@article{1895, abstract = {Major histocompatibility complex class I (MHCI) molecules were recently identified as novel regulators of synaptic plasticity. These molecules are expressed in various brain areas, especially in regions undergoing activity-dependent synaptic plasticity, but their role in the nucleus accumbens (NAc) is unknown. In this study, we investigated the effects of genetic disruption of MHCI function, through deletion of β2-microblobulin, which causes lack of cell surface expression of MHCI. First, we confirmed that MHCI molecules are expressed in the NAc core in wild-type mice. Second, we performed electrophysiological recordings with NAc core slices from wild-type and β2-microglobulin knock-out mice lacking cell surface expression of MHCI. We found that low frequency stimulation induced long-term depression in wild-type but not knock-out mice, whereas high frequency stimulation induced long-term potentiation in both genotypes, with a larger magnitude in knock-out mice. Furthermore, we demonstrated that knock-out mice showed more persistent behavioral sensitization to cocaine, which is a NAc-related behavior. Using this model, we analyzed the density of total AMPA receptors and their subunits GluR1 and GluR2 in the NAc core, by SDS-digested freeze-fracture replica labeling. After repeated cocaine exposure, the density of GluR1 was increased, but there was no change in total AMPA receptors and GluR2 levels in wildtype mice. In contrast, following repeated cocaine exposure, increased densities of total AMPA receptors, GluR1 and GluR2 were observed in knock-out mice. These results indicate that functional deficiency of MHCI enhances synaptic potentiation, induced by electrical and pharmacological stimulation.}, author = {Edamura, Mitsuhiro and Murakami, Gen and Meng, Hongrui and Itakura, Makoto and Shigemoto, Ryuichi and Fukuda, Atsuo and Nakahara, Daiichiro}, journal = {PLoS One}, number = {9}, publisher = {Public Library of Science}, title = {{Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice}}, doi = {10.1371/journal.pone.0107099}, volume = {9}, year = {2014}, } @article{1893, abstract = {Phosphatidylinositol (PtdIns) is a structural phospholipid that can be phosphorylated into various lipid signaling molecules, designated polyphosphoinositides (PPIs). The reversible phosphorylation of PPIs on the 3, 4, or 5 position of inositol is performed by a set of organelle-specific kinases and phosphatases, and the characteristic head groups make these molecules ideal for regulating biological processes in time and space. In yeast and mammals, PtdIns3P and PtdIns(3,5)P2 play crucial roles in trafficking toward the lytic compartments, whereas the role in plants is not yet fully understood. Here we identified the role of a land plant-specific subgroup of PPI phosphatases, the suppressor of actin 2 (SAC2) to SAC5, during vacuolar trafficking and morphogenesis in Arabidopsis thaliana. SAC2-SAC5 localize to the tonoplast along with PtdIns3P, the presumable product of their activity. In SAC gain- and loss-of-function mutants, the levels of PtdIns monophosphates and bisphosphates were changed, with opposite effects on the morphology of storage and lytic vacuoles, and the trafficking toward the vacuoles was defective. Moreover, multiple sac knockout mutants had an increased number of smaller storage and lytic vacuoles, whereas extralarge vacuoles were observed in the overexpression lines, correlating with various growth and developmental defects. The fragmented vacuolar phenotype of sac mutants could be mimicked by treating wild-type seedlings with PtdIns(3,5)P2, corroborating that this PPI is important for vacuole morphology. Taken together, these results provide evidence that PPIs, together with their metabolic enzymes SAC2-SAC5, are crucial for vacuolar trafficking and for vacuolar morphology and function in plants.