bluuebunny/crossref_metadata_2025_split huggingface dataset:
A three-dimensional histological cell atlas of the developing human brain
Authors: Jayakumar Jaikishan , Sivaprakasam Mohanasankar , Verma Richa , Bota Mihail , Joseph Jayaraj , Mulay Supriti , Kumutha Jayaraman , Srinivasan Chitra , Suresh S , Latha S. , Kumar Harish E , Bhaduri Aparna , Nowakowski Tomasz J. , Roy Prasun K , Savoia Stephen , Banerjee Samik , Tward Daniel , Mitra Partha P 
Published: December 2024

AbstractThe human brain is believed to contain a full complement of neurons by the time of birth together with a substantial amount of the connectivity architecture, even though a significant amount of growth occurs postnatally. The developmental process leading to this outcome is not well understood in humans in comparison with model organisms. Previous magnetic resonance imaging (MRI) studies give three-dimensional coverage but not cellular resolution. In contrast, sparsely sampled histological or spatial omics analyses have provided cellular resolution but not dense whole brain coverage. To address the unmet need to provide a quantitative spatiotemporal map of developing human brain at cellular resolution, we leveraged tape-transfer assisted serial section histology to obtain contiguous histological series and unbiased imaging with dense coverage. Interleaved 20μ thick Nissl and H&E series and MRI volumes are co-registered into multimodal reference volumes with 60μ isotropic resolution, together with atlas annotations and a stereotactic coordinate system based on skull landmarks. The histological atlas volumes have significantly more contrast and texture than the MRI volumes. We computationally detect cells brain-wide to obtain quantitative characterization of the cytoarchitecture of the developing brain at 13-14 and 20-21 gestational weeks, providing the first comprehensive regional cell counts and characterizing the differential growth of the different brain compartments. Morphological characteristics permit segmentation of cell types from histology. We detected and quantified brain-wide distribution of mitotic figures representing dividing cells, providing an unprecedented spatiotemporal atlas of proliferative dynamics in the developing human brain. Further, we characterized the abundance and distribution of Cajal-Retzius cells, a transient cell population that plays essential roles in organizing glutamatergic cortical neurons into layers. Together, our study provides an unprecedented quantitative window into the developing human brain and the reference volumes and coordinate space should be useful for integrating spatial omics data sets with dense histological context.
The pseudoknot structure of a viral RNA reveals a conserved mechanism for programmed exoribonuclease resistance
Authors: Gezelle Jeanine G. , Korn Sophie M. , McDonald Jayden T. , Gong Zhen , Erickson Anna , Huang Chih-Hung , Yang Feiyue , Cronin Matt , Kuo Yen-Wen , Wimberly Brian T. , Steckelberg Anna-Lena 
Published: December 2024

AbstractExoribonuclease-resistant RNAs (xrRNAs) are viral RNA structures that block degradation by cellular 5′-3′ exoribonucleases to produce subgenomic viral RNAs during infection. Initially discovered in flaviviruses, xrRNAs have since been identified in wide range of RNA viruses, including those that infect plants. High sequence variability among viral xrRNAs raises questions about the shared molecular features that characterize this functional RNA class. Here, we present the first structure of a plant-virus xrRNA in its active exoribonuclease-resistant conformation. The xrRNA forms a 9 base pair pseudoknot that creates a knot-like topology similar to that of flavivirus xrRNAs, despite lacking sequence similarity. Biophysical assays confirm a compact pseudoknot structure in solution, and functional studies validate its relevance bothin vitroand during infection. Our study reveals how viral RNAs achieve a common functional outcome through highly divergent sequences and identifies the knot-like topology as a defining feature of xrRNAs.
Cryogenic electron tomography and elemental analysis of mitochondrial granules in human retinal ganglion cells
Authors: Wu Gong-Her , Hou Cathy , Thron Andrew , Patel Hirenkumar Rajendra , Spillane Liam , Gupte Sanket Rajan , Yeung-Levy Serena , Gulati Sahil , Booth Christopher , Liao Yaping Joyce , Chiu Wah 
Published: December 2024

