bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long non-coding RNA maternally expressed gene 3, miR-125a-5p, CXCL13, and NF-kB in patients with immune thrombocytopenia
Authors: Naguib Mervat , El Sawy Shereen , Rashed Laila , AlHelf Maha , Abdelgwad Marwa 
Published: April 2023

AbstractThe main aim of this study was to assess the expression level of circulating long non-coding RNA maternally expressed gene 3 (lncRNA-MEG3), microRNA (miR-125a-5P), the chemokine C-X-C motif ligand13 (CXCL13), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in immune thrombocytopenia (ITP) cases and to study its relation to the disease severity and treatment response. This case-control study included 45 patients newly diagnosed as ITP and 45 healthy subjects. We assessed complete blood count, antinuclear antibodies, hepatitis B and C virus serology, lncRNA-MEG3, miR-125a-5P, and CXCL13 expression in serum by real-time PCR and NF-kb protein by ELISA. In ITP patients compared to control, lncRNA-MEG3 was significantly increased, and miRNA-125a-5P was decreased, and this was associated with higher CXCL13 and NF-kB levels (P < 0.001, for all).There was a significant negative correlation between platelet count and lncRNA-MEG3, CXCL13, and NF-kb, while a positive correlation with miR-125a-5p in ITP patients. Patients who responded to steroids had significantly higher miR-125a-5p (P = 0.016) and significantly lower lncRNA-MEG3 (P < 0.001), CXCL13 (P = 0.005), and NF-kb (p = 0.002). Based on the ROC curves, lncRNA-MEG3 displayed the highest area under the curve (AUC) in the identification of organ bleeding (AUC = 0.805), the response to steroids (AUC = 0.853), and the need for splenectomy (AUC = 0.75).
Superfluid response of an atomically thin gate-tuned van der Waals superconductor
Authors: Jarjour Alexander , Ferguson G. M. , Schaefer Brian T. , Lee Menyoung , Loh Yen Lee , Trivedi Nandini , Nowack Katja C. 
Published: April 2023

AbstractA growing number of two-dimensional superconductors are being discovered in the family of exfoliated van der Waals materials. Due to small sample volume, the superfluid response of these materials has not been characterized. Here, we use a local magnetic probe to directly measure this key property of the tunable, gate-induced superconducting state in MoS2. We find that the backgate changes the transition temperature non-monotonically whereas the superfluid stiffness at low temperature and the normal state conductivity monotonically increase. In some devices, we find direct signatures in agreement with a Berezinskii-Kosterlitz-Thouless transition, whereas in others we find a broadened onset of the superfluid response. We show that the observed behavior is consistent with disorder playing an important role in determining the properties of superconducting MoS2. Our work demonstrates that magnetic property measurements are within reach for superconducting devices based on exfoliated sheets and reveals that the superfluid response significantly deviates from simple BCS-like behavior.
The RNA-binding protein landscapes differ between mammalian organs and cultured cells
Authors: Perez-Perri Joel I. , Ferring-Appel Dunja , Huppertz Ina , Schwarzl Thomas , Sahadevan Sudeep , Stein Frank , Rettel Mandy , Galy Bruno , Hentze Matthias W. 
Published: April 2023

AbstractSystem-wide approaches have unveiled an unexpected breadth of the RNA-bound proteomes of cultured cells. Corresponding information regarding RNA-binding proteins (RBPs) of mammalian organs is still missing, largely due to technical challenges. Here, we describe ex vivo enhanced RNA interactome capture (eRIC) to characterize the RNA-bound proteomes of three different mouse organs. The resulting organ atlases encompass more than 1300 RBPs active in brain, kidney or liver. Nearly a quarter (291) of these had formerly not been identified in cultured cells, with more than 100 being metabolic enzymes. Remarkably, RBP activity differs between organs independent of RBP abundance, suggesting organ-specific levels of control. Similarly, we identify systematic differences in RNA binding between animal organs and cultured cells. The pervasive RNA binding of enzymes of intermediary metabolism in organs points to tightly knit connections between gene expression and metabolism, and displays a particular enrichment for enzymes that use nucleotide cofactors. We describe a generically applicable refinement of the eRIC technology and provide an instructive resource of RBPs active in intact mammalian organs, including the brain.
Peripersonal encoding of forelimb proprioception in the mouse somatosensory cortex
Authors: Alonso Ignacio , Scheer Irina , Palacio-Manzano Mélanie , Frézel-Jacob Noémie , Philippides Antoine , Prsa Mario 
Published: April 2023

AbstractConscious perception of limb movements depends on proprioceptive neural responses in the somatosensory cortex. In contrast to tactile sensations, proprioceptive cortical coding is barely studied in the mammalian brain and practically non-existent in rodent research. To understand the cortical representation of this important sensory modality we developed a passive forelimb displacement paradigm in behaving mice and also trained them to perceptually discriminate where their limb is moved in space. We delineated the rodent proprioceptive cortex with wide-field calcium imaging and optogenetic silencing experiments during behavior. Our results reveal that proprioception is represented in both sensory and motor cortical areas. In addition, behavioral measurements and responses of layer 2/3 neurons imaged with two-photon microscopy reveal that passive limb movements are both perceived and encoded in the mouse cortex as a spatial direction vector that interfaces the limb with the body’s peripersonal space.
Single-shot isotropic differential interference contrast microscopy
Authors: Wang Xinwei , Wang Hao , Wang Jinlu , Liu Xingsi , Hao Huijie , Tan You Sin , Zhang Yilei , Zhang He , Ding Xiangyan , Zhao Weisong , Wang Yuhang , Lu Zhengang , Liu Jian , Yang Joel K. W. , Tan Jiubin , Li Haoyu , Qiu Cheng-Wei , Hu Guangwei , Ding Xumin 
Published: April 2023

AbstractDifferential interference contrast (DIC) microscopy allows high-contrast, low-phototoxicity, and label-free imaging of transparent biological objects, and has been applied in the field of cellular morphology, cell segmentation, particle tracking, optical measurement and others. Commercial DIC microscopy based on Nomarski or Wollaston prism resorts to the interference of two polarized waves with a lateral differential offset (shear) and axial phase shift (bias). However, the shear generated by these prisms is limited to the rectilinear direction, unfortunately resulting in anisotropic contrast imaging. Here we propose an ultracompact metasurface-assisted isotropic DIC (i-DIC) microscopy based on a grand original pattern of radial shear interferometry, that converts the rectilinear shear into rotationally symmetric along radial direction, enabling single-shot isotropic imaging capabilities. The i-DIC presents a complementary fusion of typical meta-optics, traditional microscopes and integrated optical system, and showcases the promising and synergetic advancements in edge detection, particle motion tracking, and label-free cellular imaging.
Targeting neuronal lysosomal dysfunction caused by β-glucocerebrosidase deficiency with an enzyme-based brain shuttle construct
Authors: Gehrlein Alexandra , Udayar Vinod , Anastasi Nadia , Morella Martino L. , Ruf Iris , Brugger Doris , von der Mark Sophia , Thoma Ralf , Rufer Arne , Heer Dominik , Pfahler Nina , Jochner Anton , Niewoehner Jens , Wolf Luise , Fueth Matthias , Ebeling Martin , Villaseñor Roberto , Zhu Yanping , Deen Matthew C. , Shan Xiaoyang , Ehsaei Zahra , Taylor Verdon , Sidransky Ellen , Vocadlo David J. , Freskgård Per-Ola , Jagasia Ravi 
Published: April 2023

AbstractMutations in glucocerebrosidase cause the lysosomal storage disorder Gaucher’s disease and are the most common risk factor for Parkinson’s disease. Therapies to restore the enzyme’s function in the brain hold great promise for treating the neurological implications. Thus, we developed blood-brain barrier penetrant therapeutic molecules by fusing transferrin receptor-binding moieties to β-glucocerebrosidase (referred to as GCase-BS). We demonstrate that these fusion proteins show significantly increased uptake and lysosomal efficiency compared to the enzyme alone. In a cellular disease model, GCase-BS rapidly rescues the lysosomal proteome and lipid accumulations beyond known substrates. In a mouse disease model, intravenous injection of GCase-BS leads to a sustained reduction of glucosylsphingosine and can lower neurofilament-light chain plasma levels. Collectively, these findings demonstrate the potential of GCase-BS for treating GBA1-associated lysosomal dysfunction, provide insight into candidate biomarkers, and may ultimately open a promising treatment paradigm for lysosomal storage diseases extending beyond the central nervous system.
Antimicrobial exposure is associated with decreased survival in triple-negative breast cancer
Authors: Ransohoff Julia D. , Ritter Victor , Purington Natasha , Andrade Karen , Han Summer , Liu Mina , Liang Su-Ying , John Esther M. , Gomez Scarlett L. , Telli Melinda L. , Schapira Lidia , Itakura Haruka , Sledge George W. , Bhatt Ami S. , Kurian Allison W. 
Published: April 2023

