bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOXC11 drives lung adenocarcinoma progression through transcriptional regulation of SPHK1
Authors: Peng Xin , Liu Xiaoli , Hu Wanshan , Zhou Yanling , Ouyang Lianlian , Peng Xintong , Long Yao , Sun Jingyue , Tao Tania , Chen Ling , Shi Ying , Tao Yongguang , Xiao Desheng , Liu Shuang 
Published: February 2023

AbstractLung adenocarcinoma (LUAD) is a fatal threat to human health, while the mechanism remains unclear, and the therapy brings limited therapeutic effects. Transcription factor Homeobox C11 (HOXC11) was previously proved to be related to hind limbs and metanephric development during the embryonic phase, and its role in tumors has been gradually recognized. Our study found that HOXC11 overexpressed in LUAD and was associated with worse overall survival. Moreover, its expression in lung cancer was regulated by IκB kinase α (IKKα), a pivotal kinase in NF-κB signaling, which was related to the ubiquitination of HOXC11. We further proved that HOXC11 could enhance the ability of proliferation, migration, invasion, colony formation, and the progression of the cell cycle in LUAD cells. Meanwhile, it also accelerated the formation of subcutaneous and lung metastases tumors. In contrast, loss of HOXC11 in LUAD cells significantly inhibited these malignant phenotypes. At the same time, HOXC11 regulated the expression of sphingosine kinase 1 (SPHK1) by directly binding to its promoter region. Therefore, we conclude that HOXC11 impacts the development of LUAD and facilitates lung cancer progression by promoting the expression of SPHK1.
A first-in-class POLRMT specific inhibitor IMT1 suppresses endometrial carcinoma cell growth
Authors: Li Shu-ping , Ou Li , Zhang Yan , Shen Fang-rong , Chen You-guo 
Published: February 2023

AbstractExploring novel molecularly-targeted therapies for endometrial carcinoma is important. The current study explored the potential anti-endometrial carcinoma activity by a first-in-class POLRMT (RNA polymerase mitochondrial) inhibitor IMT1. In patient-derived primary human endometrial carcinoma cells and established lines, treatment with IMT1 potently inhibited cell viability, proliferation, cell-cycle progression and motility, while inducing robust caspase-apoptosis activation. Treatment with the PLORMT inhibitor impaired mitochondrial functions, leading to mtDNA (mitochondrial DNA) transcription inhibition, mitochondrial membrane potential decline, reactive oxygen species formation, oxidative stress and ATP loss in the endometrial carcinoma cells. Similarly, POLRMT depletion, through shRNA-induced silencing or CRISPR/Cas9-caused knockout (KO), inhibited primary endometrial carcinoma cell proliferation and motility, and induced mitochondrial dysfunction and apoptosis. Importantly, IMT1 failed to induce further cytotoxicity in POLRMT-KO endometrial carcinoma cells. Contrarily, ectopic overexpression of POLRMT further augmented proliferation and motility of primary endometrial carcinoma cells. In vivo, oral administration of a single dose of IMT1 substantially inhibited endometrial carcinoma xenograft growth in the nude mice. mtDNA transcription inhibition, oxidative stress, ATP loss and apoptosis were detected in IMT1-treated endometrial carcinoma xenograft tissues. Together, targeting PLORMT by IMT1 inhibited endometrial carcinoma cell growth in vitro and in vivo.
Identification of matrix-remodeling associated 5 as a possible molecular oncotarget of pancreatic cancer
Authors: Peng Shi-qing , Zhu Xiao-ren , Zhao Ming-zhi , Zhang Yi-fan , Wang An-ran , Chen Min-bin , Ye Zhen-yu 
Published: February 2023

