@article{7026, abstract = {Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90% of the variation in cellular response can be decomposed into three principal components (PCs) that have clear biological interpretations. We demonstrate that the third PC captures emergent transcriptional programs that are dependent on both drugs and can predict antagonism with a third drug targeting the emergent pathway. We further show that emergent gene expression patterns are most pronounced at a drug ratio where the drug interaction is strongest, providing a guideline for future measurements. Our results provide a readily applicable recipe for uncovering emergent responses in other systems and for higher-order drug combinations. A record of this paper’s transparent peer review process is included in the Supplemental Information.}, author = {Lukacisin, Martin and Bollenbach, Tobias}, issn = {2405-4712}, journal = {Cell Systems}, number = {5}, pages = {423--433.e1--e3}, publisher = {Cell Press}, title = {{Emergent gene expression responses to drug combinations predict higher-order drug interactions}}, doi = {10.1016/j.cels.2019.10.004}, volume = {9}, year = {2019}, } @article{7034, abstract = {We find a graph of genus 5 and its drawing on the orientable surface of genus 4 with every pair of independent edges crossing an even number of times. This shows that the strong Hanani–Tutte theorem cannot be extended to the orientable surface of genus 4. As a base step in the construction we use a counterexample to an extension of the unified Hanani–Tutte theorem on the torus.}, author = {Fulek, Radoslav and Kynčl, Jan}, issn = {1439-6912}, journal = {Combinatorica}, number = {6}, pages = {1267--1279}, publisher = {Springer Nature}, title = {{Counterexample to an extension of the Hanani-Tutte theorem on the surface of genus 4}}, doi = {10.1007/s00493-019-3905-7}, volume = {39}, year = {2019}, } @inproceedings{7032, abstract = {Optical frequency combs (OFCs) are light sources whose spectra consists of equally spaced frequency lines in the optical domain [1]. They have great potential for improving high-capacity data transfer, all-optical atomic clocks, spectroscopy, and high-precision measurements [2].}, author = {Rueda Sanchez, Alfredo R and Sedlmeir, Florian and Leuchs, Gerd and Kuamri, Madhuri and Schwefel, Harald G. L.}, booktitle = {2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference}, isbn = {9781728104690}, location = {Munich, Germany}, publisher = {IEEE}, title = {{Electro-optic frequency comb generation in lithium niobate whispering gallery mode resonators}}, doi = {10.1109/cleoe-eqec.2019.8873300}, year = {2019}, } @article{7095, abstract = {BAX, a member of the BCL2 gene family, controls the committed step of the intrinsic apoptotic program. Mitochondrial fragmentation is a commonly observed feature of apoptosis, which occurs through the process of mitochondrial fission. BAX has consistently been associated with mitochondrial fission, yet how BAX participates in the process of mitochondrial fragmentation during apoptosis remains to be tested. Time-lapse imaging of BAX recruitment and mitochondrial fragmentation demonstrates that rapid mitochondrial fragmentation during apoptosis occurs after the complete recruitment of BAX to the mitochondrial outer membrane (MOM). The requirement of a fully functioning BAX protein for the fission process was demonstrated further in BAX/BAK-deficient HCT116 cells expressing a P168A mutant of BAX. The mutant performed fusion to restore the mitochondrial network. but was not demonstrably recruited to the MOM after apoptosis induction. Under these conditions, mitochondrial fragmentation was blocked. Additionally, we show that loss of the fission protein, dynamin-like protein 1 (DRP1), does not temporally affect the initiation time or rate of BAX recruitment, but does reduce the final level of BAX recruited to the MOM during the late phase of BAX recruitment. These correlative observations suggest a model where late-stage BAX oligomers play a functional part of the mitochondrial fragmentation machinery in apoptotic cells.}, author = {Maes, Margaret E and Grosser, J. A. and Fehrman, R. L. and Schlamp, C. L. and Nickells, R. W.