SummaryCombining three-dimensional (3D) visualization with elemental analysis of vitrified cells can provide crucial insights into subcellular structures and elemental compositions in their native environments. We present a coordinated approach using cryogenic electron energy loss spectroscopy (cryoEELS) and cryogenic electron tomography (cryoET) to characterize the elemental distribution and ultrastructure of vitrified cells. We applied this method to examine calcium disposition in the mitochondria of cultured human retinal ganglion cells (RGCs) exposed to pro-calcifying conditions relevant to optic disc drusen pathology. Our cryoEELS analysis revealed mitochondrial granules with elevated calcium signals, offering direct evidence of mitochondrial calcification. Additionally, cryoET coupled with artificial intelligence-based analysis enabled quantification of the volume and spatial distribution of these calcium granules. This integrated workflow can be broadly applied to various cell types, facilitating the study of ultrastructure and elemental distribution in subcellular structures under diverse physiological and pathological conditions, as well as in response to therapeutic interventions.
TGF-β expressed by M2 macrophages promotes wound healing by inhibiting TSG-6 expression by mesenchymal stem cells
Authors: Eom Young Woo , Hong Ju-Eun , Jung Pil Young , Yoon Yongdae , Yoo Sang-Hyeon , Hong Jiyun , Rhee Ki-Jong , Regmi Bhupendra , Fatima Saher , Kim Moon Young , Baik Soon Koo , Kwon Hye Youn 
Published: December 2024

AbstractWound healing involves the collaboration of multiple cells, including macrophages and fibroblasts, and requires the coordination of cytokines, growth factors, and matrix proteins to regulate the repair response. In this study, we investigated how M2 macrophages regulate expression of the anti-fibrotic and anti-inflammatory regulator tumor necrosis factor-α (TNF-α)-stimulated gene 6 (TSG-6) secreted by adipose tissue-derived stem cells (ASCs) during wound healing. Interleukin (IL)-4/IL-13, which is used to differentiate macrophage M2 phenotypes, increases TSG-6 in ASCs; however, M2 macrophages significantly decrease TSG-6 in ASCs. Transforming growth factor (TGF)-β expression was increased, and TNF-α expression was decreased in M2 macrophages. TGF-β inhibited IL-4/IL-13-induced ASC TSG-6 expression. In addition, TSG-6 suppressed TGF-β-triggered wound closure and fibrogenic responses in LX-2 cells. Collectively, TSG-6 inhibited wound healing, but M2 macrophage-expressed TGF-β prevented TSG-6 production from ASCs, which ultimately helped wound healing. Our results indicate that the balance of TNF-α and TGF-β levels during wound healing regulates TSG-6 production from ASCs, which may ultimately modulate the healing process. Our study findings could contribute to novel therapeutic strategies that manipulate the delicate balance between TNF-α and TGF-β to enhance wound repair and mitigate fibrosis.
Evaluation of Dreem headband for sleep staging and EEG spectral analysis in people living with Alzheimer’s and older adults
Authors: Ravindran Kiran K G , della Monica Ciro , Atzori Giuseppe , Hassanin Hana , Nilforooshan Ramin , Revell Victoria , Dijk Derk-Jan 
Published: December 2024

