bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topological heavy fermions in magnetic field
Authors: Singh Keshav , Chew Aaron , Herzog-Arbeitman Jonah , Bernevig B. Andrei , Vafek Oskar 
Published: June 2024

AbstractThe recently introduced topological heavy fermion model (THFM) provides a means for interpreting the low-energy electronic degrees of freedom of the magic angle twisted bilayer graphene as hybridization amidst highly dispersing topological conduction and weakly dispersing localized heavy fermions. In order to understand the Landau quantization of the ensuing electronic spectrum, a generalization of THFM to include the magnetic field B is desired, but currently missing. Here we provide a systematic derivation of the THFM in B and solve the resulting model to obtain the interacting Hofstadter spectra for single particle charged excitations. While naive minimal substitution within THFM fails to correctly account for the total number of magnetic subbands within the narrow band i.e., its total Chern number, our method—based on projecting the light and heavy fermions onto the irreducible representations of the magnetic translation group— reproduces the correct total Chern number. Analytical results presented here offer an intuitive understanding of the nature of the (strongly interacting) Hofstadter bands.
Microenvironment regulation breaks the Faradaic efficiency-current density trade-off for electrocatalytic deuteration using D2O
Authors: He Meng , Li Rui , Cheng Chuanqi , Liu Cuibo , Zhang Bin 
Published: June 2024

AbstractThe high Faradaic efficiency (FE) of the electrocatalytic deuteration of organics with D2O at a large current density is significant for deuterated electrosynthesis. However, the FE and current density are the two ends of a seesaw because of the severe D2 evolution side reaction at nearly industrial current densities. Herein, we report a combined scenario of a nanotip-enhanced electric field and surfactant-modified interface microenvironment to enable the electrocatalytic deuteration of arylacetonitrile in D2O with an 80% FE at −100 mA cm−2. The increased concentration with low activation energy of arylacetonitrile due to the large electric field along the tips and the accelerated arylacetonitrile transfer and suppressed D2 evolution by the surfactant-created deuterophobic microenvironment contribute to breaking the trade-off between a high FE and large current density. Furthermore, the application of our strategy in other deuteration reactions with improved Faradaic efficiencies at −100 mA cm−2 rationalizes the design concept.
Palladium-catalyzed Suzuki-Miyaura cross-couplings of stable glycal boronates for robust synthesis of C-1 glycals
Authors: Chen Anrong , Han Yang , Wu Rongfeng , Yang Bo , Zhu Lijuan , Zhu Feng 
Published: June 2024

AbstractC-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki–Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp2)-C(sp), C(sp2)-C(sp2), and C(sp2)-C(sp3) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products.
Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast
Authors: Gou Yuanwei , Li Dongfang , Zhao Minghui , Li Mengxin , Zhang Jiaojiao , Zhou Yilian , Xiao Feng , Liu Gaofei , Ding Haote , Sun Chenfan , Ye Cuifang , Dong Chang , Gao Jucan , Gao Di , Bao Zehua , Huang Lei , Xu Zhinan , Lian Jiazhang 
Published: June 2024

AbstractWhile sanguinarine has gained recognition for antimicrobial and antineoplastic activities, its complex conjugated structure and low abundance in plants impede broad applications. Here, we demonstrate the complete biosynthesis of sanguinarine and halogenated derivatives using highly engineered yeast strains. To overcome sanguinarine cytotoxicity, we establish a splicing intein-mediated temperature-responsive gene expression system (SIMTeGES), a simple strategy that decouples cell growth from product synthesis without sacrificing protein activity. To debottleneck sanguinarine biosynthesis, we identify two reticuline oxidases and facilitated functional expression of flavoproteins and cytochrome P450 enzymes via protein molecular engineering. After comprehensive metabolic engineering, we report the production of sanguinarine at a titer of 448.64 mg L−1. Additionally, our engineered strain enables the biosynthesis of fluorinated sanguinarine, showcasing the biotransformation of halogenated derivatives through more than 15 biocatalytic steps. This work serves as a blueprint for utilizing yeast as a scalable platform for biomanufacturing diverse benzylisoquinoline alkaloids and derivatives.
Single missense mutations in Vi capsule synthesis genes confer hypervirulence to Salmonella Typhi
Authors: Lee Gi Young , Song Jeongmin 
Published: June 2024

