Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression

Angiogenesis involves the formation of new blood vessels by sprouting or splitting of existing blood vessels. During sprouting, a highly motile type of endothelial cell, called the tip cell, migrates from the blood vessels followed by stalk cells, an endothelial cell type that forms the body of the sprout. To get more insight into how tip cells contribute to angiogenesis, we extended an existing computational model of vascular network formation based on the cellular Potts model with tip and stalk differentiation, without making a priori assumptions about the differences between tip cells and stalk cells. To predict potential differences, we looked for parameter values that make tip cells (a) move to the sprout tip, and (b) change the morphology of the angiogenic networks. The screening predicted that if tip cells respond less effectively to an endothelial chemoattractant than stalk cells, they move to the tips of the sprouts, which impacts the morphology of the networks. A comparison of this model prediction with genes expressed differentially in tip and stalk cells revealed that the endothelial chemoattractant Apelin and its receptor APJ may match the model prediction. To test the model prediction we inhibited Apelin signaling in our model and in an \emph{in vitro} model of angiogenic sprouting, and found that in both cases inhibition of Apelin or of its receptor APJ reduces sprouting. Based on the prediction of the computational model, we propose that the differential expression of Apelin and APJ yields a "self-generated" gradient mechanisms that accelerates the extension of the sprout.Comment: 48 pages, 10 figures, 8 supplementary figures. Accepted for publication in PLoS ON

Som en sköld runt hjärtat - Unga vuxnas erfarenheter av att medicinera mot depression

Syftet med denna kvalitativa studie var att genom halvstrukturerade intervjuer undersöka unga vuxnas erfarenheter av att medicinera mot depression, samt hur de förstår sitt tillstånd som deprimerade. Elva informanter mellan 20 och 30 år, som diagnostiserats med depression och använt SSRI eller SNRI, intervjuades, och materialet analyserades med hjälp av tematisk analys. Resultatet visade att informanterna använder flera olika förklaringsmodeller till depression, vilket skapade osäkerhet och en något fragmentarisk självframställning. En neurokemisk och genetisk syn fanns närvarande, liksom en KBT-diskurs, med stort fokus på beteenden, självarbete, ansvar och kontroll. Vidare fanns även samhällskrav som orsak till depression med, och en genusaspekt i synen på depressionens orsaker och uttryck. Det senare rörde främst dubbla roller, oro över utseende och självdestruktivitet som specifikt kvinnliga erfarenheter. Informanterna var något ambivalenta till antidepressiv medicinering, även om de flesta upplevt sig hjälpta av den, och föredrog generellt psykoterapi som behandlingsmetod. Att medicinera innebar ökad aktivitet och bättre vardagligt fungerande för informanterna. Samtidigt beskrevs en negativ upplevelse av känslomässig avtrubbning av flertalet. Informanterna tillskrev depressionen en mening, främst då den inneburit en ökad insikt i sig själv och andra.The purpose of this qualitative study was to explore how young adults experience depression and antidepressant medication, and how they understand their condition. Using semi-structured interviews, eleven interviewees between the ages of 20 and 30, who had been diagnosed with depression and had medicated with SSRI or SNRI, were interviewed, and the results were analyzed using thematic analysis. The result showed that the interviewees use different models to explain depression, which created uncertainty and a somewhat fragmented self representation. A neurochemical and genetic view was present, as well as a CBT-discourse, with a strong emphasis on behavior, self-work, responsibility and control. An explanation based on societal demands was also present, and a gender perspective on the causes and expressions of depression. The latter involved double roles, appearance anxiety and self destructive behavior as typically female experiences. The informants were to some extent ambivalent towards antidepressant medication, although most of them felt they had been helped by it, and generally preferred psychotherapy as a treatment method. The main effects of the medication was a rise in activity level and a better everyday functioning. At the same time, an emotional blunting was experienced by the majority. The interviewees ascribed a meaning to depression, in that it gave them increased insight in the self and in others

