bluuebunny/crossref_metadata_2025 huggingface dataset:
The Response of Repetitive Very‐Long‐Period Seismic Signals at Aso Volcano to Periodic Loading
Authors: Niu Jieming , Song Teh‐Ru Alex
Published: April 2021

Triggering of volcano seismic activity and eruptions by tides, atmosphere pressure, rainfall, and earthquakes have been in constant debate. However, there is limited evidence concerning the triggering of very‐long‐period signals (VLPs), which are closely linked to volcano conduit dynamics. Persistent and repetitive VLP event beneath the Aso volcano, historically termed long‐period tremor (LPT), manifests episodic pressurization and depressurization events in a crack‐like shallow conduit. Here we show that LPT activity display no appreciable spectral peaks associated with major diurnal/semidiurnal tidal constituents or barometric pressure. Instead, passing surface waves of ∼0.01 m/s from the 2011 Tohoku earthquake elevated LPT activity and preferentially increased the likelihood of depressurization events. We suggest that the hydrothermal reservoir near the LPT source behaves like a confined (unconfined) aquifer against short‐period (long‐period) stress. A high stress rate of ∼102 Pa/s is sufficient to enhance the permeability of the conduit plug/wall and preferentially promotes depressurization events.
On the Species Dependence of Ion Escapes Across the Magnetopause
Authors: Zhou Xu‐Zhi , Zhang Xuan , Li Jing‐Huan , Zong Qiu‐Gang
Published: April 2021

Recent observations and particle‐tracing models have revealed a counterintuitive difference between the behaviors of magnetospheric protons and oxygen ions when they encounter the magnetopause. The oxygen ions usually meander around the magnetopause without a full escape to the magnetosheath, whereas the protons can more easily stream across the magnetopause despite their smaller gyroradii. Here, we analytically identify the mechanisms that cause this species dependence. As magnetospheric ions drift toward the magnetopause, the grazing angle of their magnetopause encounter is constrained within a narrow range near 0°, with its maximum being proportional to the square root of the ion gyroradius. It is the grazing angle that largely determines the follow‐up ion motion. The ions with larger grazing angles would meander around the magnetopause, whereas the meandering motion for ions with smaller grazing angles could be easily disrupted to enable their escape even if the normal magnetic field is very weak.
Temporal relationship between body mass index and uric acid and their joint impact on blood pressure in children and adults: the Bogalusa Heart Study
Authors: Yun Miaoying , Zhang Tao , Li Shengxu , Wang Xuan , Fan Lijun , Yan Yinkun , Bazzano Lydia , He Jiang , Chen Wei
Published: April 2021

Objective

This study aimed to examine the temporal relationship between body mass index (BMI) and uric acid (UA), and their joint effect on blood pressure (BP) in children and adults.

Methods

The longitudinal cohorts for temporal relationship analyses consisted of 564 and 911 subjects examined twice 5–14 years apart from childhood to adulthood. The cross-sectional cohorts for mediation analyses consisted of 3102 children and 3402 nondiabetic adults. Cross-lagged panel analysis models were used to examine the temporal relationship between BMI and UA, and mediation analysis models the mediation effect of UA on the BMI–BP association.

Results

After adjusting for age, race, sex and follow-up years in children, and additionally smoking and alcohol drinking in adults, the path coefficients (standardized regression coefficients) from baseline BMI to follow-up UA (0.145 in children and 0.068 in adults) were significant, but the path coefficients from baseline UA to follow-up BMI (0.011 in children and 0.016 in adults) were not. In mediation analyses, indirect effects through UA on the BMI-systolic BP association were estimated at 0.028 (mediation effect = 8.8%) in children and 0.033 (mediation effect = 13.5%) in adults (P < 0.001 for both). Direct effects of BMI on systolic BP (0.289 in children and 0.212 in adults) were significant. The mediation effect parameters did not differ significantly between Blacks and Whites.

Conclusions

Changes in BMI precede alterations in UA, and the BMI–BP association is in part mediated through BMI-related increase in UA both in children and in adults. These findings have implications for addressing mechanisms of obesity hypertension beginning in early life.
Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2
Authors: Liu Yang , Tang Tianchi , Yang Xiaosheng , Qin Peng , Wang Pusen , Zhang Huiping , Bai Min , Wu Rong , Li Fan
Published: April 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.
Protein tyrosine phosphatase receptor type D gene promotes radiosensitivity via STAT3 dephosphorylation in nasopharyngeal carcinoma
Authors: Lin Yanling , Zhou Xiaohan , Yang Kaifan , Chen Yuting , Wang Lingzhi , Luo Wenxiao , Li Yujiang , Liao Jinrong , Zhou Yingtong , Lei Yiming , Zhang Yanting , Wu Dehua , Cai Longmei
Published: April 2021

