@phdthesis{7902,
  abstract     = {Mosaic genetic analysis has been widely used in different model organisms such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific fashion. More recently, and less easily conducted, mosaic genetic analysis in mice has also been enabled with the ambition to shed light on human gene function and disease. These genetic tools are of particular interest, but not restricted to, the study of the brain. Notably, the MADM technology offers a genetic approach in mice to visualize and concomitantly manipulate small subsets of genetically defined cells at a clonal level and single cell resolution. MADM-based analysis has already advanced the study of genetic mechanisms regulating brain development and is expected that further MADM-based analysis of genetic alterations will continue to reveal important insights on the fundamental principles of development and disease to potentially assist in the development of new therapies or treatments.
In summary, this work completed and characterized the necessary genome-wide genetic tools to perform MADM-based analysis at single cell level of the vast majority of mouse genes in virtually any cell type and provided a protocol to perform lineage tracing using the novel MADM resource. Importantly, this work also explored and revealed novel aspects of biologically relevant events in an in vivo context, such as the chromosome-specific bias of chromatid sister segregation pattern, the generation of cell-type diversity in the cerebral cortex and in the cerebellum and finally, the relevance of the interplay between the cell-autonomous gene function and cell-non-autonomous (community) effects in radial glial progenitor lineage progression.
This work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation.},
  author       = {Contreras, Ximena},
  issn         = {2663-337X},
  pages        = {214},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Genetic dissection of neural development in health and disease at single cell resolution}},
  doi          = {10.15479/AT:ISTA:7902},
  year         = {2020},
}

@article{8190,
  author       = {Sixt, Michael K and Huttenlocher, Anna},
  issn         = {1540-8140},
  journal      = {The Journal of Cell Biology},
  number       = {8},
  publisher    = {Rockefeller University Press},
  title        = {{Zena Werb (1945-2020): Cell biology in context}},
  doi          = {10.1083/jcb.202007029},
  volume       = {219},
  year         = {2020},
}

@phdthesis{8350,
  abstract     = {Cytoplasm is a gel-like crowded environment composed of tens of thousands of macromolecules, organelles, cytoskeletal networks and cytosol. The structure of the cytoplasm is thought to be highly organized and heterogeneous due to the crowding of its constituents and their effective compartmentalization. In such an environment, the diffusive dynamics of the molecules is very restricted, an effect that is further amplified by clustering and anchoring of molecules. Despite the jammed nature of the cytoplasm at the microscopic scale, large-scale reorganization of cytoplasm is essential for important cellular functions, such as nuclear positioning and cell division. How such mesoscale reorganization of the cytoplasm is achieved, especially for very large cells such as oocytes or syncytial tissues that can span hundreds of micrometers in size, has only begun to be understood.
In this thesis, I focus on the recent advances in elucidating the molecular, cellular and biophysical principles underlying cytoplasmic organization across different scales, structures and species. First, I outline which of these principles have been identified by reductionist approaches, such as in vitro reconstitution assays, where boundary conditions and components can be modulated at ease. I then describe how the theoretical and experimental framework established in these reduced systems have been applied to their more complex in vivo counterparts, in particular oocytes and embryonic syncytial structures, and discuss how such complex biological systems can initiate symmetry breaking and establish patterning.
Specifically, I examine an example of large-scale reorganizations taking place in zebrafish embryos, where extensive cytoplasmic streaming leads to the segregation of cytoplasm from yolk granules along the animal-vegetal axis of the embryo. Using biophysical experimentation and theory, I investigate the forces underlying this process, to show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the embryo. This wave functions in segregation by both pulling cytoplasm animally and pushing yolk granules vegetally. Cytoplasm pulling is mediated by bulk actin network flows exerting friction forces on the cytoplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. This study defines a novel role of bulk actin polymerization waves in embryo polarization via cytoplasmic segregation. Lastly, I describe the cytoplasmic reorganizations taking place during zebrafish oocyte maturation, where the initial segregation of the cytoplasm and yolk granules occurs. Here, I demonstrate a previously uncharacterized wave of microtubule aster formation, traveling the oocyte along the animal-vegetal axis. Further research is required to determine the role of such microtubule structures in cytoplasmic reorganizations therein.
Collectively, these studies provide further evidence for the coupling between cell cytoskeleton and cell cycle machinery, which can underlie a core self-organizing mechanism for orchestrating large-scale reorganizations in a cell-cycle-tunable manner, where the modulations of the force-generating machinery and cytoplasmic mechanics can be harbored to fulfill cellular functions.},
  author       = {Shamipour, Shayan},
  issn         = {2663-337X},
  pages        = {107},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Bulk actin dynamics drive phase segregation in zebrafish oocytes }},
  doi          = {10.15479/AT:ISTA:8350},
  year         = {2020},
}