AbstractPancreatic cancer has an extremely poor prognosis. Here we examined expression, potential functions and underlying mechanisms of MXRA5 (matrix remodeling associated 5) in pancreatic cancer. Bioinformatics studies revealed that MXRA5 transcripts are significantly elevated in pancreatic cancer tissues, correlating with the poor overall survival, high T-stage, N1 and pathologic stage of the patients. MXRA5 mRNA and protein expression is significantly elevated in microarray pancreatic cancer tissues and different pancreatic cancer cells. In primary and immortalized (BxPC-3 and PANC-1 lines) pancreatic cancer cells, shRNA-induced MXRA5 silencing or CRISPR/Cas9-mediated MXRA5 knockout suppressed cell survival, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while provoking cell apoptosis. Conversely, forced overexpression of MXRA5 further promoted pancreatic cancer cell progression and EMT. Bioinformatics studies and the protein chip analyses revealed that differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in MXRA5-overexpressed primary pancreatic cancer cells were enriched in the PI3K-Akt-mTOR cascade. Indeed, Akt-mTOR activation in primary human pancreatic cancer cells was inhibited by MXRA5 shRNA or knockout, but was augmented following MXRA5 overexpression. In vivo, the growth of MXRA5 KO PANC-1 xenografts was largely inhibited in nude mice. Moreover, intratumoral injection of adeno-associated virus-packed MXRA5 shRNA potently inhibited primary pancreatic cancer cell growth in nude mice. Akt-mTOR activation was also largely inhibited in the MXRA5-depleted pancreatic cancer xenografts. Contrarily MXRA5 overexpression promoted primary pancreatic cancer cell growth in nude mice. Together, overexpressed MXRA5 is important for pancreatic cancer cell growth possibly through promoting EMT and Akt-mTOR activation. MXRA5 could be a potential therapeutic oncotarget for pancreatic cancer.
Dark microbiome and extremely low organics in Atacama fossil delta unveil Mars life detection limits
Authors: Azua-Bustos Armando , Fairén Alberto G. , González-Silva Carlos , Prieto-Ballesteros Olga , Carrizo Daniel , Sánchez-García Laura , Parro Victor , Fernández-Martínez Miguel Ángel , Escudero Cristina , Muñoz-Iglesias Victoria , Fernández-Sampedro Maite , Molina Antonio , Villadangos Miriam García , Moreno-Paz Mercedes , Wierzchos Jacek , Ascaso Carmen , Fornaro Teresa , Brucato John Robert , Poggiali Giovanni , Manrique Jose Antonio , Veneranda Marco , López-Reyes Guillermo , Sanz-Arranz Aurelio , Rull Fernando , Ollila Ann M. , Wiens Roger C. , Reyes-Newell Adriana , Clegg Samuel M. , Millan Maëva , Johnson Sarah Stewart , McIntosh Ophélie , Szopa Cyril , Freissinet Caroline , Sekine Yasuhito , Fukushi Keisuke , Morida Koki , Inoue Kosuke , Sakuma Hiroshi , Rampe Elizabeth 
Published: February 2023

AbstractIdentifying unequivocal signs of life on Mars is one of the most important objectives for sending missions to the red planet. Here we report Red Stone, a 163-100 My alluvial fan–fan delta that formed under arid conditions in the Atacama Desert, rich in hematite and mudstones containing clays such as vermiculite and smectites, and therefore geologically analogous to Mars. We show that Red Stone samples display an important number of microorganisms with an unusual high rate of phylogenetic indeterminacy, what we refer to as “dark microbiome”, and a mix of biosignatures from extant and ancient microorganisms that can be barely detected with state-of-the-art laboratory equipment. Our analyses by testbed instruments that are on or will be sent to Mars unveil that although the mineralogy of Red Stone matches that detected by ground-based instruments on the red planet, similarly low levels of organics will be hard, if not impossible to detect in Martian rocks depending on the instrument and technique used. Our results stress the importance in returning samples to Earth for conclusively addressing whether life ever existed on Mars.
Social complexity, life-history and lineage influence the molecular basis of castes in vespid wasps
Authors: Wyatt Christopher Douglas Robert , Bentley Michael Andrew , Taylor Daisy , Favreau Emeline , Brock Ryan Edward , Taylor Benjamin Aaron , Bell Emily , Leadbeater Ellouise , Sumner Seirian 
Published: February 2023

AbstractA key mechanistic hypothesis for the evolution of division of labour in social insects is that a shared set of genes co-opted from a common solitary ancestral ground plan (a genetic toolkit for sociality) regulates caste differentiation across levels of social complexity. Using brain transcriptome data from nine species of vespid wasps, we test for overlap in differentially expressed caste genes and use machine learning models to predict castes using different gene sets. We find evidence of a shared genetic toolkit across species representing different levels of social complexity. We also find evidence of additional fine-scale differences in predictive gene sets, functional enrichment and rates of gene evolution that are related to level of social complexity, lineage and of colony founding. These results suggest that the concept of a shared genetic toolkit for sociality may be too simplistic to fully describe the process of the major transition to sociality.
Variant Plateau’s law in atomically thin transition metal dichalcogenide dome networks
Authors: Liu Boqing , Yildirim Tanju , Lü Tieyu , Blundo Elena , Wang Li , Jiang Lixue , Zou Hongshuai , Zhang Lijun , Zhao Huijun , Yin Zongyou , Tian Fangbao , Polimeni Antonio , Lu Yuerui 
Published: February 2023

