bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA
Authors: Cheng Min-Jing , Wu Yan-Yi , Zeng Hao , Zhang Tian-Hong , Hu Yan-Xia , Liu Shi-Yi , Cui Rui-Qin , Hu Chun-Xia , Zou Quan-Ming , Li Chuang-Chuang , Ye Wen-Cai , Huang Wei , Wang Lei 
Published: July 2024

AbstractThe development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.
Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors
Authors: Kim YeEun , Calderon Ariel A. , Favaro Patricia , Glass David R. , Tsai Albert G. , Ho Daniel , Borges Luciene , Greenleaf William J. , Bendall Sean C. 
Published: July 2024

AbstractLymphoid specification in human hematopoietic progenitors is not fully understood. To better associate lymphoid identity with protein-level cell features, we conduct a highly multiplexed single-cell proteomic screen on human bone marrow progenitors. This screen identifies terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase intrinsic to VDJ recombination, broadly expressed within CD34+ progenitors prior to B/T cell emergence. While these TdT+ cells coincide with granulocyte-monocyte progenitor (GMP) immunophenotype, their accessible chromatin regions show enrichment for lymphoid-associated transcription factor (TF) motifs. TdT expression on GMPs is inversely related to the SLAM family member CD84. Prospective isolation of CD84lo GMPs demonstrates robust lymphoid potentials ex vivo, while still retaining significant myeloid differentiation capacity, akin to LMPPs. This multi-omic study identifies human bone marrow lymphoid-primed progenitors, further defining the lympho-myeloid axis in human hematopoiesis.
Global protein turnover quantification in Escherichia coli reveals cytoplasmic recycling under nitrogen limitation
Authors: Gupta Meera , Johnson Alex N. T. , Cruz Edward R. , Costa Eli J. , Guest Randi L. , Li Sophia Hsin-Jung , Hart Elizabeth M. , Nguyen Thao , Stadlmeier Michael , Bratton Benjamin P. , Silhavy Thomas J. , Wingreen Ned S. , Gitai Zemer , Wühr Martin 
Published: July 2024

AbstractProtein turnover is critical for proteostasis, but turnover quantification is challenging, and even in well-studied E. coli, proteome-wide measurements remain scarce. Here, we quantify the turnover rates of ~3200 E. coli proteins under 13 conditions by combining heavy isotope labeling with complement reporter ion quantification and find that cytoplasmic proteins are recycled when nitrogen is limited. We use knockout experiments to assign substrates to the known cytoplasmic ATP-dependent proteases. Surprisingly, none of these proteases are responsible for the observed cytoplasmic protein degradation in nitrogen limitation, suggesting that a major proteolysis pathway in E. coli remains to be discovered. Lastly, we show that protein degradation rates are generally independent of cell division rates. Thus, we present broadly applicable technology for protein turnover measurements and provide a rich resource for protein half-lives and protease substrates in E. coli, complementary to genomics data, that will allow researchers to study the control of proteostasis.
Clinical features associated with NeoRAS wild-type metastatic colorectal cancer A SCRUM-Japan GOZILA substudy
Authors: Osumi Hiroki , Shinozaki Eiji , Nakamura Yoshiaki , Esaki Taito , Yasui Hisateru , Taniguchi Hiroya , Satake Hironaga , Sunakawa Yu , Komatsu Yoshito , Kagawa Yoshinori , Denda Tadamichi , Shiozawa Manabu , Satoh Taroh , Nishina Tomohiro , Goto Masahiro , Takahashi Naoki , Kato Takeshi , Bando Hideaki , Yamaguchi Kensei , Yoshino Takayuki 
Published: July 2024

