bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis sensitization in glioma: exploring the regulatory mechanism of SOAT1 and its therapeutic implications
Authors: Sun Shicheng , Qi Guoliang , Chen Hao , He Dong , Ma Dengzhen , Bie Yifan , Xu Linzong , Feng Bin , Pang Qi , Guo Hua , Zhang Rui 
Published: November 2023

AbstractGlioma, the most common primary malignant tumor of the central nervous system, lacks effective targeted therapies. This study investigates the role of SOAT1, a key gene involved in cholesterol esterification, in glioma prognosis and its association with ferroptosis. Although the impact of SOAT1 on glioma prognosis has been recognized, its precise mechanism remains unclear. In this study, we demonstrate that inhibiting SOAT1 increases the sensitivity of glioma cells to ferroptosis, both in vitro and in vivo. Mechanistically, SOAT1 positively modulates the expression of SLC40A1, an iron transporter, resulting in enhanced intracellular iron outflow, reduced intracellular iron levels, and subsequent disruption of ferroptosis. Importantly, we find that SOAT1 regulates ferroptosis independently of SREBPs, which are known to be involved in ferroptosis regulation. Furthermore, we identify the involvement of the PI3K-AKT-mTOR signaling pathway in mediating the regulatory effects of SOAT1 on SLC40A1 expression and ferroptosis sensitivity. These findings highlight the contribution of intracellular signaling cascades in the modulation of ferroptosis by SOAT1. We show that inhibiting SOAT1 enhances the efficacy of radiotherapy in gliomas, both in vitro and in vivo, by promoting sensitivity to ferroptosis. This suggests that targeting SOAT1 could potentially improve therapeutic outcomes for glioma patients. In summary, this study uncovers the pivotal role of SOAT1 as a link between cholesterol esterification and ferroptosis in glioma. Our findings underscore the potential of SOAT1 as a promising clinical therapeutic target, providing new avenues for the development of effective treatments for glioma. Further research is warranted to unravel the complete regulatory mechanisms of SOAT1 and explore its clinical applications.
Characterization of BRCA2 R3052Q variant in mice supports its functional impact as a low-risk variant
Authors: Mishra Arun Prakash , Hartford Suzanne , Chittela Rajani Kant , Sahu Sounak , Kharat Suhas S. , Alvaro-Aranda Lucia , Contreras-Perez Aida , Sullivan Teresa , Martin Betty K. , Albaugh Mary , Southon Eileen , Burkett Sandra , Karim Baktiar , Carreira Aura , Tessarollo Lino , Sharan Shyam K. 
Published: November 2023

AbstractPathogenic variants in BRCA2 are known to significantly increase the lifetime risk of developing breast and ovarian cancers. Sequencing-based genetic testing has resulted in the identification of thousands of BRCA2 variants that are considered to be variants of uncertain significance (VUS) because the disease risk associated with them is unknown. One such variant is p.Arg3052Gln, which has conflicting interpretations of pathogenicity in the ClinVar variant database. Arginine at position 3052 in BRCA2 plays an important role in stabilizing its C-terminal DNA binding domain. We have generated a knock-in mouse model expressing this variant to examine its role on growth and survival in vivo. Homozygous as well as hemizygous mutant mice are viable, fertile and exhibit no overt phenotype. While we did not observe any hematopoietic defects in adults, we did observe a marked reduction in the in vitro proliferative ability of fetal liver cells that were also hypersensitive to PARP inhibitor, olaparib. In vitro studies performed on embryonic and adult fibroblasts derived from the mutant mice showed significant reduction in radiation induced RAD51 foci formation as well as increased genomic instability after mitomycin C treatment. We observed mis-localization of a fraction of R3052Q BRCA2 protein to the cytoplasm which may explain the observed in vitro phenotypes. Our findings suggest that BRCA2 R3052Q should be considered as a hypomorphic variant.
Three-degrees-of-freedom orientation manipulation of small untethered robots with a single anisotropic soft magnet
Authors: Wang Heng , Cui Junhao , Tian Kuan , Han Yuxiang 
Published: November 2023