@article{8434,
  abstract     = {Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin-binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex, an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell-edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.This article has an associated First Person interview with the first author of the paper. },
  author       = {Dimchev, Georgi A and Amiri, Behnam and Humphries, Ashley C. and Schaks, Matthias and Dimchev, Vanessa and Stradal, Theresia E. B. and Faix, Jan and Krause, Matthias and Way, Michael and Falcke, Martin and Rottner, Klemens},
  issn         = {1477-9137},
  journal      = {Journal of Cell Science},
  keywords     = {Cell Biology},
  number       = {7},
  publisher    = {The Company of Biologists},
  title        = {{Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation}},
  doi          = {10.1242/jcs.239020},
  volume       = {133},
  year         = {2020},
}

@phdthesis{8983,
  abstract     = {Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers.},
  author       = {Emtenani, Shamsi},
  issn         = {2663-337X},
  pages        = {141},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Metabolic regulation of Drosophila macrophage tissue invasion}},
  doi          = {10.15479/AT:ISTA:8983},
  year         = {2020},
}

@unpublished{8557,
  abstract     = {The infiltration of immune cells into tissues underlies the establishment of tissue resident macrophages, and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio which are themselves required for invasion. Cortical F-actin levels are critical as expressing a dominant active form of Diaphanous, a actin polymerizing Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo imaging shows that Dfos is required to enhance the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the mechanical properties of the macrophage nucleus from affecting tissue entry. We thus identify tuning the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.},
  author       = {Belyaeva, Vera and Wachner, Stephanie and Gridchyn, Igor and Linder, Markus and Emtenani, Shamsi and György, Attila and Sibilia, Maria and Siekhaus, Daria E},
  booktitle    = {bioRxiv},
  title        = {{Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance}},
  doi          = {10.1101/2020.09.18.301481},
  year         = {2020},
}

@article{8002,
  abstract     = {Wound healing in plant tissues, consisting of rigid cell wall-encapsulated cells, represents a considerable challenge and occurs through largely unknown mechanisms distinct from those in animals. Owing to their inability to migrate, plant cells rely on targeted cell division and expansion to regenerate wounds. Strict coordination of these wound-induced responses is essential to ensure efficient, spatially restricted wound healing. Single-cell tracking by live imaging allowed us to gain mechanistic insight into the wound perception and coordination of wound responses after laser-based wounding in Arabidopsis root. We revealed a crucial contribution of the collapse of damaged cells in wound perception and detected an auxin increase specific to cells immediately adjacent to the wound. This localized auxin increase balances wound-induced cell expansion and restorative division rates in a dose-dependent manner, leading to tumorous overproliferation when the canonical TIR1 auxin signaling is disrupted. Auxin and wound-induced turgor pressure changes together also spatially define the activation of key components of regeneration, such as the transcription regulator ERF115. Our observations suggest that the wound signaling involves the sensing of collapse of damaged cells and a local auxin signaling activation to coordinate the downstream transcriptional responses in the immediate wound vicinity.},
  author       = {Hörmayer, Lukas and Montesinos López, Juan C and Marhavá, Petra and Benková, Eva and Yoshida, Saiko and Friml, Jiří},
  issn         = {1091-6490},
  journal      = {Proceedings of the National Academy of Sciences of the United States of America},
  number       = {26},
  publisher    = {National Academy of Sciences},
  title        = {{Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots}},
  doi          = {10.1073/pnas.2003346117},
  volume       = {117},
  year         = {2020},
}