AbstractMany bacterial pathogens, including the human exclusive pathogen Salmonella Typhi, express capsular polysaccharides as a crucial virulence factor. Here, through S. Typhi whole genome sequence analyses and functional studies, we found a list of single point mutations that make S. Typhi hypervirulent. We discovered a single point mutation in the Vi biosynthesis enzymes that control Vi polymerization or acetylation is enough to result in different capsule variants of S. Typhi. All variant strains are pathogenic, but the hyper Vi capsule variants are particularly hypervirulent, as demonstrated by the high morbidity and mortality rates observed in infected mice. The hypo Vi capsule variants have primarily been identified in Africa, whereas the hyper Vi capsule variants are distributed worldwide. Collectively, these studies increase awareness about the existence of different capsule variants of S. Typhi, establish a solid foundation for numerous future studies on S. Typhi capsule variants, and offer valuable insights into strategies to combat capsulated bacteria.
Rbpms2 promotes female fate upstream of the nutrient sensing Gator2 complex component Mios
Authors: Wilson Miranda L. , Romano Shannon N. , Khatri Nitya , Aharon Devora , Liu Yulong , Kaufman Odelya H. , Draper Bruce W. , Marlow Florence L. 
Published: June 2024

AbstractReproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.
A prefrontal motor circuit initiates persistent movement
Authors: Wang Yihan , Sun Qian-Quan 
Published: June 2024

AbstractPersistence reinforces continuous action, which benefits animals in many aspects. Diverse external or internal signals may trigger animals to start a persistent movement. However, it is unclear how the brain decides to persist with current actions by selecting specific information. Using single-unit extracellular recordings and opto-tagging in awake mice, we demonstrated that a group of dorsal mPFC (dmPFC) motor cortex projecting (MP) neurons initiate a persistent movement by selectively encoding contextual information rather than natural valence. Inactivation of dmPFC MP neurons impairs the initiation and reduces neuronal activity in the insular and motor cortex. After the persistent movement is initiated, the dmPFC MP neurons are not required to maintain it. Finally, a computational model suggests that a successive sensory stimulus acts as an input signal for the dmPFC MP neurons to initiate a persistent movement. These results reveal a neural initiation mechanism on the persistent movement.
Inter-continental variability in the relationship of oxidative potential and cytotoxicity with PM2.5 mass
Authors: Salana Sudheer , Yu Haoran , Dai Zhuying , Subramanian P. S. Ganesh , Puthussery Joseph V. , Wang Yixiang , Singh Ajit , Pope Francis D. , Leiva G. Manuel A. , Rastogi Neeraj , Tripathi Sachchida Nand , Weber Rodney J. , Verma Vishal 
Published: June 2024

AbstractMost fine ambient particulate matter (PM2.5)-based epidemiological models use globalized concentration-response (CR) functions assuming that the toxicity of PM2.5 is solely mass-dependent without considering its chemical composition. Although oxidative potential (OP) has emerged as an alternate metric of PM2.5 toxicity, the association between PM2.5 mass and OP on a large spatial extent has not been investigated. In this study, we evaluate this relationship using 385 PM2.5 samples collected from 14 different sites across 4 different continents and using 5 different OP (and cytotoxicity) endpoints. Our results show that the relationship between PM2.5 mass vs. OP (and cytotoxicity) is largely non-linear due to significant differences in the intrinsic toxicity, resulting from a spatially heterogeneous chemical composition of PM2.5. These results emphasize the need to develop localized CR functions incorporating other measures of PM2.5 properties (e.g., OP) to better predict the PM2.5-attributed health burdens.
Biosynthesis of GMGT lipids by a radical SAM enzyme associated with anaerobic archaea and oxygen-deficient environments
Authors: Li Yanan , Yu Ting , Feng Xi , Zhao Bo , Chen Huahui , Yang Huan , Chen Xing , Zhang Xiao-Hua , Anderson Hayden R. , Burns Noah Z. , Zeng Fuxing , Tao Lizhi , Zeng Zhirui 
Published: June 2024

AbstractArchaea possess characteristic membrane-spanning lipids that are thought to contribute to the adaptation to extreme environments. However, the biosynthesis of these lipids is poorly understood. Here, we identify a radical S-adenosyl-L-methionine (SAM) enzyme that synthesizes glycerol monoalkyl glycerol tetraethers (GMGTs). The enzyme, which we name GMGT synthase (Gms), catalyzes the formation of a C(sp3)–C(sp3) linkage between the two isoprenoid chains of glycerol dialkyl glycerol tetraethers (GDGTs). This conclusion is supported by heterologous expression of gene gms from a GMGT-producing species in a methanogen, as well as demonstration of in vitro activity using purified Gms enzyme. Additionally, we show that genes encoding putative Gms homologs are present in obligate anaerobic archaea and in metagenomes obtained from oxygen-deficient environments, and appear to be absent in metagenomes from oxic settings.
Cross-feeding of bifidobacteria promotes intestinal homeostasis: a lifelong perspective on the host health
Authors: Xiao Meifang , Zhang Chuan , Duan Hui , Narbad Arjan , Zhao Jianxin , Chen Wei , Zhai Qixiao , Yu Leilei , Tian Fengwei 
Published: June 2024

