Numerous studies have demonstrated population genetic structuring in marine species, yet few have investigated the effect of vertical zonation on gene flow and population structure. Here we use three sympatric, closely related clinid species, Clinus cottoides, C. superciliosus and Muraenoclinus dor- salis, to test whether zonation on South African intertidal rocky sho res affects phylogeographic patterns. We show that the high-shore restricted species has reduced gene flow and considerably higher FST val- ues (FST = 0.9) than the mid- and low-shore species (FST < 0.14). Additionally, we provide evidence for remarkably different demographic and evolutionary histories, ranging from extreme population bottle- necks to population persistence, which are probably linked to effective population size and habitat spe- cialisation. This study further highlights the need for a multispecies approach to unravel the biological and evolutionary processes that drive extant population geneti c patterns in marine species, as even closely related species with similar life histories show highly variable results.
Despite recent advances in radiotherapy, chemotherapy, and surgical techniques, glioblastoma multiforme (GBM) prognosis remains dismal. There is an urgent need for new therapeutic strategies. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intense interest in recent years because they can provide sustained, controlled, and targeted delivery. Here, we investigate the mechanisms involved in the antiproliferative effect of indomethacin-loaded lipid-core nanocapsules (IndOH-LNC) in glioma cells. IndOH-LNC were able to reduce cell viability by inducing apoptotic cell death in C6 and U138-MG glioma cell lines. Interestingly, IndOH-LNC did not affect the viability of primary astrocytes, suggesting that this formulation selectively targeted transformed cells. Mechanistically, IndOH-LNC induced inhibition of cell growth and cell-cycle arrest to be correlated with the inactivation of AKT and β-catenin and the activation of GSK-3β. IndOH-LNC also induced G0/G1 and/or G2/M phase arrest, which was accompanied by a decrease in the levels of cyclin D1, cyclin B1, pRb, and pcdc2 and an increase in the levels of Wee1 CDK inhibitor p21(WAF1). Additionally, IndOH-LNC promoted GBM cell differentiation, observed as upregulation of glial fibrillary acidic protein (GFAP) protein and downregulation of nestin and CD133. Taken together, the crosstalk among antiproliferative effects, cell-cycle arrest, apoptosis, and cell differentiation should be considered when tailoring pharmacological interventions aimed at reducing glioma growth by using formulations with multiples targets, such as IndOH-LNC.
The purpose of this study was to verify the outcome of the emergency one stage resection and anastomosis procedure for patients with obstructed colorectal cancer.
Based on the maximization of entropy, microwave sensors are becoming standard approaches for converting point surface velocity measurements into discharge. Unfortunately, this conversion is conditioned by cross-section regularity and by the need to take the surface measures above the vertical where the maximum velocity occurs. Cross-section irregularities and the presence of floodplains, vegetation and/or local bed depressions can change the theoretical applicability conditions of the proposed methods and, due to the wandering of the current, the microwave sensor must be continuously moved to track the maximum velocity. We describe the theoretical development and practical application of a new approach to operationally convert surface velocity and water level, measured using a fixed installation, into discharge. The resulting equation that links the surface point velocity measurement to the discharge is a function of two parameters describing the velocity distribution within the cross-section plus an additional correction factor which describes the non-homogeneity of the different vertical slices into which the cross-section is divided. Interesting results of the approach are shown for the gauging section of Tavagnasco on the Dora Baltea River in Italy with high performances both in terms of calibration and validation.
