bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Full Vector Archeomagnetic Data From Northern Mexico
Authors: Tchibinda Madingou B. , Perrin M. , Hervé G. , Hernàndez Cardona A. , Alva‐Valdivia L. M. , Cruz Antillón R. 
Published: September 2021

AbstractSeveral regional secular variation curves of the geomagnetic field have been proposed for Mexico over the last millennia. Despite a fairly large number of archeomagnetic data, these curves remain imprecise because of an uneven quality and geographic distribution, with a lack of data in Northern Mexico. Nine pottery kilns were sampled in Casas de Fuego, an archeological site in the Chihuahua state. These kilns belong to the Casas Grandes culture and were in use between 1250 and 1450 CE. Rock magnetic experiments indicate that the main magnetic phase is a Ti‐poor titanomagnetite in the SD range. Mean characteristic directions per kiln were estimated by alternating field and/or thermal demagnetization, and archeointensities with the Thellier‐Thellier protocol, after correction for anisotropy and cooling effects. The nine directions and eight intensities agree with data from USA and Mexico but do not support the peak in inclination modeled by the Mexican secular variation curve around 1200–1300 CE. For the last millennium, the Western North American curve is consistent with the SHAWQ2k global model, and better reflects the secular variation in Northern Mexico. For intensity, neither the SHAWQ2k model nor the regional intensity curve can depict the rapid secular variation that likely occurs circa 1500 CE. The Casas de Fuego results are the first full vector determinations obtained in Northern Mexico.
Programmed cell death 10 promotes metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma via PP2Ac-mediated YAP activation
Authors: Sun Bo , Zhong Fang-Jing , Xu Cong , Li Yi-Ming , Zhao Yan-Rong , Cao Mo-Mo , Yang Lian-Yue 
Published: September 2021

AbstractTumour metastasis is the main cause of postoperative tumour recurrence and mortality in patients with hepatocellular carcinoma (HCC), but the underlying mechanism remains unclear. Accumulating evidence has demonstrated that programmed cell death 10 (PDCD10) plays an important role in many biological processes. However, the role of PDCD10 in HCC progression is still elusive. In this study, we aimed to explore the clinical significance and molecular function of PDCD10 in HCC. PDCD10 is significantly upregulated in HCC, which also correlates with aggressive clinicopathological characteristics and predicts poor prognosis of HCC patients after liver resection. High PDCD10 expression promotes HCC cell proliferation, migration, and invasion in vitro and tumour growth, metastasis in vivo. In addition, PDCD10 could facilitate epithelial-to-mesenchymal transition (EMT) of HCC cells. In terms of the mechanism, PDCD10 directly binds to the catalytic subunit of protein phosphatase 2A (PP2Ac) and increases its enzymatic activity, leading to the interaction of YAP and dephosphorylation of the YAP protein. This interaction contributes to YAP nuclear translocation and transcriptional activation. PP2Ac is necessary for PDCD10-mediated HCC progression. Knocking down PP2Ac abolished the tumour-promoting role of PDCD10 in the migration, invasion and EMT of HCC. Moreover, a PP2Ac inhibitor (LB100) could restrict tumour growth and metastasis of HCC with high PDCD10 expression. Collectively, PDCD10 promotes EMT and the progression of HCC by interacting with PP2Ac to promote YAP activation, which provides new insight into the mechanism of cancer metastasis. PDCD10 may be a potential prognostic biomarker and therapeutic target for HCC.
Single-cell RNA-Seq reveals transcriptional heterogeneity and immune subtypes associated with disease activity in human myasthenia gravis
Authors: Jin Wanlin , Yang Qi , Peng Yuyao , Yan Chengkai , Li Yi , Luo Zhaohui , Xiao Bo , Xu Liqun , Yang Huan 
Published: September 2021

