bluuebunny/crossref_metadata_2025_split huggingface dataset:
A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma
Authors: Zhou Royce W. , Xu Jia , Martin Tiphaine C. , Zachem Alexis L. , He John , Ozturk Sait , Demircioglu Deniz , Bansal Ankita , Trotta Andrew P. , Giotti Bruno , Gryder Berkley , Shen Yao , Wu Xuewei , Carcamo Saul , Bosch Kaitlyn , Hopkins Benjamin , Tsankov Alexander , Steinhagen Randolph , Jones Drew R. , Asara John , Chipuk Jerry E. , Brody Rachel , Itzkowitz Steven , Chio Iok In Christine , Hasson Dan , Bernstein Emily , Parsons Ramon E. 
Published: October 2022

AbstractTumors exhibit enhancer reprogramming compared to normal tissue. The etiology is largely attributed to cell-intrinsic genomic alterations. Here, using freshly resected primary CRC tumors and patient-matched adjacent normal colon, we find divergent epigenetic landscapes between CRC tumors and cell lines. Intriguingly, this phenomenon extends to highly recurrent aberrant super-enhancers gained in CRC over normal. We find one such super-enhancer activated in epithelial cancer cells due to surrounding inflammation in the tumor microenvironment. We restore this super-enhancer and its expressed gene, PDZK1IP1, following treatment with cytokines or xenotransplantation into nude mice, thus demonstrating cell-extrinsic etiology. We demonstrate mechanistically that PDZK1IP1 enhances the reductive capacity CRC cancer cells via the pentose phosphate pathway. We show this activation enables efficient growth under oxidative conditions, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Collectively, these observations highlight the significance of epigenomic profiling on primary specimens.
Anisotropic long-range spin transport in canted antiferromagnetic orthoferrite YFeO3
Authors: Das Shubhankar , Ross A. , Ma X. X. , Becker S. , Schmitt C. , van Duijn F. , Galindez-Ruales E. F. , Fuhrmann F. , Syskaki M.-A. , Ebels U. , Baltz V. , Barra A.-L. , Chen H. Y. , Jakob G. , Cao S. X. , Sinova J. , Gomonay O. , Lebrun R. , Kläui M. 
Published: October 2022

AbstractIn antiferromagnets, the efficient transport of spin-waves has until now only been observed in the insulating antiferromagnet hematite, where circularly (or a superposition of pairs of linearly) polarized spin-waves diffuse over long distances. Here, we report long-distance spin-transport in the antiferromagnetic orthoferrite YFeO3, where a different transport mechanism is enabled by the combined presence of the Dzyaloshinskii-Moriya interaction and externally applied fields. The magnon decay length is shown to exceed hundreds of nanometers, in line with resonance measurements that highlight the low magnetic damping. We observe a strong anisotropy in the magnon decay lengths that we can attribute to the role of the magnon group velocity in the transport of spin-waves in antiferromagnets. This unique mode of transport identified in YFeO3opens up the possibility of a large and technologically relevant class of materials, i.e., canted antiferromagnets, for long-distance spin transport.
Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke
Authors: Chen Lingyan , Peters James E. , Prins Bram , Persyn Elodie , Traylor Matthew , Surendran Praveen , Karthikeyan Savita , Yonova-Doing Ekaterina , Di Angelantonio Emanuele , Roberts David J. , Watkins Nicholas A. , Ouwehand Willem H. , Danesh John , Lewis Cathryn M. , Bronson Paola G. , Markus Hugh S. , Burgess Stephen , Butterworth Adam S. , Howson Joanna M. M. 
Published: October 2022

AbstractStroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.62 × 10−4). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P ≤ 0.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke.
SARS-COV-2 antibody responses to AZD1222 vaccination in West Africa
Authors: Abdullahi Adam , Oladele David , Owusu Michael , Kemp Steven A. , Ayorinde James , Salako Abideen , Fink Douglas , Ige Fehintola , Ferreira Isabella A. T. M. , Meng Bo , Sylverken Augustina Angelina , Onwuamah Chika , Boadu Kwame Ofori , Osuolale Kazeem , Frimpong James Opoku , Abubakar Rufai , Okuruawe Azuka , Abdullahi Haruna Wisso , Liboro Gideon , Agyemang Lawrence Duah , Ayisi-Boateng Nana Kwame , Odubela Oluwatosin , Ohihoin Gregory , Ezechi Oliver , Kamasah Japhet Senyo , Ameyaw Emmanuel , Arthur Joshua , Kyei Derrick Boakye , Owusu Dorcas Ohui , Usman Olagoke , Mogaji Sunday , Dada Adedamola , Agyei George , Ebrahimi Soraya , Gutierrez Lourdes Ceron , Aliyu Sani H. , Doffinger Rainer , Audu Rosemary , Adegbola Richard , Mlcochova Petra , Phillips Richard Odame , Solako Babatunde Lawal , Gupta Ravindra K. 
Published: October 2022