Radiotherapy is essential to the treatment of nasopharyngeal carcinoma (NPC) and acquired or innate resistance to this therapeutic modality is a major clinical problem. However, the underlying molecular mechanisms in the radiation resistance in NPC are not fully understood. Here, we reanalyzed the microarray data from public databases and identified the protein tyrosine phosphatase receptor type D (PTPRD) as a candidate gene. We found thatPTPRDwas downregulated in clinical NPC tissues and NPC cell lines with its promoter hypermethylated. Functional assays revealed thatPTPRDoverexpression sensitized NPC to radiation in vitro and in vivo. Importantly, miR-454-3p directly targetsPTPRDto inhibit its expression and biological effect. Interestingly, mechanistic analyses indicate thatPTPRDdirectly dephosphorylates STAT3 to enhance Autophagy-Related 5(ATG5)transcription, resulting in triggering radiation-induced autophagy. The immunohistochemical staining of 107 NPC revealed that lowPTPRDand high p-STAT3 levels predicted poor clinical outcome. Overall, we showed thatPTPRDpromotes radiosensitivity by triggering radiation-induced autophagy via the dephosphorylation of STAT3, thus providing a potentially useful predictive biomarker for NPC radiosensitivity and drug target for NPC radiosensitization.
CARD10 cleavage by MALT1 restricts lung carcinoma growth in vivo
Authors: Israël Laura , Glück Anton , Berger Marjorie , Coral Marine , Ceci Melanie , Unterreiner Adeline , Rubert Joëlle , Bardet Maureen , Ginster Stefanie , Golding-Ochsenbein Alexandra M. , Martin Kea , Hoyler Thomas , Calzascia Thomas , Wieczorek Grazyna , Hillenbrand Rainer , Ferretti Stéphane , Ferrero Enrico , Bornancin Frédéric
Published: April 2021

CARD-CC complexes involving BCL10 and MALT1 are major cellular signaling hubs. They govern NF-κB activation through their scaffolding properties as well as MALT1 paracaspase function, which cleaves substrates involved in NF-κB regulation. In human lymphocytes, gain-of-function defects in this pathway lead to lymphoproliferative disorders. CARD10, the prototypical CARD-CC protein in non-hematopoietic cells, is overexpressed in several cancers and has been associated with poor prognosis. However, regulation of CARD10 remains poorly understood. Here, we identified CARD10 as the first MALT1 substrate in non-hematopoietic cells and showed that CARD10 cleavage by MALT1 at R587 dampens its capacity to activate NF-κB. Preventing CARD10 cleavage in the lung tumor A549 cell line increased basal levels of IL-6 and extracellular matrix components in vitro, and led to increased tumor growth in a mouse xenograft model, suggesting that CARD10 cleavage by MALT1 might be a built-in mechanism controlling tumorigenicity.
Evolutionary stasis of a deep subsurface microbial lineage
Authors: Becraft Eric D , Lau Vetter Maggie C Y , Bezuidt Oliver K I , Brown Julia M , Labonté Jessica M , Kauneckaite-Griguole Kotryna , Salkauskaite Ruta , Alzbutas Gediminas , Sackett Joshua D , Kruger Brittany R , Kadnikov Vitaly , van Heerden Esta , Moser Duane , Ravin Nikolai , Onstott Tullis , Stepanauskas Ramunas
Published: April 2021

Sulfate-reducing bacteria Candidatus Desulforudis audaxviator (CDA) were originally discovered in deep fracture fluids accessed via South African gold mines and have since been found in geographically widespread deep subsurface locations. In order to constrain models for subsurface microbial evolution, we compared CDA genomes from Africa, North America and Eurasia using single cell genomics. Unexpectedly, 126 partial single amplified genomes from the three continents, a complete genome from of an isolate from Eurasia, and metagenome-assembled genomes from Africa and Eurasia shared >99.2% average nucleotide identity, low frequency of SNP’s, and near-perfectly conserved prophages and CRISPRs. Our analyses reject sample cross-contamination, recent natural dispersal, and unusually strong purifying selection as likely explanations for these unexpected results. We therefore conclude that the analyzed CDA populations underwent only minimal evolution since their physical separation, potentially as far back as the breakup of Pangea between 165 and 55 Ma ago. High-fidelity DNA replication and repair mechanisms are the most plausible explanation for the highly conserved genome of CDA. CDA presents a stark contrast to the current model organisms in microbial evolutionary studies, which often develop adaptive traits over far shorter periods of time.
CAR-T cell therapy: current limitations and potential strategies
Authors: Sterner Robert C. , Sterner Rosalie M.
Published: April 2021

Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.
Sequential targeting of PI3Kδ and LAG3 as an effective anti-cancer approach
Authors: Lauder Sarah N. , Vanhaesebroeck Bart , Gallimore Awen
Published: April 2021

Emerging studies have demonstrated the potential of PI3Kδ blockade as an immunotherapy for solid tumours. In pre-clinical models, we recently demonstrated that anti-LAG3 immune checkpoint blockade vastly potentiated PI3Kδ-based immunotherapy, enabling successful tumour control in all treated mice.
MLL5 improves ATRA driven differentiation and promotes xenotransplant engraftment in acute promyelocytic leukemia model
Authors: Pereira-Martins Diego A. , Weinhäuser Isabel , Coelho-Silva Juan Luiz , França-Neto Pedro L. , Almeida Luciana Y. , Bianco Thiago M. , Silva Cleide L. , França Rafael F. , Traina Fabiola , Rego Eduardo M. , Schuringa Jan Jacob , Lucena-Araujo Antonio R.
Published: April 2021