AbstractMyasthenia gravis (MG) is a rare autoimmune disease. Although the impact of immune cell disorder in MG has been extensively studied, little is known about the transcriptomes of individual cells. Here, we assessed the transcriptional profiles of 39,243 cells by single-cell sequencing and identified 13 major cell clusters, along with 39 subgroups of cells derived from patients with new-onset myasthenia gravis and healthy controls. We found that B cells, CD4+T cells, and monocytes exhibited more heterogeneity in MG patients. CD4+T cells were expanded in MG patients. We reclustered B cells and CD4+T cells, and predict their essential regulators. Further analyses demonstrated that B cells in MG exhibited higher transcriptional activity towards plasma cell differentiation, CD4+T cell subsets were unbalanced, and inflammatory pathways of monocytes were highly activated. Notably, we discovered a disease-relevant subgroup, CD180−B cells. Increased CD180−B cells in MG are indicative of a high IgG composition and were associated with disease activity and the anti-AChR antibody. Together, our data further the understanding of the cellular heterogeneity involved in the pathogenesis of MG and provide large cell-type-specific markers for subsequent research.
Development and biological characterization of a clinical gene transfer vector for the treatment of MAK-associated retinitis pigmentosa
Authors: Tucker Budd A. , Burnight Erin R. , Cranston Cathryn M. , Ulferts Mallory J. , Luse Meagan A. , Westfall Trudi , Scott C. Anthony , Marsden Autumn , Gibson-Corley Katherine , Wiley Luke A. , Han Ian C. , Slusarski Diane C. , Mullins Robert F. , Stone Edwin M. 
Published: September 2021

AbstractBy combining next generation whole exome sequencing and induced pluripotent stem cell (iPSC) technology we found that an Alu repeat inserted in exon 9 of the MAK gene results in a loss of normal MAK transcript and development of human autosomal recessive retinitis pigmentosa (RP). Although a relatively rare cause of disease in the general population, the MAK variant is enriched in individuals of Jewish ancestry. In this population, 1 in 55 individuals are carriers and one third of all cases of recessive RP is caused by this gene. The purpose of this study was to determine if a viral gene augmentation strategy could be used to safely restore functional MAK protein as a step toward a treatment for early stage MAK-associated RP. Patient iPSC-derived photoreceptor precursor cells were generated and transduced with viral vectors containing the MAK transcript. One week after transduction, transcript and protein could be detected via rt-PCR and western blotting respectively. Using patient-derived fibroblast cells and mak knockdown zebra fish we demonstrate that over-expression of the retinal MAK transgene restored the cells ability to regulate primary cilia length. In addition, the visual defect in mak knockdown zebrafish was mitigated via treatment with the retinal MAK transgene. There was no evidence of local or systemic toxicity at 1-month or 3-months following subretinal delivery of clinical grade vector into wild type rats. The findings reported here will help pave the way for initiation of a phase 1 clinical trial for the treatment of patients with MAK-associated RP.
Glycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses
Authors: Broszeit Frederik , van Beek Rosanne J. , Unione Luca , Bestebroer Theo M. , Chapla Digantkumar , Yang Jeong-Yeh , Moremen Kelley W. , Herfst Sander , Fouchier Ron A. M. , de Vries Robert P. , Boons Geert-Jan 
Published: September 2021

AbstractDuring circulation in humans and natural selection to escape antibody recognition for decades, A/H3N2 influenza viruses emerged with altered receptor specificities. These viruses lost the ability to agglutinate erythrocytes critical for antigenic characterization and give low yields and acquire adaptive mutations when cultured in eggs and cells, contributing to recent vaccine challenges. Examination of receptor specificities of A/H3N2 viruses reveals that recent viruses compensated for decreased binding of the prototypic human receptor by recognizing α2,6-sialosides on extended LacNAc moieties. Erythrocyte glycomics shows an absence of extended glycans providing a rationale for lack of agglutination by recent A/H3N2 viruses. A glycan remodeling approach installing functional receptors on erythrocytes, allows antigenic characterization of recent A/H3N2 viruses confirming the cocirculation of antigenically different viruses in humans. Computational analysis of HAs in complex with sialosides having extended LacNAc moieties reveals that mutations distal to the RBD reoriented the Y159 side chain resulting in an extended receptor binding site.
Slow update of internal representations impedes synchronization in autism
Authors: Vishne Gal , Jacoby Nori , Malinovitch Tamar , Epstein Tamir , Frenkel Or , Ahissar Merav 
Published: September 2021