AbstractReal-world data on vaccine-elicited neutralising antibody responses for two-dose AZD1222 in African populations are limited. We assessed baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using binding antibodies analysis coupled with pseudotyped virus neutralisation assays in two cohorts from West Africa: Nigerian healthcare workers (n = 140) and a Ghanaian community cohort (n = 527) pre and post vaccination. We found 44 and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59 and 39% respectively with anti-receptor binding domain (RBD) IgG-specific antibodies. Previous IgG anti-N positivity significantly increased post two-dose neutralizing antibody titres in both populations. Serological evidence of breakthrough infection was observed in 8/49 (16%). Neutralising antibodies were observed to wane in both populations, especially in anti-N negative participants with an observed waning rate of 20% highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.
HIV-1 CD4-binding site germline antibody–Env structures inform vaccine design
Authors: Dam Kim-Marie A. , Barnes Christopher O. , Gristick Harry B. , Schoofs Till , Gnanapragasam Priyanthi N. P. , Nussenzweig Michel C. , Bjorkman Pamela J. 
Published: October 2022

AbstractBG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we report 4.1 Å and 3.4 Å single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures reveal critical Env contacts by BG24iGL and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24iGL variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276gp120 glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.
An intrinsic temporal order of c-JUN N-terminal phosphorylation regulates its activity by orchestrating co-factor recruitment
Authors: Waudby Christopher A. , Alvarez-Teijeiro Saul , Josue Ruiz E. , Suppinger Simon , Pinotsis Nikos , Brown Paul R. , Behrens Axel , Christodoulou John , Mylona Anastasia 
Published: October 2022

AbstractProtein phosphorylation is a major regulatory mechanism of cellular signalling. The c-JUN proto-oncoprotein is phosphorylated at four residues within its transactivation domain (TAD) by the JNK family kinases, but the functional significance of c-JUN multisite phosphorylation has remained elusive. Here we show that c-JUN phosphorylation by JNK exhibits defined temporal kinetics, with serine63 and serine73 being phosphorylated more rapidly than threonine91 and threonine93. We identify the positioning of the phosphorylation sites relative to the kinase docking motif, and their primary sequence, as the main factors controlling phosphorylation kinetics. Functional analysis reveals three c-JUN phosphorylation states: unphosphorylated c-JUN recruits the MBD3 repressor, serine63/73 doubly-phosphorylated c-JUN binds to the TCF4 co-activator, whereas the fully phosphorylated form disfavours TCF4 binding attenuating JNK signalling. Thus, c-JUN phosphorylation encodes multiple functional states that drive a complex signalling response from a single JNK input.
A scalable platform to discover antimicrobials of ribosomal origin
Authors: Ayikpoe Richard S. , Shi Chengyou , Battiste Alexander J. , Eslami Sara M. , Ramesh Sangeetha , Simon Max A. , Bothwell Ian R. , Lee Hyunji , Rice Andrew J. , Ren Hengqian , Tian Qiqi , Harris Lonnie A. , Sarksian Raymond , Zhu Lingyang , Frerk Autumn M. , Precord Timothy W. , van der Donk Wilfred A. , Mitchell Douglas A. , Zhao Huimin 
Published: October 2022

AbstractRibosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new antimicrobials in the face of rising antibiotic resistance. Here, we report a scalable platform that combines high-throughput bioinformatics with automated biosynthetic gene cluster refactoring for rapid evaluation of uncharacterized gene clusters. As a proof of concept, 96 RiPP gene clusters that originate from diverse bacterial phyla involving 383 biosynthetic genes are refactored in a high-throughput manner using a biological foundry with a success rate of 86%. Heterologous expression of all successfully refactored gene clusters inEscherichia colienables the discovery of 30 compounds covering six RiPP classes: lanthipeptides, lasso peptides, graspetides, glycocins, linear azol(in)e-containing peptides, and thioamitides. A subset of the discovered lanthipeptides exhibit antibiotic activity, with one class II lanthipeptide showing low µM activity againstKlebsiella pneumoniae, an ESKAPE pathogen. Overall, this work provides a robust platform for rapidly discovering RiPPs.
Topological phononics arising from fluid-solid interactions
Authors: Wu Xiaoxiao , Fan Haiyan , Liu Tuo , Gu Zhongming , Zhang Ruo-Yang , Zhu Jie , Zhang Xiang 
Published: October 2022

