bluuebunny/crossref_metadata_2025 huggingface dataset:
The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis
Authors: Zhou Ming , Coruh Ceyda , Xu Guanghui , Martins Laura M. , Bourbousse Clara , Lambolez Alice , Law Julie A.
Published: January 2022

DNA methylation shapes the epigenetic landscape of the genome, plays critical roles in regulating gene expression, and ensures transposon silencing. As is evidenced by the numerous defects associated with aberrant DNA methylation landscapes, establishing proper tissue-specific methylation patterns is critical. Yet, how such differences arise remains a largely open question in both plants and animals. Here we demonstrate that CLASSY1-4 (CLSY1-4), four locus-specific regulators of DNA methylation, also control tissue-specific methylation patterns, with the most striking pattern observed in ovules where CLSY3 and CLSY4 control DNA methylation at loci with a highly conserved DNA motif. On a more global scale, we demonstrate that specific clsy mutants are sufficient to shift the epigenetic landscape between tissues. Together, these findings reveal substantial epigenetic diversity between tissues and assign these changes to specific CLSY proteins, elucidating how locus-specific targeting combined with tissue-specific expression enables the CLSYs to generate epigenetic diversity during plant development.
Boundary conductance in macroscopic bismuth crystals
Authors: Kang Woun , Spathelf Felix , Fauqué Benoît , Fuseya Yuki , Behnia Kamran
Published: January 2022

The interface between a solid and vacuum can become electronically distinct from the bulk. This feature, encountered in the case of quantum Hall effect, has a manifestation in insulators with topologically protected metallic surface states. Non-trivial Berry curvature of the Bloch waves or periodically driven perturbation are known to generate it. Here, by studying the angle-dependent magnetoresistance in prismatic bismuth crystals of different shapes, we detect a robust surface contribution to electric conductivity when the magnetic field is aligned parallel to a two-dimensional boundary between the three-dimensional crystal and vacuum. The effect is absent in antimony, which has an identical crystal symmetry, a similar Fermi surface structure and equally ballistic carriers, but an inverted band symmetry and a topological invariant of opposite sign. Our observation confirms that the boundary interrupting the cyclotron orbits remains metallic in bismuth, which is in agreement with what was predicted by Azbel decades ago. However, the absence of the effect in antimony indicates an intimate link between band symmetry and this boundary conductance.
Transglutaminase 3 crosslinks the secreted gel-forming mucus component Mucin-2 and stabilizes the colonic mucus layer
Authors: Sharpen Jack D. A. , Dolan Brendan , Nyström Elisabeth E. L. , Birchenough George M. H. , Arike Liisa , Martinez-Abad Beatriz , Johansson Malin E. V. , Hansson Gunnar C. , Recktenwald Christian V.
Published: January 2022

The colonic mucus layer is organized as a two-layered system providing a physical barrier against pathogens and simultaneously harboring the commensal flora. The factors contributing to the organization of this gel network are not well understood. In this study, the impact of transglutaminase activity on this architecture was analyzed. Here, we show that transglutaminase TGM3 is the major transglutaminase-isoform expressed and synthesized in the colon. Furthermore, intrinsic extracellular transglutaminase activity in the secreted mucus was demonstrated in vitro and ex vivo. Absence of this acyl-transferase activity resulted in faster degradation of the major mucus component the MUC2 mucin and changed the biochemical properties of mucus. Finally, TGM3-deficient mice showed an early increased susceptibility to Dextran Sodium Sulfate-induced colitis. Here, we report that natural isopeptide cross-linking by TGM3 is important for mucus homeostasis and protection of the colon from inflammation, reducing the risk of colitis.
A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control
Authors: Schroeder Griffin M. , Cavender Chapin E. , Blau Maya E. , Jenkins Jermaine L. , Mathews David H. , Wedekind Joseph E.
Published: January 2022

Riboswitches are structured non-coding RNAs often located upstream of essential genes in bacterial messenger RNAs. Such RNAs regulate expression of downstream genes by recognizing a specific cellular effector. Although nearly 50 riboswitch classes are known, only a handful recognize multiple effectors. Here, we report the 2.60-Å resolution co-crystal structure of a class I type I preQ1-sensing riboswitch that reveals two effectors stacked atop one another in a single binding pocket. These effectors bind with positive cooperativity in vitro and both molecules are necessary for gene regulation in bacterial cells. Stacked effector recognition appears to be a hallmark of the largest subgroup of preQ1 riboswitches, including those from pathogens such as Neisseria gonorrhoeae. We postulate that binding to stacked effectors arose in the RNA World to closely position two substrates for RNA-mediated catalysis. These findings expand known effector recognition capabilities of riboswitches and have implications for antimicrobial development.
Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans
Authors: Possik Elite , Schmitt Clémence , Al-Mass Anfal , Bai Ying , Côté Laurence , Morin Johanne , Erb Heidi , Oppong Abel , Kahloan Wahab , Parker J. Alex , Madiraju S. R. Murthy , Prentki Marc
Published: January 2022

