bluuebunny/crossref_metadata_2025_split huggingface dataset:
Satellite‐Observed Vegetation Responses to Intraseasonal Precipitation Variability
Authors: Harris Bethan L. , Taylor Christopher M. , Weedon Graham P. , Talib Joshua , Dorigo Wouter , van der Schalie Robin 
Published: July 2022

AbstractThere is limited understanding of how vegetation responds to intraseasonal modes of rainfall variability despite their importance in many tropical regions. We use observations of precipitation and X‐band Vegetation Optical Depth (VOD) from 2000 to 2018 to assess the relationships between rainfall and vegetation water content on 25–60‐day timescales. Cross‐spectral analysis identifies coherent intraseasonal relationships between precipitation and VOD, mostly in arid or semi‐arid regions where vegetation is water‐limited. Changes in VOD tend to lag anomalous rainfall, usually within 7 days. The fastest vegetation response is observed in sparsely vegetated areas (median 3 days). Following strong intraseasonal wet events, anomalously high VOD can persist for 2 months after the rainfall peak. This vegetation response can feed back onto the atmosphere, so improved representation of vegetation responses in models has the potential to improve subseasonal‐to‐seasonal forecasts.
The interaction of early life factors and depression-associated loci affecting the age at onset of the depression
Authors: Chen Yujing , Pan Chuyu , Cheng Shiqiang , Li Chun’e , Zhang Huijie , Zhang Zhen , Zhang Jingxi , Yao Yao , Meng Peilin , Yang Xuena , Liu Li , Cheng Bolun , Jia Yumeng , Wen Yan , Zhang Feng 
Published: July 2022

AbstractMultiple previous studies explored the associations between early life factors and the age at onset of the depression. However, they only focused on the influence of environmental or genetic factors, without considering the interactions between them. Based on previous genome-wide association study (GWAS) data, we first calculated polygenic risk score (PRS) for depression. Regression analyses were conducted to assess the interacting effects of depression PRS and 5 early life factors, including felt hated by family member (N = 40,112), physically abused by family (N = 40,464), felt loved (N = 35633), and sexually molested (N = 41,595) in childhood and maternal smoking during pregnancy (N = 38,309), on the age at onset of the depression. Genome-wide environment interaction studies (GWEIS) were then performed to identify the genes interacting with early life factors for the age at onset of the depression. In regression analyses, we observed significant interacting effects of felt loved as a child and depression PRS on the age at onset of depression in total sample (β = 0.708, P = 5.03 × 10−3) and males (β = 1.421, P = 7.64 × 10−4). GWEIS identified a novel candidate loci interacting with felt loved as a child at GSAP (rs2068031, P = 4.24 × 10–8) and detected several genes with suggestive significance association, such as CMYA5 (rs7343, P = 2.03 × 10–6) and KIRREL3 (rs535603, P = 4.84 × 10–6) in males. Our results indicate emotional care in childhood may affect the age at onset of depression, especially in males, and GSAP plays an important role in their interaction.
Enhanced top-down sensorimotor processing in somatic anxiety
Authors: Bouziane Ismail , Das Moumita , Friston Karl J. , Caballero-Gaudes Cesar , Ray Dipanjan 
Published: July 2022

AbstractFunctional neuroimaging research on anxiety has traditionally focused on brain networks associated with the psychological aspects of anxiety. Here, instead, we target the somatic aspects of anxiety. Motivated by the growing appreciation that top-down cortical processing plays a crucial role in perception and action, we used resting-state functional MRI data from the Human Connectome Project and Dynamic Causal Modeling (DCM) to characterize effective connectivity among hierarchically organized regions in the exteroceptive, interoceptive, and motor cortices. In people with high (fear-related) somatic arousal, top-down effective connectivity was enhanced in all three networks: an observation that corroborates well with the phenomenology of anxiety. The anxiety-associated changes in connectivity were sufficiently reliable to predict whether a new participant has mild or severe somatic anxiety. Interestingly, the increase in top-down connections to sensorimotor cortex were not associated with fear affect scores, thus establishing the (relative) dissociation between somatic and cognitive dimensions of anxiety. Overall, enhanced top-down effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of trait somatic anxiety.
Beyond controlling cell size: functional analyses of S6K in tumorigenesis
Authors: Wu Xueji , Xie Wei , Xie Wenxuan , Wei Wenyi , Guo Jianping 
Published: July 2022