AbstractSince its fundamental inception from soap bubbles, Plateau’s law has sparked extensive research in equilibrated states. However, most studies primarily relied on liquids, foams or cellular structures, whereas its applicability has yet to be explored in nano-scale solid films. Here, we observed a variant Plateau’s law in networks of atomically thin domes made of solid two-dimensional (2D) transition metal dichalcogenides (TMDs). Discrete layer-dependent van der Waals (vdWs) interaction energies were experimentally and theoretically obtained for domes protruding in different TMD layers. Significant surface tension differences from layer-dependent vdWs interaction energies manifest in a variant of this fundamental law. The equivalent surface tension ranges from 2.4 to 3.6 N/m, around two orders of magnitude greater than conventional liquid films, enabling domes to sustain high gas pressure and exist in a fundamentally variant nature for several years. Our findings pave the way towards exploring variant discretised states with applications in opto-electro-mechanical devices.
A bivalent remipede toxin promotes calcium release via ryanodine receptor activation
Authors: Maxwell Michael J. , Thekkedam Chris , Lamboley Cedric , Chin Yanni K.-Y. , Crawford Theo , Smith Jennifer J. , Liu Junyu , Jia Xinying , Vetter Irina , Laver Derek R. , Launikonis Bradley S. , Dulhunty Angela , Undheim Eivind A. B. , Mobli Mehdi 
Published: February 2023

AbstractMultivalent ligands of ion channels have proven to be both very rare and highly valuable in yielding unique insights into channel structure and pharmacology. Here, we describe a bivalent peptide from the venom of Xibalbanus tulumensis, a troglobitic arthropod from the enigmatic class Remipedia, that causes persistent calcium release by activation of ion channels involved in muscle contraction. The high-resolution solution structure of φ-Xibalbin3-Xt3a reveals a tandem repeat arrangement of inhibitor-cysteine knot (ICK) domains previously only found in spider venoms. The individual repeats of Xt3a share sequence similarity with a family of scorpion toxins that target ryanodine receptors (RyR). Single-channel electrophysiology and quantification of released Ca2+ stores within skinned muscle fibers confirm Xt3a as a bivalent RyR modulator. Our results reveal convergent evolution of RyR targeting toxins in remipede and scorpion venoms, while the tandem-ICK repeat architecture is an evolutionary innovation that is convergent with toxins from spider venoms.
Abstract representations emerge naturally in neural networks trained to perform multiple tasks
Authors: Johnston W. Jeffrey , Fusi Stefano 
Published: February 2023

AbstractHumans and other animals demonstrate a remarkable ability to generalize knowledge across distinct contexts and objects during natural behavior. We posit that this ability to generalize arises from a specific representational geometry, that we call abstract and that is referred to as disentangled in machine learning. These abstract representations have been observed in recent neurophysiological studies. However, it is unknown how they emerge. Here, using feedforward neural networks, we demonstrate that the learning of multiple tasks causes abstract representations to emerge, using both supervised and reinforcement learning. We show that these abstract representations enable few-sample learning and reliable generalization on novel tasks. We conclude that abstract representations of sensory and cognitive variables may emerge from the multiple behaviors that animals exhibit in the natural world, and, as a consequence, could be pervasive in high-level brain regions. We also make several specific predictions about which variables will be represented abstractly.
Attosecond-Angstrom free-electron-laser towards the cold beam limit
Authors: Habib A. F. , Manahan G. G. , Scherkl P. , Heinemann T. , Sutherland A. , Altuiri R. , Alotaibi B. M. , Litos M. , Cary J. , Raubenheimer T. , Hemsing E. , Hogan M. J. , Rosenzweig J. B. , Williams P. H. , McNeil B. W. J. , Hidding B. 
Published: February 2023

