bluuebunny/crossref_metadata_2025_split huggingface dataset:
The intestinal MUC2 mucin C-terminus is stabilized by an extra disulfide bond in comparison to von Willebrand factor and other gel-forming mucins
Authors: Gallego Pablo , Garcia-Bonete Maria-Jose , Trillo-Muyo Sergio , Recktenwald Christian V. , Johansson Malin E. V. , Hansson Gunnar C. 
Published: April 2023

AbstractThe MUC2 mucin polymer is the main building unit of the intestinal mucus layers separating intestinal microbiota from the host epithelium. The MUC2 mucin is a large glycoprotein with a C-terminal domain similar to the MUC5AC and MUC5B mucins and the von Willebrand factor (VWF). A structural model of the C-terminal part of MUC2, MUC2-C, was generated by combining Cryo-electron microscopy, AlphaFold prediction, information of its glycosylation, and small angle X-ray scattering information. The globular VWD4 assembly in the N-terminal of MUC2-C is followed by 3.5 linear VWC domains that form an extended flexible structure before the C-terminal cystine-knot. All gel-forming mucins and VWF form tail-tail disulfide-bonded dimers in their C-terminal cystine-knot domain, but interestingly the MUC2 mucin has an extra stabilizing disulfide bond on the N-terminal side of the VWD4 domain, likely essential for a stable intestinal mucus barrier.
The evolution and international spread of extensively drug resistant Shigella sonnei
Authors: Mason Lewis C. E. , Greig David R. , Cowley Lauren A. , Partridge Sally R. , Martinez Elena , Blackwell Grace A. , Chong Charlotte E. , De Silva P. Malaka , Bengtsson Rebecca J. , Draper Jenny L. , Ginn Andrew N. , Sandaradura Indy , Sim Eby M. , Iredell Jonathan R. , Sintchenko Vitali , Ingle Danielle J. , Howden Benjamin P. , Lefèvre Sophie , Njamkepo Elisabeth , Weill François-Xavier , Ceyssens Pieter-Jan , Jenkins Claire , Baker Kate S. 
Published: April 2023

AbstractShigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common including against World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin. Recently, an MSM-associated outbreak of extended-spectrum β-lactamase producing, extensively drug resistant S. sonnei was reported in the United Kingdom. Here, we aimed to identify the genetic basis, evolutionary history, and international dissemination of the outbreak strain. Our genomic epidemiological analyses of 3,304 isolates from the United Kingdom, Australia, Belgium, France, and the United States of America revealed an internationally connected outbreak with a most recent common ancestor in 2018 carrying a low-fitness cost resistance plasmid, previously observed in travel associated sublineages of S. flexneri. Our results highlight the persistent threat of horizontally transmitted antimicrobial resistance and the value of continuing to work towards early and open international sharing of genomic surveillance data.
Topological antichiral surface states in a magnetic Weyl photonic crystal
Authors: Xi Xiang , Yan Bei , Yang Linyun , Meng Yan , Zhu Zhen-Xiao , Chen Jing-Ming , Wang Ziyao , Zhou Peiheng , Shum Perry Ping , Yang Yihao , Chen Hongsheng , Mandal Subhaskar , Liu Gui-Geng , Zhang Baile , Gao Zhen 
Published: April 2023