Metabolic stress due to nutrient excess and lipid accumulation is at the root of many age-associated disorders and the identification of therapeutic targets that mimic the beneficial effects of calorie restriction has clinical importance. Here, using C. elegans as a model organism, we study the roles of a recently discovered enzyme at the heart of metabolism in mammalian cells, glycerol-3-phosphate phosphatase (G3PP) (gene name Pgp) that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol. We identify three Pgp homologues in C. elegans (pgph) and demonstrate in vivo that their protein products have G3PP activity, essential for glycerol synthesis. We demonstrate that PGPH/G3PP regulates the adaptation to various stresses, in particular hyperosmolarity and glucotoxicity. Enhanced G3PP activity reduces fat accumulation, promotes healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility. Thus, PGP/G3PP can be considered as a target for age-related metabolic disorders.
Observation of ballistic upstream modes at fractional quantum Hall edges of graphene
Authors: Kumar Ravi , Srivastav Saurabh Kumar , Spånslätt Christian , Watanabe K. , Taniguchi T. , Gefen Yuval , Mirlin Alexander D. , Das Anindya
Published: January 2022

The presence of “upstream” modes, moving against the direction of charge current flow in the fractional quantum Hall (FQH) phases, is critical for the emergence of renormalized modes with exotic quantum statistics. Detection of excess noise at the edge is a smoking gun for the presence of upstream modes. Here, we report noise measurements at the edges of FQH states realized in dual graphite-gated bilayer graphene devices. A noiseless dc current is injected at one of the edge contacts, and the noise generated at contacts at length, L = 4 μm and 10 μm away along the upstream direction is studied. For integer and particle-like FQH states, no detectable noise is measured. By contrast, for “hole-conjugate” FQH states, we detect a strong noise proportional to the injected current, unambiguously proving the existence of upstream modes. The noise magnitude remains independent of length, which matches our theoretical analysis demonstrating the ballistic nature of upstream energy transport, quite distinct from the diffusive propagation reported earlier in GaAs-based systems.
Determinants of synapse diversity revealed by super-resolution quantal transmission and active zone imaging
Authors: Newman Zachary L. , Bakshinskaya Dariya , Schultz Ryan , Kenny Samuel J. , Moon Seonah , Aghi Krisha , Stanley Cherise , Marnani Nadia , Li Rachel , Bleier Julia , Xu Ke , Isacoff Ehud Y.
Published: January 2022

Neural circuit function depends on the pattern of synaptic connections between neurons and the strength of those connections. Synaptic strength is determined by both postsynaptic sensitivity to neurotransmitter and the presynaptic probability of action potential evoked transmitter release (Pr). Whereas morphology and neurotransmitter receptor number indicate postsynaptic sensitivity, presynaptic indicators and the mechanism that sets Pr remain to be defined. To address this, we developed QuaSOR, a super-resolution method for determining Pr from quantal synaptic transmission imaging at hundreds of glutamatergic synapses at a time. We mapped the Pr onto super-resolution 3D molecular reconstructions of the presynaptic active zones (AZs) of the same synapses at the Drosophila larval neuromuscular junction (NMJ). We find that Pr varies greatly between synapses made by a single axon, quantify the contribution of key AZ proteins to Pr diversity and find that one of these, Complexin, suppresses spontaneous and evoked transmission differentially, thereby generating a spatial and quantitative mismatch between release modes. Transmission is thus regulated by the balance and nanoscale distribution of release-enhancing and suppressing presynaptic proteins to generate high signal-to-noise evoked transmission.
Multi-mode excitation drives disorder during the ultrafast melting of a C4-symmetry-broken phase
Authors: Perez-Salinas Daniel , Johnson Allan S. , Prabhakaran Dharmalingam , Wall Simon
Published: January 2022

Spontaneous C4-symmetry breaking phases are ubiquitous in layered quantum materials, and often compete with other phases such as superconductivity. Preferential suppression of the symmetry broken phases by light has been used to explain non-equilibrium light induced superconductivity, metallicity, and the creation of metastable states. Key to understanding how these phases emerge is understanding how C4 symmetry is restored. A leading approach is based on time-dependent Ginzburg-Landau theory, which explains the coherence response seen in many systems. However, we show that, for the case of the single layered manganite La0.5Sr1.5MnO4, the theory fails. Instead, we find an ultrafast inhomogeneous disordering transition in which the mean-field order parameter no longer reflects the atomic-scale state of the system. Our results suggest that disorder may be common to light-induced phase transitions, and methods beyond the mean-field are necessary for understanding and manipulating photoinduced phases.
Design principles for site-selective hydroxylation by a Rieske oxygenase
Authors: Liu Jianxin , Tian Jiayi , Perry Christopher , Lukowski April L. , Doukov Tzanko I. , Narayan Alison R. H. , Bridwell-Rabb Jennifer
Published: January 2022

