@article{6819, abstract = {Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome.}, author = {Antoniou, Michael N. and Nicolas, Armel and Mesnage, Robin and Biserni, Martina and Rao, Francesco V. and Martin, Cristina Vazquez}, issn = {1756-0500}, journal = {BMC Research Notes}, publisher = {BioMed Central}, title = {{Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells}}, doi = {10.1186/s13104-019-4534-3}, volume = {12}, year = {2019}, } @misc{9784, abstract = {Additional file 1: Table S1. Kinetics of MDA-MB-231 cell growth in either the presence or absence of 100Â mg/L glyphosate. Cell counts are given at day-1 of seeding flasks and following 6-days of continuous culture. Note: no differences in cell numbers were observed between negative control and glyphosate treated cultures.}, author = {Antoniou, Michael N. and Nicolas, Armel and Mesnage, Robin and Biserni, Martina and Rao, Francesco V. and Martin, Cristina Vazquez}, publisher = {Springer Nature}, title = {{MOESM1 of Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells}}, doi = {10.6084/m9.figshare.9411761.v1}, year = {2019}, } @misc{9839, abstract = {More than 100 years after Grigg’s influential analysis of species’ borders, the causes of limits to species’ ranges still represent a puzzle that has never been understood with clarity. The topic has become especially important recently as many scientists have become interested in the potential for species’ ranges to shift in response to climate change—and yet nearly all of those studies fail to recognise or incorporate evolutionary genetics in a way that relates to theoretical developments. I show that range margins can be understood based on just two measurable parameters: (i) the fitness cost of dispersal—a measure of environmental heterogeneity—and (ii) the strength of genetic drift, which reduces genetic diversity. Together, these two parameters define an ‘expansion threshold’: adaptation fails when genetic drift reduces genetic diversity below that required for adaptation to a heterogeneous environment. When the key parameters drop below this expansion threshold locally, a sharp range margin forms. When they drop below this threshold throughout the species’ range, adaptation collapses everywhere, resulting in either extinction or formation of a fragmented metapopulation. Because the effects of dispersal differ fundamentally with dimension, the second parameter—the strength of genetic drift—is qualitatively different compared to a linear habitat. In two-dimensional habitats, genetic drift becomes effectively independent of selection. It decreases with ‘neighbourhood size’—the number of individuals accessible by dispersal within one generation. Moreover, in contrast to earlier predictions, which neglected evolution of genetic variance and/or stochasticity in two dimensions, dispersal into small marginal populations aids adaptation. This is because the reduction of both genetic and demographic stochasticity has a stronger effect than the cost of dispersal through increased maladaptation. The expansion threshold thus provides a novel, theoretically justified, and testable prediction for formation of the range margin and collapse of the species’ range.}, author = {Polechova, Jitka}, publisher = {Dryad}, title = {{Data from: Is the sky the limit? On the expansion threshold of a species' range}}, doi = {10.5061/dryad.5vv37}, year = {2019}, } @article{8408, abstract = {Aromatic residues are located at structurally important sites of many proteins. Probing their interactions and dynamics can provide important functional insight but is challenging in large proteins. Here, we introduce approaches to characterize dynamics of phenylalanine residues using 1H-detected fast magic-angle spinning (MAS) NMR combined with a tailored isotope-labeling scheme. Our approach yields isolated two-spin systems that are ideally suited for artefact-free dynamics measurements, and allows probing motions effectively without molecular-weight limitations. The application to the TET2 enzyme assembly of ~0.5 MDa size, the currently largest protein assigned by MAS NMR, provides insights into motions occurring on a wide range of time scales (ps-ms). We quantitatively probe ring flip motions, and show the temperature dependence by MAS NMR measurements down to 100 K. Interestingly, favorable line widths are observed down to 100 K, with potential implications for DNP NMR. Furthermore, we report the first 13C R1ρ MAS NMR relaxation-dispersion measurements and detect structural excursions occurring on a microsecond time scale in the entry pore to the catalytic chamber and at a trimer interface that was proposed as exit pore. We show that the labeling scheme with deuteration at ca. 50 kHz MAS provides superior resolution compared to 100 kHz MAS experiments with protonated, uniformly 13C-labeled samples.}, author = {Gauto, Diego F. and Macek, Pavel and Barducci, Alessandro and Fraga, Hugo and Hessel, Audrey and Terauchi, Tsutomu and Gajan, David and Miyanoiri, Yohei and Boisbouvier, Jerome and Lichtenecker, Roman and Kainosho, Masatsune and Schanda, Paul}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {28}, pages = {11183--11195}, publisher = {American Chemical Society}, title = {{Aromatic ring dynamics, thermal activation, and transient conformations of a 468 kDa enzyme by specific 1H–13C labeling and fast magic-angle spinning NMR}}, doi = {10.1021/jacs.9b04219}, volume = {141}, year = {2019}, } @article{8418, abstract = {For the Restricted Circular Planar 3 Body Problem, we show that there exists an open set U in phase space of fixed measure, where the set of initial points which lead to collision is O(μ120) dense as μ→0.