Abstract“NeoRAS WT” refers to the loss of RAS mutations (MTs) following first-line treatment in metastatic colorectal cancer (mCRC). We evaluate the incidence and clinicopathological characteristics of NeoRAS WT mCRC using next-generation sequencing of plasma circulating tumor DNA. Patients with mCRC enrolled in the GOZILA study initially diagnosed with tissue RAS MT mCRC and received subsequent systemic therapy are eligible. NeoRAS WT is defined as the absence of detectable RAS MT in plasma and assessed in all eligible patients (Group A) and in a subgroup with at least one somatic alteration detected in plasma (Group B). Overall, 478 patients are included. NeoRAS WT prevalence is 19.0% (91/478) in Group A and 9.8% (42/429) in Group B. Absence of liver or lymph node metastasis and tissue RAS MTs other than KRAS exon 2 MTs are significantly associated with NeoRAS WT emergence. Overall, 1/6 and 2/6 patients with NeoRAS WT treated with anti-EGFR monoclonal antibodies (mAbs) show partial response and stable disease for ≥6 months, respectively. NeoRAS WT mCRC is observed at a meaningful prevalence, and anti-EGFR mAb-based therapy may be effective.
Co-coding of head and whisker movements by both VPM and POm thalamic neurons
Authors: Oram Tess Baker , Tenzer Alon , Saraf-Sinik Inbar , Yizhar Ofer , Ahissar Ehud 
Published: July 2024

AbstractRodents continuously move their heads and whiskers in a coordinated manner while perceiving objects through whisker-touch. Studies in head-fixed rodents showed that the ventroposterior medial (VPM) and posterior medial (POm) thalamic nuclei code for whisker kinematics, with POm involvement reduced in awake animals. To examine VPM and POm involvement in coding head and whisker kinematics in awake, head-free conditions, we recorded thalamic neuronal activity and tracked head and whisker movements in male mice exploring an open arena. Using optogenetic tagging, we found that in freely moving mice, both nuclei equally coded whisker kinematics and robustly coded head kinematics. The fraction of neurons coding head kinematics increased after whisker trimming, ruling out whisker-mediated coding. Optogenetic activation of thalamic neurons evoked overt kinematic changes and increased the fraction of neurons leading changes in head kinematics. Our data suggest that VPM and POm integrate head and whisker information and can influence head kinematics during tactile perception.
Polylogarithmic-depth controlled-NOT gates without ancilla qubits
Authors: Claudon Baptiste , Zylberman Julien , Feniou César , Debbasch Fabrice , Peruzzo Alberto , Piquemal Jean-Philip 
Published: July 2024

AbstractControlled operations are fundamental building blocks of quantum algorithms. Decomposing n-control-NOT gates (Cn(X)) into arbitrary single-qubit and CNOT gates, is a crucial but non-trivial task. This study introduces Cn(X) circuits outperforming previous methods in the asymptotic and non-asymptotic regimes. Three distinct decompositions are presented: an exact one using one borrowed ancilla with a circuit depth $$\Theta (\log {(n)}^{3})$$
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, an approximating one without ancilla qubits with a circuit depth $${{{{{{{\mathcal{O}}}}}}}}(\log {(n)}^{3}\log (1/\epsilon ))$$
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and an exact one with an adjustable-depth circuit which decreases with the number m≤n of ancilla qubits available as $${{{{{{{\mathcal{O}}}}}}}}(\log {(n/\lfloor m/2\rfloor )}^{3}+\log (\lfloor m/2\rfloor ))$$
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. The resulting exponential speedup is likely to have a substantial impact on fault-tolerant quantum computing by improving the complexities of countless quantum algorithms with applications ranging from quantum chemistry to physics, finance and quantum machine learning.
Local read haplotagging enables accurate long-read small variant calling
Authors: Kolesnikov Alexey , Cook Daniel , Nattestad Maria , Brambrink Lucas , McNulty Brandy , Gorzynski John , Goenka Sneha , Ashley Euan A. , Jain Miten , Miga Karen H. , Paten Benedict , Chang Pi-Chuan , Carroll Andrew , Shafin Kishwar 
Published: July 2024