@inproceedings{9633,
  abstract     = {The search for biologically faithful synaptic plasticity rules has resulted in a large body of models. They are usually inspired by – and fitted to – experimental data, but they rarely produce neural dynamics that serve complex functions. These failures suggest that current plasticity models are still under-constrained by existing data. Here, we present an alternative approach that uses meta-learning to discover plausible synaptic plasticity rules. Instead of experimental data, the rules are constrained by the functions they implement and the structure they are meant to produce. Briefly, we parameterize synaptic plasticity rules by a Volterra expansion and then use supervised learning methods (gradient descent or evolutionary strategies) to minimize a problem-dependent loss function that quantifies how effectively a candidate plasticity rule transforms an initially random network into one with the desired function. We first validate our approach by re-discovering previously described plasticity rules, starting at the single-neuron level and “Oja’s rule”, a simple Hebbian plasticity rule that captures the direction of most variability of inputs to a neuron (i.e., the first principal component). We expand the problem to the network level and ask the framework to find Oja’s rule together with an anti-Hebbian rule such that an initially random two-layer firing-rate network will recover several principal components of the input space after learning. Next, we move to networks of integrate-and-fire neurons with plastic inhibitory afferents. We train for rules that achieve a target firing rate by countering tuned excitation. Our algorithm discovers a specific subset of the manifold of rules that can solve this task. Our work is a proof of principle of an automated and unbiased approach to unveil synaptic plasticity rules that obey biological constraints and can solve complex functions.},
  author       = {Confavreux, Basile J and Zenke, Friedemann and Agnes, Everton J. and Lillicrap, Timothy and Vogels, Tim P},
  booktitle    = {34th Conference on Neural Information Processing Systems},
  issn         = {1049-5258},
  location     = {Vancouver, Canada},
  pages        = {16398--16408},
  publisher    = {Neural Information Processing Systems Foundation},
  title        = {{A meta-learning approach to (re)discover plasticity rules that carve a desired function into a neural network}},
  volume       = {33},
  year         = {2020},
}

@phdthesis{7258,
  abstract     = {Many flows encountered in nature and applications are characterized by a chaotic motion known as turbulence. Turbulent flows generate intense friction with pipe walls and are responsible for considerable amounts of energy losses at world scale. The nature of turbulent friction and techniques aimed at reducing it have been subject of extensive research over the last century, but no definite answer has been found yet. In this thesis we show that in pipes at moderate turbulent Reynolds numbers friction is better described by the power law first introduced by Blasius and not by the Prandtl–von Kármán formula. At higher Reynolds numbers, large scale motions gradually become more important in the flow and can be related to the change in scaling of friction. Next, we present a series of new techniques that can relaminarize turbulence by suppressing a key mechanism that regenerates it at walls, the lift–up effect. In addition, we investigate the process of turbulence decay in several experiments and discuss the drag reduction potential. Finally, we examine the behavior of friction under pulsating conditions inspired by the human heart cycle and we show that under such circumstances turbulent friction can be reduced to produce energy savings.},
  author       = {Scarselli, Davide},
  issn         = {2663-337X},
  pages        = {174},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{New approaches to reduce friction in turbulent pipe flow}},
  doi          = {10.15479/AT:ISTA:7258},
  year         = {2020},
}

@unpublished{9750,
  abstract     = {Tension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact.},
  author       = {Slovakova, Jana and Sikora, Mateusz K and Caballero Mancebo, Silvia and Krens, Gabriel and Kaufmann, Walter and Huljev, Karla and Heisenberg, Carl-Philipp J},
  booktitle    = {bioRxiv},
  pages        = {41},
  title        = {{Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion}},
  doi          = {10.1101/2020.11.20.391284},
  year         = {2020},
}

