@article{1908, abstract = {In large populations, multiple beneficial mutations may be simultaneously spreading. In asexual populations, these mutations must either arise on the same background or compete against each other. In sexual populations, recombination can bring together beneficial alleles from different backgrounds, but tightly linked alleles may still greatly interfere with each other. We show for well-mixed populations that when this interference is strong, the genome can be seen as consisting of many effectively asexual stretches linked together. The rate at which beneficial alleles fix is thus roughly proportional to the rate of recombination and depends only logarithmically on the mutation supply and the strength of selection. Our scaling arguments also allow us to predict, with reasonable accuracy, the fitness distribution of fixed mutations when the mutational effect sizes are broad. We focus on the regime in which crossovers occur more frequently than beneficial mutations, as is likely to be the case for many natural populations.}, author = {Weissman, Daniel and Hallatschek, Oskar}, journal = {Genetics}, number = {4}, pages = {1167 -- 1183}, publisher = {Genetics Society of America}, title = {{The rate of adaptation in large sexual populations with linear chromosomes}}, doi = {10.1534/genetics.113.160705}, volume = {196}, year = {2014}, } @article{1911, abstract = {The topological Tverberg theorem has been generalized in several directions by setting extra restrictions on the Tverberg partitions. Restricted Tverberg partitions, defined by the idea that certain points cannot be in the same part, are encoded with graphs. When two points are adjacent in the graph, they are not in the same part. If the restrictions are too harsh, then the topological Tverberg theorem fails. The colored Tverberg theorem corresponds to graphs constructed as disjoint unions of small complete graphs. Hell studied the case of paths and cycles. In graph theory these partitions are usually viewed as graph colorings. As explored by Aharoni, Haxell, Meshulam and others there are fundamental connections between several notions of graph colorings and topological combinatorics. For ordinary graph colorings it is enough to require that the number of colors q satisfy q>Δ, where Δ is the maximal degree of the graph. It was proven by the first author using equivariant topology that if q>Δ 2 then the topological Tverberg theorem still works. It is conjectured that q>KΔ is also enough for some constant K, and in this paper we prove a fixed-parameter version of that conjecture. The required topological connectivity results are proven with shellability, which also strengthens some previous partial results where the topological connectivity was proven with the nerve lemma.}, author = {Engström, Alexander and Noren, Patrik}, journal = {Discrete & Computational Geometry}, number = {1}, pages = {207 -- 220}, publisher = {Springer}, title = {{Tverberg's Theorem and Graph Coloring}}, doi = {10.1007/s00454-013-9556-3}, volume = {51}, year = {2014}, } @article{1916, abstract = {Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.}, author = {Novarino, Gaia and Fenstermaker, Ali and Zaki, Maha and Hofree, Matan and Silhavy, Jennifer and Heiberg, Andrew and Abdellateef, Mostafa and Rosti, Başak and Scott, Eric and Mansour, Lobna and Masri, Amira and Kayserili, Hülya and Al Aama, Jumana and Abdel Salam, Ghada and Karminejad, Ariana and Kara, Majdi and Kara, Bülent and Bozorgmehri, Bita and Ben Omran, Tawfeg and Mojahedi, Faezeh and Mahmoud, Iman and Bouslam, Naïma and Bouhouche, Ahmed and Benomar, Ali and Hanein, Sylvain and Raymond, Laure and Forlani, Sylvie and Mascaro, Massimo and Selim, Laila and Shehata, Nabil and Al Allawi, Nasir and Bindu, Parayil and Azam, Matloob and Günel, Murat and Caglayan, Ahmet and Bilgüvar, Kaya and Tolun, Aslihan and Issa, Mahmoud and Schroth, Jana and Spencer, Emily and Rosti, Rasim and Akizu, Naiara and Vaux, Keith and Johansen, Anide and Koh, Alice and Megahed, Hisham and Dürr, Alexandra and Brice, Alexis and Stévanin, Giovanni and Gabriel, Stacy and Ideker, Trey and Gleeson, Joseph}, journal = {Science}, number = {6170}, pages = {506 -- 511}, publisher = {American Association