bluuebunny/crossref_metadata_2025_split huggingface dataset:
HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification
Authors: Wang Jiayu , Zhu Mengxin , Zhu Jinghan , Li Juntao , Zhu Xingchao , Wang Kun , Shen Kanger , Yang Kexi , Ni Xiangyu , Liu Xin , Zhang Guangbo , Xi Qinhua , Shi Tongguo , Chen Weichang 
Published: November 2023

AbstractAerobic glycolysis has been shown to play a key role in tumor cell proliferation and metastasis. However, how it is directly regulated is largely unknown. Here, we found that HES1 expression was significantly higher in CRC tissues than that in adjacent normal tissues. Moreover, high HES1 expression is associated with poor survival in CRC patients. HES1 knockdown markedly inhibited cell growth and metastasis both in vitro and in vivo. Additionally, silencing of HES1 suppressed aerobic glycolysis of CRC cells. Mechanistic studies revealed that HES1 knockdown decreased the expression of GLUT1, a key gene of aerobic glycolysis, in CRC cells. GLUT1 overexpression abolished the effects of HES1 knockdown on cell aerobic glycolysis, proliferation, migration and invasion. ChIP-PCR and dual-luciferase reporter gene assay showed that HES1 directly bound the promoter of IGF2BP2 and promoted IGF2BP2 expression. Furthermore, our data indicated that IGF2BP2 recognized and bound the m6A site in the GLUT1 mRNA and enhanced its stability. Taken together, our findings suggest that HES1 has a significant promotion effect on CRC aerobic glycolysis and progression by enhancing the stability of m6A-modified GLUT1 mRNA in an IGF2BP2-dependent manner, which may become a viable therapeutic target for the treatment of CRC in humans.
Confined-microtubule assembly shapes three-dimensional cell wall structures in xylem vessels
Authors: Sasaki Takema , Saito Kei , Inoue Daisuke , Serk Henrik , Sugiyama Yuki , Pesquet Edouard , Shimamoto Yuta , Oda Yoshihisa 
Published: November 2023

AbstractProperly patterned deposition of cell wall polymers is prerequisite for the morphogenesis of plant cells. A cortical microtubule array guides the two-dimensional pattern of cell wall deposition. Yet, the mechanism underlying the three-dimensional patterning of cell wall deposition is poorly understood. In metaxylem vessels, cell wall arches are formed over numerous pit membranes, forming highly organized three-dimensional cell wall structures. Here, we show that the microtubule-associated proteins, MAP70-5 and MAP70-1, regulate arch development. The map70-1 map70-5 plants formed oblique arches in an abnormal orientation in pits. Microtubules fit the aperture of developing arches in wild-type cells, whereas microtubules in map70-1 map70-5 cells extended over the boundaries of pit arches. MAP70 caused the bending and bundling of microtubules. These results suggest that MAP70 confines microtubules within the pit apertures by altering the physical properties of microtubules, thereby directing the growth of pit arches in the proper orientation. This study provides clues to understanding how plants develop three-dimensional structure of cell walls.
Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson’s disease mouse model
Authors: Fang Tracy-Shi Zhang , Sun Yu , Pearce Andrew C. , Eleuteri Simona , Kemp Mark , Luckhurst Christopher A. , Williams Rachel , Mills Ross , Almond Sarah , Burzynski Laura , Márkus Nóra M. , Lelliott Christopher J. , Karp Natasha A. , Adams David J. , Jackson Stephen P. , Zhao Jin-Feng , Ganley Ian G. , Thompson Paul W. , Balmus Gabriel , Simon David K. 
Published: November 2023

AbstractMutations in SNCA, the gene encoding α-synuclein (αSyn), cause familial Parkinson’s disease (PD) and aberrant αSyn is a key pathological hallmark of idiopathic PD. This α-synucleinopathy leads to mitochondrial dysfunction, which may drive dopaminergic neurodegeneration. PARKIN and PINK1, mutated in autosomal recessive PD, regulate the preferential autophagic clearance of dysfunctional mitochondria (“mitophagy”) by inducing ubiquitylation of mitochondrial proteins, a process counteracted by deubiquitylation via USP30. Here we show that loss of USP30 in Usp30 knockout mice protects against behavioral deficits and leads to increased mitophagy, decreased phospho-S129 αSyn, and attenuation of SN dopaminergic neuronal loss induced by αSyn. These observations were recapitulated with a potent, selective, brain-penetrant USP30 inhibitor, MTX115325, with good drug-like properties. These data strongly support further study of USP30 inhibition as a potential disease-modifying therapy for PD.
A 5+1 assemble-to-activate mechanism of the Lon proteolytic machine
Authors: Li Shanshan , Hsieh Kan-Yen , Kuo Chiao-I , Lin Tzu-Chi , Lee Szu-Hui , Chen Yi-Ru , Wang Chun-Hsiung , Ho Meng-Ru , Ting See-Yeun , Zhang Kaiming , Chang Chung-I 
Published: November 2023