}, author = {Nováková, Petra and Hirsch, Sibylle and Feraru, Elena and Tejos, Ricardo and Van Wijk, Ringo and Viaene, Tom and Heilmann, Mareike and Lerche, Jennifer and De Rycke, Riet and Feraru, Mugurel and Grones, Peter and Van Montagu, Marc and Heilmann, Ingo and Munnik, Teun and Friml, Jirí}, journal = {PNAS}, number = {7}, pages = {2818 -- 2823}, publisher = {National Academy of Sciences}, title = {{SAC phosphoinositide phosphatases at the tonoplast mediate vacuolar function in Arabidopsis}}, doi = {10.1073/pnas.1324264111}, volume = {111}, year = {2014}, } @article{1896, abstract = {Biopolymer length regulation is a complex process that involves a large number of biological, chemical, and physical subprocesses acting simultaneously across multiple spatial and temporal scales. An illustrative example important for genomic stability is the length regulation of telomeres - nucleoprotein structures at the ends of linear chromosomes consisting of tandemly repeated DNA sequences and a specialized set of proteins. Maintenance of telomeres is often facilitated by the enzyme telomerase but, particularly in telomerase-free systems, the maintenance of chromosomal termini depends on alternative lengthening of telomeres (ALT) mechanisms mediated by recombination. Various linear and circular DNA structures were identified to participate in ALT, however, dynamics of the whole process is still poorly understood. We propose a chemical kinetics model of ALT with kinetic rates systematically derived from the biophysics of DNA diffusion and looping. The reaction system is reduced to a coagulation-fragmentation system by quasi-steady-state approximation. The detailed treatment of kinetic rates yields explicit formulas for expected size distributions of telomeres that demonstrate the key role played by the J factor, a quantitative measure of bending of polymers. The results are in agreement with experimental data and point out interesting phenomena: an appearance of very long telomeric circles if the total telomere density exceeds a critical value (excess mass) and a nonlinear response of the telomere size distributions to the amount of telomeric DNA in the system. The results can be of general importance for understanding dynamics of telomeres in telomerase-independent systems as this mode of telomere maintenance is similar to the situation in tumor cells lacking telomerase activity. Furthermore, due to its universality, the model may also serve as a prototype of an interaction between linear and circular DNA structures in various settings.}, author = {Kollár, Richard and Bod'ová, Katarína and Nosek, Jozef and Tomáška, Ľubomír}, journal = {Physical Review E Statistical Nonlinear and Soft Matter Physics}, number = {3}, publisher = {American Institute of Physics}, title = {{Mathematical model of alternative mechanism of telomere length maintenance}}, doi = {10.1103/PhysRevE.89.032701}, volume = {89}, year = {2014}, } @article{1897, abstract = {GNOM is one of the most characterized membrane trafficking regulators in plants, with crucial roles in development. GNOM encodes an ARF-guanine nucleotide exchange factor (ARF-GEF) that activates small GTPases of the ARF (ADP ribosylation factor) class to mediate vesicle budding at endomembranes. The crucial role of GNOM in recycling of PIN auxin transporters and other proteins to the plasma membrane was identified in studies using the ARF-GEF inhibitor brefeldin A (BFA). GNOM, the most prominent regulator of recycling in plants, has been proposed to act and localize at so far elusive recycling endosomes. Here, we report the GNOM localization in context of its cellular function in Arabidopsis thaliana. State-of-the-art imaging, pharmacological interference, and ultrastructure analysis show that GNOM predominantly localizes to Golgi apparatus. Super-resolution confocal live imaging microscopy identified GNOM and its closest homolog GNOM-like 1 at distinct subdomains on Golgi cisternae. Short-term BFA treatment stabilizes GNOM at the Golgi apparatus, whereas prolonged exposures results in GNOM translocation to trans-Golgi network (TGN)/early endosomes (EEs). Malformed TGN/EE in gnom mutants suggests a role for GNOM in maintaining TGN/EE function. Our results redefine the subcellular action of GNOM and reevaluate the identity and function of recycling endosomes in plants.