@article{8529,
  abstract     = {Practical quantum networks require low-loss and noise-resilient optical interconnects as well as non-Gaussian resources for entanglement distillation and distributed quantum computation. The latter could be provided by superconducting circuits but existing solutions to interface the microwave and optical domains lack either scalability or efficiency, and in most cases the conversion noise is not known. In this work we utilize the unique opportunities of silicon photonics, cavity optomechanics and superconducting circuits to demonstrate a fully integrated, coherent transducer interfacing the microwave X and the telecom S bands with a total (internal) bidirectional transduction efficiency of 1.2% (135%) at millikelvin temperatures. The coupling relies solely on the radiation pressure interaction mediated by the femtometer-scale motion of two silicon nanobeams reaching a <jats:italic>V</jats:italic><jats:sub><jats:italic>π</jats:italic></jats:sub> as low as 16 μV for sub-nanowatt pump powers. Without the associated optomechanical gain, we achieve a total (internal) pure conversion efficiency of up to 0.019% (1.6%), relevant for future noise-free operation on this qubit-compatible platform.},
  author       = {Arnold, Georg M and Wulf, Matthias and Barzanjeh, Shabir and Redchenko, Elena and Rueda Sanchez, Alfredo R and Hease, William J and Hassani, Farid and Fink, Johannes M},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
  publisher    = {Springer Nature},
  title        = {{Converting microwave and telecom photons with a silicon photonic nanomechanical interface}},
  doi          = {10.1038/s41467-020-18269-z},
  volume       = {11},
  year         = {2020},
}

@article{9114,
  abstract     = {Microwave photonics lends the advantages of fiber optics to electronic sensing and communication systems. In contrast to nonlinear optics, electro-optic devices so far require classical modulation fields whose variance is dominated by electronic or thermal noise rather than quantum fluctuations. Here we demonstrate bidirectional single-sideband conversion of X band microwave to C band telecom light with a microwave mode occupancy as low as 0.025 ± 0.005 and an added output noise of less than or equal to 0.074 photons. This is facilitated by radiative cooling and a triply resonant ultra-low-loss transducer operating at millikelvin temperatures. The high bandwidth of 10.7 MHz and total (internal) photon conversion
efficiency of 0.03% (0.67%) combined with the extremely slow heating rate of 1.1 added output noise photons per second for the highest available pump power of 1.48 mW puts near-unity efficiency pulsed quantum transduction within reach. Together with the non-Gaussian resources of superconducting qubits this might provide the practical foundation to extend the range and scope of current quantum networks in analogy to electrical repeaters in classical fiber optic communication.},
  author       = {Hease, William J and Rueda Sanchez, Alfredo R and Sahu, Rishabh and Wulf, Matthias and Arnold, Georg M and Schwefel, Harald G.L. and Fink, Johannes M},
  issn         = {2691-3399},
  journal      = {PRX Quantum},
  number       = {2},
  publisher    = {American Physical Society},
  title        = {{Bidirectional electro-optic wavelength conversion in the quantum ground state}},
  doi          = {10.1103/prxquantum.1.020315},
  volume       = {1},
  year         = {2020},
}

@unpublished{8831,
  abstract     = {Holes in planar Ge have high mobilities, strong spin-orbit interaction and electrically tunable g-factors, and are therefore emerging as a promising candidate for hybrid superconductorsemiconductor devices. This is further motivated by the observation of supercurrent transport in planar Ge Josephson Field effect transistors (JoFETs). A key challenge towards hybrid germanium quantum technology is the design of high quality interfaces and superconducting contacts that are robust against magnetic fields. By combining the assets of Al, which has a long superconducting coherence, and Nb, which has a significant superconducting gap, we form low-disordered JoFETs with large ICRN products that are capable of withstanding high magnetic fields. We furthermore demonstrate the ability of phase-biasing individual JoFETs opening up an avenue to explore topological superconductivity in planar Ge. The persistence of superconductivity in the reported hybrid devices beyond 1.8 T paves the way towards integrating spin qubits and proximity-induced superconductivity on the same chip.},
  author       = {Aggarwal, Kushagra and Hofmann, Andrea C and Jirovec, Daniel and Prieto Gonzalez, Ivan and Sammak, Amir and Botifoll, Marc and Marti-Sanchez, Sara and Veldhorst, Menno and Arbiol, Jordi and Scappucci, Giordano and Katsaros, Georgios},
  booktitle    = {arXiv},
  title        = {{Enhancement of proximity induced superconductivity in planar Germanium}},
  doi          = {10.48550/arXiv.2012.00322},
  year         = {2020},
}

