bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian disturbances and frailty risk in older adults
Authors: Cai Ruixue , Gao Lei , Gao Chenlu , Yu Lei , Zheng Xi , Bennett David A. , Buchman Aron S. , Hu Kun , Li Peng 
Published: November 2023

AbstractFrailty is characterized by diminished resilience to stressor events. It is associated with adverse future health outcomes and impedes healthy aging. The circadian system orchestrates ~24-h rhythms in bodily functions in synchrony with the day-night cycle, and disturbed circadian regulation plays an important role in many age-related health consequences. We investigated prospective associations of circadian disturbances with incident frailty in over 1000 older adults who had been followed annually for up to 16 years. We found that decreased rhythm strength, reduced stability, or increased variation were associated with a higher risk of incident frailty and faster progress of frailty over time. Perturbed circadian rest-activity rhythms may be an early sign or risk factor for frailty in older adults.
A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences
Authors: Gleichman Amy J. , Kawaguchi Riki , Sofroniew Michael V. , Carmichael S. Thomas 
Published: November 2023

AbstractAstrocytes, one of the most prevalent cell types in the central nervous system (CNS), are critically involved in neural function. Genetically manipulating astrocytes is an essential tool in understanding and affecting their roles. Adeno-associated viruses (AAVs) enable rapid genetic manipulation; however, astrocyte specificity of AAVs can be limited, with high off-target expression in neurons and sparsely in endothelial cells. Here, we report the development of a cassette of four copies of six miRNA targeting sequences (4x6T) which triggers transgene degradation specifically in neurons and endothelial cells. In combination with the GfaABC1D promoter, 4x6T increases astrocytic specificity of Cre with a viral reporter from <50% to >99% in multiple serotypes in mice, and confers astrocyte specificity in multiple recombinases and reporters. We also present empty vectors to add 4x6T to other cargo, independently and in Cre/Dre-dependent forms. This toolbox of AAVs allows rapid manipulation of astrocytes throughout the CNS, is compatible with different AAV serotypes, and demonstrates the efficacy of using multiplexed miRNA targeting sequences to decrease expression in multiple off-target cell populations simultaneously.
Simulation-guided engineering of split GFPs with efficient β-strand photodissociation
Authors: Shamsudin Yasmin , Walker Alice R. , Jones Chey M. , Martínez Todd J. , Boxer Steven G. 
Published: November 2023

AbstractGreen fluorescent proteins (GFPs) are ubiquitous for protein tagging and live-cell imaging. Split-GFPs are widely used to study protein-protein interactions by fusing proteins of interest to split GFP fragments that create a fluorophore upon typically irreversible complementation. Thus, controlled dissociation of the fragments is desirable. Although we have found that split strands can be photodissociated, the quantum efficiency of light-induced photodissociation of split GFPs is low. Traditional protein engineering approaches to increase efficiency, including extensive mutagenesis and screening, have proved difficult to implement. To reduce the search space, key states in the dissociation process are modeled by combining classical and enhanced sampling molecular dynamics with QM/MM calculations, enabling the rational design and engineering of split GFPs with up to 20-fold faster photodissociation rates using non-intuitive amino acid changes. This demonstrates the feasibility of modeling complex molecular processes using state-of-the-art computational methods, and the potential of integrating computational methods to increase the success rate in protein engineering projects.
Unconventional structure and mechanisms for membrane interaction and translocation of the NF-κB-targeting toxin AIP56
Authors: Lisboa Johnny , Pereira Cassilda , Pinto Rute D. , Rodrigues Inês S. , Pereira Liliana M. G. , Pinheiro Bruno , Oliveira Pedro , Pereira Pedro José Barbosa , Azevedo Jorge E. , Durand Dominique , Benz Roland , do Vale Ana , dos Santos Nuno M. S. 
Published: November 2023