AbstractAs a substrate and major effector of the mammalian target of rapamycin complex 1 (mTORC1), the biological functions of ribosomal protein S6 kinase (S6K) have been canonically assigned for cell size control by facilitating mRNA transcription, splicing, and protein synthesis. However, accumulating evidence implies that diverse stimuli and upstream regulators modulate S6K kinase activity, leading to the activation of a plethora of downstream substrates for distinct pathobiological functions. Beyond controlling cell size, S6K simultaneously plays crucial roles in directing cell apoptosis, metabolism, and feedback regulation of its upstream signals. Thus, we comprehensively summarize the emerging upstream regulators, downstream substrates, mouse models, clinical relevance, and candidate inhibitors for S6K and shed light on S6K as a potential therapeutic target for cancers.
Activation of the JNKs/ATM-p53 axis is indispensable for the cytoprotection of dermal fibroblasts exposed to UVB radiation
Authors: Mavrogonatou Eleni , Angelopoulou Maria , Rizou Sophia V. , Pratsinis Harris , Gorgoulis Vassilis G. , Kletsas Dimitris 
Published: July 2022

AbstractAlthough UVB radiation is mainly absorbed by the epidermis, ~5–10% of its photons reach and affect the upper part of the dermis. Physiologically relevant UVB doses, able to provoke erythema, induce apoptosis in human dermal fibroblasts in vitro, as well as in the dermis of SKH-1 mice. Given the sparse and even contradictory existing information on the effect of UVB radiation on dermal fibroblasts’ viability, aim of this work was to unravel the crucial signaling pathways regulating the survival of UVB-treated human dermal fibroblasts. We found that UVB radiation immediately stimulates the phosphorylation of MAPK family members, as well as Akt, and is genotoxic leading to the delayed ATM-p53 axis activation. Akt phosphorylation after UVB radiation is EGFR-mediated and EGFR inhibition leads to a further decrease of viability, while the Akt activator SC79 rescues fibroblasts to an extent by a mechanism involving Nrf2 activation. The known Nrf2 activator sulforaphane also exerts a partial protective effect, although by acting in a distinct mechanism from SC79. On the other hand, inhibition of JNKs or of the ATM-p53 axis leads to a complete loss of viability after UVB irradiation. Interestingly, JNKs activation is necessary for p53 phosphorylation, while the ATM-p53 pathway is required for the long-term activation of JNKs and Akt, reassuring the protection from UVB. Although UVB radiation results in intense and prolonged increase of intracellular ROS levels, classical anti-oxidants, such as Trolox, are unable to affect Akt, JNKs, or p53 phosphorylation and to reverse the loss of fibroblasts’ viability. Collectively, here we provide evidence that the main viability-regulating UVB-triggered biochemical pathways act synergistically towards the protection of human dermal fibroblasts, with EGFR/Akt and Nrf2 serving as auxiliary anti-apoptotic machineries, while JNKs/ATM-p53 activation and interplay being overriding and indispensable for the perpetuation of cellular defense and the maintenance of cell viability.
Sunlight-driven nitrate loss records Antarctic surface mass balance
Authors: Akers Pete D. , Savarino Joël , Caillon Nicolas , Servettaz Aymeric P. M. , Le Meur Emmanuel , Magand Olivier , Martins Jean , Agosta Cécile , Crockford Peter , Kobayashi Kanon , Hattori Shohei , Curran Mark , van Ommen Tas , Jong Lenneke , Roberts Jason L. 
Published: July 2022