@article{8986,
  abstract     = {Flowering plants display the highest diversity among plant species and have notably shaped terrestrial landscapes. Nonetheless, the evolutionary origin of their unprecedented morphological complexity remains largely an enigma. Here, we show that the coevolution of cis-regulatory and coding regions of PIN-FORMED (PIN) auxin transporters confined their expression to certain cell types and directed their subcellular localization to particular cell sides, which together enabled dynamic auxin gradients across tissues critical to the complex architecture of flowering plants. Extensive intraspecies and interspecies genetic complementation experiments with PINs from green alga up to flowering plant lineages showed that PIN genes underwent three subsequent, critical evolutionary innovations and thus acquired a triple function to regulate the development of three essential components of the flowering plant Arabidopsis: shoot/root, inflorescence, and floral organ. Our work highlights the critical role of functional innovations within the PIN gene family as essential prerequisites for the origin of flowering plants.},
  author       = {Zhang, Yuzhou and Rodriguez Solovey, Lesia and Li, Lanxin and Zhang, Xixi and Friml, Jiří},
  issn         = {2375-2548},
  journal      = {Science Advances},
  number       = {50},
  publisher    = {AAAS},
  title        = {{Functional innovations of PIN auxin transporters mark crucial evolutionary transitions during rise of flowering plants}},
  doi          = {10.1126/sciadv.abc8895},
  volume       = {6},
  year         = {2020},
}

@article{8283,
  abstract     = {Drought and salt stress are the main environmental cues affecting the survival, development, distribution, and yield of crops worldwide. MYB transcription factors play a crucial role in plants’ biological processes, but the function of pineapple MYB genes is still obscure. In this study, one of the pineapple MYB transcription factors, AcoMYB4, was isolated and characterized. The results showed that AcoMYB4 is localized in the cell nucleus, and its expression is induced by low temperature, drought, salt stress, and hormonal stimulation, especially by abscisic acid (ABA). Overexpression of AcoMYB4 in rice and Arabidopsis enhanced plant sensitivity to osmotic stress; it led to an increase in the number stomata on leaf surfaces and lower germination rate under salt and drought stress. Furthermore, in AcoMYB4 OE lines, the membrane oxidation index, free proline, and soluble sugar contents were decreased. In contrast, electrolyte leakage and malondialdehyde (MDA) content increased significantly due to membrane injury, indicating higher sensitivity to drought and salinity stresses. Besides the above, both the expression level and activities of several antioxidant enzymes were decreased, indicating lower antioxidant activity in AcoMYB4 transgenic plants. Moreover, under osmotic stress, overexpression of AcoMYB4 inhibited ABA biosynthesis through a decrease in the transcription of genes responsible for ABA synthesis (ABA1 and ABA2) and ABA signal transduction factor ABI5. These results suggest that AcoMYB4 negatively regulates osmotic stress by attenuating cellular ABA biosynthesis and signal transduction pathways. },
  author       = {Chen, Huihuang and Lai, Linyi and Li, Lanxin and Liu, Liping and Jakada, Bello Hassan and Huang, Youmei and He, Qing and Chai, Mengnan and Niu, Xiaoping and Qin, Yuan},
  issn         = {1422-0067},
  journal      = {International Journal of Molecular Sciences},
  number       = {16},
  publisher    = {MDPI},
  title        = {{AcoMYB4, an Ananas comosus L. MYB transcription factor, functions in osmotic stress through negative regulation of ABA signaling}},
  doi          = {10.3390/ijms21165727},
  volume       = {21},
  year         = {2020},
}

@article{9160,
  abstract     = {Auxin is a key hormonal regulator, that governs plant growth and development in concert with other hormonal pathways. The unique feature of auxin is its polar, cell-to-cell transport that leads to the formation of local auxin maxima and gradients, which coordinate initiation and patterning of plant organs. The molecular machinery mediating polar auxin transport is one of the important points of interaction with other hormones. Multiple hormonal pathways converge at the regulation of auxin transport and form a regulatory network that integrates various developmental and environmental inputs to steer plant development. In this review, we discuss recent advances in understanding the mechanisms that underlie regulation of polar auxin transport by multiple hormonal pathways. Specifically, we focus on the post-translational mechanisms that contribute to fine-tuning of the abundance and polarity of auxin transporters at the plasma membrane and thereby enable rapid modification of the auxin flow to coordinate plant growth and development.},
  author       = {Semeradova, Hana and Montesinos López, Juan C and Benková, Eva},
  issn         = {2590-3462},
  journal      = {Plant Communications},
  number       = {3},
  publisher    = {Elsevier},
  title        = {{All roads lead to auxin: Post-translational regulation of auxin transport by multiple hormonal pathways}},
  doi          = {10.1016/j.xplc.2020.100048},
  volume       = {1},
  year         = {2020},
}