AbstractThroughout the life span of a host, bifidobacteria have shown superior colonization and glycan abilities. Complex glycans, such as human milk oligosaccharides and plant glycans, that reach the colon are directly internalized by the transport system of bifidobacteria, cleaved into simple structures by extracellular glycosyl hydrolase, and transported to cells for fermentation. The glycan utilization of bifidobacteria introduces cross-feeding activities between bifidobacterial strains and other microbiota, which are influenced by host nutrition and regulate gut homeostasis. This review discusses bifidobacterial glycan utilization strategies, focusing on the cross-feeding involved in bifidobacteria and its potential health benefits. Furthermore, the impact of cross-feeding on the gut trophic niche of bifidobacteria and host health is also highlighted. This review provides novel insights into the interactions between microbe-microbe and host-microbe.
The survival benefit of adjuvant trastuzumab with or without chemotherapy in the management of small (T1mic, T1a, T1b, T1c), node negative HER2+ breast cancer
Authors: Johnson Kai C. C. , Ni Ai , Quiroga Dionisia , Pariser Ashley C. , Sudheendra Preeti K. , Williams Nicole O. , Sardesai Sagar D. , Cherian Mathew , Stover Daniel G. , Gatti-Mays Margaret , Ramaswamy Bhuvaneswari , Lustberg Maryam , Jhawar Sachin , Skoracki Roman , Wesolowski Robert 
Published: June 2024

AbstractThere is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/− chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS). Of the 1,184 patients, 436 received locoregional therapy alone. We found a statistically significant improvement in iDFS (HR 0.73, P = 0.003) and OS (HR 0.63, P = 0.023) on univariate analysis with adjuvant trastuzumab with or without chemotherapy which remained statistically significant on multivariate analysis. Three-arm univariate analysis found that iDFS was significantly improved with trastuzumab monotherapy (P = 0.003) and combination therapy (P = 0.027) compared to observation. Subgroup data suggests that T1b/c tumors derive the greatest benefit.
Structure and transcription of integrated HPV DNA in vulvar carcinomas
Authors: Van Arsdale Anne , Turker Lauren , Chang Yoke-Chen , Gould Joshua , Harmon Bryan , Maggi Elaine C. , Meshcheryakova Olga , Brown Maxwell P. , Luong Dana , Van Doorslaer Koenraad , Einstein Mark H. , Kuo Dennis Y. S. , Zheng Deyou , Haas Brian J. , Lenz Jack , Montagna Cristina 
Published: June 2024

AbstractHPV infections are associated with a fraction of vulvar cancers. Through hybridization capture and DNA sequencing, HPV DNA was detected in five of thirteen vulvar cancers. HPV16 DNA was integrated into human DNA in three of the five. The insertions were in introns of human NCKAP1, C5orf67, and LRP1B. Integrations in NCKAP1 and C5orf67 were flanked by short direct repeats in the human DNA, consistent with HPV DNA insertions at sites of abortive, staggered, endonucleolytic incisions. The insertion in C5orf67 was present as a 36 kbp, human-HPV-hetero-catemeric DNA as either an extrachromosomal circle or a tandem repeat within the human genome. The human circularization/repeat junction was defined at single nucleotide resolution. The integrated viral DNA segments all retained an intact upstream regulatory region and the adjacent viral E6 and E7 oncogenes. RNA sequencing revealed that the only HPV genes consistently transcribed from the integrated viral DNAs were E7 and E6*I. The other two HPV DNA+ tumors had coinfections, but no evidence for integration. HPV-positive and HPV-negative vulvar cancers exhibited contrasting human, global gene expression patterns partially overlapping with previously observed differences between HPV-positive and HPV-negative cervical and oropharyngeal cancers. A substantial fraction of the differentially expressed genes involved immune system function. Thus, transcription and HPV DNA integration in vulvar cancers resemble those in other HPV-positive cancers. This study emphasizes the power of hybridization capture coupled with DNA and RNA sequencing to identify a broad spectrum of HPV types, determine human genome integration status of viral DNAs, and elucidate their structures.
Mucosal bivalent live attenuated vaccine protects against human metapneumovirus and respiratory syncytial virus in mice
Authors: Ogonczyk-Makowska Daniela , Brun Pauline , Vacher Clémence , Chupin Caroline , Droillard Clément , Carbonneau Julie , Laurent Emilie , Dulière Victoria , Traversier Aurélien , Terrier Olivier , Julien Thomas , Galloux Marie , Paul Stéphane , Eléouët Jean-François , Fouret Julien , Hamelin Marie-Eve , Pizzorno Andrés , Boivin Guy , Rosa-Calatrava Manuel , Dubois Julia 
Published: June 2024