AbstractStandard proxies for reconstructing surface mass balance (SMB) in Antarctic ice cores are often inaccurate or coarsely resolved when applied to more complicated environments away from dome summits. Here, we propose an alternative SMB proxy based on photolytic fractionation of nitrogen isotopes in nitrate observed at 114 sites throughout East Antarctica. Applying this proxy approach to nitrate in a shallow core drilled at a moderate SMB site (Aurora Basin North), we reconstruct 700 years of SMB changes that agree well with changes estimated from ice core density and upstream surface topography. For the under-sampled transition zones between dome summits and the coast, we show that this proxy can provide past and present SMB values that reflect the immediate local environment and are derived independently from existing techniques.
Extreme purifying selection against point mutations in the human genome
Authors: Dukler Noah , Mughal Mehreen R. , Ramani Ritika , Huang Yi-Fei , Siepel Adam 
Published: July 2022

AbstractLarge-scale genome sequencing has enabled the measurement of strong purifying selection in protein-coding genes. Here we describe a new method, called ExtRaINSIGHT, for measuring such selection in noncoding as well as coding regions of the human genome. ExtRaINSIGHT estimates the prevalence of “ultraselection” by the fractional depletion of rare single-nucleotide variants, after controlling for variation in mutation rates. Applying ExtRaINSIGHT to 71,702 whole genome sequences from gnomAD v3, we find abundant ultraselection in evolutionarily ancient miRNAs and neuronal protein-coding genes, as well as at splice sites. By contrast, we find much less ultraselection in other noncoding RNAs and transcription factor binding sites, and only modest levels in ultraconserved elements. We estimate that ~0.4–0.7% of the human genome is ultraselected, implying ~ 0.26–0.51 strongly deleterious mutations per generation. Overall, our study sheds new light on the genome-wide distribution of fitness effects by combining deep sequencing data and classical theory from population genetics.
Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement
Authors: Liu Jiaye , Wang Yang , Mu Chunyang , Li Meng , Li Kewei , Li Shan , Wu Wenshuang , Du Lingyao , Zhang Xiaoyun , Li Chuan , Peng Wei , Shen Junyi , Liu Yang , Yang Dujiang , Zhang Kaixiang , Ning Qingyang , Fu Xiaoying , Zeng Yu , Ni Yinyun , Zhou Zongguang , Liu Yi , Hu Yiguo , Zheng Xiaofeng , Wen Tianfu , Li Zhihui , Liu Yong 
Published: July 2022

AbstractCancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.
Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC
Authors: Saddawi-Konefka Robert , O’Farrell Aoife , Faraji Farhoud , Clubb Lauren , Allevato Michael M. , Jensen Shawn M. , Yung Bryan S. , Wang Zhiyong , Wu Victoria H. , Anang Nana-Ama , Msari Riyam Al , Schokrpur Shiruyeh , Pietryga Ida Franiak , Molinolo Alfredo A. , Mesirov Jill P. , Simon Aaron B. , Fox Bernard A. , Bui Jack D. , Sharabi Andrew , Cohen Ezra E. W. , Califano Joseph A. , Gutkind J. Silvio 
Published: July 2022

AbstractDespite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises the possibility that standard of care treatments delivered in concert may compromise the tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models in which we map tumor-draining lymphatics and develop models for regional lymphablation with surgery or radiation. We find that lymphablation eliminates the tumor ICI response, worsening overall survival and repolarizing the tumor- and peripheral-immune compartments. Mechanistically, within tumor-draining lymphatics, we observe an upregulation of conventional type I dendritic cells and type I interferon signaling and show that both are necessary for the ICI response and lost with lymphablation. Ultimately, we provide a mechanistic understanding of how standard oncologic therapies targeting regional lymphatics impact the tumor response to immune-oncology therapy in order to define rational, lymphatic-preserving treatment sequences that mobilize systemic antitumor immunity, achieve optimal tumor responses, control regional metastatic disease, and confer durable antitumor immunity.
Cell landscape of larval and adult Xenopus laevis at single-cell resolution
Authors: Liao Yuan , Ma Lifeng , Guo Qile , E Weigao , Fang Xing , Yang Lei , Ruan Fanwei , Wang Jingjing , Zhang Peijing , Sun Zhongyi , Chen Haide , Lin Zhongliang , Wang Xueyi , Wang Xinru , Sun Huiyu , Fang Xiunan , Zhou Yincong , Chen Ming , Shen Wanhua , Guo Guoji , Han Xiaoping 
Published: July 2022

