@article{1534, abstract = {PIN proteins are auxin export carriers that direct intercellular auxin flow and in turn regulate many aspects of plant growth and development including responses to environmental changes. The Arabidopsis R2R3-MYB transcription factor FOUR LIPS (FLP) and its paralogue MYB88 regulate terminal divisions during stomatal development, as well as female reproductive development and stress responses. Here we show that FLP and MYB88 act redundantly but differentially in regulating the transcription of PIN3 and PIN7 in gravity-sensing cells of primary and lateral roots. On the one hand, FLP is involved in responses to gravity stimulation in primary roots, whereas on the other, FLP and MYB88 function complementarily in establishing the gravitropic set-point angles of lateral roots. Our results support a model in which FLP and MYB88 expression specifically determines the temporal-spatial patterns of PIN3 and PIN7 transcription that are closely associated with their preferential functions during root responses to gravity.}, author = {Wang, Hongzhe and Yang, Kezhen and Zou, Junjie and Zhu, Lingling and Xie, Zidian and Morita, Miyoterao and Tasaka, Masao and Friml, Jirí and Grotewold, Erich and Beeckman, Tom and Vanneste, Steffen and Sack, Fred and Le, Jie}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Transcriptional regulation of PIN genes by FOUR LIPS and MYB88 during Arabidopsis root gravitropism}}, doi = {10.1038/ncomms9822}, volume = {6}, year = {2015}, } @article{1535, abstract = {Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuronlike” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress.}, author = {Vandael, David H and Marcantoni, Andrea and Carbone, Emilio}, journal = {Current Molecular Pharmacology}, number = {2}, pages = {149 -- 161}, publisher = {Bentham Science Publishers}, title = {{Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells}}, doi = {10.2174/1874467208666150507105443}, volume = {8}, year = {2015}, } @article{1536, abstract = {Strigolactones, first discovered as germination stimulants for parasitic weeds [1], are carotenoid-derived phytohormones that play major roles in inhibiting lateral bud outgrowth and promoting plant-mycorrhizal symbiosis [2-4]. Furthermore, strigolactones are involved in the regulation of lateral and adventitious root development, root cell division [5, 6], secondary growth [7], and leaf senescence [8]. Recently, we discovered the strigolactone transporter Petunia axillaris PLEIOTROPIC DRUG RESISTANCE 1 (PaPDR1), which is required for efficient mycorrhizal colonization and inhibition of lateral bud outgrowth [9]. However, how strigolactones are transported through the plant remained unknown. Here we show that PaPDR1 exhibits a cell-type-specific asymmetric localization in different root tissues. In root tips, PaPDR1 is co-expressed with the strigolactone biosynthetic gene DAD1 (CCD8), and it is localized at the apical membrane of root hypodermal cells, presumably mediating the shootward transport of strigolactone. Above the root tip, in the hypodermal passage cells that form gates for the entry of mycorrhizal fungi, PaPDR1 is present in the outer-lateral membrane, compatible with its postulated function as strigolactone exporter from root to soil. Transport studies are in line with our localization studies since (1) a papdr1 mutant displays impaired transport of strigolactones out of the root tip to the shoot as well as into the rhizosphere and (2) DAD1 expression and PIN1/PIN2 levels change in plants deregulated for PDR1 expression, suggestive of variations in endogenous strigolactone contents. In conclusion, our results indicate that the polar localizations of PaPDR1 mediate directional shootward strigolactone transport as well as localized exudation into the soil.}, author = {Sasse, Joëlle and Simon, Sibu and Gübeli, Christian and Liu, Guowei and Cheng, Xi and Friml, Jirí and Bouwmeester, Harro and Martinoia, Enrico and Borghi, Lorenzo}, journal = {Current Biology}, number = {5}, pages = {647 -- 655}, publisher = {Cell Press}, title = {{Asymmetric localizations of the ABC transporter PaPDR1 trace paths of directional strigolactone transport}}, doi = {10.1016/j.cub.2015.01.015}, volume = {25}, year = {2015}, } @article{1538, abstract = {Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time.