AbstractMagnetic actuation has been well exploited for untethered manipulation and locomotion of small-scale robots in complex environments such as intracorporeal lumens. Most existing magnetic actuation systems employ a permanent magnet onboard the robot. However, only 2-DoF orientation of the permanent-magnet robot can be controlled since no torque can be generated about its axis of magnetic moment, which limits the dexterity of manipulation. Here, we propose a new magnetic actuation method using a single soft magnet with an anisotropic geometry (e.g., triaxial ellipsoids) for full 3-DoF orientation manipulation. The fundamental actuation principle of anisotropic magnetization and 3-DoF torque generation are analytically modeled and experimentally validated. The hierarchical orientation stability about three principal axes is investigated, based on which we propose and validate a multi-step open-loop control strategy to alternatingly manipulate the direction of the longest axis of the soft magnet and the rotation about it for dexterous 3-DoF orientation manipulation.
PET/CT based cross-modal deep learning signature to predict occult nodal metastasis in lung cancer
Authors: Zhong Yifan , Cai Chuang , Chen Tao , Gui Hao , Deng Jiajun , Yang Minglei , Yu Bentong , Song Yongxiang , Wang Tingting , Sun Xiwen , Shi Jingyun , Chen Yangchun , Xie Dong , Chen Chang , She Yunlang 
Published: November 2023

AbstractOccult nodal metastasis (ONM) plays a significant role in comprehensive treatments of non-small cell lung cancer (NSCLC). This study aims to develop a deep learning signature based on positron emission tomography/computed tomography to predict ONM of clinical stage N0 NSCLC. An internal cohort (n = 1911) is included to construct the deep learning nodal metastasis signature (DLNMS). Subsequently, an external cohort (n = 355) and a prospective cohort (n = 999) are utilized to fully validate the predictive performances of the DLNMS. Here, we show areas under the receiver operating characteristic curve of the DLNMS for occult N1 prediction are 0.958, 0.879 and 0.914 in the validation set, external cohort and prospective cohort, respectively, and for occult N2 prediction are 0.942, 0.875 and 0.919, respectively, which are significantly better than the single-modal deep learning models, clinical model and physicians. This study demonstrates that the DLNMS harbors the potential to predict ONM of clinical stage N0 NSCLC.
Precise solid-phase synthesis of CoFe@FeOx nanoparticles for efficient polysulfide regulation in lithium/sodium-sulfur batteries
Authors: Chen Yanping , Yao Yu , Zhao Wantong , Wang Lifeng , Li Haitao , Zhang Jiangwei , Wang Baojun , Jia Yi , Zhang Riguang , Yu Yan , Liu Jian 
Published: November 2023

AbstractComplex metal nanoparticles distributed uniformly on supports demonstrate distinctive physicochemical properties and thus attract a wide attention for applications. The commonly used wet chemistry methods display limitations to achieve the nanoparticle structure design and uniform dispersion simultaneously. Solid-phase synthesis serves as an interesting strategy which can achieve the fabrication of complex metal nanoparticles on supports. Herein, the solid-phase synthesis strategy is developed to precisely synthesize uniformly distributed CoFe@FeOx core@shell nanoparticles. Fe atoms are preferentially exsolved from CoFe alloy bulk to the surface and then be carburized into a FexC shell under thermal syngas atmosphere, subsequently the formed FexC shell is passivated by air, obtaining CoFe@FeOx with a CoFe alloy core and a FeOx shell. This strategy is universal for the synthesis of MFe@FeOx (M = Co, Ni, Mn). The CoFe@FeOx exhibits bifunctional effect on regulating polysulfides as the separator coating layer for Li-S and Na-S batteries. This method could be developed into solid-phase synthetic systems to construct well distributed complex metal nanoparticles.
Adaptive traits of cysts of the snow alga Sanguina nivaloides unveiled by 3D subcellular imaging
Authors: Ezzedine Jade A. , Uwizeye Clarisse , Si Larbi Grégory , Villain Gaelle , Louwagie Mathilde , Schilling Marion , Hagenmuller Pascal , Gallet Benoît , Stewart Adeline , Petroutsos Dimitris , Devime Fabienne , Salze Pascal , Liger Lucie , Jouhet Juliette , Dumont Marie , Ravanel Stéphane , Amato Alberto , Valay Jean-Gabriel , Jouneau Pierre-Henri , Falconet Denis , Maréchal Eric 
Published: November 2023

AbstractSanguina nivaloides is the main alga forming red snowfields in high mountains and Polar Regions. It is non-cultivable. Analysis of environmental samples by X-ray tomography, focused-ion-beam scanning-electron-microscopy, physicochemical and physiological characterization reveal adaptive traits accounting for algal capacity to reside in snow. Cysts populate liquid water at the periphery of ice, are photosynthetically active, can survive for months, and are sensitive to freezing. They harbor a wrinkled plasma membrane expanding the interface with environment. Ionomic analysis supports a cell efflux of K+, and assimilation of phosphorus. Glycerolipidomic analysis confirms a phosphate limitation. The chloroplast contains thylakoids oriented in all directions, fixes carbon in a central pyrenoid and produces starch in peripheral protuberances. Analysis of cells kept in the dark shows that starch is a short-term carbon storage. The biogenesis of cytosolic droplets shows that they are loaded with triacylglycerol and carotenoids for long-term carbon storage and protection against oxidative stress.
Lipases and carboxylesterases affect moth sex pheromone compounds involved in interspecific mate recognition
Authors: de Fouchier Arthur , Fruitet Elise , Lievers Rik , Kuperus Peter , Emerson Jennifer , Gould Fred , Heckel David G. , Groot Astrid T. 
Published: November 2023

