bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase-dependent amplification of working memory content and performance
Authors: ten Oever Sanne , De Weerd Peter , Sack Alexander T. 
Published: April 2020

AbstractSuccessful working memory performance has been related to oscillatory mechanisms operating in low-frequency ranges. Yet, their mechanistic interaction with the distributed neural activity patterns representing the content of the memorized information remains unclear. Here, we record EEG during a working memory retention interval, while a task-irrelevant, high-intensity visual impulse stimulus is presented to boost the read-out of distributed neural activity related to the content held in working memory. Decoding of this activity with a linear classifier reveals significant modulations of classification accuracy by oscillatory phase in the theta/alpha ranges at the moment of impulse presentation. Additionally, behavioral accuracy is highest at the phases showing maximized decoding accuracy. At those phases, behavioral accuracy is higher in trials with the impulse compared to no-impulse trials. This constitutes the first evidence in humans that working memory information is maximized within limited phase ranges, and that phase-selective, sensory impulse stimulation can improve working memory.
Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection
Authors: Adland Emily , Millar Jane , Bengu Nomonde , Muenchhoff Maximilian , Fillis Rowena , Sprenger Kenneth , Ntlantsana Vuyokasi , Roider Julia , Vieira Vinicius , Govender Katya , Adamson John , Nxele Nelisiwe , Ochsenbauer Christina , Kappes John , Mori Luisa , van Lobenstein Jeroen , Graza Yeney , Chinniah Kogielambal , Kapongo Constant , Bhoola Roopesh , Krishna Malini , Matthews Philippa C. , Poderos Ruth Penya , Lluch Marta Colomer , Puertas Maria C. , Prado Julia G. , McKerrow Neil , Archary Moherndran , Ndung’u Thumbi , Groll Andreas , Jooste Pieter , Martinez-Picado Javier , Altfeld Marcus , Goulder Philip 
Published: April 2020

AbstractFemale children and adults typically generate more efficacious immune responses to vaccines and infections than age-matched males, but also suffer greater immunopathology and autoimmune disease. We here describe, in a cohort of > 170 in utero HIV-infected infants from KwaZulu-Natal, South Africa, fetal immune sex differences resulting in a 1.5–2-fold increased female susceptibility to intrauterine HIV infection. Viruses transmitted to females have lower replicative capacity (p = 0.0005) and are more type I interferon-resistant (p = 0.007) than those transmitted to males. Cord blood cells from females of HIV-uninfected sex-discordant twins are more activated (p = 0.01) and more susceptible to HIV infection in vitro (p = 0.03). Sex differences in outcome include superior maintenance of aviraemia among males (p = 0.007) that is not explained by differential antiretroviral therapy adherence. These data demonstrate sex-specific innate immune selection of HIV associated with increased female susceptibility to in utero infection and enhanced functional cure potential among infected males.
Ribosome profiling at isoform level reveals evolutionary conserved impacts of differential splicing on the proteome
Authors: Reixachs-Solé Marina , Ruiz-Orera Jorge , Albà M. Mar , Eyras Eduardo 
Published: April 2020

AbstractThe differential production of transcript isoforms from gene loci is a key cellular mechanism. Yet, its impact in protein production remains an open question. Here, we describe ORQAS (ORF quantification pipeline for alternative splicing), a pipeline for the translation quantification of individual transcript isoforms using ribosome-protected mRNA fragments (ribosome profiling). We find evidence of translation for 40–50% of the expressed isoforms in human and mouse, with 53% of the expressed genes having more than one translated isoform in human, and 33% in mouse. Differential splicing analysis revealed that about 40% of the splicing changes at RNA level are concordant with changes in translation. Furthermore, orthologous cassette exons between human and mouse preserve the directionality of the change, and are enriched in microexons in a comparison between glia and glioma. ORQAS leverages ribosome profiling to uncover a widespread and evolutionarily conserved impact of differential splicing on translation, particularly of microexon-containing isoforms.
Glycogen metabolism regulates macrophage-mediated acute inflammatory responses
Authors: Ma Jingwei , Wei Keke , Liu Junwei , Tang Ke , Zhang Huafeng , Zhu Liyan , Chen Jie , Li Fei , Xu Pingwei , Chen Jie , Liu Jincheng , Fang Haiqing , Tang Liang , Wang Dianheng , Zeng Liping , Sun Weiwei , Xie Jing , Liu Yuying , Huang Bo 
Published: April 2020

