bluuebunny/crossref_metadata_2025_split huggingface dataset:
USP10 deubiquitinates Tau, mediating its aggregation
Authors: Wei Zhen , Zeng Kuan , Hu Jichang , Li Xing , Huang Fang , Zhang Bin , Wang Jian-Zhi , Liu Rong , Li Hong-Lian , Wang Xiaochuan 
Published: August 2022

AbstractNormal Tau promotes the assembly and stabilization of microtubules, thus, maintaining axon transport. In Alzheimer’s disease (AD), Tau aggregation causes it to lose these above-mentioned functions. However, the molecular mechanism leading to Tau aggregation in AD remains ambiguous. Here, we report that USP10, one of the important deubiquitinases (DUBs), is involved in Tau aggregation. We found that USP10 is upregulated in postmortem human AD and APP/PS1 mice brains, but not in P301S mice brains. Moreover, in primary neuronal cultures, Aβ42 induces a dose-dependent USP10 upregulation, an increase in the levels of both total and phosphorylated Tau, as well as a markedly elevated Tau binding with USP10, that is accompanied by a significantly decreased Tau ubiquitination. In addition, overexpression of USP10 directly causes an increase in the levels of total and phosphorylated Tau, induces Tau aggregation, and delays in Tau degradation. Results from mass spectrometry, reciprocal immunoprecipitation, and immunofluorescence assays strongly prove Tau’s interaction with USP10. This is further supported by the Tau307–326K and Tau341–378K peptides’ competitive inhibition of Tau binding with USP10, attenuating Tau hyperphosphorylation and Tau deubiquitination. Together, our data strongly indicate that USP10 plays a critical role in mediating Tau aggregation via downregulating its ubiquitination and thus slowing down Tau turnover. Inhibition of USP10-Tau interaction might be therapeutically useful in the management of AD and related tauopathies.
MYBL1 induces transcriptional activation of ANGPT2 to promote tumor angiogenesis and confer sorafenib resistance in human hepatocellular carcinoma
Authors: Zhu Jinrong , Wu Yongqi , Yu Yijian , Li Yan , Shen Jianfei , Zhang Rongxin 
Published: August 2022

AbstractAngiogenesis is considered as an important process in tumor growth, metastasis of hepatocellular carcinoma (HCC) and associated with cancer progression, suggesting that an important research and development field of clinical molecular targeted drugs for HCC. However, the molecular mechanisms underlying tumor angiogenesis in HCC remains elusive. In the current study, we demonstrate that upregulation of AMYB proto-oncogene-like 1 (MYBL1) was associated with high endothelial vessel (EV) density and contributed to poor prognosis of HCC patient. Functionally, MYBL1 overexpressing enhanced the capacity of HCC cells to induce tube formation, migration of HUVECs, neovascularization in CAMs, finally, enhanced HCC cells metastasis, while silencing MYBL1 had the converse effect. Furthermore, HCC cells with high MYBL1 expression were more resistance to sorafenib treatment. We observed that CD31 staining was significantly increased in tumors formed by MYBL1-overexpressing cells but decreased in MYBL1-silenced tumors. Mechanistically, MYBL1 binds to the ANGPT2 promoter and transcriptionally upregulate ANGPT2 mRNA expression. Strikingly, treatment with monoclonal antibody against ANGPT2 significantly inhibited the growth of MYBL1-overexpressing tumors and efficiently impaired angiogenesis. Furthermore, the histone post-translational factors: protein arginine methyltransferase 5 (PRMT5), MEP50, and WDR5 were required for MYBL1-mediated ANGPT2 upregulation. Importantly, we confirmed the correlation between MYBL1 and ANGPT2 expression in a large cohort of clinical HCC samples and several published datasets in pancreatic cancer, esophageal carcinoma, stomach adenocarcinoma, and colon cancer. Our results demonstrate that MYBL1 upregulated the ANGPT2 expression, then induced angiogenesis and confer sorafenib resistance to HCC cells, and MYBL1 may represent a novel prognostic biomarker and therapeutic target for patients with HCC.
Untangling the network effects of productivity and prominence among scientists
Authors: Li Weihua , Zhang Sam , Zheng Zhiming , Cranmer Skyler J. , Clauset Aaron 
Published: August 2022