}, issn = {2045-2322}, journal = {Scientific Reports}, publisher = {Springer Nature}, title = {{Completion of BAX recruitment correlates with mitochondrial fission during apoptosis}}, doi = {10.1038/s41598-019-53049-w}, volume = {9}, year = {2019}, } @article{7097, abstract = {Early endosomes, also called sorting endosomes, are known to mature into late endosomesvia the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence isthought to be maintained by the continual fusion of transport vesicles from the plasmamembrane and thetrans-Golgi network (TGN). Here we show instead that endocytosis isdispensable and post-Golgi vesicle transport is crucial for the formation of endosomes andthe subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all threeproteins required for endosomal nucleotide exchange on Vps21p arefirst recruited to theTGN before transport to the endosome, namely the GEF Vps9p and the epsin-relatedadaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, withVps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These resultsprovide a different view of endosome formation and identify the TGN as a critical location forregulating progress through the endolysosomal trafficking pathway.}, author = {Nagano, Makoto and Toshima, Junko Y. and Siekhaus, Daria E and Toshima, Jiro}, issn = {2399-3642}, journal = {Communications Biology}, number = {1}, publisher = {Springer Nature}, title = {{Rab5-mediated endosome formation is regulated at the trans-Golgi network}}, doi = {10.1038/s42003-019-0670-5}, volume = {2}, year = {2019}, } @article{7099, author = {Kasugai, Yu and Vogel, Elisabeth and Hörtnagl, Heide and Schönherr, Sabine and Paradiso, Enrica and Hauschild, Markus and Göbel, Georg and Milenkovic, Ivan and Peterschmitt, Yvan and Tasan, Ramon and Sperk, Günther and Shigemoto, Ryuichi and Sieghart, Werner and Singewald, Nicolas and Lüthi, Andreas and Ferraguti, Francesco}, issn = {0896-6273}, journal = {Neuron}, number = {4}, pages = {781--794.e4}, publisher = {Elsevier}, title = {{Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning}}, doi = {10.1016/j.neuron.2019.08.013}, volume = {104}, year = {2019}, } @article{6455, abstract = {During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells are molecularly temporally patterned is poorly understood. We used single-cell RNA sequencing at high temporal resolution to trace the lineage of the molecular identities of successive generations of apical progenitors (APs) and their daughter neurons in mouse embryos. We identified a core set of evolutionarily conserved, temporally patterned genes that drive APs from internally driven to more exteroceptive states. We found that the Polycomb repressor complex 2 (PRC2) epigenetically regulates AP temporal progression. Embryonic age–dependent AP molecular states are transmitted to their progeny as successive ground states, onto which essentially conserved early postmitotic differentiation programs are applied, and are complemented by later-occurring environment-dependent signals. Thus, epigenetically regulated temporal molecular birthmarks present in progenitors act in their postmitotic progeny to seed adult neuronal diversity.}, author = {Telley, L and Agirman, G and Prados, J and Amberg, Nicole and Fièvre, S and Oberst, P and Bartolini, G and Vitali, I and Cadilhac, C and Hippenmeyer, Simon and Nguyen, L and Dayer, A and Jabaudon, D}, issn = {1095-9203}, journal = {Science}, number = {6440}, publisher = {AAAS}, title = {{Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex}}, doi = {10.1126/science.aav2522}, volume = {364}, year = {2019}, } @article{6586, abstract = {The bottom-up assembly of colloidal nanocrystals is a versatile methodology to produce composite nanomaterials with precisely tuned electronic properties. Beyond the synthetic control over crystal domain size, shape, crystal phase, and composition, solution-processed nanocrystals allow exquisite surface engineering. This provides additional means to modulate the nanomaterial characteristics and particularly its electronic transport properties. For instance, inorganic surface ligands can be used to tune the type and concentration of majority carriers or to modify the electronic band structure. Herein, we report the thermoelectric properties of SnTe nanocomposites obtained from the consolidation of surface-engineered SnTe nanocrystals into macroscopic pellets. A CdSe-based ligand is selected to (i) converge the light and heavy bands through partial Cd alloying and (ii) generate CdSe nanoinclusions as a secondary phase within the SnTe matrix, thereby reducing the thermal conductivity. These SnTe-CdSe nanocomposites possess thermoelectric figures of merit of up to 1.3 at 850 K, which is, to the best of our knowledge, the highest thermoelectric figure of merit reported for solution-processed SnTe.