}, author = {Ruess, Jakob and Parise, Francesca and Milias Argeitis, Andreas and Khammash, Mustafa and Lygeros, John}, journal = {PNAS}, number = {26}, pages = {8148 -- 8153}, publisher = {National Academy of Sciences}, title = {{Iterative experiment design guides the characterization of a light-inducible gene expression circuit}}, doi = {10.1073/pnas.1423947112}, volume = {112}, year = {2015}, } @article{1539, abstract = {Many stochastic models of biochemical reaction networks contain some chemical species for which the number of molecules that are present in the system can only be finite (for instance due to conservation laws), but also other species that can be present in arbitrarily large amounts. The prime example of such networks are models of gene expression, which typically contain a small and finite number of possible states for the promoter but an infinite number of possible states for the amount of mRNA and protein. One of the main approaches to analyze such models is through the use of equations for the time evolution of moments of the chemical species. Recently, a new approach based on conditional moments of the species with infinite state space given all the different possible states of the finite species has been proposed. It was argued that this approach allows one to capture more details about the full underlying probability distribution with a smaller number of equations. Here, I show that the result that less moments provide more information can only stem from an unnecessarily complicated description of the system in the classical formulation. The foundation of this argument will be the derivation of moment equations that describe the complete probability distribution over the finite state space but only low-order moments over the infinite state space. I will show that the number of equations that is needed is always less than what was previously claimed and always less than the number of conditional moment equations up to the same order. To support these arguments, a symbolic algorithm is provided that can be used to derive minimal systems of unconditional moment equations for models with partially finite state space. }, author = {Ruess, Jakob}, journal = {Journal of Chemical Physics}, number = {24}, publisher = {American Institute of Physics}, title = {{Minimal moment equations for stochastic models of biochemical reaction networks with partially finite state space}}, doi = {10.1063/1.4937937}, volume = {143}, year = {2015}, } @article{1540, abstract = {Plant sexual reproduction involves highly structured and specialized organs: stamens (male) and gynoecia (female, containing ovules). These organs synchronously develop within protective flower buds, until anthesis, via tightly coordinated mechanisms that are essential for effective fertilization and production of viable seeds. The phytohormone auxin is one of the key endogenous signalling molecules controlling initiation and development of these, and other, plant organs. In particular, its uneven distribution, resulting from tightly controlled production, metabolism and directional transport, is an important morphogenic factor. In this review we discuss how developmentally controlled and localized auxin biosynthesis and transport contribute to the coordinated development of plants' reproductive organs, and their fertilized derivatives (embryos) via the regulation of auxin levels and distribution within and around them. Current understanding of the links between de novo local auxin biosynthesis, auxin transport and/or signalling is presented to highlight the importance of the non-cell autonomous action of auxin production on development and morphogenesis of reproductive organs and embryos. An overview of transcription factor families, which spatiotemporally define local auxin production by controlling key auxin biosynthetic enzymes, is also presented.}, author = {Robert, Hélène and Crhák Khaitová, Lucie and Mroue, Souad and Benková, Eva}, journal = {Journal of Experimental Botany}, number = {16}, pages = {5029 -- 5042}, publisher = {Oxford University Press}, title = {{The importance of localized auxin production for morphogenesis of reproductive organs and embryos in Arabidopsis}}, doi = {10.1093/jxb/erv256}, volume = {66}, year = {2015}, } @inproceedings{1541, abstract = {We present XSpeed a parallel state-space exploration algorithm for continuous systems with linear dynamics and nondeterministic inputs. The motivation of having parallel algorithms is to exploit the computational power of multi-core processors to speed-up performance. The parallelization is achieved on two fronts. First, we propose a parallel implementation of the support function algorithm by sampling functions in parallel. Second, we propose a parallel state-space exploration by slicing the time horizon and computing the reachable states in the time slices in parallel. The second method can be however applied only to a class of linear systems with invertible dynamics and fixed input. A GP-GPU implementation is also presented following a lazy evaluation strategy on support functions. The parallel algorithms are implemented in the tool XSpeed. We evaluated the performance on two benchmarks including an 28 dimension Helicopter model. Comparison with the sequential counterpart shows a maximum speed-up of almost 7× on a 6 core, 12 thread Intel Xeon CPU E5-2420 processor. Our GP-GPU implementation shows a maximum speed-up of 12× over the sequential implementation and 53× over SpaceEx (LGG scenario), the state of the art tool for reachability analysis of linear hybrid systems. Experiments illustrate that our parallel algorithm with time slicing not only speeds-up performance but also improves precision.