AbstractNontrivial band topologies have been discovered in classical systems and hold great potential for device applications. Unlike photons, sound has fundamentally different dynamics and symmetries in fluids and solids, represented as scalar and vector fields, respectively. So far, searches for topological phononic materials have only concerned sound in either fluids or solids alone, overlooking their intricate interactions in “mixtures”. Here, we report an approach for topological phononics employing such unique interplay, and demonstrate the realization of type-II nodal rings, elusive in phononics, in a simple three-dimensional phononic crystal. Type-II nodal rings, as line degeneracies in momentum space with exotic properties from strong tilting, are directly observed through ultrasonic near-field scanning. Strongly tilted drumhead surface states, the hallmark phenomena, are also experimentally demonstrated. This phononic approach opens a door to explore topological physics in classical systems, which is easy to implement that can be used for designing high-performance acoustic devices.
Selective activation of four quasi-equivalent C–H bonds yields N-doped graphene nanoribbons with partial corannulene motifs
Authors: Gao Yixuan , Huang Li , Cao Yun , Richter Marcus , Qi Jing , Zheng Qi , Yang Huan , Ma Ji , Chang Xiao , Fu Xiaoshuai , Palma Carlos-Andres , Lu Hongliang , Zhang Yu-Yang , Cheng Zhihai , Lin Xiao , Ouyang Min , Feng Xinliang , Du Shixuan , Gao Hong-Jun 
Published: October 2022

AbstractSelective C–H bond activation is one of the most challenging topics for organic reactions. The difficulties arise not only from the high C–H bond dissociation enthalpies but also the existence of multiple equivalent/quasi-equivalent reaction sites in organic molecules. Here, we successfully achieve the selective activation of four quasi-equivalent C–H bonds in a specially designed nitrogen-containing polycyclic hydrocarbon (N-PH). Density functional theory calculations reveal that the adsorption of N-PH on Ag(100) differentiates the activity of the four ortho C(sp3) atoms in the N-heterocycles into two groups, suggesting a selective dehydrogenation, which is demonstrated by sequential-annealing experiments of N-PH/Ag(100). Further annealing leads to the formation of N-doped graphene nanoribbons with partial corannulene motifs, realized by the C–H bond activation process. Our work provides a route of designing precursor molecules with ortho C(sp3) atom in an N-heterocycle to realize surface-induced selective dehydrogenation in quasi-equivalent sites.
Two-dimensional multiferroic material of metallic p-doped SnSe
Authors: Du Ruofan , Wang Yuzhu , Cheng Mo , Wang Peng , Li Hui , Feng Wang , Song Luying , Shi Jianping , He Jun 
Published: October 2022

AbstractTwo-dimensional multiferroic materials have garnered broad interests attributed to their magnetoelectric properties and multifunctional applications. Multiferroic heterostructures have been realized, nevertheless, the direct coupling between ferroelectric and ferromagnetic order in a single material still remains challenging, especially for two-dimensional materials. Here, we develop a physical vapor deposition approach to synthesize two-dimensional p-doped SnSe. The local phase segregation of SnSe2 microdomains and accompanying interfacial charge transfer results in the emergence of degenerate semiconductor and metallic feature in SnSe. Intriguingly, the room-temperature ferrimagnetism has been demonstrated in two-dimensional p-doped SnSe with the Curie temperature approaching to ~337 K. Meanwhile, the ferroelectricity is maintained even under the depolarizing field introduced by SnSe2. The coexistence of ferrimagnetism and ferroelectricity in two-dimensional p-doped SnSe verifies its multiferroic feature. This work presents a significant advance for exploring the magnetoelectric coupling in two-dimensional limit and constructing high-performance logic devices to extend Moore’s law.
A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection
Authors: Calvert Clara , Carruthers Jade , Denny Cheryl , Donaghy Jack , Hillman Sam , Hopcroft Lisa E. M. , Hopkins Leanne , Goulding Anna , Lindsay Laura , McLaughlin Terry , Moore Emily , Pan Jiafeng , Taylor Bob , Almaghrabi Fatima , Auyeung Bonnie , Bhaskaran Krishnan , Gibbons Cheryl L. , Katikireddi Srinivasa Vittal , McCowan Colin , Murray Josie , O’Leary Maureen , Ritchie Lewis D. , Shah Syed Ahmar , Simpson Colin R. , Robertson Chris , Sheikh Aziz , Stock Sarah J. , Wood Rachael 
Published: October 2022

AbstractData on the safety of COVID-19 vaccines in early pregnancy are limited. We conducted a national, population-based, matched cohort study assessing associations between COVID-19 vaccination and miscarriage prior to 20 weeks gestation and, separately, ectopic pregnancy. We identified women in Scotland vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Matched, unvaccinated women from the pre-pandemic and, separately, pandemic periods were used as controls. Here we show no association between vaccination and miscarriage (adjusted Odds Ratio [aOR], pre-pandemic controls = 1.02, 95% Confidence Interval [CI] = 0.96–1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92–1.38). We undertook additional analyses examining confirmed SARS-CoV-2 infection as the exposure and similarly found no association with miscarriage or ectopic pregnancy. Our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19.
Facet effect of hematite on the hydrolysis of phthalate esters under ambient humidity conditions
Authors: Jin Xin , Wu Dingding , Liu Cun , Huang Shuhan , Zhou Ziyan , Wu Hao , Chen Xiru , Huang Meiying , Zhou Shaoda , Gu Cheng 
Published: October 2022