}, author = {Naramoto, Satoshi and Otegui, Marisa and Kutsuna, Natsumaro and De Rycke, Riet and Dainobu, Tomoko and Karampelias, Michael and Fujimoto, Masaru and Feraru, Elena and Miki, Daisuke and Fukuda, Hiroo and Nakano, Akihiko and Friml, Jirí}, journal = {Plant Cell}, number = {7}, pages = {3062 -- 3076}, publisher = {American Society of Plant Biologists}, title = {{Insights into the localization and function of the membrane trafficking regulator GNOM ARF-GEF at the Golgi apparatus in Arabidopsis}}, doi = {10.1105/tpc.114.125880}, volume = {26}, year = {2014}, } @article{1899, abstract = {Asymmetric cell divisions allow stem cells to balance proliferation and differentiation. During embryogenesis, murine epidermis expands rapidly from a single layer of unspecified basal layer progenitors to a stratified, differentiated epithelium. Morphogenesis involves perpendicular (asymmetric) divisions and the spindle orientation protein LGN, but little is known about how the apical localization of LGN is regulated. Here, we combine conventional genetics and lentiviral-mediated in vivo RNAi to explore the functions of the LGN-interacting proteins Par3, mInsc and Gα i3. Whereas loss of each gene alone leads to randomized division angles, combined loss of Gnai3 and mInsc causes a phenotype of mostly planar divisions, akin to loss of LGN. These findings lend experimental support for the hitherto untested model that Par3-mInsc and Gα i3 act cooperatively to polarize LGN and promote perpendicular divisions. Finally, we uncover a developmental switch between delamination-driven early stratification and spindle-orientation-dependent differentiation that occurs around E15, revealing a two-step mechanism underlying epidermal maturation.}, author = {Williams, Scott and Ratliff, Lyndsay and Postiglione, Maria P and Knoblich, Juergen and Fuchs, Elaine}, journal = {Nature Cell Biology}, number = {8}, pages = {758 -- 769}, publisher = {Nature Publishing Group}, title = {{Par3-mInsc and Gα i3 cooperate to promote oriented epidermal cell divisions through LGN}}, doi = {10.1038/ncb3001}, volume = {16}, year = {2014}, } @article{1898, abstract = {Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported invivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission upto ~1 kHz. Presynaptic APs are ultrafast, with ~100μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca2+ channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling.}, author = {Ritzau Jost, Andreas and Delvendahl, Igor and Rings, Annika and Byczkowicz, Niklas and Harada, Harumi and Shigemoto, Ryuichi and Hirrlinger, Johannes and Eilers, Jens and Hallermann, Stefan}, journal = {Neuron}, number = {1}, pages = {152 -- 163}, publisher = {Elsevier}, title = {{Ultrafast action potentials mediate kilohertz signaling at a central synapse}}, doi = {10.1016/j.neuron.2014.08.036}, volume = {84}, year = {2014}, } @article{1906, abstract = {In this paper, we introduce a novel scene representation for the visualization of large-scale point clouds accompanied by a set of high-resolution photographs. Many real-world applications deal with very densely sampled point-cloud data, which are augmented with photographs that often reveal lighting variations and inaccuracies in registration. Consequently, the high-quality representation of the captured data, i.e., both point clouds and photographs together, is a challenging and time-consuming task. We propose a two-phase approach, in which the first (preprocessing) phase generates multiple overlapping surface patches and handles the problem of seamless texture generation locally for each patch. The second phase stitches these patches at render-time to produce a high-quality visualization of the data. As a result of the proposed localization of the global texturing problem, our algorithm is more than an order of magnitude faster than equivalent mesh-based texturing techniques. Furthermore, since our preprocessing phase requires only a minor fraction of the whole data set at once, we provide maximum flexibility when dealing with growing data sets.