Rieske oxygenases exploit the reactivity of iron to perform chemically challenging C–H bond functionalization reactions. Thus far, only a handful of Rieske oxygenases have been structurally characterized and remarkably little information exists regarding how these enzymes use a common architecture and set of metallocenters to facilitate a diverse range of reactions. Herein, we detail how two Rieske oxygenases SxtT and GxtA use different protein regions to influence the site-selectivity of their catalyzed monohydroxylation reactions. We present high resolution crystal structures of SxtT and GxtA with the native β-saxitoxinol and saxitoxin substrates bound in addition to a Xenon-pressurized structure of GxtA that reveals the location of a substrate access tunnel to the active site. Ultimately, this structural information allowed for the identification of six residues distributed between three regions of SxtT that together control the selectivity of the C–H hydroxylation event. Substitution of these residues produces a SxtT variant that is fully adapted to exhibit the non-native site-selectivity and substrate scope of GxtA. Importantly, we also found that these selectivity regions are conserved in other structurally characterized Rieske oxygenases, providing a framework for predictively repurposing and manipulating Rieske oxygenases as biocatalysts.
Conformal elasticity of mechanism-based metamaterials
Authors: Czajkowski Michael , Coulais Corentin , van Hecke Martin , Rocklin D. Zeb
Published: January 2022

Deformations of conventional solids are described via elasticity, a classical field theory whose form is constrained by translational and rotational symmetries. However, flexible metamaterials often contain an additional approximate symmetry due to the presence of a designer soft strain pathway. Here we show that low energy deformations of designer dilational metamaterials will be governed by a scalar field theory, conformal elasticity, in which the nonuniform, nonlinear deformations observed under generic loads correspond with the well-studied—conformal—maps. We validate this approach using experiments and finite element simulations and further show that such systems obey a holographic bulk-boundary principle, which enables an analytic method to predict and control nonuniform, nonlinear deformations. This work both presents a unique method of precise deformation control and demonstrates a general principle in which mechanisms can generate special classes of soft deformations.
An anionic ligand snap-locks a long-range interaction in a magnesium-folded riboswitch
Authors: Yadav Rajeev , Widom Julia R. , Chauvier Adrien , Walter Nils G.
Published: January 2022

The archetypical transcriptional crcB fluoride riboswitch from Bacillus cereus is an intricately structured non-coding RNA element enhancing gene expression in response to toxic levels of fluoride. Here, we used single molecule FRET to uncover three dynamically interconverting conformations appearing along the transcription process: two distinct undocked states and one pseudoknotted docked state. We find that the fluoride anion specifically snap-locks the magnesium-induced, dynamically docked state. The long-range, nesting, single base pair A40-U48 acts as the main linchpin, rather than the multiple base pairs comprising the pseudoknot. We observe that the proximally paused RNA polymerase further fine-tunes the free energy to promote riboswitch docking. Finally, we show that fluoride binding at short transcript lengths is an early step toward partitioning folding into the docked conformation. These results reveal how the anionic fluoride ion cooperates with the magnesium-associated RNA to govern regulation of downstream genes needed for fluoride detoxification of the cell.
Spin mapping of intralayer antiferromagnetism and field-induced spin reorientation in monolayer CrTe2
Authors: Xian Jing-Jing , Wang Cong , Nie Jin-Hua , Li Rui , Han Mengjiao , Lin Junhao , Zhang Wen-Hao , Liu Zhen-Yu , Zhang Zhi-Mo , Miao Mao-Peng , Yi Yangfan , Wu Shiwei , Chen Xiaodie , Han Junbo , Xia Zhengcai , Ji Wei , Fu Ying-Shuang
Published: January 2022

Intrinsic antiferromagnetism in van der Waals (vdW) monolayer (ML) crystals enriches our understanding of two-dimensional (2D) magnetic orders and presents several advantages over ferromagnetism in spintronic applications. However, studies of 2D intrinsic antiferromagnetism are sparse, owing to the lack of net magnetisation. Here, by combining spin-polarised scanning tunnelling microscopy and first-principles calculations, we investigate the magnetism of vdW ML CrTe2, which has been successfully grown through molecular-beam epitaxy. We observe a stable antiferromagnetic (AFM) order at the atomic scale in the ML crystal, whose bulk is ferromagnetic, and correlate its imaged zigzag spin texture with the atomic lattice structure. The AFM order exhibits an intriguing noncollinear spin reorientation under magnetic fields, consistent with its calculated moderate magnetic anisotropy. The findings of this study demonstrate the intricacy of 2D vdW magnetic materials and pave the way for their in-depth analysis.
Evolution of microscopic heterogeneity and dynamics in choline chloride-based deep eutectic solvents
Authors: Spittle Stephanie , Poe Derrick , Doherty Brian , Kolodziej Charles , Heroux Luke , Haque Md Ashraful , Squire Henry , Cosby Tyler , Zhang Yong , Fraenza Carla , Bhattacharyya Sahana , Tyagi Madhusudan , Peng Jing , Elgammal Ramez A. , Zawodzinski Thomas , Tuckerman Mark , Greenbaum Steve , Gurkan Burcu , Burda Clemens , Dadmun Mark , Maginn Edward J. , Sangoro Joshua
Published: January 2022