From spawner habitat selection to stock-recruitment: Implications for assessment

The relationship between the spawning stock size and subsequent number of recruits is a central concept in fisheries ecology. The influence of habitat selection of spawning individuals on the stock-recruitment relationship is poorly known. Here we explore how each of four different spawner behaviors might influence the stock-recruitment relationship and estimates of its parameters in the two most commonly used stock-recruitment functions (Beverton-Holt and Ricker). Using simulated stock-recruitment data generated by four different spawner behaviors applied to multiple discrete habitats, we show that when spawners were distributed proportionally to local carrying capacities, there was small or no bias in estimated recruitment and stock-recruitment parameters. For an ideal free distribution of spawners, larger bias in the estimates of recruitment and stock-recruitment parameters was obtained, whereas a random and a stepwise spawner behavior introduced the largest bias. Using stock-recruitment data corresponding to a "realistic " range of population densities and adding measurement error (20%-60%) to the simulated stock-recruitment data generated larger variation in the estimation bias than what was introduced by the spawner behavior. Thus, for exploited stocks at low population density and where spawning stock size and recruitment cannot be observed perfectly, partial observation of the possible spawner abundance range and measurement error might be of higher concern for management

Continuous vs. pulsating flow boiling. Part 1: Experimental comparison and visualization

High heat exchanger performance is crucial to meet efficiency standards with low cost and environmental impact. Heat transfer performance may be improved by passive and active enhancement techniques applicable to air, liquid and phase change heat exchangers. This experimental study investigates an active method for flow boiling heat transfer enhancement by means of fluid flow pulsation. The pulsations are believed to increase the flow boiling heat transfer by means of better bulk fluid mixing, wall wetting and flow-regime destabilization. The pulsations are introduced by a flow modulating expansion device and compared with continuous flow from a stepper-motor expansion valve. The cycle time range from 1 to 9 seconds for the pulsations. Transient heat transfer coefficients are measured downstream from the expansion valve at low vapor qualities and the time-averaged heat transfer coefficients are compared to those with continuous fluid flow. The results show that the pulsations improve the time-averaged heat transfer coefficient by up to 5 % at low cycle time, whereas the pulsations reduce the time-averaged heat transfer coefficient by up to 8 % at high cycle time and heat flux. The latter reduction is adhered to significant dry-out when the expansion valve is closed. The test section consists of the two exchangeable expansion valves and a tube-in-tube evaporator with four subsections for measuring the heat transfer coefficient. Refrigerant R134a flows internally and water flows externally. The inner tube internal diameter is 8 mm and each subsection is 0.25 m long. Temperatures in and out of each subsection are measured as well as the water flow rate. Wall temperatures are measured outside on the internal tube in the top and the bottom of each subsection as well as refrigerant temperature, pressure and flow rate. The evaporation temperature is kept at 5°C during the experiments and the fluid state before the expansion valve is kept at a condensing temperature and subcooling of 32.5°C and 2 K, respectively. The time-averaged refrigerant mass flux varies from 41 to 167 kg/m2s, vapor qualities from 0.18 to 0.59 and heat fluxes from 0.8 to 45 kW/m2. The paper includes a description of the test rig, the data reduction method, uncertainty propagation and the results and comparison.

Continuous vs. pulsating flow boiling. Part 1: Experimental comparison and visualization

High heat exchanger performance is crucial to meet efficiency standards with low cost and environmental impact. Heat transfer performance may be improved by passive and active enhancement techniques applicable to air, liquid and phase change heat exchangers. This experimental study investigates an active method for flow boiling heat transfer enhancement by means of fluid flow pulsation. The pulsations are believed to increase the flow boiling heat transfer by means of better bulk fluid mixing, wall wetting and flow-regime destabilization. The pulsations are introduced by a flow modulating expansion device and compared with continuous flow from a stepper-motor expansion valve. The cycle time range from 1 to 9 seconds for the pulsations. Transient heat transfer coefficients are measured downstream from the expansion valve at low vapor qualities and the time-averaged heat transfer coefficients are compared to those with continuous fluid flow. The results show that the pulsations improve the time-averaged heat transfer coefficient by up to 5 % at low cycle time, whereas the pulsations reduce the time-averaged heat transfer coefficient by up to 8 % at high cycle time and heat flux. The latter reduction is adhered to significant dry-out when the expansion valve is closed. The test section consists of the two exchangeable expansion valves and a tube-in-tube evaporator with four subsections for measuring the heat transfer coefficient. Refrigerant R134a flows internally and water flows externally. The inner tube internal diameter is 8 mm and each subsection is 0.25 m long. Temperatures in and out of each subsection are measured as well as the water flow rate. Wall temperatures are measured outside on the internal tube in the top and the bottom of each subsection as well as refrigerant temperature, pressure and flow rate. The evaporation temperature is kept at 5°C during the experiments and the fluid state before the expansion valve is kept at a condensing temperature and subcooling of 32.5°C and 2 K, respectively. The time-averaged refrigerant mass flux varies from 41 to 167 kg/m2s, vapor qualities from 0.18 to 0.59 and heat fluxes from 0.8 to 45 kW/m2. The paper includes a description of the test rig, the data reduction method, uncertainty propagation and the results and comparison.