}, author = {Ray, Rajarshi and Gurung, Amit and Das, Binayak and Bartocci, Ezio and Bogomolov, Sergiy and Grosu, Radu}, location = {Haifa, Israel}, pages = {3 -- 18}, publisher = {Springer}, title = {{XSpeed: Accelerating reachability analysis on multi-core processors}}, doi = {10.1007/978-3-319-26287-1_1}, volume = {9434}, year = {2015}, } @article{1542, abstract = {The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. }, author = {Paixao, Tiago and Badkobeh, Golnaz and Barton, Nicholas H and Çörüş, Doğan and Dang, Duccuong and Friedrich, Tobias and Lehre, Per and Sudholt, Dirk and Sutton, Andrew and Trubenova, Barbora}, journal = { Journal of Theoretical Biology}, pages = {28 -- 43}, publisher = {Elsevier}, title = {{Toward a unifying framework for evolutionary processes}}, doi = {10.1016/j.jtbi.2015.07.011}, volume = {383}, year = {2015}, } @article{1543, abstract = {A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta.}, author = {Olvera Carrillo, Yadira and Van Bel, Michiel and Van Hautegem, Tom and Fendrych, Matyas and Huysmans, Marlies and Šimášková, Mária and Van Durme, Matthias and Buscaill, Pierre and Rivas, Susana and Coll, Núria and Coppens, Frederik and Maere, Steven and Nowack, Moritz}, journal = {Plant Physiology}, number = {4}, pages = {2684 -- 2699}, publisher = {American Society of Plant Biologists}, title = {{A conserved core of programmed cell death indicator genes discriminates developmentally and environmentally induced programmed cell death in plants}}, doi = {10.1104/pp.15.00769}, volume = {169}, year = {2015}, } @inbook{1544, abstract = {Cell division in prokaryotes and eukaryotes is commonly initiated by the well-controlled binding of proteins to the cytoplasmic side of the cell membrane. However, a precise characterization of the spatiotemporal dynamics of membrane-bound proteins is often difficult to achieve in vivo. Here, we present protocols for the use of supported lipid bilayers to rebuild the cytokinetic machineries of cells with greatly different dimensions: the bacterium Escherichia coli and eggs of the vertebrate Xenopus laevis. Combined with total internal reflection fluorescence microscopy, these experimental setups allow for precise quantitative analyses of membrane-bound proteins. The protocols described to obtain glass-supported membranes from bacterial and vertebrate lipids can be used as starting points for other reconstitution experiments. We believe that similar biochemical assays will be instrumental to study the biochemistry and biophysics underlying a variety of complex cellular tasks, such as signaling, vesicle trafficking, and cell motility.}, author = {Nguyen, Phuong and Field, Christine and Groen, Aaron and Mitchison, Timothy and Loose, Martin}, booktitle = {Building a Cell from its Components Parts}, pages = {223 -- 241}, publisher = {Academic Press}, title = {{Using supported bilayers to study the spatiotemporal organization of membrane-bound proteins}}, doi = {10.1016/bs.mcb.2015.01.007}, volume = {128}, year = {2015}, } @inproceedings{10748, abstract = {The study of fluxoid states and fluxoid dynamics in mesoscopic iron-based superconducting rings is valuable for characterizing the basic properties of the superconductor, and may also provide important insight into the superconducting paring symmetry. We report the fabrications of micron-sized rings and disks from thin films of Fe(Se, Te) grown by molecular beam epitaxy. In order to study fluxoid states in rings we developed a custom-tailored version of magnetic force microscopy (MFM). This technique has a number of qualitative advantages for working with mesoscopic superconducting samples in comparison to the conventional MFM and other imaging techniques. We observed metastable fluxoid states in rings of different sizes. Thermally activated fluxoid dynamics of these states was studied and modeled. In addition, we found different regimes of interaction between Fe(Se, Te) ring and MFM tip which are explained. Possibilities of the existence of exotic vortex states and proposals for experiments to test the symmetry of the superconducting order parameter in iron based superconductors are analyzed.}, author = {Polshyn, Hryhoriy and Zhang, Can and Naibert, Tyler and Eckstein, James and Budakian, Raffi}, booktitle = {APS March Meeting 2015}, issn = {0003-0503}, location = {San Antonio, TX, United States}, number = {1}, publisher = {American Physical Society}, title = {{Study of Fe (Se, Te) micron-sized rings by magnetic force microscopy}}, volume = {60}, year = {2015}, } @article{10794, abstract = {Mathematical models are of fundamental importance in the understanding of complex population dynamics. For instance, they can be used to predict the population evolution starting from different initial conditions or to test how a system responds to external perturbations. For this analysis to be meaningful in real applications, however, it is of paramount importance to choose an appropriate model structure and to infer the model parameters from measured data. While many parameter inference methods are available for models based on deterministic ordinary differential equations, the same does not hold for more detailed individual-based models. Here we