Deep eutectic solvents (DESs) are an emerging class of non-aqueous solvents that are potentially scalable, easy to prepare and functionalize for many applications ranging from biomass processing to energy storage technologies. Predictive understanding of the fundamental correlations between local structure and macroscopic properties is needed to exploit the large design space and tunability of DESs for specific applications. Here, we employ a range of computational and experimental techniques that span length-scales from molecular to macroscopic and timescales from picoseconds to seconds to study the evolution of structure and dynamics in model DESs, namely Glyceline and Ethaline, starting from the parent compounds. We show that systematic addition of choline chloride leads to microscopic heterogeneities that alter the primary structural relaxation in glycerol and ethylene glycol and result in new dynamic modes that are strongly correlated to the macroscopic properties of the DES formed.
Electron-momentum dependence of electron-phonon coupling underlies dramatic phonon renormalization in YNi2B2C
Authors: Kurzhals Philipp , Kremer Geoffroy , Jaouen Thomas , Nicholson Christopher W. , Heid Rolf , Nagel Peter , Castellan John-Paul , Ivanov Alexandre , Muntwiler Matthias , Rumo Maxime , Salzmann Bjoern , Strocov Vladimir N. , Reznik Dmitry , Monney Claude , Weber Frank
Published: January 2022

Electron-phonon coupling, i.e., the scattering of lattice vibrations by electrons and vice versa, is ubiquitous in solids and can lead to emergent ground states such as superconductivity and charge-density wave order. A broad spectral phonon line shape is often interpreted as a marker of strong electron-phonon coupling associated with Fermi surface nesting, i.e., parallel sections of the Fermi surface connected by the phonon momentum. Alternatively broad phonons are known to arise from strong atomic lattice anharmonicity. Here, we show that strong phonon broadening can occur in the absence of both Fermi surface nesting and lattice anharmonicity, if electron-phonon coupling is strongly enhanced for specific values of electron-momentum, k. We use inelastic neutron scattering, soft x-ray angle-resolved photoemission spectroscopy measurements and ab-initio lattice dynamical and electronic band structure calculations to demonstrate this scenario in the highly anisotropic tetragonal electron-phonon superconductor YNi2B2C. This new scenario likely applies to a wide range of compounds.
Rapid antigen testing as a reactive response to surges in nosocomial SARS-CoV-2 outbreak risk
Authors: Smith David R. M. , Duval Audrey , Zahar Jean Ralph ,   the EMAE-MESuRS Working Group on Nosocomial SARS-CoV-2 Modelling, Hendrickx Niels , Jean Kévin , Jijón Sofía , Oodally Ajmal , Shirreff George , Tamandjou Cynthia , Opatowski Lulla , Temime Laura
Published: January 2022

Healthcare facilities are vulnerable to SARS-CoV-2 introductions and subsequent nosocomial outbreaks. Antigen rapid diagnostic testing (Ag-RDT) is widely used for population screening, but its health and economic benefits as a reactive response to local surges in outbreak risk are unclear. We simulate SARS-CoV-2 transmission in a long-term care hospital with varying COVID-19 containment measures in place (social distancing, face masks, vaccination). Across scenarios, nosocomial incidence is reduced by up to 40-47% (range of means) with routine symptomatic RT-PCR testing, 59-63% with the addition of a timely round of Ag-RDT screening, and 69-75% with well-timed two-round screening. For the latter, a delay of 4-5 days between the two screening rounds is optimal for transmission prevention. Screening efficacy varies depending on test sensitivity, test type, subpopulations targeted, and community incidence. Efficiency, however, varies primarily depending on underlying outbreak risk, with health-economic benefits scaling by orders of magnitude depending on the COVID-19 containment measures in place.
A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
Authors: Wong Derek P. , Roy Nand K. , Zhang Keman , Anukanth Anusha , Asthana Abhishek , Shirkey-Son Nicole J. , Dunmire Samantha , Jones Bryan J. , Lahr Walker S. , Webber Beau R. , Moriarity Branden S. , Caimi Paolo , Parameswaran Reshmi
Published: January 2022

B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers.
Towards a generic prototyping approach for therapeutically-relevant peptides and proteins in a cell-free translation system
Authors: Wu Yue , Cui Zhenling , Huang Yen-Hua , de Veer Simon J. , Aralov Andrey V. , Guo Zhong , Moradi Shayli V. , Hinton Alexandra O. , Deuis Jennifer R. , Guo Shaodong , Chen Kai-En , Collins Brett M. , Vetter Irina , Herzig Volker , Jones Alun , Cooper Matthew A. , King Glenn F. , Craik David J. , Alexandrov Kirill , Mureev Sergey
Published: January 2022

Advances in peptide and protein therapeutics increased the need for rapid and cost-effective polypeptide prototyping. While in vitro translation systems are well suited for fast and multiplexed polypeptide prototyping, they suffer from misfolding, aggregation and disulfide-bond scrambling of the translated products. Here we propose that efficient folding of in vitro produced disulfide-rich peptides and proteins can be achieved if performed in an aggregation-free and thermodynamically controlled folding environment. To this end, we modify an E. coli-based in vitro translation system to allow co-translational capture of translated products by affinity matrix. This process reduces protein aggregation and enables productive oxidative folding and recycling of misfolded states under thermodynamic control. In this study we show that the developed approach is likely to be generally applicable for prototyping of a wide variety of disulfide-constrained peptides, macrocyclic peptides with non-native bonds and antibody fragments in amounts sufficient for interaction analysis and biological activity assessment.
MicroRNA-365 regulates human cardiac action potential duration
Authors: Esfandyari Dena , Idrissou Bio Maria Ghéo , Hennis Konstantin , Avramopoulos Petros , Dueck Anne , El-Battrawy Ibrahim , Grüter Laurenz , Meier Melanie Annemarie , Näger Anna Christina , Ramanujam Deepak , Dorn Tatjana , Meitinger Thomas , Hagl Christian , Milting Hendrik , Borggrefe Martin , Fenske Stefanie , Biel Martin , Dendorfer Andreas , Sassi Yassine , Moretti Alessandra , Engelhardt Stefan
Published: January 2022