AbstractMoth sex pheromones are a classical model for studying sexual selection. Females typically produce a species-specific pheromone blend that attracts males. Revealing the enzymes involved in the interspecific variation in blend composition is key for understanding the evolution of these sexual communication systems. The nature of the enzymes involved in the variation of acetate esters, which are prominent compounds in moth pheromone blends, remains unclear. We identify enzymes involved in acetate degradation using two closely related moth species: Heliothis (Chloridea) subflexa and H. (C.) virescens, which have different quantities of acetate esters in their sex pheromone. Through comparative transcriptomic analyses and CRISPR/Cas9 knockouts, we show that two lipases and two esterases from H. virescens reduce the levels of pheromone acetate esters when expressed in H. subflexa females. Together, our results show that lipases and carboxylesterases are involved in tuning Lepidoptera pheromones composition.
Morphological evolution of bird wings follows a mechanical sensitivity gradient determined by the aerodynamics of flapping flight
Authors: Rader Jonathan A. , Hedrick Tyson L. 
Published: November 2023

AbstractThe physical principles that govern the function of biological structures also mediate their evolution, but the evolutionary drivers of morphological traits within complex structures can be difficult to predict. Here, we use morphological traits measured from 1096 3-dimensional bird wing scans from 178 species to test the interaction of two frameworks for relating morphology to evolution. We examine whether the evolutionary rate (σ2) and mode is dominated by the modular organization of the wing into handwing and armwing regions, and/or the relationship between trait morphology and functional output (i.e. mechanical sensitivity, driven here by flapping flight aerodynamics). Our results support discretization of the armwing and handwing as morphological modules, but morphological disparity andσ2varied continuously with the mechanical sensitivity gradient and were not modular. Thus, mechanical sensitivity should be considered an independent and fundamental driver of evolutionary dynamics in biomechanical traits, distinct from morphological modularity.
Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT
Authors: Khan Farha , Elgeti Matthias , Grandfield Samuel , Paz Aviv , Naughton Fiona B. , Marcoline Frank V. , Althoff Thorsten , Ermolova Natalia , Wright Ernest M. , Hubbell Wayne L. , Grabe Michael , Abramson Jeff 
Published: November 2023

AbstractSodium-dependent glucose transporters (SGLTs) couple a downhill Na+ ion gradient to actively transport sugars. Here, we investigate the impact of the membrane potential on vSGLT structure and function using sugar uptake assays, double electron-electron resonance (DEER), electrostatic calculations, and kinetic modeling. Negative membrane potentials, as present in all cell types, shift the conformational equilibrium of vSGLT towards an outward-facing conformation, leading to increased sugar transport rates. Electrostatic calculations identify gating charge residues responsible for this conformational shift that when mutated reduce galactose transport and eliminate the response of vSGLT to potential. Based on these findings, we propose a comprehensive framework for sugar transport via vSGLT, where the cellular membrane potential facilitates resetting of the transporter after cargo release. This framework holds significance not only for SGLTs but also for other transporters and channels.
The TDRD3-USP9X complex and MIB1 regulate TOP3B homeostasis and prevent deleterious TOP3B cleavage complexes
Authors: Saha Sourav , Huang Shar-yin Naomi , Yang Xi , Saha Liton Kumar , Sun Yilun , Khandagale Prashant , Jenkins Lisa M. , Pommier Yves 
Published: November 2023

