bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tectonic Evolution of the Condrey Mountain Schist: An Intact Record of Late Jurassic to Early Cretaceous Franciscan Subduction and Underplating
Authors: Tewksbury‐Christle C. M. , Behr W. M. , Helper M. A. , Stockli D. F. 
Published: March 2024

AbstractThe Klamath Mountains in northern California and southern Oregon are thought to record 200+ m.y. of subduction and terrane accretion, whereas the outboard Franciscan Complex records ocean‐continent subduction along the North American margin. Unraveling the Klamath Mountains' Late Jurassic history could help constrain this transition in subduction style. Key is the Mesozoic Condrey Mountain Schist (CMS), comprising, in part, a subduction complex that occupies a structural window through older, overlying central Klamath thrust sheets but with otherwise uncertain relationships to more outboard Klamath or Franciscan terranes. The CMS consists of two units (upper and lower), which could be correlated with (a) other Klamath terranes, (b) the Franciscan, or (c) neither based on regional structures and limited extant age data. Upper CMS protolith and metamorphic dates overlap with other Klamath terranes, but the lower CMS remains enigmatic. We used multiple geochronometers to constrain the timing of lower CMS deposition and metamorphism. Maximum depositional ages (MDAs) derived from detrital zircon geochronology of metasedimentary rocks are 153–135 Ma. Metamorphic ages from white mica K‐Ar and Rb‐Sr multi‐mineral isochrons from intercalated and coherently deformed metamafic lenses are 133–116 Ma. Lower CMS MDAs (<153 Ma) predominantly postdate other Klamath terrane ages, but subduction metamorphism appears to start before the earliest coherent Franciscan underplating (ca. 123 Ma). The lower CMS thus occupies a spatial and temporal position between the Klamath Mountains and Franciscan and preserves a non‐retrogressed record of the Franciscan Complex's early history (>123 Ma), otherwise only partially preserved in retrogressed Franciscan high grade blocks.
Advances in single-cell omics and multiomics for high-resolution molecular profiling
Authors: Lim Jongsu , Park Chanho , Kim Minjae , Kim Hyukhee , Kim Junil , Lee Dong-Sung 
Published: March 2024

AbstractSingle-cell omics technologies have revolutionized molecular profiling by providing high-resolution insights into cellular heterogeneity and complexity. Traditional bulk omics approaches average signals from heterogeneous cell populations, thereby obscuring important cellular nuances. Single-cell omics studies enable the analysis of individual cells and reveal diverse cell types, dynamic cellular states, and rare cell populations. These techniques offer unprecedented resolution and sensitivity, enabling researchers to unravel the molecular landscape of individual cells. Furthermore, the integration of multimodal omics data within a single cell provides a comprehensive and holistic view of cellular processes. By combining multiple omics dimensions, multimodal omics approaches can facilitate the elucidation of complex cellular interactions, regulatory networks, and molecular mechanisms. This integrative approach enhances our understanding of cellular systems, from development to disease. This review provides an overview of the recent advances in single-cell and multimodal omics for high-resolution molecular profiling. We discuss the principles and methodologies for representatives of each omics method, highlighting the strengths and limitations of the different techniques. In addition, we present case studies demonstrating the applications of single-cell and multimodal omics in various fields, including developmental biology, neurobiology, cancer research, immunology, and precision medicine.
Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations
Authors: Schleifer Charles H. , O’Hora Kathleen P. , Fung Hoki , Xu Jennifer , Robinson Taylor-Ann , Wu Angela S. , Kushan-Wells Leila , Lin Amy , Ching Christopher R. K. , Bearden Carrie E. 
Published: March 2024

AbstractThe 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in a total of 385 scans from 22qDel (n = 96, scans = 191, 53.1% female), 22qDup (n = 37, scans = 64, 45.9% female), and TD controls (n = 80, scans = 130, 51.2% female), across a wide age range (5.5–49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the linear effects of 22q11.2 gene dosage and non-linear effects of age were characterized with generalized additive mixed models (GAMMs). Positive gene dosage effects (volume increasing with copy number) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.
CircNUP54 promotes hepatocellular carcinoma progression via facilitating HuR cytoplasmic export and stabilizing BIRC3 mRNA
Authors: Tang Chenwei , Zhuang Hongkai , Wang Wentao , Wang Qingbin , Ma Xiaowu , Wang Bingkun , Zhang Ziyu , Jiang Jiahao , Xie Zhiqin , Tan Wenliang , Yang Lei , Liu Songyao , Hua Yonglin , Xiao Yuxin , Ding Baoshan , Chen Yajin , Shang Changzhen 
Published: March 2024

