Implications of Regurgitative Feeding on Plastic Loads in Northern Fulmars (Fulmarus glacialis): A Study from Svalbard

Procellariiform seabirds like northern fulmars (Fulmarus glacialis) are prone to ingest and accumulate floating plastic pieces. In the North Sea region, there is a long tradition to use beached fulmars as biomonitors for marine plastic pollution. Monitoring data revealed consistently lower plastic burdens in adult fulmars compared to younger age classes. Those findings were hypothesized to partly result from parental transfer of plastic to chicks. However, no prior study has examined this mechanism in fulmars by comparing plastic burdens in fledglings and older fulmars shortly after the chick-rearing period. Therefore, we investigated plastic ingestion in 39 fulmars from Kongsfjorden (Svalbard), including 21 fledglings and 18 older fulmars (adults/older immatures). We found that fledglings (50–60 days old) had significantly more plastic than older fulmars. While plastic was found in all fledglings, two older fulmars contained no and several older individuals barely any plastic. These findings supported that fulmar chicks from Svalbard get fed high quantities of plastic by their parents. Adverse effects of plastic on fulmars were indicated by one fragment that perforated the stomach and possibly one thread perforating the intestine. Negative correlations between plastic mass and body fat in fledglings and older fulmars were not significant

Function-structure approach reveals novel insights on the interplay of Immunoglobulin G 1 proteoforms and Fc gamma receptor IIa allotypes

Human Fc gamma receptor IIa (FcγRIIa) or CD32a has two major allotypes with a single amino acid difference at position 131 (histidine or arginine). Differences in FcγRIIa allotypes are known to impact immunological responses such as the clinical outcome of therapeutic monoclonal antibodies (mAbs). FcγRIIa is involved in antibody-dependent cellular phagocytosis (ADCP), which is an important contributor to the mechanism-of-action of mAbs by driving phagocytic clearance of cancer cells. Hence, understanding the impact of individual mAb proteoforms on the binding to FcγRIIa, and its different allotypes, is crucial for defining meaningful critical quality attributes (CQAs). Here, we report a function-structure based approach guided by novel FcγRIIa affinity chromatography-mass spectrometry (AC-MS) assays to assess individual IgG1 proteoforms. This allowed to unravel allotype-specific differences of IgG1 proteoforms on FcγRIIa binding. FcγRIIa AC-MS confirmed and refined structure-function relationships of IgG1 glycoform interactions. For example, the positive impact of afucosylation was higher than galactosylation for FcγRIIa Arg compared to FcγRIIa His. Moreover, we observed FcγRIIa allotype-opposing and IgG1 proteoform integrity-dependent differences in the binding response of stress-induced IgG1 proteoforms comprising asparagine 325 deamidation. The FcγRIIa-allotype dependent binding differences resolved by AC-MS were in line with functional ADCP-surrogate bioassay models. The molecular basis of the observed allotype specificity and proteoform selectivity upon asparagine 325 deamidation was elucidated using molecular dynamics. The observed differences were attributed to the contributions of an inter-molecular salt bridge between IgG1 and FcγRIIa Arg and the contribution of an intra-molecular hydrophobic pocket in IgG1. Our work highlights the unprecedented structural and functional resolution of AC-MS approaches along with predictive biological significance of observed affinity differences within relevant cell-based methods. This makes FcγRIIa AC-MS an invaluable tool to streamline the CQA assessment of therapeutic mAbs

On the simulation of fluid-structure-interaction using flexible coupling algorithms