@article{7889,
  abstract     = {Autoluminescent plants engineered to express a bacterial bioluminescence gene cluster in plastids have not been widely adopted because of low light output. We engineered tobacco plants with a fungal bioluminescence system that converts caffeic acid (present in all plants) into luciferin and report self-sustained luminescence that is visible to the naked eye. Our findings could underpin development of a suite of imaging tools for plants.},
  author       = {Mitiouchkina, Tatiana and Mishin, Alexander S. and Gonzalez Somermeyer, Louisa and Markina, Nadezhda M. and Chepurnyh, Tatiana V. and Guglya, Elena B. and Karataeva, Tatiana A. and Palkina, Kseniia A. and Shakhova, Ekaterina S. and Fakhranurova, Liliia I. and Chekova, Sofia V. and Tsarkova, Aleksandra S. and Golubev, Yaroslav V. and Negrebetsky, Vadim V. and Dolgushin, Sergey A. and Shalaev, Pavel V. and Shlykov, Dmitry and Melnik, Olesya A. and Shipunova, Victoria O. and Deyev, Sergey M. and Bubyrev, Andrey I. and Pushin, Alexander S. and Choob, Vladimir V. and Dolgov, Sergey V. and Kondrashov, Fyodor and Yampolsky, Ilia V. and Sarkisyan, Karen S.},
  issn         = {1546-1696},
  journal      = {Nature Biotechnology},
  pages        = {944--946},
  publisher    = {Springer Nature},
  title        = {{Plants with genetically encoded autoluminescence}},
  doi          = {10.1038/s41587-020-0500-9},
  volume       = {38},
  year         = {2020},
}

@phdthesis{7525,
  abstract     = {The medial habenula (MHb) is an evolutionary conserved epithalamic structure important for the modulation of emotional memory. It is involved in regulation of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and feeding behavior. MHb receives inputs from septal regions and projects exclusively to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project to different subnuclei of MHb: the bed nucleus of anterior commissure projects to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore, the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively. Importantly, these projections have unique features of prominent co-release of different neurotransmitters and requirement of a peculiar type of calcium channel for release. In general, synaptic neurotransmission requires an activity-dependent influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels. The calcium channel family most commonly involved in neurotransmitter release comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits, respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements. This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique mechanisms of glutamate release in this pathway. One potential example of such uniqueness is the facilitation of release by GABAB receptor (GBR) activation. Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting presynaptic calcium channels. MHb shows the highest expression levels of GBR in the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are associated with auxiliary subunits, called potassium channel tetramerization domain containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b may be involved in the unique mechanisms of neurotransmitter release mediated by Cav2.3 and regulated by GBRs in this pathway. 
In the present study, we first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482. We next found that baclofen, a GBR agonist, has facilitatory effects on release from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed exclusively in ventral MHb may have a role in the facilitatory effects of GBR activation. In a heterologous expression system using HEK cells, we found that KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely in presynaptic active zone in IPN with KCTD12b being present only in rostral/central but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3, KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating that they may form complexes regulating vesicle release in rostral IPN. 
On electrophysiological studies of wild type (WT) mice, we found that paired-pulse ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8 KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO mice, the mean variance analysis revealed significantly lower release probability in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8 and KCTD12b KO mice, and found the facilitation of release remained in both KO mice, indicating that the peculiar effects of the GBR activation in this pathway do not depend on the selective expression of these KCTD subunits in ventral MHb. However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in its termination in the absence of KCTD12b. Consistent with these functional findings, replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the release probability and termination of the GBR effect in the absence of KCTD12b.
In summary, our study provided new insights into the physiological roles of presynaptic Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal circuit. Future studies will be required to identify the exact molecular mechanism underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals. It remains to be determined whether the prominent presence of presynaptic KCTDs at active zone could exert similar neuromodulatory functions in different pathways of the brain.
},
  author       = {Bhandari, Pradeep},
  issn         = {2663-337X},
  keywords     = {Cav2.3, medial habenula (MHb), interpeduncular nucleus (IPN)},
  pages        = {79},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway}},
  doi          = {10.15479/AT:ISTA:7525},
  year         = {2020},
}