Abnormalities of ventricular action potential cause malignant cardiac arrhythmias and sudden cardiac death. Here, we aim to identify microRNAs that regulate the human cardiac action potential and ask whether their manipulation allows for therapeutic modulation of action potential abnormalities. Quantitative analysis of the microRNA targetomes in human cardiac myocytes identifies miR-365 as a primary microRNA to regulate repolarizing ion channels. Action potential recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes show that elevation of miR-365 significantly prolongs action potential duration in myocytes derived from a Short-QT syndrome patient, whereas specific inhibition of miR-365 normalizes pathologically prolonged action potential in Long-QT syndrome myocytes. Transcriptome analyses in these cells at bulk and single-cell level corroborate the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional action potential-regulating genes by this microRNA. Whole-cell patch-clamp experiments confirm miR-365-dependent regulation of repolarizing ionic current Iks. Finally, refractory period measurements in human myocardial slices substantiate the regulatory effect of miR-365 on action potential in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac action potential duration by targeting key factors of cardiac repolarization.
Single-dispersed polyoxometalate clusters embedded on multilayer graphene as a bifunctional electrocatalyst for efficient Li-S batteries
Authors: Lei Jie , Fan Xiao-Xiang , Liu Ting , Xu Pan , Hou Qing , Li Ke , Yuan Ru-Ming , Zheng Ming-Sen , Dong Quan-Feng , Chen Jia-Jia
Published: January 2022

The redox reactions occurring in the Li-S battery positive electrode conceal various and critical electrocatalytic processes, which strongly influence the performances of this electrochemical energy storage system. Here, we report the development of a single-dispersed molecular cluster catalyst composite comprising of a polyoxometalate framework ([Co4(PW9O34)2]10−) and multilayer reduced graphene oxide. Due to the interfacial charge transfer and exposure of unsaturated cobalt sites, the composite demonstrates efficient polysulfides adsorption and reduced activation energy for polysulfides conversion, thus serving as a bifunctional electrocatalyst. When tested in full Li-S coin cell configuration, the composite allows for a long-term Li-S battery cycling with a capacity fading of 0.015% per cycle after 1000 cycles at 2 C (i.e., 3.36 A g−1). An areal capacity of 4.55 mAh cm−2 is also achieved with a sulfur loading of 5.6 mg cm−2 and E/S ratio of 4.5 μL mg−1. Moreover, Li-S single-electrode pouch cells tested with the bifunctional electrocatalyst demonstrate a specific capacity of about 800 mAh g−1 at a sulfur loading of 3.6 mg cm−2 for 100 cycles at 0.2 C (i.e., 336 mA g−1) with E/S ratio of 5 μL mg−1.
Neutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding
Authors: Gajdos Lukas , Blakeley Matthew P. , Haertlein Michael , Forsyth V. Trevor , Devos Juliette M. , Imberty Anne
Published: January 2022

The opportunistic pathogen Pseudomonas aeruginosa, a major cause of nosocomial infections, uses carbohydrate-binding proteins (lectins) as part of its binding to host cells. The fucose-binding lectin, LecB, displays a unique carbohydrate-binding site that incorporates two closely located calcium ions bridging between the ligand and protein, providing specificity and unusually high affinity. Here, we investigate the mechanisms involved in binding based on neutron crystallography studies of a fully deuterated LecB/fucose/calcium complex. The neutron structure, which includes the positions of all the hydrogen atoms, reveals that the high affinity of binding may be related to the occurrence of a low-barrier hydrogen bond induced by the proximity of the two calcium ions, the presence of coordination rings between the sugar, calcium and LecB, and the dynamic behaviour of bridging water molecules at room temperature. These key structural details may assist in the design of anti-adhesive compounds to combat multi-resistance bacterial infections.
BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1
Authors: Chen Dan , Gervai Judit Z. , Póti Ádám , Németh Eszter , Szeltner Zoltán , Szikriszt Bernadett , Gyüre Zsolt , Zámborszky Judit , Ceccon Marta , d’Adda di Fagagna Fabrizio , Szallasi Zoltan , Richardson Andrea L. , Szüts Dávid
Published: January 2022