AbstractBacterial AB toxins are secreted key virulence factors that are internalized by target cells through receptor-mediated endocytosis, translocating their enzymatic domain to the cytosol from endosomes (short-trip) or the endoplasmic reticulum (long-trip). To accomplish this, bacterial AB toxins evolved a multidomain structure organized into either a single polypeptide chain or non-covalently associated polypeptide chains. The prototypical short-trip single-chain toxin is characterized by a receptor-binding domain that confers cellular specificity and a translocation domain responsible for pore formation whereby the catalytic domain translocates to the cytosol in an endosomal acidification-dependent way. In this work, the determination of the three-dimensional structure of AIP56 shows that, instead of a two-domain organization suggested by previous studies, AIP56 has three-domains: a non-LEE encoded effector C (NleC)-like catalytic domain associated with a small middle domain that contains the linker-peptide, followed by the receptor-binding domain. In contrast to prototypical single-chain AB toxins, AIP56 does not comprise a typical structurally complex translocation domain; instead, the elements involved in translocation are scattered across its domains. Thus, the catalytic domain contains a helical hairpin that serves as a molecular switch for triggering the conformational changes necessary for membrane insertion only upon endosomal acidification, whereas the middle and receptor-binding domains are required for pore formation.
Mesenchymal stromal cells alleviate depressive and anxiety-like behaviors via a lung vagal-to-brain axis in male mice
Authors: Huang Jing , Huang Weijun , Yi Junzhe , Deng Yiwen , Li Ruijie , Chen Jieying , Shi Jiahao , Qiu Yuan , Wang Tao , Chen Xiaoyong , Zhang Xiaoran , Xiang Andy Peng 
Published: November 2023

AbstractMajor depressive disorder (MDD) is one of the most common and disabling mental disorders, and current strategies remain inadequate. Although mesenchymal stromal cells (MSCs) have shown beneficial effects in experimental models of depression, underlying mechanisms remain elusive. Here, using murine depression models, we demonstrated that MSCs could alleviate depressive and anxiety-like behaviors not due to a reduction in proinflammatory cytokines, but rather activation of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons. Mechanistically, peripheral delivery of MSCs activated pulmonary innervating vagal sensory neurons, which projected to the nucleus tractus solitarius, inducing the release of 5-HT in DRN. Furthermore, MSC-secreted brain-derived neurotrophic factor activated lung sensory neurons through tropomyosin receptor kinase B (TrkB), and inhalation of a TrkB agonist also achieved significant therapeutic effects in male mice. This study reveals a role of peripheral MSCs in regulating central nervous system function and demonstrates a potential “lung vagal-to-brain axis” strategy for MDD.
Profiling stress-triggered RNA condensation with photocatalytic proximity labeling
Authors: Ren Ziqi , Tang Wei , Peng Luxin , Zou Peng 
Published: November 2023

AbstractStress granules (SGs) are highly dynamic cytoplasmic membrane-less organelles that assemble when cells are challenged by stress. RNA molecules are sorted into SGs where they play important roles in maintaining the structural stability of SGs and regulating gene expression. Herein, we apply a proximity-dependent RNA labeling method, CAP-seq, to comprehensively investigate the content of SG-proximal transcriptome in live mammalian cells. CAP-seq captures 457 and 822 RNAs in arsenite- and sorbitol-induced SGs in HEK293T cells, respectively, revealing that SG enrichment is positively correlated with RNA length and AU content, but negatively correlated with translation efficiency. The high spatial specificity of CAP-seq dataset is validated by single-molecule FISH imaging. We further apply CAP-seq to map dynamic changes in SG-proximal transcriptome along the time course of granule assembly and disassembly processes. Our data portray a model of AU-rich and translationally repressed SG nanostructure that are memorized long after the removal of stress.
High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq
Authors: Benotmane Jasim Kada , Kueckelhaus Jan , Will Paulina , Zhang Junyi , Ravi Vidhya M. , Joseph Kevin , Sankowski Roman , Beck Jürgen , Lee-Chang Catalina , Schnell Oliver , Heiland Dieter Henrik 
Published: November 2023