Although the mixed lineage leukemia 5 (MLL5) gene has prognostic implications in acute promyelocyte leukemia (APL), the underlying mechanism remains to be elucidated. Here, we demonstrate the critical role exerted by MLL5 in APL regarding cell proliferation and resistance to drug-induced apoptosis, through mtROS regulation. Additionally, MLL5 overexpression increased the responsiveness of APL leukemic cells to all-trans retinoic acid (ATRA)-induced differentiation, via regulation of the epigenetic modifiers SETD7 and LSD1. In silico analysis indicated that APL blasts with MLL5high transcript levels were associated with retinoic acid binding and downstream signaling, while MLL5low blasts displayed decreased expression of epigenetic modifiers (such as KMT2C, PHF8 and ARID4A). Finally, APL xenograft transplants demonstrated improved engraftment of MLL5-expressing cells and increased myeloid differentiation over time. Concordantly, evaluation of engrafted blasts revealed increased responsiveness of MLL5-expressing cells to ATRA-induced granulocytic differentiation. Together, we describe the epigenetic changes triggered by the interaction of MLL5 and ATRA resulting in enhanced granulocytic differentiation.
Membrane lymphotoxin-α2β is a novel tumor necrosis factor (TNF) receptor 2 (TNFR2) agonist
Authors: Kucka Kirstin , Lang Isabell , Zhang Tengyu , Siegmund Daniela , Medler Juliane , Wajant Harald
Published: April 2021

In the early 1990s, it has been described that LTα and LTβ form LTα2β and LTαβ2heterotrimers, which bind to TNFR1 and LTβR, respectively. Afterwards, the LTαβ2–LTβR system has been intensively studied while the LTα2β–TNFR1 interaction has been ignored to date, presumably due to the fact that at the time of identification of the LTα2β–TNFR1 interaction one knew already two ligands for TNFR1, namely TNF and LTα. Here, we show that LTα2β interacts not only with TNFR1 but also with TNFR2. We furthermore demonstrate that membrane-bound LTα2β (memLTα2β), despite its asymmetric structure, stimulates TNFR1 and TNFR2 signaling. Not surprising in view of its ability to interact with TNFR2, LTα2β is inhibited by Etanercept, which is approved for the treatment of rheumatoid arthritis and also inhibits TNF and LTα.
Single loss of a Trp53 allele triggers an increased oxidative, DNA damage and cytokine inflammatory responses through deregulation of IκBα expression
Authors: Marruecos Laura , Manils Joan , Moreta Cristina , Gómez Diana , Filgaira Ingrid , Serafin Anna , Cañas Xavier , Espinosa Lluís , Soler Concepció
Published: April 2021

Dose of Trp53, the main keeper of genome stability, influences tumorigenesis; however, the causes underlying and driving tumorigenesis over time by the loss of a single p53 allele are still poorly characterized. Here, we found that single p53 allele loss specifically impacted the oxidative, DNA damage and inflammatory status of hematopoietic lineages. In particular, single Trp53 allele loss in mice triggered oxidative stress in peripheral blood granulocytes and spleenocytes, whereas lack of two Trp53 alleles produced enhanced oxidative stress in thymus cells, resulting in a higher incidence of lymphomas in the Trp53 knockout (KO) mice compared with hemizygous (HEM). In addition, single or complete loss of Trp53 alleles, as well as p53 downregulation, led to a differential increase in basal, LPS- and UVB-induced expression of a plethora of pro-inflammatory cytokine, such as interleukin-12 (Il-12a), TNFα (Tnfa) and interleukin (Il-23a) in bone marrow-derived macrophage cells (BMDMs) compared to WT cells. Interestingly, p53-dependent increased inflammatory gene expression correlated with deregulated expression of the NF-κB pathway inhibitor IκBα. Chromatin immunoprecipitation data revealed decreased p65 binding to Nfkbia in the absence of p53 and p53 binding to Nfkbia promoter, uncovering a novel crosstalk mechanism between p53 and NF-κB transcription factors. Overall, our data suggest that single Trp53 allele loss can drive a sustained inflammatory, DNA damage and oxidative stress response that, over time, facilitate and support carcinogenesis.
LncRNA MALAT1 promotes gastric cancer progression via inhibiting autophagic flux and inducing fibroblast activation
Authors: Wang Zhenqiang , Wang Xinjing , Zhang Tianqi , Su Liping , Liu Bingya , Zhu Zhenggang , Li Chen
Published: April 2021

Autophagy defection contributes to inflammation dysregulation, which plays an important role in gastric cancer (GC) progression. Various studies have demonstrated that long noncoding RNA could function as novel regulators of autophagy. Previously, long noncoding RNA MALAT1 was reported upregulated in GC cells and could positively regulate autophagy in various cancers. Here, we for the first time found that MALAT1 could promote interleukin-6 (IL-6) secretion in GC cells by blocking autophagic flux. Moreover, IL-6 induced by MALAT1 could activate normal to cancer-associated fibroblast conversion. The interaction between GC cells and cancer-associated fibroblasts in the tumour microenvironment could facilitate cancer progression. Mechanistically, MALAT1 overexpression destabilized the PTEN mRNA in GC cells by competitively interacting with the RNA-binding protein ELAVL1 to activate the AKT/mTOR pathway for impairing autophagic flux. As a consequence of autophagy inhibition, SQSTM1 accumulation promotes NF-κB translocation to elevate IL-6 expression. Overall, these results demonstrated that intercellular interaction between GC cells and fibroblasts was mediated by autophagy inhibition caused by increased MALAT1 that promotes GC progression, providing novel prevention and therapeutic strategies for GC.
Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
Authors: Maurya Bhawana , Surabhi Satya , Das Rituparna , Pandey Pranjali , Mukherjee Ashim , Mutsuddi Mousumi
Published: April 2021

