MIMICA V5.1, user guide

This document introduces the MISU-MIT Cloud and Aerosol (MIMICA) model, an atmospheric model dedicated to the simulation of clouds and other atmospheric processes at high resolution. The document contains a detailed description of the code, as well as an extended section serving as a manual for new or experienced users

Effects of short-term variability of meteorological variables on soil temperature in permafrost regions

Effects of the short-term temporal variability of meteorological variables on soil temperature in northern high-latitude regions have been investigated. For this, a process-oriented land surface model has been driven using an artificially manipulated climate dataset. Short-term climate variability mainly impacts snow depth, and the thermal diffusivity of lichens and bryophytes. These impacts of climate variability on insulating surface layers together substantially alter the heat exchange between atmosphere and soil. As a result, soil temperature is 0.1 to 0.8 ∘C higher when climate variability is reduced. Earth system models project warming of the Arctic region but also increasing variability of meteorological variables and more often extreme meteorological events. Therefore, our results show that projected future increases in permafrost temperature and active-layer thickness in response to climate change will be lower (i) when taking into account future changes in short-term variability of meteorological variables and (ii) when representing dynamic snow and lichen and bryophyte functions in land surface models

Chemistry Climate Model Simulations of Polar Stratospheric Ozone

Stratospheric ozone (O3) plays a crucial role in protecting organisms on Earth from lethal shortwave solar radiation. Because it is radiatively active, O3 also determines the temperature structure of the stratosphere, so its distribution affects the circulation. For these reasons, understanding polar stratospheric O3 has been a high priority of the scientific community for decades. Of primary interest in recent years is explaining and predicting variations in O3 in a changing climate. Stratospheric O3 distributions are affected by both chemistry and transport, which in turn are controlled by temperature, circulation, and dynamics. Hence, investigations of polar stratospheric O3 require the separation of these intertwined processes, and an understanding of the relevant feedbacks. Investigations of these processes require global observations as well as coupled chemistry climate model simulations. This thesis focuses on chemical O3 loss due to halogen and odd nitrogen (NOX) catalytic cycles, and utilizes satellite measurements from several instruments and the Specified Dynamics Whole Atmosphere Community Climate Model (SD-WACCM). The science questions are: (1) Is SD-WACCM a tool sophisticated enough for quantitative O3 evolution investigations? (2) How much O3 loss can be accurately attributed to the stratospheric O3 loss processes induced by halogens, energetic particle precipitation, and NOX individually? (3) Why is the observed O3 in the Arctic 2010/2011 winter exceptionally low, despite high dynamical variability, which is usually associated with less O3 loss? The questions are addressed by: (1) iteratively evaluating and improving SD-WACCM simulations of the Arctic 2004/2005 winter through comparisons with satellite observations; (2) comparing multiple experimental SD-WACCM simulations of the Antarctic 2005 winter omitting individual O3 loss processes to a reference simulation; (3) testing a hypothesis by means of a comprehensive model simulation of the Arctic 2010/11 winter season. Conclusions of this thesis are: (1) SD-WACCM is a useful tool to quantify polar stratospheric O3 evolution after including several model improvements; (2) 74% of total column O3 loss can be attributed robustly to halogen chemistry preceded by heterogeneous chemistry; (3) severe O3 loss in Arctic 2010/11 results in part from enhanced chlorine activation due to the high dynamical variability. The work of this thesis improved SD-WACCM and adds an unprecedented evaluation regarding O3 variability and O3 loss in the stratosphere. Exact quantification of individual O3 loss processes became possible even for extreme seasons. Hence this thesis enables analyses of polar stratospheric winter seasons on a level of detail that was not possible before

Genetic analysis of β1 integrin “activation motifs” in mice

Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin β cytoplasmic domains. Talin binding disrupts the salt bridge between the α/β tails, leading to tail separation and integrin activation. We analyzed mice in which we mutated the tyrosines of the β1 tail and the membrane-proximal aspartic acid required for the salt bridge. Tyrosine-to-alanine substitutions abolished β1 integrin functions and led to a β1 integrin–null phenotype in vivo. Surprisingly, neither the substitution of the tyrosines with phenylalanine nor the aspartic acid with alanine resulted in an obvious defect. These data suggest that the NPXY motifs of the β1 integrin tail are essential for β1 integrin function, whereas tyrosine phosphorylation and the membrane-proximal salt bridge between α and β1 tails have no apparent function under physiological conditions in vivo