consider, in particular, stochastic models in which the time evolution of the species abundances is described by a continuous-time Markov chain. These models are governed by a master equation that is typically difficult to solve. Consequently, traditional inference methods that rely on iterative evaluation of parameter likelihoods are computationally intractable. The aim of this paper is to present recent advances in parameter inference for continuous-time Markov chain models, based on a moment closure approximation of the parameter likelihood, and to investigate how these results can help in understanding, and ultimately controlling, complex systems in ecology. Specifically, we illustrate through an agricultural pest case study how parameters of a stochastic individual-based model can be identified from measured data and how the resulting model can be used to solve an optimal control problem in a stochastic setting. In particular, we show how the matter of determining the optimal combination of two different pest control methods can be formulated as a chance constrained optimization problem where the control action is modeled as a state reset, leading to a hybrid system formulation.}, author = {Parise, Francesca and Lygeros, John and Ruess, Jakob}, issn = {2296-665X}, journal = {Frontiers in Environmental Science}, keywords = {General Environmental Science}, publisher = {Frontiers}, title = {{Bayesian inference for stochastic individual-based models of ecological systems: a pest control simulation study}}, doi = {10.3389/fenvs.2015.00042}, volume = {3}, year = {2015}, } @inproceedings{10796, abstract = {We consider concurrent mean-payoff games, a very well-studied class of two-player (player 1 vs player 2) zero-sum games on finite-state graphs where every transition is assigned a reward between 0 and 1, and the payoff function is the long-run average of the rewards. The value is the maximal expected payoff that player 1 can guarantee against all strategies of player 2. We consider the computation of the set of states with value 1 under finite-memory strategies for player 1, and our main results for the problem are as follows: (1) we present a polynomial-time algorithm; (2) we show that whenever there is a finite-memory strategy, there is a stationary strategy that does not need memory at all; and (3) we present an optimal bound (which is double exponential) on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy).}, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus}, booktitle = {Proceedings of the Twenty-Sixth Annual ACM-SIAM Symposium on Discrete Algorithms}, isbn = {978-161197374-7}, location = {San Diego, CA, United States}, number = {1}, pages = {1018--1029}, publisher = {SIAM}, title = {{The value 1 problem under finite-memory strategies for concurrent mean-payoff games}}, doi = {10.1137/1.9781611973730.69}, volume = {2015}, year = {2015}, } @article{1106, abstract = {Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a β-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect.}, author = {Isrie, Mala and Breuss, Martin and Tian, Guoling and Hansen, Andi H and Cristofoli, Francesca and Morandell, Jasmin and Kupchinsky, Zachari A and Sifrim, Alejandro and Rodriguez Rodriguez, Celia and Dapena, Elena P and Doonanco, Kurston and Leonard, Norma and Tinsa, Faten and Moortgat, Stéphanie and Ulucan, Hakan and Koparir, Erkan and Karaca, Ender and Katsanis, Nicholas and Marton, Valeria and Vermeesch, Joris R and Davis, Erica E and Cowan, Nicholas J and Keays, David and Van Esch, Hilde}, journal = {The American Journal of Human Genetics}, number = {6}, pages = {790 -- 800}, publisher = {Cell Press}, title = {{Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type}}, doi = {10.1016/j.ajhg.2015.10.014}, volume = {97}, year = {2015}, } @article{11073, abstract = {Human cancer cells bear complex chromosome rearrangements that can be potential drivers of cancer development. However, the molecular mechanisms underlying these rearrangements have been unclear. Zhang et al. use a new technique combining live-cell imaging and single-cell sequencing to demonstrate that chromosomes mis-segregated to micronuclei frequently undergo chromothripsis-like rearrangements in the subsequent cell cycle.}, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {7}, pages = {1502--1504}, publisher = {Elsevier}, title = {{Linking micronuclei to chromosome fragmentation}}, doi = {10.1016/j.cell.2015.06.005}, volume = {161}, year = {2015}, } @article{11074, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {10}, pages = {PR397--R399}, publisher = {Elsevier}, title = {{Chromothripsis}}, doi = {10.1016/j.cub.2015.02.033}, volume = {25}, year = {2015}, } @article{11075, abstract = {Previously, we identified the nucleoporin gp210/Nup210 as a critical regulator of muscle and neuronal differentiation, but how this nucleoporin exerts its function and whether it modulates nuclear pore complex (NPC) activity remain unknown. Here, we show that gp210/Nup210 mediates muscle cell differentiation in vitro via its conserved N-terminal domain that extends into