Maheshvara (mahe), an RNA helicase that is widely conserved across taxa, regulates Notch signaling and neuronal development in Drosophila. In order to identify novel components regulated by mahe, transcriptome profiling of ectopic mahe was carried out and this revealed striking upregulation of JAK/STAT pathway components like upd1, upd2, upd3, and socs36E. Further, significant downregulation of the pathway components in mahe loss-of-function mutant as well as upon lowering the level of mahe by RNAi, supported and strengthened our transcriptome data. Parallelly, we observed that mahe, induced caspase-dependent apoptosis in photoreceptor neurons, and this phenotype was significantly modulated by JAK/STAT pathway components. RNA immunoprecipitation unveiled the presence of JAK/STAT tyrosine kinase hopscotch (hop) transcripts in the complex immunoprecipitated with Mahe, which ultimately resulted in stabilization and elevation of hop transcripts. Additionally, we also observed the surge in activity of downstream transcription factor Stat92E, which is indicative of activation of the JAK/STAT signaling, and this in turn led to apoptosis via upregulation of hid. Taken together, our data provide a novel regulation of JAK/STAT pathway by RNA helicase Maheshvara, which ultimately promotes apoptosis.
Functional comparison of SARS-CoV-2 with closely related pangolin and bat coronaviruses
Authors: Nie Jianhui , Li Qianqian , Zhang Li , Cao Yang , Zhang Yue , Li Tao , Wu Jiajing , Liu Shuo , Zhang Mengyi , Zhao Chenyan , Liu Huan , Nie Lingling , Qin Haiyang , Wang Meng , Lu Qiong , Li Xiaoyu , Liu Junkai , Liang Haoyu , Jiang Taijiao , Duan Kai , Yang Xiaoming , Shen Yuelei , Huang Weijin , Wang Youchun
Published: April 2021

The origin and intermediate host for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is yet to be determined. Coronaviruses found to be closely related to SARS-CoV-2 include RaTG13 derived from bat and two clusters (PCoV-GD and PCoV-GX) of coronaviruses identified in pangolin. Here, we studied the infectivity and antigenicity patterns of SARS-CoV-2 and the three related coronaviruses. Compared with the other three viruses, RaTG13 showed almost no infectivity to a variety of cell lines. The two pangolin coronaviruses and SARS-CoV-2 showed similar infectious activity. However, in SARS-CoV-2-susceptible cell lines, the pangolin coronaviruses presented even higher infectivity. The striking difference between the SARS-CoV-2 and pangolin coronaviruses is that the latter can infect porcine cells, which could be partially attributed to an amino acid difference at the position of 498 of the spike protein. The infection by SARS-CoV-2 was mainly mediated by Furin and TMPRSS2, while PCoV-GD and PCoV-GX mainly depend on Cathepsin L. Extensive cross-neutralization was found between SARS-CoV-2 and PCoV-GD. However, almost no cross-neutralization was observed between PCoV-GX and SARS-CoV-2 or PCoV-GD. More attention should be paid to pangolin coronaviruses and to investigate the possibility of these coronaviruses spreading across species to become zoonoses among pigs or humans.
T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses
Authors: Ogbe Ane , Kronsteiner Barbara , Skelly Donal T. , Pace Matthew , Brown Anthony , Adland Emily , Adair Kareena , Akhter Hossain Delowar , Ali Mohammad , Ali Serat-E , Angyal Adrienn , Ansari M. Azim , Arancibia-Cárcamo Carolina V. , Brown Helen , Chinnakannan Senthil , Conlon Christopher , de Lara Catherine , de Silva Thushan , Dold Christina , Dong Tao , Donnison Timothy , Eyre David , Flaxman Amy , Fletcher Helen , Gardner Joshua , Grist James T. , Hackstein Carl-Philipp , Jaruthamsophon Kanoot , Jeffery Katie , Lambe Teresa , Lee Lian , Li Wenqin , Lim Nicholas , Matthews Philippa C. , Mentzer Alexander J. , Moore Shona C. , Naisbitt Dean J. , Ogese Monday , Ogg Graham , Openshaw Peter , Pirmohamed Munir , Pollard Andrew J. , Ramamurthy Narayan , Rongkard Patpong , Rowland-Jones Sarah , Sampson Oliver , Screaton Gavin , Sette Alessandro , Stafford Lizzie , Thompson Craig , Thomson Paul J. , Thwaites Ryan , Vieira Vinicius , Weiskopf Daniela , Zacharopoulou Panagiota ,   Oxford Immunology Network Covid-19 Response T Cell Consortium, Chalk Jeremy , Kerr Georgina , Phalora Prabhjeet , Csala Anna , Jones Mathew , Robinson Nicola , Brown Rachael , Hutchings Claire , Provine Nicholas , Ratcliff Jeremy , Amini Ali ,   Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team, Borak Martyna , Dimitriadis Stavros , Fordwoh Thomas , Horsington Bryn , Johnson Sile , Morrow Jordan , Warren Yolanda , Wells Charlie , Turtle Lance , Klenerman Paul , Goulder Philip , Frater John , Barnes Eleanor , Dunachie Susanna
Published: April 2021