AbstractAutism is a neurodevelopmental disorder characterized by impaired social skills, motor and perceptual atypicalities. These difficulties were explained within the Bayesian framework as either reflecting oversensitivity to prediction errors or – just the opposite – slow updating of such errors. To test these opposing theories, we administer paced finger-tapping, a synchronization task that requires use of recent sensory information for fast error-correction. We use computational modelling to disentangle the contributions of error-correction from that of noise in keeping temporal intervals, and in executing motor responses. To assess the specificity of tapping characteristics to autism, we compare performance to both neurotypical individuals and individuals with dyslexia. Only the autism group shows poor sensorimotor synchronization. Trial-by-trial modelling reveals typical noise levels in interval representations and motor responses. However, rate of error correction is reduced in autism, impeding synchronization ability. These results provide evidence for slow updating of internal representations in autism.
Aluminum nitride nanophotonics for beyond-octave soliton microcomb generation and self-referencing
Authors: Liu Xianwen , Gong Zheng , Bruch Alexander W. , Surya Joshua B. , Lu Juanjuan , Tang Hong X. 
Published: September 2021

AbstractFrequency microcombs, alternative to mode-locked laser and fiber combs, enable miniature rulers of light for applications including precision metrology, molecular fingerprinting and exoplanet discoveries. To enable frequency ruling functions, microcombs must be stabilized by locking their carrier-envelope offset frequency. So far, the microcomb stabilization remains compounded by the elaborate optics external to the chip, thus evading its scaling benefit. To address this challenge, here we demonstrate a nanophotonic chip solution based on aluminum nitride thin films, which simultaneously offer optical Kerr nonlinearity for generating octave soliton combs and quadratic nonlinearity for enabling heterodyne detection of the offset frequency. The agile dispersion control of crystalline aluminum nitride photonics permits high-fidelity generation of solitons with features including 1.5-octave spectral span, dual dispersive waves, and sub-terahertz repetition rates down to 220 gigahertz. These attractive characteristics, aided by on-chip phase-matched aluminum nitride waveguides, allow the full determination of the offset frequency. Our proof-of-principle demonstration represents an important milestone towards fully integrated self-locked microcombs for portable optical atomic clocks and frequency synthesizers.
Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells
Authors: Zhang Jiang , Le Gras Stéphanie , Pouxvielh Kevin , Faure Fabrice , Fallone Lucie , Kern Nicolas , Moreews Marion , Mathieu Anne-Laure , Schneider Raphaël , Marliac Quentin , Jung Mathieu , Berton Aurore , Hayek Simon , Vidalain Pierre-Olivier , Marçais Antoine , Dodard Garvin , Dejean Anne , Brossay Laurent , Ghavi-Helm Yad , Walzer Thierry 
Published: September 2021

AbstractEOMES and T-BET are related T-box transcription factors that control natural killer (NK) cell development. Here we demonstrate that EOMES and T-BET regulate largely distinct gene sets during this process. EOMES is dominantly expressed in immature NK cells and drives early lineage specification by inducing hallmark receptors and functions. By contrast, T-BET is dominant in mature NK cells, where it induces responsiveness to IL-12 and represses the cell cycle, likely through transcriptional repressors. Regardless, many genes with distinct functions are co-regulated by the two transcription factors. By generating two gene-modified mice facilitating chromatin immunoprecipitation of endogenous EOMES and T-BET, we show a strong overlap in their DNA binding targets, as well as extensive epigenetic changes during NK cell differentiation. Our data thus suggest that EOMES and T-BET may distinctly govern, via differential expression and co-factors recruitment, NK cell maturation by inserting partially overlapping epigenetic regulations.
Quantum state tomography of molecules by ultrafast diffraction
Authors: Zhang Ming , Zhang Shuqiao , Xiong Yanwei , Zhang Hankai , Ischenko Anatoly A. , Vendrell Oriol , Dong Xiaolong , Mu Xiangxu , Centurion Martin , Xu Haitan , Miller R. J. Dwayne , Li Zheng 
Published: September 2021

