bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annual aboveground carbon uptake enhancements from assisted gene flow in boreal black spruce forests are not long-lasting
Authors: Girardin Martin P. , Isabel Nathalie , Guo Xiao Jing , Lamothe Manuel , Duchesne Isabelle , Lenz Patrick 
Published: February 2021

AbstractAssisted gene flow between populations has been proposed as an adaptive forest management strategy that could contribute to the sequestration of carbon. Here we provide an assessment of the mitigation potential of assisted gene flow in 46 populations of the widespread boreal conifer Picea mariana, grown in two 42-year-old common garden experiments and established in contrasting Canadian boreal regions. We use a dendroecological approach taking into account phylogeographic structure to retrospectively analyse population phenotypic variability in annual aboveground net primary productivity (NPP). We compare population NPP phenotypes to detect signals of adaptive variation and/or the presence of phenotypic clines across tree lifespans, and assess genotype‐by‐environment interactions by evaluating climate and NPP relationships. Our results show a positive effect of assisted gene flow for a period of approximately 15 years following planting, after which there was little to no effect. Although not long lasting, well-informed assisted gene flow could accelerate the transition from carbon source to carbon sink after disturbance.
Eltrombopag directly inhibits BAX and prevents cell death
Authors: Spitz Adam Z. , Zacharioudakis Emmanouil , Reyna Denis E. , Garner Thomas P. , Gavathiotis Evripidis 
Published: February 2021

AbstractThe BCL-2 family protein BAX has essential activity in mitochondrial regulation of cell death. While BAX activity ensures tissue homeostasis, when dysregulated it contributes to aberrant cell death in several diseases. During cellular stress BAX is transformed from an inactive cytosolic conformation to a toxic mitochondrial oligomer. Although the BAX transformation process is not well understood, drugs that interfere with this process are useful research tools and potential therapeutics. Here, we show that Eltrombopag, an FDA-approved drug, is a direct inhibitor of BAX. Eltrombopag binds the BAX trigger site distinctly from BAX activators, preventing them from triggering BAX conformational transformation and simultaneously promoting stabilization of the inactive BAX structure. Accordingly, Eltrombopag is capable of inhibiting BAX-mediated apoptosis induced by cytotoxic stimuli. Our data demonstrate structure-function insights into a mechanism of BAX inhibition and reveal a mechanism for Eltrombopag that may expand its use in diseases of uncontrolled cell death.
High-efficiency magnetic refrigeration using holmium
Authors: Terada Noriki , Mamiya Hiroaki 
Published: February 2021

AbstractMagnetic refrigeration (MR) is a method of cooling matter using a magnetic field. Traditionally, it has been studied for use in refrigeration near room temperature; however, recently MR research has also focused on a target temperature as low as 20 K for hydrogen liquefaction. Most research to date has employed high magnetic fields (at least 5 T) to obtain a large entropy change, which requires a superconducting magnet and, therefore, incurs a large energy cost. Here we propose an alternative highly efficient cooling technique in which small magnetic field changes, Δμ0H≤ 0.4 T, can obtain a cooling efficiency of −ΔSM/Δμ0H = 32 J kg−1K−1T−1, which is one order of magnitude higher than what has been achieved using typical magnetocaloric materials. Our method uses holmium, which exhibits a steep magnetization change with varying temperature and magnetic field. The proposed technique can be implemented using permanent magnets, making it a suitable alternative to conventional gas compression–based cooling for hydrogen liquefaction.
The evolution of critical thermal limits of life on Earth
Authors: Bennett Joanne M. , Sunday Jennifer , Calosi Piero , Villalobos Fabricio , Martínez Brezo , Molina-Venegas Rafael , Araújo Miguel B. , Algar Adam C. , Clusella-Trullas Susana , Hawkins Bradford A. , Keith Sally A. , Kühn Ingolf , Rahbek Carsten , Rodríguez Laura , Singer Alexander , Morales-Castilla Ignacio , Olalla-Tárraga Miguel Ángel 
Published: February 2021