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.
Variable number tandem repeats mediate the expression of proximal genes
Authors: Bakhtiari Mehrdad , Park Jonghun , Ding Yuan-Chun , Shleizer-Burko Sharona , Neuhausen Susan L. , Halldórsson Bjarni V. , Stefánsson Kári , Gymrek Melissa , Bafna Vineet
Published: April 2021

Variable number tandem repeats (VNTRs) account for significant genetic variation in many organisms. In humans, VNTRs have been implicated in both Mendelian and complex disorders, but are largely ignored by genomic pipelines due to the complexity of genotyping and the computational expense. We describe adVNTR-NN, a method that uses shallow neural networks to genotype a VNTR in 18 seconds on 55X whole genome data, while maintaining high accuracy. We use adVNTR-NN to genotype 10,264 VNTRs in 652 GTEx individuals. Associating VNTR length with gene expression in 46 tissues, we identify 163 “eVNTRs”. Of the 22 eVNTRs in blood where independent data is available, 21 (95%) are replicated in terms of significance and direction of association. 49% of the eVNTR loci show a strong and likely causal impact on the expression of genes and 80% have maximum effect size at least 0.3. The impacted genes are involved in diseases including Alzheimer’s, obesity and familial cancers, highlighting the importance of VNTRs for understanding the genetic basis of complex diseases.
Multi-phase seismic source imprint of tropical cyclones
Authors: Retailleau Lise , Gualtieri Lucia
Published: April 2021

The coupling between the ocean activity driven by winds and the solid Earth generates seismic signals recorded by seismometers worldwide. The 2–10 s period band, known as secondary microseism, represents the largest background seismic wavefield. While moving over the ocean, tropical cyclones generate particularly strong and localized sources of secondary microseisms that are detected remotely by seismic arrays. We assess and compare the seismic sources of P, SV, and SH waves associated with typhoon Ioke (2006) during its extra-tropical transition. To understand their generation mechanisms, we compare the observed multi-phase sources with theoretical sources computed with a numerical ocean wave model, and we assess the influence of the ocean resonance (or ocean site effect) and coastal reflection of ocean waves. We show how the location and lateral extent of the associated seismic source is period- and phase-dependent. This information is crucial for the use of body waves for ambient noise imaging and gives insights about the sea state, complementary to satellite data.
Policy assessments for the carbon emission flows and sustainability of Bitcoin blockchain operation in China
Authors: Jiang Shangrong , Li Yuze , Lu Quanying , Hong Yongmiao , Guan Dabo , Xiong Yu , Wang Shouyang
Published: April 2021

The growing energy consumption and associated carbon emission of Bitcoin mining could potentially undermine global sustainable efforts. By investigating carbon emission flows of Bitcoin blockchain operation in China with a simulation-based Bitcoin blockchain carbon emission model, we find that without any policy interventions, the annual energy consumption of the Bitcoin blockchain in China is expected to peak in 2024 at 296.59 Twh and generate 130.50 million metric tons of carbon emission correspondingly. Internationally, this emission output would exceed the total annualized greenhouse gas emission output of the Czech Republic and Qatar. Domestically, it ranks in the top 10 among 182 cities and 42 industrial sectors in China. In this work, we show that moving away from the current punitive carbon tax policy to a site regulation policy which induces changes in the energy consumption structure of the mining activities is more effective in limiting carbon emission of Bitcoin blockchain operation.
Deficiency of TMEM53 causes a previously unknown sclerosing bone disorder by dysregulation of BMP-SMAD signaling
Authors: Guo Long , Iida Aritoshi , Bhavani Gandham SriLakshmi , Gowrishankar Kalpana , Wang Zheng , Xue Jing-yi , Wang Juan , Miyake Noriko , Matsumoto Naomichi , Hasegawa Takanori , Iizuka Yusuke , Matsuda Masashi , Nakashima Tomoki , Takechi Masaki , Iseki Sachiko , Yambe Shinsei , Nishimura Gen , Koseki Haruhiko , Shukunami Chisa , Girisha Katta M. , Ikegawa Shiro
Published: April 2021

