bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOE4alters the lipid droplet proteome and modulates droplet dynamics
Authors: Friday Cassi M. , Stephens Isaiah O. , Smith Cathryn T. , Lee Sangderk , Satish Diksha , Devanney Nicholas A. , Cohen Sarah , Morganti Josh M. , Gordon Scott M. , Johnson Lance A. 
Published: December 2024

ABSTRACTExcess lipid droplet (LD) accumulation is associated with several pathological states, including Alzheimer’s disease (AD). However, the mechanism(s) by which changes in LD composition and dynamics contribute to pathophysiology of these disorders remains unclear. Apolipoprotein E (ApoE) is a droplet associated protein with a common risk variant (E4) that confers the largest increase in genetic risk for late-onset AD. E4 is associated with both increased neuroinflammation and excess LD accumulation. In the current study, we sought to quantitatively profile the lipid and protein composition of LDs between the ‘neutral’ E3 and risk variant E4, to gain insight into potential LD-driven contributions to AD pathogenesis. Targeted replacement mice expressing human E3 or E4 were injected with saline or lipopolysaccharide (LPS), and after 24 hours, hepatic lipid droplets were isolated for proteomic and lipidomic analyses. Lipidomics revealed a shift in the distribution of glycerophospholipids in E4 LDs with a concomitant increase in phosphatidylcholine species, and overall, the baseline profile of E4 LDs resembled that of the LPS-treated groups. Quantitative proteomics showed that LDs from E4 mice are enriched for proteins involved in protein/vesicle transport but have decreased levels of proteins involved in fatty acid β-oxidation. Interestingly, proteins associated with LDs showed substantial overlap with previously published lists of AD postmortem tissue and microglia ‘omics studies, suggesting a potential role for LDs in modulating AD risk or progression. Given this, we exposed primary microglia from the same E3 or E4 mice to exogenous lipid, inflammatory stimulation, necroptotic N2A cells (nN2A), or a combination of treatments to evaluate LD formation and its impact on the cells’ immune state. Microglia from E4 mice accumulated more LDs in every condition tested – at baseline and following addition of fatty acids, LPS stimulation, or nN2As. E4 microglia also secreted significantly more cytokines (TNF, IL-1β, IL-10) than E3 microglia in the control, oleic acid, and nN2A treatment conditions, yet showed a blunted response to LPS. In sum, these results suggest that E4 microglia accumulate more LDs compared to E3 microglia and that E4 is associated with a basal LD composition that resembles a pro-inflammatory cell. Together with the high overlap of the LD proteome with established AD-associated datasets, these data further support the idea that alterations in LD dynamics, particularly within microglia, may contribute to the increased risk for AD associated withAPOE4.
Vascular endothelial growth factor-D improves lung vascular integrity during acute lung injury
Authors: Yuan Yifan , Sharma Lokesh , Tang Wenwen , Yoon Yongdae , Kirk Shannon , Raredon Micha Sam Brickman , Ahangari Farida , Khoury Johad , Hong Qian , Luan Yi , Yuan Qianying , Lujia Chen , Ke Yunbo , Birukov Konstantin G , Simons Michael , Wu Dianqing (Dan) , Niklason Laura E , Kaminski Naftali 
Published: December 2024