The fibronectin-binding integrins α5β1 and αvβ3 differentially modulate RhoA–GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis

We have studied the formation of different types of cell matrix adhesions in cells that bind to fibronectin via either α5β1 or αvβ3. In both cases, cell adhesion to fibronectin leads to a rapid decrease in RhoA activity. However, α5β1 but not αvβ3 supports high levels of RhoA activity at later stages of cell spreading, which are associated with a translocation of focal contacts to peripheral cell protrusions, recruitment of tensin into fibrillar adhesions, and fibronectin fibrillogenesis. Expression of an activated mutant of RhoA stimulates αvβ3-mediated fibrillogenesis. Despite the fact that α5β1-mediated adhesion to the central cell-binding domain of fibronectin supports activation of RhoA, other regions of fibronectin are required for the development of α5β1-mediated but not αvβ3-mediated focal contacts. Using chimeras of β1 and β3 subunits, we find that the extracellular domain of β1 controls RhoA activity. By expressing both β1 and β3 at high levels, we show that β1-mediated control of the levels of β3 is important for the distribution of focal contacts. Our findings demonstrate that the pattern of fibronectin receptors expressed on a cell dictates the ability of fibronectin to stimulate RhoA-mediated organization of cell matrix adhesions

RhoA Drives T-Cell Activation and Encephalitogenic Potential in an Animal Model of Multiple Sclerosis

T-cells are known to be intimately involved in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). T-cell activation is controlled by a range of intracellular signaling pathways regulating cellular responses such as proliferation, cytokine production, integrin expression, and migration. These processes are crucial for the T-cells’ ability to mediate inflammatory processes in autoimmune diseases such as MS. RhoA is a ubiquitously expressed small GTPase well described as a regulator of the actin cytoskeleton. It is essential for embryonic development and together with other Rho GTPases controls various cellular processes such as cell development, shaping, proliferation, and locomotion. However, the specific contribution of RhoA to these processes in T-cells in general, and in autoreactive T-cells in particular, has not been fully characterized. Using mice with a T-cell specific deletion of the RhoA gene (RhoAfl/flLckCre+), we investigated the role of RhoA in T-cell development, functionality, and encephalitogenic potential in EAE. We show that lack of RhoA specifically in T-cells results in reduced numbers of mature T-cells in thymus and spleen but normal counts in peripheral blood. EAE induction in RhoAfl/flLckCre+ mice results in significantly reduced disease incidence and severity, which coincides with a reduced CNS T-cell infiltration. Besides presenting reduced migratory capacity, both naïve and autoreactive effector T-cells from RhoAfl/flLckCre+ mice show decreased viability, proliferative capacity, and an activation profile associated with reduced production of Th1 pro-inflammatory cytokines. Our study demonstrates that RhoA is a central regulator of several archetypical T-cell responses, and furthermore points toward RhoA as a new potential therapeutic target in diseases such as MS, where T-cell activity plays a central role

Cytoskeletal Stability in the Auditory Organ In Vivo : RhoA Is Dispensable for Wound Healing but Essential for Hair Cell Development

Wound healing in the inner ear sensory epithelia is performed by the apical domains of supporting cells (SCs). Junctional F-actin belts of SCs are thin during development but become exceptionally thick during maturation. The functional significance of the thick belts is not fully understood. We have studied the role of F-actin belts during wound healing in the developing and adult cochlea of mice in vivo. We show that the thick belts serve as intracellular scaffolds that preserve the positions of surviving cells in the cochlear sensory epithelium. Junctions associated with the thick F-actin belts did not readily disassemble during wound healing. To compensate for this, basolateral membranes of SCs participated in the closure of surface breach. Because not only neighboring but also distant SCs contributed to wound healing by basolateral protrusions, this event appears to be triggered by contact-independent diffusible signals. In the search for regulators of wound healing, we inactivated RhoA in SCs, which, however, did not limit wound healing. RhoA inactivation in developing outer hair cells (OHCs) caused myosin II delocalization from the perijunctional domain and apical cell-surface enlargement. These abnormalities led to the extrusion of OHCs from the epithelium. These results demonstrate the importance of stability of the apical domain, both in wound repair by SCs and in development of OHCs, and that only this latter function is regulated by RhoA. Because the correct cytoarchitecture of the cochlear sensory epithelium is required for normal hearing, the stability of cell apices should be maintained in regenerative and protective interventions.Peer reviewe