bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fault Throw and Regional Uplift Histories From Drainage Analysis: Evolution of Southern Italy
Authors: Quye‐Sawyer Jennifer , Whittaker Alexander C. , Roberts Gareth G. , Rood Dylan H. 
Published: March 2021

AbstractLandscapes can record elevation changes caused by multiple tectonic processes. Here, we show how coeval histories of spatially coincident normal faulting and regional uplift can be deconvolved from river networks. We focus on Calabria, a tectonically active region incised by rivers containing knickpoints and knickzones. Marine fauna indicate that Calabria has been uplifted by >1 km since ∼0.8–1.2 Ma, which we used to calibrate parameters in a stream power erosional model. To deconvolve the local and regional uplift contributions to topography, we performed a spatiotemporal inversion of 994 fluvial longitudinal profiles. Uplift rates from fluvial inversion replicate the spatial trend of rates derived from dated Mid‐Late Pleistocene marine terraces, and the magnitude of predicted uplift rates matches the majority of marine terrace uplift rates. We used the predicted uplift history to analyze long‐term fault throw, and combined throw estimates with ratios of footwall uplift to hanging wall subsidence to isolate the nonfault related contribution to uplift. Increases in fault throw rate—which may suggest fault linkage and growth—have been identified on two major faults from fluvial inverse modeling, and total fault throw is consistent with independent estimates. The temporal evolution of nonfault related regional uplift is similar at three locations. Our results may be consistent with toroidal mantle flow generating uplift, perhaps if faulting reduces the strength of the overriding plate. In conclusion, fluvial inverse modeling can be an effective technique to quantify fault array evolution and can deconvolve different sources of uplift that are superimposed in space and time.
Random‐Walk Modeling of Reactive Transport in Porous Media With a Reduced‐Order Chemical Basis of Conservative Components
Authors: Sole‐Mari Guillem , Schmidt Michael J. , Bolster Diogo , Fernàndez‐Garcia Daniel 
Published: March 2021

AbstractIn this work we employ a reduced‐order basis of conservative chemical components to model reactive transport using a Lagrangian (particle tracking) method. While this practice is well‐understood in the Eulerian (grid‐based) context, its adaptation to a Lagrangian context requires a novel reformulation of particle transport properties. Because the number of conservative‐species particles need not change during simulation, spatial resolution stays constant in time, and there is no increase in computational expense due to increasing numbers of product particles. Additionally, this treatment simplifies the interaction between equilibrium and kinetic reactions and allows the use of species‐dependent transport operators at the same time. We apply this method to model a suite of simple test problems that include equilibrium and kinetic reactions, and results exhibit excellent match with base‐case Eulerian results. Finally, we apply the new method to model a 2D problem concerning the mobilization of cadmium by a CO2 leak, showing the potential applicability of the proposed methodology.
Melting Dynamics of Late Cretaceous Lamprophyres in Central Asia Suggest a Mechanism to Explain Many Continental Intraplate Basaltic Suite Magmatic Provinces
Authors: Dai Hong‐Kun , Oliveira Beñat , Zheng Jian‐Ping , Griffin William L. , Afonso Juan Carlos , Xiong Qing , O'Reilly Suzanne Y. 
Published: March 2021

AbstractIntraplate small‐volume mafic magmatism is spatially and temporally widespread in central and eastern Asia, but the relevant melting dynamics have remained enigmatic. Here, we report Ar‐Ar ages, mineral and whole‐rock compositions on newly found ∼81 Ma lamprophyre dykes from central Asia, aiming to constrain the source characteristics and the melting dynamics in this intraplate setting. Mineral chemistry of the lamprophyres shows that pre‐emplacement magmas equilibrated at 970–1060°C (probably at the base of the crust) and contained 1.4–2.1 wt% water. The source region of the lamprophyres is shown to have H contents equivalent to H2O = ∼150 ppm, and to be lithologically heterogeneous with silica‐deficient pyroxenite embedded in peridotite. Because of the thermodynamic complexities involved in calculating melting scenarios with major elements for such mantle domains, we have conducted a grid search with a forward‐modeling methodology that can simulate the adiabatic decompression melting of a lithologically heterogeneous mantle using incompatible trace elements. The modeling results indicate that original melting occurred at a potential temperature of ∼1400°C under a thinned lithosphere (∼70 km, corresponding to a final melting pressure of 2.3 GPa). Combining these conditions with constraints from regional geology and the tectonic history, the lamprophyres are inferred to have formed by decompression melting induced by small‐scale asthenospheric upwellings due to the edge effects under a corrugated lithospheric lower boundary. We suggest that this scenario has global relevance and represents a likely mechanism for the initiation of relatively small‐scale intraplate magmatism within continents.
A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1
Authors: Yanagi Kumiko , Morimoto Noriko , Iso Manami , Abe Yukimi , Okamura Kohji , Nakamura Tomoo , Matsubara Yoichi , Kaname Tadashi 
Published: March 2021

AbstractAuriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM_006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1.
Ultrahigh numerical aperture meta-fibre for flexible optical trapping
Authors: Plidschun Malte , Ren Haoran , Kim Jisoo , Förster Ronny , Maier Stefan A. , Schmidt Markus A. 
Published: March 2021

AbstractStrong focusing on diffraction-limited spots is essential for many photonic applications and is particularly relevant for optical trapping; however, all currently used approaches fail to simultaneously provide flexible transportation of light, straightforward implementation, compatibility with waveguide circuitry, and strong focusing. Here, we demonstrate the design and 3D nanoprinting of an ultrahigh numerical aperture meta-fibre for highly flexible optical trapping. Taking into account the peculiarities of the fibre environment, we implemented an ultrathin meta-lens on the facet of a modified single-mode optical fibre via direct laser writing, leading to a diffraction-limited focal spot with a record-high numerical aperture of up to NA ≈ 0.9. The unique capabilities of this flexible, cost-effective, bio- and fibre-circuitry-compatible meta-fibre device were demonstrated by optically trapping microbeads and bacteria for the first time with only one single-mode fibre in combination with diffractive optics. Our study highlights the relevance of the unexplored but exciting field of meta-fibre optics to a multitude of fields, such as bioanalytics, quantum technology and life sciences.
Musashi-2 (MSI2) regulates epidermal growth factor receptor (EGFR) expression and response to EGFR inhibitors in EGFR-mutated non-small cell lung cancer (NSCLC)
Authors: Makhov Petr , Bychkov Igor , Faezov Bulat , Deneka Alexander , Kudinov Alexander , Nicolas Emmanuelle , Brebion Rohan , Avril Eleanor , Cai Kathy Q. , Kharin Leonid V. , Voloshin Mark , Frantsiyants Elena , Karnaukhov Nikolay , Kit Oleg I. , Topchu Iuliia , Fazliyeva Rushaniya , Nikonova Anna S. , Serebriiskii Ilya G. , Borghaei Hossein , Edelman Martin , Dulaimi Essel , Golemis Erica A. , Boumber Yanis 
Published: March 2021

AbstractNon-small cell lung cancer (NSCLC) has limited treatment options. Expression of the RNA-binding protein (RBP) Musashi-2 (MSI2) is elevated in a subset of non-small cell lung cancer (NSCLC) tumors upon progression, and drives NSCLC metastasis. We evaluated the mechanism of MSI2 action in NSCLC to gain therapeutically useful insights. Reverse phase protein array (RPPA) analysis of MSI2-depleted versus control KrasLA1/+; Trp53R172HΔG/+ NSCLC cell lines identified EGFR as a MSI2-regulated protein. MSI2 control of EGFR expression and activity in an NSCLC cell line panel was studied using RT-PCR, Western blots, and RNA immunoprecipitation. Functional consequences of MSI2 depletion were explored for cell growth and response to EGFR-targeting drugs, in vitro and in vivo. Expression relationships were validated using human tissue microarrays. MSI2 depletion significantly reduced EGFR protein expression, phosphorylation, or both. Comparison of protein and mRNA expression indicated a post-transcriptional activity of MSI2 in control of steady state levels of EGFR. RNA immunoprecipitation analysis demonstrated that MSI2 directly binds to EGFR mRNA, and sequence analysis predicted MSI2 binding sites in the murine and human EGFR mRNAs. MSI2 depletion selectively impaired cell proliferation in NSCLC cell lines with activating mutations of EGFR (EGFRmut). Further, depletion of MSI2 in combination with EGFR inhibitors such as erlotinib, afatinib, and osimertinib selectively reduced the growth of EGFRmut NSCLC cells and xenografts. EGFR and MSI2 were significantly co-expressed in EGFRmut human NSCLCs. These results define MSI2 as a direct regulator of EGFR protein expression, and suggest inhibition of MSI2 could be of clinical value in EGFRmut NSCLC.
Inhibition of mTOR signaling by genetic removal of p70 S6 kinase 1 increases anxiety-like behavior in mice
Authors: Koehl Muriel , Ladevèze Elodie , Catania Caterina , Cota Daniela , Abrous Djoher Nora 
Published: March 2021

AbstractThe mechanistic target of rapamycin (mTOR) is a ubiquitously expressed kinase that acts through two complexes, mTORC1 and mTORC2, to regulate protein homeostasis, as well as long lasting forms of synaptic and behavioral plasticity. Alteration of the mTOR pathway is classically involved in neurodegenerative disorders, and it has been linked to dysregulation of cognitive functions and affective states. However, information concerning the specific involvement of the p70 S6 kinase 1 (S6K1), a downstream target of the mTORC1 pathway, in learning and memory processes and in the regulation of affective states remains scant. To fill this gap, we exposed adult male mice lacking S6K1 to a battery of behavioral tests aimed at measuring their learning and memory capabilities by evaluating reference memory and flexibility with the Morris water maze, and associative memory using the contextual fear conditioning task. We also studied their anxiety-like and depression-like behaviors by, respectively, performing elevated plus maze, open field, light-dark emergence tests, and sucrose preference and forced swim tests. We found that deleting S6K1 leads to a robust anxious phenotype concomitant with associative learning deficits; these symptoms are associated with a reduction of adult neurogenesis and neuronal atrophy in the hippocampus. Collectively, these results provide grounds for the understanding of anxiety reports after treatments with mTOR inhibitors and will be critical for developing novel compounds targeting anxiety.
Predicting alcohol use disorder remission: a longitudinal multimodal multi-featured machine learning approach
Authors: Kinreich Sivan , McCutcheon Vivia V. , Aliev Fazil , Meyers Jacquelyn L. , Kamarajan Chella , Pandey Ashwini K. , Chorlian David B. , Zhang Jian , Kuang Weipeng , Pandey Gayathri , Viteri Stacey Subbie-Saenz de. , Francis Meredith W. , Chan Grace , Bourdon Jessica L. , Dick Danielle M. , Anokhin Andrey P. , Bauer Lance , Hesselbrock Victor , Schuckit Marc A. , Nurnberger John I. , Foroud Tatiana M. , Salvatore Jessica E. , Bucholz Kathleen K. , Porjesz Bernice 
Published: March 2021

AbstractPredictive models for recovering from alcohol use disorder (AUD) and identifying related predisposition biomarkers can have a tremendous impact on addiction treatment outcomes and cost reduction. Our sample (N = 1376) included individuals of European (EA) and African (AA) ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA) who were initially assessed as having AUD (DSM-5) and reassessed years later as either having AUD or in remission. To predict this difference in AUD recovery status, we analyzed the initial data using multimodal, multi-features machine learning applications including EEG source-level functional brain connectivity, Polygenic Risk Scores (PRS), medications, and demographic information. Sex and ancestry age-matched stratified analyses were performed with supervised linear Support Vector Machine application and were calculated twice, once when the ancestry was defined by self-report and once defined by genetic data. Multifeatured prediction models achieved higher accuracy scores than models based on a single domain and higher scores in male models when the ancestry was based on genetic data. The AA male group model with PRS, EEG functional connectivity, marital and employment status features achieved the highest accuracy of 86.04%. Several discriminative features were identified, including collections of PRS related to neuroticism, depression, aggression, years of education, and alcohol consumption phenotypes. Other discriminated features included being married, employed, medication, lower default mode network and fusiform connectivity, and higher insula connectivity. Results highlight the importance of increasing genetic homogeneity of analyzed groups, identifying sex, and ancestry-specific features to increase prediction scores revealing biomarkers related to AUD remission.
The association between family history and genomic burden with schizophrenia mortality: a Swedish population-based register and genetic sample study
Authors: Kowalec Kaarina , Lu Yi , Song Jie , Dalman Christina , Hultman Christina M. , Larsson Henrik , Lichtenstein Paul , Sullivan Patrick F. 
Published: March 2021

AbstractIndividuals with schizophrenia (SCZ) have a 2–3-fold higher risk of mortality than the general population. Heritability of mortality in psychiatric disorders has been proposed; however, few have investigated SCZ family history and genetic variation, with all-cause and specific causes of death. We aimed to identify correlates of SCZ mortality using genetic epidemiological and genetic modelling in two samples: a Swedish national population sample and a genotyped subsample. In the Swedish national population sample followed from the first SCZ treatment contact until emigration, death or end of the follow-up, we investigated a standardised measure of SCZ family history. In a subgroup with comprehensive genetic data, we investigated the impact of common and rare genetic variation. Cox proportional hazards regression was used to estimate the association between various factors and mortality (all and specific causes). A total of 13727 SCZ cases fulfilled criteria for the population-based analyses (1268 deaths, 9.2%). The genomic subset contained 4991 cases (1353 deaths, 27.1%). Somatic mutations associated with clonal hematopoiesis with unknown drivers were associated with all-cause mortality (HR 1.77, 95% CI: 1.26–2.49). No other heritable measures were associated with all-cause mortality nor with any specific causes of death. Future studies in larger, comparable cohorts are warranted to further understand the association between hereditary measures and mortality in SCZ.
Magnetic resonance imaging for individual prediction of treatment response in major depressive disorder: a systematic review and meta-analysis
Authors: Cohen Sem E. , Zantvoord Jasper B. , Wezenberg Babet N. , Bockting Claudi L. H. , van Wingen Guido A. 
Published: March 2021

AbstractNo tools are currently available to predict whether a patient suffering from major depressive disorder (MDD) will respond to a certain treatment. Machine learning analysis of magnetic resonance imaging (MRI) data has shown potential in predicting response for individual patients, which may enable personalized treatment decisions and increase treatment efficacy. Here, we evaluated the accuracy of MRI-guided response prediction in MDD. We conducted a systematic review and meta-analysis of all studies using MRI to predict single-subject response to antidepressant treatment in patients with MDD. Classification performance was calculated using a bivariate model and expressed as area under the curve, sensitivity, and specificity. In addition, we analyzed differences in classification performance between different interventions and MRI modalities. Meta-analysis of 22 samples including 957 patients showed an overall area under the bivariate summary receiver operating curve of 0.84 (95% CI 0.81–0.87), sensitivity of 77% (95% CI 71–82), and specificity of 79% (95% CI 73–84). Although classification performance was higher for electroconvulsive therapy outcome prediction (n = 285, 80% sensitivity, 83% specificity) than medication outcome prediction (n = 283, 75% sensitivity, 72% specificity), there was no significant difference in classification performance between treatments or MRI modalities. Prediction of treatment response using machine learning analysis of MRI data is promising but should not yet be implemented into clinical practice. Future studies with more generalizable samples and external validation are needed to establish the potential of MRI to realize individualized patient care in MDD.
Transcriptome alterations are enriched for synapse-associated genes in the striatum of subjects with obsessive-compulsive disorder
Authors: Piantadosi Sean C. , McClain Lora L. , Klei Lambertus , Wang Jiebiao , Chamberlain Brittany L. , Springer Sara A. , Lewis David A. , Devlin Bernie , Ahmari Susanne E. 
Published: March 2021