AbstractChiral edge states that propagate oppositely at two parallel strip edges are a hallmark feature of Chern insulators which were first proposed in the celebrated two-dimensional (2D) Haldane model. Subsequently, counterintuitive antichiral edge states that propagate in the same direction at two parallel strip edges were discovered in a 2D modified Haldane model. Recently, chiral surface states, the 2D extension of one-dimensional (1D) chiral edge states, have also been observed in a photonic analogue of a 3D Haldane model. However, despite many recent advances in antichiral edge states and chiral surface states, antichiral surface states, the 2D extension of 1D antichiral edge states, have never been realized in any physical system. Here, we report the experimental observation of antichiral surface states by constructing a 3D modified Haldane model in a magnetic Weyl photonic crystal with two pairs of frequency-shifted Weyl points (WPs). The 3D magnetic Weyl photonic crystal consists of gyromagnetic cylinders with opposite magnetization in different triangular sublattices of a 3D honeycomb lattice. Using microwave field-mapping measurements, unique properties of antichiral surface states have been observed directly, including the antichiral robust propagation, tilted surface dispersion, a single open Fermi arc connecting two projected WPs and a single Fermi loop winding around the surface Brillouin zone (BZ). These results extend the scope of antichiral topological states and enrich the family of magnetic Weyl semimetals.
The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot
Authors: Loiseau Chloé , Windels Etthel M. , Gygli Sebastian M. , Jugheli Levan , Maghradze Nino , Brites Daniela , Ross Amanda , Goig Galo , Reinhard Miriam , Borrell Sonia , Trauner Andrej , Dötsch Anna , Aspindzelashvili Rusudan , Denes Rebecca , Reither Klaus , Beisel Christian , Tukvadze Nestani , Avaliani Zaza , Stadler Tanja , Gagneux Sebastien 
Published: April 2023

AbstractMultidrug-resistant tuberculosis (MDR-TB) is among the most frequent causes of death due to antimicrobial resistance. Although only 3% of global TB cases are MDR, geographical hotspots with up to 40% of MDR-TB have been observed in countries of the former Soviet Union. While the quality of TB control and patient-related factors are known contributors to such hotspots, the role of the pathogen remains unclear. Here we show that in the country of Georgia, a known hotspot of MDR-TB, MDR Mycobacterium tuberculosis strains of lineage 4 (L4) transmit less than their drug-susceptible counterparts, whereas most MDR strains of L2 suffer no such defect. Our findings further indicate that the high transmission fitness of these L2 strains results from epistatic interactions between the rifampicin resistance-conferring mutation RpoB S450L, compensatory mutations in the RNA polymerase, and other pre-existing genetic features of L2/Beijing clones that circulate in Georgia. We conclude that the transmission fitness of MDR M. tuberculosis strains is heterogeneous, but can be as high as drug-susceptible forms, and that such highly drug-resistant and transmissible strains contribute to the emergence and maintenance of hotspots of MDR-TB. As these strains successfully overcome the metabolic burden of drug resistance, and given the ongoing rollout of new treatment regimens against MDR-TB, proper surveillance should be implemented to prevent these strains from acquiring resistance to the additional drugs.
Order-disorder phase transition driven by interlayer sliding in lead iodides
Authors: Cha Seyeong , Lee Giyeok , Lee Sol , Ryu Sae Hee , Sohn Yeongsup , An Gijeong , Kang Changmo , Kim Minsu , Kim Kwanpyo , Soon Aloysius , Kim Keun Su 
Published: April 2023

AbstractA variety of phase transitions have been found in two-dimensional layered materials, but some of their atomic-scale mechanisms are hard to clearly understand. Here, we report the discovery of a phase transition whose mechanism is identified as interlayer sliding in lead iodides, a layered material widely used to synthesize lead halide perovskites. The low-temperature crystal structure of lead iodides is found not 2H polytype as known before, but non-centrosymmetric 4H polytype. This undergoes the order-disorder phase transition characterized by the abrupt spectral broadening of valence bands, taken by angle-resolved photoemission, at the critical temperature of 120 K. It is accompanied by drastic changes in simultaneously taken photocurrent and photoluminescence. The transmission electron microscopy is used to reveal that lead iodide layers stacked in the form of 4H polytype at low temperatures irregularly slide over each other above 120 K, which can be explained by the low energy barrier of only 10.6 meV/atom estimated by first principles calculations. Our findings suggest that interlayer sliding is a key mechanism of the phase transitions in layered materials, which can significantly affect optoelectronic and optical characteristics.
Conformational cycle of human polyamine transporter ATP13A2
Authors: Mu Jianqiang , Xue Chenyang , Fu Lei , Yu Zongjun , Nie Minhan , Wu Mengqi , Chen Xinmeng , Liu Kun , Bu Ruiqian , Huang Ying , Yang Baisheng , Han Jianming , Jiang Qianru , Chan Kevin C. , Zhou Ruhong , Li Huilin , Huang Ancheng , Wang Yong , Liu Zhongmin 
Published: April 2023

AbstractDysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson’s disease and autosomal recessive spastic paraplegia 78, is a transporter with a critical role in balancing the polyamine concentration between the lysosome and the cytosol. Here, to better understand human ATP13A2-mediated polyamine transport, we use single-particle cryo-electron microscopy to solve high-resolution structures of human ATP13A2 in six intermediate states, including the putative E2 structure for the P5 subfamily of the P-type ATPases. These structures comprise a nearly complete conformational cycle spanning the polyamine transport process and capture multiple substrate binding sites distributed along the transmembrane regions, suggesting a potential polyamine transport pathway. Integration of high-resolution structures, biochemical assays, and molecular dynamics simulations allows us to obtain a better understanding of the structural basis of how hATP13A2 transports polyamines, providing a mechanistic framework for ATP13A2-related diseases.
Segmentation strategy of de novo designed four-helical bundles expands protein oligomerization modalities for cell regulation
Authors: Merljak Estera , Malovrh Benjamin , Jerala Roman 
Published: April 2023

AbstractProtein–protein interactions govern most biological processes. New protein assemblies can be introduced through the fusion of selected proteins with di/oligomerization domains, which interact specifically with their partners but not with other cellular proteins. While four-helical bundle proteins (4HB) have typically been assembled from two segments, each comprising two helices, here we show that they can be efficiently segmented in various ways, expanding the number of combinations generated from a single 4HB. We implement a segmentation strategy of 4HB to design two-, three-, or four-chain combinations for the recruitment of multiple protein components. Different segmentations provide new insight into the role of individual helices for 4HB assembly. We evaluate 4HB segmentations for potential use in mammalian cells for the reconstitution of a protein reporter, transcriptional activation, and inducible 4HB assembly. Furthermore, the implementation of trimerization is demonstrated as a modular chimeric antigen receptor for the recognition of multiple cancer antigens.
RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes
Authors: Subramanian Megha , McIninch James , Zlatev Ivan , Schlegel Mark K. , Kaittanis Charalambos , Nguyen Tuyen , Agarwal Saket , Racie Timothy , Alvarado Martha Arbaiza , Wassarman Kelly , Collins Thomas S. , Chickering Tyler , Brown Christopher R. , Schmidt Karyn , Castoreno Adam B. , Shulga-Morskaya Svetlana , Stamenova Elena , Buckowing Kira , Berman Daniel , Barry Joseph D. , Bisbe Anna , Maier Martin A. , Fitzgerald Kevin , Jadhav Vasant 
Published: April 2023

AbstractAdeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein hepatocyte-directed AAV transgene expression is silenced using the clinically validated modality of chemically modified small interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies.
Light-independent regulation of algal photoprotection by CO2 availability
Authors: Ruiz-Sola M. Águila , Flori Serena , Yuan Yizhong , Villain Gaelle , Sanz-Luque Emanuel , Redekop Petra , Tokutsu Ryutaro , Küken Anika , Tsichla Angeliki , Kepesidis Georgios , Allorent Guillaume , Arend Marius , Iacono Fabrizio , Finazzi Giovanni , Hippler Michael , Nikoloski Zoran , Minagawa Jun , Grossman Arthur R. , Petroutsos Dimitris 
Published: April 2023

AbstractPhotosynthetic algae have evolved mechanisms to cope with suboptimal light and CO2 conditions. When light energy exceeds CO2 fixation capacity, Chlamydomonas reinhardtii activates photoprotection, mediated by LHCSR1/3 and PSBS, and the CO2 Concentrating Mechanism (CCM). How light and CO2 signals converge to regulate these processes remains unclear. Here, we show that excess light activates photoprotection- and CCM-related genes by altering intracellular CO2 concentrations and that depletion of CO2 drives these responses, even in total darkness. High CO2 levels, derived from respiration or impaired photosynthetic fixation, repress LHCSR3/CCM genes while stabilizing the LHCSR1 protein. Finally, we show that the CCM regulator CIA5 also regulates photoprotection, controlling LHCSR3 and PSBS transcript accumulation while inhibiting LHCSR1 protein accumulation. This work has allowed us to dissect the effect of CO2 and light on CCM and photoprotection, demonstrating that light often indirectly affects these processes by impacting intracellular CO2 levels.
Coupled mixed-potential and thermal-hydraulics model for long-term corrosion of copper canisters in deep geological repository
Authors: Chae Nakkyu , Park Samuel , Seo Seungjin , Foster Richard I. , Ju Heejae , Choi Sungyeol 
Published: April 2023