AbstractThe rapid development of high-throughput single-cell RNA sequencing technology offers a good opportunity to dissect cell heterogeneity of animals. A large number of organism-wide single-cell atlases have been constructed for vertebrates such asHomo sapiens,Macaca fascicularis,Mus musculusandDanio rerio. However, an intermediate taxon that links mammals to vertebrates of more ancient origin is still lacking. Here, we construct the firstXenopuscell landscape to date, including larval and adult organs. Common cell lineage-specific transcription factors have been identified in vertebrates, including fish, amphibians and mammals. The comparison of larval and adult erythrocytes identifies stage-specific hemoglobin subtypes, as well as a common type of cluster containing both larval and adult hemoglobin, mainly at NF59. In addition, cell lineages originating from all three layers exhibits both antigen processing and presentation during metamorphosis, indicating a common regulatory mechanism during metamorphosis. Overall, our study provides a large-scale resource for research onXenopusmetamorphosis and adult organs.
Single-cell transcriptome atlas of the human corpus cavernosum
Authors: Zhao LiangYu , Han Sha , Su HengChuan , Li JianYing , Zhi ErLei , Li Peng , Yao ChenCheng , Tian RuHui , Chen HuiXing , Chen HuiRong , Luo JiaQiang , Shi ChenKun , Ji ZhiYong , Hu JianLin , Wu Gang , Zhou WeiDong , Tang YuXin , Chen YuZhuo , Lin GuiTing , Lue Tom F. , Wu DengLong , Li Zheng 
Published: July 2022

AbstractThe corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.
Integrin α3β1 promotes vessel formation of glioblastoma-associated endothelial cells through calcium-mediated macropinocytosis and lysosomal exocytosis
Authors: Bae Eunnyung , Huang Ping , Müller-Greven Gaёlle , Hambardzumyan Dolores , Sloan Andrew Edward , Nowacki Amy S. , Marko Nicholas , Carlin Cathleen R. , Gladson Candece L. 
Published: July 2022

AbstractTherapeutic targeting of angiogenesis in glioblastoma has yielded mixed outcomes. Investigation of tumor-associated angiogenesis has focused on the factors that stimulate the sprouting, migration, and hyperproliferation of the endothelial cells. However, little is known regarding the processes underlying the formation of the tumor-associated vessels. To address this issue, we investigated vessel formation in CD31+ cells isolated from human glioblastoma tumors. The results indicate that overexpression of integrin α3β1 plays a central role in the promotion of tube formation in the tumor-associated endothelial cells in glioblastoma. Blocking α3β1 function reduced sprout and tube formation in the tumor-associated endothelial cells and vessel density in organotypic cultures of glioblastoma. The data further suggest a mechanistic model in which integrin α3β1-promoted calcium influx stimulates macropinocytosis and directed maturation of the macropinosomes in a manner that promotes lysosomal exocytosis during nascent lumen formation. Altogether, our data indicate that integrin α3β1 may be a therapeutic target on the glioblastoma vasculature.
Structure and assembly of cargo Rubisco in two native α-carboxysomes
Authors: Ni Tao , Sun Yaqi , Burn Will , Al-Hazeem Monsour M. J. , Zhu Yanan , Yu Xiulian , Liu Lu-Ning , Zhang Peijun 
Published: July 2022