for the Advancement of Science}, title = {{Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders}}, doi = {10.1126/science.1247363}, volume = {343}, year = {2014}, } @article{1917, abstract = {Auxin-binding protein 1 (ABP1) was discovered nearly 40 years ago and was shown to be essential for plant development and morphogenesis, but its mode of action remains unclear. Here, we report that the plasma membrane-localized transmembrane kinase (TMK) receptor-like kinases interact with ABP1 and transduce auxin signal to activate plasma membrane-associated ROPs [Rho-like guanosine triphosphatases (GTPase) from plants], leading to changes in the cytoskeleton and the shape of leaf pavement cells in Arabidopsis. The interaction between ABP1 and TMK at the cell surface is induced by auxin and requires ABP1 sensing of auxin. These findings show that TMK proteins and ABP1 form a cell surface auxin perception complex that activates ROP signaling pathways, regulating nontranscriptional cytoplasmic responses and associated fundamental processes.}, author = {Xu, Tongda and Dai, Ning and Chen, Jisheng and Nagawa, Shingo and Cao, Min and Li, Hongjiang and Zhou, Zimin and Chen, Xu and De Rycke, Riet and Rakusová, Hana and Wang, Wen and Jones, Alan and Friml, Jirí and Patterson, Sara and Bleecker, Anthony and Yang, Zhenbiao}, journal = {Science}, number = {6174}, pages = {1025 -- 1028}, publisher = {American Association for the Advancement of Science}, title = {{Cell surface ABP1-TMK auxin sensing complex activates ROP GTPase signaling}}, doi = {10.1126/science.1245125}, volume = {343}, year = {2014}, } @article{1920, abstract = {Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-termadaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation.}, author = {Wang, Wen and Nakadate, Kazuhiko and Masugi Tokita, Miwako and Shutoh, Fumihiro and Aziz, Wajeeha and Tarusawa, Etsuko and Lörincz, Andrea and Molnár, Elek and Kesaf, Sebnem and Li, Yunqing and Fukazawa, Yugo and Nagao, Soichi and Shigemoto, Ryuichi}, journal = {PNAS}, number = {1}, pages = {E188 -- E193}, publisher = {National Academy of Sciences}, title = {{Distinct cerebellar engrams in short-term and long-term motor learning}}, doi = {10.1073/pnas.1315541111}, volume = {111}, year = {2014}, } @article{1915, abstract = {ROPs (Rho of plants) belong to a large family of plant-specific Rho-like small GTPases that function as essential molecular switches to control diverse cellular processes including cytoskeleton organization, cell polarization, cytokinesis, cell differentiation and vesicle trafficking. Although the machineries of vesicle trafficking and cell polarity in plants have been individually well addressed, how ROPs co-ordinate those processes is still largely unclear. Recent progress has been made towards an understanding of the coordination of ROP signalling and trafficking of PIN (PINFORMED) transporters for the plant hormone auxin in both root and leaf pavement cells. PIN transporters constantly shuttle between the endosomal compartments and the polar plasma membrane domains, therefore the modulation of PIN-dependent auxin transport between cells is a main developmental output of ROP-regulated vesicle trafficking. The present review focuses on these cellular mechanisms, especially the integration of ROP-based vesicle trafficking and plant cell polarity.}, author = {Chen, Xu and Friml, Jirí}, issn = {1470-8752}, journal = {Biochemical Society Transactions}, number = {1}, pages = {212 -- 218}, publisher = {Portland Press}, title = {{Rho-GTPase-regulated vesicle trafficking in plant cell polarity}}, doi = {10.1042/BST20130269}, volume = {42}, year = {2014}, } @article{1919, abstract = {Long-lasting memories are formed when the stimulus is temporally distributed (spacing effect). However, the synaptic mechanisms underlying this robust phenomenon and the precise time course of the synaptic modifications that occur during learning remain unclear. Here we examined the adaptation of horizontal optokinetic response in mice that underwent 1 h of massed and spaced training at varying intervals. Despite similar acquisition by all training protocols, 1 h of spacing produced the highest memory retention at 24 h, which lasted for 1 mo. The distinct