AbstractOur current understanding of how sugar metabolism affects inflammatory pathways in macrophages is incomplete. Here, we show that glycogen metabolism is an important event that controls macrophage-mediated inflammatory responses. IFN-γ/LPS treatment stimulates macrophages to synthesize glycogen, which is then channeled through glycogenolysis to generate G6P and further through the pentose phosphate pathway to yield abundant NADPH, ensuring high levels of reduced glutathione for inflammatory macrophage survival. Meanwhile, glycogen metabolism also increases UDPG levels and the receptor P2Y14 in macrophages. The UDPG/P2Y14 signaling pathway not only upregulates the expression of STAT1 via activating RARβ but also promotes STAT1 phosphorylation by downregulating phosphatase TC45. Blockade of this glycogen metabolic pathway disrupts acute inflammatory responses in multiple mouse models. Glycogen metabolism also regulates inflammatory responses in patients with sepsis. These findings show that glycogen metabolism in macrophages is an important regulator and indicate strategies that might be used to treat acute inflammatory diseases.
Quantifying the heterogeneity of macromolecular machines by mass photometry
Authors: Sonn-Segev Adar , Belacic Katarina , Bodrug Tatyana , Young Gavin , VanderLinden Ryan T. , Schulman Brenda A. , Schimpf Johannes , Friedrich Thorsten , Dip Phat Vinh , Schwartz Thomas U. , Bauer Benedikt , Peters Jan-Michael , Struwe Weston B. , Benesch Justin L. P. , Brown Nicholas G. , Haselbach David , Kukura Philipp 
Published: April 2020

AbstractSample purity is central to in vitro studies of protein function and regulation, and to the efficiency and success of structural studies using techniques such as x-ray crystallography and cryo-electron microscopy (cryo-EM). Here, we show that mass photometry (MP) can accurately characterize the heterogeneity of a sample using minimal material with high resolution within a matter of minutes. To benchmark our approach, we use negative stain electron microscopy (nsEM), a popular method for EM sample screening. We include typical workflows developed for structure determination that involve multi-step purification of a multi-subunit ubiquitin ligase and chemical cross-linking steps. When assessing the integrity and stability of large molecular complexes such as the proteasome, we detect and quantify assemblies invisible to nsEM. Our results illustrate the unique advantages of MP over current methods for rapid sample characterization, prioritization and workflow optimization.
Structural insights into the mechanism and inhibition of transglutaminase-induced ubiquitination by the Legionella effector MavC
Authors: Mu Yajuan , Wang Yue , Huang Yanfei , Li Dong , Han Youyou , Chang Min , Fu Jiaqi , Xie Yongchao , Ren Jie , Wang Hao , Zhang Yi , Luo Zhao-Qing , Feng Yue 
Published: April 2020