Defects in BRCA1, BRCA2 and other genes of the homology-dependent DNA repair (HR) pathway cause an elevated rate of mutagenesis, eliciting specific mutation patterns including COSMIC signature SBS3. Using genome sequencing of knock-out cell lines we show that Y family translesion synthesis (TLS) polymerases contribute to the spontaneous generation of base substitution and short insertion/deletion mutations in BRCA1 deficient cells, and that TLS on DNA adducts is increased in BRCA1 and BRCA2 mutants. The inactivation of 53BP1 in BRCA1 mutant cells markedly reduces TLS-specific mutagenesis, and rescues the deficiency of template switch–mediated gene conversions in the immunoglobulin V locus of BRCA1 mutant chicken DT40 cells. 53BP1 also promotes TLS in human cellular extracts in vitro. Our results show that HR deficiency–specific mutagenesis is largely caused by TLS, and suggest a function for 53BP1 in regulating the choice between TLS and error-free template switching in replicative DNA damage bypass.
Probing dark exciton navigation through a local strain landscape in a WSe2 monolayer
Authors: Gelly Ryan J. , Renaud Dylan , Liao Xing , Pingault Benjamin , Bogdanovic Stefan , Scuri Giovanni , Watanabe Kenji , Taniguchi Takashi , Urbaszek Bernhard , Park Hongkun , Lončar Marko
Published: January 2022

In WSe2 monolayers, strain has been used to control the energy of excitons, induce funneling, and realize single-photon sources. Here, we developed a technique for probing the dynamics of free excitons in nanoscale strain landscapes in such monolayers. A nanosculpted tapered optical fiber is used to simultaneously generate strain and probe the near-field optical response of WSe2 monolayers at 5 K. When the monolayer is pushed by the fiber, its lowest energy states shift by as much as 390 meV (>20% of the bandgap of a WSe2 monolayer). Polarization and lifetime measurements of these red-shifting peaks indicate they originate from dark excitons. We conclude free dark excitons are funneled to high-strain regions during their long lifetime and are the principal participants in drift and diffusion at cryogenic temperatures. This insight supports proposals on the origin of single-photon sources in WSe2 and demonstrates a route towards exciton traps for exciton condensation.
Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2
Authors: Gupta Kapil , Toelzer Christine , Williamson Maia Kavanagh , Shoemark Deborah K. , Oliveira A. Sofia F. , Matthews David A. , Almuqrin Abdulaziz , Staufer Oskar , Yadav Sathish K. N. , Borucu Ufuk , Garzoni Frederic , Fitzgerald Daniel , Spatz Joachim , Mulholland Adrian J. , Davidson Andrew D. , Schaffitzel Christiane , Berger Imre
Published: January 2022

As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid deletion encompassing a furin recognition motif and S1/S2 cleavage site. We elucidate the structure, function and molecular dynamics of this spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Our results reveal long-range allosteric communication between functional domains that differ in the wild-type and the deletion variant and support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.
Ultralow-temperature-driven water-based sorption refrigeration enabled by low-cost zeolite-like porous aluminophosphate
Authors: Liu Zhangli , Xu Jiaxing , Xu Min , Huang Caifeng , Wang Ruzhu , Li Tingxian , Huai Xiulan
Published: January 2022

Thermally driven water-based sorption refrigeration is considered a promising strategy to realize near-zero-carbon cooling applications by addressing the urgent global climate challenge caused by conventional chlorofluorocarbon (CFC) refrigerants. However, developing cost-effective and high-performance water-sorption porous materials driven by low-temperature thermal energy is still a significant challenge. Here, we propose a zeolite-like aluminophosphate with SFO topology (EMM-8) for water-sorption-driven refrigeration. The EMM-8 is characterized by 12-membered ring channels with large accessible pore volume and exhibits high water uptake of 0.28 g·g−1 at P/P0 = 0.2, low-temperature regeneration of 65 °C, fast adsorption kinetics, remarkable hydrothermal stability, and scalable fabrication. Importantly, the water-sorption-based chiller with EMM-8 shows the potential of achieving a record coefficient of performance (COP) of 0.85 at an ultralow-driven temperature of 63 °C. The working performance makes EMM-8 a practical alternative to realize high-efficient ultra-low-temperature-driven refrigeration.
Selectively tuning ionic thermopower in all-solid-state flexible polymer composites for thermal sensing
Authors: Chi Cheng , An Meng , Qi Xin , Li Yang , Zhang Ruihan , Liu Gongze , Lin Chongjia , Huang He , Dang Hao , Demir Baris , Wang Yan , Ma Weigang , Huang Baoling , Zhang Xing
Published: January 2022

There has been increasing interest in the emerging ionic thermoelectric materials with huge ionic thermopower. However, it’s challenging to selectively tune the thermopower of all-solid-state polymer materials because the transportation of ions in all-solid-state polymers is much more complex than those of liquid-dominated gels. Herein, this work provides all-solid-state polymer materials with a wide tunable thermopower range (+20~−6 mV K−1), which is different from previously reported gels. Moreover, the mechanism of p-n conversion in all-solid-state ionic thermoelectric polymer material at the atomic scale was presented based on the analysis of Eastman entropy changes by molecular dynamics simulation, which provides a general strategy for tuning ionic thermopower and is beneficial to understand the fundamental mechanism of the p-n conversion. Furthermore, a self-powered ionic thermoelectric thermal sensor fabricated by the developed p- and n-type polymers demonstrated high sensitivity and durability, extending the application of ionic thermoelectric materials.
Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes
Authors: Albayram Mehmet Sait , Smith Garrett , Tufan Fatih , Tuna Ibrahim Sacit , Bostancıklıoğlu Mehmet , Zile Michael , Albayram Onder
Published: January 2022

Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Here we show dural lymphatic structures along the dural venous sinuses in dorsal regions and along cranial nerves in the ventral regions in the human brain. 3D T2-Fluid Attenuated Inversion Recovery magnetic resonance imaging relies on internal signals of protein rich lymphatic fluid rather than contrast media and is used in the present study to visualize the major human dural lymphatic structures. Moreover we detect direct connections between lymphatic fluid channels along the cranial nerves and vascular structures and the cervical lymph nodes. We also identify age-related cervical lymph node atrophy and thickening of lymphatics channels in both dorsal and ventral regions, findings which reflect the reduced lymphatic output of the aged brain.
Age influences on the molecular presentation of tumours
Authors: Li Constance H. , Haider Syed , Boutros Paul C.
Published: January 2022

Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterise them, we analyse age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour (0.077 mutations per megabase per year) and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but higher activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes such as CDKN2A and CREBBP are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations like SUFU loss and ATRX mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.
Cosmogenic radionuclides reveal an extreme solar particle storm near a solar minimum 9125 years BP
Authors: Paleari Chiara I. , Mekhaldi Florian , Adolphi Florian , Christl Marcus , Vockenhuber Christof , Gautschi Philip , Beer Jürg , Brehm Nicolas , Erhardt Tobias , Synal Hans-Arno , Wacker Lukas , Wilhelms Frank , Muscheler Raimund
Published: January 2022

During solar storms, the Sun expels large amounts of energetic particles (SEP) that can react with the Earth’s atmospheric constituents and produce cosmogenic radionuclides such as14C,10Be and36Cl. Here we present10Be and36Cl data measured in ice cores from Greenland and Antarctica. The data consistently show one of the largest10Be and36Cl production peaks detected so far, most likely produced by an extreme SEP event that hit Earth 9125 years BP (before present, i.e., before 1950 CE), i.e., 7176 BCE. Using the36Cl/10Be ratio, we demonstrate that this event was characterized by a very hard energy spectrum and was possibly up to two orders of magnitude larger than any SEP event during the instrumental period. Furthermore, we provide10Be-based evidence that, contrary to expectations, the SEP event occurred near a solar minimum.
Matrix mechanics regulates epithelial defence against cancer by tuning dynamic localization of filamin
Authors: Pothapragada Shilpa P. , Gupta Praver , Mukherjee Soumi , Das Tamal
Published: January 2022

In epithelia, normal cells recognize and extrude out newly emerged transformed cells by competition. This process is the most fundamental epithelial defence against cancer, whose occasional failure promotes oncogenesis. However, little is known about what factors determine the success or failure of this defence. Here we report that mechanical stiffening of extracellular matrix attenuates the epithelial defence against HRasV12-transformed cells. Using photoconversion labelling, protein tracking, and loss-of-function mutations, we attribute this attenuation to stiffening-induced perinuclear sequestration of a cytoskeletal protein, filamin. On soft matrix mimicking healthy epithelium, filamin exists as a dynamically single population, which moves to the normal cell-transformed cell interface to initiate the extrusion of transformed cells. However, on stiff matrix mimicking fibrotic epithelium, filamin redistributes into two dynamically distinct populations, including a new perinuclear pool that cannot move to the cell-cell interface. A matrix stiffness-dependent differential between filamin-Cdc42 and filamin-perinuclear cytoskeleton interaction controls this distinctive filamin localization and hence, determines the success or failure of epithelial defence on soft versus stiff matrix. Together, our study reveals how pathological matrix stiffening leads to a failed epithelial defence at the initial stage of oncogenesis.
Following excited-state chemical shifts in molecular ultrafast x-ray photoelectron spectroscopy
Authors: Mayer D. , Lever F. , Picconi D. , Metje J. , Alisauskas S. , Calegari F. , Düsterer S. , Ehlert C. , Feifel R. , Niebuhr M. , Manschwetus B. , Kuhlmann M. , Mazza T. , Robinson M. S. , Squibb R. J. , Trabattoni A. , Wallner M. , Saalfrank P. , Wolf T. J. A. , Gühr M.
Published: January 2022

The conversion of photon energy into other energetic forms in molecules is accompanied by charge moving on ultrafast timescales. We directly observe the charge motion at a specific site in an electronically excited molecule using time-resolved x-ray photoelectron spectroscopy (TR-XPS). We extend the concept of static chemical shift from conventional XPS by the excited-state chemical shift (ESCS), which is connected to the charge in the framework of a potential model. This allows us to invert TR-XPS spectra to the dynamic charge at a specific atom. We demonstrate the power of TR-XPS by using sulphur 2p-core-electron-emission probing to study the UV-excited dynamics of 2-thiouracil. The method allows us to discover that a major part of the population relaxes to the molecular ground state within 220–250 fs. In addition, a 250-fs oscillation, visible in the kinetic energy of the TR-XPS, reveals a coherent exchange of population among electronic states.
A record thermoelectric efficiency in tellurium-free modules for low-grade waste heat recovery
Authors: Bu Zhonglin , Zhang Xinyue , Hu Yixin , Chen Zhiwei , Lin Siqi , Li Wen , Xiao Chong , Pei Yanzhong
Published: January 2022