kinetics of memory are strongly correlated with the reduction of floccular parallel fiber-Purkinje cell synapses but not with AMPA receptor (AMPAR) number and synapse size. After the spaced training, we observed 25%, 23%, and 12% reduction in AMPAR density, synapse size, and synapse number, respectively. Four hours after the spaced training, half of the synapses and Purkinje cell spines had been eliminated, whereas AMPAR density and synapse size were recovered in remaining synapses. Surprisingly, massed training also produced long-term memory and halving of synapses; however, this occurred slowly over days, and the memory lasted for only 1 wk. This distinct kinetics of structural plasticity may serve as a basis for unique temporal profiles in the formation and decay of memory with or without intervals.}, author = {Aziz, Wajeeha and Wang, Wen and Kesaf, Sebnem and Mohamed, Alsayed and Fukazawa, Yugo and Shigemoto, Ryuichi}, journal = {PNAS}, number = {1}, pages = {E194 -- E202}, publisher = {National Academy of Sciences}, title = {{Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning}}, doi = {10.1073/pnas.1303317110}, volume = {111}, year = {2014}, } @article{1918, abstract = {As the nuclear charge Z is continuously decreased an N-electron atom undergoes a binding-unbinding transition. We investigate whether the electrons remain bound and whether the radius of the system stays finite as the critical value Zc is approached. Existence of a ground state at Zc is shown under the condition Zc < N-K, where K is the maximal number of electrons that can be removed at Zc without changing the energy.}, author = {Bellazzini, Jacopo and Frank, Rupert and Lieb, Élliott and Seiringer, Robert}, journal = {Reviews in Mathematical Physics}, number = {1}, publisher = {World Scientific Publishing}, title = {{Existence of ground states for negative ions at the binding threshold}}, doi = {10.1142/S0129055X13500219}, volume = {26}, year = {2014}, } @article{1914, abstract = {Targeting membrane proteins for degradation requires the sequential action of ESCRT sub-complexes ESCRT-0 to ESCRT-III. Although this machinery is generally conserved among kingdoms, plants lack the essential ESCRT-0 components. A new report closes this gap by identifying a novel protein family that substitutes for ESCRT-0 function in plants.}, author = {Sauer, Michael and Friml, Jirí}, journal = {Current Biology}, number = {1}, pages = {R27 -- R29}, publisher = {Cell Press}, title = {{Plant biology: Gatekeepers of the road to protein perdition}}, doi = {10.1016/j.cub.2013.11.019}, volume = {24}, year = {2014}, } @article{1925, abstract = {In the past decade carbon nanotubes (CNTs) have been widely studied as a potential drug-delivery system, especially with functionality for cellular targeting. Yet, little is known about the actual process of docking to cell receptors and transport dynamics after internalization. Here we performed single-particle studies of folic acid (FA) mediated CNT binding to human carcinoma cells and their transport inside the cytosol. In particular, we employed molecular recognition force spectroscopy, an atomic force microscopy based method, to visualize and quantify docking of FA functionalized CNTs to FA binding receptors in terms of binding probability and binding force. We then traced individual fluorescently labeled, FA functionalized CNTs after specific uptake, and created a dynamic 'roadmap' that clearly showed trajectories of directed diffusion and areas of nanotube confinement in the cytosol. Our results demonstrate the potential of a single-molecule approach for investigation of drug-delivery vehicles and their targeting capacity.}, author = {Lamprecht, Constanze and Plochberger, Birgit and Ruprecht, Verena and Wieser, Stefan and Rankl, Christian and Heister, Elena and Unterauer, Barbara and Brameshuber, Mario and Danzberger, Jürgen and Lukanov, Petar and Flahaut, Emmanuel and Schütz, Gerhard and Hinterdorfer, Peter and Ebner, Andreas}, journal = {Nanotechnology}, number = {12}, publisher = {IOP Publishing}, title = {{A single-molecule approach to explore binding uptake and transport of cancer cell targeting nanotubes}}, doi = {10.1088/0957-4484/25/12/125704}, volume = {25}, year = {2014}, }