Bone formation represents a heritable trait regulated by many signals and complex mechanisms. Its abnormalities manifest themselves in various diseases, including sclerosing bone disorder (SBD). Exploration of genes that cause SBD has significantly improved our understanding of the mechanisms that regulate bone formation. Here, we discover a previously unknown type of SBD in four independent families caused by bi-allelic loss-of-function pathogenic variants in TMEM53, which encodes a nuclear envelope transmembrane protein. Tmem53-/- mice recapitulate the human skeletal phenotypes. Analyses of the molecular pathophysiology using the primary cells from the Tmem53-/- mice and the TMEM53 knock-out cell lines indicates that TMEM53 inhibits BMP signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of BMP2-activated Smad proteins. Pathogenic variants in the patients impair the TMEM53-mediated blocking effect, thus leading to overactivated BMP signaling that promotes bone formation and contributes to the SBD phenotype. Our results establish a previously unreported SBD entity (craniotubular dysplasia, Ikegawa type) and contribute to a better understanding of the regulation of BMP signaling and bone formation.
Creating polar antivortex in PbTiO3/SrTiO3 superlattice
Authors: Abid Adeel Y. , Sun Yuanwei , Hou Xu , Tan Congbing , Zhong Xiangli , Zhu Ruixue , Chen Haoyun , Qu Ke , Li Yuehui , Wu Mei , Zhang Jingmin , Wang Jinbin , Liu Kaihui , Bai Xuedong , Yu Dapeng , Ouyang Xiaoping , Wang Jie , Li Jiangyu , Gao Peng
Published: April 2021

Nontrivial topological structures offer a rich playground in condensed matters and promise alternative device configurations for post-Moore electronics. While recently a number of polar topologies have been discovered in confined ferroelectric PbTiO3 within artificially engineered PbTiO3/SrTiO3 superlattices, little attention was paid to possible topological polar structures in SrTiO3. Here we successfully create previously unrealized polar antivortices within the SrTiO3 of PbTiO3/SrTiO3 superlattices, accomplished by carefully engineering their thicknesses guided by phase-field simulation. Field- and thermal-induced Kosterlitz–Thouless-like topological phase transitions have also been demonstrated, and it was discovered that the driving force for antivortex formation is electrostatic instead of elastic. This work completes an important missing link in polar topologies, expands the reaches of topological structures, and offers insight into searching and manipulating polar textures.
Spin photogalvanic effect in two-dimensional collinear antiferromagnets
Authors: Xiao Rui-Chun , Shao Ding-Fu , Li Yu-Hang , Jiang Hua
Published: April 2021

Recent discovered two-dimensional (2D) antiferromagnetic (AFM) van der Waals quantum materials have attracted increasing interest due to the emergent exotic physical phenomena. The spintronic properties utilizing the intrinsic AFM state in 2D antiferromagnets, however, have been rarely found. Here we show that the spin photogalvanic effect (SPGE), which has been predicted in three-dimensional (3D) antiferromagnets, can intrinsically emerge in 2D antiferromagnets for promising spintronic applications. Based on the symmetry analysis of possible AFM orders in the honeycomb lattice, we conclude suitable 2D AFM candidate materials for realizing the SPGE. We choose two experimentally synthesized 2D collinear AFM materials, monolayer MnPS3, and bilayer CrCl3, as representative materials to perform first-principles calculations, and find that they support sizable SPGE. The SPGE in collinear 2D AFM materials can be utilized to generate pure spin current in a contactless and ultra-fast way.
Simulating virtual images in optical trap displays
Authors: Rogers Wesley , Smalley Daniel
Published: April 2021

Optical trap displays (OTD) are an emerging display technology with the ability to create full-color images in air. Like all volumetric displays, OTDs lack the ability to show virtual images. However, in this paper we show that it is possible to instead simulate virtual images by employing a time-varying perspective projection backdrop.
WLTC and real-driving emissions for an autochthonous biofuel from wine-industry waste
Authors: Lapuerta Magín , Rodríguez-Fernández José , Ramos Ángel , Donoso David , Canoira Laureano
Published: April 2021

Residues from the wine industry constitute an abundant feedstock for biodiesel production in wine-producing countries. The use of grapeseed oil, together with bioethanol obtained from distillation of wine surplus or grape skins and stalks and wine lees, as reagents in the transesterification reaction, results in a mixture of fatty acid ethyl esters (FAEE), which is a fully renewable, autochthonous, and waste-derived biofuel. In this work, a blend of FAEE produced from grape seed oil with diesel fuel was selected based on a study of fuel properties, and the optimal blend, with 30% v/v of FAEE, was tested in a Euro 6 engine following the Worldwide harmonized Light-duty Test Cycle (WLTC) and a Real Driving Emissions Cycle (RDE), as required in the new certification procedures. Engine performance and emissions from this blend and a commercial diesel fuel were compared. The FAEE blend showed a significant potential to reduce particle emissions, both in mass and number (from 23% in number to 46.5% in mass for WLTC, and from 56% in number to 61% in mass for RDE), and CO (25.5% for WLTC and 39% for RDE) but penalized NOx (32% higher in WLTC and 26.4% higher in RDE).
Identification of PDGFRα-positive interstitial cells in the distal segment of the murine vas deferens
Authors: Hiroshige Tasuku , Uemura Kei-Ichiro , Hirashima Shingo , Hino Kiyosato , Togo Akinobu , Ohta Keisuke , Igawa Tsukasa , Nakamura Kei-Ichiro
Published: April 2021