Low-grade heat accounts for >50% of the total dissipated heat sources in industries. An efficient recovery of low-grade heat into useful electricity not only reduces the consumption of fossil-fuels but also releases the subsequential environmental-crisis. Thermoelectricity offers an ideal solution, yet low-temperature efficient materials have continuously been limited to Bi2Te3-alloys since the discovery in 1950s. Scarcity of tellurium and the strong property anisotropy cause high-cost in both raw-materials and synthesis/processing. Here we demonstrate cheap polycrystalline antimonides for even more efficient thermoelectric waste-heat recovery within 600 K than conventional tellurides. This is enabled by a design of Ni/Fe/Mg3SbBi and Ni/Sb/CdSb contacts for both a prevention of chemical diffusion and a low interfacial resistivity, realizing a record and stable module efficiency at a temperature difference of 270 K. In addition, the raw-material cost  to the output power ratio in this work is reduced to be only 1/15 of that of conventional Bi2Te3-modules.
Catalytic production of low-carbon footprint sustainable natural gas
Authors: Si Xiaoqin , Lu Rui , Zhao Zhitong , Yang Xiaofeng , Wang Feng , Jiang Huifang , Luo Xiaolin , Wang Aiqin , Feng Zhaochi , Xu Jie , Lu Fang
Published: January 2022

Natural gas is one of the foremost basic energy sources on earth. Although biological process appears as promising valorization routes to transfer biomass to sustainable methane, the recalcitrance of lignocellulosic biomass is the major limitation for the production of mixing gas to meet the natural gas composition of pipeline transportation. Here we develop a catalytic-drive approach to directly transfer solid biomass to bio-natural gas which can be suitable for the current infrastructure. A catalyst with Ni2Al3 alloy phase enables nearly complete conversion of various agricultural and forestry residues, the total carbon yield of gas products reaches up to 93% after several hours at relative low-temperature (300 degrees Celsius). And the catalyst shows powerful processing capability for the production of natural gas during thirty cycles. A low-carbon footprint is estimated by a preliminary life cycle assessment, especially for the low hydrogen pressure and non-fossil hydrogen, and technical economic analysis predicts that this process is an economically competitive production process.
Identification of a modular super-enhancer in murine retinal development
Authors: Honnell Victoria , Norrie Jackie L. , Patel Anand G. , Ramirez Cody , Zhang Jiakun , Lai Yu-Hsuan , Wan Shibiao , Dyer Michael A.
Published: January 2022

Super-enhancers are expansive regions of genomic DNA comprised of multiple putative enhancers that contribute to the dynamic gene expression patterns during development. This is particularly important in neurogenesis because many essential transcription factors have complex developmental stage– and cell–type specific expression patterns across the central nervous system. In the developing retina, Vsx2 is expressed in retinal progenitor cells and is maintained in differentiated bipolar neurons and Müller glia. A single super-enhancer controls this complex and dynamic pattern of expression. Here we show that deletion of one region disrupts retinal progenitor cell proliferation but does not affect cell fate specification. The deletion of another region has no effect on retinal progenitor cell proliferation but instead leads to a complete loss of bipolar neurons. This prototypical super-enhancer may serve as a model for dissecting the complex gene expression patterns for neurogenic transcription factors during development. Moreover, it provides a unique opportunity to alter expression of individual transcription factors in particular cell types at specific stages of development. This provides a deeper understanding of function that cannot be achieved with traditional knockout mouse approaches.
Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine
Authors: Hendrickson Sara M. , Thomas Archana , Prongay Kamm , Haertel Andrew J. , Garzel Laura M. , Gill Leanne , Barr Tasha , Rhoades Nicholas S. , Reader Rachel , Galan Mark , Carroll Julie M. , Roberts Charles T. , Gao Lina , Amanna Ian J. , Messaoudi Ilhem , Slifka Mark K.
Published: January 2022

Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.
Ultra-low threshold lasing through phase front engineering via a metallic circular aperture
Authors: Wang Zhixin , Kapsalidis Filippos , Wang Ruijun , Beck Mattias , Faist Jérôme
Published: January 2022

Semiconductor lasers with extremely low threshold power require a combination of small volume active region with high-quality-factor cavities. For ridge lasers with highly reflective coatings, an ultra-low threshold demands significantly suppressing the diffraction loss at the facets of the laser. Here, we demonstrate that introducing a subwavelength aperture in the metallic highly reflective coating of a laser can correct the phase front, thereby counter-intuitively enhancing both its modal reflectivity and transmissivity at the same time. Theoretical and experimental results manifest a decreasing in the mirror loss by over 40% and an increasing in the transmissivity by 104. Implementing this method on a small-cavity quantum cascade laser, room-temperature continuous-wave lasing operation at 4.5 μm wavelength with an electrical consumption power of only 143 mW is achieved. Our work suggests possibilities for future portable applications and can be implemented in a broad range of optoelectronic systems.