AbstractMany AAA+ (ATPases associated with diverse cellular activities) proteins function as protein or DNA remodelers by threading the substrate through the central pore of their hexameric assemblies. In this ATP-dependent translocating state, the substrate is gripped by the pore loops of the ATPase domains arranged in a universal right-handed spiral staircase organization. However, the process by which a AAA+ protein is activated to adopt this substrate-pore-loop arrangement remains unknown. We show here, using cryo-electron microscopy (cryo-EM), that the activation process of the Lon AAA+ protease may involve a pentameric assembly and a substrate-dependent incorporation of the sixth protomer to form the substrate-pore-loop contacts seen in the translocating state. Based on the structural results, we design truncated monomeric mutants that inhibit Lon activity by binding to the native pentamer and demonstrated that expressing these monomeric mutants in Escherichia coli cells containing functional Lon elicits specific phenotypes associated with lon deficiency, including the inhibition of persister cell formation. These findings uncover a substrate-dependent assembly process for the activation of a AAA+ protein and demonstrate a targeted approach to selectively inhibit its function within cells.
Melting and defect transitions in FeO up to pressures of Earth’s core-mantle boundary
Authors: Dobrosavljevic Vasilije V. , Zhang Dongzhou , Sturhahn Wolfgang , Chariton Stella , Prakapenka Vitali B. , Zhao Jiyong , Toellner Thomas S. , Pardo Olivia S. , Jackson Jennifer M. 
Published: November 2023

AbstractThe high-pressure melting curve of FeO controls key aspects of Earth’s deep interior and the evolution of rocky planets more broadly. However, existing melting studies on wüstite were conducted across a limited pressure range and exhibit substantial disagreement. Here we use an in-situ dual-technique approach that combines a suite of >1000 x-ray diffraction and synchrotron Mössbauer measurements to report the melting curve for Fe1-xO wüstite to pressures of Earth’s lowermost mantle. We further observe features in the data suggesting an order-disorder transition in the iron defect structure several hundred kelvin below melting. This solid-solid transition, suggested by decades of ambient pressure research, is detected across the full pressure range of the study (30 to 140 GPa). At 136 GPa, our results constrain a relatively high melting temperature of 4140 ± 110 K, which falls above recent temperature estimates for Earth’s present-day core-mantle boundary and supports the viability of solid FeO-rich structures at the roots of mantle plumes. The coincidence of the defect order-disorder transition with pressure-temperature conditions of Earth’s mantle base raises broad questions about its possible influence on key physical properties of the region, including rheology and conductivity.
Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation
Authors: Joshi Ashish , Walimbe Anuja , Avni Anamika , Rai Sandeep K. , Arora Lisha , Sarkar Snehasis , Mukhopadhyay Samrat 
Published: November 2023

AbstractBiomolecular condensates formed via phase separation of proteins and nucleic acids are thought to be associated with a wide range of cellular functions and dysfunctions. We dissect critical molecular events associated with phase separation of an intrinsically disordered prion-like low-complexity domain of Fused in Sarcoma by performing single-molecule studies permitting us to access the wealth of molecular information that is skewed in conventional ensemble experiments. Our single-molecule FRET experiments reveal the coexistence of two conformationally distinct subpopulations in the monomeric form. Single-droplet single-molecule FRET studies coupled with fluorescence correlation spectroscopy, picosecond time-resolved fluorescence anisotropy, and vibrational Raman spectroscopy indicate that structural unwinding switches intramolecular interactions into intermolecular contacts allowing the formation of a dynamic network within condensates. A disease-related mutation introduces enhanced structural plasticity engendering greater interchain interactions that can accelerate pathological aggregation. Our findings provide key mechanistic underpinnings of sequence-encoded dynamically-controlled structural unzipping resulting in biological phase separation.
Io’s polar volcanic thermal emission indicative of magma ocean and shallow tidal heating models
Authors: Davies Ashley Gerard , Perry Jason E. , Williams David A. , Nelson David M. 
Published: November 2023