AbstractUnderstanding how species’ thermal limits have evolved across the tree of life is central to predicting species’ responses to climate change. Here, using experimentally-derived estimates of thermal tolerance limits for over 2000 terrestrial and aquatic species, we show that most of the variation in thermal tolerance can be attributed to a combination of adaptation to current climatic extremes, and the existence of evolutionary ‘attractors’ that reflect either boundaries or optima in thermal tolerance limits. Our results also reveal deep-time climate legacies in ectotherms, whereby orders that originated in cold paleoclimates have presently lower cold tolerance limits than those with warm thermal ancestry. Conversely, heat tolerance appears unrelated to climate ancestry. Cold tolerance has evolved more quickly than heat tolerance in endotherms and ectotherms. If the past tempo of evolution for upper thermal limits continues, adaptive responses in thermal limits will have limited potential to rescue the large majority of species given the unprecedented rate of contemporary climate change.
Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients
Authors: Xydia Maria , Rahbari Raheleh , Ruggiero Eliana , Macaulay Iain , Tarabichi Maxime , Lohmayer Robert , Wilkening Stefan , Michels Tillmann , Brown Daniel , Vanuytven Sebastiaan , Mastitskaya Svetlana , Laidlaw Sean , Grabe Niels , Pritsch Maria , Fronza Raffaele , Hexel Klaus , Schmitt Steffen , Müller-Steinhardt Michael , Halama Niels , Domschke Christoph , Schmidt Manfred , von Kalle Christof , Schütz Florian , Voet Thierry , Beckhove Philipp 
Published: February 2021

AbstractRegulatory CD4+ T cells (Treg) prevent tumor clearance by conventional T cells (Tconv) comprising a major obstacle of cancer immune-surveillance. Hitherto, the mechanisms of Treg repertoire formation in human cancers remain largely unclear. Here, we analyze Treg clonal origin in breast cancer patients using T-Cell Receptor and single-cell transcriptome sequencing. While Treg in peripheral blood and breast tumors are clonally distinct, Tconv clones, including tumor-antigen reactive effectors (Teff), are detected in both compartments. Tumor-infiltrating CD4+ cells accumulate into distinct transcriptome clusters, including early activated Tconv, uncommitted Teff, Th1 Teff, suppressive Treg and pro-tumorigenic Treg. Trajectory analysis suggests early activated Tconv differentiation either into Th1 Teff or into suppressive and pro-tumorigenic Treg. Importantly, Tconv, activated Tconv and Treg share highly-expanded clones contributing up to 65% of intratumoral Treg. Here we show that Treg in human breast cancer may considerably stem from antigen-experienced Tconv converting into secondary induced Treg through intratumoral activation.
Patient-derived xenografts and organoids model therapy response in prostate cancer
Authors: Karkampouna Sofia , La Manna Federico , Benjak Andrej , Kiener Mirjam , De Menna Marta , Zoni Eugenio , Grosjean Joël , Klima Irena , Garofoli Andrea , Bolis Marco , Vallerga Arianna , Theurillat Jean-Philippe , De Filippo Maria R. , Genitsch Vera , Keller David , Booij Tijmen H. , Stirnimann Christian U. , Eng Kenneth , Sboner Andrea , Ng Charlotte K. Y. , Piscuoglio Salvatore , Gray Peter C. , Spahn Martin , Rubin Mark A. , Thalmann George N. , Kruithof-de Julio Marianna 
Published: February 2021

AbstractTherapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe an androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa). RNA and whole-exome sequencing of the PDX tissue and organoids confirmed transcriptomic and genomic similarity to primary tumor. PNPCa harbors BRCA2 and CHD1 somatic mutations, shows an SPOP/FOXA1-like transcriptomic signature and microsatellite instability, which occurs in 3% of advanced PCa and has never been modeled in vivo. Comparison of the treatment-naïve PNPCa with additional metastatic PDXs (BM18, LAPC9), in a medium-throughput organoid screen of FDA-approved compounds, revealed differential drug sensitivities. Multikinase inhibitors (ponatinib, sunitinib, sorafenib) were broadly effective on all PDX- and patient-derived organoids from advanced cases with acquired resistance to standard-of-care compounds. This proof-of-principle study may provide a preclinical tool to screen drug responses to standard-of-care and newly identified, repurposed compounds.
Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections
Authors: Bénard Alan , Jacobsen Anne , Brunner Maximilian , Krautz Christian , Klösch Bettina , Swierzy Izabela , Naschberger Elisabeth , Podolska Malgorzata J. , Kouhestani Dina , David Paul , Birkholz Torsten , Castellanos Ixchel , Trufa Denis , Sirbu Horia , Vetter Marcel , Kremer Andreas E. , Hildner Kai , Hecker Andreas , Edinger Fabian , Tenbusch Matthias , Mühl-Zürbes Petra , Steinkasserer Alexander , Richter Enrico , Streeck Hendrik , Berger Marc M. , Brenner Thorsten , Weigand Markus A. , Swirski Filip K. , Schett Georg , Grützmann Robert , Weber Georg F. 
Published: February 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNα and IFNλ levels when compared to non-severe COVID-19 patients. In a mouse model of pulmonary HSV-1 infection, treatment with recombinant IL-3 reduces viral load and mortality. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating pDCs into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells, both, in mice and in COVID-19 negative patients exhibiting pulmonary diseases. This study identifies IL-3 as a predictive disease marker for SARS-CoV-2 infections and as a potential therapeutic target for pulmunory viral infections.
Direct supercritical angle localization microscopy for nanometer 3D superresolution
Authors: Dasgupta Anindita , Deschamps Joran , Matti Ulf , Hübner Uwe , Becker Jan , Strauss Sebastian , Jungmann Ralf , Heintzmann Rainer , Ries Jonas 
Published: February 2021

