Contribuição das células-tronco mesenquimais para as propriedades tumorigênicas de células de glioblastoma humano

Células-tronco mesenquimais (CTM) apresentam tropismo a tumores, sendo importantes componentes do estroma tumoral. No cérebro, o nicho perivascular é uma importante fonte de CTM, as quais podem contribuir direta e/ou indiretamente para o desenvolvimento de tumores, embora os mecanismos envolvidos sejam pouco conhecidos. No presente trabalho, investigou-se a influência de CTM sobre a proliferação, capacidade invasiva e tumorigenicidade de células de Glioblastoma (GBM) humano. Sabe-se que CTM produzem TGFB1, uma citocina multifuncional envolvida em imunomodulação, proliferação, migração e transição epitelial-mesenquimal de células tumorais. Experimentos in vitro, realizados com meios condicionados de CTM de cordão umbilical humano com silenciamento permanente do gene TGFB1, demonstraram que o TGFB1 secretado por CTM é capaz de aumentar significativamente a proliferação e viabilidade de células de GBM humano da linhagem U87FP635. Esses resultados revelam uma importante ação parácrina dessa citocina regulatória, quando produzida por outros tipos celulares contidos no microambiente tumoral. Entretanto, sob condições experimentais que melhor mimetizam o microambiente tumoral, detectou-se que CTM também afetam o comportamento de células tumorais por um mecanismo alternativo, dependente de contato celular, mas independente dos níveis de TGFB1 secretados pelas CTM. Sob condições de cocultivo celular, envolvendo contato físico entre CTM e células de GBM U87FP635, detectou-se um aumento significativo na quantidade de células tumorais viáveis. Quando cultivadas na forma de esferoides tumorais, o contato com CTM aumentou a capacidade invasiva das células U87FP635. Finalmente, em modelo in vivo ectópico de GBM, células U87FP635 geraram tumores mais desenvolvidos quando coinjetadas com CTM. Esses efeitos pró-tumorigênicos foram observados tanto em contato com CTM controles, quanto com CTM contendo o gene TGFB1 permanentemente silenciado. Assim, esses achados indicam que CTM podem exercer efeitos pró-tumorigênicos por dois mecanismos alternativos e independentes: ação parácrina de TGFB1 secretado por CTM e ação mediada por contato célula-célula. Nas condições experimentais testadas, o mecanismo dependente de contato célula-célula demonstrou ser predominante. O estudo proteômico do secretoma dessas células identificou 126 proteínas diferencialmente expressas além de 10 proteínas exclusivamente detectadas em meios condicionados de cocultivos de CTM com células de GBM U87FP635. Cerca de 80% dessas proteínas exclusivamente secretadas pelo contato célula-célula são componentes de exossomos e estão envolvidas em proliferação celular e desenvolvimento tecidual. Esses resultados apontam uma interação dinâmica de comunicação entre CTM e células tumorais, e revelam algumas proteínas interessantes potencialmente envolvidas em uma ação pró-tumorigênica de CTM mediada por contato celular

Kids Alive! Support for Children of Parents with Cancer: An Exemplar Program for Children of Parents with Cancer

Cancer in a parent or caregiver is an event that affects the whole family. The roles and responsibilities of the diagnosed parent, as well as those of each family member, are affected at the time of diagnosis and throughout the progression of the illness. According to the American Cancer Society, there will be an estimated 1,665,540 new cancer cases diagnosed and 585,720 cancer deaths in 2014. This staggering statistic means there are a number of cancer diagnoses that will directly affect thousands of parents and their children. Past research suggests this upheaval in the system is particularly stressful on children and can lead to a number of responses including anxiety, depression, distress, and other negative reactions. Despite the large number of parents and caregivers diagnosed with cancer in the United States each year, there are relatively few support groups aimed at supporting children affected by parental cancer. Support groups provide opportunities to serve this population in a number of advantageous ways by providing safety, support, and a sense of community. Additionally, support groups allow this population of young people to express their fears and worries, connect to others going through similar circumstances, and explore their parent's diagnosis in a context that is helpful and developmentally appropriate. Past research has found that children who do not receive support during this life-changing event can be negatively affected throughout the life span. On the other hand, this event can be a time to build a child's resilience and provide the structure through which they may thrive in adversity. Support groups offer the opportunity to address this difficult event and lead to positive results. Kids Alive! is one such group that has been proactive in support for children of parents diagnosed with cancer since 1995. Kids Alive!, a support group that runs out of Porter Hospital in Denver Colorado, uses Joseph Campbell's Hero's Journey to structure monthly groups. The Hero's Journey, described in Campbell's The Hero with a Thousand Faces (1949), focuses on a set pattern that all heroes must go through during their journey towards an ultimate victory and self-discovery. Kids Alive! incorporates this journey into a curriculum aimed at helping children explore their thoughts and feelings around their parent's cancer and leads to a realization that they are not alone on this journey. Over the course of eight months, children in Kids Alive! receive support and solidarity that leads to life-changing experiences and an understanding of what a diagnosis of cancer in a parent can mean. Kids Alive! consists of professionals and volunteers who take time to recognize and support this underserved population. The program has led to positive outcomes for nearly two decades and consistently increases the numbers of children and families served. The purpose of this paper is to describe the Kids Alive! program as an exemplar program that addresses these problems by utilizing protective factors research has found in this population. Further, this paper will discuss areas of future research while providing the model of an effective program aimed at serving an important population. Additionally, the model of Kids Alive! will be described through this paper in a way that allows for other oncology settings to consider this relatively simple program that provides consistently positive results.

