bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Delineation of Urban Hydrological Processes in Coupled Regional Climate Models
Authors: Yu Miao , Wu Huan , Yin Jinfang , Liang Xudong , Miao Shiguang 
Published: November 2022

AbstractAs the resolution of global and regional numerical weather prediction (NWP) models increases, urban parameterizations are increasingly important because urbanization has significant impacts on the surface energy and water balance. However, NWP models tend to fail to accurately simulate the surface latent heat flux, with most urban canopy models lacking or oversimplifying urban hydrological and vegetation processes. In this study, we develop an urban hydrology scheme and couple it with WRF/BEP + BEM, which improves the regional model performance in urban areas at high resolution. The evaluation results show improved model accuracy not only for the surface latent heat flux but also for the air temperature and humidity. The vertical section analysis suggests that the urban hydrology scheme can have impacts on the boundary layer to a height of 1,000 m. Consequently, improved precipitation simulation causes reasonable prediction of urban surface water depth, which is valuable for early warning of waterlogging.
Observation of mechanical bound states in the continuum in an optomechanical microresonator
Authors: Yu Yue , Xi Xiang , Sun Xiankai 
Published: November 2022

AbstractBound states in the continuum (BICs) are a type of waves that are perfectly confined in the continuous spectrum of radiating waves without interaction with them. Here, we fabricated, with CMOS-compatible processes on a silicon chip, a wheel-shaped optomechanical microresonator, in which we experimentally observed the BIC in the micromechanical domain. The BIC results from destructive interference between two dissipative mechanical modes of the microresonator under broken azimuthal symmetry. Such BICs can be obtained from devices with large and robust supporting structures with variable sizes, which substantially reduces fabrication difficulty and allows for versatile application environments. Our results open a new way of phonon trapping in micromechanical structures with dissipation channels, and produce long phonon lifetimes that are desired in many mechanical applications such as mechanical oscillators, sensors, and quantum information processors.
Single-cell analyses reveal novel molecular signatures and pathogenesis in cutaneous T cell lymphoma
Authors: Xue Xiaotong , Wang Zhenzhen , Mi Zihao , Liu Tingting , Wang Chuan , Shi Peidian , Sun Lele , Yang Yongliang , Li Wenchao , Wang Zhe , Liu Hong , Zhang Furen 
Published: November 2022

AbstractSézary syndrome (SS) is a rare and aggressive type of cutaneous T cell lymphoma (CTCL) with a poor prognosis. Intra-tumoral heterogeneity caused by different disease compartments (e.g., skin, blood) and poor understanding of the pathogenesis has created obstacles to the precise diagnosis and targeted treatment of the disease. Here we performed a comprehensive analysis by integrating single-cell transcriptomic data of 40,333 peripheral blood mononuclear cells (PBMCs) and 41,580 skin cells, as well as single-cell chromatin accessibility data of 11,058 PBMCs from an SS patient and matched healthy controls (HCs). Validation and functional investigation were carried out in an independent cohort consisting of SS patients, mycosis fungoides (MF) patients, psoriatic erythroderma patients, and HCs, as well as multiple cell lines. The analysis revealed that skin-derived Sézary cells (SCs) had a shifting trend to more advanced mature phenotypes compared to blood-derived SCs. A series of specific marker genes (TOX, DNM3, KLHL42, PGM2L1, and SESN3) shared in blood- and skin-derived SCs were identified, facilitating the diagnosis and prognosis of MF/SS. Moreover, luciferase reporter assays and gene knockdown assays were used to verify that KLHL42 was transcriptionally activated by GATA3 in SS. Functional assays indicated that KLHL42 silencing significantly inhibited aggressive CTCL cell proliferation and promoted its apoptosis. Therefore, targeting inhibition KLHL42 might serve as a promising therapeutic approach in CTCL.
JUND/linc00976 promotes cholangiocarcinoma progression and metastasis, inhibits ferroptosis by regulating the miR-3202/GPX4 axis
Authors: Lei Shan , Cao Wenpeng , Zeng Zhirui , Zhang Zhixue , Jin Bangming , Tian Qianting , Wu Yingming , Zhang Tuo , Li Dahuan , Hu Chujiao , Lan Jinzhi , Zhang Jinjuan , Chen Tengxiang 
Published: November 2022