AbstractThe distribution of Io’s volcanic activity probably reflects the position and magnitude of internal tidal heating, but full mapping of the moon has not been possible due to a lack of polar coverage. Here we use new observations of Io’s polar regions by the Juno spacecraft Jovian Infrared Auroral Mapper to complete near-infrared coverage, revealing the global distribution and magnitude of thermal emission from Io’s currently erupting volcanoes. We show that the distribution of volcanic heat flow from 266 active hot spots is consistent with the presence of a global magma ocean and/or shallow asthenospheric heating. We find that Io’s polar volcanoes are less energetic but approximately the same in number per unit area than those at lower latitudes. We also find that volcanic heat flow in the north polar cap is greater than that in the south. The low volcanic advection seen at Io’s poles is therefore at odds with measurements of background temperature, showing that Io’s poles are anomalously warm. We suggest that the differences in volcanic thermal emission from Io’s poles compared with those at lower latitudes are indicative of lithospheric dichotomies that inhibit volcanic advection towards Io’s poles, particularly in the south polar region.
Unsupervised classification for region of interest in X-ray ptychography
Authors: Lin Dergan , Jiang Yi , Deng Junjing , Di Zichao Wendy 
Published: November 2023

AbstractX-ray ptychography offers high-resolution imaging of large areas at a high computational cost due to the large volume of data provided. To address the cost issue, we propose a physics-informed unsupervised classification algorithm that is performed prior to reconstruction and removes data outside the region of interest (RoI) based on the multimodal features present in the diffraction patterns. The preprocessing time for the proposed method is inconsequential in contrast to the resource-intensive reconstruction process, leading to an impressive reduction in the data workload to a mere 20% of the initial dataset. This capability consequently reduces computational time dramatically while preserving reconstruction quality. Through further segmentation of the diffraction patterns, our proposed approach can also detect features that are smaller than beam size and correctly classify them as within the RoI.
Post-testicular sperm maturation in ancient holostean species
Authors: Dzyuba Viktoriya , Shelton William L. , Hiott Ana E. , Cosson Jacky , Bondarenko Olga , Kholodnyy Vitaliy , Dzyuba Borys 
Published: November 2023

AbstractFish speciation was accompanied by changes in the urogenital system anatomy. In evolutionarily modern Teleostei, male reproductive tracts are fully separated from the excretory system, while in evolutionarily ancient Chondrostei and Holostei, the excretory and reproductive tracts are not separated. Sturgeon post-testicular sperm maturation (PTSM) occurring as a result of sperm/urine mixing is phenomenologically well described, while, in holosteans, functional intimacy of seminal ducts with kidney ducts and the existence of PTSM still need to be addressed. In Lepisosteus platostomus (Holostei), sperm samples were collected from testes (TS), efferent ducts (EDS), and Wolffian ducts (WDS). While WDS was motile, no motility was found in TS and EDS. The existence of PTSM was checked by in vitro PTSM procedure. After TS and EDS incubation in seminal fluid from WDS, no more than 5% motile spermatozoa were observed in TS, whereas in EDS the motility percentage was up to 75%. Experimental dyeing of urogenital ducts in gars and sturgeons revealed some differences in the interconnection between sperm ducts and kidneys. It is concluded that post-testicular sperm maturation occurs in gars and suggests that infraclass Holostei occupies an intermediate evolutionary position between Teleostei and Chondrostei in the anatomical arrangement of the urogenital system.
A novel method for identifying key genes in macroevolution based on deep learning with attention mechanism
Authors: Mao Jiawei , Cao Yong , Zhang Yan , Huang Biaosheng , Zhao Youjie 
Published: November 2023