Quantum Dot-Sensitized Solar Cells Based on Directly Adsorbed Zinc Copper Indium Sulfide Colloids

Heavy metal-based quantum dots (QDs) have demonstrated to behave as efficient sensitizers in QD-sensitized solar cells (QDSSCs), as attested by the countless works and encouraging efficiencies reported so far. However, their intrinsic toxicity has arisen as a major issue for the prospects of commercialization. Here, we examine the potential of environmentally friendly zinc copper indium sulfide (ZCIS) QDs for the fabrication of liquid-junction QDSSCs by means of photoelectrochemical measurements. A straightforward approach to directly adsorb ZCIS QDs on TiO2 from a colloidal dispersion is presented. Incident photon-to-current efficiency (IPCE) spectra of sensitized photoanodes show a marked dependence on the adsorption time, with longer times leading to poorer performances. Cyclic voltammograms point to a blockage of the channels of the mesoporous TiO2 film by the agglomeration of QDs as the main reason for the decrease in efficiency. Photoanodes were also submitted to the ZnS treatment. Its effects on electron recombination with the electrolyte are analyzed through electrochemical impedance spectroscopy and photopotential measurements. The corresponding results bring out the role of the ZnS coating as a barrier layer preventing electron leakage toward the electrolyte, as argued in other QD-sensitized systems. The beneficial effect of the ZnS coating is ultimately reflected on the power conversion efficiency of complete devices, reaching values of 2 %. In a more general vein, through these findings, we aim to call the attention to the potentiality of this quaternary alloy, virtually unexplored as a light harvester for sensitized devices.

Des-re-territorialização e áreas protegidas na Amazônia: reflexões a partir do caso da Estação Ecológica da Terra do Meio-Pa-Brasil

A criação de espaços territoriais especialmente protegidos é uma estratégia utilizada pelo homem desde a antiguidade, objetivando a reserva de áreas com características naturais necessárias à manutenção ou à reprodução cultural de populações humanas específicas, regulando e limitando o acesso e a apropriação de certos recursos e/ou reservando-os para usos ou futuros. Os processos de criação dessas “áreas especialmente protegidas” foram contudo intensificados, no final do século XX, com a percepção da finitude dos recursos naturais, e acelerados pelo florescimento e a consolidação do capitalismo, agora “globalizado”. Quando tais processos, são orientados por interesses diversos de grupos sociais hegemônicos, são comuns não só a desestruturação do modo de vida dos usuários dos recursos naturais tradicionalmente relacionados aos “territórios especiais”, como também a expulsão de grupos não-hegemônicos neles já instalados, sempre que suas práticas culturais sejam consideradas como incompatíveis com os fins e os objetivos da área que se pretende proteger. Entre os tipos de área especialmente protegida estabelecidos pela legislação brasileira, encontram-se as Unidades de Conservação da Natureza (UC). Criadas por Lei com o objetivo de conservar a biodiversidade brasileira, as UC vem sendo palco de diversos conflitos ambientais envolvendo populações tradicionais em todos os biomas brasileiros, mas pode ser mais facilmente evidenciada na Amazônia, aonde a megabiodiversidade a proteger se sobrepõe a territórios ocupados por diversas etnias indígenas e outros povos tradicionais. Os conflitos são intensificados quando a categoria de manejo da UC criada restringe o acesso e altera os modos de apropriação e/ou dos usos tradicionais dos recursos naturais da área por parte dos residentes, inclusive impedindo a continuidade da permanência das populações no interior da UC, no caso o grupo das UC de Proteção Integral. À luz dos debates que vem sendo travados no campo da ecologia política, tais processos conflituosos estariam associados à desterritorialização dos grupos afetados pela criação da UC, nos quais o Estado brasileiro seria o responsável direto. Independentemente das diversas abordagens acadêmicas para o conceito de “território”, entende-se atualmente que a territorialização e a desterritorialização (com consequente reterritorialização) são processos interrelacionados e circularmente conectados, não podendo ser compreendidos separadamente. Assim, o objetivo do presente trabalho é contribuir para a compreensão desses processos de des-re-terrritorialização, avaliando como alguns mecanismos previstos na Lei do Sistema Nacional das Unidades de Conservação para o reassentamento das populações anteriormente residentes vem sendo aplicados, no sentido de promover processos de reterritorialização. As reflexões apresentadas se dão a partir do caso dos ribeirinhos e colonos residentes na Estação Ecológica da Terra do Meio, Pará, Brasil. A partir da avaliação, são propostas alternativas para minimizar a situação de injustiça ambiental na qual se encontram esses atores sociais específicos.

