanentes é proporcionar níveis consistentes de qualidade de serviço. Esse segmento é profundamente afetado pelo comportamento dos seus líderes e das suas características pessoais e especialmente pela maneira como influenciam os seus colaboradores a alcançarem um resultado. Sendo assim, a presente dissertação tem como objetivo geral conhecer, identificar e analisar os estilos e comportamentos de liderança praticados pelos líderes dos vários departamentos de uma unidade hoteleira do Grande Porto. Para isso, recorremos ao estudo de caso, que inclui as metodologias quantitativa e qualitativa, por forma a identificar o(s) estilo(s) de liderança presente(s) no hotel. As conclusões que resultaram da aplicação das entrevistas e do inquérito por questionário mostram que o líder atual da unidade hoteleira em estudo é o líder democrático.

Precious transition metals: the importance of Zn2+, Mn2+ and Cu2+ in the human pathogen Enterococcus faecalis

Dissertation presented to obtain the Ph.D degree in Biology

Visual and verbal processing effects on human memory

In this study in the field of Consumer Behavior, brand name memory of consumers with regard to verbal and visual incongruent and congruent information such as memory structure of brands was tested. Hence, four experimental groups with different constellations of verbal and visual congruity and incongruity were created to compare their brand name memory performance. The experiment was conducted in several classes with 128 students, each group with 32 participants. It was found that brands, which are presented in a congruent or moderately incongruent relation to their brand schema, result in a better brand recall than their incongruent counterparts. A difference between visual congruity and moderately incongruity could not be confirmed. In contrast to visual incongruent information, verbal incongruent information does not result in a worse brand recall performance.

Occurrences of flesh flies (Diptera: Sarcophagidae) on human cadavers in Switzerland, and their importance as forensic indicators.

From 1993 to 2008, criminal investigations were conducted in the western part of Switzerland with special attention to blowfly and flesh fly species in order to estimate the post-mortem interval when requested by the police authorities. Flesh flies were found in only 33 cases out of 160. Five species of the genus Sarcophaga were identified (S. africa, S. argyrostoma, S. caerulescens, S. similis and S. sp.). The main species found on corpses (larval stage) was S. argyrostoma. The thermal constant (K) calculated for this species in Switzerland is 380.6 ± 16.3 (mean ± S.D.) degree-days. With the exception of S. caerulescens, found three times in the larval stage on corpses, the three other species are of minor forensic importance. S. argyrostoma is found during summer and indoors. This species colonises dead bodies, usually the same day as blowfly species, and it could be used to estimate the post-mortem interval. Other species are discussed in the light of current knowledge on their biology and ecology. It is recommended that voucher material be deposited in a museum, allowing further studies by relevant specialists, thereby helping investigators and avoiding misidentifications.

Transfer of ultrasmall iron oxide nanoparticles from human brain-derived endothelial cells to human glioblastoma cells.

Nanoparticles (NPs) are being used or explored for the development of biomedical applications in diagnosis and therapy, including imaging and drug delivery. Therefore, reliable tools are needed to study the behavior of NPs in biological environment, in particular the transport of NPs across biological barriers, including the blood-brain tumor barrier (BBTB), a challenging question. Previous studies have addressed the translocation of NPs of various compositions across cell layers, mostly using only one type of cells. Using a coculture model of the human BBTB, consisting in human cerebral endothelial cells preloaded with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) and unloaded human glioblastoma cells grown on each side of newly developed ultrathin permeable silicon nitride supports as a model of the human BBTB, we demonstrate for the first time the transfer of USPIO NPs from human brain-derived endothelial cells to glioblastoma cells. The reduced thickness of the permeable mechanical support compares better than commercially available polymeric supports to the thickness of the basement membrane of the cerebral vascular system. These results are the first report supporting the possibility that USPIO NPs could be directly transferred from endothelial cells to glioblastoma cells across a BBTB. Thus, the use of such ultrathin porous supports provides a new in vitro approach to study the delivery of nanotherapeutics to brain cancers. Our results also suggest a novel possibility for nanoparticles to deliver therapeutics to the brain using endothelial to neural cells transfer.