AbstractSpatial resolution of the T cell repertoire is essential for deciphering cancer-associated immune dysfunction. Current spatially resolved transcriptomic technologies are unable to directly annotate T cell receptors (TCR). We present spatially resolved T cell receptor sequencing (SPTCR-seq), which integrates optimized target enrichment and long-read sequencing for highly sensitive TCR sequencing. The SPTCR computational pipeline achieves yield and coverage per TCR comparable to alternative single-cell TCR technologies. Our comparison of PCR-based and SPTCR-seq methods underscores SPTCR-seq’s superior ability to reconstruct the entire TCR architecture, including V, D, J regions and the complementarity-determining region 3 (CDR3). Employing SPTCR-seq, we assess local T cell diversity and clonal expansion across spatially discrete niches. Exploration of the reciprocal interaction of the tumor microenvironmental and T cells discloses the critical involvement of NK and B cells in T cell exhaustion. Integrating spatially resolved omics and TCR sequencing provides as a robust tool for exploring T cell dysfunction in cancers and beyond.
Tracking lake drainage events and drained lake basin vegetation dynamics across the Arctic
Authors: Chen Yating , Cheng Xiao , Liu Aobo , Chen Qingfeng , Wang Chengxin 
Published: November 2023

AbstractWidespread lake drainage can lead to large-scale drying in Arctic lake-rich areas, affecting hydrology, ecosystems and permafrost carbon dynamics. To date, the spatio-temporal distribution, driving factors, and post-drainage dynamics of lake drainage events across the Arctic remain unclear. Using satellite remote sensing and surface water products, we identify over 35,000 (~0.6% of all lakes) lake drainage events in the northern permafrost zone between 1984 and 2020, with approximately half being relatively understudied non-thermokarst lakes. Smaller, thermokarst, and discontinuous permafrost area lakes are more susceptible to drainage compared to their larger, non-thermokarst, and continuous permafrost area counterparts. Over time, discontinuous permafrost areas contribute more drained lakes annually than continuous permafrost areas. Following drainage, vegetation rapidly colonizes drained lake basins, with thermokarst drained lake basins showing significantly higher vegetation growth rates and greenness levels than their non-thermokarst counterparts. Under warming, drained lake basins are likely to become more prevalent and serve as greening hotspots, playing an important role in shaping Arctic ecosystems.
Topographic axonal projection at single-cell precision supports local retinotopy in the mouse superior colliculus
Authors: Molotkov Dmitry , Ferrarese Leiron , Boissonnet Tom , Asari Hiroki 
Published: November 2023

AbstractRetinotopy, like all long-range projections, can arise from the axons themselves or their targets. The underlying connectivity pattern, however, remains elusive at the fine scale in the mammalian brain. To address this question, we functionally mapped the spatial organization of the input axons and target neurons in the female mouse retinocollicular pathway at single-cell resolution using in vivo two-photon calcium imaging. We found a near-perfect retinotopic tiling of retinal ganglion cell axon terminals, with an average error below 30 μm or 2° of visual angle. The precision of retinotopy was relatively lower for local neurons in the superior colliculus. Subsequent data-driven modeling ascribed it to a low input convergence, on average 5.5 retinal ganglion cell inputs per postsynaptic cell in the superior colliculus. These results indicate that retinotopy arises largely from topographically precise input from presynaptic cells, rather than elaborating local circuitry to reconstruct the topography by postsynaptic cells.
A neotropical perspective on the uniqueness of the Holocene among interglacials
Authors: Schiferl J. , Kingston M. , Åkesson C. M. , Valencia B. G. , Rozas-Davila A. , McGee D. , Woods A. , Chen C. Y. , Hatfield R. G. , Rodbell D. T. , Abbott M. B. , Bush M. B. 
Published: November 2023

AbstractUnderstanding how tropical systems have responded to large-scale climate change, such as glacial-interglacial oscillations, and how human impacts have altered those responses is key to current and future ecology. A sedimentary record recovered from Lake Junín, in the Peruvian Andes (4085 m elevation) spans the last 670,000 years and represents the longest continuous and empirically-dated record of tropical vegetation change to date. Spanning seven glacial-interglacial oscillations, fossil pollen and charcoal recovered from the core showed the general dominance of grasslands, although during the warmest times some Andean forest trees grew above their modern limits near the lake. Fire was very rare until the last 12,000 years, when humans were in the landscape. Here we show that, due to human activity, our present interglacial, the Holocene, has a distinctive vegetation composition and ecological trajectory compared with six previous interglacials. Our data reinforce the view that modern vegetation assemblages of high Andean grasslands and the presence of a defined tree line are aspects of a human-modified landscape.
A palisade-shaped membrane reservoir is required for rapid ring cell inflation in Drechslerella dactyloides
Authors: Chen Yue , Liu Jia , Kang Seogchan , Wei Dongsheng , Fan Yani , Xiang Meichun , Liu Xingzhong 
Published: November 2023