AbstractLong noncoding RNAs (lncRNAs) are a novel class of noncoding RNAs that have emerged as critical regulators and biomarkers in various cancers. Nevertheless, the expression profile and mechanistic function of lncRNAs in cholangiocarcinoma (CCA) remain unclear. Herein, we examined the expression levels of linc00976 in clinical specimens and cell lines using reverse transcription-quantitative PCR. In total, 50 patients with CCA were enrolled to analyze the correlation between linc00976 expression and clinical characteristics of CCA. Loss- and gain-of-function experiments were performed to investigate the biological effects of linc00976 on proliferation, ferroptosis, migration, and invasion of CCA cells in vitro and in vivo. In situ hybridization, RNA immunoprecipitation, bioinformatic databases, RNA pull-down assay, a dual-luciferase reporter assay, mRNA sequencing, chromatin immunoprecipitation–PCR, and rescue experiments were performed to elucidate the underlying mechanisms of linc00976-induced competitive endogenous RNA regulatory networks. We characterized a novel and abundant lncRNA, linc00976, that functions as a pro-oncogenic regulator of CCA progression. Compared with normal controls, linc00976 was dramatically upregulated in CCA tissue samples and cell lines. Patients with CCA exhibiting high linc00976 expression had a highly advanced clinical stage, substantial lymph node metastasis, and poor overall survival. Knockdown of linc00976 significantly repressed proliferation and metastasis and promoted ferroptosis of CCA cells both in vitro and in vivo, whereas linc00976 overexpression exerted the opposite effect. Mechanistically, linc00976 competitively interacted with miR-3202 to upregulate GPX4 expression, thus contributing to the malignant biological behavior of CCA cells. Moreover, we demonstrated that JUND specifically interacts with the linc00976 promoter and activates linc00976 transcription. Accordingly, JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating CCA tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. These findings suggest that targeting linc00976 may afford a promising therapeutic strategy for patients with CCA.
An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma
Authors: Darawshi Odai , Muz Barbara , Naamat Shiri Gershon , Praveen Bellam , Mahameed Mohamed , Goldberg Karin , Dipta Priya , Shmuel Miriam , Forno Francesca , Boukeileh Shatha , Pahima Hadas , Hermann Julia , Raab Marc S. , Poos Alexandra M. , Weinhold Niels , Rosenbluh Chaggai , Gatt Moshe E. , Palm Wilhelm , Azab Abdel Kareem , Tirosh Boaz 
Published: November 2022

AbstractMultiple myeloma (MM) causes approximately 20% of deaths from blood cancers. Notwithstanding significant therapeutic progress, such as with proteasome inhibitors (PIs), MM remains incurable due to the development of resistance. mTORC1 is a key metabolic regulator, which frequently becomes dysregulated in cancer. While mTORC1 inhibitors reduce MM viability and synergize with other therapies in vitro, clinically, mTORC1 inhibitors are not effective for MM. Here we show that the inactivation of mTORC1 is an intrinsic response of MM to PI treatment. Genetically enforced hyperactivation of mTORC1 in MM was sufficient to compromise tumorigenicity in mice. In vitro, mTORC1-hyperactivated MM cells gained sensitivity to PIs and hypoxia. This was accompanied by increased mitochondrial stress and activation of the eIF2α kinase HRI, which initiates the integrated stress response. Deletion of HRI elevated the toxicity of PIs in wt and mTORC1-activated MM. Finally, we identified the drug PMA as a robust inducer of mTORC1 activity, which synergized with PIs in inducing MM cell death. These results help explain the clinical inefficacy of mTORC1 inhibitors in MM. Our data implicate mTORC1 induction and/or HRI inhibition as pharmacological strategies to enhance MM therapy by PIs.
Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense
Authors: Horáková Eva , Lecordier Laurence , Cunha Paula , Sobotka Roman , Changmai Piya , Langedijk Catharina J. M. , Abbeele Jan Van Den , Vanhollebeke Benoit , Lukeš Julius 
Published: November 2022

AbstractResistance to African trypanosomes in humans relies in part on the high affinity targeting of a trypanosome lytic factor 1 (TLF1) to a trypanosome haptoglobin-hemoglobin receptor (HpHbR). While TLF1 avoidance by the inactivation of HpHbR contributes to Trypanosoma brucei gambiense human infectivity, the evolutionary trade-off of this adaptation is unknown, as the physiological function of the receptor remains to be elucidated. Here we show that uptake of hemoglobin via HpHbR constitutes the sole heme import pathway in the trypanosome bloodstream stage. T. b. gambiense strains carrying the inactivating mutation in HpHbR, as well as genetically engineered T. b. brucei HpHbR knock-out lines show only trace levels of intracellular heme and lack hemoprotein-based enzymatic activities, thereby providing an uncommon example of aerobic parasitic proliferation in the absence of heme. We further show that HpHbR facilitates the developmental progression from proliferating long slender forms to cell cycle-arrested stumpy forms in T. b. brucei. Accordingly, T. b. gambiense was found to be poorly competent for slender-to-stumpy differentiation unless a functional HpHbR receptor derived from T. b. brucei was genetically restored. Altogether, we identify heme-deficient metabolism and disrupted cellular differentiation as two distinct HpHbR-dependent evolutionary trade-offs for T. b. gambiense human infectivity.
Donor-strand exchange drives assembly of the TasA scaffold in Bacillus subtilis biofilms
Authors: Böhning Jan , Ghrayeb Mnar , Pedebos Conrado , Abbas Daniel K. , Khalid Syma , Chai Liraz , Bharat Tanmay A. M. 
Published: November 2022

