bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Has the Ferrel Cell Contributed to the Maintenance of Antarctic Sea Ice at Low Levels From 2016 to 2022?
Authors: Wang Shaoyin , Liu Jiping , Wei Zixin , Yang Dongxia , Li Hua , Ding Suoyi , Hui Fengming , Cheng Xiao 
Published: July 2024

AbstractThis study investigates the specific circulation anomalies that have sustained the low Antarctic sea ice state since 2016. Firstly, we find a significant strengthening and southward shift in the Ferrel Cell (FC) during 2016–2022, resulting in a marked increase in southward transport of heat and moisture. Secondly, this enhanced FC is closely associated with a stronger mid‐latitude wave pattern. This pattern is zonally asymmetric and greatly amplifies the poleward advections of heat and moisture, leading to the increased downward longwave radiation, more liquid precipitation and sea ice retreat in specific regions, including the western Pacific and Indian Ocean sectors, Ross and northern Weddell Seas. The mechanism deduced from the short‐term period is further supported by the results of 40 ensemble members of simulations. The southward expansion of the FC and sea ice decline are closely linked to La Niña‐like conditions but may also be driven by anthropogenic global warming.
The South Pole‐Aitken Basin: Constraints on Impact Excavation, Melt, and Ejecta
Authors: Citron R. I. , Smith D. E. , Stewart S. T. , Hood L. L. , Zuber M. T. 
Published: July 2024

AbstractThe formation and evolution of the South Pole‐Aitken (SPA) basin is critical to relating large impact basin formation and modification to lunar geophysical evolution. Most prior models of the SPA impact were conducted in 2D, making it difficult to compare model output to the 3D crustal structure and ejecta distribution. In order to better constrain the parameters of the SPA impactor and the expected post impact distribution of crust and ejecta, we conducted numerical simulations of the SPA impact in 3D. We tested a wide range of impact parameters and constrained model results with recent geophysical data. We found the crustal structure of the SPA basin is best fit by an oblique impact (30–45°) of a 350–400 km diameter projectile impacting at 12–16 km/s. The impact excavated material from as deep as 80–120 km, and ejecta was deposited in a butterfly pattern with a forbidden region uprange of the impact.
Intranasal adenovirus-vectored Omicron vaccine induced nasal immunoglobulin A has superior neutralizing potency than serum antibodies
Authors: Chen Si , Zhang Zhengyuan , Wang Qian , Yang Qi , Yin Li , Ning Lishan , Chen Zhilong , Tang Jielin , Deng Weiqi , He Ping , Li Hengchun , Shi Linjing , Deng Yijun , Liu Zijian , Bu Hemeng , Zhu Yaohui , Liu Wenming , Qu Linbing , Feng Liqiang , Xiong Xiaoli , Sun Baoqing , Zhong Nanshan , Li Feng , Li Pingchao , Chen Xinwen , Chen Ling 
Published: July 2024

AbstractThe upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6–3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.
Onvansertib treatment overcomes olaparib resistance in high-grade ovarian carcinomas
Authors: Chiappa Michela , Decio Alessandra , Guarrera Luca , Mengoli Ilaria , Karki Anju , Yemane Divora , Ghilardi Carmen , Scanziani Eugenio , Canesi Simone , Barbera Maria C. , Craparotta Ilaria , Bolis Marco , Fruscio Robert , Grasselli Chiara , Ceruti Tommaso , Zucchetti Massimo , Patterson Jesse C. , Lu Robin A. , Yaffe Micheal B. , Ridinger Maya , Damia Giovanna , Guffanti Federica 
Published: July 2024