AbstractFusion of individual vesicles carrying membrane-building materials with the plasma membrane (PM) enables gradual cell expansion and shape change. Constricting ring (CR) cells of carnivorous fungi triple in size within 0.1-1 s to capture passing nematodes. Here, we investigated how a carnivorous fungus, Drechslerella dactyloides, executes rapid and irreversible PM expansion during CR inflation. During CR maturation, vesicles carrying membrane-building materials accumulate and fuse, forming a structure named the Palisade-shaped Membrane-building Structure (PMS) around the rumen side of ring cells. After CR inflation, the PMS disappears, with partially inflated cells displaying wavy PM and fully inflated cells exhibiting smooth PM, suggesting that the PMS serves as the reservoir for membrane-building materials to enable rapid and extensive PM expansion. The DdSnc1, a v-SNARE protein, accumulates at the inner side of ring cells and is necessary for PMS formation and CR inflation. This study elucidates the unique cellular mechanisms underpinning rapid CR inflation.
Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape
Authors: Goovaerts Seppe , Hoskens Hanne , Eller Ryan J. , Herrick Noah , Musolf Anthony M. , Justice Cristina M. , Yuan Meng , Naqvi Sahin , Lee Myoung Keun , Vandermeulen Dirk , Szabo-Rogers Heather L. , Romitti Paul A. , Boyadjiev Simeon A. , Marazita Mary L. , Shaffer John R. , Shriver Mark D. , Wysocka Joanna , Walsh Susan , Weinberg Seth M. , Claes Peter 
Published: November 2023

AbstractThe cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yielding 30 genome-wide significant loci. Follow-up analyses indicate that these loci overlap with genomic risk loci for sagittal craniosynostosis, show elevated activity cranial neural crest cells, are enriched for processes related to skeletal development, and are shared with the face and brain. We present supporting evidence of regional localization for several of the identified genes based on expression patterns in the cranial vault bones of E15.5 mice. Overall, our study provides a comprehensive overview of the genetics underlying normal-range cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.
Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype
Authors: Fitzpatrick Amanda , Iravani Marjan , Mills Adam , Vicente David , Alaguthurai Thanussuyah , Roxanis Ioannis , Turner Nicholas C. , Haider Syed , Tutt Andrew N. J. , Isacke Clare M. 
Published: November 2023

AbstractBreast cancer leptomeningeal metastasis (BCLM), where tumour cells grow along the lining of the brain and spinal cord, is a devastating development for patients. Investigating this metastatic site is hampered by difficulty in accessing tumour material. Here, we utilise cerebrospinal fluid (CSF) cell-free DNA (cfDNA) and CSF disseminated tumour cells (DTCs) to explore the clonal evolution of BCLM and heterogeneity between leptomeningeal and extracranial metastatic sites. Somatic alterations with potential therapeutic actionability were detected in 81% (17/21) of BCLM cases, with 19% detectable in CSF cfDNA only. BCLM was enriched in genomic aberrations in adherens junction and cytoskeletal genes, revealing a lobular-like breast cancer phenotype. CSF DTCs were cultured in 3D to establish BCLM patient-derived organoids, and used for the successful generation of BCLM in vivo models. These data reveal that BCLM possess a unique genomic aberration profile and highlight potential cellular dependencies in this hard-to-treat form of metastatic disease.
The structural and functional investigation into an unusual nitrile synthase
Authors: Li Hao , Huang Jian-Wen , Dai Longhai , Zheng Haibin , Dai Si , Zhang Qishan , Yao Licheng , Yang Yunyun , Yang Yu , Min Jian , Guo Rey-Ting , Chen Chun-Chi 
Published: November 2023