AbstractMany bacteria in nature exist in multicellular communities termed biofilms, where cells are embedded in an extracellular matrix that provides rigidity to the biofilm and protects cells from chemical and mechanical stresses. In the Gram-positive model bacteriumBacillus subtilis, TasA is the major protein component of the biofilm matrix, where it has been reported to form functional amyloid fibres contributing to biofilm structure and stability. Here, we present electron cryomicroscopy structures of TasA fibres, which show that, rather than forming amyloid fibrils, TasA monomers assemble into fibres through donor-strand exchange, with each subunit donating a β-strand to complete the fold of the next subunit along the fibre. Combining electron cryotomography, atomic force microscopy, and mutational studies, we show how TasA fibres congregate in three dimensions to form abundant fibre bundles that are essential forB. subtilisbiofilm formation. Our study explains the previously observed biochemical properties of TasA and shows how a bacterial extracellular globular protein can assemble from monomers into β-sheet-rich fibres, and how such fibres assemble into bundles in biofilms.
Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis
Authors: Paul Souren , Kaplan Mark H. , Khanna Dinesh , McCourt Preston M. , Saha Anjan K. , Tsou Pei-Suen , Anand Mahek , Radecki Alexander , Mourad Mohamad , Sawalha Amr H. , Markovitz David M. , Contreras-Galindo Rafael 
Published: November 2022

AbstractCentromere defects in Systemic Sclerosis (SSc) have remained unexplored despite the fact that many centromere proteins were discovered in patients with SSc. Here we report that lesion skin fibroblasts from SSc patients show marked alterations in centromeric DNA. SSc fibroblasts also show DNA damage, abnormal chromosome segregation, aneuploidy (only in diffuse cutaneous (dcSSc)) and micronuclei (in all types of SSc), some of which lose centromere identity while retaining centromere DNA sequences. Strikingly, we find cytoplasmic “leaking” of centromere proteins in limited cutaneous SSc (lcSSc) fibroblasts. Cytoplasmic centromere proteins co-localize with antigen presenting MHC Class II molecules, which correlate precisely with the presence of anti-centromere antibodies. CENPA expression and micronuclei formation correlate highly with activation of the cGAS-STING/IFN-β pathway as well as markers of reactive oxygen species (ROS) and fibrosis, ultimately suggesting a link between centromere alterations, chromosome instability, SSc autoimmunity, and fibrosis.
Pre-equilibrium biosensors as an approach towards rapid and continuous molecular measurements
Authors: Maganzini Nicolò , Thompson Ian , Wilson Brandon , Soh Hyongsok Tom 
Published: November 2022

AbstractAlmost all biosensors that use ligand-receptor binding operate under equilibrium conditions. However, at low ligand concentrations, the equilibration with the receptor (e.g., antibodies and aptamers) becomes slow and thus equilibrium-based biosensors are inherently limited in making measurements that are both rapid and sensitive. In this work, we provide a theoretical foundation for a method through which biosensors can quantitatively measure ligand concentration before reaching equilibrium. Rather than only measuring receptor binding at a single time-point, the pre-equilibrium approach leverages the receptor’s kinetic response to instantaneously quantify the changing ligand concentration. Importantly, by analyzing the biosensor output in frequency domain, rather than in the time domain, we show the degree to which noise in the biosensor affects the accuracy of the pre-equilibrium approach. Through this analysis, we provide the conditions under which the signal-to-noise ratio of the biosensor can be maximized for a given target concentration range and rate of change. As a model, we apply our theoretical analysis to continuous insulin measurement and show that with a properly selected antibody, the pre-equilibrium approach could make the continuous tracking of physiological insulin fluctuations possible.
Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration
Authors: Tran Viviane , Nahlé Sarah , Robert Amélie , Desanlis Inès , Killoran Ryan , Ehresmann Sophie , Thibault Marie-Pier , Barford David , Ravichandran Kodi S. , Sauvageau Martin , Smith Matthew J. , Kmita Marie , Côté Jean-François 
Published: November 2022