AbstractWhile inequalities in science are common, most efforts to understand them treat scientists as isolated individuals, ignoring the network effects of collaboration. Here, we develop models that untangle the network effects of productivity defined as paper counts, and prominence referring to high-impact publications, of individual scientists from their collaboration networks. We find that gendered differences in the productivity and prominence of mid-career researchers can be largely explained by differences in their coauthorship networks. Hence, collaboration networks act as a form of social capital, and we find evidence of their transferability from senior to junior collaborators, with benefits that decay as researchers age. Collaboration network effects can also explain a large proportion of the productivity and prominence advantages held by researchers at prestigious institutions. These results highlight a substantial role of social networks in driving inequalities in science, and suggest that collaboration networks represent an important form of unequally distributed social capital that shapes who makes what scientific discoveries.
Photocatalytic cyclization of nitrogen-centered radicals with carbon nitride through promoting substrate/catalyst interaction
Authors: Yang Mingcheng , Lian Ronghong , Zhang Xirui , Wang Chong , Cheng Jiajia , Wang Xinchen 
Published: August 2022

AbstractThe use of metal-free carbon nitride and light to drive catalytic transformations constitutes a sustainable strategy for organic synthesis. At the moment, enhancing the intrinsic activity of CN catalysts by tuning the interfacial coupling between catalyst and substrate remains challenging. Herein, we demonstrate that urea-derived carbon nitride catalysts with the abundant −NH2 groups and the relative positive charged surface could effectively complex with the deprotonated anionic intermediate to improve the adsorption of organic reactants on the catalyst surface. The decreased oxidation potential and upshift in its highest occupied molecular orbital position make the electron abstraction kinetics by the catalyst more energetically favorable. The prepared catalyst is thus utilized for the photocatalytic cyclization of nitrogen-centered radicals for the synthesis of diverse pharmaceutical-related compounds (33 examples) with high activity and reusability, which shows competent performance to the homogeneous catalysts.
Light-responsive self-strained organic semiconductor for large flexible OFET sensing array
Authors: Li Mingliang , Zheng Jing , Wang Xiaoge , Yu Runze , Wang Yunteng , Qiu Yi , Cheng Xiang , Wang Guozhi , Chen Gang , Xie Kefeng , Tang Jinyao 
Published: August 2022

AbstractWith the wide application of organic semiconductors (OSCs), researchers are now grappling with a new challenge: design and synthesize OSCs materials with specific functions to satisfy the requirements of high-performance semiconductor devices. Strain engineering is an effective method to improve the semiconductor material’s carrier mobility, which is fundamentally originated from the rearrangement of the atomic packing model of materials under mechanic stress. Here, we design and synthesize a new OSC material named AZO-BTBT-8 based on high-mobility benzo[b]benzo[4,5]thieno[2,3-d]thiophene (BTBT) as the semiconductor backbone. Octane is employed to increase molecular flexibility and solubility, and azobenzene at the other end of the BTBT backbone provides photoisomerization properties and structural balance. Notably, the AZO-BTBT-8 photoisomerization leads to lattice strain in thin-film devices, where exceptional device performance enhancement is realized. On this basis, a large-scale flexible organic field-effect transistor (OFET) device array is fabricated and realizes high-resolution UV imaging with reversible light response.
Split westerlies over Europe in the early Little Ice Age
Authors: Hu Hsun-Ming , Shen Chuan-Chou , Chiang John C. H. , Trouet Valerie , Michel Véronique , Tsai Hsien-Chen , Valensi Patricia , Spötl Christoph , Starnini Elisabetta , Zunino Marta , Chien Wei-Yi , Sung Wen-Hui , Chien Yu-Tang , Chang Ping , Korty Robert 
Published: August 2022

AbstractThe Little Ice Age (LIA; ca. 1450–1850 C.E.) is the best documented cold period of the past millennium, characterized by high-frequency volcanism, low solar activity, and high variability of Arctic sea-ice cover. Past studies of LIA Atlantic circulation changes have referenced the North Atlantic Oscillation (NAO), but recent studies have noted that LIA climate patterns appear to possess complexity not captured by an NAO analogue. Here, we present a new precipitation-sensitive stalagmite record from northern Italy that covers the past 800 years. We show that in the early LIA (1470–1610 C.E.), increased atmospheric ridging over northern Europe split the climatological westerlies away from central and northern Europe, possibly caused by concurrent Artic sea-ice reduction. With ongoing ice melting in the northern high latitudes and decreasing solar irradiance in the coming years, the early LIA may potentially serve as an analogue for European hydroclimatic conditions in the coming decades.
Designing isolation guidelines for COVID-19 patients with rapid antigen tests
Authors: Jeong Yong Dam , Ejima Keisuke , Kim Kwang Su , Joohyeon Woo , Iwanami Shoya , Fujita Yasuhisa , Jung Il Hyo , Aihara Kazuyuki , Shibuya Kenji , Iwami Shingo , Bento Ana I. , Ajelli Marco 
Published: August 2022