}, author = {Arikan, Murat and Preiner, Reinhold and Scheiblauer, Claus and Jeschke, Stefan and Wimmer, Michael}, journal = {IEEE Transactions on Visualization and Computer Graphics}, number = {9}, pages = {1280 -- 1292}, publisher = {IEEE}, title = {{Large-scale point-cloud visualization through localized textured surface reconstruction}}, doi = {10.1109/TVCG.2014.2312011}, volume = {20}, year = {2014}, } @article{1905, abstract = {The unprecedented polymorphism in the major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection from parasites. However, do parasites also drive divergence at MHC loci between host populations, or do the effects of balancing selection maintain similarities among populations? We examined MHC variation in populations of the livebearing fish Poecilia mexicana and characterized their parasite communities. Poecilia mexicana populations in the Cueva del Azufre system are locally adapted to darkness and the presence of toxic hydrogen sulphide, representing highly divergent ecotypes or incipient species. Parasite communities differed significantly across populations, and populations with higher parasite loads had higher levels of diversity at class II MHC genes. However, despite different parasite communities, marked divergence in adaptive traits and in neutral genetic markers, we found MHC alleles to be remarkably similar among host populations. Our findings indicate that balancing selection from parasites maintains immunogenetic diversity of hosts, but this process does not promote MHC divergence in this system. On the contrary, we suggest that balancing selection on immunogenetic loci may outweigh divergent selection causing divergence, thereby hindering host divergence and speciation. Our findings support the hypothesis that balancing selection maintains MHC similarities among lineages during and after speciation (trans-species evolution).}, author = {Tobler, Michael and Plath, Martin and Riesch, Rüdiger and Schlupp, Ingo and Grasse, Anna V and Munimanda, Gopi and Setzer, C and Penn, Dustin and Moodley, Yoshan}, issn = {1420-9101}, journal = {Journal of Evolutionary Biology}, number = {5}, pages = {960 -- 974}, publisher = {Wiley}, title = {{Selection from parasites favours immunogenetic diversity but not divergence among locally adapted host populations}}, doi = {10.1111/jeb.12370}, volume = {27}, year = {2014}, } @article{1902, abstract = {In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux.We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates.}, author = {Hall, Barry and Acar, Hande and Nandipati, Anna and Barlow, Miriam}, issn = {1537-1719}, journal = {Molecular Biology and Evolution}, number = {1}, pages = {232 -- 238}, publisher = {Oxford University Press}, title = {{Growth rates made easy}}, doi = {10.1093/molbev/mst187}, volume = {31}, year = {2014}, } @article{1901, abstract = {In plants, the patterning of stem cell-enriched meristems requires a graded auxin response maximum that emerges from the concerted action of polar auxin transport, auxin biosynthesis, auxin metabolism, and cellular auxin response machinery. However, mechanisms underlying this auxin response maximum-mediated root stem cell maintenance are not fully understood. Here, we present unexpected evidence that WUSCHEL-RELATED HOMEOBOX 5 (WOX5) transcription factor modulates expression of auxin biosynthetic genes in the quiescent center (QC) of the root and thus provides a robust mechanism for the maintenance of auxin response maximum in the root tip. This WOX5 action is balanced through the activity of indole-3-acetic acid 17 (IAA17) auxin response repressor. Our combined genetic, cell biology, and computational modeling studies revealed a previously uncharacterized feedback loop linking WOX5-mediated auxin production to IAA17-dependent repression of auxin responses. This WOX5-IAA17 feedback circuit further assures the maintenance of auxin response maximum in the root tip and thereby contributes to the maintenance of distal stem cell (DSC) populations. Our experimental studies and in silico computer simulations both demonstrate that the WOX5-IAA17 feedback circuit is essential for the maintenance of auxin gradient in the root tip and the auxin-mediated root DSC differentiation.}, author = {Tian, Huiyu and Wabnik, Krzysztof T and Niu, Tiantian and Li, Hongjiang and Yu, Qianqian and Pollmann, Stephan and Vanneste, Steffen and Govaerts, Willy and Rolčík, Jakub and Geisler, Markus and Friml, Jirí and Ding, Zhaojun}, journal = {Molecular Plant}, number = {2}, pages = {277 -- 289}, publisher = {Oxford University Press}, title = {{WOX5-IAA17 feedback circuit-mediated cellular auxin response is crucial for the patterning of root stem cell niches in arabidopsis}}, doi = {10.1093/mp/sst118}, volume = {7}, year = {2014}, }