bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular determinants of response to PD-L1 blockade across tumor types
Authors: Banchereau Romain , Leng Ning , Zill Oliver , Sokol Ethan , Liu Gengbo , Pavlick Dean , Maund Sophia , Liu Li-Fen , Kadel Edward , Baldwin Nicole , Jhunjhunwala Suchit , Nickles Dorothee , Assaf Zoe June , Bower Daniel , Patil Namrata , McCleland Mark , Shames David , Molinero Luciana , Huseni Mahrukh , Sanjabi Shomyseh , Cummings Craig , Mellman Ira , Mariathasan Sanjeev , Hegde Priti , Powles Thomas 
Published: June 2021

AbstractImmune checkpoint inhibitors targeting the PD-1/PD-L1 axis lead to durable clinical responses in subsets of cancer patients across multiple indications, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC) and renal cell carcinoma (RCC). Herein, we complement PD-L1 immunohistochemistry (IHC) and tumor mutation burden (TMB) with RNA-seq in 366 patients to identify unifying and indication-specific molecular profiles that can predict response to checkpoint blockade across these tumor types. Multiple machine learning approaches failed to identify a baseline transcriptional signature highly predictive of response across these indications. Signatures described previously for immune checkpoint inhibitors also failed to validate. At the pathway level, significant heterogeneity is observed between indications, in particular within the PD-L1+tumors. mUC and NSCLC are molecularly aligned, with cell cycle and DNA damage repair genes associated with response in PD-L1- tumors. At the gene level, the CDK4/6 inhibitorCDKN2Ais identified as a significant transcriptional correlate of response, highlighting the association of non-immune pathways to the outcome of checkpoint blockade. This cross-indication analysis reveals molecular heterogeneity between mUC, NSCLC and RCC tumors, suggesting that indication-specific molecular approaches should be prioritized to formulate treatment strategies.
Structure and transport mechanism of P5B-ATPases
Authors: Li Ping , Wang Kaituo , Salustros Nina , Grønberg Christina , Gourdon Pontus 
Published: June 2021

AbstractIn human cells, P5B-ATPases execute the active export of physiologically important polyamines such as spermine from lysosomes to the cytosol, a function linked to a palette of disorders. Yet, the overall shape of P5B-ATPases and the mechanisms of polyamine recognition, uptake and transport remain elusive. Here we describe a series of cryo-electron microscopy structures of a yeast homolog of human ATP13A2-5, Ypk9, determined at resolutions reaching 3.4 Å, and depicting three separate transport cycle intermediates, including spermine-bound conformations. Surprisingly, in the absence of cargo, Ypk9 rests in a phosphorylated conformation auto-inhibited by the N-terminus. Spermine uptake is accomplished through an electronegative cleft lined by transmembrane segments 2, 4 and 6. Despite the dramatically different nature of the transported cargo, these findings pinpoint shared principles of transport and regulation among the evolutionary related P4-, P5A- and P5B-ATPases. The data also provide a framework for analysis of associated maladies, such as Parkinson’s disease.
A genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression
Authors: Taxiarchi Chrysanthi , Beaghton Andrea , Don Nayomi Illansinhage , Kyrou Kyros , Gribble Matthew , Shittu Dammy , Collins Scott P. , Beisel Chase L. , Galizi Roberto , Crisanti Andrea 
Published: June 2021

AbstractCRISPR-based gene drives offer promising means to reduce the burden of pests and vector-borne diseases. These techniques consist of releasing genetically modified organisms carrying CRISPR-Cas nucleases designed to bias their inheritance and rapidly propagate desired modifications. Gene drives can be intended to reduce reproductive capacity of harmful insects or spread anti-pathogen effectors through wild populations, even when these confer fitness disadvantages. Technologies capable of halting the spread of gene drives may prove highly valuable in controlling, counteracting, and even reverting their effect on individual organisms as well as entire populations. Here we show engineering and testing of a genetic approach, based on the germline expression of a phage-derived anti-CRISPR protein (AcrIIA4), able to inactivate CRISPR-based gene drives and restore their inheritance to Mendelian rates in the malaria vector Anopheles gambiae. Modeling predictions and cage testing show that a single release of male mosquitoes carrying the AcrIIA4 protein can block the spread of a highly effective suppressive gene drive preventing population collapse of caged malaria mosquitoes.
Quantitative 3D real-space analysis of Laves phase supraparticles
Authors: Wang Da , van der Wee Ernest B. , Zanaga Daniele , Altantzis Thomas , Wu Yaoting , Dasgupta Tonnishtha , Dijkstra Marjolein , Murray Christopher B. , Bals Sara , van Blaaderen Alfons 
Published: June 2021

AbstractAssembling binary mixtures of nanoparticles into crystals, gives rise to collective properties depending on the crystal structure and the individual properties of both species. However, quantitative 3D real-space analysis of binary colloidal crystals with a thickness of more than 10 layers of particles has rarely been performed. Here we demonstrate that an excess of one species in the binary nanoparticle mixture suppresses the formation of icosahedral order in the self-assembly in droplets, allowing the study of bulk-like binary crystal structures with a spherical morphology also called supraparticles. As example of the approach, we show single-particle level analysis of over 50 layers of Laves phase binary crystals of hard-sphere-like nanoparticles using electron tomography. We observe a crystalline lattice composed of a random mixture of the Laves phases. The number ratio of the binary species in the crystal lattice matches that of a perfect Laves crystal. Our methodology can be applied to study the structure of a broad range of binary crystals, giving insights into the structure formation mechanisms and structure-property relations of nanomaterials.
Nanoengineering of cathode layers for solid oxide fuel cells to achieve superior power densities
Authors: Develos-Bagarinao Katherine , Ishiyama Tomohiro , Kishimoto Haruo , Shimada Hiroyuki , Yamaji Katsuhiko 
Published: June 2021

AbstractSolid oxide fuel cells (SOFCs) are power-generating devices with high efficiencies and considered as promising alternatives to mitigate energy and environmental issues associated with fossil fuel technologies. Nanoengineering of electrodes utilized for SOFCs has emerged as a versatile tool for significantly enhancing the electrochemical performance but needs to overcome issues for integration into practical cells suitable for widespread application. Here, we report an innovative concept for high-performance thin-film cathodes comprising nanoporous La0.6Sr0.4CoO3−δ cathodes in conjunction with highly ordered, self-assembled nanocomposite La0.6Sr0.4Co0.2Fe0.8O3−δ (lanthanum strontium cobalt ferrite) and Ce0.9Gd0.1O2−δ (gadolinia-doped ceria) cathode layers prepared using pulsed laser deposition. Integration of the nanoengineered cathode layers into conventional anode-supported cells enabled the achievement of high current densities at 0.7 V reaching ~2.2 and ~4.7 A/cm2 at 650 °C and 700 °C, respectively. This result demonstrates that tuning material properties through an effective nanoengineering approach could significantly boost the electrochemical performance of cathodes for development of next-generation SOFCs with high power output.
Light-driven decarboxylative deuteration enabled by a divergently engineered photodecarboxylase
Authors: Xu Jian , Fan Jiajie , Lou Yujiao , Xu Weihua , Wang Zhiguo , Li Danyang , Zhou Haonan , Lin Xianfu , Wu Qi 
Published: June 2021

AbstractDespite the well-established chemical processes for C-D bond formation, the toolbox of enzymatic methodologies for deuterium incorporation has remained underdeveloped. Here we describe a photodecarboxylase from Chlorella variabilis NC64A (CvFAP)-catalyzed approach for the decarboxylative deuteration of various carboxylic acids by employing D2O as a cheap and readily available deuterium source. Divergent protein engineering of WT-CvFAP is implemented using Focused Rational Iterative Site-specific Mutagenesis (FRISM) as a strategy for expanding the substrate scope. Using specific mutants, several series of substrates including different chain length acids, racemic substrates as well as bulky cyclic acids are successfully converted into the deuterated products (>40 examples). In many cases WT-CvFAP fails completely. This approach also enables the enantiocomplementary kinetic resolution of racemic acids to afford chiral deuterated products, which can hardly be accomplished by existing methods. MD simulations explain the results of improved catalytic activity and stereoselectivity of WT CvFAP and mutants.
Super-resolving material microstructure image via deep learning for microstructure characterization and mechanical behavior analysis
Authors: Jung Jaimyun , Na Juwon , Park Hyung Keun , Park Jeong Min , Kim Gyuwon , Lee Seungchul , Kim Hyoung Seop 
Published: June 2021

AbstractThe digitized format of microstructures, or digital microstructures, plays a crucial role in modern-day materials research. Unfortunately, the acquisition of digital microstructures through experimental means can be unsuccessful in delivering sufficient resolution that is necessary to capture all relevant geometric features of the microstructures. The resolution-sensitive microstructural features overlooked due to insufficient resolution may limit one’s ability to conduct a thorough microstructure characterization and material behavior analysis such as mechanical analysis based on numerical modeling. Here, a highly efficient super-resolution imaging based on deep learning is developed using a deep super-resolution residual network to super-resolved low-resolution (LR) microstructure data for microstructure characterization and finite element (FE) mechanical analysis. Microstructure characterization and FE model based mechanical analysis using the super-resolved microstructure data not only proved to be as accurate as those based on high-resolution (HR) data but also provided insights on local microstructural features such as grain boundary normal and local stress distribution, which can be only partially considered or entirely disregarded in LR data-based analysis.
Fiber-specific white matter alterations in early-stage tremor-dominant Parkinson’s disease
Authors: Andica Christina , Kamagata Koji , Saito Yuya , Uchida Wataru , Fujita Shohei , Hagiwara Akifumi , Akashi Toshiaki , Wada Akihiko , Ogawa Takashi , Hatano Taku , Hattori Nobutaka , Aoki Shigeki 
Published: June 2021

AbstractUsing a fixel-based analysis (FBA), we assessed the fiber-specific white matter (WM) alterations in nonmedicated patients with early-stage Parkinson’s disease (PD) with tremor-dominant (TD; n = 53; mean age, 61.7 ± 8.7 years) and postural instability and gait disorder (PIGD; n = 27; mean age, 57.8 ± 8.1 years) motor subtypes and age- and sex-matched healthy controls (HC; n = 43; mean age, 61.6 ± 9.2 years) from Parkinson’s Progression Markers Initiative dataset. FBA revealed significantly increased macrostructural fiber cross section and a combination of fiber density and cross section metrics within the corticospinal tract in patients with TD-PD compared with HC. Nonetheless, no significant changes in FBA-derived metrics were found in patients with PIGD-PD compared with HC or patients with TD-PD. Our results may provide evidence of WM neural compensation mechanisms in patients with TD-PD marked by increases in fiber bundle size and the ability to relay information between brain regions.
Perception during use of force and the likelihood of firing upon an unarmed person
Authors: Biggs Adam T. , Hamilton Joseph A. , Jensen Andrew E. , Huffman Greg H. , Suss Joel , Dunn Timothy L. , Sherwood Sarah , Hirsch Dale A. , Rhoton Jayson , Kelly Karen R. , Markwald Rachel R. 
Published: June 2021

AbstractStress can impact perception, especially during use-of-force. Research efforts can thus advance both theory and practice by examining how perception during use-of-force might drive behavior. The current study explored the relationship between perceptual judgments and performance during novel close-combat training. Analyses included perceptual judgments from close-combat assessments conducted pre-training and post-training that required realistic use-of-force decisions in addition to an artificially construed stress-inoculation event used as a training exercise. Participants demonstrated significant reductions in situational awareness while under direct fire, which correlated to increased physiological stress. The initial likelihood of firing upon an unarmed person predicted the perceptual shortcomings of later stress-inoculation training. Subsequently, likelihood of firing upon an unarmed person was reduced following the stress-inoculation training. These preliminary findings have several implications for low or zero-cost solutions that might help trainers identify individuals who are underprepared for field responsibilities.
Coral distribution and bleaching vulnerability areas in Southwestern Atlantic under ocean warming
Authors: Bleuel Jessica , Pennino Maria Grazia , Longo Guilherme O. 
Published: June 2021

AbstractGlobal climate change is a major threat to reefs by increasing the frequency and severity of coral bleaching events over time, reducing coral cover and diversity. Ocean warming may cause shifts in coral communities by increasing temperatures above coral’s upper thermal limits in tropical regions, and by making extratropical regions (marginal reefs) more suitable and potential refugia. We used Bayesian models to project coral occurrence, cover and bleaching probabilities in Southwestern Atlantic and predicted how these probabilities will change under a high-emission scenario (RCP8.5). By overlapping these projections, we categorized areas that combine high probabilities of coral occurrence, cover and bleaching as vulnerability-hotspots. Current coral occurrence and cover probabilities were higher in the tropics (1°S–20°S) but both will decrease and shift to new suitable extratropical reefs (20°S–27°S; tropicalization) with ocean warming. Over 90% of the area present low and mild vulnerability, while the vulnerability-hotspots represent ~ 3% under current and future scenarios, but include the most biodiverse reef complex in South Atlantic (13°S–18°S; Abrolhos Bank). As bleaching probabilities increase with warming, the least vulnerable areas that could act as potential refugia are predicted to reduce by 50%. Predicting potential refugia and highly vulnerable areas can inform conservation actions to face climate change.
Genome-wide association analyses identify genotype-by-environment interactions of growth traits in Simmental cattle
Authors: Braz Camila U. , Rowan Troy N. , Schnabel Robert D. , Decker Jared E. 
Published: June 2021

AbstractUnderstanding genotype-by-environment interactions (G × E) is crucial to understand environmental adaptation in mammals and improve the sustainability of agricultural production. Here, we present an extensive study investigating the interaction of genome-wide SNP markers with a vast assortment of environmental variables and searching for SNPs controlling phenotypic variance (vQTL) using a large beef cattle dataset. We showed that G × E contribute 10.1%, 3.8%, and 2.8% of the phenotypic variance of birth weight, weaning weight, and yearling weight, respectively. G × E genome-wide association analysis (GWAA) detected a large number of G × E loci affecting growth traits, which the traditional GWAA did not detect, showing that functional loci may have non-additive genetic effects regardless of differences in genotypic means. Further, variance-heterogeneity GWAA detected loci enriched with G × E effects without requiring prior knowledge of the interacting environmental factors. Functional annotation and pathway analysis of G × E genes revealed biological mechanisms by which cattle respond to changes in their environment, such as neurotransmitter activity, hypoxia-induced processes, keratinization, hormone, thermogenic and immune pathways. We unraveled the relevance and complexity of the genetic basis of G × E underlying growth traits, providing new insights into how different environmental conditions interact with specific genes influencing adaptation and productivity in beef cattle and potentially across mammals.
The highly conserved FOXJ1 target CFAP161 is dispensable for motile ciliary function in mouse and Xenopus
Authors: Beckers Anja , Fuhl Franziska , Ott Tim , Boldt Karsten , Brislinger Magdalena Maria , Walentek Peter , Schuster-Gossler Karin , Hegermann Jan , Alten Leonie , Kremmer Elisabeth , Przykopanski Adina , Serth Katrin , Ueffing Marius , Blum Martin , Gossler Achim 
Published: June 2021

AbstractCilia are protrusions of the cell surface and composed of hundreds of proteins many of which are evolutionary and functionally well conserved. In cells assembling motile cilia the expression of numerous ciliary components is under the control of the transcription factor FOXJ1. Here, we analyse the evolutionary conserved FOXJ1 target CFAP161 in Xenopus and mouse. In both species Cfap161 expression correlates with the presence of motile cilia and depends on FOXJ1. Tagged CFAP161 localises to the basal bodies of multiciliated cells of the Xenopus larval epidermis, and in mice CFAP161 protein localises to the axoneme. Surprisingly, disruption of the Cfap161 gene in both species did not lead to motile cilia-related phenotypes, which contrasts with the conserved expression in cells carrying motile cilia and high sequence conservation. In mice mutation of Cfap161 stabilised the mutant mRNA making genetic compensation triggered by mRNA decay unlikely. However, genes related to microtubules and cilia, microtubule motor activity and inner dyneins were dysregulated, which might buffer the Cfap161 mutation.
The gastrin-releasing peptide/bombesin system revisited by a reverse-evolutionary study considering Xenopus
Authors: Hirooka Asuka , Hamada Mayuko , Fujiyama Daiki , Takanami Keiko , Kobayashi Yasuhisa , Oti Takumi , Katayama Yukitoshi , Sakamoto Tatsuya , Sakamoto Hirotaka 
Published: June 2021

AbstractBombesin is a putative antibacterial peptide isolated from the skin of the frog, Bombina bombina. Two related (bombesin-like) peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been found in mammals. The history of GRP/bombesin discovery has caused little attention to be paid to the evolutionary relationship of GRP/bombesin and their receptors in vertebrates. We have classified the peptides and their receptors from the phylogenetic viewpoint using a newly established genetic database and bioinformatics. Here we show, by using a clawed frog (Xenopus tropicalis), that GRP is not a mammalian counterpart of bombesin and also that, whereas the GRP system is widely conserved among vertebrates, the NMB/bombesin system has diversified in certain lineages, in particular in frog species. To understand the derivation of GRP system in the ancestor of mammals, we have focused on the GRP system in Xenopus. Gene expression analyses combined with immunohistochemistry and Western blotting experiments demonstrated that GRP peptides and their receptors are distributed in the brain and stomach of Xenopus. We conclude that GRP peptides and their receptors have evolved from ancestral (GRP-like peptide) homologues to play multiple roles in both the gut and the brain as one of the ‘gut-brain peptide’ systems.
Recanalization strategies in childhood stroke in Germany
Authors: Olivieri Martin , Sorg Anna-Lisa , Weinberger Raphael , Kurnik Karin , Bidlingmaier Christoph , Juranek Sabrina , Hoffmann Florian , Reiter Karl , Bonfert Michaela , Tacke Moritz , Borggraefe Ingo , Heinen Florian , Gerstl Lucia 
Published: June 2021

AbstractChildhood arterial ischemic stroke (CAIS) is a rare event. Diverse etiologies, risk factors, symptoms and stroke mimics hamper obtaining a fast diagnosis and implementing immediate recanalization strategies. Over a period of 3 years (2015–2017), the data of 164 pediatric patients (> 28 days of life-18 years) with a first episode of AIS were submitted to a hospital-based nationwide surveillance system for rare disorders (ESPED). We report a subgroup analysis of patients who have undergone recanalization therapy and compare these data with those of the whole group. Twenty-eight patients (17%) with a median age of 12.2 years (range 3.3–16.9) received recanalization therapy. Hemiparesis, facial weakness and speech disturbance were the main presenting symptoms. The time from onset of symptoms to confirmation of diagnosis was significantly shorter in the intervention group (4.1 h vs. 20.4 h, p ≤ 0.0001). Only in one patient occurred a minor bleed. Cardiac disease as predisposing risk factor was more common in the recanalization group. Recanalization therapies are feasible and increasingly applied in children with AIS. High awareness, timely diagnosis and a large amount of expertise may improve time to treatment and make hyperacute therapy an option for more patients.
MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer
Authors: Hsu En-Chi , Shen Michelle , Aslan Merve , Liu Shiqin , Kumar Manoj , Garcia-Marques Fernando , Nguyen Holly M. , Nolley Rosalie , Pitteri Sharon J. , Corey Eva , Brooks James D. , Stoyanova Tanya 
Published: June 2021

AbstractNeuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer that rarely develops de novo in primary tumors and is commonly acquired during the development of treatment resistance. NEPC is characterized by gain of neuroendocrine markers and loss of androgen receptor (AR), making it resistant to current therapeutic strategies targeting the AR signaling axis. Here, we report that MCM2, MCM3, MCM4, and MCM6 (MCM2/3/4/6) are elevated in human NEPC and high levels of MCM2/3/4/6 are associated with liver metastasis and poor survival in prostate cancer patients. MCM2/3/4/6 are four out of six proteins that form a core DNA helicase (MCM2-7) responsible for unwinding DNA forks during DNA replication. Inhibition of MCM2-7 by treatment with ciprofloxacin inhibits NEPC cell proliferation and migration in vitro, significantly delays NEPC tumor xenograft growth, and partially reverses the neuroendocrine phenotype in vivo. Our study reveals the clinical relevance of MCM2/3/4/6 proteins in NEPC and suggests that inhibition of MCM2-7 may represent a new therapeutic strategy for NEPC.
Possibility of information encoding/decoding using the memory effect in fractional-order capacitive devices
Authors: Allagui Anis , Elwakil Ahmed S. 
Published: June 2021

AbstractIn this study, we show that the discharge voltage pattern of a supercapacitor exhibiting fractional-order behavior from the same initial steady-state voltage into a constant resistor is dependent on the past charging voltage profile. The charging voltage was designed to follow a power-law function, i.e. $$v_c(t)=V_{cc} \left( {t}/{t_{ss}}\right) ^p \;(0<t \leqslant t_{ss})$$

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(charging time duration between zero voltage to the terminal voltage $$V_{cc}$$

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) act as two variable parameters. We used this history-dependence of the dynamic behavior of the device to uniquely retrieve information pre-coded in the charging waveform pattern. Furthermore, we provide an analytical model based on fractional calculus that explains phenomenologically the information storage mechanism. The use of this intrinsic material memory effect may lead to new types of methods for information storage and retrieval.