Evidence for limited adaptive responsiveness to large-scale spatial variation of habitat quality

The ability of organisms to adapt their foraging behaviour to spatial variations in food availability and habitat quality is crucial to maximize energy intake and hence fitness. Under ideal conditions, habitat selection should result in a spatial distribution of individuals such that their fitness (energy reserves or condition) is roughly equal across habitats of varying quality. Using 11 yr of field data on Atlantic cod Gadus morhua distribution along the Greenland shelf, we investigated the foraging behaviour and life history of cod in heterogeneous environments. We combined information on energy reserves of cod with spatially resolved diet composition data to derive a measure of habitat quality and heterogeneity. Energy reserves in individual fish were best explained by the particular area they inhabited, whereas growth, population density, food quantity and interannual effects were of minor importance. Condition differed on relatively small spatial scales, at which cod would be capable of redistributing in favour of high-quality habitats. Our results indicate that particular areas may persistently allow higher fitness by sustaining high-conditioned individuals but suggest that replenishment of well-conditioned individuals in these high-quality habitats may take longer than expected. We conclude that cod exhibited limited scope in its behavioural response to spatial variation of habitat quality, leading to persistent spatio-temporal differences in energy reserves. Current climate change and fishing activities alter ecosystems and affect habitat heterogeneity, and the adaptive responsiveness of species to such changes in habitat quality is important in natural resource management

Perfusable Tissue Bioprinted into a 3D-Printed Tailored Bioreactor System

Bioprinting provides a powerful tool for regenerative medicine, as it allows tissue construction with a patient’s specific geometry. However, tissue culture and maturation, commonly supported by dynamic bioreactors, are needed. We designed a workflow that creates an implant-specific bioreactor system, which is easily producible and customizable and supports cell cultivation and tissue maturation. First, a bioreactor was designed and different tissue geometries were simulated regarding shear stress and nutrient distribution to match cell culture requirements. These tissues were then directly bioprinted into the 3D-printed bioreactor. To prove the ability of cell maintenance, C2C12 cells in two bioinks were printed into the system and successfully cultured for two weeks. Next, human mesenchymal stem cells (hMSCs) were successfully differentiated toward an adipocyte lineage. As the last step of the presented strategy, we developed a prototype of an automated mobile docking station for the bioreactor. Overall, we present an open-source bioreactor system that is adaptable to a wound-specific geometry and allows cell culture and differentiation. This interdisciplinary roadmap is intended to close the gap between the lab and clinic and to integrate novel 3D-printing technologies for regenerative medicine

3D printing of bioreactors in tissue engineering: A generalised approach

3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process

Prognostic Impact of the Get-with-the-Guidelines Heart-Failure Risk Score (GWTG-HF) after Transcatheter Aortic Valve Replacement in Patients with Low-Flow–Low-Gradient Aortic Valve Stenosis

Objectives: This study examined the prognostic value of the get-with-the-guidelines heart-failure risk score (GWTG-HF) on mortality in patients with low-flow–low-gradient aortic valve stenosis (LFLG-AS) after transcatheter aortic valve implantation (TAVI). Background: Data on feasibility of TAVI and mortality prediction in the LFLG-AS population are scarce. Clinical risk assessment in this particular population is difficult, and a score has not yet been established for this purpose. Methods: A total of 212 heart failure (HF) patients with real LFLG-AS were enrolled. Patients were classified into low-risk (n = 108), intermediate-risk (n = 90) and high-risk (n = 14) groups calculated by the GWTG-HF score. Clinical outcomes of cardiovascular events according to Valve Academic Research Consortium (VARC-2) recommendations and composite endpoint of death and hospitalization for heart failure (HHF) were assessed at discharge and 1 year of follow-up. Results: Baseline parameters of the groups showed a median age of 81.0 years [77.0; 84.0] (79.0 vs. 82.0 vs. 86.0, respectively p p = 0.004) and median indexed stroke volume of 26.7 mL/m2 [22.0; 31.0] (28.2 vs. 25.8 vs. 25.0, p = 0.004). The groups significantly differed at follow-up in terms of all-cause mortality (10.2 vs. 21.1 vs. 28.6%; p p = 0.011). No differences in postprocedural aortic valve area (1.9 vs. 1.7 vs. 1.9 cm2, p = 0.518) or rate of device failure (5.6 vs. 6.8 vs. 7.7%, p = 0.731) could be observed. After adjustment for known predictors, the GWTG score (HR 1.07 [1.01–1.14], p = 0.030) as well as pacemaker implantation (HR 3.97 [1.34–11.75], p = 0.013) turned out to be possible predictors for mortality. An increase in stroke volume index (SVI) was, in contrast, protective (HR 0.90 [0.83–0.97]; p = 0.006). Conclusions: The GWTG score may predict mortality after TAVI in LFLG-AS HF patients. Interestingly, all groups showed similar intrahospital event and mortality rates, independent of calculated mortality risk. Low SVI and new conduction disturbances associated with PPI after THV implantation had negative impact on mid-term outcome in post-TAVI HF-patients

Validation of Blood Volume Fraction Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Porcine Skeletal Muscle