@article{8139,
  abstract     = {Clathrin-mediated endocytosis (CME) is a crucial cellular process implicated in many aspects of plant growth, development, intra- and inter-cellular signaling, nutrient uptake and pathogen defense. Despite these significant roles, little is known about the precise molecular details of how it functions in planta. In order to facilitate the direct quantitative study of plant CME, here we review current routinely used methods and present refined, standardized quantitative imaging protocols which allow the detailed characterization of CME at multiple scales in plant tissues. These include: (i) an efficient electron microscopy protocol for the imaging of Arabidopsis CME vesicles in situ, thus providing a method for the detailed characterization of the ultra-structure of clathrin-coated vesicles; (ii) a detailed protocol and analysis for quantitative live-cell fluorescence microscopy to precisely examine the temporal interplay of endocytosis components during single CME events; (iii) a semi-automated analysis to allow the quantitative characterization of global internalization of cargos in whole plant tissues; and (iv) an overview and validation of useful genetic and pharmacological tools to interrogate the molecular mechanisms and function of CME in intact plant samples.},
  author       = {Johnson, Alexander J and Gnyliukh, Nataliia and Kaufmann, Walter and Narasimhan, Madhumitha and Vert, G and Bednarek, SY and Friml, Jiří},
  issn         = {1477-9137},
  journal      = {Journal of Cell Science},
  number       = {15},
  publisher    = {The Company of Biologists},
  title        = {{Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis}},
  doi          = {10.1242/jcs.248062},
  volume       = {133},
  year         = {2020},
}

@phdthesis{8340,
  abstract     = {Mitochondria are sites of oxidative phosphorylation in eukaryotic cells. Oxidative phosphorylation operates by a chemiosmotic mechanism made possible by redox-driven proton pumping machines which establish a proton motive force across the inner mitochondrial membrane. This electrochemical proton gradient is used to drive ATP synthesis, which powers the majority of cellular processes such as protein synthesis, locomotion and signalling. In this thesis I investigate the structures and molecular mechanisms of two inner mitochondrial proton pumping enzymes, respiratory complex I and transhydrogenase. I present the first high-resolution structure of the full transhydrogenase from any species, and a significantly improved structure of complex I. Improving the resolution from 3.3 Å available previously to up to 2.3 Å in this thesis allowed us to model bound water molecules, crucial in the proton pumping mechanism. For both enzymes, up to five cryo-EM datasets with different substrates and inhibitors bound were solved to delineate the catalytic cycle and understand the proton pumping mechanism. In transhydrogenase, the proton channel is gated by reversible detachment of the NADP(H)-binding domain which opens the proton channel to the opposite sites of the membrane. In complex I, the proton channels are gated by reversible protonation of key glutamate and lysine residues and breaking of the water wire connecting the proton pumps with the quinone reduction site. The tight coupling between the redox and the proton pumping reactions in transhydrogenase is achieved by controlling the NADP(H) exchange which can only happen when the NADP(H)-binding domain interacts with the membrane domain. In complex I, coupling is achieved by cycling of the whole complex between the closed state, in which quinone can get reduced, and the open state, in which NADH can induce quinol ejection from the binding pocket. On the basis of these results I propose detailed mechanisms for catalytic cycles of transhydrogenase and complex I that are consistent with a large amount of previous work. In both enzymes, conformational and electrostatic mechanisms contribute to the overall catalytic process. Results presented here could be used for better understanding of the human pathologies arising from deficiencies of complex I or transhydrogenase and could be used to develop novel therapies.},
  author       = {Kampjut, Domen},
  isbn         = {978-3-99078-008-4},
  issn         = {2663-337X},
  pages        = {242},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes}},
  doi          = {10.15479/AT:ISTA:8340},
  year         = {2020},
}