AbstractProtein ubiquitination is one of the most prevalent post-translational modifications, controlling virtually every process in eukaryotic cells. Recently, the Legionella effector MavC was found to mediate a unique ubiquitination through transglutamination, linking ubiquitin (Ub) to UBE2N through UbGln40 in a process that can be inhibited by another Legionella effector, Lpg2149. Here, we report the structures of MavC/UBE2N/Ub ternary complex, MavC/UBE2N-Ub (product) binary complex, and MavC/Lpg2149 binary complex. During the ubiquitination, the loop containing the modification site K92 of UBE2N undergoes marked conformational change, and Lpg2149 inhibits this ubiquitination through competing with Ub to bind MavC. Moreover, we found that MavC itself also exhibits weak deubiquitinase activity towards this non-canonical ubiquitination. Together, our study not only provides insights into the mechanism and inhibition of this transglutaminase-induced ubiquitination by MavC, but also sheds light on the future studies into UBE2N inhibition by this modification and deubiquitinases of this unique ubiquitination.
Dietary lipids fuel GPX4-restricted enteritis resembling Crohn’s disease
Authors: Mayr Lisa , Grabherr Felix , Schwärzler Julian , Reitmeier Isabelle , Sommer Felix , Gehmacher Thomas , Niederreiter Lukas , He Gui-Wei , Ruder Barbara , Kunz Kai T. R. , Tymoszuk Piotr , Hilbe Richard , Haschka David , Feistritzer Clemens , Gerner Romana R. , Enrich Barbara , Przysiecki Nicole , Seifert Markus , Keller Markus A. , Oberhuber Georg , Sprung Susanne , Ran Qitao , Koch Robert , Effenberger Maria , Tancevski Ivan , Zoller Heinz , Moschen Alexander R. , Weiss Günter , Becker Christoph , Rosenstiel Philip , Kaser Arthur , Tilg Herbert , Adolph Timon E. 
Published: April 2020

AbstractThe increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn’s disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD.
The morphology, molecular development and ecological function of pseudonectaries on Nigella damascena (Ranunculaceae) petals
Authors: Liao Hong , Fu Xuehao , Zhao Huiqi , Cheng Jie , Zhang Rui , Yao Xu , Duan Xiaoshan , Shan Hongyan , Kong Hongzhi 
Published: April 2020

AbstractPseudonectaries, or false nectaries, the glistening structures that resemble nectaries or nectar droplets but do not secrete nectar, show considerable diversity and play important roles in plant-animal interactions. The morphological nature, optical features, molecular underpinnings and ecological functions of pseudonectaries, however, remain largely unclear. Here, we show that pseudonectaries ofNigella damascena(Ranunculaceae) are tiny, regional protrusions covered by tightly arranged, non-secretory polygonal epidermal cells with flat, smooth and reflective surface, and are clearly visible even under ultraviolet light and bee vision. We also show that genes associated with cell division, chloroplast development and wax formation are preferably expressed in pseudonectaries. Specifically,NidaYABBY5, an abaxial gene with ectopic expression in pseudonectaries, is indispensable for pseudonectary development: knockdown of it led to complete losses of pseudonectaries. Notably, when flowers without pseudonectaries were arrayed beside those with pseudonectaries, clear differences were observed in the visiting frequency, probing time and visiting behavior of pollinators (i.e., honey bees), suggesting that pseudonectaries serve as both visual attractants and nectar guides.
Capturing the primordial Kras mutation initiating urethane carcinogenesis
Authors: Li Siqi , MacAlpine David M. , Counter Christopher M. 
Published: April 2020

AbstractThe environmental carcinogen urethane exhibits a profound specificity for pulmonary tumors driven by an oncogenic Q61L/R mutation in the gene Kras. Similarly, the frequency, isoform, position, and substitution of oncogenic RAS mutations are often unique to human cancers. To elucidate the principles underlying this RAS mutation tropism of urethane, we adapted an error-corrected, high-throughput sequencing approach to detect mutations in murine Ras genes at great sensitivity. This analysis not only captured the initiating Kras mutation days after urethane exposure, but revealed that the sequence specificity of urethane mutagenesis, coupled with transcription and isoform locus, to be major influences on the extreme tropism of this carcinogen.
The effects of contemporaneous peer punishment on cooperation with the future
Authors: Lohse Johannes , Waichman Israel 
Published: April 2020