AbstractAppropriate isolation guidelines for COVID-19 patients are warranted. Currently, isolating for fixed time is adopted in most countries. However, given the variability in viral dynamics between patients, some patients may no longer be infectious by the end of isolation, whereas others may still be infectious. Utilizing viral test results to determine isolation length would minimize both the risk of prematurely ending isolation of infectious patients and the unnecessary individual burden of redundant isolation of noninfectious patients. In this study, we develop a data-driven computational framework to compute the population-level risk and the burden of different isolation guidelines with rapid antigen tests (i.e., lateral flow tests). Here, we show that when the detection limit is higher than the infectiousness threshold values, additional consecutive negative results are needed to ascertain infectiousness status. Further, rapid antigen tests should be designed to have lower detection limits than infectiousness threshold values to minimize the length of prolonged isolation.
Integrated multi-omics reveals cellular and molecular interactions governing the invasive niche of basal cell carcinoma
Authors: Yerly Laura , Pich-Bavastro Christine , Di Domizio Jeremy , Wyss Tania , Tissot-Renaud Stéphanie , Cangkrama Michael , Gilliet Michel , Werner Sabine , Kuonen François 
Published: August 2022

AbstractTumors invade the surrounding tissues to progress, but the heterogeneity of cell types at the tumor-stroma interface and the complexity of their potential interactions hampered mechanistic insight required for efficient therapeutic targeting. Here, combining single-cell and spatial transcriptomics on human basal cell carcinomas, we define the cellular contributors of tumor progression. In the invasive niche, tumor cells exhibit a collective migration phenotype, characterized by the expression of cell-cell junction complexes. In physical proximity, we identify cancer-associated fibroblasts with extracellular matrix-remodeling features. Tumor cells strongly express the cytokine Activin A, and increased Activin A-induced gene signature is found in adjacent cancer-associated fibroblast subpopulations. Altogether, our data identify the cell populations and their transcriptional reprogramming contributing to the spatial organization of the basal cell carcinoma invasive niche. They also demonstrate the power of integrated spatial and single-cell multi-omics to decipher cancer-specific invasive properties and develop targeted therapies.
Global systematic review with meta-analysis shows that warming effects on terrestrial plant biomass allocation are influenced by precipitation and mycorrhizal association
Authors: Zhou Lingyan , Zhou Xuhui , He Yanghui , Fu Yuling , Du Zhenggang , Lu Meng , Sun Xiaoying , Li Chenghao , Lu Chunyan , Liu Ruiqiang , Zhou Guiyao , Bai Shahla Hosseni , Thakur Madhav P. 
Published: August 2022

AbstractBiomass allocation in plants is fundamental for understanding and predicting terrestrial carbon storage. Yet, our knowledge regarding warming effects on root: shoot ratio (R/S) remains limited. Here, we present a meta-analysis encompassing more than 300 studies and including angiosperms and gymnosperms as well as different biomes (cropland, desert, forest, grassland, tundra, and wetland). The meta-analysis shows that average warming of 2.50 °C (median = 2 °C) significantly increases biomass allocation to roots with a mean increase of 8.1% in R/S. Two factors associate significantly with this response to warming: mean annual precipitation and the type of mycorrhizal fungi associated with plants. Warming-induced allocation to roots is greater in drier habitats when compared to shoots (+15.1% in R/S), while lower in wetter habitats (+4.9% in R/S). This R/S pattern is more frequent in plants associated with arbuscular mycorrhizal fungi, compared to ectomycorrhizal fungi. These results show that precipitation variability and mycorrhizal association can affect terrestrial carbon dynamics by influencing biomass allocation strategies in a warmer world, suggesting that climate change could influence belowground C sequestration.
A film-lever actuated switch technology for multifunctional, on-demand, and robust manipulation of liquids
Authors: Liang Chao , Yang Zihang , Jiang Hanqing 
Published: August 2022