O presente artigo objetiva relatar a experiência da implantação do Gerenciamento de Caso em Ambulatório de Psiquiatria, descrevendo competências e práticas das enfermeiras. O modelo passou por diversas alterações até consolidar-se no atual. Cada enfermeira atua visando garantir continuidade e qualidade do tratamento através de estratégias de acolhimento, psicoeducação, elaboração e implementação do processo de enfermagem e do plano terapêutico multiprofissional. A taxa de abandono de tratamento correspondeu a 11%, baixa quando comparada a estudos semelhantes. A experiência permitiu um cuidado coordenado e efetivo, além do aumento da autonomia das enfermeiras, aliado à responsabilização pelo cuidado longitudinal dispensado ao paciente.Descritores: Administração de Caso, Enfermagem Psiquiátrica, Papel do Profissional da Enfermagem.Case management in psychiatric ambulatory care, competences, and nursing practiceThis article aims to describe the experience of the implementation of Case Management in Psychiatric Ambulatory Care, the competences, and nursing practices. The model underwent many changes before assuming its current form. Each nurse works aiming at assuring the continuance and quality of the care through strategies of welcoming, psychoeducation, preparation, and implementation of the nursing process and the multi-professional therapeutic plan. The care abandonment rate corresponded to 11%, which is low when compared to similar students. The experience allowed for a coordinated and effective care, besides increased autonomy of the nurses, related to the responsibility for longitudinal care to the patient.Descriptors: Case Management, Psychiatric Nursing, Role of the Nursing Professional.Gerencia de caso en ambulatorio de psiquiatría, competencias y práctica de la enfermeríaEl presente artículo tiene como objetivo relatar la experiencia de la implantación de la Gerencia de Caso en Ambulatorio de Investigación, describiendo competencias y prácticas de las enfermeras. El modelo pasó por diversas alteraciones hasta consolidarse en el actual. Cada enfermera actúa buscando garantizar la continuidad y la calidad del tratamiento a través de estrategias de acogida, psicoeducación, elaboración e implementación del proceso de enfermería y del plan terapéutico multiprofesional. La tasa de abandono de tratamiento correspondió al 11%, baja cuando comparada a estudios semejantes. La experiencia permitió un cuidado coordinado y efectivo más allá del aumento de la autonomía de las enfermeras, aliado a la responsabilización por el cuidado longitudinal dispensado al paciente.Descriptores: Administración de Caso, Enfermería Psiquiátrica, Papel del Profesional de Enfermería.
This research project is a collaboration between the Sinskey laboratory at MIT and the Worden laboratory at Michigan State University. The goal of the project is to produce Isobutanol (IBT), a branched-chain alcohol that can serve as a drop-in transportation fuel, through the engineered microbial biosynthesis of Carbon Dioxide, Hydrogen, and Oxygen using a novel bioreactor. This final technical report presents the findings of both the biological engineering work at MIT that extended the native branched-chain amino acid pathway of the wild type Ralstonia eutropha H16 to perform this biosynthesis, as well as the unique design, modeling, and construction of a bioreactor for incompatible gasses at Michigan State that enabled the operational testing of the complete system. This 105 page technical report summarizing the three years of research includes 72 figures and 11 tables of findings. Ralstonia eutropha (also known as Cupriavidus necator) is a Gram-negative, facultatively chemolithoautotrophic bacteria. It has been the principle organism used for the study of polyhydroxybutyrate (PHB) polymer biosynthesis. The wild-type Ralstonia eutropha H16 produces PHB as an intracellular carbon storage material while under nutrient stress in the presence of excess carbon. Under this stress, it can accumulate approximately 80 % of its cell dry weight (CDW) as this intracellular polymer. With the restoration of the required nutrients, the cells are then able to catabolize this polymer. If extracted from the cell, this PHB polymer can be processed into biodegradable and biocompatible plastics, however for this research, it is the efficient metabolic pathway channeling the captured carbon that is of interest. R. eutropha is further unique in that it contains two carbon-fixation Calvin–Benson–Bassham cycle operons, two oxygen-tolerant hydrogenases, and several formate dehydrogenases. It has also been much studied for its ability in the presence of oxygen, to fix carbon dioxide into complex cellular molecules using the energy from hydrogen. In this research project, engineered strains of R. eutropha redirected the excess carbon from PHB storage into the production of isobutanol and 3-methyl-1-butanol (branched-chain higher alcohols). These branched-chain higher alcohols can be used directly as substitutes for fossil-based fuels and are seen as alternative biofuels to ethanol and biodiesel. Importantly, these alcohols have approximately 98 % of the energy content of gasoline, 17 % higher than the current gasoline additive ethanol, without impacting corn market production for feed or food. Unlike ethanol, these branched-chain alcohols have low vapor pressure, hygroscopicity, and water solubility, which make them readily compatible with the existing pipelines, gasoline pumps, and engines in our transportation infrastructure. While the use of alternative energies from solar, wind, geothermal, and hydroelectric has spread for stationary power applications, these energy sources cannot be effectively or efficiently employed in current or future transportation systems. With the ongoing concerns of fossil fuel availability and price stability over the long term, alternative biofuels like branched-chain higher alcohols hold promise as a suitable transportation fuel in the future. We showed in our research that various