Abstract3D single molecule localization microscopy (SMLM) is an emerging superresolution method for structural cell biology, as it allows probing precise positions of proteins in cellular structures. In supercritical angle localization microscopy (SALM), z-positions of single fluorophores are extracted from the intensity of supercritical angle fluorescence, which strongly depends on their distance to the coverslip. Here, we realize the full potential of SALM and improve its z-resolution by more than four-fold compared to the state-of-the-art by directly splitting supercritical and undercritical emission, using an ultra-high NA objective, and applying fitting routines to extract precise intensities of single emitters. We demonstrate nanometer isotropic localization precision on DNA origami structures, and on clathrin coated vesicles and microtubules in cells, illustrating the potential of SALM for cell biology.
Ice-nucleating proteins are activated by low temperatures to control the structure of interfacial water
Authors: Roeters Steven J. , Golbek Thaddeus W. , Bregnhøj Mikkel , Drace Taner , Alamdari Sarah , Roseboom Winfried , Kramer Gertjan , Šantl-Temkiv Tina , Finster Kai , Pfaendtner Jim , Woutersen Sander , Boesen Thomas , Weidner Tobias 
Published: February 2021

AbstractIce-nucleation active (INA) bacteria can promote the growth of ice more effectively than any other known material. Using specialized ice-nucleating proteins (INPs), they obtain nutrients from plants by inducing frost damage and, when airborne in the atmosphere, they drive ice nucleation within clouds, which may affect global precipitation patterns. Despite their evident environmental importance, the molecular mechanisms behind INP-induced freezing have remained largely elusive. We investigate the structural basis for the interactions between water and the ice-nucleating protein InaZ from the INA bacterium Pseudomonas syringae. Using vibrational sum-frequency generation (SFG) and two-dimensional infrared spectroscopy, we demonstrate that the ice-active repeats of InaZ adopt a β-helical structure in solution and at water surfaces. In this configuration, interaction between INPs and water molecules imposes structural ordering on the adjacent water network. The observed order of water increases as the interface is cooled to temperatures close to the melting point of water. Experimental SFG data combined with molecular-dynamics simulations and spectral calculations show that InaZ reorients at lower temperatures. This reorientation can enhance water interactions, and thereby the effectiveness of ice nucleation.
Experimental evidence for the existence of a second partially-ordered phase of ice VI
Authors: Yamane Ryo , Komatsu Kazuki , Gouchi Jun , Uwatoko Yoshiya , Machida Shinichi , Hattori Takanori , Ito Hayate , Kagi Hiroyuki 
Published: February 2021

AbstractIce exhibits extraordinary structural variety in its polymorphic structures. The existence of a new form of diversity in ice polymorphism has recently been debated in both experimental and theoretical studies, questioning whether hydrogen-disordered ice can transform into multiple hydrogen-ordered phases, contrary to the known one-to-one correspondence between disordered ice and its ordered phase. Here, we report a high-pressure phase, ice XIX, which is a second hydrogen-partially-ordered phase of ice VI. We demonstrate that disordered ice undergoes different manners of hydrogen ordering, which are thermodynamically controlled by pressure in the case of ice VI. Such multiplicity can appear in all disordered ice, and it widely provides a research approach to deepen our knowledge, for example of the crucial issues of ice: the centrosymmetry of hydrogen-ordered configurations and potentially induced (anti-)ferroelectricity. Ultimately, this research opens up the possibility of completing the phase diagram of ice.
Deep learning the collisional cross sections of the peptide universe from a million experimental values
Authors: Meier Florian , Köhler Niklas D. , Brunner Andreas-David , Wanka Jean-Marc H. , Voytik Eugenia , Strauss Maximilian T. , Theis Fabian J. , Mann Matthias 
Published: February 2021

