@article{1892, abstract = {Behavioural variation among conspecifics is typically contingent on individual state or environmental conditions. Sex-specific genetic polymorphisms are enigmatic because they lack conditionality, and genes causing adaptive trait variation in one sex may reduce Darwinian fitness in the other. One way to avoid such genetic antagonism is to control sex-specific traits by inheritance via sex chromosomes. Here, controlled laboratory crossings suggest that in snail-brooding cichlid fish a single locus, two-allele polymorphism located on a sex-linked chromosome of heterogametic males generates an extreme reproductive dimorphism. Both natural and sexual selection are responsible for exceptionally large body size of bourgeois males, creating a niche for a miniature male phenotype to evolve. This extreme intrasexual dimorphism results from selection on opposite size thresholds caused by a single ecological factor, empty snail shells used as breeding substrate. Paternity analyses reveal that in the field parasitic dwarf males sire the majority of offspring in direct sperm competition with large nest owners exceeding their size more than 40 times. Apparently, use of empty snail shells as breeding substrate and single locus sex-linked inheritance of growth are the major ecological and genetic mechanisms responsible for the extreme intrasexual diversity observed in Lamprologus callipterus.}, author = {Ocana, Sabine and Meidl, Patrick and Bonfils, Danielle and Taborsky, Michael}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1794}, publisher = {The Royal Society}, title = {{Y-linked Mendelian inheritance of giant and dwarf male morphs in shell-brooding cichlids}}, doi = {10.1098/rspb.2014.0253}, volume = {281}, year = {2014}, } @article{1891, abstract = {We provide theoretical tests of a novel experimental technique to determine mechanostability of proteins based on stretching a mechanically protected protein by single-molecule force spectroscopy. This technique involves stretching a homogeneous or heterogeneous chain of reference proteins (single-molecule markers) in which one of them acts as host to the guest protein under study. The guest protein is grafted into the host through genetic engineering. It is expected that unraveling of the host precedes the unraveling of the guest removing ambiguities in the reading of the force-extension patterns of the guest protein. We study examples of such systems within a coarse-grained structure-based model. We consider systems with various ratios of mechanostability for the host and guest molecules and compare them to experimental results involving cohesin I as the guest molecule. For a comparison, we also study the force-displacement patterns in proteins that are linked in a serial fashion. We find that the mechanostability of the guest is similar to that of the isolated or serially linked protein. We also demonstrate that the ideal configuration of this strategy would be one in which the host is much more mechanostable than the single-molecule markers. We finally show that it is troublesome to use the highly stable cystine knot proteins as a host to graft a guest in stretching studies because this would involve a cleaving procedure.}, author = {Chwastyk, Mateusz and Galera Prat, Albert and Sikora, Mateusz K and Gómez Sicilia, Àngel and Carrión Vázquez, Mariano and Cieplak, Marek}, journal = {Proteins: Structure, Function and Bioinformatics}, number = {5}, pages = {717 -- 726}, publisher = {Wiley-Blackwell}, title = {{Theoretical tests of the mechanical protection strategy in protein nanomechanics}}, doi = {10.1002/prot.24436}, volume = {82}, year = {2014}, } @article{1884, abstract = {Unbiased high-throughput massively parallel sequencing methods have transformed the process of discovery of novel putative driver gene mutations in cancer. In chronic lymphocytic leukemia (CLL), these methods have yielded several unexpected findings, including the driver genes SF3B1, NOTCH1 and POT1. Recent analysis, utilizing down-sampling of existing datasets, has shown that the discovery process of putative drivers is far from complete across cancer. In CLL, while driver gene mutations affecting >10% of patients were efficiently discovered with previously published CLL cohorts of up to 160 samples subjected to whole exome sequencing (WES), this sample size has only 0.78 power to detect drivers affecting 5% of patients, and only 0.12 power for drivers affecting 2% of patients. These calculations emphasize the need to apply unbiased WES to larger patient cohorts.}, author = {Landau, Dan and Stewart, Chip and Reiter, Johannes and Lawrence, Michael and Sougnez, Carrie and Brown, Jennifer and Lopez Guillermo, Armando and Gabriel, Stacey and Lander, Eric and Neuberg, Donna and López Otín, Carlos and Campo, Elias and Getz, Gad and Wu, Catherine}, journal = {Blood}, number = {21}, pages = {1952 -- 1952}, publisher = {American Society of Hematology}, title = {{Novel putative driver gene mutations in chronic lymphocytic leukemia (CLL): results from a combined analysis of whole exome sequencing of 262 primary CLL aamples}}, volume = {124}, year = {2014}, } @article{1889, abstract = {We study translation-invariant quasi-free states for a system of fermions with two-particle interactions. The associated energy functional is similar to the BCS functional but also includes direct and exchange energies. We show that for suitable short-range interactions, these latter terms only lead to a renormalization of the chemical potential, with the usual properties of the BCS functional left unchanged. Our analysis thus represents a rigorous justification of part of the BCS approximation. We give bounds on the critical temperature below which the system displays superfluidity.}, author = {Bräunlich, Gerhard and Hainzl, Christian and Seiringer, Robert}, journal = {Reviews in Mathematical Physics}, number = {7}, publisher = {World Scientific Publishing}, title = {{Translation-invariant quasi-free states for fermionic systems and the BCS approximation}}, doi = {10.1142/S0129055X14500123}, volume = {26}, year = {2014}, } @article{1894, abstract = {Background: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute the considerable insight to the Epsilonproteobacterial Dsb systems, which have been poorly understood so far.}, author = {Grabowska, Anna and Wywiał, Ewa and Dunin Horkawicz, Stanislaw and Łasica, Anna and Wösten, Marc and Nagy-Staron, Anna A and Godlewska, Renata and Bocian Ostrzycka, Katarzyna and Pieńkowska, Katarzyna and Łaniewski, Paweł and Bujnicki, Janusz and Van Putten, Jos and Jagusztyn Krynicka, Elzbieta}, journal = {PLoS One}, number = {9}, publisher = {Public Library of Science}, title = {{Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA}}, doi = {10.1371/journal.pone.0106247}, volume = {9}, year = {2014}, } @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}, }