AbstractLong-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and enabled rapid genetic diagnosis in clinical settings. Rapidly evolving third-generation sequencing platforms like Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) are introducing newer platforms and data types. It has been demonstrated that variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve the genotyping accuracy. However, using local haplotype information creates an overhead as variant calling needs to be performed multiple times which ultimately makes it difficult to extend to new data types and platforms as they get introduced. In this work, we have developed a local haplotype approximate method that enables state-of-the-art variant calling performance with multiple sequencing platforms including PacBio Revio system, ONT R10.4 simplex and duplex data. This addition of local haplotype approximation simplifies long-read variant calling with DeepVariant.
Contact-electro-catalytic CO2 reduction from ambient air
Authors: Wang Nannan , Jiang Wenbin , Yang Jing , Feng Haisong , Zheng Youbin , Wang Sheng , Li Bofan , Heng Jerry Zhi Xiong , Ong Wai Chung , TAN Hui Ru , Zhang Yong-Wei , Wang Daoai , Ye Enyi , Li Zibiao 
Published: July 2024

AbstractTraditional catalytic techniques often encounter obstacles in the search for sustainable solutions for converting CO2 into value-added products because of their high energy consumption and expensive catalysts. Here, we introduce a contact-electro-catalysis approach for CO2 reduction reaction, achieving a CO Faradaic efficiency of 96.24%. The contact-electro-catalysis is driven by a triboelectric nanogenerator consisting of electrospun polyvinylidene fluoride loaded with single Cu atoms-anchored polymeric carbon nitride (Cu-PCN) catalysts and quaternized cellulose nanofibers (CNF). Mechanistic investigation reveals that the single Cu atoms on Cu-PCN can effectively enrich electrons during contact electrification, facilitating electron transfer upon their contact with CO2 adsorbed on quaternized CNF. Furthermore, the strong adsorption of CO2 on quaternized CNF allows efficient CO2 capture at low concentrations, thus enabling the CO2 reduction reaction in the ambient air. Compared to the state-of-the-art air-based CO2 reduction technologies, contact-electro-catalysis achieves a superior CO yield of 33 μmol g−1 h−1. This technique provides a solution for reducing airborne CO2 emissions while advancing chemical sustainability strategy.
Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs
Authors: Garibyan Mher , Hoffman Tyler , Makaske Thijs , Do Stephanie K. , Wu Yifan , Williams Brian A. , March Alexander R. , Cho Nathan , Pedroncelli Nicolas , Lima Ricardo Espinosa , Soto Jennifer , Jackson Brooke , Santoso Jeffrey W. , Khademhosseini Ali , Thomson Matt , Li Song , McCain Megan L. , Morsut Leonardo 
Published: July 2024

AbstractSynthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.
Tradeoff between speed and robustness in primordium initiation mediated by auxin-CUC1 interaction
Authors: Kong Shuyao , Zhu Mingyuan , Pan David , Lane Brendan , Smith Richard S. , Roeder Adrienne H. K. 
Published: July 2024

AbstractRobustness is the reproducible development of a phenotype despite stochastic noise. It often involves tradeoffs with other performance metrics, but the mechanisms underlying such tradeoffs were largely unknown. An Arabidopsis flower robustly develops four sepals from four precisely positioned auxin maxima. The development related myb-like 1 (drmy1) mutant generates noise in auxin signaling that disrupts robustness in sepal initiation. Here, we find that increased expression of CUP-SHAPED COTYLEDON1 (CUC1), a boundary specification transcription factor, in drmy1 underlies this loss of robustness. CUC1 surrounds and amplifies stochastic auxin noise in drmy1 to form variably positioned auxin maxima and sepal primordia. Removing CUC1 from drmy1 provides time for noisy auxin signaling to resolve into four precisely positioned auxin maxima, restoring robust sepal initiation. However, removing CUC1 decreases the intensity of auxin maxima and slows down sepal initiation. Thus, CUC1 increases morphogenesis speed but impairs robustness against auxin noise. Further, using a computational model, we find that the observed phenotype can be explained by the effect of CUC1 in repolarizing PIN FORMED1 (PIN1), a polar auxin transporter. Lastly, our model predicts that reducing global growth rate improves developmental robustness, which we validate experimentally. Thus, our study illustrates a tradeoff between speed and robustness during development.
GLP-1 receptor agonists’ impact on cardio-renal outcomes and mortality in T2D with acute kidney disease
Authors: Pan Heng-Chih , Chen Jui-Yi , Chen Hsing-Yu , Yeh Fang-Yu , Sun Chiao-Yin , Huang Thomas Tao-Min , Wu Vin-Cent 
Published: July 2024