AbstractCircular RNAs (circRNAs) have been implicated in tumorigenesis and progression of various cancers. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) have not been fully elucidated. Herein, a new oncogenic circRNA, hsa_circ_0070039 (circNUP54), was identified to be significantly upregulated in HCC through circRNA sequencing. As verified in 68 HCC samples, circNUP54 overexpression was correlated with aggressive cancerous behaviors and poor outcomes. Moreover, the function experiments showed that knockdown of circNUP54 inhibited the malignant progression of HCC in vitro and in vivo, whereas overexpression of circNUP54 had the opposite role. Mechanistic investigations carried out by RNA pull-down, RNA immunoprecipitation, and immunofluorescence revealed that circNUP54 interacted with the RNA-binding protein Hu-antigen R (HuR) and promoted its cytoplasmic export. The cytoplasmic accumulation of HuR stabilized the downstream BIRC3 mRNA through its binding to the 3′ UTR region. Consequently, the encoded protein of BIRC3, cellular inhibitor of apoptosis 2 (cIAP2), proceeded to activate the NF-κB signal pathway and ultimately contributed to HCC progression. In addition, depletion of BIRC3 rescued the pro-tumorigenic effect of circNUP54 on HCC cells. Overall, this study demonstrated that circNUP54 facilitates HCC progression via regulating the HuR/BIRC3/NF-κB axis, which may serve as a promising therapeutic target for HCC treatment.
Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer
Authors: Liu Hongfu , Zhou Dongdong , Liu Dongqin , Xu Xi , Zhang Kai , Hu Ruxia , Xiong Peng , Wang Changxin , Zeng Xiangfu , Wang Liefeng , Zhang Shuyong 
Published: March 2024

AbstractColorectal cancer (CRC) is the third most common cancer associated with a poor prognosis. Effective targeted therapy alone or in combination for treating advanced CRC remains to be a major clinical challenge. Here, we propose the therapeutic efficacy and molecular mechanism underlying RC48, a FDA-approved anti-HER2 antibody conjugate via a cleavable linker to the microtubule inhibitor monomethyl auristatin E (MMAE), either alone or in combination with gemcitabine (GEM) in various models of HER2-positive advanced CRC. Our findings demonstrated that HER2 was widely expressed and located on the plasma membrane of CRC patient specimens, PDX xenograft tumors and cell lines. It confirmed that RC48 alone significantly targeted and eradicated HER2 positive CRC tumor in these models. Moreover, we screened a panel of FDA-approved first-line chemotherapy drugs in vitro. We found that GEM exhibited stronger antiproliferative activity compared to the other first-line anti-cancer agents. Furthermore, combination therapy of RC48 and GEM significantly showed synergetic antitumor activity in vitro and in vivo. To gain further mechanistic insights into the combination therapy, we performed RNA-seq analysis. The results revealed that combination treatment of RC48 and GEM regulated multiple signaling pathways, such as PI3K-AKT, MAPK, p53, Foxo, apoptosis, cell cycle and cell senescence, etc., to exert its antitumor activity in CRC cells. Collectively, these preclinical findings demonstrated that RC48 alone or combinational therapy exerted promising antitumor activity, and meriting the preclinical framework for combinational therapy of anti-HER2 drug conjugate drug and chemotherapy drugs for HER2-positive patients with advanced CRC.
Transmission and dynamics of mother-infant gut viruses during pregnancy and early life
Authors: Garmaeva Sanzhima , Sinha Trishla , Gulyaeva Anastasia , Kuzub Nataliia , Spreckels Johanne E. , Andreu-Sánchez Sergio , Gacesa Ranko , Vich Vila Arnau , Brushett Siobhan , Kruk Marloes ,   Lifelines NEXT cohort study, Dotinga Aafje , Gordijn Sanne , Jankipersadsing Soesma , de Jonge Ank , de Kroon Marlou L. A. , Koppelman Gerard H. , Peters Lilian L. , Prins Jelmer R. , Reijneveld Sijmen A. , Swertz Morris A. , Verkade Henkjan J. , Dekens Jackie , Sikkema Jan , Kuipers Folkert , Shkoporov Andrey N. , Hill Colin , Scherjon Sicco , Wijmenga Cisca , Fu Jingyuan , Kurilshikov Alexander , Zhernakova Alexandra 
Published: March 2024

