4,079 research outputs found

    A synthetic Escherichia coli predator–prey ecosystem

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    We have constructed a synthetic ecosystem consisting of two Escherichia coli populations, which communicate bi-directionally through quorum sensing and regulate each other's gene expression and survival via engineered gene circuits. Our synthetic ecosystem resembles canonical predator–prey systems in terms of logic and dynamics. The predator cells kill the prey by inducing expression of a killer protein in the prey, while the prey rescue the predators by eliciting expression of an antidote protein in the predator. Extinction, coexistence and oscillatory dynamics of the predator and prey populations are possible depending on the operating conditions as experimentally validated by long-term culturing of the system in microchemostats. A simple mathematical model is developed to capture these system dynamics. Coherent interplay between experiments and mathematical analysis enables exploration of the dynamics of interacting populations in a predictable manner

    Tolerance to the Prophylactic Effects of Carbamazepine and Related Mood Stabilizers in the Treatment of Bipolar Disorders

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    Tolerance development after successful long-term treatment of bipolar disorder is under recognized, as are ways to prevent or show its occurrence or reverse it once it has occurred. We review the clinical literature which suggests that tolerance can develop to most treatment approaches in bipolar illness and present an animal model of tolerance development to anticonvulsant effects of carbamazepine or lamotrigine on amgydala-kindled seizures. In this model tolerance does not have a pharmacokinetic basis, but is contingent upon the drug being present in the brain at the time of amygdala stimulation. The occurrence of seizures in the absence of drug is sufficient to reverse tolerance and re-establish anticonvulsant efficacy. Based on the model, we hypothesize that some episode-induced compensatory adaptive changes in gene expression fail to occur in tolerant subjects and that episodes off medication re-induce these changes and renew drug effectiveness. Approaches that slow or reverse tolerance development in the animal model are reviewed so that they can be tested for their applicability in the clinic. Criteria for assessing tolerance development are offered in the hope that this will facilitate a more systemic literature about its prevalence, prevention, and reversal. Careful longitudinal monitoring of episode occurrence is essential to understanding tolerance development in the affective disorder and its treatment

    Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles

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    Short dwell-time and poor penetration of the bladder permeability barrier (BPB) are the main obstacles to intravesical treatments for bladder diseases, and is evidenced by the lack of such therapeutic options on the market. Herein, we demonstrate that by finely tuning the molecular weight of our cationic polymer mucoadhesive nanoparticles, we enhanced our gene transfer, leading to improved adherence and penetrance through the BPB in a safe and efficient manner. Specifically, increasing the polymer molecular weight from 45 kDa to 83 kDa enhanced luciferase plasmid transfer to the healthy murine bladder, leading to 1.35 ng/g luciferase protein expression in the urothelium and lamina propria regions. The relatively higher molecular weight polymer (83 kDa) did not induce morphologic changes or inflammatory responses in the bladder. This approach of altering polymer molecular weight for prolonging gene transfer residence time and deeper penetration through the BPB could be the basis for the design of future gene therapies for bladder diseases

    Down-regulation of GP130 signaling sensitizes bladder cancer to cisplatin by impairing Ku70 DNA repair signaling and promoting apoptosis

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    Chemoresistance is one of the barriers for the development of bladder cancer treatments. Previously, we showed that glycoprotein-130 (GP130) is overexpressed in chemoresistant bladder cancer cells and that knocking down GP130 expression reduced cell viability. In our current work, we showed that down-regulation of GP130 sensitized bladder cancer cells to cisplatin-based chemotherapy by activating DNA repair signaling. We performed immunohistochemistry and demonstrated a positive correlation between the levels of Ku70, an initiator of canonical non-homologous end joining repair (c-NHEJ) and suppressor of apoptosis, and GP130 in human bladder cancer specimens. GP130 knockdown by SC144, a small molecule inhibitor, in combination with cisplatin, increased the number of DNA lesions, specifically DNA double-stranded breaks, with a subsequent increase in apoptosis and reduced cell viability. Furthermore, GP130 inhibition attenuated Ku70 expression in bladder and breast cancer cells as well as in transformed kidney cells. In addition, we fabricated a novel polymer-lipid hybrid delivery system to facilitate GP130 siRNA delivery that had a similar efficiency when compared with Lipofectamine, but induced less toxicity

    Using a model of group psychotherapy to support social research on sensitive topics