AbstractDisorders in pulmonary vascular integrity are a prominent feature in many lung diseases. Paracrine signaling is highly enriched in the lung and plays a crucial role in regulating vascular homeostasis. However, the specific local cell-cell crosstalk signals that maintain pulmonary microvascular stability in adult animals and humans remain largely unexplored. In this study, we employed single-cell RNA-sequencing (scRNAseq)-based computational pipelines to systematically profile ligand-receptor (L/R) interactions within the lung microvascular niche and identified vascular endothelial growth factor-D (VEGF-D) as a key local factor with previously unrecognized barrier-protective properties in models of acute lung injury. Our scRNAseq data revealed that, under physiological conditions, soluble L/R interactions between mesenchymal cells, in particular alveolar fibroblast, and microvascular endothelial cells are predominantly associated with pathways involved in maintaining vascular integrity as compared to all other cells. Upon treatment with top identified ligands, we found that VEGF-D significantly enhanced endothelial barrier function and conferred protection against inflammatory challenges induced by tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and thrombin. This barrier-protective effect of VEGF-D was significantly attenuated by inhibition of VEGFR2, either through siRNA knockdown or pharmacological blockade using specific VEGFR2 inhibitors. Intravenous administration of recombinant VEGF-D in lipopolysaccharides (LPS)-induced acute lung injury models significantly reduced vascular permeability (7339 ± 2510 (LPS) v.s. 5350 ± 1821 (LPS + VEGF-D),p< 0.05), immune cell infiltration (0.791 ± 0.199 x 106WBC/mL (LPS) v.s. 0.540 ± 0.190 x 106WBC/mL (LPS + VEGF-D),p< 0.01), and the expression of pro-inflammatory markers TNF-α and IL-6 in the lung tissue. This effect was abolished inVEGFR2iECKOmice, confirming that VEGF-D mediates its effects via VEGFR2-dependent signaling. This study demonstrates an unexpected protective role for VEGF-D in promoting lung endothelial barrier integrity and suggests that paracrine signaling from the alveolar fibroblast niche contributes critically to lung capillary homeostasis.
Multiscale analysis and functional validation of the cellular and genetic determinants of skeletal disease
Authors: Chai Ryan C. , Lundberg Mischa , Freudenthal Bernard , Smith James T. , Boughton Andrew P. , Zhang Yuandan , Flynn Kaitlyn A. , Frysz Monika , Corr Alexander P. , Khoo Weng Hua , Komla-Ebri Davide , Dack Michael R.G. , Guilfoyle Siobhan E. , Logan John G. , Butterfield Natalie C. , Leitch Victoria D. , Pollard Andrea S. , Mäkitie Riikka E. , McDonald Michelle M. , Youlten Scott E. , Sergio C. Marcelo , Evans David M. , Powell Joseph E. , de Leeuw Christiaan A. , Ewing Adam D. , Eisman John A. , Blank Robert D. , Phan Tri Giang ,   International Federation of Musculoskeletal Research Societies (IFMRS) Big Data Working Group, Baldock Paul A. , Duncan Emma L. , Williams Graham R. , Bassett J. H. Duncan , Croucher Peter I. , Kemp John P. 
Published: December 2024

AbstractMusculoskeletal diseases are a major global health burden. Development of new bone-active therapies is hindered by limited understanding of the complex interactions between the cells and genes that regulate the skeleton. To unravel this complexity, we systematically annotated all cells in bone and defined the genes that control their function at single-cell resolution. Integration with data from human gene-mapping studies of rare skeletal disorders and common skeletal disease traits identified novel disease genes, which we validated by functional analysis in more than one thousand genetic mouse models. This multiscale approach expands the repertoire of cells that regulate bone to include endothelial and vascular smooth muscle cells. This also revealed hundreds of skeletal disease-associated genes in this landscape of cells as potential drug targets. The cellular and genetic mechanisms revealed by this approach overcomes knowledge gaps and helps to accelerate development of next generation therapies to treat skeletal diseases.
Evidence for white matter intrinsic connectivity networks at rest and during a task: a large-scale study and templates
Authors: Itkyal Vaibhavi , Iraji Armin , Jensen Kyle M. , LaGrow Theodore J. , Duda Marlena , Turner Jessica A. , Liu Jingyu , Wu Lei , Du Yuhui , Fries Jill , Fu Zening , Kochunov Peter , Belger A , Ford J M , Mathalon D H , Pearlson G D , Potkin S G , Preda A , van Erp T G M , Yang K , Sawa A , Hutchison K , Osuch E A , Theberge Jean , Abbott C , Mueller B A , Chen Jiayu , Sui J , Adali Tulay , Calhoun Vince D. 
Published: December 2024