}, author = {Ibáñez, Maria and Hasler, Roger and Genç, Aziz and Liu, Yu and Kuster, Beatrice and Schuster, Maximilian and Dobrozhan, Oleksandr and Cadavid, Doris and Arbiol, Jordi and Cabot, Andreu and Kovalenko, Maksym V.}, issn = {1520-5126}, journal = {Journal of the American Chemical Society}, number = {20}, pages = {8025--8029}, publisher = {American Chemical Society}, title = {{Ligand-mediated band engineering in bottom-up assembled SnTe nanocomposites for thermoelectric energy conversion}}, doi = {10.1021/jacs.9b01394}, volume = {141}, year = {2019}, } @article{6174, abstract = {We propose a scaling theory for the many-body localization (MBL) phase transition in one dimension, building on the idea that it proceeds via a “quantum avalanche.” We argue that the critical properties can be captured at a coarse-grained level by a Kosterlitz-Thouless (KT) renormalization group (RG) flow. On phenomenological grounds, we identify the scaling variables as the density of thermal regions and the length scale that controls the decay of typical matrix elements. Within this KT picture, the MBL phase is a line of fixed points that terminates at the delocalization transition. We discuss two possible scenarios distinguished by the distribution of rare, fractal thermal inclusions within the MBL phase. In the first scenario, these regions have a stretched exponential distribution in the MBL phase. In the second scenario, the near-critical MBL phase hosts rare thermal regions that are power-law-distributed in size. This points to the existence of a second transition within the MBL phase, at which these power laws change to the stretched exponential form expected at strong disorder. We numerically simulate two different phenomenological RGs previously proposed to describe the MBL transition. Both RGs display a universal power-law length distribution of thermal regions at the transition with a critical exponent αc=2, and continuously varying exponents in the MBL phase consistent with the KT picture.}, author = {Dumitrescu, Philipp T. and Goremykina, Anna and Parameswaran, Siddharth A. and Serbyn, Maksym and Vasseur, Romain}, issn = {2469-9969}, journal = {Physical Review B}, number = {9}, publisher = {American Physical Society}, title = {{Kosterlitz-Thouless scaling at many-body localization phase transitions}}, doi = {10.1103/physrevb.99.094205}, volume = {99}, year = {2019}, } @article{6366, abstract = {Plants have a remarkable capacity to adjust their growth and development to elevated ambient temperatures. Increased elongation growth of roots, hypocotyls and petioles in warm temperatures are hallmarks of seedling thermomorphogenesis. In the last decade, significant progress has been made to identify the molecular signaling components regulating these growth responses. Increased ambient temperature utilizes diverse components of the light sensing and signal transduction network to trigger growth adjustments. However, it remains unknown whether temperature sensing and responses are universal processes that occur uniformly in all plant organs. Alternatively, temperature sensing may be confined to specific tissues or organs, which would require a systemic signal that mediates responses in distal parts of the plant. Here we show that Arabidopsis (Arabidopsis thaliana) seedlings show organ-specific transcriptome responses to elevated temperatures, and that thermomorphogenesis involves both autonomous and organ-interdependent temperature sensing and signaling. Seedling roots can sense and respond to temperature in a shoot-independent manner, whereas shoot temperature responses require both local and systemic processes. The induction of cell elongation in hypocotyls requires temperature sensing in cotyledons, followed by generation of a mobile auxin signal. Subsequently, auxin travels to the hypocotyl where it triggers local brassinosteroid-induced cell elongation in seedling stems, which depends upon a distinct, permissive temperature sensor in the hypocotyl.}, author = {Bellstaedt, Julia and Trenner, Jana and Lippmann, Rebecca and Poeschl, Yvonne and Zhang, Xixi and Friml, Jiří and Quint, Marcel and Delker, Carolin}, issn = {1532-2548}, journal = {Plant Physiology}, number = {2}, pages = {757--766}, publisher = {ASPB}, title = {{A mobile auxin signal connects temperature sensing in cotyledons with growth responses in hypocotyls}}, doi = {10.1104/pp.18.01377}, volume = {180}, year = {2019}, }