AbstractMacroevolution can be regarded as the result of evolutionary changes of synergistically acting genes. Unfortunately, the importance of these genes in macroevolution is difficult to assess and hence the identification of macroevolutionary key genes is a major challenge in evolutionary biology. In this study, we designed various word embedding libraries of natural language processing (NLP) considering the multiple mechanisms of evolutionary genomics. A novel method (IKGM) based on three types of attention mechanisms (domain attention, kmer attention and fused attention) were proposed to calculate the weights of different genes in macroevolution. Taking 34 species of diurnal butterflies and nocturnal moths in Lepidoptera as an example, we identified a few of key genes with high weights, which annotated to the functions of circadian rhythms, sensory organs, as well as behavioral habits etc. This study not only provides a novel method to identify the key genes of macroevolution at the genomic level, but also helps us to understand the microevolution mechanisms of diurnal butterflies and nocturnal moths in Lepidoptera.
Clinical outcomes and actual consequence of lung nodules incidentally detected on chest radiographs by artificial intelligence
Authors: Hwang Shin Hye , Shin Hyun Joo , Kim Eun-Kyung , Lee Eun Hye , Lee Minwook 
Published: November 2023

AbstractThis study evaluated how often clinically significant lung nodules were detected unexpectedly on chest radiographs (CXR) by artificial intelligence (AI)—based detection software, and whether co-existing findings can aid in differential diagnosis of lung nodules. Patients (> 18 years old) with AI-detected lung nodules at their first visit from March 2021 to February 2022, except for those in the pulmonology or thoracic surgery departments, were retrospectively included. Three radiologists categorized nodules into malignancy, active inflammation, post-inflammatory sequelae, or “other” groups. Characteristics of the nodule and abnormality scores of co-existing lung lesions were compared. Approximately 1% of patients (152/14,563) had unexpected lung nodules. Among 73 patients with follow-up exams, 69.9% had true positive nodules. Increased abnormality scores for nodules were significantly associated with malignancy (odds ratio [OR] 1.076, P = 0.001). Increased abnormality scores for consolidation (OR 1.033, P = 0.040) and pleural effusion (OR 1.025, P = 0.041) were significantly correlated with active inflammation–type nodules. Abnormality scores for fibrosis (OR 1.036, P = 0.013) and nodules (OR 0.940, P = 0.001) were significantly associated with post-inflammatory sequelae categorization. AI-based lesion-detection software of CXRs in daily practice can help identify clinically significant incidental lung nodules, and referring accompanying lung lesions may help classify the nodule.
The mosquito Aedes aegypti requires a gut microbiota for normal fecundity, longevity and vector competence
Authors: Harrison Ruby E. , Yang Xiushuai , Eum Jai Hoon , Martinson Vincent G. , Dou Xiaoyi , Valzania Luca , Wang Yin , Boyd Bret M. , Brown Mark R. , Strand Michael R. 
Published: November 2023

AbstractMosquitoes shift from detritus-feeding larvae to blood-feeding adults that can vector pathogens to humans and other vertebrates. The sugar and blood meals adults consume are rich in carbohydrates and protein but are deficient in other nutrients including B vitamins. Facultatively hematophagous insects like mosquitoes have been hypothesized to avoid B vitamin deficiencies by carryover of resources from the larval stage. However, prior experimental studies have also used adults with a gut microbiota that could provision B vitamins. Here, we used Aedes aegypti, which is the primary vector of dengue virus (DENV), to ask if carryover effects enable normal function in adults with no microbiota. We show that adults with no gut microbiota produce fewer eggs, live longer with lower metabolic rates, and exhibit reduced DENV vector competence but are rescued by provisioning B vitamins or recolonizing the gut with B vitamin autotrophs. We conclude carryover effects do not enable normal function.
Shape-controlled synthesis and self-assembly of highly uniform upconverting calcium fluoride nanocrystals
Authors: Paik Taejong , Greybush Nicholas J. , Najmr Stan , Woo Ho Young , Hong Seong Vin , Kim Seung Hyeon , Lee Jennifer D. , Kagan Cherie R. , Murray Christopher B. 
Published: November 2023

A novel synthetic method to tailor the shapes of highly uniform upconverting CaF2 NCs is demonstrated. We investigate the shape-dependent self-assemblies, and size, shape, and dopant composition-dependent upconversion luminescence of CaF2 NCs.
Hybrid energy storage for the optimized configuration of integrated energy system considering battery‐life attenuation
Authors: Zeng Xianqiang , Xiao Peng , Zhou Yun , Li Hengjie 
Published: November 2023