AbstractUnderstanding white matter (WM) functional connectivity is crucial for unraveling brain function and dysfunction. In this study, we present a novel WM intrinsic connectivity network (ICN) template derived from over 100,000 fMRI scans, identifying 97 robust WM ICNs using spatially constrained independent component analysis (scICA). This WM template, combined with a previously identified gray matter (GM) ICN template from the same dataset, was applied to analyze a resting-state fMRI (rs-fMRI) dataset from the Bipolar-Schizophrenia Network on Intermediate Phenotypes 2 (BSNIP2; 590 subjects) and a task-based fMRI dataset from the MIND Clinical Imaging Consortium (MCIC; 75 subjects). Our analysis highlights distinct spatial maps for WM and GM ICNs, with WM ICNs showing higher frequency profiles. Modular structure within WM ICNs and interactions between WM and GM modules were identified. Task-based fMRI revealed event-related BOLD signals in WM ICNs, particularly within the corticospinal tract, lateralized to finger movement. Notable differences in static functional network connectivity (sFNC) matrices were observed between controls (HC) and schizophrenia (SZ) subjects in both WM and GM networks. This open-source WM NeuroMark template and automated pipeline offer a powerful tool for advancing WM connectivity research across diverse datasets.
Adaptive decision-making by ants in response to past, imminent, and predicted adversity
Authors: Notomi Yusuke , Dobata Shigeto , Kazawa Tomoki , Maezawa So , Namiki Shigehiro , Kanzaki Ryohei , Haupt Stephan Shuichi 
Published: December 2024

ABSTRACTMany animals exhibit innate behaviours, which are often interpreted as hard-wired, reflex-like responses, particularly in insects. Among these behaviours, beacon-aiming—an approach towards dark areas or objects—is observed in many animals; however, its functional significance remains unclear, and some ant species do not exhibit it. Here we show that in one such species,Camponotus japonicus,the behaviour was triggered only under adverse substrate conditions, such as during the crossing of liquid-covered surfaces, regardless of the locomotor patterns like walking or swimming, or the mere presence of water, or when walking upside-down. Once initiated, beacon-aiming persists even under normal substrate conditions, as demonstrated by ants transitioning from water-covered to dry substrates suitable for comfortable walking. This behavioural flexibility indicates that the innate behaviour is not hard-wired but modulated by internal states. Furthermore, changes in internal states may serve adaptive decision-making, potentially allowing ants to prepare for future adverse conditions. The isolated ants on a water-surrounded platform gradually established an attraction to the direction of the beacon before ultimately swimming towards it. These findings suggest that beacon-aiming is regulated by internal states, especially anxiety-like states formed in response to past, imminent, and predicted adverse substrate conditions in ants.
The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing
Authors: Fowler Colin E. , O’Hearn Natalie A. , Salus Griffin J. , Singh Arundeep , Boutz Paul L. , Lees Jacqueline A. 
Published: December 2024

SummaryProtein arginine methyltransferase 5 (PRMT5) is a promising cancer target, yet it’s unclear which PRMT5 roles underlie this vulnerability. Here, we establish that PRMT5 inhibition induces a special class of unspliced introns, called detained introns (DIs). To interrogate the impact of DIs, we depleted CLNS1A, a PRMT5 cofactor that specifically enables Sm protein methylation. We found that many, but not all, cell lines are CLNS1A-dependent and established that loss of viability is linked to loss of Sm protein methylation and DI upregulation. Finally, we discovered that PRMT5-regulated DIs, and the impacted genes, are highly conserved across human, and also mouse, cell lines but display little interspecies conservation. Despite this, human and mouse DIs have convergent impacts on proliferation by affecting essential components of proliferation-regulating complexes. Together, these data argue that the PRMT5-splicing axis, including appropriate DI splicing, underlies cancer’s vulnerability to PRMT5 inhibitors.
The clumped isotope signatures of multiple methanogenesis metabolisms
Authors: Li Jiawen , Ash Jeanine L. , Cobban Alec , Kubik Briana C. , Rizzo Gabriella , Thompson Mia , Guibourdenche Laetitia , Berger Stefanie , Morra Kaycee , Lin Ying , Mueller Elliott P. , Masterson Andrew L. , Stein Rebekah , Fogel Marilyn , Torres Mark A. , Feng Xiahong , Holden James F. , Martini Anna , Welte Cornelia U. , Jetten Mike , Young Edward D. , Leavitt William D. 
Published: December 2024