<div><p>The purpose of this study was to assess the accuracy of fractional blood volume (<i>v</i>_<i>b</i>) estimates in low-perfused and low-vascularized tissue using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The results of different MRI methods were compared with histology to evaluate the accuracy of these methods under clinical conditions. <i>v</i>_<i>b</i> was estimated by DCE-MRI using a 3D gradient echo sequence with k-space undersampling in five muscle groups in the hind leg of 9 female pigs. Two gadolinium-based contrast agents (CA) were used: a rapidly extravasating, extracellular, gadolinium-based, low-molecular-weight contrast agent (LMCA, gadoterate meglumine) and an extracellular, gadolinium-based, albumin-binding, slowly extravasating blood pool contrast agent (BPCA, gadofosveset trisodium). LMCA data were evaluated using the extended Tofts model (ETM) and the two-compartment exchange model (2CXM). The images acquired with administration of the BPCA were used to evaluate the accuracy of <i>v</i>_<i>b</i> estimation with a bolus deconvolution technique (BD) and a method we call equilibrium MRI (EqMRI). The latter calculates the ratio of the magnitude of the relaxation rate change in the tissue curve at an approximate equilibrium state to the height of the same area of the arterial input function (AIF). Immunohistochemical staining with isolectin was used to label endothelium. A light microscope was used to estimate the fractional vascular area by relating the vascular region to the total tissue region (immunohistochemical vessel staining, IHVS). In addition, the percentage fraction of vascular volume was determined by multiplying the microvascular density (MVD) with the average estimated capillary lumen, , where <i>d</i> = 8<i>μ</i>m is the assumed capillary diameter (microvascular density estimation, MVDE). Except for ETM values, highly significant correlations were found between most of the MRI methods investigated. In the cranial thigh, for example, the <i>v</i>_<i>b</i> medians (interquartile range, IQRs) of IHVS, MVDE, BD, EqMRI, 2CXM and ETM were <i>v</i>_<i>b</i> = 0.7(0.3)%, 1.1(0.4)%, 1.1(0.4)%, 1.4(0.3)%, 1.2(1.8)% and 0.1(0.2)%, respectively. Variances, expressed by the difference between third and first quartiles (IQR) were highest for the 2CXM for all muscle groups. High correlations between the values in four muscle groups—medial, cranial, lateral thigh and lower leg - estimated with MRI and histology were found between BD and EqMRI, MVDE and 2CXM and IHVS and ETM. Except for the ETM, no significant differences between the <i>v</i>_<i>b</i> medians of all MRI methods were revealed with the Wilcoxon rank sum test. The same holds for all muscle regions using the 2CXM and MVDE. Except for cranial thigh muscle, no significant difference was found between EqMRI and MVDE. And except for the cranial thigh and the lower leg muscle, there was also no significant difference between the <i>v</i>_<i>b</i> medians of BD and MVDE. Overall, there was good <i>v</i>_<i>b</i> agreement between histology and the BPCA MRI methods and the 2CXM LMCA approach with the exception of the ETM method. Although LMCA models have the advantage of providing excellent curve fits and can in principle determine more physiological parameters than BPCA methods, they yield more inaccurate results.</p></div

Box plots of the model parameter <i>v</i>_<i>b</i> obtained with the different models and methods in the different skeletal muscle regions of the pigs’ hind legs.

<p>Box plots of the model parameter <i>v</i>_<i>b</i> obtained with the different models and methods in the different skeletal muscle regions of the pigs’ hind legs.</p

Mass spectrometric metabolic fingerprinting of 2-Deoxy-D-Glucose (2-DG)-induced inhibition of glycolysis and comparative analysis of methionine restriction versus glucose restriction under perfusion culture in the murine L929 model system

All forms of restriction, from caloric to amino acid to glucose restriction, have been established in recent years as therapeutic options for various diseases, including cancer. However, usually there is no direct comparison between the different restriction forms. Additionally, many cell culture experiments take place under static conditions. In this work, we used a closed perfusion culture in murine L929 cells over a period of 7 days to compare methionine restriction (MetR) and glucose restriction (LowCarb) in the same system and analysed the metabolome by liquid chromatography mass spectrometry (LC-MS). In addition, we analysed the inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) over a period of 72 h. 2-DG induced very fast a low-energy situation by a reduced glycolysis metabolite flow rate resulting in pyruvate, lactate, and ATP depletion. Under perfusion culture, both MetR and LowCarb were established on the metabolic level. Interestingly, over the period of 7 days, the metabolome of MetR and LowCarb showed more similarities than differences. This leads to the conclusion that the conditioned medium, in addition to the different restriction forms, substantially reprogramm the cells on the metabolic level

Spearman correlation coefficients of the individual results of the four MRI methods for the muscle groups in the hind legs of the pigs and Wicoxon rank sum test results between the different MRI methods and between MRI and histology.

<p>Spearman correlation coefficients of the individual results of the four MRI methods for the muscle groups in the hind legs of the pigs and Wicoxon rank sum test results between the different MRI methods and between MRI and histology.</p

Light microscopy image of a histological preparation from the medial thigh muscle with vascular endothelium stained brown by isolectin.

<p>The selection was performed by semiautomatic analysis of the images with the microscope’s morphometry software to determine the area, number and diameter of the vessels. The outer borders of the segmented vessels are labeled in green.</p

For the EqMRI method, the same BPCA relaxation rate changes as in Fig 3 are shown as black circles.

<p>No correction with respect to the arterial hematocrit level was performed at this point. Red solid lines represent the estimated average equilibrium states of a) the AIF in the aorta and in b) the medial thigh muscle (black circles) according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170841#pone.0170841.e018" target="_blank">Eq (14)</a> are shown.</p