AbstractPhthalate esters (PAEs) have been extensively used as additives in plastics and wallcovering, causing severe environmental contamination and increasing public health concerns. Here, we find that hematite nanoparticles with specific facet-control can efficiently catalyze PAEs hydrolysis under ambient humidity conditions, with the hydrolysis rates 2 orders of magnitude higher than that in water saturated condition. The catalytic performance of hematite shows a significant facet-dependence with the reactivity in the order {012} > {104} ≫ {001}, related to the atomic array of surface undercoordinated Fe. The {012} and {104} facets with the proper neighboring Fe-Fe distance of 0.34-0.39 nm can bidentately coordinate with PAEs, and thus induce much stronger Lewis-acid catalysis. Our study may inspire the development of nanomaterials with appropriate surface atomic arrays, improves our understanding for the natural transformation of PAEs under low humidity environment, and provides a promising approach to remediate/purify the ambient air contaminated by PAEs.
A small molecule inhibitor prevents gut bacterial genotoxin production
Authors: Volpe Matthew R. , Velilla José A. , Daniel-Ivad Martin , Yao Jenny J. , Stornetta Alessia , Villalta Peter W. , Huang Hsin-Che , Bachovchin Daniel A. , Balbo Silvia , Gaudet Rachelle , Balskus Emily P. 
Published: October 2022

AbstractThe human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin’s biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a clbP deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis.
NMR lineshape analysis using analytical solutions of multi-state chemical exchange with applications to kinetics of host–guest systems
Authors: Březina Václav , Hanyková Lenka , Velychkivska Nadiia , Hill Jonathan P. , Labuta Jan 
Published: October 2022

AbstractNuclear magnetic resonance (NMR) lineshape analysis is a powerful tool for the study of chemical kinetics. Here we provide techniques for analysis of the relationship between experimentally observed spin kinetics (transitions between different environments $$A,B,\dots$$

A
,
B
,
⋯

) and corresponding chemical kinetics (transitions between distinct chemical species; e.g., free host and complexed host molecule). The advantages of using analytical solutions for two-, three- or generally N-state exchange lineshapes (without J-coupling) over the widely used numerical calculation for NMR spectral fitting are presented. Several aspects of exchange kinetics including the generalization of coalescence conditions in two-state exchange, the possibility of multiple processes between two states, and differences between equilibrium and steady-state modes are discussed. ‘Reduced equivalent schemes’ are introduced for spin kinetics containing fast-exchanging states, effectively reducing the number of exchanging states. The theoretical results have been used to analyze a host–guest system containing an oxoporphyrinogen complexed with camphorsulfonic acid and several other literature examples, including isomerization, protein kinetics, or enzymatic reactions. The theoretical treatment and experimental examples present an expansion of the systematic approach to rigorous analyses of systems with rich chemical kinetics through NMR lineshape analysis.
A lightweight convolutional neural network model with receptive field block for C-shaped root canal detection in mandibular second molars
Authors: Zhang Lijuan , Xu Feng , Li Ying , Zhang Huimin , Xi Ziyi , Xiang Jie , Wang Bin 
Published: October 2022

AbstractRapid and accurate detection of a C-shaped root canal on mandibular second molars can assist dentists in diagnosis and treatment. Oral panoramic radiography is one of the most effective methods of determining the root canal of teeth. There are already some traditional methods based on deep learning to learn the characteristics of C-shaped root canal tooth images. However, previous studies have shown that the accuracy of detecting the C-shaped root canal still needs to be improved. And it is not suitable for implementing these network structures with limited hardware resources. In this paper, a new lightweight convolutional neural network is designed, which combined with receptive field block (RFB) for optimizing feature extraction. In order to optimize the hardware resource requirements of the model, a lightweight, multi-branch, convolutional neural network model was developed in this study. To improve the feature extraction ability of the model for C-shaped root canal tooth images, RFB has been merged with this model. RFB has achieved excellent results in target detection and classification. In the multiscale receptive field block, some small convolution kernels are used to replace the large convolution kernels, which allows the model to extract detailed features and reduce the computational complexity. Finally, the accuracy and area under receiver operating characteristics curve (AUC) values of C-shaped root canals on the image data of our mandibular second molars were 0.9838 and 0.996, respectively. The results show that the deep learning model proposed in this paper is more accurate and has lower computational complexity than many other similar studies. In addition, score-weighted class activation maps (Score-CAM) were generated to localize the internal structure that contributed to the predictions.