Preventing collapse in Ukraine: The EU should finance the grass roots directly. CEPS Commentary, 10 December 2014

With the aim of averting the total collapse of the Ukrainian economy, Daniel Gros and Steven Blockmans urge the EU to ​offer a minimum of macro-financial assistance to improve governance, fight corruption and harmonise laws with the EU acquis, while beefing up financing channelled directly to the grass roots.

Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis

Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centrioles duplicate once per cell cycle, and duplication is coordinated by Polo-like kinase 4 (Plk4). We previously demonstrated that Plk4 accumulation is autoregulated by its own kinase activity. However, loss of heterozygosity of Plk4 in mouse embryonic fibroblasts has been proposed to cause cytokinesis failure as a primary event, leading to centrosome amplification and gross chromosomal abnormalities. Using targeted gene disruption, we show that human epithelial cells with one inactivated Plk4 allele undergo neither cytokinesis failure nor increase in centrosome amplification. Plk4 is shown to localize exclusively at the centrosome, with none in the spindle midbody. Substantial depletion of Plk4 by small interfering RNA leads to loss of centrioles and subsequent spindle defects that lead to a modest increase in the rate of cytokinesis failure. Therefore, Plk4 is a centriole-localized kinase that does not directly regulate cytokinesis.

Manipulation of the Quorum Sensing Signal AI-2 Affects the Antibiotic-Treated Gut Microbiota

The mammalian gut microbiota harbors a diverse ecosystem where hundreds of bacterial species interact with each other and their host. Given that bacteria use signals to communicate and regulate group behaviors (quorum sensing), we asked whether such communication between different commensal species can influence the interactions occurring in this environment. We engineered the enteric bacterium, Escherichia coli, to manipulate the levels of the interspecies quorum sensing signal, autoinducer-2 (AI-2), in the mouse intestine and investigated the effect upon antibiotic-induced gut microbiota dysbiosis. E. coli that increased intestinal AI-2 levels altered the composition of the antibiotic-treated gut microbiota, favoring the expansion of the Firmicutes phylum. This significantly increased the Firmicutes/Bacteroidetes ratio, to oppose the strong effect of the antibiotic, which had almost cleared the Firmicutes. This demonstrates that AI-2 levels influence the abundance of the major phyla of the gut microbiota, the balance of which is known to influence human health.

Maternal separation followed by isolation-housing differentially affects prepulse inhibition of the acoustic startle response in C57BL/6 mice

Exposure to chronic stress is associated with an increased incidence of neuropsychiatric dysfunction. The current study evaluated two competing hypotheses, the cumulative stress and the match/mismatch hypothesis of neuropsychiatric dysfunction, using two paradigms relating to exposure to “stress”: pre-weaning maternal separation and post-weaning isolation-housing. C57BL/6 offspring were reared under four conditions: typical animal facility rearing (AFR, control), early handling (EH, daily 15 min separation from dam), maternal separation (MS, daily 4 hr separation from dam), and maternal and peer separation (MPS, daily 4 hr separation from dam and from littermates). After weaning, mice were either housed socially (2–3/cage) or in isolation (1/cage) and then tested for prepulse inhibition in adulthood. Isolation-housed MPS subjects displayed greater deficits in prepulse inhibition relative to socially-housed MPS subjects while socially-housed AFR subjects displayed greater deficits in prepulse inhibition relative to isolation-housed AFR subjects. The results indicate that these treatment conditions represent a potentially valuable model for evaluating the match/mismatch hypothesis in regards to neuropsychiatric dysfunction.

Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects.