bluuebunny/crossref_metadata_2025_split huggingface dataset:
INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer
Authors: Rodgers Samuel J. , Ooms Lisa M. , Oorschot Viola M. J. , Schittenhelm Ralf B. , Nguyen Elizabeth V. , Hamila Sabryn A. , Rynkiewicz Natalie , Gurung Rajendra , Eramo Matthew J. , Sriratana Absorn , Fedele Clare G. , Caramia Franco , Loi Sherene , Kerr Genevieve , Abud Helen E. , Ramm Georg , Papa Antonella , Ellisdon Andrew M. , Daly Roger J. , McLean Catriona A. , Mitchell Christina A. 
Published: May 2021

AbstractINPP4B suppresses PI3K/AKT signaling by converting PI(3,4)P2 to PI(3)P and INPP4B inactivation is common in triple-negative breast cancer. Paradoxically, INPP4B is also a reported oncogene in other cancers. How these opposing INPP4B roles relate to PI3K regulation is unclear. We report PIK3CA-mutant ER+ breast cancers exhibit increased INPP4B mRNA and protein expression and INPP4B increased the proliferation and tumor growth of PIK3CA-mutant ER+ breast cancer cells, despite suppression of AKT signaling. We used integrated proteomics, transcriptomics and imaging to demonstrate INPP4B localized to late endosomes via interaction with Rab7, which increased endosomal PI3Kα-dependent PI(3,4)P2 to PI(3)P conversion, late endosome/lysosome number and cargo trafficking, resulting in enhanced GSK3β lysosomal degradation and activation of Wnt/β-catenin signaling. Mechanistically, Wnt inhibition or depletion of the PI(3)P-effector, Hrs, reduced INPP4B-mediated cell proliferation and tumor growth. Therefore, INPP4B facilitates PI3Kα crosstalk with Wnt signaling in ER+ breast cancer via PI(3,4)P2 to PI(3)P conversion on late endosomes, suggesting these tumors may be targeted with combined PI3K and Wnt/β-catenin therapies.
Evolution of spin excitations from bulk to monolayer FeSe
Authors: Pelliciari Jonathan , Karakuzu Seher , Song Qi , Arpaia Riccardo , Nag Abhishek , Rossi Matteo , Li Jiemin , Yu Tianlun , Chen Xiaoyang , Peng Rui , García-Fernández Mirian , Walters Andrew C. , Wang Qisi , Zhao Jun , Ghiringhelli Giacomo , Feng Donglai , Maier Thomas A. , Zhou Ke-Jin , Johnston Steven , Comin Riccardo 
Published: May 2021

AbstractIn ultrathin films of FeSe grown on SrTiO3 (FeSe/STO), the superconducting transition temperature Tc is increased by almost an order of magnitude, raising questions on the pairing mechanism. As in other superconductors, antiferromagnetic spin fluctuations have been proposed to mediate SC making it essential to study the evolution of the spin dynamics of FeSe from the bulk to the ultrathin limit. Here, we investigate the spin excitations in bulk and monolayer FeSe/STO using resonant inelastic x-ray scattering (RIXS) and quantum Monte Carlo (QMC) calculations. Despite the absence of long-range magnetic order, bulk FeSe displays dispersive magnetic excitations reminiscent of other Fe-pnictides. Conversely, the spin excitations in FeSe/STO are gapped, dispersionless, and significantly hardened relative to its bulk counterpart. By comparing our RIXS results with simulations of a bilayer Hubbard model, we connect the evolution of the spin excitations to the Fermiology of the two systems revealing a remarkable reconfiguration of spin excitations in FeSe/STO, essential to understand the role of spin fluctuations in the pairing mechanism.
Health improvement framework for actionable treatment planning using a surrogate Bayesian model
Authors: Nakamura Kazuki , Kojima Ryosuke , Uchino Eiichiro , Ono Koh , Yanagita Motoko , Murashita Koichi , Itoh Ken , Nakaji Shigeyuki , Okuno Yasushi 
Published: May 2021

AbstractClinical decision-making regarding treatments based on personal characteristics leads to effective health improvements. Machine learning (ML) has been the primary concern of diagnosis support according to comprehensive patient information. A prominent issue is the development of objective treatment processes in clinical situations. This study proposes a framework to plan treatment processes in a data-driven manner. A key point of the framework is the evaluation of the actionability for personal health improvements by using a surrogate Bayesian model in addition to a high-performance nonlinear ML model. We first evaluate the framework from the viewpoint of its methodology using a synthetic dataset. Subsequently, the framework is applied to an actual health checkup dataset comprising data from 3132 participants, to lower systolic blood pressure and risk of chronic kidney disease at the individual level. We confirm that the computed treatment processes are actionable and consistent with clinical knowledge for improving these values. We also show that the improvement processes presented by the framework can be clinically informative. These results demonstrate that our framework can contribute toward decision-making in the medical field, providing clinicians with deeper insights.
Reversible formation of coordination bonds in Sn-based metal-organic frameworks for high-performance lithium storage
Authors: Liu Jingwei , Xie Daixi , Xu Xiufang , Jiang Luozhen , Si Rui , Shi Wei , Cheng Peng 
Published: May 2021

AbstractSn-based compounds with buffer matrixes possessing high theoretical capacity, low working voltage, and alleviation of the volume expansion of Sn are ideal materials for lithium storage. However, it is challenging to confine well-dispersed Sn within a lithium active matrix because low-melting-point Sn tends to agglomerate. Here, we apply a metal-organic framework (MOF) chemistry between Sn-nodes and lithium active ligands to create two Sn-based MOFs comprising Sn2(dobdc) and Sn2(dobpdc) with extended ligands from H4dobdc (2,5-dioxido-1,4-benzenedicarboxylate acid) to H4dobpdc (4,4’-dioxidobiphenyl-3,3’-dicarboxylate acid) with molecule-level homodispersion of Sn in organic matrixes for lithium storage. The enhanced utilization of active sites and reaction kinetics are achieved by the isoreticular expansion of the organic linkers. The reversible formation of coordination bonds during lithium storage processes is revealed by X-ray absorption fine structure characterization, providing an in-depth understanding of the lithium storage mechanism in coordination compounds.
A graph-based network for predicting chemical reaction pathways in solid-state materials synthesis
Authors: McDermott Matthew J. , Dwaraknath Shyam S. , Persson Kristin A. 
Published: May 2021

AbstractAccelerated inorganic synthesis remains a significant challenge in the search for novel, functional materials. Many of the principles which enable “synthesis by design” in synthetic organic chemistry do not exist in solid-state chemistry, despite the availability of extensive computed/experimental thermochemistry data. In this work, we present a chemical reaction network model for solid-state synthesis constructed from available thermochemistry data and devise a computationally tractable approach for suggesting likely reaction pathways via the application of pathfinding algorithms and linear combination of lowest-cost paths in the network. We demonstrate initial success of the network in predicting complex reaction pathways comparable to those reported in the literature for YMnO3, Y2Mn2O7, Fe2SiS4, and YBa2Cu3O6.5. The reaction network presents opportunities for enabling reaction pathway prediction, rapid iteration between experimental/theoretical results, and ultimately, control of the synthesis of solid-state materials.
An electronic neuromorphic system for real-time detection of high frequency oscillations (HFO) in intracranial EEG
Authors: Sharifshazileh Mohammadali , Burelo Karla , Sarnthein Johannes , Indiveri Giacomo 
Published: May 2021

AbstractThe analysis of biomedical signals for clinical studies and therapeutic applications can benefit from embedded devices that can process these signals locally and in real-time. An example is the analysis of intracranial EEG (iEEG) from epilepsy patients for the detection of High Frequency Oscillations (HFO), which are a biomarker for epileptogenic brain tissue. Mixed-signal neuromorphic circuits offer the possibility of building compact and low-power neural network processing systems that can analyze data on-line in real-time. Here we present a neuromorphic system that combines a neural recording headstage with a spiking neural network (SNN) processing core on the same die for processing iEEG, and show how it can reliably detect HFO, thereby achieving state-of-the-art accuracy, sensitivity, and specificity. This is a first feasibility study towards identifying relevant features in iEEG in real-time using mixed-signal neuromorphic computing technologies.
Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer
Authors: Wang Jieti , Li Ruochen , Cao Yifan , Gu Yun , Fang Hanji , Fei Yuchao , Lv Kunpeng , He Xudong , Lin Chao , Liu Hao , Zhang Heng , Li He , He Hongyong , Xu Jiejie , Huang Hua 
Published: May 2021

AbstractStudies that examined an association between CD8+T and prognosis in gastric cancer are inconsistent, and a distinct population of CXCR5+CD8+T associated with better overall survival has been reported among various malignancies. Here, we show that the abundance of intratumoral CXCR5+CD8+T cells is associated with better overall survival in patients with gastric cancer. Patients with TNM II + III gastric cancer with higher intratumoral CXCR5+CD8+T cell infiltration are more likely to benefit from adjuvant chemotherapy. Microsatellite-unstable and Epstein–Barr virus positive tumors are enriched with CXCR5+CD8+T cells. Gastric cancer infiltrating CXCR5+CD8+T cells represent a specific subtype of stem-like CD8+T with effector memory feature. Identification of the clinical significance and phenotype of gastric cancer infiltrating CXCR5+CD8+T provides a roadmap for patient stratification and trials of targeted therapies.
Sulfide catabolism ameliorates hypoxic brain injury
Authors: Marutani Eizo , Morita Masanobu , Hirai Shuichi , Kai Shinichi , Grange Robert M. H. , Miyazaki Yusuke , Nagashima Fumiaki , Traeger Lisa , Magliocca Aurora , Ida Tomoaki , Matsunaga Tetsuro , Flicker Daniel R. , Corman Benjamin , Mori Naohiro , Yamazaki Yumiko , Batten Annabelle , Li Rebecca , Tanaka Tomohiro , Ikeda Takamitsu , Nakagawa Akito , Atochin Dmitriy N. , Ihara Hideshi , Olenchock Benjamin A. , Shen Xinggui , Nishida Motohiro , Hanaoka Kenjiro , Kevil Christopher G. , Xian Ming , Bloch Donald B. , Akaike Takaaki , Hindle Allyson G. , Motohashi Hozumi , Ichinose Fumito 
Published: May 2021

AbstractThe mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.
Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors
Authors: Delgado Irene , Giovinazzo Giovanna , Temiño Susana , Gauthier Yves , Balsalobre Aurelio , Drouin Jacques , Torres Miguel 
Published: May 2021

AbstractMeis1 and Meis2 are homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Elimination of Meis genes after limb induction has shown their role in limb proximo-distal patterning; however, limb development in the complete absence of Meis function has not been studied. Here, we report thatMeis1/2inactivation in the lateral plate mesoderm of mouse embryos leads to limb agenesis. Meis and Tbx factors converge in this function, extensively co-binding with Tbx to genomic sites and co-regulating enhancers ofFgf10, a critical factor in limb initiation. Limbs with three deleted Meis alleles show proximal-specific skeletal hypoplasia and agenesis of posterior skeletal elements. This failure in posterior specification results from an early role of Meis factors in establishing the limb antero-posterior prepattern required forShhactivation. Our results demonstrate roles for Meis transcription factors in early limb development and identify their involvement in previously undescribed interaction networks that regulate organogenesis.
Label-free characterization of organic nanocarriers reveals persistent single molecule cores for hydrocarbon sequestration
Authors: McAfee Terry , Ferron Thomas , Cordova Isvar A. , Pickett Phillip D. , McCormick Charles L. , Wang Cheng , Collins Brian A. 
Published: May 2021

AbstractSelf-assembled molecular nanostructures embody an enormous potential for new technologies, therapeutics, and understanding of molecular biofunctions. Their structure and function are dependent on local environments, necessitating in-situ/operando investigations for the biggest leaps in discovery and design. However, the most advanced of such investigations involve laborious labeling methods that can disrupt behavior or are not fast enough to capture stimuli-responsive phenomena. We utilize X-rays resonant with molecular bonds to demonstrate an in-situ nanoprobe that eliminates the need for labels and enables data collection times within seconds. Our analytical spectral model quantifies the structure, molecular composition, and dynamics of a copolymer micelle drug delivery platform using resonant soft X-rays. We additionally apply this technique to a hydrocarbon sequestrating polysoap micelle and discover that the critical organic-capturing domain does not coalesce upon aggregation but retains distinct single-molecule cores. This characteristic promotes its efficiency of hydrocarbon sequestration for applications like oil spill remediation and drug delivery. Such a technique enables operando, chemically sensitive investigations of any aqueous molecular nanostructure, label-free.
Finding gene network topologies for given biological function with recurrent neural network
Authors: Shen Jingxiang , Liu Feng , Tu Yuhai , Tang Chao 
Published: May 2021

AbstractSearching for possible biochemical networks that perform a certain function is a challenge in systems biology. For simple functions and small networks, this can be achieved through an exhaustive search of the network topology space. However, it is difficult to scale this approach up to larger networks and more complex functions. Here we tackle this problem by training a recurrent neural network (RNN) to perform the desired function. By developing a systematic perturbative method to interrogate the successfully trained RNNs, we are able to distill the underlying regulatory network among the biological elements (genes, proteins, etc.). Furthermore, we show several cases where the regulation networks found by RNN can achieve the desired biological function when its edges are expressed by more realistic response functions, such as the Hill-function. This method can be used to link topology and function by helping uncover the regulation logic and network topology for complex tasks.
Non-invasive super-resolution imaging through dynamic scattering media
Authors: Wang Dong , Sahoo Sujit K. , Zhu Xiangwen , Adamo Giorgio , Dang Cuong 
Published: May 2021

AbstractSuper-resolution imaging has been revolutionizing technical analysis in various fields from biological to physical sciences. However, many objects are hidden by strongly scattering media such as biological tissues that scramble light paths, create speckle patterns and hinder object’s visualization, let alone super-resolution imaging. Here, we demonstrate non-invasive super-resolution imaging through scattering media based on a stochastic optical scattering localization imaging (SOSLI) technique. After capturing multiple speckle patterns of photo-switchable point sources, our computational approach utilizes the speckle correlation property of scattering media to retrieve an image with a 100-nm resolution, an eight-fold enhancement compared to the diffraction limit. More importantly, we demonstrate our SOSLI to do non-invasive super-resolution imaging through not only static scattering media, but also dynamic scattering media with strong decorrelation such as biological tissues. Our approach paves the way to non-invasively visualize various samples behind scattering media at nanometer levels of detail.
Subcellular three-dimensional imaging deep through multicellular thick samples by structured illumination microscopy and adaptive optics
Authors: Lin Ruizhe , Kipreos Edward T. , Zhu Jie , Khang Chang Hyun , Kner Peter 
Published: May 2021

AbstractStructured Illumination Microscopy enables live imaging with sub-diffraction resolution. Unfortunately, optical aberrations can lead to loss of resolution and artifacts in Structured Illumination Microscopy rendering the technique unusable in samples thicker than a single cell. Here we report on the combination of Adaptive Optics and Structured Illumination Microscopy enabling imaging with 150 nm lateral and 570 nm axial resolution at a depth of 80 µm throughCaenorhabditis elegans. We demonstrate that Adaptive Optics improves the three-dimensional resolution, especially along the axial direction, and reduces artifacts, successfully realizing 3D-Structured Illumination Microscopy in a variety of biological samples.
Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling
Authors: Yeh Fu-Lung , Chang Shang-Lin , Ahmed Golam Rizvee , Liu Hsin-I , Tung Luh , Yeh Chung-Shu , Lanier Leah Stands , Maeder Corina , Lin Che-Min , Tsai Shu-Chun , Hsiao Wan-Yi , Chang Wei-Hau , Chang Tien-Hsien 
Published: May 2021

AbstractSplicing, a key step in the eukaryotic gene-expression pathway, converts precursor messenger RNA (pre-mRNA) into mRNA by excising introns and ligating exons. This task is accomplished by the spliceosome, a macromolecular machine that must undergo sequential conformational changes to establish its active site. Each of these major changes requires a dedicated DExD/H-box ATPase, but how these enzymes are activated remain obscure. Here we show that Prp28, a yeast DEAD-box ATPase, transiently interacts with the conserved 5′ splice-site (5′SS) GU dinucleotide and makes splicing-dependent contacts with the U1 snRNP protein U1C, and U4/U6.U5 tri-snRNP proteins, Prp8, Brr2, and Snu114. We further show that Prp28’s ATPase activity is potentiated by the phosphorylated Npl3, but not the unphosphorylated Npl3, thus suggesting a strategy for regulating DExD/H-box ATPases. We propose that Npl3 is a functional counterpart of the metazoan-specific Prp28 N-terminal region, which can be phosphorylated and serves as an anchor to human spliceosome.
Caerulomycin and collismycin antibiotics share a trans-acting flavoprotein-dependent assembly line for 2,2’-bipyridine formation
Authors: Pang Bo , Liao Rijing , Tang Zhijun , Guo Shengjie , Wu Zhuhua , Liu Wen 
Published: May 2021

AbstractLinear nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) template the modular biosynthesis of numerous nonribosomal peptides, polyketides and their hybrids through assembly line chemistry. This chemistry can be complex and highly varied, and thus challenges our understanding in NRPS and PKS-programmed, diverse biosynthetic processes using amino acid and carboxylate building blocks. Here, we report that caerulomycin and collismycin peptide-polyketide hybrid antibiotics share an assembly line that involves unusual NRPS activity to engage a trans-acting flavoprotein in C-C bond formation and heterocyclization during 2,2’-bipyridine formation. Simultaneously, this assembly line provides dethiolated and thiolated 2,2’-bipyridine intermediates through differential treatment of the sulfhydryl group arising from l-cysteine incorporation. Subsequent l-leucine extension, which does not contribute any atoms to either caerulomycins or collismycins, plays a key role in sulfur fate determination by selectively advancing one of the two 2,2’-bipyridine intermediates down a path to the final products with or without sulfur decoration. These findings further the appreciation of assembly line chemistry and will facilitate the development of related molecules using synthetic biology approaches.
Cornelia de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect
Authors: Olley Gabrielle , Pradeepa Madapura M. , Grimes Graeme R. , Piquet Sandra , Polo Sophie E. , FitzPatrick David R. , Bickmore Wendy A. , Boumendil Charlene 
Published: May 2021

AbstractCornelia de Lange syndrome is a multisystem developmental disorder typically caused by mutations in the gene encoding the cohesin loader NIPBL. The associated phenotype is generally assumed to be the consequence of aberrant transcriptional regulation. Recently, we identified a missense mutation in BRD4 associated with a Cornelia de Lange-like syndrome that reduces BRD4 binding to acetylated histones. Here we show that, although this mutation reduces BRD4-occupancy at enhancers it does not affect transcription of the pluripotency network in mouse embryonic stem cells. Rather, it delays the cell cycle, increases DNA damage signalling, and perturbs regulation of DNA repair in mutant cells. This uncovers a role for BRD4 in DNA repair pathway choice. Furthermore, we find evidence of a similar increase in DNA damage signalling in cells derived from NIPBL-deficient individuals, suggesting that defective DNA damage signalling and repair is also a feature of typical Cornelia de Lange syndrome.
Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD
Authors: Bansal Sandeep , Anderson Martin , Anzueto Antonio , Brown Nicola , Compton Chris , Corbridge Thomas C. , Erb David , Harvey Catherine , Kaisermann Morrys C. , Kaye Mitchell , Lipson David A. , Martin Neil , Zhu Chang-Qing , Papi Alberto 
Published: May 2021

AbstractChronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George’s Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62–128]; P < 0.001), and significantly improved SGRQ and CAT versus TIO. Treatment safety profiles were similar. Once-daily single-inhaler FF/UMEC/VI significantly improved lung function and health status versus once-daily TIO in symptomatic moderate-to-very-severe COPD patients, with a similar safety profile.