Continuous vs. pulsating flow boiling. Part 2: Statistical comparison using response surface methodology

Design of experiments is a method for experimentation that enables the possibility to estimate effects and responses of certain factors and their interactions with statistical significance and low experimental effort. This approach includes several phases from sorting out the trivial from the vital factors, characterizing main effects, interactions, detecting non-linearity and establishing functional relationships (response surfaces) for optimizing factors and comparing categorical responses etc.. The goal of the current paper is to compare the competitive categorical heat transfer responses obtained in part 1 of the paper, using continuous and pulsating two-phase flow boiling. For in-tube continuous flow boiling in traditional tubing, the governing vital factors have been known for decades (mass flux, heat flux, vapor quality, temperature, diameter and fluid), however, for pulsating flow boiling the injection frequency (or cycle time) must be characterized too. The response surfaces are compared and tested for statistical significance in order to verify an improvement or a reduction in the time-averaged flow boiling heat transfer coefficient statistically when introducing flow pulsations. The test section consists of the two exchangeable expansion valves and a tube-in-tube evaporator with four subsections for measuring the heat transfer coefficient. Refrigerant R134a flows internally and water flows externally. The inner tube internal diameter is 8 mm and each subsection is 0.25 m long. Temperatures in and out of each subsection are measured as well as the water flow rate. Wall temperatures are measured outside on the internal tube in the top and the bottom of each subsection as well as refrigerant temperature, pressure and flow rate. The evaporation temperature is kept at 5°C during the experiments and the fluid state before the expansion valve is kept at a condensing temperature and subcooling of 32.5°C and 2 K, respectively. The time-averaged refrigerant mass flux varies from 41 to 167 kg/m2s, vapor qualities from 0.18-0.59 and heat fluxes from 0.8-45 kW/m2. The paper builds upon part 1 of the paper and includes a description of the response surface methodology, its usage and results including main effects, interactions, and response surface comparison. The main object is to compare the response surfaces for continuous and pulsation flow boiling and conclude whether pulsations may increase or decrease heat transfer with statistical significance

MANF is Required for the Postnatal Expansion and Maintenance of the Pancreatic β-Cell Mass in Mice

Global lack of mesencephalic astrocyte-derived neurotropic factor (MANF) leads to progressive postnatal loss of β-cells mass and insulin-dependent diabetes in mice. Similarly to Manf -/- mice, embryonic ablation of MANF specifically from the pancreas results in diabetes. In this study, we assessed the importance of MANF for the postnatal expansion of the pancreatic β-cell mass and for adult β-cell maintenance in mice. Detailed analysis of Pdx-1Cre +/- ::Manf fl/fl mice revealed mosaic MANF expression in postnatal pancreases and significant correlation between the number of MANF-positive β-cells and β-cell mass in individual mice. In vitro, recombinant MANF induced β-cell proliferation in islets from aged mice and protected from hyperglycemia-induced endoplasmic reticulum (ER) stress. Consequently, excision of MANF from β-cells of adult MIP-1Cre ERT ::Manf fl/fl mice resulted in reduced β-cell mass and diabetes caused largely by β-cell ER stress and apoptosis, possibly accompanied by β-cell de-differentiation and reduced rates of β-cell proliferation. Thus, MANF expression in adult mouse β-cells is needed for their maintenance in vivo. We also revealed a mechanistic link between ER stress, and inflammatory signaling pathways leading to β-cell death in the absence of MANF. Hence, MANF might be a potential target for regenerative therapy in diabetes.Peer reviewe

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Is Highly Expressed in Mouse Tissues With Metabolic Function

Peer reviewe