AbstractOccurrence of resistance to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) approved in ovarian carcinoma, has already been shown in clinical settings. Identifying combination treatments to sensitize tumor cells and/or overcome resistance to olaparib is critical. Polo-like kinase 1 (PLK1), a master regulator of mitosis, is also involved in the DNA damage response promoting homologous recombination (HR)-mediated DNA repair and in the recovery from the G2/M checkpoint. We hypothesized that PLK1 inhibition could sensitize tumor cells to PARP inhibition. Onvansertib, a highly selective PLK1 inhibitor, and olaparib were tested in vitro and in vivo in BRCA1 mutated and wild-type (wt) ovarian cancer models, including patient-derived xenografts (PDXs) resistant to olaparib. The combination of onvansertib and olaparib was additive or synergic in different ovarian cancer cell lines, causing a G2/M block of the cell cycle, DNA damage, and apoptosis, much more pronounced in cells treated with the two drugs as compared to controls and single agents treated cells. The combined treatment was well tolerated in vivo and resulted in tumor growth inhibition and a statistically increased survival in olaparib-resistant-BRCA1 mutated models. The combination was also active, although to a lesser extent, in BRCA1 wt PDXs. Pharmacodynamic analyses showed an increase in mitotic, apoptotic, and DNA damage markers in tumor samples derived from mice treated with the combination versus vehicle. We could demonstrate that in vitro onvansertib inhibited both HR and non-homologous end-joining repair pathways and in vivo induced a decrease in the number of RAD51 foci-positive tumor cells, supporting its ability to induce HR deficiency and favoring the activity of olaparib. Considering that the combination was well tolerated, these data support and foster the clinical evaluation of onvansertib with PARPis in ovarian cancer, particularly in the PARPis-resistant setting.
N6-methyladenosine-modified ALDH9A1 modulates lipid accumulation and tumor progression in clear cell renal cell carcinoma through the NPM1/IQGAP2/AKT signaling pathway
Authors: Tan Diaoyi , Miao Daojia , Zhao Chuanyi , Shi Jian , Lv Qingyang , Lu Feiyi , Ruan Hailong , Xiong Zhiyong , Zhang Xiaoping 
Published: July 2024

AbstractAldehyde dehydrogenases superfamily (ALDHs), which are ubiquitously present in various organisms with diverse subcellular localizations, play a crucial role in regulating malignant tumor progression; Nevertheless, their involvement in clear cell renal cell carcinoma (ccRCC) has not been elucidated. In this study, we performed comprehensive bioinformatics analyses on the 19 ALDHs genes, and identified ALDH9A1 as a key contributor in ccRCC. Expression patterns and clinical relevance of ALDH9A1 were determined using bioinformatics analyses, real-time PCR, western blotting, and immunohistochemistry. To explore the underlying mechanism behind the tumor suppressor role of ALDH9A1, RNA sequencing, methylated RNA immunoprecipitation, luciferase reporter assay, mass spectroscopy, immunoprecipitation, mutational studies and immunofluorescence were employed. The impact of ALDH9A1 in ccRCC progression and metabolic programming was assessed through both in vitro and in vivo. Here, this study revealed ALDH9A1 as a tumor suppressor gene in ccRCC. The fat mass and obesity associated protein (FTO) was identified as a demethylase for ALDH9A1 mRNA, resulting in its reduced stability and expression levels in ccRCC. Functional experiments demonstrated that the deficiency of ALDH9A1 in ccRCC promoted tumor proliferation, invasion, migration and lipid accumulation. Mechanistic insights illustrated that the diminished levels of ALDH9A1 resulted in the failure to sequester nucleophosmin 1 (NPM1) within cytoplasm, thereby suppressing the transcription of IQ motif containing the GTPase-activating protein 2 (IQGAP2), subsequently activating the AKT-mTOR signaling, ultimately fostering tumor progression and lipid accumulation. In conclusion, the present study highlights the robust prognostic significance of ALDH9A1 and delivers a comprehensive understanding of ALDH9A1-NPM1-IQGAP2-AKT axis in ccRCC. These findings established a solid research foundation for novel therapeutic strategies for ccRCC patients.
Neuro-ophthalmic evaluation and management of pituitary disease
Authors: Wang Michael T. M. , Meyer Juliette A. , Danesh-Meyer Helen V. 
Published: July 2024