Platelet-derived growth factor receptor-α (PDGFRα)-positive interstitial cells (ICs) are widely distributed in various organs and may be involved in the motility of various tubular organs. We, for the first time, aimed to investigate the distribution, immunohistochemical characteristics, and ultrastructure of PDGFRα-positive ICs in murine vas deferens, using confocal laser scanning microscopy, transmission electron microscopy (TEM), and immuno-electron microscopy (immuno-EM). For immunofluorescence, we used antibodies against PDGFRα and other markers of ICs. PDGFRα-positive ICs were distributed widely in the lamina propria, smooth muscles, and serosal layers. Although most PDGFRα-positive ICs labeled CD34, they did not label CD34 in the subepithelial layers. Additionally, PDGFRα-positive ICs were in close proximity to each other, as also to the surrounding cells. TEM and immuno-EM findings revealed that PDGFRα-positive ICs established close physical interactions with adjacent ICs. Extracellular vesicles were also detected around the PDGFRα-positive ICs. Our morphological findings suggest that PDGFRα-positive ICs may have several subpopulations, which can play an important role in intercellular signaling via direct contact with the IC network and the extracellular vesicles in the murine vas deferens. Further investigation on PDGFRα-positive ICs in the vas deferens may lead to understanding the vas deferens mortility.
A photoanode with hierarchical nanoforest TiO2 structure and silver plasmonic nanoparticles for flexible dye sensitized solar cell
Authors: Choudhury Brishty Deb , Lin Chen , Shawon Sk Md Ali Zaker , Soliz-Martinez Javier , Huq Hasina , Uddin Mohammed Jasim
Published: April 2021

Due to unique photovoltaic properties, the nanostructured morphologies of TiO2on flexible substrate have been studied extensively in the recent years for applications in dye sensitized solar cells (DSSCs). Microstructured electrode materials with high surface area can facilitate rapid charge transport and thus improve the light-to-current conversion efficiency. Herein we present an improved photoanode with forest like photoactive TiO2hierarchical microstructure using a simple and facile hydrothermal route. To utilize the surface plasmon resonance (SPR) and hence increase the photon conversion efficiency, a plasmonic nanoparticle Ag has also been deposited using a very feasible photoreduction method. The branched structure of the photoanode increases the dye loading by filling the space between the nanowires, whereas Ag nanoparticles play the multiple roles of dye absorption and light scattering to increase the light-to-current conversion efficiency of the device. The branched structure provides a suitable matrix for the subsequent Ag deposition. They improve the charge collection efficiency by providing the preferential electron pathways. The high-density Ag nanoparticles deposited on the forest like structure also decrease the charge recombination and therefore improve the photovoltaic efficiency of the cells. As a result, the DSSC based on this novel photoanode shows remarkably higher photon conversion efficiency (ηmax = 4.0% and ηopt = 3.15%) compared to the device based on pristine nanowire or forest-like TiO2structure. The flexibility of the device showed sustainable and efficient performance of the microcells.
Dual polarized engineering the extinction cross-section of a dielectric wire using graphene-based oligomers
Authors: Raad Shiva Hayati , Atlasbaf Zahra
Published: April 2021

In this paper, graphene-coated spherical nanoparticles are arranged around an infinite length dielectric cylinder to enhance its extinction cross-section. Initially, a single longitudinal one-dimensional periodic array is considered in different loci concerning the transverse electric (TE) incident plane wave. It is observed that regardless of the position of the particles, the extinction cross-section of the dielectric cylinder is considerably enhanced with respect to the bare one. Later, by increasing the number of longitudinal plasmonic arrays around the cylinder, each residing in a different azimuthal direction, the extinction cross-section is further manipulated to observe double pronounced Fano resonances. The origin of the Fano resonances is described by considering their planar counterparts constructed by the periodic assembly of plasmonic oligomers. Finally, the hexamer configuration is considered as the prototype, and the effect of various optical, geometrical, and material parameters on the optical response is investigated in detail. Interestingly, due to the spherical symmetry of the cells, the extinction cross-section is also enhanced for the transverse magnetic (TM) incident wave, which is unattainable using a continuous plasmonic cover made of metal or graphene. The potential application of our proposed structure is in the design of reconfigurable conformal optical absorbers and sensors.
iTRAQ-based proteome profiling revealed the role of Phytochrome A in regulating primary metabolism in tomato seedling
Authors: Thomas Sherinmol , Kumar Rakesh , Sharma Kapil , Barpanda Abhilash , Sreelakshmi Yellamaraju , Sharma Rameshwar , Srivastava Sanjeeva
Published: April 2021

In plants, during growth and development, photoreceptors monitor fluctuations in their environment and adjust their metabolism as a strategy of surveillance. Phytochromes (Phys) play an essential role in plant growth and development, from germination to fruit development. FR-light (FR) insensitive mutant (fri) carries a recessive mutation in Phytochrome A and is characterized by the failure to de-etiolate in continuous FR. Here we used iTRAQ-based quantitative proteomics along with metabolomics to unravel the role of Phytochrome A in regulating central metabolism in tomato seedlings grown under FR. Our results indicate that Phytochrome A has a predominant role in FR-mediated establishment of the mature seedling proteome. Further, we observed temporal regulation in the expression of several of the late response proteins associated with central metabolism. The proteomics investigations identified a decreased abundance of enzymes involved in photosynthesis and carbon fixation in the mutant. Profound accumulation of storage proteins in the mutant ascertained the possible conversion of sugars into storage material instead of being used or the retention of an earlier profile associated with the mature embryo. The enhanced accumulation of organic sugars in the seedlings indicates the absence of photomorphogenesis in the mutant.
A hospital-based study on clinical data, demographic data and visual function of keratoconus patients in Central China
Authors: Yang Kaili , Xu Liyan , Fan Qi , Gu Yuwei , Zhang Bo , Meng Feiying , Zhao Dongqing , Pang Chenjiu , Ren Shengwei
Published: April 2021