Der immer weitere Optimierungsbedarf im Bereich der hydraulischen Maschinen erfordert auch die Verbesserung und Erweiterung der zur Entwicklung eingesetzten Methoden. Besonders die Wechselwirkungen zwischen umströmten Bauteilen und Strömung, Fluid-Struktur-Interaktion (FSI), können durch die verfügbaren Berechnungsverfahren noch nicht ausreichend abgebildet werden. Fluid-Struktur-Wechselwirkungen werden entsprechend dem Grad der Beeinflussung in starke und schwache Kopplungen unterteilt. Die beiden physikalischen Felder, Fluid und Struktur, werden für die numerische Simulation auf diskreten Berechnungsgittern dargestellt. Bei den gängigen numerischen Ansätzen wird die Strömung auf einem raumfesten (Euler-Ansatz), die Struktur auf einem mitbewegten Gitter (Lagrange-Ansatz) beschrieben. Zur Simulation von Fluid-Struktur-Wechselwirkungen muss sich das Strömungsberechnungsgitter mit der sich verformenden Struktur mitbewegen. Aus Sicht der Numerik kommen die variablen Knotenpositionen des Fluidgitters dann als drittes, numerisches Feld hinzu. Bekannte Verfahren zur Lösung dieses Dreifeldproblems sind oft sehr speziell oder für hydraulische Maschinen nicht geeignet. Daraus ergibt sich die Aufgabenstellung dieser Arbeit; geeignete numerische Methoden zu finden, um Fluid-Struktur-Wechselwirkungen, mit dem Anwendungsschwerpunkt hydraulische Strömungsmaschinen, abzubilden. Die Verfahren, die in dieser Arbeit entwickelt werden, eignen sich zur numerischen Simulation von Fluid-Struktur-Wechselwirkungen in hydraulischen Maschinen. Der erste Schritt besteht in der Einführung der Arbitrary-Lagrange-Euler-Formulierung (ALE) der Navier-Stokes-Gleichungen für beliebig bewegte und verformte Rechengebiete. Im Hauptteil der Arbeit werden zunächst unterschiedliche Methoden zur Nachführung des Strömungsberechnungsgitters bei sich verformenden Gebietsrändern diskutiert und untersucht. Die algebraischen Verfahren haben gegenüber den Pseudostrukturmethoden dabei einen klaren Vorteil in Bezug auf die Rechenzeit und die erzeugte Gitterqualität. Es folgt die Herleitung und Diskussion partitionierter Kopplungsalgorithmen zur Kopplung von Strömungs- und Struktursimulation. Das ausgewählte Verfahren wird über eine neu entwickelte Programmierschnittstelle an das Programm FENFLOSS angebunden. Untersuchungen zeigen ein stabiles Verhalten und numerische Testfälle können gut nachgebildet werden. Im Anwendungsteil wird das entwickelte Verfahren auf einen Tragflügel und ein Rotorblatt einer Meeresturbine angewendet.The ongoing request for optimisation in hydraulic machinery requires also the improvement and enhancement of methods used in their development. Especially, fluid-structure-interactions (FSI), i.e. the interaction between parts in a fluid and the fluid flow itself, are not represented accurately enough with the methods currently available. According to the degree of interaction, strong and weak coupling are distinguished. In order to solve a problem with numerical simulation methods the respective physical fields, fluid and structure, have to be discritised in space. Commonly used numerical approaches use a spacially-fixed (Euler-Approach) and a material-fixed (Lagrange-Approach) computational mesh for fluid and structure, respectively. To simulate FSI the fluid grid has to be able to deform with the flexible structure determining its boundaries. Seen from the numerical point of view, the nodal positions of the fluid mesh are a third field that has to be included into the solution of the problem. Known procedures are often designed to work for special tasks, but they are not suitable to work for applications in the field of hydraulic machinery. Hence, the task of this work is to find adequate numerical methods that work for the simulation of fluid-structure-interactions in hydraulic machinery. The methods developped in this thesis will be suitable for the numerical solution of fluid-structure-interactions in hydraulic machinery. First, the Arbitrary-Lagrange-Euler-Formulation (ALE) of the Navier-Stokes-Equations is introduced to describe the fluid on arbitrarily moving computational meshes. In a second step, the main part of the work, different moving-mesh algorithms for the mesh adaption are discussed and examined. It turns out that algebraic procedures have certain advantages compared to the ones using differential equations to update the mesh, e.g. computing time and produced mesh quality. Further, partitioned fluid-structure-coupling-algorithms are derived and discussed. The chosen method is implemented using a newly developped programming interface of the flow simulation program FENFLOSS. In tests with chosen benchmark problems it shows a stable behaviour and the known results are reproduced with convincing quality. The last part shows the results obtained with two applications, a flexible wing in unsteady flow and the hydroelastics of a tidal turbine runner blade

AtMyb41 Regulates Transcriptional and Metabolic Responses to Osmotic Stress in Arabidopsis[W][OA]

Myb transcription factors have been implicated in a wide variety of plant-specific processes, including secondary metabolism, cell shape determination, cell differentiation, and stress responses. Very recently, AtMyb41 from Arabidopsis (Arabidopsis thaliana) was described as a gene transcriptionally regulated in response to salinity, desiccation, cold, and abscisic acid. The corresponding transcription factor was suggested to control stress responses linked to cell wall modifications. In this work, we have characterized AtMyb41 further by subjecting independent AtMyb41-overexpressing lines to detailed transcriptome and metabolome analysis. Our molecular data indicate that AtMyb41 is involved in distinct cellular processes, including control of primary metabolism and negative regulation of short-term transcriptional responses to osmotic stress

Dissection of Symbiosis and Organ Development by Integrated Transcriptome Analysis of Lotus japonicus Mutant and Wild-Type Plants

Genetic analyses of plant symbiotic mutants has led to the identification of key genes involved in Rhizobium-legume communication as well as in development and function of nitrogen fixing root nodules. However, the impact of these genes in coordinating the transcriptional programs of nodule development has only been studied in limited and isolated studies. Here, we present an integrated genome-wide analysis of transcriptome landscapes in Lotus japonicus wild-type and symbiotic mutant plants. Encompassing five different organs, five stages of the sequentially developed determinate Lotus root nodules, and eight mutants impaired at different stages of the symbiotic interaction, our data set integrates an unprecedented combination of organ- or tissue-specific profiles with mutant transcript profiles. In total, 38 different conditions sampled under the same well-defined growth regimes were included. This comprehensive analysis unravelled new and unexpected patterns of transcriptional regulation during symbiosis and organ development. Contrary to expectations, none of the previously characterized nodulins were among the 37 genes specifically expressed in nodules. Another surprise was the extensive transcriptional response in whole root compared to the susceptible root zone where the cellular response is most pronounced. A large number of transcripts predicted to encode transcriptional regulators, receptors and proteins involved in signal transduction, as well as many genes with unknown function, were found to be regulated during nodule organogenesis and rhizobial infection. Combining wild type and mutant profiles of these transcripts demonstrates the activation of a complex genetic program that delineates symbiotic nitrogen fixation. The complete data set was organized into an indexed expression directory that is accessible from a resource database, and here we present selected examples of biological questions that can be addressed with this comprehensive and powerful gene expression data set