AbstractPrevious studies have explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing cardiovascular events in type 2 diabetes. Here we show that GLP-1 RAs are associated with lower risks of mortality, major cardiovascular events (MACEs), and major adverse kidney events (MAKEs) in type 2 diabetes patients with acute kidney disease (AKD). Utilizing global data from the TriNetX database (2002/09/01-2022/12/01) and propensity score matching, we compare 7511 GLP-1 RAs users to non-users among 165,860 AKD patients. The most common causes of AKI are sepsis (55.2%) and cardiorenal syndrome (34.2%). After a median follow-up of 2.3 years, GLP-1 RAs users exhibit reduced risks of mortality (adjusted hazard ratio [aHR]: 0.57), MACEs (aHR: 0.88), and MAKEs (aHR: 0.73). External validation in a multicenter dataset of 1245 type 2 diabetes patients with AKD supports the favorable outcomes. These results emphasize the potential of GLP-1 RAs in individualized treatment for this population.
Ising meson spectroscopy on a noisy digital quantum simulator
Authors: Lamb Christopher , Tang Yicheng , Davis Robert , Roy Ananda 
Published: July 2024

AbstractQuantum simulation has the potential to be an indispensable technique for the investigation of non-perturbative phenomena in strongly-interacting quantum field theories (QFTs). In the modern quantum era, with Noisy Intermediate Scale Quantum (NISQ) simulators widely available and larger-scale quantum machines on the horizon, it is natural to ask: what non-perturbative QFT problems can be solved with the existing quantum hardware? We show that existing noisy quantum machines can be used to analyze the energy spectrum of several strongly-interacting 1+1D QFTs, which exhibit non-perturbative effects like ‘quark confinement’ and ‘false vacuum decay’. We perform quench experiments on IBM’s quantum simulators to compute the energy spectrum of 1+1D quantum Ising model with a longitudinal field. Our results demonstrate that digital quantum simulation in the NISQ era has the potential to be a viable alternative to numerical techniques such as density matrix renormalization group or the truncated conformal space methods for analyzing QFTs.
TracrRNA reprogramming enables direct PAM-independent detection of RNA with diverse DNA-targeting Cas12 nucleases
Authors: Jiao Chunlei , Peeck Natalia L. , Yu Jiaqi , Ghaem Maghami Mohammad , Kono Sarah , Collias Daphne , Martinez Diaz Sandra L. , Larose Rachael , Beisel Chase L. 
Published: July 2024