AbstractWe use a laboratory version of the intergenerational goods game (IGG) to investigate whether peer punishment facilitates the successful provision of multigenerational public goods. In our experiment, groups (generations) decide sequentially about the provision of a multigenerational public good through the voluntary contributions of their members. Successful provision requires that contributions meet a threshold and exclusively benefits members of future generations. Provision costs are borne only by the current generation. We compare a baseline condition without a punishment institution to a treatment condition where peer punishment can be inflicted exclusively on members of the same generation but not on members of past or future generations. We find that without punishment the likelihood of reaching the contribution threshold is low and that making punishment available within a generation is partially successful in sustaining cooperation in a succession of multiple generations.
A nitrogen-doped nanotube molecule with atom vacancy defects
Authors: Ikemoto Koki , Yang Seungmin , Naito Hisashi , Kotani Motoko , Sato Sota , Isobe Hiroyuki 
Published: April 2020

AbstractNitrogen-doped carbon nanotubes have attracted attention in various fields, but lack of congeners with discrete molecular structures has hampered developments based on in-depth, chemical understandings. In this study, a nanotube molecule doped periodically with multiple nitrogen atoms has been synthesized by combining eight 2,4,6-trisubstituted pyridine units with thirty-two 1,3,5-trisubstituted benzene units. A synthetic strategy involving geodesic phenine frameworks is sufficiently versatile to tolerate pyridine units without requiring synthetic detours. Crystallographic analyses adopting aspherical multipole atom models reveal the presence of axially rotated structures as a minor disordered structure, which also provides detailed molecular and electronic structures. The nitrogen atoms on the nanotube serve as chemically distinct sites covered with negatively charged surfaces, and they increase the chance of electron injections by lowering the energy levels of the unoccupied orbitals that should serve as electron acceptors.
A superelastochromic crystal
Authors: Mutai Toshiki , Sasaki Toshiyuki , Sakamoto Shunichi , Yoshikawa Isao , Houjou Hirohiko , Takamizawa Satoshi 
Published: April 2020

AbstractChromism—color changes by external stimuli—has been intensively studied to develop smart materials because of easily detectability of the stimuli by eye or common spectroscopy as color changes. Luminescent chromism has particularly attracted research interest because of its high sensitivity. The color changes typically proceed in a one-way, two-state cycle, i.e. a stimulus-induced state will restore the initial state by another stimuli. Chromic systems showing instant, biphasic color switching and spontaneous reversibility will have wider practical applicability. Here we report luminescent chromism having such characteristics shown by mechanically controllable phase transitions in a luminescent organosuperelastic crystal. In mechanochromic luminescence, superelasticity—diffusion-less plastic deformation with spontaneous shape recoverability—enables real-time, reversible, and stepless control of the abundance ratio of biphasic color emissions via a single-crystal-to-single-crystal transformation by controlling a single stimulus, force stress. The unique chromic system, referred to as superelastochromism, holds potential for realizing informative molecule-based mechanical sensing.
Adrenergic stress constrains the development of anti-tumor immunity and abscopal responses following local radiation
Authors: Chen Minhui , Qiao Guanxi , Hylander Bonnie L. , Mohammadpour Hemn , Wang Xiang-Yang , Subjeck John R. , Singh Anurag K. , Repasky Elizabeth A. 
Published: April 2020

AbstractThe abscopal effect following ionizing radiation therapy (RT) is considered to be a rare event. This effect does occur more frequently when combined with other therapies, including immunotherapy. Here we demonstrate that the frequency of abscopal events following RT alone is highly dependent upon the degree of adrenergic stress in the tumor-bearing host. Using a combination of physiologic, pharmacologic and genetic strategies, we observe improvements in the control of both irradiated and non-irradiated distant tumors, including metastatic tumors, when adrenergic stress or signaling through β-adrenergic receptor is reduced. Further, we observe cellular and molecular evidence of improved, antigen-specific, anti-tumor immune responses which also depend upon T cell egress from draining lymph nodes. These data suggest that blockade of β2 adrenergic stress signaling could be a useful, safe, and feasible strategy to improve efficacy in cancer patients undergoing radiation therapy.
Kinesin-1 regulates antigen cross-presentation through the scission of tubulations from early endosomes in dendritic cells
Authors: Belabed Meriem , Mauvais François-Xavier , Maschalidi Sophia , Kurowska Mathieu , Goudin Nicolas , Huang Jian-Dong , Fischer Alain , de Saint Basile Geneviève , van Endert Peter , Sepulveda Fernando E. , Ménasché Gaël 
Published: April 2020