AbstractThe size and shape of peptide ions in the gas phase are an under-explored dimension for mass spectrometry-based proteomics. To investigate the nature and utility of the peptide collisional cross section (CCS) space, we measure more than a million data points from whole-proteome digests of five organisms with trapped ion mobility spectrometry (TIMS) and parallel accumulation-serial fragmentation (PASEF). The scale and precision (CV < 1%) of our data is sufficient to train a deep recurrent neural network that accurately predicts CCS values solely based on the peptide sequence. Cross section predictions for the synthetic ProteomeTools peptides validate the model within a 1.4% median relative error (R > 0.99). Hydrophobicity, proportion of prolines and position of histidines are main determinants of the cross sections in addition to sequence-specific interactions. CCS values can now be predicted for any peptide and organism, forming a basis for advanced proteomics workflows that make full use of the additional information.
Entry of spores into intestinal epithelial cells contributes to recurrence of Clostridioides difficile infection
Authors: Castro-Córdova Pablo , Mora-Uribe Paola , Reyes-Ramírez Rodrigo , Cofré-Araneda Glenda , Orozco-Aguilar Josué , Brito-Silva Christian , Mendoza-León María José , Kuehne Sarah A. , Minton Nigel P. , Pizarro-Guajardo Marjorie , Paredes-Sabja Daniel 
Published: February 2021

AbstractClostridioides difficile spores produced during infection are important for the recurrence of the disease. Here, we show that C. difficile spores gain entry into the intestinal mucosa via pathways dependent on host fibronectin-α5β1 and vitronectin-αvβ1. The exosporium protein BclA3, on the spore surface, is required for both entry pathways. Deletion of the bclA3 gene in C. difficile, or pharmacological inhibition of endocytosis using nystatin, leads to reduced entry into the intestinal mucosa and reduced recurrence of the disease in a mouse model. Our findings indicate that C. difficile spore entry into the intestinal barrier can contribute to spore persistence and infection recurrence, and suggest potential avenues for new therapies.
Non-CG methylation and multiple histone profiles associate child abuse with immune and small GTPase dysregulation
Authors: Lutz Pierre-Eric , Chay Marc-Aurèle , Pacis Alain , Chen Gary G. , Aouabed Zahia , Maffioletti Elisabetta , Théroux Jean-François , Grenier Jean-Christophe , Yang Jennie , Aguirre Maria , Ernst Carl , Redensek Adriana , van Kempen Léon C. , Yalcin Ipek , Kwan Tony , Mechawar Naguib , Pastinen Tomi , Turecki Gustavo 
Published: February 2021

AbstractEarly-life adversity (ELA) is a major predictor of psychopathology, and is thought to increase lifetime risk by epigenetically regulating the genome. Here, focusing on the lateral amygdala, a major brain site for emotional homeostasis, we describe molecular cross-talk among multiple mechanisms of genomic regulation, including 6 histone marks and DNA methylation, and the transcriptome, in subjects with a history of ELA and controls. In the healthy brain tissue, we first uncover interactions between different histone marks and non-CG methylation in the CAC context. Additionally, we find that ELA associates with methylomic changes that are as frequent in the CAC as in the canonical CG context, while these two forms of plasticity occur in sharply distinct genomic regions, features, and chromatin states. Combining these multiple data indicates that immune-related and small GTPase signaling pathways are most consistently impaired in the amygdala of ELA individuals. Overall, this work provides insights into genomic brain regulation as a function of early-life experience.
Acoustofluidic rotational tweezing enables high-speed contactless morphological phenotyping of zebrafish larvae
Authors: Chen Chuyi , Gu Yuyang , Philippe Julien , Zhang Peiran , Bachman Hunter , Zhang Jinxin , Mai John , Rufo Joseph , Rawls John F. , Davis Erica E. , Katsanis Nicholas , Huang Tony Jun 
Published: February 2021