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    This article describes the exploratory use of professional therapeutic support by social researchers working on a sensitive topic. Talking to recently bereaved parents about the financial implications of their child's death was expected to be demanding work, and the research design included access to an independent psychotherapeutic service. Using this kind of professional support is rare within the general social research community, and it is useful to reflect on the process. There are likely to be implications for collection and interpretation of data, research output and the role and experience of the therapist. Here, the primary focus is the potential impact on researcher well-being

    Entrepreneurial capital, social values and Islamic traditions: exploring the growth of women-owned enterprises in Pakistan

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    Main ArticleThis study seeks to explore the variables contributing to the growth of women-owned enterprises in the Islamic Republic of Pakistan. Based on a previously established multivariate model, it uses two econometric approaches: first classifying variables into predetermined blocks; and second, using the general to specific approach. Statistical analyses and in-depth interviews confirm that women entrepreneurs’ personal resources and social capital have a significant role in their business growth. Further, it reveals that the moral support of immediate family, independent mobility and being allowed to meet with men play a decisive role in the sales and employment growth of women-owned enterprises in an Islamic country such as Pakistan

    The incidence of psychoses in diverse settings, INTREPID (2): a feasibility study in India, Nigeria, and Trinidad.

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    BACKGROUND: There are striking global inequities in our knowledge of the incidence, aetiology, and outcome of psychotic disorders. For example, only around 10% of research on incidence of psychotic disorders originates in low- and middle-income countries. We established INTREPID I to develop, implement, and evaluate, in sites in India (Chengalpet), Nigeria (Ibadan), and Trinidad (Tunapuna-Piarco), methods for identifying and recruiting untreated cases of psychosis, as a basis for investigating incidence and, subsequently, risk factors, phenomenology, and outcome. In this paper, we compare case characteristics and incidence rates across the sites. METHOD: In each site, to identify untreated cases of psychoses in defined catchment areas, we established case detection systems comprising mental health services, traditional and spiritual healers, and key informants. RESULTS: Rates of all untreated psychoses were 45.9 (per 1 00 000 person-years) in Chengalpet, 31.2 in Ibadan, and 36.9 in Tunapuna-Piarco. Duration of psychosis prior to detection was substantially longer in Chengalpet (median 232 weeks) than in Ibadan (median 13 weeks) and Tunapuna-Piarco (median 38 weeks). When analyses were restricted to cases with a short duration (i.e. onset within preceding 2 years) only, rates were 15.5 in Chengalpet, 29.1 in Ibadan, and 26.5 in Tunapuna-Piarco. Further, there was evidence of age and sex differences across sites, with an older average age of onset in Chengalpet and higher rates among women in Ibadan. CONCLUSION: Our findings suggest there may be differences in rates of psychoses and in the clinical and demographic profiles of cases across economically and socially distinct settings

    Envolvimento de "stakeholders" em direcção à construção sustentåvel

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    A mudança de paradigma requerida para evoluir na direcção da construção sustentåvel exige a conjugação efectiva de diferentes condiçÔes determinantes, que inclui a percepção, comportamento e envolvimento de partes em todo o processo, em particular os actores que efectam, bem como aqueles que são afectados pela tomada de decisão. Para além das formas convencionais de envolvimento dos stokholders, novas formas de cooperação precisam de ser exploradas. O presente artigo tem por obectivo reflectir sobre a melhor estratégia de gestão a aplicar nos actores-chave num contexto de networking sobre construção sustentåvel em Portugal. A anålise efectuada permitiu verificar que o sucesso de uma plataforma de cooperação estå condicionada pela participação dos actores-chave, pelo que hå necessidade de fazer o mapeamento, a hierarquização e a definição de uma estratégia de gestão que maximize asua cooperação, isto é, que vå ao encontro das necessidades de cada um deles, para que a plataforma de cooperação se torne um efectivo espaço de partilha, diålogo, aprendizagem e inovação

    Scoliosis in patients with Prader Willi Syndrome – comparisons of conservative and surgical treatment

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    In children with Prader Willi syndrome (PWS), besides growth hormone (GH) therapy, control of the food environment and regular exercise, surgical treatment of scoliosis deformities seems the treatment of choice, even though the risks of spinal surgery in this specific population is very high. Therefore the question arises as to whether the risks of spinal surgery outweigh the benefits in a condition, which bears significant risks per se. The purpose of this systematic review of the Pub Med literature was to find mid or long-term results of spinal fusion surgery in patients with PWS, and to present the conservative treatment in a case study of nine patients with this condition
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