AbstractIntroductionPortable electroencephalography (EEG) devices offer the potential for accurate quantification of sleep at home but have not been evaluated in relevant populations.MethodsWe assessed the Dreem headband (DHB), and its automated sleep staging algorithm in 62 older adults [Age (mean±SD) 70.5±6.7 years; 12 Alzheimer’s]. The accuracy of sleep measures, epoch-by-epoch staging, and the quality of EEG signals for quantitative EEG (qEEG) analysis was compared to standard polysomnography (PSG) in a sleep laboratory.ResultsThe DHB algorithm accurately estimated total sleep time (TST) and sleep efficiency (SEFF) with a Symmetric Mean Absolute Percentage Error (SMAPE) <10%. Wake after sleep onset (WASO) and number of awakenings (NAW) were underestimated (WASO: ∼17 minutes; NAW: ∼9 counts) with SMAPE <20%. Sleep onset latency (SOL) was overestimated by ∼30 minutes when using the entire DHB recording period, but it was accurate (Bias: 0.3 minutes) when estimated over the lights-off period. Stage N3 and total non-rapid eye movement (REM) sleep durations were estimated accurately (Bias <20 minutes), while REM sleep was overestimated (∼25 minutes; SMAPE: ∼24%). Epoch-by-epoch sleep/wake classification showed acceptable performance (MCC=0.77±0.17) and 5-stage sleep classification was moderate (MCC=0.54±0.14). After artefact removal, 73% of the recordings were usable for qEEG analysis. Concordance (p<0.001) of EEG band power ranged from moderate to good: slow wave activity r2=0.57; theta r2=0.56; alpha r2=0.65; sigma power r2=0.34.ConclusionDHB algorithm provides accurate estimates of several sleep measures and qEEG metrics. However, further improvement in REM detection is needed to enhance its utility for research and clinical applications.Statement of SignificanceWearable electroencephalography (EEG) devices such as the Dreem headband (DHB), hold promise for accurate monitoring of sleep at home and improving our understanding of neurodegenerative conditions. This study is important because it provides a comprehensive evaluation of the DHB in older adults, including people living with Alzheimer’s. The DHB automatic sleep staging algorithm demonstrated good concordance with polysomnography for most standard sleep statistics, and epoch-by-epoch sleep/wake classification. A novel aspect of the study is the evaluation of the suitability of the DHB EEG signal for quantitative EEG analysis. Our findings highlight the DHB’s key strengths and provide critical recommendations for improving usability and performance to establish its potential utility for large-scale, objective sleep monitoring in community-dwelling older adults.
Coordinated repression of totipotency-associated gene loci by histone methyltransferase EHMT2 through binding to LINE-1 regulatory elements
Authors: Chatterjee K , Uyehara CM , Kasliwal K , Madhuranath S , Scourzic L , Polyzos A , Apostolou E , Stadtfeld M 
Published: December 2024

SUMMARYMouse embryonic stem cells (mESCs) and other naïve pluripotent stem cells can reverse typical developmental trajectories and, at low frequency, de-differentiate into 2-cell-like cells (2CLCs) that resemble the mammalian embryo during zygotic genome activation (ZGA). This affords the opportunity to reveal molecular principles that govern the pre-implantation stages of mammalian development. We leveraged a multipurpose allele for acute protein depletion and efficient immunoprecipitation to dissect the molecular functions of the chromatin repressor EHMT2, a candidate antagonist of the mESC-to-2CLC transition. This allowed us to define categories of EHMT2 target genes characterized by distinct modes of EHMT2 chromatin engagement and repression. Most notably, EHMT2 directly represses large clusters of co-regulated gene loci that comprise a significant fraction of the 2CLC-specific transcriptome by initiating H3K9me2 spreading from distal LINE-1 elements. EHMT2 counteracts the recruitment of the activator DPPA2/4 to promoter-proximal endogenous retroviral elements (ERVs) at 2CLC genes. EHMT2 depletion elevates the expression of ZGA-associated transcripts in 2CLCs and synergizes with spliceosome inhibition and retinoic acid signaling in facilitating the mESC-to-2CLC transition. In contrast to ZGA-associated genes, repression of germ layer-associated transcripts by EHMT2 occurs outside of gene clusters in collaboration with ZFP462 and entails binding to non-repeat enhancers. Our observations show that EHMT2 attenuates the bidirectional differentiation potential of mouse pluripotent stem cells and define molecular modes for locus-specific transcriptional repression by this essential histone methyltransferase.
Actin dysregulation induces immune evasion via oxidative stress-activated PD-L1 in gastric cancer
Authors: Seo Yoojeong , Jang Jinho , Ko Kyung-Pil , Zou Gengyi , Huang Yuanjian , Zhang Shengzhe , Zhang Jie , Jun Sohee , Chu Wonhong , Venkatesan Vishwa , Dhakshinamoorthy Sanjana , Park Jae-Il 
Published: December 2024

