bluuebunny/crossref_metadata_2025_split huggingface dataset:
A MYC-rearrangement is a negative prognostic factor in stage II, but not in stage I diffuse large B-cell lymphoma
Authors: de Jonge A. V. , Bult J. A. A. , Karssing D. F. E. , Nijland M. , Chamuleau M. E. D. , Brink M. 
Published: January 2024

AbstractMYC oncogene rearrangements (MYC-R) negatively affect survival in patients with Ann Arbor stage III–IV diffuse large B-cell lymphoma (DLBCL), but their impact in limited stage (LS) I–II is unclear. Therefore, we assessed the impact of MYC-R on progression-free survival (PFS) and overall survival (OS) in LS DLBCL patients at the population level. We identified 1,434 LS DLBCL patients with known MYC-R status diagnosed between 2014 and 2020, who received R-CHOP(-like) regimens using the Netherlands Cancer Registry, with survival follow-up until February 2022. Stage I patients with (n = 83, 11%) and without (n = 650, 89%) a MYC-R had similar 2-years PFS (89% and 93%, p = 0.63) and OS (both 95%, p = 0.22). Conversely, stage II DLBCL patients with a MYC-R (n = 90, 13%) had inferior survival outcomes compared to stage II patients without a MYC-R (n = 611, 87%) (PFS 70% vs. 89%, p = 0.001; OS 79% vs. 94%, p < 0.0001). Both single MYC-R (single hit, n = 36) and concurrent BCL2 and/or BCL6 rearrangements (double/triple hit, n = 39) were associated with increased mortality and relapse risk. In conclusion, in stage II DLBCL a MYC-R is negatively associated with survival. In stage I DLBCL, however, survival outcomes are excellent irrespective of MYC-R status. This challenges the diagnostic assessment of MYC-R in stage I DLBCL patients.
Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease
Authors: Liu Meng-Lu , Ma Shuaipeng , Tai Wenjiao , Zhong Xiaoling , Ni Haoqi , Zou Yuhua , Wang Jingcheng , Zhang Chun-Li 
Published: January 2024

AbstractEffective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients. Mechanistically, it works as an inhibitor of MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, and normalizes subcellular distribution of RANGAP1 and TDP-43. Finally, in an ALS mouse model we show that inhibiting MAP4Ks preserves motor neurons and significantly extends animal lifespan.
Cullin5 drives experimental asthma exacerbations by modulating alveolar macrophage antiviral immunity
Authors: Zhang Haibo , Xue Keke , Li Wen , Yang Xinyi , Gou Yusen , Su Xiao , Qian Feng , Sun Lei 
Published: January 2024

AbstractAsthma exacerbations caused by respiratory viral infections are a serious global health problem. Impaired antiviral immunity is thought to contribute to the pathogenesis, but the underlying mechanisms remain understudied. Here using mouse models we find that Cullin5 (CUL5), a key component of Cullin-RING E3 ubiquitin ligase 5, is upregulated and associated with increased neutrophil count and influenza-induced exacerbations of house dust mite-induced asthma. By contrast, CUL5 deficiency mitigates neutrophilic lung inflammation and asthma exacerbations by augmenting IFN-β production. Mechanistically, following thymic stromal lymphopoietin stimulation, CUL5 interacts with O-GlcNAc transferase (OGT) and induces Lys48-linked polyubiquitination of OGT, blocking the effect of OGT on mitochondrial antiviral-signaling protein O-GlcNAcylation and RIG-I signaling activation. Our results thus suggest that, in mouse models, pre-existing allergic injury induces CUL5 expression, impairing antiviral immunity and promoting neutrophilic inflammation for asthma exacerbations. Targeting of the CUL5/IFN-β signaling axis may thereby serve as a possible therapy for treating asthma exacerbations.
The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation
Authors: Li Mingsen , Guo Huizhen , Wang Bofeng , Han Zhuo , Wu Siqi , Liu Jiafeng , Huang Huaxing , Zhu Jin , An Fengjiao , Lin Zesong , Mo Kunlun , Tan Jieying , Liu Chunqiao , Wang Li , Deng Xin , Li Guigang , Ji Jianping , Ouyang Hong 
Published: January 2024

AbstractProper differentiation of corneal epithelial cells (CECs) from limbal stem/progenitor cells (LSCs) is required for maintenance of ocular homeostasis and clear vision. Here, using a single-cell transcriptomic atlas, we delineate the comprehensive and refined molecular regulatory dynamics during human CEC development and differentiation. We find that RORA is a CEC-specific molecular switch that initiates and drives LSCs to differentiate into mature CECs by activating PITX1. RORA dictates CEC differentiation by establishing CEC-specific enhancers and chromatin interactions between CEC gene promoters and distal regulatory elements. Conversely, RORA silences LSC-specific promoters and disrupts promoter-anchored chromatin loops to turn off LSC genes. Collectively, our work provides detailed and comprehensive insights into the transcriptional dynamics and RORA-mediated epigenetic remodeling underlying human corneal epithelial differentiation.
Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability
Authors: Gorman Jason , Cheung Crystal Sao-Fong , Duan Zhijian , Ou Li , Wang Maple , Chen Xuejun , Cheng Cheng , Biju Andrea , Sun Yaping , Wang Pengfei , Yang Yongping , Zhang Baoshan , Boyington Jeffrey C. , Bylund Tatsiana , Charaf Sam , Chen Steven J. , Du Haijuan , Henry Amy R. , Liu Tracy , Sarfo Edward K. , Schramm Chaim A. , Shen Chen-Hsiang , Stephens Tyler , Teng I-Ting , Todd John-Paul , Tsybovsky Yaroslav , Verardi Raffaello , Wang Danyi , Wang Shuishu , Wang Zhantong , Zheng Cheng-Yan , Zhou Tongqing , Douek Daniel C. , Mascola John R. , Ho David D. , Ho Mitchell , Kwong Peter D. 
Published: January 2024

AbstractLassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV. Cryo-EM analyses reveal D5 to recognize a cleavage-dependent site-of-vulnerability at the trimer apex. The recognized site appears specific to GPC intermediates, with protomers lacking full cleavage between GP1 and GP2 subunits. Guinea pig immunizations with the prefusion-stabilized cleavage-intermediate LASV GPC, first as trimer and then as a nanoparticle, induce neutralizing responses, targeting multiple epitopes including that of D5; we identify a neutralizing antibody (GP23) from the immunized guinea pigs. Collectively, our findings define a prefusion-stabilized GPC trimer, reveal an apex-situated site-of-vulnerability, and demonstrate elicitation of LASV-neutralizing responses by a cleavage-intermediate LASV trimer.
Helical reconstruction of VP39 reveals principles for baculovirus nucleocapsid assembly
Authors: Benning Friederike M. C. , Jenni Simon , Garcia Coby Y. , Nguyen Tran H. , Zhang Xuewu , Chao Luke H. 
Published: January 2024

AbstractBaculoviruses are insect-infecting pathogens with wide applications as biological pesticides, in vitro protein production vehicles and gene therapy tools. Its cylindrical nucleocapsid, which encapsulates and protects the circular double-stranded viral DNA encoding proteins for viral replication and entry, is formed by the highly conserved major capsid protein VP39. The mechanism for VP39 assembly remains unknown. We use electron cryomicroscopy to determine a 3.2 Å helical reconstruction of an infectious nucleocapsid of Autographa californica multiple nucleopolyhedrovirus, revealing how dimers of VP39 assemble into a 14-stranded helical tube. We show that VP39 comprises a distinct protein fold conserved across baculoviruses, which includes a Zinc finger domain and a stabilizing intra-dimer sling. Analysis of sample polymorphism shows that VP39 assembles in several closely-related helical geometries. This VP39 reconstruction reveals general principles for baculoviral nucleocapsid assembly.
Galvanic corrosion behavior of welded joint in marine atmosphere environment based on capillary microcell
Authors: Wang Xinyu , Huang Feng , Hu Qian , Zhang Jiawei , Liu Jing 
Published: January 2024

AbstractThe kinetical behavior and mechanism of micro-galvanic corrosion of Q690 bainitic weathering steel welded joint in marine atmosphere were investigated. The results showed that a micro-galvanic corrosion cell formed among different regions of the Q690 welded joint. The kinetical behavior of micro-galvanic corrosion could be divided into four stages: the initiation and development of micro-galvanic corrosion, the decreasing of galvanic corrosion rate, the polarity reversal of galvanic couple, and the disappearance of galvanic effect. The difference of corrosion rate between Q690 steel and its welded joint is closely related to the micro-galvanic corrosion kinetic behavior.
Antigen self-anchoring onto bacteriophage T5 capsid-like particles for vaccine design
Authors: Vernhes Emeline , Larbi Chérif Linda , Ducrot Nicolas , Vanbergue Clément , Ouldali Malika , Zig Lena , Sidibe N’diaye , Hoos Sylviane , Ramirez-Chamorro Luis , Renouard Madalena , Rossier Ombeline , England Patrick , Schoehn Guy , Boulanger Pascale , Benihoud Karim 
Published: January 2024

AbstractThe promises of vaccines based on virus-like particles stimulate demand for universal non-infectious virus-like platforms that can be efficiently grafted with large antigens. Here, we harnessed the modularity and extreme affinity of the decoration protein pb10 for the capsid of bacteriophage T5. SPR experiments demonstrated that pb10 fused to mCherry or to the model antigen ovalbumin (Ova) retained picomolar affinity for DNA-free T5 capsid-like particles (T5-CLPs), while cryo-EM studies attested to the full occupancy of the 120 capsid binding sites. Mice immunization with CLP-bound pb10-Ova chimeras elicited strong long-lasting anti-Ova humoral responses involving a large panel of isotypes, as well as CD8+ T cell responses, without any extrinsic adjuvant. Therefore, T5-CLP constitutes a unique DNA-free bacteriophage capsid able to display a regular array of large antigens through highly efficient chemical-free anchoring. Its ability to elicit robust immune responses paves the way for further development of this novel vaccination platform.
FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy
Authors: van der Weijden Vera A. , Stötzel Maximilian , Iyer Dhanur P. , Fauler Beatrix , Gralinska Elzbieta , Shahraz Mohammed , Meierhofer David , Vingron Martin , Rulands Steffen , Alexandrov Theodore , Mielke Thorsten , Bulut-Karslioglu Aydan 
Published: January 2024

AbstractMammalian developmental timing is adjustable in vivo by preserving pre-implantation embryos in a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development in vitro, yet how embryonic dormancy is maintained is not known. Here we show that mouse embryos in diapause are sustained by using lipids as primary energy source. In vitro, supplementation of embryos with the metabolite l-carnitine balances lipid consumption, puts the embryos in deeper dormancy and boosts embryo longevity. We identify FOXO1 as an essential regulator of the energy balance in dormant embryos and propose, through meta-analyses of dormant cell signatures, that it may be a common regulator of dormancy across adult tissues. Our results lift a constraint on in vitro embryo survival and suggest that lipid metabolism may be a critical metabolic transition relevant for longevity and stem cell function across tissues.
Multifunctional sulfonium-based treatment for perovskite solar cells with less than 1% efficiency loss over 4,500-h operational stability tests
Authors: Suo Jiajia , Yang Bowen , Mosconi Edoardo , Bogachuk Dmitry , Doherty Tiarnan A. S. , Frohna Kyle , Kubicki Dominik J. , Fu Fan , Kim YeonJu , Er-Raji Oussama , Zhang Tiankai , Baldinelli Lorenzo , Wagner Lukas , Tiwari Ayodhya N. , Gao Feng , Hinsch Andreas , Stranks Samuel D. , De Angelis Filippo , Hagfeldt Anders 
Published: January 2024

AbstractThe stabilization of grain boundaries and surfaces of the perovskite layer is critical to extend the durability of perovskite solar cells. Here we introduced a sulfonium-based molecule, dimethylphenethylsulfonium iodide (DMPESI), for the post-deposition treatment of formamidinium lead iodide perovskite films. The treated films show improved stability upon light soaking and remains in the black α phase after two years ageing under ambient condition without encapsulation. The DMPESI-treated perovskite solar cells show less than 1% performance loss after more than 4,500 h at maximum power point tracking, yielding a theoretical T80 of over nine years under continuous 1-sun illumination. The solar cells also display less than 5% power conversion efficiency drops under various ageing conditions, including 100 thermal cycles between 25 °C and 85 °C and an 1,050-h damp heat test.
Bdellovibrio bacteriovorus uses chimeric fibre proteins to recognize and invade a broad range of bacterial hosts
Authors: Caulton Simon G. , Lambert Carey , Tyson Jess , Radford Paul , Al-Bayati Asmaa , Greenwood Samuel , Banks Emma J. , Clark Callum , Till Rob , Pires Elisabete , Sockett R. Elizabeth , Lovering Andrew L. 
Published: January 2024

AbstractPredatory bacteria, like the model endoperiplasmic bacterium Bdellovibrio bacteriovorus, show several adaptations relevant to their requirements for locating, entering and killing other bacteria. The mechanisms underlying prey recognition and handling remain obscure. Here we use complementary genetic, microscopic and structural methods to address this deficit. During invasion, the B. bacteriovorus protein CpoB concentrates into a vesicular compartment that is deposited into the prey periplasm. Proteomic and structural analyses of vesicle contents reveal several fibre-like proteins, which we name the mosaic adhesive trimer (MAT) superfamily, and show localization on the predator surface before prey encounter. These dynamic proteins indicate a variety of binding capabilities, and we confirm that one MAT member shows specificity for surface glycans from a particular prey. Our study shows that the B. bacteriovorus MAT protein repertoire enables a broad means for the recognition and handling of diverse prey epitopes encountered during bacterial predation and invasion.
A deep learning system for predicting time to progression of diabetic retinopathy
Authors: Dai Ling , Sheng Bin , Chen Tingli , Wu Qiang , Liu Ruhan , Cai Chun , Wu Liang , Yang Dawei , Hamzah Haslina , Liu Yuexing , Wang Xiangning , Guan Zhouyu , Yu Shujie , Li Tingyao , Tang Ziqi , Ran Anran , Che Haoxuan , Chen Hao , Zheng Yingfeng , Shu Jia , Huang Shan , Wu Chan , Lin Shiqun , Liu Dan , Li Jiajia , Wang Zheyuan , Meng Ziyao , Shen Jie , Hou Xuhong , Deng Chenxin , Ruan Lei , Lu Feng , Chee Miaoli , Quek Ten Cheer , Srinivasan Ramyaa , Raman Rajiv , Sun Xiaodong , Wang Ya Xing , Wu Jiarui , Jin Hai , Dai Rongping , Shen Dinggang , Yang Xiaokang , Guo Minyi , Zhang Cuntai , Cheung Carol Y. , Tan Gavin Siew Wei , Tham Yih-Chung , Cheng Ching-Yu , Li Huating , Wong Tien Yin , Jia Weiping 
Published: January 2024

AbstractDiabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754–0.846 and integrated Brier scores of 0.153–0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1–5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.
Structural biases in disordered proteins are prevalent in the cell
Authors: Moses David , Guadalupe Karina , Yu Feng , Flores Eduardo , Perez Anthony R. , McAnelly Ralph , Shamoon Nora M. , Kaur Gagandeep , Cuevas-Zepeda Estefania , Merg Andrea D. , Martin Erik W. , Holehouse Alex S. , Sukenik Shahar 
Published: January 2024

AbstractIntrinsically disordered proteins and protein regions (IDPs) are prevalent in all proteomes and are essential to cellular function. Unlike folded proteins, IDPs exist in an ensemble of dissimilar conformations. Despite this structural plasticity, intramolecular interactions create sequence-specific structural biases that determine an IDP ensemble’s three-dimensional shape. Such structural biases can be key to IDP function and are often measured in vitro, but whether those biases are preserved inside the cell is unclear. Here we show that structural biases in IDP ensembles found in vitro are recapitulated inside human-derived cells. We further reveal that structural biases can change in a sequence-dependent manner due to changes in the intracellular milieu, subcellular localization, and intramolecular interactions with tethered well-folded domains. We propose that the structural sensitivity of IDP ensembles can be leveraged for biological function, can be the underlying cause of IDP-driven pathology or can be used to design disorder-based biosensors and actuators.
RNA and phosphoprotein profiles of TP53- and PTEN-knockouts in MCF10A at baseline and responding to DNA damage
Authors: Lin ChenWei , Schoenherr Regine M. , Voytovich Uliana J. , Ivey Richard G. , Kennedy Jacob J. , Whiteaker Jeffrey R. , Wang Pei , Paulovich Amanda G. 
Published: January 2024