AbstractMany CRISPR-Cas immune systems generate guide (g)RNAs using trans-activating CRISPR RNAs (tracrRNAs). Recent work revealed that Cas9 tracrRNAs could be reprogrammed to convert any RNA-of-interest into a gRNA, linking the RNA’s presence to Cas9-mediated cleavage of double-stranded (ds)DNA. Here, we reprogram tracrRNAs from diverse Cas12 nucleases, linking the presence of an RNA-of-interest to dsDNA cleavage and subsequent collateral single-stranded DNA cleavage—all without the RNA necessarily encoding a protospacer-adjacent motif (PAM). After elucidating nuclease-specific design rules, we demonstrate PAM-independent RNA detection with Cas12b, Cas12e, and Cas12f nucleases. Furthermore, rationally truncating the dsDNA target boosts collateral cleavage activity, while the absence of a gRNA reduces background collateral activity and enhances sensitivity. Finally, we apply this platform to detect 16 S rRNA sequences from five different bacterial pathogens using a universal reprogrammed tracrRNA. These findings extend tracrRNA reprogramming to diverse dsDNA-targeting Cas12 nucleases, expanding the flexibility and versatility of CRISPR-based RNA detection.
Silicon photocathode functionalized with osmium complex catalyst for selective catalytic conversion of CO2 to methane
Authors: Li Xing-Yi , Zhu Ze-Lin , Dagnaw Fentahun Wondu , Yu Jie-Rong , Wu Zhi-Xing , Chen Yi-Jing , Zhou Mu-Han , Wang Tieyu , Tong Qing-Xiao , Jian Jing-Xin 
Published: July 2024

AbstractSolar-driven CO2 reduction to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving selective production of specific products remains a significant challenge. We showcase two osmium complexes, przpOs, and trzpOs, as CO2 reduction catalysts for selective CO2-to-methane conversion. Kinetically, the przpOs and trzpOs exhibit high CO2 reduction catalytic rate constants of 0.544 and 6.41 s−1, respectively. Under AM1.5 G irradiation, the optimal Si/TiO2/trzpOs have CH4 as the main product and >90% Faradaic efficiency, reaching −14.11 mA cm−2 photocurrent density at 0.0 VRHE. Density functional theory calculations reveal that the N atoms on the bipyrazole and triazole ligands effectively stabilize the CO2-adduct intermediates, which tend to be further hydrogenated to produce CH4, leading to their ultrahigh CO2-to-CH4 selectivity. These results are comparable to cutting-edge Si-based photocathodes for CO2 reduction, revealing a vast research potential in employing molecular catalysts for the photoelectrochemical conversion of CO2 to methane.
Effects of diets on risks of cancer and the mediating role of metabolites
Authors: Fan Yi , Hu Chanchan , Xie Xiaoxu , Weng Yanfeng , Chen Chen , Wang Zhaokun , He Xueqiong , Jiang Dongxia , Huang Shaodan , Hu Zhijian , Liu Fengqiong 
Published: July 2024

AbstractResearch on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.
Overhauser enhanced liquid state nuclear magnetic resonance spectroscopy in one and two dimensions
Authors: Levien Marcel , Yang Luming , van der Ham Alex , Reinhard Maik , John Michael , Purea Armin , Ganz Jürgen , Marquardsen Thorsten , Tkach Igor , Orlando Tomas , Bennati Marina 
Published: July 2024

AbstractNuclear magnetic resonance (NMR) is fundamental in the natural sciences, from chemical analysis and structural biology, to medicine and physics. Despite its enormous achievements, one of its most severe limitations is the low sensitivity, which arises from the small population difference of nuclear spin states. Methods such as dissolution dynamic nuclear polarization and parahydrogen induced hyperpolarization can enhance the NMR signal by several orders of magnitude, however, their intrinsic limitations render multidimensional hyperpolarized liquid-state NMR a challenge. Here, we report an instrumental design for 9.4 Tesla liquid-state dynamic nuclear polarization that enabled enhanced high-resolution NMR spectra in one and two-dimensions for small molecules, including drugs and metabolites. Achieved enhancements of up to two orders of magnitude translate to signal acquisition gains up to a factor of 10,000. We show that hyperpolarization can be transferred between nuclei, allowing DNP-enhanced two-dimensional 13C–13C correlation experiments at 13C natural abundance. The enhanced sensitivity opens up perspectives for structural determination of natural products or characterization of drugs, available in small quantities. The results provide a starting point for a broader implementation of DNP in liquid-state NMR.