AbstractMethane is a potent greenhouse gas, an important energy source, and a potential biosignature on extraterrestrial planetary bodies. The relative abundances of doubly substituted (“clumped”) methane isotopologues (13CH3D and12CH2D2) offer important information on the sources and sinks of methane. However, the clumped isotope signatures of microbially produced methane from different methanogenic pathways lack a systematic investigation. In this study, we provide a dataset encompassing the relative isotopologue abundances produced by hydrogenotrophic, methylotrophic, acetoclastic, and methoxydotrophic methanogenesis. We find that a statistical “combinatorial effect” generates significant differences in12CH2D2compositions between hydrogenotrophic methanogenesis and other pathways. The thermodynamic drive of methanogenic reactions and phylogenetic affiliation may also influence the isotope compositions of methane. Our study provides new experimental constraints on the isotope signatures of different microbial methanogenic pathways, and evidence of the mechanisms responsible for the observed differences.TeaserA novel stable isotope tool to track and differentiate sources of biological methane.
Establishment of a Chikungunya virus pseudotype system strictly dependent on viral protein expression
Authors: Tanaka Atsushi , Miyazawa Takayuki 
Published: December 2024

AbstractChikungunya virus (CHIKV) is an enveloped RNA virus that causes Chikungunya fever in humans. It is classified into the arboviruses (arthropod-borne viruses) and is transmitted by mosquitoes. Therefore, mosquitoes can replicate many types of cells derived from mammals or insects. In this study, we tried to establish the widely useable Chikungunya virus pseudotype-system adapting various viral species, and we demonstrated the production of Chikungunya pseudotype virus baring the envelope protein from two different viral families, Coronaviridae or Rhabdoviridae i.e., severe acute respiratory syndrome coronavirus 2 spike protein (CoV-2-S) or vesicular stomatitis virus glycoprotein (VSV-G), respectively. We found that the capsid protein of Chikungunya virus is not always necessary in the formation of Chikungunya virus-based pseudotypes, but that the capsid protein increases the efficiency of expression of the sub-genomic RNA which codes the labeled genes. Our established pseudotype virus-producing system supplied a sufficient titer of virions for application to most virological experiments that showed more than 104focus forming units (FFU)/ml. The pseudotype infections were strictly dependent on compatibility between the viral envelope protein and its receptor and there was no false-positive background infection. Our established pseudotype virus system can be used as a robust platform to study various virus infections and for screening and in-depth evaluation of neutralizing antibodies and antiviral agents.
Suppression of meiotic crossovers in pericentromeric heterochromatin requires synaptonemal complex and meiotic recombination factors inDrosophila melanogaster
Authors: Pazhayam Nila M. , Sagar Sasha , Sekelsky Jeff 
Published: December 2024

AbstractThe centromere effect (CE) is a meiotic phenomenon that ensures meiotic crossover suppression in pericentromeric regions. Despite being a critical safeguard against nondisjunction, the mechanisms behind the CE remain unknown. Previous studies have shown that various regions of theDrosophilapericentromere, encompassing proximal euchromatin, beta and alpha heterochromatin, undergo varying levels of crossover suppression, raising the question of whether distinct mechanisms establish the CE in these different regions. To address this question, we asked whether different pericentromeric regions respond differently to mutations that impair various features that may play a role in the CE. In flies with a mutation that affects the synaptonemal complex (SC), a structure is hypothesized to have important roles in recombination and crossover patterning, we observed a significant redistribution of pericentromeric crossovers from proximal euchromatin towards beta heterochromatin but not alpha heterochromatin, indicating a role for the SC in suppressing crossovers in beta heterochromatin. In flies mutant formei-218orrec, which encode components of a critical pro-crossover complex, there was a more extreme redistribution of pericentromeric crossovers towards both beta and alpha heterochromatin, suggesting an important role for these meiotic recombination factors in suppressing heterochromatic crossovers. Lastly, we mapped crossovers in flies mutant forSu(var)3-9. Although we expected a strong alleviation of crossover suppression in heterochromatic regions, no changes in pericentromeric crossover distribution were observed in this mutant, indicating that this vital heterochromatin factor is dispensable to prevent crossovers in heterochromatin. Our results indicate that the meiotic machinery plays a bigger role in suppressing crossovers than the chromatin state.
Three-coupled-channel analysis of
Zc(3900)
involving
DD¯*
,
πJ/ψ
, and
ρηc
Authors: Yu Kang , Wang Guang-Juan , Wu Jia-Jun , Yang Zhi 
Published: December 2024