AbstractCarboxysomes are a family of bacterial microcompartments in cyanobacteria and chemoautotrophs. They encapsulate Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrase catalyzing carbon fixation inside a proteinaceous shell. How Rubisco complexes pack within the carboxysomes is unknown. Using cryo-electron tomography, we determine the distinct 3D organization of Rubisco inside two distant α-carboxysomes from a marine α-cyanobacterium Cyanobium sp. PCC 7001 where Rubiscos are organized in three concentric layers, and from a chemoautotrophic bacterium Halothiobacillus neapolitanus where they form intertwining spirals. We further resolve the structures of native Rubisco as well as its higher-order assembly at near-atomic resolutions by subtomogram averaging. The structures surprisingly reveal that the authentic intrinsically disordered linker protein CsoS2 interacts with Rubiscos in native carboxysomes but functions distinctively in the two α-carboxysomes. In contrast to the uniform Rubisco-CsoS2 association in the Cyanobium α-carboxysome, CsoS2 binds only to the Rubiscos close to the shell in the Halo α-carboxysome. Our findings provide critical knowledge of the assembly principles of α-carboxysomes, which may aid in the rational design and repurposing of carboxysome structures for new functions.
KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data
Authors: Crowl Sam , Jordan Ben T. , Ahmed Hamza , Ma Cynthia X. , Naegle Kristen M. 
Published: July 2022

AbstractKinase inhibitors as targeted therapies have played an important role in improving cancer outcomes. However, there are still considerable challenges, such as resistance, non-response, patient stratification, polypharmacology, and identifying combination therapy where understanding a tumor kinase activity profile could be transformative. Here, we develop a graph- and statistics-based algorithm, called KSTAR, to convert phosphoproteomic measurements of cells and tissues into a kinase activity score that is generalizable and useful for clinical pipelines, requiring no quantification of the phosphorylation sites. In this work, we demonstrate that KSTAR reliably captures expected kinase activity differences across different tissues and stimulation contexts, allows for the direct comparison of samples from independent experiments, and is robust across a wide range of dataset sizes. Finally, we apply KSTAR to clinical breast cancer phosphoproteomic data and find that there is potential for kinase activity inference from KSTAR to complement the current clinical diagnosis of HER2 status in breast cancer patients.
Dielectric catastrophe at the Wigner-Mott transition in a moiré superlattice
Authors: Tang Yanhao , Gu Jie , Liu Song , Watanabe Kenji , Taniguchi Takashi , Hone James C. , Mak Kin Fai , Shan Jie 
Published: July 2022

AbstractThe bandwidth-tuned Wigner-Mott transition is an interaction-driven phase transition from a generalized Wigner crystal to a Fermi liquid. Because the transition is generally accompanied by both magnetic and charge-order instabilities, it remains unclear if a continuous Wigner-Mott transition exists. Here, we demonstrate bandwidth-tuned metal-insulator transitions at fixed fractional fillings of a MoSe2/WS2 moiré superlattice. The bandwidth is controlled by an out-of-plane electric field. The dielectric response is probed optically with the 2s exciton in a remote WSe2 sensor layer. The exciton spectral weight is negligible for the metallic state with a large negative dielectric constant. It continuously vanishes when the transition is approached from the insulating side, corresponding to a diverging dielectric constant or a ‘dielectric catastrophe’ driven by the critical charge dynamics near the transition. Our results support the scenario of continuous Wigner-Mott transitions in two-dimensional triangular lattices and stimulate future explorations of exotic quantum phases in their vicinities.
Active multiband varifocal metalenses based on orbital angular momentum division multiplexing
Authors: Zheng Ruixuan , Pan Ruhao , Geng Guangzhou , Jiang Qiang , Du Shuo , Huang Lingling , Gu Changzhi , Li Junjie 
Published: July 2022

AbstractMetalenses as miniature flat lenses exhibit a substantial potential in replacing traditional optical component. Although the metalenses have been intensively explored, their functions are limited by poor active ability, narrow operating band and small depth of field (DOF). Here, we show a dielectric metalens consisting of TiO2 nanofins array with ultrahigh aspect ratio to realize active multiband varifocal function. Regulating the orbital angular momentum (OAM) by the phase assignment covering the 2π range, its focal lengths can be switched from 5 mm to 35 mm. This active optical multiplexing uses the physical properties of OAM channels to selectively address and decode the vortex beams. The multiband capability and large DOFs with conversion efficiency of 49% for this metalens are validated for both 532 nm and 633 nm, and the incidence wavelength can further change the focal lengths. This non-mechanical tunable metalens demonstrates the possibility of active varifocal metalenses.