AbstractModern biomedical research and preclinical pharmaceutical development rely heavily on the phenotyping of small vertebrate models for various diseases prior to human testing. In this article, we demonstrate an acoustofluidic rotational tweezing platform that enables contactless, high-speed, 3D multispectral imaging and digital reconstruction of zebrafish larvae for quantitative phenotypic analysis. The acoustic-induced polarized vortex streaming achieves contactless and rapid (~1 s/rotation) rotation of zebrafish larvae. This enables multispectral imaging of the zebrafish body and internal organs from different viewing perspectives. Moreover, we develop a 3D reconstruction pipeline that yields accurate 3D models based on the multi-view images for quantitative evaluation of basic morphological characteristics and advanced combinations of metrics. With its contactless nature and advantages in speed and automation, our acoustofluidic rotational tweezing system has the potential to be a valuable asset in numerous fields, especially for developmental biology, small molecule screening in biochemistry, and pre-clinical drug development in pharmacology.
Towards tellurium-free thermoelectric modules for power generation from low-grade heat
Authors: Ying Pingjun , He Ran , Mao Jun , Zhang Qihao , Reith Heiko , Sui Jiehe , Ren Zhifeng , Nielsch Kornelius , Schierning Gabi 
Published: February 2021

AbstractThermoelectric technology converts heat into electricity directly and is a promising source of clean electricity. Commercial thermoelectric modules have relied on Bi2Te3-based compounds because of their unparalleled thermoelectric properties at temperatures associated with low-grade heat (<550 K). However, the scarcity of elemental Te greatly limits the applicability of such modules. Here we report the performance of thermoelectric modules assembled from Bi2Te3-substitute compounds, including p-type MgAgSb and n-type Mg3(Sb,Bi)2, by using a simple, versatile, and thus scalable processing routine. For a temperature difference of ~250 K, whereas a single-stage module displayed a conversion efficiency of ~6.5%, a module using segmented n-type legs displayed a record efficiency of ~7.0% that is comparable to the state-of-the-art Bi2Te3-based thermoelectric modules. Our work demonstrates the feasibility and scalability of high-performance thermoelectric modules based on sustainable elements for recovering low-grade heat.
Transcription activation by a sliding clamp
Authors: Shi Jing , Wen Aijia , Jin Sha , Gao Bo , Huang Yang , Feng Yu 
Published: February 2021

AbstractTranscription activation of bacteriophage T4 late genes is accomplished by a transcription activation complex containing RNA polymerase (RNAP), the promoter specificity factor gp55, the coactivator gp33, and a universal component of cellular DNA replication, the sliding clamp gp45. Although genetic and biochemical studies have elucidated many aspects of T4 late gene transcription, no precise structure of the transcription machinery in the process is available. Here, we report the cryo-EM structures of a gp55-dependent RNAP-promoter open complex and an intact gp45-dependent transcription activation complex. The structures reveal the interactions between gp55 and the promoter DNA that mediate the recognition of T4 late promoters. In addition to the σR2 homology domain, gp55 has a helix-loop-helix motif that chaperons the template-strand single-stranded DNA of the transcription bubble. Gp33 contacts both RNAP and the upstream double-stranded DNA. Gp45 encircles the DNA and tethers RNAP to it, supporting the idea that gp45 switches the promoter search from three-dimensional diffusion mode to one-dimensional scanning mode.
Bifurcation in brain dynamics reveals a signature of conscious processing independent of report
Authors: Sergent Claire , Corazzol Martina , Labouret Ghislaine , Stockart François , Wexler Mark , King Jean-Rémi , Meyniel Florent , Pressnitzer Daniel 
Published: February 2021

AbstractAn outstanding challenge for consciousness research is to characterize the neural signature of conscious access independently of any decisional processes. Here we present a model-based approach that uses inter-trial variability to identify the brain dynamics associated with stimulus processing. We demonstrate that, even in the absence of any task or behavior, the electroencephalographic response to auditory stimuli shows bifurcation dynamics around 250–300 milliseconds post-stimulus. Namely, the same stimulus gives rise to late sustained activity on some trials, and not on others. This late neural activity is predictive of task-related reports, and also of reports of conscious contents that are randomly sampled during task-free listening. Source localization further suggests that task-free conscious access recruits the same neural networks as those associated with explicit report, except for frontal executive components. Studying brain dynamics through variability could thus play a key role for identifying the core signatures of conscious access, independent of report.