AbstractTOP3B is stabilized by TDRD3. Hypothesizing that TDRD3 recruits a deubiquitinase, we find that TOP3B interacts with USP9X via TDRD3. Inactivation of USP9X destabilizes TOP3B, and depletion of both TDRD3 and USP9X does not promote further TOP3B ubiquitylation. Additionally, we observe that MIB1 mediates the ubiquitylation and proteasomal degradation of TOP3B by directly interacting with TOP3B independently of TDRD3. Combined depletion of USP9X, TDRD3 and MIB1 causes no additional increase in TOP3B levels compared to MIB1 knockdown alone indicating that the TDRD3-USP9X complex works downstream of MIB1. To comprehend why cells degrade TOP3B in the absence of TDRD3, we measured TOP3Bccs. Lack of TDRD3 increases TOP3Bccs in DNA and RNA, and induced R-loops, γH2AX and growth defect. Biochemical experiments confirm that TDRD3 increases the turnover of TOP3B. Our work provides molecular insights into the mechanisms by which TDRD3 protect cells from deleterious TOP3Bccs which are otherwise removed by TRIM41.
A primate nigrostriatal atlas of neuronal vulnerability and resilience in a model of Parkinson’s disease
Authors: Tang Lei , Xu Nana , Huang Mengyao , Yi Wei , Sang Xuan , Shao Mingting , Li Ye , Hao Zhao-zhe , Liu Ruifeng , Shen Yuhui , Yue Feng , Liu Xialin , Xu Chuan , Liu Sheng 
Published: November 2023

AbstractThe degenerative process in Parkinson’s disease (PD) causes a progressive loss of dopaminergic neurons (DaNs) in the nigrostriatal system. Resolving the differences in neuronal susceptibility warrants an amenable PD model that, in comparison to post-mortem human specimens, controls for environmental and genetic differences in PD pathogenesis. Here we generated high-quality profiles for 250,173 cells from the substantia nigra (SN) and putamen (PT) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian macaques and matched controls. Our primate model of parkinsonism recapitulates important pathologic features in nature PD and provides an unbiased view of the axis of neuronal vulnerability and resistance. We identified seven molecularly defined subtypes of nigral DaNs which manifested a gradient of vulnerability and were confirmed by fluorescence-activated nuclei sorting. Neuronal resilience was associated with a FOXP2-centered regulatory pathway shared between PD-resistant DaNs and glutamatergic excitatory neurons, as well as between humans and nonhuman primates. We also discovered activation of immune response common to glial cells of SN and PT, indicating concurrently activated pathways in the nigrostriatal system. Our study provides a unique resource to understand the mechanistic connections between neuronal susceptibility and PD pathophysiology, and to facilitate future biomarker discovery and targeted cell therapy.
Cosmic-void observations reconciled with primordial magnetogenesis
Authors: Hosking David N. , Schekochihin Alexander A. 
Published: November 2023

AbstractIt has been suggested that the weak magnetic field hosted by the intergalactic medium in cosmic voids could be a relic from the early Universe. However, accepted models of turbulent magnetohydrodynamic decay predict that the present-day strength of fields originally generated at the electroweak phase transition (EWPT) without parity violation would be too low to explain the observed scattering ofγ-rays from TeV blazars. Here, we propose that the decay is mediated by magnetic reconnection and conserves the mean square fluctuation level of magnetic helicity. We find that the relic fields would be stronger by several orders of magnitude under this theory than was indicated by previous treatments, which restores the consistency of the EWPT-relic hypothesis with the observational constraints. Moreover, efficient EWPT magnetogenesis would produce relics at the strength required to resolve the Hubble tension via magnetic effects at recombination and seed galaxy-cluster fields close to their present-day strength.
The homeodomain transcriptional regulator DVE-1 directs a program for synapse elimination during circuit remodeling
Authors: Alexander Kellianne D. , Ramachandran Shankar , Biswas Kasturi , Lambert Christopher M. , Russell Julia , Oliver Devyn B. , Armstrong William , Rettler Monika , Liu Samuel , Doitsidou Maria , Bénard Claire , Walker Amy K. , Francis Michael M. 
Published: November 2023

AbstractThe elimination of synapses during circuit remodeling is critical for brain maturation; however, the molecular mechanisms directing synapse elimination and its timing remain elusive. We show that the transcriptional regulator DVE-1, which shares homology with special AT-rich sequence-binding (SATB) family members previously implicated in human neurodevelopmental disorders, directs the elimination of juvenile synaptic inputs onto remodeling C. elegans GABAergic neurons. Juvenile acetylcholine receptor clusters and apposing presynaptic sites are eliminated during the maturation of wild-type GABAergic neurons but persist into adulthood in dve-1 mutants, producing heightened motor connectivity. DVE-1 localization to GABAergic nuclei is required for synapse elimination, consistent with DVE-1 regulation of transcription. Pathway analysis of putative DVE-1 target genes, proteasome inhibitor, and genetic experiments implicate the ubiquitin-proteasome system in synapse elimination. Together, our findings define a previously unappreciated role for a SATB family member in directing synapse elimination during circuit remodeling, likely through transcriptional regulation of protein degradation processes.
Architecture of the baculovirus nucleocapsid revealed by cryo-EM
Authors: Jia Xudong , Gao Yuanzhu , Huang Yuxuan , Sun Linjun , Li Siduo , Li Hongmei , Zhang Xueqing , Li Yinyin , He Jian , Wu Wenbi , Venkannagari Harikanth , Yang Kai , Baker Matthew L. , Zhang Qinfen 
Published: November 2023

AbstractBaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has been widely used as a bioinsecticide and a protein expression vector. Despite their importance, very little is known about the structure of most baculovirus proteins. Here, we show a 3.2 Å resolution structure of helical cylindrical body of the AcMNPV nucleocapsid, composed of VP39, as well as 4.3 Å resolution structures of both the head and the base of the nucleocapsid composed of over 100 protein subunits. AcMNPV VP39 demonstrates some features of the HK97-like fold and utilizes disulfide-bonds and a set of interactions at its C-termini to mediate nucleocapsid assembly and stability. At both ends of the nucleocapsid, the VP39 cylinder is constricted by an outer shell ring composed of proteins AC104, AC142 and AC109. AC101(BV/ODV-C42) and AC144(ODV-EC27) form a C14 symmetric inner layer at both capsid head and base. In the base, these proteins interact with a 7-fold symmetric capsid plug, while a portal-like structure is seen in the central portion of head. Additionally, we propose an application of AlphaFold2 for model building in intermediate resolution density.
Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer
Authors: Tarantino Paolo , Gupta Hersh , Hughes Melissa E. , Files Janet , Strauss Sarah , Kirkner Gregory , Feeney Anne-Marie , Li Yvonne , Garrido-Castro Ana C. , Barroso-Sousa Romualdo , Bychkovsky Brittany L. , DiLascio Simona , Sholl Lynette , MacConaill Laura , Lindeman Neal , Johnson Bruce E. , Meyerson Matthew , Jeselsohn Rinath , Qiu Xintao , Li Rong , Long Henry , Winer Eric P. , Dillon Deborah , Curigliano Giuseppe , Cherniack Andrew D. , Tolaney Sara M. , Lin Nancy U. 
Published: November 2023

AbstractThe molecular underpinnings of HER2-low and HER2-0 (IHC 0) breast tumors remain poorly defined. Using genomic findings from 1039 patients with HER2-negative metastatic breast cancer undergoing next-generation sequencing from 7/2013-12/2020, we compare results between HER2-low (n = 487, 47%) and HER2-0 tumors (n = 552, 53%). A significantly higher number of ERBB2 alleles (median copy count: 2.05) are observed among HER2-low tumors compared to HER2-0 (median copy count: 1.79; P = 2.36e-6), with HER2-0 tumors harboring a higher rate of ERBB2 hemideletions (31.1% vs. 14.5%). No other genomic alteration reaches significance after accounting for multiple hypothesis testing, and no significant differences in tumor mutational burden are observed between HER2-low and HER2-0 tumors (median: 7.26 mutations/megabase vs. 7.60 mutations/megabase, p = 0.24). Here, we show that the genomic landscape of HER2-low and HER2-0 tumors does not differ significantly, apart from a higher ERBB2 copy count among HER2-low tumors, and a higher rate of ERBB2 hemideletions in HER2-0 tumors.
Diurnal switches in diazotrophic lifestyle increase nitrogen contribution to cereals
Authors: Tang Yuqian , Qin Debin , Tian Zhexian , Chen Wenxi , Ma Yuanxi , Wang Jilong , Yang Jianguo , Yan Dalai , Dixon Ray , Wang Yi-Ping 
Published: November 2023

AbstractUncoupling of biological nitrogen fixation from ammonia assimilation is a prerequisite step for engineering ammonia excretion and improvement of plant-associative nitrogen fixation. In this study, we have identified an amino acid substitution in glutamine synthetase, which provides temperature sensitive biosynthesis of glutamine, the intracellular metabolic signal of the nitrogen status. As a consequence, negative feedback regulation of genes and enzymes subject to nitrogen regulation, including nitrogenase is thermally controlled, enabling ammonia excretion in engineered Escherichia coli and the plant-associated diazotroph Klebsiella oxytoca at 23 °C, but not at 30 °C. We demonstrate that this temperature profile can be exploited to provide diurnal oscillation of ammonia excretion when variant bacteria are used to inoculate cereal crops. We provide evidence that diurnal temperature variation improves nitrogen donation to the plant because the inoculant bacteria have the ability to recover and proliferate at higher temperatures during the daytime.