AbstractEarly development of the gut ecosystem is crucial for lifelong health. While infant gut bacterial communities have been studied extensively, the infant gut virome remains under-explored. To study the development of the infant gut virome over time and the factors that shape it, we longitudinally assess the composition of gut viruses and their bacterial hosts in 30 women during and after pregnancy and in their 32 infants during their first year of life. Using shotgun metagenomic sequencing applied to dsDNA extracted from Virus-Like Particles (VLPs) and bacteria, we generate 205 VLP metaviromes and 322 total metagenomes. With this data, we show that while the maternal gut virome composition remains stable during late pregnancy and after birth, the infant gut virome is dynamic in the first year of life. Notably, infant gut viromes contain a higher abundance of active temperate phages compared to maternal gut viromes, which decreases over the first year of life. Moreover, we show that the feeding mode and place of delivery influence the gut virome composition of infants. Lastly, we provide evidence of co-transmission of viral and bacterial strains from mothers to infants, demonstrating that infants acquire some of their virome from their mother’s gut.
Crystallization of molecular layers produced under confinement onto a surface
Authors: Tong Jincheng , de Bruyn Nathan , Alieva Adriana , Legge Elizabeth. J. , Boyes Matthew , Song Xiuju , Walisinghe Alvin J. , Pollard Andrew J. , Anderson Michael W. , Vetter Thomas , Melle-Franco Manuel , Casiraghi Cinzia 
Published: March 2024

AbstractIt is well known that molecules confined very close to a surface arrange into molecular layers. Because solid-liquid interfaces are ubiquitous in the chemical, biological and physical sciences, it is crucial to develop methods to easily access molecular layers and exploit their distinct properties by producing molecular layered crystals. Here we report a method based on crystallization in ultra-thin puddles enabled by gas blowing, which allows to produce molecular layered crystals with thickness down to the monolayer onto a surface, making them directly accessible for characterization and further processing. By selecting four molecules with different types of polymorphs, we observed exclusive crystallization of polymorphs with Van der Waals interlayer interactions, which have not been observed with traditional confinement methods. In conclusion, the gas blowing approach unveils the opportunity to perform materials chemistry under confinement onto a surface, enabling the formation of distinct crystals with selected polymorphism.
Topological barrier to Cas12a activation by circular DNA nanostructures facilitates autocatalysis and transforms DNA/RNA sensing
Authors: Deng Fei , Li Yi , Yang Biyao , Sang Rui , Deng Wei , Kansara Maya , Lin Frank , Thavaneswaran Subotheni , Thomas David M. , Goldys Ewa M. 
Published: March 2024

AbstractControl of CRISPR/Cas12a trans-cleavage is crucial for biosensor development. Here, we show that small circular DNA nanostructures which partially match guide RNA sequences only minimally activate Cas12a ribonucleoproteins. However, linearizing these structures restores activation. Building on this finding, an Autocatalytic Cas12a Circular DNA Amplification Reaction (AutoCAR) system is established which allows a single nucleic acid target to activate multiple ribonucleoproteins, and greatly increases the achievable reporter cleavage rates per target. A rate-equation-based model explains the observed near-exponential rate trends. Autocatalysis is also sustained with DNA nanostructures modified with fluorophore-quencher pairs achieving 1 aM level (<1 copy/μL) DNA detection (106 times improvement), without additional amplification, within 15 min, at room temperature. The detection range is tuneable, spanning 3 to 11 orders of magnitude. We demonstrate 1 aM level detection of SNP mutations in circulating tumor DNA from blood plasma, genomic DNA (H. Pylori) and RNA (SARS-CoV-2) without reverse transcription as well as colorimetric lateral flow tests of cancer mutations with ~100 aM sensitivity.
Neuronal miR-9 promotes HSV-1 epigenetic silencing and latency by repressing Oct-1 and Onecut family genes
Authors: Deng Yue , Lin Yuqi , Chen Siyu , Xiang Yuhang , Chen Hongjia , Qi Shuyuan , Oh Hyung Suk , Das Biswajit , Komazin-Meredith Gloria , Pesola Jean M. , Knipe David M. , Coen Donald M. , Pan Dongli 
Published: March 2024