AbstractCanister performance is a major issue for constructing reliable deep geological repositories for storing spent nuclear fuels, and corrosion resistance is main the factor determining canister durability. We developed a 2-D multiphysics model, which can predict both the corrosion rate and potential, for simulating copper canister corrosion in deep geological repositories. We found that canisters corroded through the long-cell action in a deep geological repository, the corrosion was quite limited, and the overall canister durability was around 1.7 million years. Our results demonstrated that copper exhibits sufficient corrosion resistance and that long-cell action-based corrosion cannot severely damage copper canisters.
Care by general practitioners for patients with asthma or COPD during the COVID-19 pandemic
Authors: Rijpkema Corinne , Ramerman Lotte , Homburg Maarten , Meijer Eline , Muris Jean , olde Hartman Tim , Berger Marjolein , Peters Lilian , Verheij Robert 
Published: April 2023

AbstractThe impact of the COVID-19 pandemic on general practitioners’ (GP) care for patients with asthma and/or COPD is largely unknown. To describe the impact of the pandemic on asthma or COPD-related GP care, we analysed routinely recorded electronic health records data from Dutch general practices and out-of-hours (OOH) services. During the COVID-19 pandemic (2020), the contact rates for asthma and/or COPD were significantly lower in GP practices and OOH services compared with the pre-pandemic period (2019) (respectively, 15% lower and 28% lower). The proportion of telephone contacts increased significantly with 13%-point in GP practices and 12%-point at OOH services, while the proportion of face-to-face contacts decreased. Furthermore, the proportion of high urgent contacts with OOH services decreased by 8.5%-point. To conclude, the overall contact rates in GP practices and OOH services decreased, while more contacts were remote. Lower contact rates have, after a short follow-up, not resulted in more patients with exacerbations in OOH care. However, this might still be expected after a longer follow-up.
Orbital degree of freedom induced multiple sets of second-order topological states in two-dimensional breathing Kagome crystals
Authors: Zhou Hui , Liu Hang , Ji Hongyan , Li Xuanyi , Meng Sheng , Sun Jia-Tao 
Published: April 2023

AbstractThe lattice geometry induced second-order topological corner states in breathing Kagome lattice have attracted enormous research interests, while the realistic breathing Kagome materials identified as second-order topological insulators are still lacking. Here, we report by first-principles calculations the second-order topological states emerging in two-dimensional d-orbital breathing Kagome crystals, i.e., monolayer niobium/tantalum chalcogenide halides M3QX7 (M = Nb, Ta; Q = S, Se, Te; X = Cl, Br, I). We find that the orbital degree of freedom of d orbitals can give rise to multiple sets of corner states. Combining fraction corner anomaly, orbital components and real space distribution of the corner states, we can also identify the topology of these corner states. Our work not only extends the lattice geometry induced second-order topological states to realistic materials, but also builds a clear and complete picture on their multiple sets of second-order topological states.
Cholec80-CVS: An open dataset with an evaluation of Strasberg’s critical view of safety for AI
Authors: Ríos Manuel Sebastián , Molina-Rodriguez María Alejandra , Londoño Daniella , Guillén Camilo Andrés , Sierra Sebastián , Zapata Felipe , Giraldo Luis Felipe 
Published: April 2023