China is a populous country but lacks epidemiological data on keratoconus (KC). The present study aimed to investigate the clinical data, demographic data, and visual function (VF) data of KC patients in Central China. A total of 524 KC eyes in 307 KC patients (217 bilateral and 90 unilateral) from Henan Eye Hospital were included in the current study. Demographic and VF data were assessed with questionnaires administered by well-trained staff during face-to-face interviews. Visual acuity value was examined by a qualified optometrist, and the clinical data were measured by professional clinicians. The distributions of sex, residence and education level of KC patients were compared by Chi-square tests, and the ratios of people wearing glasses and rigid gas permeable (RGP) lenses were compared by McNemar tests. General linear models/Chi-squared tests were used to compare the clinical and demographic data according to KC severity. Spearman’s correlation analysis was used to test the associations between the data and KC severity. The mean age at diagnosis was 20.98 ± 6.06 years, and males had a higher ratio of KC than females (P < 0.001). Patients in rural areas had a higher rate of KC than those in urban areas (P = 0.039), and the proportion of KC patients with a higher education level (above high school) was high (P < 0.001). A total of 68.40% of the patients reported eye rubbing and 3.52% had a positive family history. The percentage of people wearing glasses was higher than that of patients wearing RGP lenses (P < 0.001). The total VF score of KC patients was 69.35 ± 15.25. The thinnest corneal thickness (TCT) and stiffness parameter at the first applanation (SP-A1) values were inversely correlated with KC severity (P < 0.05). The mean, steep, and max keratometry (Km, Ks and Kmax) values, the RGP lens use and keratoplasty were positively correlated with KC severity (all P < 0.05). The total VF score of the eye with better VA decreased as the severity increased (r = − 0.21, P = 0.002). The present study comprehensively describes various associated features of KC patients from a tertiary hospital in Central China, providing a reference for understanding the characteristics of KC patients in China.
Author Correction: Multilayered salt water with high optical transparency for EMI shielding applications
Authors: Phan Duy Tung , Jung Chang Won
Published: April 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Large-scale shift in the structure of a kelp forest ecosystem co-occurs with an epizootic and marine heatwave
Authors: McPherson Meredith L. , Finger Dennis J. I. , Houskeeper Henry F. , Bell Tom W. , Carr Mark H. , Rogers-Bennett Laura , Kudela Raphael M.
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-01993-7
Author Correction: Passive eDNA collection enhances aquatic biodiversity analysis
Authors: Bessey Cindy , Jarman Simon Neil , Simpson Tiffany , Miller Haylea , Stewart Todd , Keesing John Kenneth , Berry Oliver
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-01994-6
Food Development: The Sensory & Consumer Approach
Authors: Porretta Sebastiano
Published: April 2021

This chapter deals with how products are currently developed, as well as the different roles, efforts and topics covered in design, and talks about the difference between what one reads in the well-documented scientific literature and common practice, including sensory analysis myths and legends. The new sensory marketing approach deals with measuring and explaining consumer emotions in order to capitalize on them in new marketing opportunities, and to maximize the profit of particular products and customer loyalty, so that they will repeat the purchase, in order to guarantee success for as long as possible. Finally, the consumer approach: for too many years, market researchers have developed all sorts of tests to ‘measure’, from food to political ideas, but in a disrupted way that doesn't quite match people's thinking. Today it is necessary to know (and not suppose) what is important for our consumer in the numerous actual market segments.
Artificial Intelligence to Identify Ideas
Authors: GanChoudhuri Somsubhra , GanChoudhuri Somrita , Upreti Himanshu
Published: April 2021

Artificial Intelligence (AI) is now portrayed as a solution provider. Once considered to be an esoteric topic for being too math-heavy, AI has now become a household term with its presence in advertisements for commonly used items such as smartphones. AI devices fall under two fundamental categories – applied and general. Applied AI which is common in nature refers to systems designed to intelligently trade stocks and shares; whereas generalized AI, less common in nature, refers to systems that are capable of handling any task. Generalized AI, an emerging field, aims at functioning as a human with an ability to deal with complex situations with analytical thinking and depth of knowledge so that it can deal with diverse topics.
Mind Genomics (BimiLeap) to Create New Ideas
Authors: Mehta-Shah Namrata , Mehta Shradha , Zemel Ryan
Published: April 2021

This chapter describe a real-market food development carried out using an online research platform (BimiLeap) that utilizes a variation of conjoint analysis, a powerful stimulus–response experiment process. The study determines what resonates in a possible consumer's mind by listing various attributes of a product, mixing them in a proprietary systematic way, presenting them to the consumer, and obtaining ratings. It simulates Nature as a full experiment, investigating the final product of the algebra of the consumer mind, how different propositions of ideas drive a person's response and how ideas influence each other.