AbstractElectron beam quality is paramount for X-ray pulse production in free-electron-lasers (FELs). State-of-the-art linear accelerators (linacs) can deliver multi-GeV electron beams with sufficient quality for hard X-ray-FELs, albeit requiring km-scale setups, whereas plasma-based accelerators can produce multi-GeV electron beams on metre-scale distances, and begin to reach beam qualities sufficient for EUV FELs. Here we show, that electron beams from plasma photocathodes many orders of magnitude brighter than state-of-the-art can be generated in plasma wakefield accelerators (PWFAs), and then extracted, captured, transported and injected into undulators without significant quality loss. These ultrabright, sub-femtosecond electron beams can drive hard X-FELs near the cold beam limit to generate coherent X-ray pulses of attosecond-Angstrom class, reaching saturation after only 10 metres of undulator. This plasma-X-FEL opens pathways for advanced photon science capabilities, such as unperturbed observation of electronic motion inside atoms at their natural time and length scale, and towards higher photon energies.
An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats
Authors: Iwasaki Mai , Lefevre Arthur , Althammer Ferdinand , Clauss Creusot Etienne , Łąpieś Olga , Petitjean Hugues , Hilfiger Louis , Kerspern Damien , Melchior Meggane , Küppers Stephanie , Krabichler Quirin , Patwell Ryan , Kania Alan , Gruber Tim , Kirchner Matthew K. , Wimmer Moritz , Fröhlich Henning , Dötsch Laura , Schimmer Jonas , Herpertz Sabine C. , Ditzen Beate , Schaaf Christian P. , Schönig Kai , Bartsch Dusan , Gugula Anna , Trenk Aleksandra , Blasiak Anna , Stern Javier E. , Darbon Pascal , Grinevich Valery , Charlet Alexandre 
Published: February 2023

AbstractThe hypothalamic neuropeptide oxytocin (OT) exerts prominent analgesic effects via central and peripheral action. However, the precise analgesic pathways recruited by OT are largely elusive. Here we discovered a subset of OT neurons whose projections preferentially terminate on OT receptor (OTR)-expressing neurons in the ventrolateral periaqueductal gray (vlPAG). Using a newly generated line of transgenic rats (OTR-IRES-Cre), we determined that most of the vlPAG OTR expressing cells targeted by OT projections are GABAergic. Ex vivo stimulation of parvocellular OT axons in the vlPAG induced local OT release, as measured with OT sensor GRAB. In vivo, optogenetically-evoked axonal OT release in the vlPAG of as well as chemogenetic activation of OTR vlPAG neurons resulted in a long-lasting increase of vlPAG neuronal activity. This lead to an indirect suppression of sensory neuron activity in the spinal cord and strong analgesia in both female and male rats. Altogether, we describe an OT-vlPAG-spinal cord circuit that is critical for analgesia in both inflammatory and neuropathic pain models.
Toward incompatible quantum limits on multiparameter estimation
Authors: Xia Binke , Huang Jingzheng , Li Hongjing , Wang Han , Zeng Guihua 
Published: February 2023

AbstractAchieving the ultimate precisions for multiple parameters simultaneously is an outstanding challenge in quantum physics, because the optimal measurements for incompatible parameters cannot be performed jointly due to the Heisenberg uncertainty principle. In this work, a criterion proposed for multiparameter estimation provides a possible way to beat this curse. According to this criterion, it is possible to mitigate the influence of incompatibility meanwhile improve the ultimate precisions by increasing the variances of the parameter generators simultaneously. For demonstration, a scheme involving high-order Hermite-Gaussian states as probes is proposed for estimating the spatial displacement and angular tilt of light at the same time, and precisions up to 1.45 nm and 4.08 nrad are achieved in experiment simultaneously. Consequently, our findings provide a deeper insight into the role of Heisenberg uncertainty principle in multiparameter estimation, and contribute in several ways to the applications of quantum metrology.
Nuclear quantum effects on zeolite proton hopping kinetics explored with machine learning potentials and path integral molecular dynamics
Authors: Bocus Massimo , Goeminne Ruben , Lamaire Aran , Cools-Ceuppens Maarten , Verstraelen Toon , Van Speybroeck Veronique 
Published: February 2023

