@article{6504, abstract = {Root gravitropism is one of the most important processes allowing plant adaptation to the land environment. Auxin plays a central role in mediating root gravitropism, but how auxin contributes to gravitational perception and the subsequent response is still unclear. Here, we showed that the local auxin maximum/gradient within the root apex, which is generated by the PIN directional auxin transporters, regulates the expression of three key starch granule synthesis genes, SS4, PGM and ADG1, which in turn influence the accumulation of starch granules that serve as a statolith perceiving gravity. Moreover, using the cvxIAA‐ccvTIR1 system, we also showed that TIR1‐mediated auxin signaling is required for starch granule formation and gravitropic response within root tips. In addition, axr3 mutants showed reduced auxin‐mediated starch granule accumulation and disruption of gravitropism within the root apex. Our results indicate that auxin‐mediated statolith production relies on the TIR1/AFB‐AXR3‐mediated auxin signaling pathway. In summary, we propose a dual role for auxin in gravitropism: the regulation of both gravity perception and response.}, author = {Zhang, Yuzhou and He, P and Ma, X and Yang, Z and Pang, C and Yu, J and Wang, G and Friml, Jiří and Xiao, G}, issn = {1469-8137}, journal = {New Phytologist}, number = {2}, pages = {761--774}, publisher = {Wiley}, title = {{Auxin-mediated statolith production for root gravitropism}}, doi = {10.1111/nph.15932}, volume = {224}, year = {2019}, } @article{6506, abstract = {How does environmental complexity affect the evolution of single genes? Here, we measured the effects of a set of Bacillus subtilis glutamate dehydrogenase mutants across 19 different environments—from phenotypically homogeneous single-cell populations in liquid media to heterogeneous biofilms, plant roots and soil populations. The effects of individual gene mutations on organismal fitness were highly reproducible in liquid cultures. However, 84% of the tested alleles showed opposing fitness effects under different growth conditions (sign environmental pleiotropy). In colony biofilms and soil samples, different alleles dominated in parallel replica experiments. Accordingly, we found that in these heterogeneous cell populations the fate of mutations was dictated by a combination of selection and drift. The latter relates to programmed prophage excisions that occurred during biofilm development. Overall, for each condition, a wide range of glutamate dehydrogenase mutations persisted and sometimes fixated as a result of the combined action of selection, pleiotropy and chance. However, over longer periods and in multiple environments, nearly all of this diversity would be lost—across all the environments and conditions that we tested, the wild type was the fittest allele.}, author = {Noda-García, Lianet and Davidi, Dan and Korenblum, Elisa and Elazar, Assaf and Putintseva, Ekaterina and Aharoni, Asaph and Tawfik, Dan S.}, issn = {2058-5276}, journal = {Nature Microbiology}, number = {7}, pages = {1221–1230}, publisher = {Springer Nature}, title = {{Chance and pleiotropy dominate genetic diversity in complex bacterial environments}}, doi = {10.1038/s41564-019-0412-y}, volume = {4}, year = {2019}, } @article{6521, abstract = {Microglia have emerged as a critical component of neurodegenerative diseases. Genetic manipulation of microglia can elucidate their functional impact in disease. In neuroscience, recombinant viruses such as lentiviruses and adeno-associated viruses (AAVs) have been successfully used to target various cell types in the brain, although effective transduction of microglia is rare. In this review, we provide a short background of lentiviruses and AAVs, and strategies for designing recombinant viral vectors. Then, we will summarize recent literature on successful microglial transductions in vitro and in vivo, and discuss the current challenges. Finally, we provide guidelines for reporting the efficiency and specificity of viral targeting in microglia, which will enable the microglial research community to assess and improve methodologies for future studies.