AbstractThe biosynthesis of neurotoxin aetokthonotoxin (AETX) that features a unique structure of pentabrominated biindole nitrile involves a first-of-its-kind nitrile synthase termed AetD, an enzyme that shares very low sequence identity to known structures and catalyzes an unprecedented mechanism. In this study, we resolve the crystal structure of AetD in complex with the substrate 5,7-di-Br-L-Trp. AetD adopts the heme oxygenase like fold and forms a hydrophobic cavity within a helical bundle to accommodate the indole moiety. A diiron cluster comprising two irons that serves as a catalytic center binds to the carboxyl O and the amino N of the substrate. Notably, we demonstrate that the AetD-catalyzed reaction is independent of the bromination of the substrate and also solved crystal structures of AetD in complex with 5-Br-L-Trp and L-Trp. Altogether, the present study reveals the substrate-binding pattern and validates the diiron cluster-comprising active center of AetD, which should provide important basis to support the mechanistic investigations into this class of nitrile synthase.
Quantitative three-dimensional imaging of chemical short-range order via machine learning enhanced atom probe tomography
Authors: Li Yue , Wei Ye , Wang Zhangwei , Liu Xiaochun , Colnaghi Timoteo , Han Liuliu , Rao Ziyuan , Zhou Xuyang , Huber Liam , Dsouza Raynol , Gong Yilun , Neugebauer Jörg , Marek Andreas , Rampp Markus , Bauer Stefan , Li Hongxiang , Baker Ian , Stephenson Leigh T. , Gault Baptiste 
Published: November 2023

AbstractChemical short-range order (CSRO) refers to atoms of specific elements self-organising within a disordered crystalline matrix to form particular atomic neighbourhoods. CSRO is typically characterized indirectly, using volume-averaged or through projection microscopy techniques that fail to capture the three-dimensional atomistic architectures. Here, we present a machine-learning enhanced approach to break the inherent resolution limits of atom probe tomography enabling three-dimensional imaging of multiple CSROs. We showcase our approach by addressing a long-standing question encountered in body-centred-cubic Fe-Al alloys that see anomalous property changes upon heat treatment. We use it to evidence non-statistical B2-CSRO instead of the generally-expected D03-CSRO. We introduce quantitative correlations among annealing temperature, CSRO, and nano-hardness and electrical resistivity. Our approach is further validated on modified D03-CSRO detected in Fe-Ga. The proposed strategy can be generally employed to investigate short/medium/long-range ordering phenomena in different materials and help design future high-performance materials.
Inorganic–organic hybrid quantum dots for AOP-mediated photodegradation of ofloxacin and para-nitrophenol in diverse water matrices
Authors: Mishra Soumya Ranjan , Gadore Vishal , Ahmaruzzaman Md. 
Published: November 2023

AbstractDue to concerns about the accessibility of clean water and the quality of treated wastewater, developing a suitable solution to enhance the water quality is critical. Thus, the current study focused on the synthesis of cadmium-doped CdIn2S4 incorporated in chitosan, forming Cd/CdIn2S4@Ch quantum dots using a solvothermal technique for the efficient photodegradation of hazardous pollutants like ofloxacin and para-nitrophenol through H2O2-mediated AOP. Cd/CdIn2S4@Ch quantum dots were characterized by several advanced methods, including XRD, PL, UV-DRS, FTIR, SEM, HR-TEM, XPS, DSC, TGA, EDX, and Elemental mapping analysis. The influence of varying reaction parameters, such as the effect of organic compounds, inorganic ions, and water matrices, was also investigated. The prepared composite showed outstanding photodegradation efficiency of 85.51 ± 1.35% and 96.70 ± 1.31%, with a rate constant of 0.02334 and 0.15134 min−1, which is about 1.24 and 2.07 times higher than pristine CdIn2S4 for ofloxacin and para-nitrophenol, respectively. The COD values were reduced to 80.67 ± 1.67% for ofloxacin and 88.36 ± 1.43% for para-nitrophenol, whereas the TOC values reduced to 73.49% and 86.34%, respectively, from their initial values. The improved performance is ascribed to the encapsulation of CdIn2S4 by chitosan, leading to the self-doping of cadmium into the photocatalyst, as the incorporated cadmium doping site can generate a local electron accumulation point, improving the charge separation efficacy and surface charge mitigation capability of chitosan nanosheets even further. The scavenger experiments showed that hydroxyl and superoxide radicals played a significant part in the photodegradation of contaminants. Additionally, the quantum dots showed excellent constancy and were recyclable up to six times, suggesting exceptional stability and reusability of the manufactured photocatalyst. The fabricated Cd/CdIn2S4@Ch quantum dots could be an excellent photocatalyst for removing organic pollutants from wastewater in the near future.