AbstractHerpes simplex virus 1 (HSV-1) latent infection entails repression of viral lytic genes in neurons. By functional screening using luciferase-expressing HSV-1, we identify ten neuron-specific microRNAs potentially repressing HSV-1 neuronal replication. Transfection of miR-9, the most active candidate from the screen, decreases HSV-1 replication and gene expression in Neuro-2a cells. Ectopic expression of miR-9 from lentivirus or recombinant HSV-1 suppresses HSV-1 replication in male primary mouse neurons in culture and mouse trigeminal ganglia in vivo, and reactivation from latency in the primary neurons. Target prediction and validation identify transcription factors Oct-1, a known co-activator of HSV transcription, and all three Onecut family members as miR-9 targets. Knockdown of ONECUT2 decreases HSV-1 yields in Neuro-2a cells. Overexpression of each ONECUT protein increases HSV-1 replication in Neuro-2a cells, human induced pluripotent stem cell-derived neurons, and primary mouse neurons, and accelerates reactivation from latency in the mouse neurons. Mutagenesis, ChIP-seq, RNA-seq, ChIP-qPCR and ATAC-seq results suggest that ONECUT2 can nonspecifically bind to viral genes via its CUT domain, globally stimulate viral gene transcription, reduce viral heterochromatin and enhance the accessibility of viral chromatin. Thus, neuronal miR-9 promotes viral epigenetic silencing and latency by targeting multiple host transcription factors important for lytic gene activation.
Mapping a 50-spin-qubit network through correlated sensing
Authors: van de Stolpe G. L. , Kwiatkowski D. P. , Bradley C. E. , Randall J. , Abobeih M. H. , Breitweiser S. A. , Bassett L. C. , Markham M. , Twitchen D. J. , Taminiau T. H. 
Published: March 2024

AbstractSpins associated to optically accessible solid-state defects have emerged as a versatile platform for exploring quantum simulation, quantum sensing and quantum communication. Pioneering experiments have shown the sensing, imaging, and control of multiple nuclear spins surrounding a single electron spin defect. However, the accessible size of these spin networks has been constrained by the spectral resolution of current methods. Here, we map a network of 50 coupled spins through high-resolution correlated sensing schemes, using a single nitrogen-vacancy center in diamond. We develop concatenated double-resonance sequences that identify spin-chains through the network. These chains reveal the characteristic spin frequencies and their interconnections with high spectral resolution, and can be fused together to map out the network. Our results provide new opportunities for quantum simulations by increasing the number of available spin qubits. Additionally, our methods might find applications in nano-scale imaging of complex spin systems external to the host crystal.
A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis
Authors: Chadchan Sangappa B. , Popli Pooja , Liao Zian , Andreas Eryk , Dias Michelle , Wang Tianyuan , Gunderson Stephanie J. , Jimenez Patricia T. , Lanza Denise G. , Lanz Rainer B. , Foulds Charles E. , Monsivais Diana , DeMayo Francesco J. , Yalamanchili Hari Krishna , Jungheim Emily S. , Heaney Jason D. , Lydon John P. , Moley Kelle H. , O’Malley Bert W. , Kommagani Ramakrishna 
Published: March 2024

AbstractCellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor’s transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback mechanism to regulate P4-responsive genes. Conversely, in endometrial pathology (endometriosis), E2-induced GREB1 modulates E2-dependent gene expression to promote the growth of endometriotic lesions in mice. This differential action of GREB1 exerted by a common feed-forward mechanism with steroid receptors advances our understanding of mechanisms that underlie cell- and tissue-specific steroid hormone actions.
Static charge is an ionic molecular fragment
Authors: Fang Yan , Ao Chi Kit , Jiang Yan , Sun Yajuan , Chen Linfeng , Soh Siowling 
Published: March 2024

AbstractWhat is static charge? Despite the long history of research, the identity of static charge and mechanism by which static is generated by contact electrification are still unknown. Investigations are challenging due to the complexity of surfaces. This study involves the molecular-scale analysis of contact electrification using highly well-defined surfaces functionalized with a self-assembled monolayer of alkylsilanes. Analyses show the elementary molecular steps of contact electrification: the exact location of heterolytic cleavage of covalent bonds (i.e., Si-C bond), exact charged species generated (i.e., alkyl carbocation), and transfer of molecular fragments. The strong correlation between charge generation and molecular fragments due to their signature odd-even effects further shows that contact electrification is based on cleavage of covalent bonds and transfer of ionic molecular fragments. Static charge is thus an alkyl carbocation; in general, it is an ionic molecular fragment. This mechanism based on cleavage of covalent bonds is applicable to general types of insulating materials, such as covalently bonded polymers. The odd-even effect of charging caused by the difference of only one atom explains the highly sensitive nature of contact electrification.
Long-term monitoring of ultratrace nucleic acids using tetrahedral nanostructure-based NgAgo on wearable microneedles
Authors: Yang Bin , Wang Haonan , Kong Jilie , Fang Xueen 
Published: March 2024

AbstractReal-time and continuous monitoring of nucleic acid biomarkers with wearable devices holds potential for personal health management, especially in the context of pandemic surveillance or intensive care unit disease. However, achieving high sensitivity and long-term stability remains challenging. Here, we report a tetrahedral nanostructure-based Natronobacterium gregoryi Argonaute (NgAgo) for long-term stable monitoring of ultratrace unamplified nucleic acids (cell-free DNAs and RNAs) in vivo for sepsis on wearable device. This integrated wireless wearable consists of a flexible circuit board, a microneedle biosensor, and a stretchable epidermis patch with enrichment capability. We comprehensively investigate the recognition mechanism of nucleic acids by NgAgo/guide DNA and signal transformation within the Debye distance. In vivo experiments demonstrate the suitability for real-time monitoring of cell-free DNA and RNA with a sensitivity of 0.3 fM up to 14 days. These results provide a strategy for highly sensitive molecular recognition in vivo and for on-body detection of nucleic acid.
In-cell NMR suggests that DNA i-motif levels are strongly depleted in living human cells
Authors: Víšková Pavlína , Ištvánková Eva , Ryneš Jan , Džatko Šimon , Loja Tomáš , Živković Martina Lenarčič , Rigo Riccardo , El-Khoury Roberto , Serrano-Chacón Israel , Damha Masad J. , González Carlos , Mergny Jean-Louis , Foldynová-Trantírková Silvie , Trantírek Lukáš 
Published: March 2024

AbstractI-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single-stranded, cytosine-rich genomic regions with regulatory roles. Chromatin, protein interactions, and intracellular properties seem to govern iM formation at sites with i-motif formation propensity (iMFPS) in human cells, yet their specific contributions remain unclear. Using in-cell NMR with oligonucleotide iMFPS models, we monitor iM-associated structural equilibria in asynchronous and cell cycle-synchronized HeLa cells at 37 °C. Our findings show that iMFPS displaying pHT < 7 under reference in vitro conditions occur predominantly in unfolded states in cells, while those with pHT > 7 appear as a mix of folded and unfolded states depending on the cell cycle phase. Comparing these results with previous data obtained using an iM-specific antibody (iMab) reveals that cell cycle-dependent iM formation has a dual origin, and iM formation concerns only a tiny fraction (possibly 1%) of genomic sites with iM formation propensity. We propose a comprehensive model aligning observations from iMab and in-cell NMR and enabling the identification of iMFPS capable of adopting iM structures under physiological conditions in living human cells. Our results suggest that many iMFPS may have biological roles linked to their unfolded states.