AbstractNeuro-ophthalmic evaluation is a crucial component of the diagnostic and prognostic assessment of pituitary disease and compressive chiasmopathy, and can inform the timing of vision-restoring tumour resection surgery. The most common disease affecting the pituitary with neuro-ophthalmic implications are pituitary adenomas. Neuro-ophthalmic manifestations include decreased vision, abnormal colour vision and impaired visual field or diplopia. The recognition of these syndromes is critical to achieve early diagnosis and treatment and to improve prognosis. The pattern of vision loss in chiasmal compression is determined by the anatomical relationship between the pituitary lesion and optic chiasm, and potential visual field defects include bitemporal deficits, junctional scotomas, monocular cecocentral defects, and incongruous homonymous hemianopias. Rarer neuro-ophthalmic manifestations of pituitary disease include ophthalmoplegia, nystagmus, and obstructive hydrocephalus. There is growing evidence that demonstrates the strong diagnostic utility of optical coherence tomography (OCT) parameters in detecting the presence of compressive chiasmopathy, as well as the prognostic ability to predict the rate and degree of visual recovery following decompression surgery. Long-term neuro-ophthalmic monitoring is critical for detecting delayed vision loss following resection surgery, which may represent tumour recurrence or secondary complications.
Vasopressin and cardiovascular autonomic adjustment in chronic hypertensive pregnancy
Authors: Jovanović Mirjana , Stevanović Bojana , Pajović Vladislav , Tasić Tatjana , Lozić Maja , Đukić Ljiljana , Kosić Marija , Murphy David , Japundžić-Žigon Nina 
Published: July 2024

AbstractChronic hypertensive pregnancy (CHP) is a growing health issue with unknown etiology. Vasopressin (VP), a nonapeptide synthesized in paraventricular (PVN) and supraoptic nucleus (SON), is a well-known neuroendocrine and autonomic modulator of the cardiovascular system, related to hypertension development. We quantified gene expression of VP and its receptors, V1aR and V1bR, within the PVN and SON in CHP and normal pregnancy, and assessed levels of secreted plasma VP. Also, we evaluated autonomic cardiovascular adaptations to CHP using spectral indices of blood pressure (BPV) and heart rate (HRV) short-term variability, and spontaneous baroreflex sensitivity (BRS). Experiments were performed in female spontaneously hypertensive rats (SHRs) and in normotensive Wistar rats (WRs). Animals were equipped with a radiotelemetry probe for continuous hemodynamic recordings before and during pregnancy. BPV, HRV and BRS were assessed using spectral analysis and the sequence method, respectively. Plasma VP was determined by ELISA whilst VP, V1aR, and V1bR gene expression was analyzed by real-time-quantitative PCR (RT-qPCR). The results show that non-pregnant SHRs exhibit greater VP, V1aR, and V1bR gene expression in both PVN and SON respectively, compared to Wistar dams. Pregnancy decreased VP gene expression in the SON of SHRs but increased it in the PVN and SON of WRs. Pregnant SHRs exhibited a marked drop in plasma VP concentration associated with BP normalization. This triggered marked tachycardia, heart rate variability increase, and BRS increase in pregnant SHRs. It follows that regardless of BP normalization in late pregnancy, SHRs exhibit cardiovascular vulnerability and compensate by recruiting vagal mechanisms.
Protective alleles and precision healthcare in crewed spaceflight
Authors: Rutter Lindsay A. , MacKay Matthew J. , Cope Henry , Szewczyk Nathaniel J. , Kim JangKeun , Overbey Eliah , Tierney Braden T. , Muratani Masafumi , Lamm Ben , Bezdan Daniela , Paul Amber M. , Schmidt Michael A. , Church George M. , Giacomello Stefania , Mason Christopher E. 
Published: July 2024

AbstractCommon and rare alleles are now being annotated across millions of human genomes, and omics technologies are increasingly being used to develop health and treatment recommendations. However, these alleles have not yet been systematically characterized relative to aerospace medicine. Here, we review published alleles naturally found in human cohorts that have a likely protective effect, which is linked to decreased cancer risk and improved bone, muscular, and cardiovascular health. Although some technical and ethical challenges remain, research into these protective mechanisms could translate into improved nutrition, exercise, and health recommendations for crew members during deep space missions.
An integrated atom array-nanophotonic chip platform with background-free imaging
Authors: Menon Shankar G. , Glachman Noah , Pompili Matteo , Dibos Alan , Bernien Hannes 
Published: July 2024