AbstractObsessive-compulsive disorder (OCD) is a chronic and severe psychiatric disorder for which effective treatment options are limited. Structural and functional neuroimaging studies have consistently implicated the orbitofrontal cortex (OFC) and striatum in the pathophysiology of the disorder. Recent genetic evidence points to involvement of components of the excitatory synapse in the etiology of OCD. However, the transcriptional alterations that could link genetic risk to known structural and functional abnormalities remain mostly unknown. To assess potential transcriptional changes in the OFC and two striatal regions (caudate nucleus and nucleus accumbens) of OCD subjects relative to unaffected comparison subjects, we sequenced messenger RNA transcripts from these brain regions. In a joint analysis of all three regions, 904 transcripts were differentially expressed between 7 OCD versus 8 unaffected comparison subjects. Region-specific analyses highlighted a smaller number of differences, which concentrated in caudate and nucleus accumbens. Pathway analyses of the 904 differentially expressed transcripts showed enrichment for genes involved in synaptic signaling, with these synapse-associated genes displaying lower expression in OCD subjects relative to unaffected comparison subjects. Finally, we estimated that cell type fractions of medium spiny neurons were lower whereas vascular cells and astrocyte fractions were higher in tissue of OCD subjects. Together, these data provide the first unbiased examination of differentially expressed transcripts in both OFC and striatum of OCD subjects. These transcripts encoded synaptic proteins more often than expected by chance, and thus implicate the synapse as a vulnerable molecular compartment for OCD.
Canonical TGF-β signaling regulates the relationship between prenatal maternal depression and amygdala development in early life
Authors: Qiu Anqi , Zhang Han , Wang Changqing , Chong Yap-Seng , Shek Lynette P. , Gluckman Peter D. , Meaney Michael J. , Fortier Marielle V. , Wu Yonghui 
Published: March 2021

AbstractCanonical transforming growth factor-beta (TGF-β) signaling exerts neuroprotection and influences memory formation and synaptic plasticity. It has been considered as a new target for the prevention and treatment of depression. This study aimed to examine its modulatory role in linking prenatal maternal depressive symptoms and the amygdala volumes from birth to 6 years of age. We included mother–child dyads (birth: n = 161; 4.5 years: n = 131; 6 years: n = 162) and acquired structural brain images of children at these three time points. Perinatal maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) questionnaire to mothers at 26 weeks of pregnancy and 3 months postpartum. Our findings showed that the genetic variants of TGF-β type I transmembrane receptor (TGF-βRI) modulated the association between prenatal maternal depressive symptoms and the amygdala volume consistently from birth to 6 years of age despite a trend of significance at 4.5 years of age. Children with a lower gene expression score (GES) of TGF-βRI exhibited larger amygdala volumes in relation to greater prenatal maternal depressive symptoms. Moreover, children with a lower GES of the TGF-β type II transmembrane receptor (TGF-βRII), Smad4, and Smad7 showed larger amygdala volumes at 6 years of age in relation to greater prenatal maternal depressive symptoms. These findings support the involvement of the canonical TGF-β signaling pathway in the brain development of children in the context of in utero maternal environment. Such involvement is age-dependent.
Rewiring of purine metabolism in response to acidosis stress in glioma stem cells
Authors: Xu Xiaoyu , Wang Liping , Zang Qingce , Li Shanshan , Li Limei , Wang Zhixing , He Jiuming , Qiang Boqin , Han Wei , Zhang Ruiping , Peng Xiaozhong , Abliz Zeper 
Published: March 2021

AbstractGlioma stem cells (GSCs) contribute to therapy resistance and poor outcomes for glioma patients. A significant feature of GSCs is their ability to grow in an acidic microenvironment. However, the mechanism underlying the rewiring of their metabolism in low pH remains elusive. Here, using metabolomics and metabolic flux approaches, we cultured GSCs at pH 6.8 and pH 7.4 and found that cells cultured in low pH exhibited increased de novo purine nucleotide biosynthesis activity. The overexpression of glucose-6-phosphate dehydrogenase, encoded by G6PD or H6PD, supports the metabolic dependency of GSCs on nucleotides when cultured under acidic conditions, by enhancing the pentose phosphate pathway (PPP). The high level of reduced glutathione (GSH) under acidic conditions also causes demand for the PPP to provide NADPH. Taken together, upregulation of G6PD/H6PD in the PPP plays an important role in acidic-driven purine metabolic reprogramming and confers a predilection toward glioma progression. Our findings indicate that targeting G6PD/H6PD, which are closely related to glioma patient survival, may serve as a promising therapeutic target for improved glioblastoma therapeutics. An integrated metabolomics and metabolic flux analysis, as well as considering microenvironment and cancer stem cells, provide a precise insight into understanding cancer metabolic reprogramming.