AbstractStrasberg’s criteria to detect a critical view of safety is a widely known strategy to reduce bile duct injuries during laparoscopic cholecystectomy. In spite of its popularity and efficiency, recent studies have shown that human miss-identification errors have led to important bile duct injuries occurrence rates. Developing tools based on artificial intelligence that facilitate the identification of a critical view of safety in cholecystectomy surgeries can potentially minimize the risk of such injuries. With this goal in mind, we present Cholec80-CVS, the first open dataset with video annotations of Strasberg’s Critical View of Safety (CVS) criteria. Our dataset contains CVS criteria annotations provided by skilled surgeons for all videos in the well-known Cholec80 open video dataset. We consider that Cholec80-CVS is the first step towards the creation of intelligent systems that can assist humans during laparoscopic cholecystectomy.
Genome-wide chromatin accessibility and gene expression profiling during flatfish metamorphosis
Authors: Guerrero-Peña Laura , Suarez-Bregua Paula , Gil-Gálvez Alejandro , Naranjo Silvia , Méndez-Martínez Luis , Tur Ricardo , García-Fernández Pablo , Tena Juan J , Rotllant Josep 
Published: April 2023

AbstractMetamorphosis is a widely studied post-embryonic process in which many tissues undergo dramatic modifications to adapt to the new adult lifestyle. Flatfishes represent a good example of metamorphosis in teleost fishes. During metamorphosis of flatfish, organ regression and neoformation occur, with one of the most notable changes being the migration of one of the eyes to the other side of the body. In order to create a useful and reliable tool to advance the molecular study of metamorphosis in flatfish, we generated a chromatin accessible atlas as well as gene expression profile during four developmental stages ranging from a phylotypic to a post-metamorphic stage. We identified 29,019 differentially accessible chromatin regions and 3,253 differentially expressed genes. We found stage-specific regulatory regions and gene expression profiles, supporting the quality of the results. Our work provides strongly reproducible data for further studies to elucidate the regulatory elements that ensure successful metamorphosis in flatfish species.
Prognostic value of pre-therapeutic FDG-PET radiomic analysis in gastro-esophageal junction cancer
Authors: Amrane Karim , Thuillier Philippe , Bourhis David , Le Meur Coline , Quere Chloe , Leclere Jean-Christophe , Ferec Marc , Jestin-Le Tallec Veronique , Doucet Laurent , Alemany Pierre , Salaun Pierre-Yves , Metges Jean-Philippe , Schick Ulrike , Abgral Ronan 
Published: April 2023

AbstractThe main aim of this study was to evaluate the prognostic value of radiomic approach in pre-therapeutic18F-fluorodeoxyglucose positron-emission tomography (FDG-PET/CT) in a large cohort of patients with gastro-esophageal junction cancer (GEJC). This was a retrospective monocenter study including 97 consecutive patients with GEJC who underwent a pre-therapeutic FDG-PET and were followed up for 3 years. Standard first-order radiomic PET indices including SUVmax, SUVmean, SUVpeak, MTV and TLG and 32 textural features (TFs) were calculated using LIFEx software on PET imaging. Prognostic significance of these parameters was assessed in univariate and multivariate analysis. Relapse-free survival (RFS) and overall survival (OS) were respectively chosen as primary and secondary endpoints. An internal validation cohort was used by randomly drawing one-third of included patients. The main characteristics of this cohort were: median age of 65 years [41–88], sex ratio H/F = 83/14, 81.5% of patients with a histopathology of adenocarcinoma and 43.3% with a stage IV disease. The median follow-up was 28.5 months [4.2–108.5]. Seventy-seven (79.4%) patients had locoregional or distant progression or recurrence and 71 (73.2%) died. In univariate analysis, SUVmean, Histogram-Entropy and 2 TFs (GLCM-Homogeneity and GLCM-Energy) were significantly correlated with RFS and OS, as well as 2 others TFs (GLRLM-LRE and GLRLM-GLNU) with OS only. In multivariate analysis, Histogram-Entropy remained an independent prognostic factor of both RFS and OS whereas SUVmeanwas an independent prognostic factor of OS only. These results were partially confirmed in our internal validation cohort of 33 patients. Our results suggest that radiomic approach reveals independent prognostic factors for survival in patients with GEJC.