}, author = {Maes, Margaret E and Colombo, Gloria and Schulz, Rouven and Siegert, Sandra}, issn = {0304-3940}, journal = {Neuroscience Letters}, publisher = {Elsevier}, title = {{Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges}}, doi = {10.1016/j.neulet.2019.134310}, volume = {707}, year = {2019}, } @article{6513, abstract = {Adult intestinal stem cells are located at the bottom of crypts of Lieberkühn, where they express markers such as LGR5 1,2 and fuel the constant replenishment of the intestinal epithelium1. Although fetal LGR5-expressing cells can give rise to adult intestinal stem cells3,4, it remains unclear whether this population in the patterned epithelium represents unique intestinal stem-cell precursors. Here we show, using unbiased quantitative lineage-tracing approaches, biophysical modelling and intestinal transplantation, that all cells of the mouse intestinal epithelium—irrespective of their location and pattern of LGR5 expression in the fetal gut tube—contribute actively to the adult intestinal stem cell pool. Using 3D imaging, we find that during fetal development the villus undergoes gross remodelling and fission. This brings epithelial cells from the non-proliferative villus into the proliferative intervillus region, which enables them to contribute to the adult stem-cell niche. Our results demonstrate that large-scale remodelling of the intestinal wall and cell-fate specification are closely linked. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissues following damage5,6,7,8,9, revealing that stem-cell identity is an induced rather than a hardwired property.}, author = {Guiu, Jordi and Hannezo, Edouard B and Yui, Shiro and Demharter, Samuel and Ulyanchenko, Svetlana and Maimets, Martti and Jørgensen, Anne and Perlman, Signe and Lundvall, Lene and Mamsen, Linn Salto and Larsen, Agnete and Olesen, Rasmus H. and Andersen, Claus Yding and Thuesen, Lea Langhoff and Hare, Kristine Juul and Pers, Tune H. and Khodosevich, Konstantin and Simons, Benjamin D. and Jensen, Kim B.}, issn = {14764687}, journal = {Nature}, pages = {107--111}, publisher = {Springer Nature}, title = {{Tracing the origin of adult intestinal stem cells}}, doi = {10.1038/s41586-019-1212-5}, volume = {570}, year = {2019}, } @article{6564, abstract = {Optogenetics enables the spatio-temporally precise control of cell and animal behavior. Many optogenetic tools are driven by light-controlled protein–protein interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying light-controlled PPIs to new target proteins is challenging because it is difficult to predict which of the many available LSDs, if any, will yield robust light regulation. As a consequence, fusion protein libraries need to be prepared and tested, but methods and platforms to facilitate this process are currently not available. Here, we developed a genetic engineering strategy and vector library for the rapid generation of light-controlled PPIs. The strategy permits fusing a target protein to multiple LSDs efficiently and in two orientations. The public and expandable library contains 29 vectors with blue, green or red light-responsive LSDs, many of which have been previously applied ex vivo and in vivo. We demonstrate the versatility of the approach and the necessity for sampling LSDs by generating light-activated caspase-9 (casp9) enzymes. Collectively, this work provides a new resource for optical regulation of a broad range of target proteins in cell and developmental biology.}, author = {Tichy, Alexandra-Madelaine and Gerrard, Elliot J. and Legrand, Julien M.D. and Hobbs, Robin M. and Janovjak, Harald L}, issn = {10898638}, journal = {Journal of Molecular Biology}, number = {17}, pages = {3046--3055}, publisher = {Elsevier}, title = {{Engineering strategy and vector library for the rapid generation of modular light-controlled protein–protein interactions}}, doi = {10.1016/j.jmb.2019.05.033}, volume = {431}, year = {2019}, } @article{6552, abstract = {When animals become sick, infected cells and an armada of activated immune cells attempt to eliminate the pathogen from the body. Once infectious particles have breached the body's physical barriers of the skin or gut lining, an initially local response quickly escalates into a systemic response, attracting mobile immune cells to the site of infection. These cells complement the initial, unspecific defense with a more specialized, targeted response. This can also provide long-term immune memory and protection against future infection. The cell-autonomous defenses of the infected cells are thus aided by the actions of recruited immune cells. These specialized cells are the most mobile cells in the body, constantly patrolling through the otherwise static tissue to detect incoming pathogens. Such constant immune surveillance means infections are noticed immediately and can be rapidly cleared from the body. Some immune cells also remove infected cells that have succumbed to infection. All this prevents pathogen replication and spread to healthy tissues. Although this may involve the sacrifice of some somatic tissue, this is typically replaced quickly. Particular care is, however, given to the reproductive organs, which should always remain disease free (immune privilege). }, author = {Cremer, Sylvia}, issn = {09609822}, journal = {Current Biology}, number = {11}, pages = {R458--R463}, publisher = {Elsevier}, title = {{Social immunity in insects}}, doi = {10.1016/j.cub.2019.03.035}, volume = {29}, year = {2019}, } @article{6511, abstract = {Let U and V be two independent N by N random matrices that are distributed according to Haar measure on U(N). Let Σ be a nonnegative deterministic N by N matrix. The single ring theorem [Ann. of Math. (2) 174 (2011) 1189–1217] asserts that the empirical eigenvalue distribution of the matrix X:=UΣV∗ converges weakly, in the limit of large N, to a deterministic measure which is supported on a single ring centered at the origin in ℂ. Within the bulk regime, that is, in the interior of the single ring, we establish the convergence of the empirical eigenvalue distribution on the optimal local scale of order N−1/2+ε and establish the optimal convergence rate. The same results hold true when U and V are Haar distributed on O(N).}, author = {Bao, Zhigang and Erdös, László and Schnelli, Kevin}, issn = {00911798}, journal = {Annals of Probability}, number = {3}, pages = {1270--1334}, publisher = {Institute of Mathematical Statistics}, title = {{Local single ring theorem on optimal scale}}, doi = {10.1214/18-AOP1284}, volume = {47}, year = {2019}, } @article{6559, abstract = {Branching morphogenesis is a prototypical example of complex three-dimensional organ sculpting, required in multiple developmental settings to maximize the area of exchange surfaces. It requires, in particular, the coordinated growth of different cell types together with complex patterning to lead to robust macroscopic outputs. In recent years, novel multiscale quantitative biology approaches, together with biophysical modelling, have begun to shed new light of this topic. Here, we wish to review some of these recent developments, highlighting the generic design principles that can be abstracted across different branched organs, as well as the implications for the broader fields of stem cell, developmental and systems biology.}, author = {Hannezo, Edouard B and Simons, Benjamin D.}, issn = {18790410}, journal = {Current Opinion in Cell Biology}, pages = {99--105}, publisher = {Elsevier}, title = {{Multiscale dynamics of branching morphogenesis}}, doi = {10.1016/j.ceb.2019.04.008}, volume = {60}, year = {2019}, } @article{6566, abstract = {Methodologies that involve the use of nanoparticles as “artificial atoms” to rationally build materials in a bottom-up fashion are particularly well-suited to control the matter at the nanoscale. Colloidal synthetic routes allow for an exquisite control over such “artificial atoms” in terms of size, shape, and crystal phase as well as core and surface compositions. We present here a bottom-up approach to produce Pb–Ag–K–S–Te nanocomposites, which is a highly promising system for thermoelectric energy conversion. First, we developed a high-yield and scalable colloidal synthesis route to uniform lead sulfide (PbS) nanorods, whose tips are made of silver sulfide (Ag2S). We then took advantage of the large surface-to-volume ratio to introduce a p-type dopant (K) by replacing native organic ligands with K2Te. Upon thermal consolidation, K2Te-surface modified PbS–Ag2S nanorods yield p-type doped nanocomposites with PbTe and PbS as major phases and Ag2S and Ag2Te as embedded nanoinclusions. Thermoelectric characterization of such consolidated nanosolids showed a high thermoelectric figure-of-merit of 1 at 620 K.}, author = {Ibáñez, Maria and Genç, Aziz and Hasler, Roger and Liu, Yu and Dobrozhan, Oleksandr and Nazarenko, Olga and Mata, María de la and Arbiol, Jordi and Cabot, Andreu and Kovalenko, Maksym V.}, issn = {1936-086X}, journal = {ACS Nano}, keywords = {colloidal nanoparticles, asymmetric nanoparticles, inorganic ligands, heterostructures, catalyst assisted growth, nanocomposites, thermoelectrics}, number = {6}, pages = {6572--6580}, publisher = {American Chemical Society}, title = {{Tuning transport properties in thermoelectric nanocomposites through inorganic ligands and heterostructured building blocks}}, doi = {10.1021/acsnano.9b00346}, volume = {13}, year = {2019}, } @article{6607, abstract = {Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically.}, author = {Nguyen, Chi Huu and Glüxam, Tobias and Schlerka, Angela and Bauer, Katharina and Grandits, Alexander M. and Hackl, Hubert and Dovey, Oliver and Zöchbauer-Müller, Sabine and Cooper, Jonathan L. and Vassiliou, George S. and Stoiber, Dagmar and Wieser, Rotraud and Heller, Gerwin}, journal = {Scientific Reports}, number = {1}, publisher = {Nature Publishing Group}, title = {{SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness}}, doi = {10.1038/s41598-019-45579-0}, volume = {9}, year = {2019}, }