AbstractProton hopping is a key reactive process within zeolite catalysis. However, the accurate determination of its kinetics poses major challenges both for theoreticians and experimentalists. Nuclear quantum effects (NQEs) are known to influence the structure and dynamics of protons, but their rigorous inclusion through the path integral molecular dynamics (PIMD) formalism was so far beyond reach for zeolite catalyzed processes due to the excessive computational cost of evaluating all forces and energies at the Density Functional Theory (DFT) level. Herein, we overcome this limitation by training first a reactive machine learning potential (MLP) that can reproduce with high fidelity the DFT potential energy surface of proton hopping around the first Al coordination sphere in the H-CHA zeolite. The MLP offers an immense computational speedup, enabling us to derive accurate reaction kinetics beyond standard transition state theory for the proton hopping reaction. Overall, more than 0.6 μs of simulation time was needed, which is far beyond reach of any standard DFT approach. NQEs are found to significantly impact the proton hopping kinetics up to ~473 K. Moreover, PIMD simulations with deuterium can be performed without any additional training to compute kinetic isotope effects over a broad range of temperatures.
Order-disorder charge density wave instability in the kagome metal (Cs,Rb)V3Sb5
Authors: Subires D. , Korshunov A. , Said A. H. , Sánchez L. , Ortiz Brenden R. , Wilson Stephen D. , Bosak A. , Blanco-Canosa S. 
Published: February 2023

AbstractThe origin of the charge density wave phases in the kagome metal compound AV3Sb5 is still under great scrutiny. Here, we combine diffuse and inelastic x-ray scattering to identify a 3-dimensional precursor of the charge order at the L point that condenses into a CDW through a first order phase transition. The quasi-elastic critical scattering indicates that the dominant contribution to the diffuse precursor is the elastic central peak without phonon softening. However, the inelastic spectra show a small broadening of the Einstein-type phonon mode on approaching TCDW. Our results point to the situation where the Fermi surface instability at the L point is of order-disorder type with critical growth of quasi-static domains. The experimental data indicate that the CDW consists on an alternating Star of David and trihexagonal distortions and its dynamics goes beyond the classical weak-coupling scenario and is discussed within strong-electron phonon coupling and non-adiabatic models.
Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis
Authors: Han Younghun , Byun Jinyoung , Zhu Catherine , Sun Ryan , Roh Julia Y. , Cordell Heather J. , Lee Hyun-Sung , Shaw Vikram R. , Kang Sung Wook , Razjouyan Javad , Cooley Matthew A. , Hassan Manal M. , Siminovitch Katherine A. , Folseraas Trine , Ellinghaus David , Bergquist Annika , Rushbrook Simon M. , Franke Andre , Karlsen Tom H. , Lazaridis Konstantinos N. ,   The International PSC Study Group, Schramm Christoph , Shapiro David , Goode Elizabeth , McGlynn Katherine A. , Roberts Lewis R. , Amos Christopher I. 
Published: February 2023

AbstractPrimary sclerosing cholangitis (PSC) is a rare autoimmune bile duct disease that is strongly associated with immune-mediated disorders. In this study, we implemented multitrait joint analyses to genome-wide association summary statistics of PSC and numerous clinical and epidemiological traits to estimate the genetic contribution of each trait and genetic correlations between traits and to identify new lead PSC risk-associated loci. We identified seven new loci that have not been previously reported and one new independent lead variant in the previously reported locus. Functional annotation and fine-mapping nominated several potential susceptibility genes such as MANBA and IRF5. Network-based in silico drug efficacy screening provided candidate agents for further study of pharmacological effect in PSC.
Single-cell transcriptome profiling of the stepwise progression of head and neck cancer
Authors: Choi Ji-Hye , Lee Bok-Soon , Jang Jeon Yeob , Lee Yun Sang , Kim Hyo Jeong , Roh Jin , Shin Yoo Seob , Woo Hyun Goo , Kim Chul-Ho 
Published: February 2023

AbstractHead and neck squamous cell carcinoma (HNSCC) undergoes stepwise progression from normal tissues to precancerous leukoplakia, primary HNSCC, and metastasized tumors. To delineate the heterogeneity of tumor cells and their interactions during the progression of HNSCC, we employ single-cell RNA-seq profiling for normal to metastasized tumors. We can identify the carcinoma in situ cells in leukoplakia lesions that are not detected by pathological examination. In addition, we identify the cell type subsets of the Galectin 7B (LGALS7B)-expressing malignant cells and CXCL8-expressing fibroblasts, demonstrating that their abundance in tumor tissue is associated with unfavorable prognostic outcomes. We also demonstrate the interdependent ligand-receptor interaction of COL1A1 and CD44 between fibroblasts and malignant cells, facilitating HNSCC progression. Furthermore, we report that the regulatory T cells in leukoplakia and HNSCC tissues express LAIR2, providing a favorable environment for tumor growth. Taken together, our results update the pathobiological insights into cell-cell interactions during the stepwise progression of HNSCCs.