mutant strains of R. eutropha with isobutyraldehyde dehydrogenase activity, in combination with the overexpression of plasmid-borne, native branched-chain amino acid biosynthesis pathway genes and the overexpression of heterologous ketoisovalerate decarboxylase gene, would produce isobutanol and 3-methyl-1-butanol when initiated during nitrogen or phosphorus limitation. Early on, we isolated one mutant R. eutropha strain which produced over 180 mg/L branched-chain alcohols in flask culture while being more tolerant of isobutanol toxicity. After the targeted elimination of genes encoding several potential carbon sinks (ilvE, bkdAB, and aceE), the production titer of the improved to 270 mg/L isobutanol and 40 mg/L 3-methyl-1-butanol. Semicontinuous flask cultivation supplied the cells with sufficient nutrients while minimizing the toxicity caused by isobutanol. Under this cultivation, the R. eutropha mutant grew and produced more than 14 g/L branched-chain alcohols over the duration of 50 days. These results demonstrate that R. eutropha carbon flux can be redirected from PHB to branched-chain alcohols and that engineered R. eutropha can be cultivated over prolonged periods of time for product biosynthesis. While this bioengineering work was being done at the Sinskey laboratory at MIT, the researchers at the Worden laboratory at Michigan State were working on the design and construction of the required specialty bioreactor for incompatible gasses (BIG) that would allow the safe feeding of microbes on Carbon Dioxide, Hydrogen, and Oxygen without explosive results. The early design and assembly work in year 1 incorporated a novel microbubble generator to maximize the bioavailability of gasses within the system comprised of small scale hollow fiber reactors. The early success of the microbubble generator eliminated the need to investigate potentially toxic surfactants within the system. For operational control, the system design incorporated a Opto22-based control network. The researchers also selected the specific hollow fiber material suitable for the bioreactor application. A variety of commercially available hollow fiber membranes were compared with regard to their pore sizes, cell affinity, and potential interference to cell viability assays. The selected membrane with its spongy layer was then tested for diffusivity of O2 and CO2. The instrumented system was then fully assembled for experimentally measuring the heterotrophic growth rate of immobilized R. eutropha cells. The requisite procedures for inoculation, measurement, and cleaning were established enabling the system performance to be validated under controlled laboratory conditions. In year 2, the researchers completed the Opto22 based cross-platform control network, and the system’s communications across the Sartorius fermentation system and Bruker gas chromatograph was established via open platform communications (OPC) protocol. Using the revised system, measurements were taken of the R.eutropha cell growth rate and substrate mass transfer rate in the hollow fiber membrane. Several IBT recovery strategies were explored and resin adsorption was determined to be optimal solution for lab scale operations. The adsorption capacity of the resin column was then measured and IBT desorption using methanol has been demonstrated. With the growing body of experimental data in hand, mathematical models were constructed to demonstrate and map the cellular kinetics, mass transfer of heterotrophic and autotrophic substrates in the hollow fiber, and the adsorption process in the resin column. A structured kinetic model was constructed to describe the competition between cell mass generation and IBT production. The reactor was then scaled up from single fiber to a membrane area of 180 cm2 and then further to 1 ft2. In Year 3 of the research, the IBT mass transfer across the membrane was characterized within the system with experiments to empirically measure the IBT diffusion coefficient in the BIG spongy layer. Using the refined mathematical models, the researchers are now able to explain the experimental observations and predict bioreactor performance under a wide range of experimental conditions. The Big system is able to demonstrate continuous controlled operations with the integrated IBT recovery system. Both heterotrophic and autotrophic production have been shown during continuous operation with heterotrophic and autotrophic stages. Performance of BIG system has been measured during continuous run with alternating heterotrophic growth on fructose and autotrophic product formation on H2, CO2, and O2. Volumetric productivities of IBT at 325 mg/(L day) and of 3M1B at 50 mg/(L day) were achieved, which were comparable to that achieved under heterotrophic conditions. Using the mathematical model, researchers are able to predict system performance for scaled-up BIG system. The apparent diffusion coefficient of IBT in the spongy layer of XM-50 hollow fiber membranes has been measured at various lumen liquid flow rates. The experiment is simulated in COMSOL to validate the results. The constructed COMSOL model is able to simulate BIG system performance in both batch and continuous mode. Mathematical simulations of the system performance have been run to identify the most crucial operational conditions, identifying the rate-limiting factors in autotrophic production of IBT, and quantitating the rate of IBT catabolism. Investigations of the productivity of the production system have suggested and the modeling of the system has revealed a particular sensitivity to the catabolism of the produced IBT by the engineered R. eutropha. Experiments have been designed and executed to quantify the IBT catabolism of R. eutropha, which open up possibilities for further system improvements through future, targeted bioengineering of the strain. Finally, the researchers at Michigan State performed an economic analysis of the system, based on the collective results, and their findings are presented in full within the report