AbstractA lab-on-a-chip system with Point-of-Care testing capability offers rapid and accurate diagnostic potential and is useful in resource-limited settings where biomedical equipment and skilled professionals are not readily available. However, a Point-of-Care testing system that simultaneously possesses all required features of multifunctional dispensing, on-demand release, robust operations, and capability for long-term reagent storage is still a major challenge. Here, we describe a film-lever actuated switch technology that can manipulate liquids in any direction, provide accurate and proportional release response to the applied pneumatic pressure, as well as sustain robustness during abrupt movements and vibrations. Based on the technology, we also describe development of a polymerase chain reaction system that integrates reagent introduction, mixing and reaction functions all in one process, which accomplishes “sample-in-answer-out” performance for all clinical nasal samples from 18 patients with Influenza and 18 individual controls, in good concordance of fluorescence intensity with standard polymerase chain reaction (Pearson coefficients > 0.9). The proposed platform promises robust automation of biomedical analysis, and thus can accelerate the commercialization of a range of Point-of-Care testing devices.
Spatiotemporal-resolved protein networks profiling with photoactivation dependent proximity labeling
Authors: Zhai Yansheng , Huang Xiaoyan , Zhang Keren , Huang Yuchen , Jiang Yanlong , Cui Jingwei , Zhang Zhe , Chiu Cookson K. C. , Zhong Weiye , Li Gang 
Published: August 2022

AbstractEnzymatic-based proximity labeling approaches based on activated esters or phenoxy radicals have been widely used for mapping subcellular proteome and protein interactors in living cells. However, activated esters are poorly reactive which leads to a wide labeling radius and phenoxy radicals generated by peroxide treatment may disturb redox-sensitive pathways. Herein, we report a photoactivation-dependent proximity labeling (PDPL) method designed by genetically attaching photosensitizer protein miniSOG to a protein of interest. Triggered by blue light and tunned by irradiation time, singlet oxygen is generated, thereafter enabling spatiotemporally-resolved aniline probe labeling of histidine residues. We demonstrate its high-fidelity through mapping of organelle-specific proteomes. Side-by-side comparison of PDPL with TurboID reveals more specific and deeper proteomic coverage by PDPL. We further apply PDPL to the disease-related transcriptional coactivator BRD4 and E3 ligase Parkin, and discover previously unknown interactors. Through over-expression screening, two unreported substrates Ssu72 and SNW1 are identified for Parkin, whose degradation processes are mediated by the ubiquitination-proteosome pathway.
A mannose-sensing AraC-type transcriptional activator regulates cell–cell aggregation of Vibrio cholerae
Authors: Lee Hye-Young , Yoon Chang-Kyu , Cho Yong-Joon , Lee Jin-Woo , Lee Kyung-Ah , Lee Won-Jae , Seok Yeong-Jae 
Published: August 2022

AbstractIn addition to catalyzing coupled transport and phosphorylation of carbohydrates, the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulates various physiological processes in most bacteria. Therefore, the transcription of genes encoding the PTS is precisely regulated by transcriptional regulators depending on substrate availability. As the distribution of the mannose-specific PTS (PTSMan) is limited to animal-associated bacteria, it has been suggested to play an important role in host-bacteria interactions. In Vibrio cholerae, mannose is known to inhibit biofilm formation. During host infection, the transcription level of the V. cholerae gene encoding the putative PTSMan (hereafter referred to as manP) significantly increases, and mutations in this gene increase host survival rate. Herein, we show that an AraC-type transcriptional regulator (hereafter referred to as ManR) acts as a transcriptional activator of the mannose operon and is responsible for V. cholerae growth and biofilm inhibition on a mannose or fructose-supplemented medium. ManR activates mannose operon transcription by facilitating RNA polymerase binding to the promoter in response to mannose 6-phosphate and, to a lesser extent, to fructose 1-phosphate. When manP or manR is impaired, the mannose-induced inhibition of biofilm formation was reversed and intestinal colonization was significantly reduced in a Drosophila melanogaster infection model. Our results show that ManR recognizes mannose and fructose in the environment and facilitates V. cholerae survival in the host.
A systematic review on the effectiveness and impact of clinical decision support systems for breathlessness
Authors: Sunjaya Anthony P. , Ansari Sameera , Jenkins Christine R. 
Published: August 2022