AbstractTo enhance the utilization of renewable energy and the economic efficiency of energy system's planning and operation, this study proposes a hybrid optimization configuration method for battery/pumped hydro energy storage considering battery‐lifespan attenuation in the regionally integrated energy system (RIES). Moreover, a two‐layer optimization model was established for integrated energy system planning and operation based on the combination of the Salp Swarm algorithm and mixed‐integer linear programming. Considering wind and solar energies and multiple loads, such as electricity, cooling, and heating, the first step in this paper involved the construction of a model for the RIES incorporating hybrid energy storage and various energy‐conversion devices. Then, given a synergy among different energy sources in the system, the long‐term impact of battery‐lifespan attenuation is introduced by including battery‐replacement costs. Based on the optimization results obtained from daily operations, a hybrid energy storage‐based optimization configuration model is established to minimize the annual operational and energy‐storage investment costs. The results show that, compared to the systems with a single pumped hydro storage or battery energy storage, the system with the hybrid energy storage reduces the total system cost by 0.33% and 0.88%, respectively. Additionally, the validity of the proposed method in enhancing the economic efficiency of system planning and operation is confirmed. Furthermore, a comparative analysis is conducted of the impact of battery‐lifespan degradation on the system's economic efficiency. The results show that during the system's operation phase, the total system cost is reduced by 9.97% considering battery‐lifespan degradation than that without considering the degradation.
Extensive fatal Pyoderma gangrenosum in a dog after drug
exposure
Authors: Schaefer Laura , Kloß Elena , Henrich Manfred , Thom Nina 
Published: November 2023

AbstractA 4-year-old, spayed female mixed breed dog was presented with large crater-like,
well-demarcated, erosive and ulcerative necrotic lesions of the skin, elevated
body temperature and lethargy, that began 14 days after vaccination and
treatment with fluralaner and milbemycin/praziquantel. Cytology revealed
severe pyogranulomatous inflammation with moderate numbers of extracellular
microorganisms. Histopathologic examination showed severe multifocal
pyogranulomatous dermatitis and panniculitis with severe dermal edema and severe
neutrophilic exocytosis with band-like infiltration of the lower portion of the
epidermis consistent with pyoderma gangrenosum. Despite intensive
immunosuppressive and antimicrobial therapy and intensive inpatient care, the
dog was euthanized 16 days after admission due to complications with clinical
signs of sepsis, acute dyspnea and thoracic effusion.
Threshold collision induced dissociation of protonated water clusters
Authors: Zamith Sébastien , Kassem Ali , L’Hermite Jean-Marc , Joblin Christine , Cuny Jérôme 
Published: November 2023

We report threshold collision induced dissociation experiments on protonated water clusters thermalized at low temperature for sizes n = 19–23. Fragmentation cross sections are recorded as a function of the collision energy and analyzed with a statistical model. This model allows us to account for dissociation cascades and provides values for the dissociation energies of each cluster. These values, averaging around 0.47 eV, are in good agreement with theoretical predictions at various levels of theory. Furthermore, the dissociation energies show a trend for the n = 21 magic and n = 22 anti-magic numbers relative to their neighbours, which is also in agreement with theory. These results provide further evidence to resolve the disagreement between previously published experimental values. A careful quantitative treatment of cascade dissociation in this model introduces interdependence between the dissociation energies of neighboring sizes, which reduces the number of free fitting parameters and improves both reliability and uncertainties on absolute dissociation energies deduced from experiments.
Synthesis and antibacterial activity of 6″-decanesulfonylacetamide-functionalised amphiphilic derivatives of amikacin and kanamycin
Authors: Farr Dylan C. , Tan Lendl , Furness Juanelle , Grice I. Darren , West Nicholas P. , Houston Todd A. 
Published: November 2023

Aminoglycoside antibiotics represent the first class of successful drugs in the treatment of tuberculosis; however, mycobacteria and other bacterial species possess several drug resistance mechanisms to inactivate these natural products. In the past 15 years, a variety of amphiphilic aminoglycosides have been shown to have improved activity against infectious microorganisms and to subvert resistance mechanisms. Here, we report on four novel synthetic compounds derived from two existing potent antitubercular compounds and describe their activity against both Mycobacterium tuberculosis and Staphylococcus aureus. It was found that a decanesulfonylacetamide-based conjugate of amikacin displayed promising preliminary antitubercular activities, warranting further investigation to assess the therapeutic potential of these unique antimicrobials.