the perinuclear space. Removal of the C-terminal domain, which partially mislocalizes gp210/Nup210 away from NPCs, efficiently rescues the differentiation defect caused by the knockdown of endogenous gp210/Nup210. Unexpectedly, a gp210/Nup210 mutant lacking the NPC-targeting transmembrane and C-terminal domains is sufficient for C2C12 myoblast differentiation. We demonstrate that the endoplasmic reticulum (ER) stress-specific caspase cascade is exacerbated during Nup210 depletion and that blocking ER stress-mediated apoptosis rescues differentiation of Nup210-deficient cells. Our results suggest that the role of gp210/Nup210 in cell differentiation is mediated by its large luminal domain, which can act independently of NPC association and appears to play a pivotal role in the maintenance of nuclear envelope/ER homeostasis.}, author = {Gomez-Cavazos, J. Sebastian and HETZER, Martin W}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {6}, pages = {671--681}, publisher = {Rockefeller University Press}, title = {{The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis}}, doi = {10.1083/jcb.201410047}, volume = {208}, year = {2015}, } @article{11076, abstract = {Nuclear pore complexes (NPCs) are composed of several copies of ∼30 different proteins called nucleoporins (Nups). NPCs penetrate the nuclear envelope (NE) and regulate the nucleocytoplasmic trafficking of macromolecules. Beyond this vital role, NPC components influence genome functions in a transport-independent manner. Nups play an evolutionarily conserved role in gene expression regulation that, in metazoans, extends into the nuclear interior. Additionally, in proliferative cells, Nups play a crucial role in genome integrity maintenance and mitotic progression. Here we discuss genome-related functions of Nups and their impact on essential DNA metabolism processes such as transcription, chromosome duplication, and segregation.}, author = {Ibarra, Arkaitz and HETZER, Martin W}, issn = {1549-5477}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {4}, pages = {337--349}, publisher = {Cold Spring Harbor Laboratory}, title = {{Nuclear pore proteins and the control of genome functions}}, doi = {10.1101/gad.256495.114}, volume = {29}, year = {2015}, } @article{11077, abstract = {Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), membrane-embedded channels that mediate nuclear transport across the nuclear envelope. Recent evidence suggests that several Nups have additional roles in controlling the activation and silencing of developmental genes; however, the mechanistic details of these functions remain poorly understood. Here, we show that depletion of Nup153 in mouse embryonic stem cells (mESCs) causes the derepression of developmental genes and induction of early differentiation. This loss of stem cell identity is not associated with defects in the nuclear import of key pluripotency factors. Rather, Nup153 binds around the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb-repressive complex 1 (PRC1) to a subset of its target loci. Our results demonstrate a chromatin-associated role of Nup153 in maintaining stem cell pluripotency by functioning in mammalian epigenetic gene silencing.}, author = {Jacinto, Filipe V. and Benner, Chris and HETZER, Martin W}, issn = {1549-5477}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {12}, pages = {1224--1238}, publisher = {Cold Spring Harbor Laboratory}, title = {{The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing}}, doi = {10.1101/gad.260919.115}, volume = {29}, year = {2015}, } @article{11078, abstract = {Aging is associated with the decline of protein, cell, and organ function. Here, we use an integrated approach to characterize gene expression, bulk translation, and cell biology in the brains and livers of young and old rats. We identify 468 differences in protein abundance between young and old animals. The majority are a consequence of altered translation output, that is, the combined effect of changes in transcript abundance and translation efficiency. In addition, we identify 130 proteins whose overall abundance remains unchanged but whose sub-cellular localization, phosphorylation state, or splice-form varies. While some protein-level differences appear to be a generic property of the rats’ chronological age, the majority are specific to one organ. These may be a consequence of the organ’s physiology or the chronological age of the cells within the tissue. Taken together, our study provides an initial view of the proteome at the molecular, sub-cellular, and organ level in young and old rats.}, author = {Ori, Alessandro and Toyama, Brandon H. and Harris, Michael S. and Bock, Thomas and Iskar, Murat and Bork, Peer and Ingolia, Nicholas T. and HETZER, Martin W and Beck, Martin}, issn = {2405-4712}, journal = {Cell Systems}, keywords = {Cell Biology, Histology, Pathology and Forensic Medicine}, number = {3}, pages = {P224--237}, publisher = {Elsevier}, title = {{Integrated transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats}}, doi = {10.1016/j.cels.2015.08.012}, volume = {1}, year = {2015}, }