AbstractBreathlessness is a common presenting symptom in practice. This systematic review aimed to evaluate the impact of CDSS on breathlessness and associated diseases in real-world clinical settings. Studies published between 1 January 2000 to 10 September 2021 were systematically obtained from 14 electronic research databases including CENTRAL, Embase, Pubmed, and clinical trial registries. Main outcomes of interest were patient health outcomes, provider use, diagnostic concordance, economic evaluation, and unintended consequences. The review protocol was prospectively registered in PROSPERO (CRD42020163141). A total of 4294 records were screened and 37 studies included of which 30 were RCTs. Twenty studies were in primary care, 13 in hospital outpatient/emergency department (ED), and the remainder mixed. Study duration ranged from 2 weeks to 5 years. Most were adults (58%). Five CDSS were focused on assessment, one on assessment and management, and the rest on disease-specific management. Most studies were disease-specific, predominantly focused on asthma (17 studies), COPD (2 studies), or asthma and COPD (3 studies). CDSS for COPD, heart failure, and asthma in adults reported clinical benefits such as reduced exacerbations, improved quality of life, improved patient-reported outcomes or reduced mortality. Studies identified low usage as the main barrier to effectiveness. Clinicians identified dissonance between CDSS recommendations and real-world practice as a major barrier. This review identified potential benefits of CDSS implementation in primary care and outpatient services for adults with heart failure, COPD, and asthma in improving diagnosis, compliance with guideline recommendations, promotion of non-pharmacological interventions, and improved clinical outcomes including mortality.
Ubiquitous enhancement of nematic fluctuations across the phase diagram of iron based superconductors probed by the Nernst effect
Authors: Wuttke Christoph , Caglieris Federico , Sykora Steffen , Steckel Frank , Hong Xiaochen , Ran Sheng , Khim Seunghyun , Kappenberger Rhea , Bud’ko Sergey L. , Canfield Paul C. , Wurmehl Sabine , Aswartham Saicharan , Büchner Bernd , Hess Christian 
Published: August 2022

AbstractThe role of nematic fluctuations for unconventional superconductivity has been the subject of intense discussions for many years. In iron-based superconductors, the most established probe for electronic-nematic fluctuations, i.e. the elastoresistivity seems to imply that superconductivity is reinforced by electronic-nematic fluctuations, since the elastoresistivity amplitude peaks at or close to optimal Tc. However, on the over-doped side of the superconducting dome, the diminishing elastoresistivity suggests a negligible importance in the mechanism of superconductivity. Here we introduce the Nernst coefficient as a genuine probe for electronic nematic fluctuations, and we show that the amplitude of the Nernst coefficient tracks the superconducting dome of two prototype families of iron-based superconductors, namely Rh-doped BaFe2As2 and Co-doped LaFeAsO. Our data thus provide fresh evidence that in these systems, nematic fluctuations foster the superconductivity throughout the phase diagram.
Evidence for the contribution of HCN1 gene polymorphism (rs1501357) to working memory at both behavioral and neural levels in schizophrenia patients and healthy controls
Authors: Chen Xiongying , Zhang Qiumei , Su Yanyan , Zhao Wan , Li Yang , Du Boqi , Deng Xiaoxiang , Ji Feng , Dong Qi , Chen Chuansheng , Li Jun 
Published: August 2022

AbstractGene HCN1 polymorphism (rs1501357) has been proposed to be one of the candidate risk genes for schizophrenia in the second report of the Psychiatric Genomics Consortium–Schizophrenia Workgroup. Although animal studies repeatedly showed a role of this gene in working memory, its contribution to working memory in human samples, especially in schizophrenia patients, is still unknown. To explore the association between rs1501357 and working memory at both behavioral (Study 1) and neural (Study 2) levels, the current study involved two independent samples. Study 1 included 876 schizophrenia patients and 842 healthy controls, all of whom were assessed on a 2-back task, a dot pattern expectancy task (DPX), and a digit span task. Study 2 included 56 schizophrenia patients and 155 healthy controls, all of whom performed a 2-back task during functional magnetic resonance imaging (fMRI) scanning. In both studies, we consistently found significant genotype-by-diagnosis interaction effects. For Study 1, the interaction effects were significant for the three tasks. Patients carrying the risk allele performed worse than noncarriers, while healthy controls showed the opposite pattern. For Study 2, the interaction effects were observed at the parietal cortex and the medial frontal cortex. Patients carrying the risk allele showed increased activation at right parietal cortex and increased deactivation at the medial frontal cortex, while healthy controls showed the opposite pattern. These results suggest that the contributions of rs1501357 to working memory capability vary in different populations (i.e., schizophrenia patients vs. healthy controls), which expands our understanding of the functional impact of the HCN1 gene. Future studies should examine its associations with other cognitive functions.