AbstractUltrafast electron diffraction and time-resolved serial crystallography are the basis of the ongoing revolution in capturing at the atomic level of detail the structural dynamics of molecules. However, most experiments capture only the probability density of the nuclear wavepackets to determine the time-dependent molecular structures, while the full quantum state has not been accessed. Here, we introduce a framework for the preparation and ultrafast coherent diffraction from rotational wave packets of molecules, and we establish a new variant of quantum state tomography for ultrafast electron diffraction to characterize the molecular quantum states. The ability to reconstruct the density matrix, which encodes the amplitude and phase of the wavepacket, for molecules of arbitrary degrees of freedom, will enable the reconstruction of a quantum molecular movie from experimental x-ray or electron diffraction data.
Genetic basis and adaptation trajectory of soybean from its temperate origin to tropics
Authors: Dong Lidong , Fang Chao , Cheng Qun , Su Tong , Kou Kun , Kong Lingping , Zhang Chunbao , Li Haiyang , Hou Zhihong , Zhang Yuhang , Chen Liyu , Yue Lin , Wang Lingshuang , Wang Kai , Li Yongli , Gan Zhuoran , Yuan Xiaohui , Weller James L. , Lu Sijia , Kong Fanjiang , Liu Baohui 
Published: September 2021

AbstractSoybean (Glycine max) serves as a major source of protein and edible oils worldwide. The genetic and genomic bases of the adaptation of soybean to tropical regions remain largely unclear. Here, we identify the novel locus Time of Flowering 16 (Tof16), which confers delay flowering and improve yield at low latitudes and determines that it harbors the soybean homolog of LATE ELONGATED HYPOCOTYL (LHY). Tof16 and the previously identified J locus genetically additively but independently control yield under short-day conditions. More than 80% accessions in low latitude harbor the mutations of tof16 and j, which suggests that loss of functions of Tof16 and J are the major genetic basis of soybean adaptation into tropics. We suggest that maturity and yield traits can be quantitatively improved by modulating the genetic complexity of various alleles of the LHY homologs, J and E1. Our findings uncover the adaptation trajectory of soybean from its temperate origin to the tropics.
Parity associates with chromosomal damage in uterine leiomyomas
Authors: Kuisma Heli , Bramante Simona , Rajamäki Kristiina , Sipilä Lauri J. , Kaasinen Eevi , Kaukomaa Jaana , Palin Kimmo , Mäkinen Netta , Sjöberg Jari , Sarvilinna Nanna , Taipale Jussi , Kauppi Liisa , Tumiati Manuela , Hassinen Antti , Pitkäniemi Janne , Jalkanen Jyrki , Heikkinen Sanna , Pasanen Annukka , Heikinheimo Oskari , Bützow Ralf , Välimäki Niko , Aaltonen Lauri A. 
Published: September 2021

AbstractMechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found.
Computational synthesis of substrates by crystal cleavage
Authors: Paul Joshua T. , Galdi Alice , Parzyck Christopher , M. Shen Kyle , Maxson Jared , Hennig Richard G. 
Published: September 2021

AbstractThe discovery of substrate materials has been dominated by trial and error, opening the opportunity for a systematic search. We generate bonding networks for materials from the Materials Project and systematically break up to three bonds in the networks for three-dimensional crystals. Successful cleavage reduces the bonding network to two periodic dimensions. We identify 4693 symmetrically unique cleavage surfaces across 2133 bulk crystals, 4626 of which have a maximum Miller index of one. We characterize the likelihood of cleavage by creating monolayers of these surfaces and calculating their thermodynamic stability using density functional theory to discover 3991 potential substrates. Following, we identify distinct trends in the work of cleavage and relate them to bonding in the three-dimensional precursor. We illustrate the potential impact of the substrate database by identifying several improved epitaxial substrates for the transparent conductor BaSnO3. The open-source databases of predicted and commercial substrates are available at MaterialsWeb.org.
Changes in cortical gene expression in the muscarinic M1 receptor knockout mouse: potential relevance to schizophrenia, Alzheimer’s disease and cognition
Authors: Dean Brian , Scarr Elizabeth 
Published: September 2021