AbstractMyoblast fusion is fundamental for the development of multinucleated myofibers. Evolutionarily conserved proteins required for myoblast fusion include RAC1 and its activator DOCK1. In the current study we analyzed the contribution of the DOCK1-interacting ELMO scaffold proteins to myoblast fusion. When Elmo1−/− mice underwent muscle-specific Elmo2 genetic ablation, they exhibited severe myoblast fusion defects. A mutation in the Elmo2 gene that reduced signaling resulted in a decrease in myoblast fusion. Conversely, a mutation in Elmo2 coding for a protein with an open conformation increased myoblast fusion during development and in muscle regeneration. Finally, we showed that the dystrophic features of the Dysferlin-null mice, a model of limb-girdle muscular dystrophy type 2B, were reversed when expressing ELMO2 in an open conformation. These data provide direct evidence that the myoblast fusion process could be exploited for regenerative purposes and improve the outcome of muscle diseases.
Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus
Authors: Rivera-Calzada Angel , Arribas-Bosacoma Raquel , Ruiz-Ramos Alba , Escudero-Bravo Paloma , Boskovic Jasminka , Fernandez-Leiro Rafael , Oliver Antony W. , Pearl Laurence H. , Llorca Oscar 
Published: November 2022

AbstractDetection of cytosolic DNA is a central element of the innate immunity system against viral infection. The Ku heterodimer, a component of the NHEJ pathway of DNA repair in the nucleus, functions as DNA sensor that detects dsDNA of viruses that replicate in the cytoplasm. Vaccinia virus expresses two proteins, C4 and C16, that inactivate DNA sensing and enhance virulence. The structural basis for this is unknown. Here we determine the structure of the C16 – Ku complex using cryoEM. Ku binds dsDNA by a preformed ring but C16 sterically blocks this access route, abrogating binding to a dsDNA end and its insertion into DNA-PK, thereby averting signalling into the downstream innate immunity system. C4 replicates these activities using a domain with 54% identity to C16. Our results reveal how vaccinia virus subverts the capacity of Ku to recognize viral DNA.
Enantioselective Ugi and Ugi-azide reactions catalyzed by anionic stereogenic-at-cobalt(III) complexes
Authors: Sun Bing-Bing , Liu Kun , Gao Quan , Fang Wei , Lu Shuang , Wang Chun-Ru , Yao Chuan-Zhi , Cao Hai-Qun , Yu Jie 
Published: November 2022

AbstractUgi reactions and related variations are proven to be atom and step-economic strategies for construction of highly valuable peptide-like skeletons and nitrogenous heterocycles. The development of structurally diverse range of novel catalytic systems and the discovery of new approaches to accommodate a broader scope of terminating reagents for asymmetric Ugi four-component reaction is still in high demand. Here, we report a strategy that enables enantioselective Ugi four-component and Ugi-azide reactions employing anionic stereogenic-at-cobalt(III) complexes as catalysts. The key nitrilium intermediates, generated through the nucleophilic addition of isocyanides to the chiral ion-pair which consists of stereogenic-at-cobalt(III) complexes counteranion and a protonated iminium, are trapped by either carboxylic acids or in situ-generated hydrazoic acid, delivering α-acylamino amides and α-aminotetrazoles in good to excellent enantioselectivities (up to 99:1 e.r.).
Implications of oral streptococcal bacteriophages in autism spectrum disorder
Authors: Tong Zhan , Zhou Xin , Chu Yanan , Zhang Tianxu , Zhang Jie , Zhao Xiaoyan , Wang Zuqun , Ding Rui , Meng Qingren , Yu Jun , Wang Juan , Kang Yu 
Published: November 2022