In this work, we conduct a three-coupled-channel analysis of the Zc(3900) structure, focusing on the DD¯*, J/ψπ, and ρηc channels, based on the one-boson exchange model. Drawing from previous study on the exotic state Tcc, we only utilize one more parameter to construct the interactions between the channels. Our model successfully reproduces the experimental line shapes of the invariant mass distribution at s=4.23 and 4.26 GeV for the three channels. Additionally, the finite-volume energy levels in our model show agreement with current lattice QCD conclusion. Detailed analysis suggests that the Zc(3900) peaks in the πJ/ψ and ρηc distributions primarily arise from the triangle loop involving the D1D¯D* intermediate system. In the DD¯* distribution, the threshold peak is generated by the cascade decay mechanism enhanced by a triangle diagram. Moreover, we find a virtual pole located far from the threshold, indicating that Zc(3900) peaks are not associated with a physical pole. We conclude that the Zc(3900) peaks are predominantly caused by the threshold cusp.

Published by the American Physical Society
2024
Structure and protective effect of aluminium coated Nd-Fe-B magnets before and after grain boundary diffusion
Authors: Zhang Xianghao , Dong Bicheng , Zhang Weiyuan , Yu Guoxin , Ma Dongwei , Hu Zhihua 
Published: December 2024

Purpose
The structure and protective effect of Al-coated Nd-Fe-B magnets before and after grain boundary diffusion were studied to explore the feasibility of improving the corrosion resistance of Nd-Fe-B magnets by Al coating and Al grain boundary diffusion.

Design/methodology/approach
The Al coating was deposited on sintered Nd-Fe-B magnets by magnetron sputtering, and then the Al-coated Nd-Fe-B magnets were put into the vacuum tube furnace for grain boundary diffusion process. The influence of Al coating and grain boundary diffusion process on the corrosion resistance of Nd-Fe-B magnets was investigated using electrochemical tests.

Findings
Results showed that the Al coating thickness increases, the corrosion current density of Al-coated magnets first increases and then decreases with increasing coating time. The Al coating particles transform from small millet shaped particles to equiaxed polygonal particles, and finally to big millet shaped particles with increasing coating time. The diffusion temperature has little effect on the corrosion potential, and the corrosion current density of Al-diffused magnets after grain boundary diffusion is much higher than that of Al-coated magnets before grain boundary diffusion. The corrosion potential and corrosion current density of magnets first increase, and then decrease with increasing tempering temperature.

Originality/value
As for high intrinsic coercivity Nd-Fe-B magnets, Poor preparation of Al coatings can result in Al coatings lacking protective properties, and the Al coating should be used cautiously as the surface protective coating of magnets. Grain boundary diffusion leads to the disappearance of Al coating, and reduces the corrosion resistance of Nd-Fe-B magnets, while tempering treatment can improve the corrosion resistance of Al-diffused magnets.
Inductance calculation of high lift motor prototype for all-electric aircraft
Authors: Shang Maixia , Liu Jinglin , Li Mengqi , Chai Xiaobao 
Published: December 2024

Purpose
The purpose of this paper is to present the performance requirements for the all-electric high lift motors and the inductance calculation process for the fractional slot concentrated winding.

Design/methodology/approach
This paper presents the research work related to all-electric aircraft high lift motors and the inductance calculation process of fractional slot concentrated winding. Firstly, this paper introduces the performance requirements for the high lift motor and summarizes the general process for calculating the inductance in fractional slot motors. Secondly, the analytical model of winding armature total inductance is obtained by the winding function method. Thirdly, a straightforward calculation method is employed for determining the total slot leakage inductance. Finally, the accuracy of the inductance calculation and controllability of the motor are confirmed through finite element model and motor control strategies.

Findings
In the fractional slot concentrated winding, the armature total inductance is equal to the armature self-inductance plus the armature mutual inductance. The slot leakage inductance is divided into the slot leakage self-inductance and the slot leakage mutual inductance. This allows inductance to be obtained quickly without finite element model.

Originality/value
This paper provides the inductance results of analytical and finite element simulation; the control strategy is employed to verify the conformity of the design requirements and control performance under the rated conditions. The implementation of double verification assures the practicality and effectiveness of the high lift motor.