AbstractArrays of neutral atoms trapped in optical tweezers have emerged as a leading platform for quantum information processing and quantum simulation due to their scalability, reconfigurable connectivity, and high-fidelity operations. Individual atoms are promising candidates for quantum networking due to their capability to emit indistinguishable photons that are entangled with their internal atomic states. Integrating atom arrays with photonic interfaces would enable distributed architectures in which nodes hosting many processing qubits could be efficiently linked together via the distribution of remote entanglement. However, many atom array techniques cease to work in close proximity to photonic interfaces, with atom detection via standard fluorescence imaging presenting a major challenge due to scattering from nearby photonic devices. Here, we demonstrate an architecture that combines atom arrays with up to 64 optical tweezers and a millimeter-scale photonic chip hosting more than 100 nanophotonic cavities. We achieve high-fidelity ( ~ 99.2%), background-free imaging in close proximity to nanofabricated cavities using a multichromatic excitation and detection scheme. The atoms can be imaged while trapped a few hundred nanometers above the dielectric surface, which we verify using Stark shift measurements of the modified trapping potential. Finally, we rearrange atoms into defect-free arrays and load them simultaneously onto the same or multiple devices.
Influence of Nb/V on the corrosion behavior of high-strength anti-seismic rebar in marine environments
Authors: Zeng Zeyun , Gu Shangjun , Wang Jie , Wei Fulong , Li Zhiying , Yang Hui , Li Changrong 
Published: July 2024

AbstractIn this study, the immersion test, surface analysis, cross-section analysis, quantitative analysis and electrochemical analysis were used to study the influence of Nb/V on the corrosion behavior of high-strength anti-seismic rebar in marine environments. The corrosion results clarified that the addition of Nb/V improved the corrosion resistance of the rebar, thereby reducing the corrosion rate of the rebar and improving the stability of corrosion layers. Firstly, the addition of Nb/V promoted the transformation of unstable Fe oxyhydroxides to stable Fe oxyhydroxides in the surface corrosion layers of the rebar, thus increasing the α/(β + γ) ratio, corrosion potential and total impedance value. Secondly, the addition of Nb/V induced the formation of Nb oxides and V oxides in the surface corrosion layers of the rebar, and the existence of these oxides repaired the surface defects of corrosion layers, thus enhancing the corrosion resistance performance of surface corrosion layers of the rebar.
Magnetic-field-driven targeting of exosomes modulates immune and metabolic changes in dystrophic muscle
Authors: Villa Chiara , Secchi Valeria , Macchi Mirco , Tripodi Luana , Trombetta Elena , Zambroni Desiree , Padelli Francesco , Mauri Michele , Molinaro Monica , Oddone Rebecca , Farini Andrea , De Palma Antonella , Varela Pinzon Laura , Santarelli Federica , Simonutti Roberto , Mauri PierLuigi , Porretti Laura , Campione Marcello , Aquino Domenico , Monguzzi Angelo , Torrente Yvan 
Published: July 2024

AbstractExosomes are promising therapeutics for tissue repair and regeneration to induce and guide appropriate immune responses in dystrophic pathologies. However, manipulating exosomes to control their biodistribution and targeting them in vivo to achieve adequate therapeutic benefits still poses a major challenge. Here we overcome this limitation by developing an externally controlled delivery system for primed annexin A1 myo-exosomes (Exomyo). Effective nanocarriers are realized by immobilizing the Exomyo onto ferromagnetic nanotubes to achieve controlled delivery and localization of Exomyo to skeletal muscles by systemic injection using an external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exomyo from these ferromagnetic nanotubes in vivo to synergistically promote beneficial muscle responses in a murine animal model of Duchenne muscular dystrophy. Our findings provide insights into the development of exosome-based therapies for muscle diseases and, in general, highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution.
Contextual AI models for single-cell protein biology
Authors: Li Michelle M. , Huang Yepeng , Sumathipala Marissa , Liang Man Qing , Valdeolivas Alberto , Ananthakrishnan Ashwin N. , Liao Katherine , Marbach Daniel , Zitnik Marinka 
Published: July 2024