AbstractGrowing evidence suggests altered oral and gut microbiota in autism spectrum disorder (ASD), but little is known about the alterations and roles of phages, especially within the oral microbiota in ASD subjects. We enrolled ASD (n = 26) and neurotypical subjects (n = 26) with their oral hygiene controlled, and the metagenomes of both oral and fecal samples (n = 104) are shotgun-sequenced and compared. We observe extensive and diverse oral phageome comparable to that of the gut, and clear signals of mouth-to-gut phage strain transfer within individuals. However, the overall phageomes of the two sites are widely different and show even less similarity in the oral communities between ASD and control subjects. The ASD oral phageome exhibits significantly reduced abundance and alpha diversity, but the Streptococcal phages there are atypically enriched, often dominating the community. The over-representation of Streptococcal phages is accompanied by enriched oral Streptococcal virulence factors and Streptococcus bacteria, all exhibiting a positive correlation with the severity of ASD clinical manifestations. These changes are not observed in the parallel sampling of the gut flora, suggesting a previously unknown oral-specific association between the excessive Streptococcal phage enrichment and ASD pathogenesis. The findings provide new evidence for the independent microbiome-mouth-brain connection, deepen our understanding of how the growth dynamics of bacteriophages and oral microbiota contribute to ASD, and point to novel effective therapeutics.
Oxygen-sensitive nanoparticles reveal the spatiotemporal dynamics of oxygen reduction during magnesium implant biodegradation
Authors: Zeller-Plumhoff Berit , Akkineni Ashwini Rahul , Helmholz Heike , Orlov Dmytro , Mosshammer Maria , Kühl Michael , Willumeit-Römer Regine , Gelinsky Michael 
Published: November 2022

AbstractMagnesium (Mg) alloys are becoming increasingly important in the biomedical field as temporary bone implants. However, the biodegradation process of Mg alloys is highly complex and recent findings suggest that oxygen (O2) consumption is non-negligible. In this study, we give experimental proof of O2 consumption during Mg degradation under physiological conditions. Specifically, we study pure Mg, Mg–6 wt%Ag and Mg–5 wt%Gd in Hanks’ balanced salt solution and Dulbecco’s modified Eagle’s medium. We show that O2 consumption and hydrogen evolution are inversely correlated and that O2 concentrations remain below 7.5% in certain cases, which could have significant implications for bone healing.
Evaluation of pectin extractions and their application in the alkaline Maillard reaction
Authors: Guízar-Amezcua María-Guadalupe , Pineda-Santana Alvaro , González-Domínguez Martha-Isabel , Cajero-Zul Leonardo-Ramses , Guerrero-Ramírez Luis-Guillermo , López-Miranda Armando , Nambo Apolo , López-Mercado Janneth 
Published: November 2022

AbstractA 23 factorial design was used to evaluate the influence of temperature, catalyst and time and esterification degree (DE) of pectin obtained from mango, orange and tangerine peels as well as tamarind seeds by using the acid hydrolysis method. The study showed that a high temperature positively influenced the percentage of pectin yield for the four second generation biomasses. Nevertheless, the temperature showed a greater influence in the solubility and diffusion of the acid solvent in the tamarind seed matrix, resulting a pectin recovery 32.9%. Concerning the %DE, the most statistically significant value observed was dependent on the type of biomass studied. The %DE and the nature of the pectin are determining factors in the pectin’s final use, in the present work the pectin extracted was used to produce furfural, a precursor of high value chemicals. The furfural production was achieved through alkaline hydrolysis and enhanced using the Maillard reaction, reaching a maximum concentration of 71.8 g/L which represents a 42.1% increase from the alkaline hydrolysis.
Associations of rheumatoid arthritis and rheumatoid factor with mental health, sleep and cognition characteristics in the UK Biobank
Authors: Stanciu Ioana , Anderson Jana , Siebert Stefan , Mackay Daniel , Lyall Donald M. 
Published: November 2022

AbstractWhile previous rheumatoid arthritis (RA) studies have focussed on cardiometabolic and lifestyle factors, less research has focussed on psychological variables including mood and cognitive health, and sleep. Cross-sectional analyses tested for associations between RA and RF+ (positive rheumatoid factor) vs. mental health (depression, anxiety, neuroticism), sleep variables and cognition scores in UK Biobank (total n = 484,064). Those RF+ were more likely to report longer sleep duration (β = 0.01, SE = 0.004, p < 0.01) and less likely to get up in the morning easily (OR 0.95, 95% CI 0.92–0.99, p = 0.01). Those reporting RA were more likely to score higher for neuroticism (β = 0.05, SE = 0.01, p < 0.001), to nap during the day (OR 1.10, 95% CI 1.06–1.14, p < 0.001), have insomnia (OR 1.28, 95% CI 1.22–1.35, p < 0.001), have slower reaction times (β = 0.02, SE = 0.008, p < 0.005) and score less for fluid intelligence (β = − 0.03, SE = 0.01, p < 0.05) and less likely to get up easily (OR 0.61, 95% CI 0.58–0.64, p < 0.001). The current study suggests that prevalent RA, and RF+ status are associated with differences in mental health, sleep, and cognition, highlighting the importance of addressing these aspects in clinical settings and future research.