AbstractA wealth of proteogenomic data has been generated using cancer samples to deepen our understanding of the mechanisms of cancer and how biological networks are altered in association with somatic mutation of tumor suppressor genes, such as TP53 and PTEN. To generate functional signatures of TP53 or PTEN loss, we profiled the RNA and phosphoproteomes of the MCF10A epithelial cell line, along with its congenic TP53- or PTEN-knockout derivatives, upon perturbation with the monofunctional DNA alkylating agent methyl methanesulfonate (MMS) vs. mock treatment. To enable quantitative and reproducible mass spectrometry data generation, the cell lines were SILAC-labeled (stable isotope labeling with amino acids in cell culture), and the experimental design included label swapping and biological replicates. All data are publicly available and may be used to advance our understanding of the TP53 and PTEN tumor suppressor genes and to provide functional signatures for bioinformatic analyses of proteogenomic datasets.
Developing a sustainable grease from jojoba oil with plant waste based nanoadditives for enhancement of rolling bearing performance
Authors: Dube Ndabezinhle Ngubhe , ElKady Marwa , Noby Hussien , Nassef Mohamed G. A. 
Published: January 2024

AbstractThis paper presents a novel grease from jojoba oil and activated carbon nanoparticles (ACNPs) extracted from banana peel waste. The raw jojoba oil and ACNPs are first characterized for structural properties. Samples of jojoba grease blended with 0.5 and 1.5 wt. % ACNPs are prepared and tested for physicochemical and tribological properties as compared to plain jojoba grease. Adding ACNPs to jojoba grease improves corrosion resistance from grade 2c to 1a while increasing the dropping point from 100 to 109 °C. ACNPs enhanced the viscosity of jojoba oil by up to 33% for testing temperature range of 40–100 °C. The load-carrying capacity of jojoba grease is increased by about 60% when blended with 1.5 wt.% ACNPs. The same blending decreased both the coefficient of friction and the wear scar diameter by 38% and 24%, respectively. A customized test rig is used to test the effectiveness of the grease samples in rolling bearing lubrication in terms of vibration levels and power consumption. The novel jojoba grease proved to show exceptional reductions power consumption reaching 25%. The vibration spectra show the absence of resonant peaks at high frequencies suggesting the capability of jojoba grease to form a stable full film lubrication.
Mutations associated with autism lead to similar synaptic and behavioral alterations in both sexes of male and female mouse brain
Authors: Tripathi Manish Kumar , Ojha Shashank Kumar , Kartawy Maryam , Khaliulin Igor , Hamoudi Wajeha , Amal Haitham 
Published: January 2024

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder based on synaptic abnormalities. The estimated prevalence rate of male individuals diagnosed with ASD prevails over females is in a proportion of 4:1. Consequently, males remain the main focus in ASD studies in clinical and experimental settings. Meanwhile, some studies point to an underestimation of this disorder in females. In this work, we studied the sex differences of the synaptic and behavioral phenotypes of ASD mouse models. Juvenile male and female Shank3Δ4–22 and Cntnap2−/− mutant mice and their WT littermates were used in the experiments. The animals were subjected to a Three-Chamber Sociability Test, then euthanized, and the whole cortex was used for the evaluation of the synaptic phenotype. Protein levels of glutamatergic (NR1) and GABAergic (GAD1 and VGAT) neuronal markers were measured. Protein level of synaptophysin (Syp) was also measured. Dendritic spine density in somatosensory neurons was analyzed by Golgi staining methods. Spine Density and GAD1, NR1, VGAT, and Syp levels were significantly reduced in Shank3Δ4–22 and Cntnap2−/− mice compared to the control group irrespective of sex, indicating impaired synaptic development in the mutant mice. These results were consistent with the lack of differences in the three-chamber sociability test between male and female mice. In conclusion, female ASD mice of both mutations undergo similar synaptic aberrations as their male counterparts and need to be studied along with the male animals. Finally, this work urges the psychiatry scientific community to use both sexes in their investigations.
mRNA vaccination of rabbits alters the fecundity, but not the attachment, of adult Ixodes scapularis
Authors: Matias Jaqueline , Cui Yingjun , Lynn Geoffrey E. , DePonte Kathleen , Mesquita Emily , Muramatsu Hiromi , Alameh Mohamad G. , Dwivedi Garima , Tam Ying K. , Pardi Norbert , Weissman Drew , Fikrig Erol 
Published: January 2024

Abstract19ISP is a nucleoside-modified mRNA-lipid nanoparticle vaccine that targets 19 Ixodes scapularis proteins. We demonstrate that adult I. scapularis have impaired fecundity when allowed to engorge on 19ISP-immunized rabbits. 19ISP, therefore, has the potential to interrupt the tick reproductive cycle, without triggering some of the other effects associated with acquired tick resistance. This may lead to the development of new strategies to reduce I. scapularis populations in endemic areas.