AbstractUnderstanding protein function and developing molecular therapies require deciphering the cell types in which proteins act as well as the interactions between proteins. However, modeling protein interactions across biological contexts remains challenging for existing algorithms. Here we introduce PINNACLE, a geometric deep learning approach that generates context-aware protein representations. Leveraging a multiorgan single-cell atlas,PINNACLElearns on contextualized protein interaction networks to produce 394,760 protein representations from 156 cell type contexts across 24 tissues.PINNACLE’s embedding space reflects cellular and tissue organization, enabling zero-shot retrieval of the tissue hierarchy. Pretrained protein representations can be adapted for downstream tasks: enhancing 3D structure-based representations for resolving immuno-oncological protein interactions, and investigating drugs’ effects across cell types.PINNACLEoutperforms state-of-the-art models in nominating therapeutic targets for rheumatoid arthritis and inflammatory bowel diseases and pinpoints cell type contexts with higher predictive capability than context-free models.PINNACLE’s ability to adjust its outputs on the basis of the context in which it operates paves the way for large-scale context-specific predictions in biology.
BNP-Track: a framework for superresolved tracking
Authors: Sgouralis Ioannis , Xu Lance W. Q. , Jalihal Ameya P. , Kilic Zeliha , Walter Nils G. , Pressé Steve 
Published: July 2024

AbstractSuperresolution tools, such as PALM and STORM, provide nanoscale localization accuracy by relying on rare photophysical events, limiting these methods to static samples. By contrast, here, we extend superresolution to dynamics without relying on photodynamics by simultaneously determining emitter numbers and their tracks (localization and linking) with the same localization accuracy per frame as widefield superresolution on immobilized emitters under similar imaging conditions (≈50 nm). We demonstrate our Bayesian nonparametric track (BNP-Track) framework on both in cellulo and synthetic data. BNP-Track develops a joint (posterior) distribution that learns and quantifies uncertainty over emitter numbers and their associated tracks propagated from shot noise, camera artifacts, pixelation, background and out-of-focus motion. In doing so, we integrate spatiotemporal information into our distribution, which is otherwise compromised by modularly determining emitter numbers and localizing and linking emitter positions across frames. For this reason, BNP-Track remains accurate in crowding regimens beyond those accessible to other single-particle tracking tools.
Structural and mechanistic insights into Streptococcus pneumoniae NADPH oxidase
Authors: Dubach Victor R. A. , San Segundo-Acosta Pablo , Murphy Bonnie J. 
Published: July 2024

AbstractNicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) have a major role in the physiology of eukaryotic cells by mediating reactive oxygen species production. Evolutionarily distant proteins with the NOX catalytic core have been found in bacteria, including Streptococcus pneumoniae NOX (SpNOX), which is proposed as a model for studying NOXs because of its high activity and stability in detergent micelles. We present here cryo-electron microscopy structures of substrate-free and nicotinamide adenine dinucleotide (NADH)-bound SpNOX and of NADPH-bound wild-type and F397A SpNOX under turnover conditions. These high-resolution structures provide insights into the electron-transfer pathway and reveal a hydride-transfer mechanism regulated by the displacement of F397. We conducted structure-guided mutagenesis and biochemical analyses that explain the absence of substrate specificity toward NADPH and suggest the mechanism behind constitutive activity. Our study presents the structural basis underlying SpNOX enzymatic activity and sheds light on its potential in vivo function.
Chromosome-level genome assembly and sex chromosome identification of the pink stem borer, Sesamia inferens (Lepidoptera: Noctuidae)
Authors: Yu Xiao-Rui , Chen Xu , Bai Qing-Rong , Mu Ming-Yue , Tang Liang-De , Smagghe Guy , Zang Lian-Sheng 
Published: July 2024

AbstractThe pink stem borer, Sesamia inferens Walker (Lepidoptera: Noctuidae), is one of the most notorious pest insects of rice and maize crops in the world. Here, we generated a high-quality chromosome-level genome assembly of S. inferens, using a combination of Illumina, PacBio HiFi and Hi-C technologies. The total assembly size was 973.18 Mb with a contig N50 of 33.39 Mb, anchored to 31 chromosomes, revealing a karyotype of 30 + Z. The BUSCO analysis indicated a high completeness of 98.90% (n = 5286), including 5172 (97.8%) single-copy BUSCOs and 58 (1.1%) duplicated BUSCOs. The genome contains 58.59% (564.58 Mb) repeat elements and 26628 predicted protein-coding genes. The chromosome-level genome assembly of S. inferens provides in-depth knowledge and will be a helpful resource for the Lepidoptera and pest control research communities.