}, author = {Guardia, Marcel and Kaloshin, Vadim and Zhang, Jianlu}, issn = {0003-9527}, journal = {Archive for Rational Mechanics and Analysis}, keywords = {Mechanical Engineering, Mathematics (miscellaneous), Analysis}, number = {2}, pages = {799--836}, publisher = {Springer Nature}, title = {{Asymptotic density of collision orbits in the Restricted Circular Planar 3 Body Problem}}, doi = {10.1007/s00205-019-01368-7}, volume = {233}, year = {2019}, } @article{8416, abstract = {In this paper, we show that any smooth one-parameter deformations of a strictly convex integrable billiard table Ω0 preserving the integrability near the boundary have to be tangent to a finite dimensional space passing through Ω0.}, author = {Huang, Guan and Kaloshin, Vadim}, issn = {1609-4514}, journal = {Moscow Mathematical Journal}, number = {2}, pages = {307--327}, publisher = {American Mathematical Society}, title = {{On the finite dimensionality of integrable deformations of strictly convex integrable billiard tables}}, doi = {10.17323/1609-4514-2019-19-2-307-327}, volume = {19}, year = {2019}, } @article{8693, abstract = {We review V. I. Arnold’s 1963 celebrated paper [1] Proof of A. N. Kolmogorov’s Theorem on the Conservation of Conditionally Periodic Motions with a Small Variation in the Hamiltonian, and prove that, optimising Arnold’s scheme, one can get “sharp” asymptotic quantitative conditions (as ε → 0, ε being the strength of the perturbation). All constants involved are explicitly computed.}, author = {Chierchia, Luigi and Koudjinan, Edmond}, journal = {Regular and Chaotic Dynamics}, pages = {583–606}, publisher = {Springer}, title = {{V. I. Arnold’s “pointwise” KAM theorem}}, doi = {10.1134/S1560354719060017}, volume = {24}, year = {2019}, } @article{9018, abstract = {Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy.}, author = {Bakail, May M and Gaubert, Albane and Andreani, Jessica and Moal, Gwenaëlle and Pinna, Guillaume and Boyarchuk, Ekaterina and Gaillard, Marie-Cécile and Courbeyrette, Regis and Mann, Carl and Thuret, Jean-Yves and Guichard, Bérengère and Murciano, Brice and Richet, Nicolas and Poitou, Adeline and Frederic, Claire and Le Du, Marie-Hélène and Agez, Morgane and Roelants, Caroline and Gurard-Levin, Zachary A. and Almouzni, Geneviève and Cherradi, Nadia and Guerois, Raphael and Ochsenbein, Françoise}, issn = {2451-9456}, journal = {Cell Chemical Biology}, keywords = {Clinical Biochemistry, Molecular Medicine, Biochemistry, Molecular Biology, Pharmacology, Drug Discovery}, number = {11}, pages = {1573--1585.e10}, publisher = {Elsevier}, title = {{Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1}}, doi = {10.1016/j.chembiol.2019.09.002}, volume = {26}, year = {2019}, } @article{9530, abstract = {Background DNA methylation of active genes, also known as gene body methylation, is found in many animal and plant genomes. Despite this, the transcriptional and developmental role of such methylation remains poorly understood. Here, we explore the dynamic range of DNA methylation in honey bee, a model organism for gene body methylation. Results Our data show that CG methylation in gene bodies globally fluctuates during honey bee development. However, these changes cause no gene expression alterations. Intriguingly, despite the global alterations, tissue-specific CG methylation patterns of complete genes or exons are rare, implying robust maintenance of genic methylation during development. Additionally, we show that CG methylation maintenance fluctuates in somatic cells, while reaching maximum fidelity in sperm cells. Finally, unlike universally present CG methylation, we discovered non-CG methylation specifically in bee heads that resembles such methylation in mammalian brain tissue. Conclusions Based on these results, we propose that gene body CG methylation can oscillate during development if it is kept to a level adequate to preserve function. Additionally, our data suggest that heightened non-CG methylation is a conserved regulator of animal nervous systems.}, author = {Harris, Keith D. and Lloyd, James P. B. and Domb, Katherine and Zilberman, Daniel and Zemach, Assaf}, issn = {1756-8935}, journal = {Epigenetics and Chromatin}, publisher = {Springer Nature}, title = {{DNA methylation is maintained with high fidelity in the honey bee germline and exhibits global non-functional fluctuations during somatic development}}, doi = {10.1186/s13072-019-0307-4}, volume = {12}, year = {2019}, } @article{9586, abstract = {Consider integers 𝑘,ℓ such that 0⩽ℓ⩽(𝑘2) . Given a large graph 𝐺 , what is the fraction of 𝑘 -vertex subsets of 𝐺 which span exactly ℓ edges? When 𝐺 is empty or complete, and ℓ is zero or (𝑘2) , this fraction can be exactly 1. On the other hand, if ℓ is far from these extreme values, one might expect that this fraction is substantially smaller than 1. This was recently proved by Alon, Hefetz, Krivelevich, and Tyomkyn who initiated the systematic study of this question and proposed several natural conjectures. Let ℓ∗=min{ℓ,(𝑘2)−ℓ} . Our main result is that for any 𝑘 and ℓ , the fraction of 𝑘 -vertex subsets that span ℓ edges is at most log𝑂(1)(ℓ∗/𝑘)√ 𝑘/ℓ∗, which is best-possible up to the logarithmic factor. This improves on multiple results of Alon, Hefetz, Krivelevich, and Tyomkyn, and resolves one of their conjectures. In addition, we also make some first steps towards some analogous questions for hypergraphs. Our proofs involve some Ramsey-type arguments, and a number of different probabilistic tools, such as polynomial anticoncentration inequalities, hypercontractivity, and a coupling trick for random variables defined on a ‘slice’ of the Boolean hypercube.}, author = {Kwan, Matthew Alan and Sudakov, Benny and Tran, Tuan}, issn = {1469-7750}, journal = {Journal of the London Mathematical Society}, number = {3}, pages = {757--777}, publisher = {Wiley}, title = {{Anticoncentration for subgraph statistics}}, doi = {10.1112/jlms.12192}, volume = {99}, year = {2019}, }