AbstractLive-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses. Altogether, our results showed the versatility of the Metavac® platform and suggested that Metavac®-RSV is a promising mucosal bivalent LAV candidate to prevent pneumovirus-induced diseases.
3D atlas of the human fetal chondrocranium in the middle trimester
Authors: Kaiser Markéta , Zikmund Tomáš , Vora Siddharth , Metscher Brian , Adameyko Igor , Richman Joy M. , Kaiser Jozef 
Published: June 2024

AbstractThe chondrocranium provides the key initial support for the fetal brain, jaws and cranial sensory organs in all vertebrates. The patterns of shaping and growth of the chondrocranium set up species-specific development of the entire craniofacial complex. The 3D development of chondrocranium have been studied primarily in animal model organisms, such as mice or zebrafish. In comparison, very little is known about the full 3D human chondrocranium, except from drawings made by anatomists many decades ago. The knowledge of human-specific aspects of chondrocranial development are essential for understanding congenital craniofacial defects and human evolution. Here advanced microCT scanning was used that includes contrast enhancement to generate the first 3D atlas of the human fetal chondrocranium during the middle trimester (13 to 19 weeks). In addition, since cartilage and bone are both visible with the techniques used, the endochondral ossification of cranial base was mapped since this region is so critical for brain and jaw growth. The human 3D models are published as a scientific resource for human development.
Identification of potential modulators for human GPD1 by docking-based virtual screening, molecular dynamics simulations, binding free energy calculations, and DeLA-drug analysis
Authors: Hu Anzheng , Chen Hongwei , Pang Wenwei , Pu Xiaojie , Qi Zhongquan , Chen Haiyan 
Published: June 2024

AbstractCytosolic Glycerol-3-phosphate dehydrogenase 1 (GPD1, EC 1.1.1.8) plays a pivotal role in regulating the Embden-Meyerhof glucose glycolysis pathway (E-M pathway), as well as in conditions such as Huntington’s disease, cancer, and its potential role as a specific marker for Dormant Glioma Stem Cells. In this study, we conducted virtual screening using the ZINC database (http://zinc.docking.org/) and the GPD1 structure to identify potential GPD1 modulators. The investigation involved screening active candidate ligands using ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters, combined with molecular docking, pose analysis, and interaction analysis based on Lipinski and Veber criteria. Subsequently, the top 10 ligands were subjected to 200 ns all-atom molecular dynamics (M.D.) simulations, and binding free energies were calculated. The findings revealed that specific residues, namely TRP14, PRO94, LYS120, ASN151, THR264, ASP260, and GLN298, played a crucial role in ensuring system stability. Furthermore, through a comprehensive analysis involving molecular docking, molecular M.D., and DeLA-Drug, we identified 10 promising small molecules. These molecules represent potential lead compounds for developing effective therapeutics targeting GPD1-associated diseases, thereby contributing to a deeper understanding of GPD1-associated mechanisms. This study's significance lies in identifying key residues associated with GPD1 and discovering valuable small molecules, providing a foundation for further research and development.
Assessing spatiotemporal population density dynamics from 2000 to 2020 in megacities using urban and rural morphologies
Authors: Xie Jing , Wei Nan , Gao Quan 
Published: June 2024

AbstractRapid urbanization has resulted in the substantial population growth in metropolitan areas. However, existing research on population change of the cities predominantly draws on grid statistical data at the administrative level, overlooking the intra-urban variegation of population change. Particularly, there is a lack of attention given to the spatio-temporal change of population across different urban forms and functions. This paper therefore fills in the lacuna by clarifying the spatio-temporal characteristics of population growth in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 2000 to 2020 through the methods of local climate zone (LCZ) scheme and urban–rural gradients. The results showed that: (1) High population density was observed in the compact high-rise (LCZ 1) areas, with a noticeable decline along urban–rural gradients. (2) The city centers of GBA experienced the most significant population growth, while certain urban fringes and rural areas witnessed significant population shrinkage. (3) The rate of growth tended to slow down after 2010, but the uneven development of population-based urbanization was also noticeable, as urbanization and industrialization varied across different LCZ types and cities in GBA. This paper therefore contributes to a deeper understanding of population change and urbanization by clarifying their spatio-temporal contingences at landscape level.