AbstractAntimicrobial exposure during curative-intent treatment of triple-negative breast cancer (TNBC) may lead to gut microbiome dysbiosis, decreased circulating and tumor-infiltrating lymphocytes, and inferior outcomes. Here, we investigate the association of antimicrobial exposure and peripheral lymphocyte count during TNBC treatment with survival, using integrated electronic medical record and California Cancer Registry data in the Oncoshare database. Of 772 women with stage I-III TNBC treated with and without standard cytotoxic chemotherapy – prior to the immune checkpoint inhibitor era – most (654, 85%) used antimicrobials. Applying multivariate analyses, we show that each additional total or unique monthly antimicrobial prescription is associated with inferior overall and breast cancer-specific survival. This antimicrobial-mortality association is independent of changes in neutrophil count, is unrelated to disease severity, and is sustained through year three following diagnosis, suggesting antimicrobial exposure negatively impacts TNBC survival. These results may inform mechanistic studies and antimicrobial prescribing decisions in TNBC and other hormone receptor-independent cancers.
Thermal sensitivity of metabolic rate mirrors biogeographic differences between teleosts and elasmobranchs
Authors: Watanabe Yuuki Y. , Payne Nicholas L. 
Published: April 2023

AbstractEnvironmental temperature affects physiological functions, representing a barrier for the range expansions of ectothermic species. To understand the link between thermal physiology and biogeography, a key question is whether among-species thermal sensitivity of metabolic rates is mechanistically constrained or buffered through physiological remodeling over evolutionary time. The former conception, the Universal Temperature Dependence hypothesis, predicts similar among- and within-species thermal sensitivity. The latter conception, the Metabolic Cold Adaptation hypothesis, predicts lower among-species thermal sensitivity than within-species sensitivity. Previous studies that tested these hypotheses for fishes overwhelmingly investigated teleosts with elasmobranchs understudied. Here, we show that among-species thermal sensitivity of resting metabolic rates is lower than within-species sensitivity in teleosts but not in elasmobranchs. Further, species richness declines with latitude more rapidly in elasmobranchs than in teleosts. Metabolic Cold Adaptation exhibited by teleosts might underpin their high diversity at high latitudes, whereas the inflexible thermal sensitivity approximated by Universal Temperature Dependence of elasmobranchs might explain their low diversity at high latitudes.
Diffusive excitonic bands from frustrated triangular sublattice in a singlet-ground-state system
Authors: Gao Bin , Chen Tong , Wu Xiao-Chuan , Flynn Michael , Duan Chunruo , Chen Lebing , Huang Chien-Lung , Liebman Jesse , Li Shuyi , Ye Feng , Stone Matthew B. , Podlesnyak Andrey , Abernathy Douglas L. , Adroja Devashibhai T. , Duc Le Manh , Huang Qingzhen , Nevidomskyy Andriy H. , Morosan Emilia , Balents Leon , Dai Pengcheng 
Published: April 2023

AbstractMagnetic order in most materials occurs when magnetic ions with finite moments arrange in a particular pattern below the ordering temperature. Intriguingly, if the crystal electric field (CEF) effect results in a spin-singlet ground state, a magnetic order can still occur due to the exchange interactions between neighboring ions admixing the excited CEF levels. The magnetic excitations in such a state are spin excitons generally dispersionless in reciprocal space. Here we use neutron scattering to study stoichiometric Ni2Mo3O8, where Ni2+ions form a bipartite honeycomb lattice comprised of two triangular lattices, with ions subject to the tetrahedral and octahedral crystalline environment, respectively. We find that in both types of ions, the CEF excitations have nonmagnetic singlet ground states, yet the material has magnetic order. Furthermore, CEF spin excitons from the tetrahedral sites form a dispersive diffusive pattern around the Brillouin zone boundary, likely due to spin entanglement and geometric frustrations.
Near-atomic architecture of Singapore grouper iridovirus and implications for giant virus assembly
Authors: Zhao Zhennan , Huang Youhua , Liu Congcong , Zhu Dongjie , Gao Shuaixin , Liu Sheng , Peng Ruchao , Zhang Ya , Huang Xiaohong , Qi Jianxun , Wong Catherine C. L. , Zhang Xinzheng , Wang Peiyi , Qin Qiwei , Gao George F. 
Published: April 2023

AbstractSingapore grouper iridovirus (SGIV), one of the nucleocytoviricota viruses (NCVs), is a highly pathogenic iridovirid. SGIV infection results in massive economic losses to the aquaculture industry and significantly threatens global biodiversity. In recent years, high morbidity and mortality in aquatic animals have been caused by iridovirid infections worldwide. Effective control and prevention strategies are urgently needed. Here, we present a near-atomic architecture of the SGIV capsid and identify eight types of capsid proteins. The viral inner membrane-integrated anchor protein colocalizes with the endoplasmic reticulum (ER), supporting the hypothesis that the biogenesis of the inner membrane is associated with the ER. Additionally, immunofluorescence assays indicate minor capsid proteins (mCPs) could form various building blocks with major capsid proteins (MCPs) before the formation of a viral factory (VF). These results expand our understanding of the capsid assembly of NCVs and provide more targets for vaccine and drug design to fight iridovirid infections.
Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders
Authors: Eide Per Kristian , Lashkarivand Aslan , Pripp Are , Valnes Lars Magnus , Hovd Markus Herberg , Ringstad Geir , Blennow Kaj , Zetterberg Henrik 
Published: April 2023

AbstractClearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-β (Aβ40 and Aβ42), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function.
An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters
Authors: Deng Shaofeng , Liu Ying , Tam Rachel Chun-Yee , Chen Pin , Zhang Anna Jinxia , Mok Bobo Wing-Yee , Long Teng , Kukic Anja , Zhou Runhong , Xu Haoran , Song Wenjun , Chan Jasper Fuk-Woo , To Kelvin Kai-Wang , Chen Zhiwei , Yuen Kwok-Yung , Wang Pui , Chen Honglin 
Published: April 2023

AbstractCurrent available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
Authors: Mao Mao , Qu Xiaoli , Zhang Yabo , Gu Bingsong , Li Chen , Liu Rongzhi , Li Xiao , Zhu Hui , He Jiankang , Li Dichen 
Published: April 2023

AbstractRecapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.
Collagen breaks at weak sacrificial bonds taming its mechanoradicals
Authors: Rennekamp Benedikt , Karfusehr Christoph , Kurth Markus , Ünal Aysecan , Monego Debora , Riedmiller Kai , Gryn’ova Ganna , Hudson David M. , Gräter Frauke 
Published: April 2023

AbstractCollagen is a force-bearing, hierarchical structural protein important to all connective tissue. In tendon collagen, high load even below macroscopic failure level creates mechanoradicals by homolytic bond scission, similar to polymers. The location and type of initial rupture sites critically decide on both the mechanical and chemical impact of these micro-ruptures on the tissue, but are yet to be explored. We here use scale-bridging simulations supported by gel electrophoresis and mass spectrometry to determine breakage points in collagen. We find collagen crosslinks, as opposed to the backbone, to harbor the weakest bonds, with one particular bond in trivalent crosslinks as the most dominant rupture site. We identify this bond as sacrificial, rupturing prior to other bonds while maintaining the material’s integrity. Also, collagen’s weak bonds funnel ruptures such that the potentially harmful mechanoradicals are readily stabilized. Our results suggest this unique failure mode of collagen to be tailored towards combatting an early onset of macroscopic failure and material ageing.
Glucose depletion enables Candida albicans mating independently of the epigenetic white-opaque switch
Authors: Guan Guobo , Tao Li , Li Chao , Xu Ming , Liu Ling , Bennett Richard J. , Huang Guanghua 
Published: April 2023

AbstractThe human fungal pathogen Candida albicans can switch stochastically and heritably between a “white” phase and an “opaque” phase. Opaque cells are the mating-competent form of the species, whereas white cells are thought to be essentially “sterile”. Here, we report that glucose depletion, a common nutrient stress, enables C. albicans white cells to undergo efficient sexual mating. The relative expression levels of pheromone-sensing and mating-associated genes (including STE2/3, MFA1, MFα1, FIG1, FUS1, and CEK1/2) are increased under glucose depletion conditions, while expression of mating repressors TEC1 and DIG1 is decreased. Cph1 and Tec1, factors that act downstream of the pheromone MAPK pathway, play opposite roles in regulating white cell mating as TEC1 deletion or CPH1 overexpression promotes white cell mating. Moreover, inactivation of the Cph1 repressor Dig1 increases white cell mating ~4000 fold in glucose-depleted medium relative to that in the presence of glucose. Our findings reveal that the white-to-opaque epigenetic switch may not be a prerequisite for sexual mating in C. albicans in nature.
Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens
Authors: Wang Rui , Shu Xian , Zhao Huiwei , Xue Qiong , Liu Chao , Wu Aici , Cheng Feiyue , Wang Lingyun , Zhang Yihan , Feng Jie , Wu Nannan , Li Ming 
Published: April 2023

AbstractCreTA, CRISPR-regulated toxin-antitoxin (TA), safeguards CRISPR-Cas immune systems by inducing cell dormancy/death upon their inactivation. Here, we characterize a bacterial CreTA associating with the I-F CRISPR-Cas in Acinetobacter. CreT is a distinct bactericidal small RNA likely targeting several essential RNA molecules that are required to initiate protein synthesis. CreA guides the CRISPR effector to transcriptionally repress CreT. We further demonstrate a proof-of-concept antimicrobial strategy named ATTACK, which AssociaTes TA and CRISPR-Cas to Kill multidrug resistant (MDR) pathogens. In this design, CRISPR-Cas is programed to target antibiotic resistance gene(s) to selectively kill MDR pathogens or cure their resistance, and when CRISPR-Cas is inactivated or suppressed by unwanted genetic or non-genetic events/factors, CreTA triggers cell death as the last resort. Our data highlight the diversity of RNA toxins coevolving with CRISPR-Cas, and illuminate a combined strategy of CRISPR and TA antimicrobials to ‘ATTACK’ MDR pathogens.