AbstractPostmortem and neuroimaging studies show low levels of cortical muscarinic M1 receptors (CHRM1) in patients with schizophrenia which is significant because CHRM signalling has been shown to change levels of gene expression and cortical gene expression is altered in schizophrenia. We decided to identify CHRM1-mediated changes in cortical gene expression by measuring levels of RNA in the cortex of the Chrm1−/−mouse (n = 10), where there would be no signalling by that receptor, and in wild type mouse (n = 10) using the Affymetrix Mouse Exon 1.0 ST Array. We detected RNA for 15,501 annotated genes and noncoding RNA of which 1,467 RNAs were higher and 229 RNAs lower in the cortex of the Chrm1−/−mouse. Pathways and proteins affected by the changes in cortical gene expression in the Chrm1−/−are linked to the molecular pathology of schizophrenia. Our human cortical gene expression data showed 47 genes had altered expression in Chrm1−/−mouse and the frontal pole from patients with schizophrenia with the change in expression of 44 genes being in opposite directions. In addition, genes with altered levels of expression in the Chrm1−/−mouse have been shown to affect amyloid precursor protein processing which is associated with the pathophysiology of Alzheimer’s disease, and 69 genes with altered expression in the Chrm1−/−mouse are risk genes associated with human cognitive ability. Our findings argue CHRM1-mediated changes in gene expression are relevant to the pathophysiologies of schizophrenia and Alzheimer’s disease and the maintenance of cognitive ability in humans.
Unique clinical features and long term follow up of survivors of sudden cardiac death in an Asian multicenter study
Authors: Huang Pang-Shuo , Cheng Jen-Fang , Ko Wen-Chin , Chang Shu-Hsuan , Lin Tin-Tse , Chen Jien-Jiun , Chiu Fu-Chun , Lin Lian-Yu , Lai Ling-Ping , Lin Jiunn-Lee , Tsai Chia-Ti 
Published: September 2021

AbstractThere has been no long-term clinical follow-up data of survivors or victims of sudden cardiac death (SCD). The Taiwan multi-center sudden arrhythmia death syndrome follow-up and clinical study (TFS-SADS) is a collaborative multi-center study with median follow-up time 43 months. In this cohort, the clinical characteristics of these SADS patients were compared with those with ischemic heart disease (IHD). In this SCD cohort, around half (42%) were patients with IHD, which was different from Caucasian SCD cohorts. Among those with normal heart, most had Brugada syndrome (BrS). Compared to those with SADS, patients with IHD were older, more males and more comorbidities, more arrhythmic death, and lower left ventricular ejection fraction. In the long-term follow-up, patients with SADS had a better survival than those with IHD (p < 0.001). In the Cox regression analysis to identify the independent predictors of mortality, older age, lower LVEF, prior myocardial infarction and history of out-of-hospital cardiac arrest were associated with higher mortality and beta blocker use and idiopathic ventricular fibrillation or tachycardia (IVF/IVT) with a better survival during follow-up. History of prior MI was associated with more arrhythmic death. Several distinct features of SCD were found in the Asia–Pacific region, such as higher proportion of SADS, poorer prognosis of LQTS and better prognosis of IVF/IVT. Patients with SADS had a better survival than those with IHD. For those with SADS, patients with channelopathy had a better survival than those with cardiomyopathy.
CXCL9 as a key biomarker of vitiligo activity and prediction of the success of cultured melanocyte transplantation
Authors: Lin Fuquan , Hu Wenting , Xu Wen , Zhou Miaoni , Xu Ai‑E. 
Published: September 2021

AbstractThis study aimed to investigate the potential biomarkers of vitiligo by evaluating the disease activity and curative effect of autologous cultured pure melanocyte transplantation (CMT) on patients. Altogether, 36patients with stable vitiligo were treated with CMT. Blister fluid samples were collected from patients with stable vitiligo. Patients with active vitiligo were matched with healthy controls. The chemokine levels in the serum and blister fluid samples were measured using Luminex. The curative effect on patients with stable vitiligo was evaluated 6 months after treatment. Treatment responses were defined according to the extent of repigmentation as effective (if 50% or more repigmentation was achieved) or ineffective (if less than 50% or worse repigmentation was achieved). Patients received re-transplantation if the initial treatment was ineffective. The levels of C-X-C motif chemokine ligand (CXCL)9 and CXCL10 in blister fluid samples were significantly lower in stable patients than in active participants. Receiver operating characteristic analysis revealed that the levels of CXCL9 and CXCL10 were sensitive and specific in diagnosing active vitiligo. Further, 65.6% (21/32) of patients who received CMT had effective treatment responses. The high CXCL9 level in the blister fluid was a significant predictor of ineffective treatment responses. The treatment response was significantly enhanced after treatment. Four patients with ineffective treatment responses received anti-inflammatory treatment and re-transplantation. The CXCL9 and CXCL10 levels in the blister fluid were related to the presence of active vitiligo. Also, the CXCL9 level was a predictor of the effectiveness of CMT in treating vitiligo.