AbstractDendritic cells (DCs) constitute a specialized population of immune cells that present exogenous antigen (Ag) on major histocompatibility complex (MHC) class I molecules to initiate CD8 + T cell responses against pathogens and tumours. Although cross-presentation depends critically on the trafficking of Ag-containing intracellular vesicular compartments, the molecular machinery that regulates vesicular transport is incompletely understood. Here, we demonstrate that mice lacking Kif5b (the heavy chain of kinesin-1) in their DCs exhibit a major impairment in cross-presentation and thus a poor in vivo anti-tumour response. We find that kinesin-1 critically regulates antigen cross-presentation in DCs, by controlling Ag degradation, the endosomal pH, and MHC-I recycling. Mechanistically, kinesin-1 appears to regulate early endosome maturation by allowing the scission of endosomal tubulations. Our results highlight kinesin-1’s role as a molecular checkpoint that modulates the balance between antigen degradation and cross-presentation.
Machine-learning structural and electronic properties of metal halide perovskites using a hierarchical convolutional neural network
Authors: Saidi Wissam A. , Shadid Waseem , Castelli Ivano E. 
Published: April 2020

AbstractThe development of statistical tools based on machine learning (ML) and deep networks is actively sought for materials design problems. While structure-property relationships can be accurately determined using quantum mechanical methods, these first-principles calculations are computationally demanding, limiting their use in screening a large set of candidate structures. Herein, we use convolutional neural networks to develop a predictive model for the electronic properties of metal halide perovskites (MHPs) that have a billions-range materials design space. We show that a well-designed hierarchical ML approach has a higher fidelity in predicting properties of the MHPs compared to straight-forward methods. In this architecture, each neural network element has a designated role in the estimation process from predicting complex features of the perovskites such as lattice constant and octahedral till angle to narrowing down possible ranges for the values of interest. Using the hierarchical ML scheme, the obtained root-mean-square errors for the lattice constants, octahedral angle and bandgap for the MHPs are 0.01 Å, 5°, and 0.02 eV, respectively. Our study underscores the importance of a careful network design and a hierarchical approach to alleviate issues associated with imbalanced dataset distributions, which is invariably common in materials datasets.
The association between second to fourth digit ratio, reproductive and general health among women: findings from an Israeli pregnancy cohort
Authors: Tabachnik Maya , Sheiner Eyal , Wainstock Tamar 
Published: April 2020

AbstractThe ratio between the length of second and fourth digits (2D:4D) is a putative biomarker for prenatal testosterone and estrogen exposure. The aim of the study was to examine the association between 2D:4D and women’s general and reproductive health. This analysis was conducted within a prospective pregnancy cohort study. The study population included 187 women. 2D:4D was measured directly in both hands using a digital caliper. Multivariable linear and logistic models were used to study the associations between digit ratio and the studied health characteristics. Mean age of the participants was 30.7 ± 4.9 years. The mean age at menarche was 12.9 ± 1.4 years. Right hand 2D:4D mean ± SD was 0.965 ± 0.03. Left hand 2D:4D mean ± SD was 0.956 ± 0.03. An association was found between right 2D:4D and age at menarche, with older age in women with 2D:4D ≥ mean versus 2D:4D < mean (13.2 ± 1.5 and 12.8 ± 1.3 respectively, b = 0.48, 95%CI:0.06–0.91) while controlling for ethnicity. Higher 2D:4D was also associated with heavier menses bleeding and dysmenorrhea. There is an association between 2D:4D and sub optimal reproductive characteristics, including later age at menarche, heavier menses bleeding and dysmenorrhea. These findings support the association between the intrauterine period and reproductive characteristics. Further studies are required to support our findings.