AbstractDiffuse gastric adenocarcinoma (DGAC) is an aggressive malignancy with limited therapeutic options, poor prognosis, and poorly understood biology. CRACD, an actin polymerization regulator, is often inactivated in gastric cancer, including DGAC. We found that genetic engineering of murine gastric organoids withCracdablation combined withKrasmutation andTrp53loss induced aberrant cell plasticity, hyperproliferation, and hypermucinosis, the features that recapitulate DGAC transcriptional signatures. Notably, CRACD inactivation remodeled the immune landscape for immune evasion through PD-L1 enrichment in tumor cells. Mechanistically, CRACD loss disrupted actin dynamics, generating reactive oxygen species that activated HIF1α, which transactivatedPD-L1. Pharmacologic inhibition of HIF1α or PD-L1 restored immune surveillance and suppressed tumorigenesis. These findings reveal a novel role of actin homeostasis in limiting cell plasticity and immune evasion, position CRACD as a potential biomarker for stratifying patients with DGAC, and highlight HIF1α and PD-L1 as actionable therapeutic targets.
Global patterns of genetic admixture reveal effects of language contact
Authors: Graff Anna , Blasi Damián E. , Ringen Erik J. , Bajić Vladimir , Bavelier Daphné , Shimizu Kentaro K. , Pakendorf Brigitte , Barbieri Chiara , Bickel Balthasar 
Published: December 2024

AbstractWhen speakers of different languages are in contact, they often borrow features like sounds, words, or syntactic patterns from one language to the other, but the lack of historical data has hampered estimation of this effect at a global scale. We break out of this impasse by using genetic admixture as a proxy for population contact. We find that language pairs whose speaker populations underwent genetic admixture or that are located in the same geo-historical area share more features than others, suggesting borrowing. The effect varies strongly across features, partly following expectations from differences in lifelong learnability, partly responding to differences in social imbalances during contact. Additionally, we find that for some features, admixture decreases sharing. This likely reflects signals of divergence (schismogenesis) under contact.
MorphoDiff: Cellular Morphology Painting with Diffusion Models
Authors: Navidi Zeinab , Ma Jun , Miglietta Esteban A. , Liu Le , Carpenter Anne E. , Cimini Beth A. , Haibe-Kains Benjamin , Wang Bo 
Published: December 2024

AbstractUnderstanding cellular responses to external stimuli is critical for parsing biological mechanisms and advancing therapeutic development. High-content image-based assays provide a cost-effective approach to examine cellular phenotypes induced by diverse interventions, which offers valuable insights into biological processes and cellular states. In this paper, we introduce MorphoDiff, a generative pipeline to predict high-resolution cell morphological responses under different conditions based on perturbation encoding. To the best of our knowledge, MorphoDiff is the first framework capable of producing guided, high-resolution predictions of cell morphology that generalize across both chemical and genetic interventions. The model integrates perturbation embeddings as guiding signals within a 2D latent diffusion model. The comprehensive computational, biological, and visual validations across three open-source Cell Painting datasets show that MorphoDiff can generate high-fidelity images and produce meaningful biology signals under various interventions. We envision the model will facilitate efficient in silico exploration of perturbational landscapes towards more effective drug discovery studies.
Structure of the type VI secretion system protein VgrS fromSalmonellaTyphimurium
Authors: Sachar Kartik , Van Schepdael Matthew , Winters Karsen L. , Prehna Gerd 
Published: December 2024

SUMMARYEnteric bacterial pathogens employ various strategies to colonize the intestine and cause diseases ranging from gastroenteritis to systemic infections. For example,Salmonella entericautilizes a nanomachine known as the type VI secretion system (T6SS) to facilitate colonization of the host gut. However, the varied mechanistic details of how the T6SS is loaded with effector proteins remains to be elucidated. Here, we present an X-ray crystal structure of theSalmonellaTyphimurium VgrG (VgrS) that serves as platform for T6SS effector loading. Compared to other known structures of VgrG proteins, the VgrS trimer adopts an alternative open conformation composed of a domain-swap between the monomers in the gp27 region. Additionally, a comparative structural analysis of VgrS with other VgrG proteins reveals molecular variations that may contribute to specific effector loading mechanisms. Our structural data and molecular analysis highlight the observation that the T6SS of each bacterial species or strain is unique.
Conformational dynamics of a histidine molecular switch in a cation/proton antiporter
Authors: Pecorilla Cristina , Altmeyer Anton , Haapanen Outi , Lee Yongchan , Zickermann Volker , Sharma Vivek 
Published: December 2024

AbstractMultisubunit Mrp type sodium proton (Na+/H+) antiporters are indispensable for the growth of alkali and salt tolerant bacteria and archaea under challenging conditions. Several subunits of the membrane protein complex are closely related to the membrane bound subunits of mitochondrial respiratory complex I, a key enzyme in aerobic energy metabolism. The molecular mechanism of ion translocation by complex I and Mrp antiporters has remained largely unknown and is the subject of intense debate. Here, we combine the power of site-directed mutagenesis and large-scale atomistic molecular dynamics simulations to elucidate the molecular basis of proton-conducting function of the MrpA subunit of the antiporter. We show that point mutations directly affect the transport activity by perturbing the conformational dynamics of a key histidine residue that acts as a molecular switch. Importantly, we find that charge and protonation state variations drive hydrogen bonding rearrangements and hydration changes, which result in coupled sidechain and backbone level conformational changes of the histidine and neighboring residues. We propose the histidine switch as a unique functional element central to proton transport function in Mrp antiporters and respiratory complex I.Significance statementEnergy conversion in biology is catalyzed by several membrane-bound enzyme complexes that drive transmembrane charge translocation. A key question is how these charges are moved against a membrane gradient in an efficient manner, i.e., what kind of gating and fail-safe mechanisms are employed by the proteins to ensure charge transfer directionality. By studying cation/proton Mrp antiporter, which shares homology with the mitochondrial complex I, we describe a conserved histidine residue acting as a molecular switch crucial for gating transfer of protons. Our work emphasizes the functional significance of conserved and conformationally mobile motifs in proteins. The results will benefit the mechanistic understanding of naturally existing proteins and design of artificial enzymes.
Self-renewal without niche instruction, feedback or fine-tuning
Authors: MacArthur Ben D , Greulich Philip 
Published: December 2024

AbstractTo self-renew, stem cells must precisely balance proliferation and differentiation. Typically, this is achieved under feedback from the niche; yet many stem cells also possess an intrinsic self-renewal program that allows them to do so autonomously, as required. However, because self-renewal implies a stable equilibrium – in which the expected stem cell number neither increases nor decreases over time – this seems to require fine-tuning to a critical point. Here, we show that this is not the case: self-renewal can, in principle, be easily achieved without the need for extrinsic instruction, feedback or finetuning, by a simple ‘dimerization cycle’ that uses partitioning errors at cell division to reliably establish asymmetric divisions and perfectly balance symmetric divisions.
Research data management in institutional repositories: an architectural approach using data lakehouses
Authors: He Zilong , Fang Wei 
Published: December 2024

Purpose
This paper aims to address the pressing challenges in research data management within institutional repositories, focusing on the escalating volume, heterogeneity and multi-source nature of research data. The aim is to enhance the data services provided by institutional repositories and modernise their role in the research ecosystem.

Design/methodology/approach
The authors analyse the evolution of data management architectures through literature review, emphasising the advantages of data lakehouses. Using the design science research methodology, the authors develop an end-to-end data lakehouse architecture tailored to the needs of institutional repositories. This design is refined through interviews with data management professionals, institutional repository administrators and researchers.

Findings
The authors present a comprehensive framework for data lakehouse architecture, comprising five fundamental layers: data collection, data storage, data processing, data management and data services. Each layer articulates the implementation steps, delineates the dependencies between them and identifies potential obstacles with corresponding mitigation strategies.

Practical implications
The proposed data lakehouse architecture provides a practical and scalable solution for institutional repositories to manage research data. It offers a range of benefits, including enhanced data management capabilities, expanded data services, improved researcher experience and a modernised institutional repository ecosystem. The paper also identifies and addresses potential implementation obstacles and provides valuable guidance for institutions embarking on the adoption of this architecture. The implementation in a university library showcases how the architecture enhances data sharing among researchers and empowers institutional repository administrators with comprehensive oversight and control of the university’s research data landscape.

Originality/value
This paper enriches the theoretical knowledge and provides a comprehensive research framework and paradigm for scholars in research data management. It details a pioneering application of the data lakehouse architecture in an academic setting, highlighting its practical benefits and adaptability to meet the specific needs of institutional repositories.