bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Vegetation Responses to Underground Nuclear Explosions Through Integrated Analyses
Authors: Solander Kurt C. , Collins Adam D. , Swanson Erika , Margolis Ellis Q. , Crawford Brandon , Miller Elizabeth , Chen Min , Lavadie‐Bulnes Anita , Ryan Max , Borrego Isaac , Sevanto Sanna , Schultz‐Fellenz Emily
Published: April 2021

Vegetation has the potential to respond to underground nuclear explosions, yet these links have not been fully explored. Given the lack of previously described signatures, the changes in vegetation are possibly subtle. The integration of multiple different data streams is potentially a useful approach to improve signal detection. Here, we investigate whether semi‐arid vegetation growth patterns responded to eight legacy underground nuclear tests at the Nevada National Security Site in southern Nevada, USA. We tested for spatial and temporal changes in vegetation cover, tree growth patterns, and tree leaf spectral properties using ground‐based measurements, including those from tree‐rings and hyperspectral surface vegetation reflectance, as well as space‐based measurements of Normalized Difference Vegetation Index (NDVI) from Landsat. Multiple data streams suggest a localized (<1.2 km) spatial pattern whereby tree growth is enhanced closer to the source of the underground test relative to sites further away. We also observed a more regional (>1.2–9 km) pattern whereby tree growth is suppressed coincident with a drought beginning 1 year before the 1989 tests, but continuing in the 5 years following the tests, which is anomalous relative to what is expected based on the response of tree growth to previous droughts. Quantification of the relative effects of the tests on vegetation remains a challenge due to the coincident drought and the potential for other disturbances to have impacted tree growth at this time, but the integration of these data reveals a more nuanced growth response than any other one data set indicates alone.
Holographic Calibration of Phased Array Telescopes
Authors: Kiefner U. , Wayth R. B. , Davidson D. B. , Sokolowski M.
Published: April 2021

In radio astronomy, holography is a commonly used technique to create an image of the electric field distribution in the aperture of a dish antenna. The image is used to detect imperfections in the reflector surface. Similarly, holography can be applied to phased array telescopes, in order to measure the complex gains of the receive paths of individual antennas. In this paper, a holographic technique is suggested to calibrate the digital beamformer of a phased array telescope. The effectiveness of the technique was demonstrated by applying it on data from the Engineering Development Array 2, one of the prototype stations of the low frequency component of the Square Kilometre Array. The calibration method is very quick and requires few resources. In contrast to holography for dish antennas, it works without a reference antenna. We demonstrate the utility of this technique for initial station commissioning and verification as well as for routine station calibration.
Subsurface Migration of Methane From Oil Sands Thermal Recovery Operations
Authors: Mohammadi Mohammadjavad , Jafari Raad Seyed Mostafa , Zirrahi Mohsen , Hassanzadeh Hassan
Published: April 2021

Steam injection into oil sands reservoirs for bitumen extraction leads to the in situ generation of gases (mainly methane). Many oil sands formations have permeable cap rocks that may allow these gases to migrate to the overlying formations and pose environmental challenges to the groundwater. We present a detailed analysis of the long‐term fate of the in situ generated gases over the course of thermal oil recovery operations. The impacts of capillary barriers on upward migration of the in situ generated gases are quantified. Our findings reveal that the upward migration of gases over a 100‐year period in formations with continuous flow barriers with a permeability of less than ∼1 × 10−18 m2 is negligible. However, for formations with discontinuous flow barriers, the migrated gas can potentially leak to the surface depending on the capillary entry pressure of the preferential pathways (e.g., sand layers). In this case, the upward migration is primarily controlled by high permeability pathways. It was found that the migrated gas is effectively trapped by the residual and dissolution trapping mechanisms, and the gas migration to the overlying formations is prevented or significantly reduced by capillary pressure of sand layers. The results indicate that the migrated gas to the shallow groundwater is primarily comprised of methane and is free of CO2 and H2S. These results provide valuable insights into the long‐term fate of these gases in thermal oil recovery operations. They also offer potential opportunities for the development of regulatory frameworks and screening considerations for caprock/seal integrity/risk assessments.
Deficiency of optineurin enhances osteoclast differentiation by attenuating the NRF2-mediated antioxidant response
Authors: Xue Peng , Hu Xiangxiang , Chang Emily , Wang Lufei , Chen Minghui , Wu Tai-Hsien , Lee Dong-Joon , Foster Brian L. , Tseng Henry C. , Ko Ching-Chang
Published: April 2021

Abnormally increased resorption contributes to bone degenerative diseases such as Paget’s disease of bone (PDB) through unclear mechanisms. Recently, the optineurin (OPTN) gene has been implicated in PDB, and global OPTN knockout mice (Optn−/−) were shown to exhibit increased formation of osteoclasts (osteoclastogenesis). Growing evidence, including our own, has demonstrated that intracellular reactive oxygen species (ROS) stimulated by receptor activator of nuclear factor kappa-B ligand (RANKL) can act as signaling molecules to promote osteoclastogenesis. Here, we report that OPTN interacts with nuclear factor erythroid-derived factor 2-related factor 2 (NRF2), the master regulator of the antioxidant response, defining a pathway through which RANKL-induced ROS could be regulated for osteoclastogenesis. In this study, monocytes fromOptn−/−and wild-type (Optn+/+) mice were utilized to differentiate into osteoclasts, and both qRT-PCR and tartrate-resistant acid phosphatase (TRAP) staining showed that theOptn−/−monocytes exhibited enhanced osteoclastogenesis compared to theOptn+/+cells. CellROX®staining, qRT-PCR, and Western blotting indicated that OPTN deficiency reduced the basal expression ofNrf2, inhibited the expression of NRF2-responsive antioxidants, and increased basal and RANKL-induced intracellular ROS levels, leading to enhanced osteoclastogenesis. Coimmunoprecipitation (co-IP) showed direct interaction, and immunofluorescence staining showed perinuclear colocalization of the OPTN-NRF2 granular structures during differentiation. Finally, curcumin and the other NRF2 activators attenuated the hyperactive osteoclastogenesis induced by OPTN deficiency. Collectively, our findings reveal a novel OPTN-mediated mechanism for regulating the NRF2-mediated antioxidant response in osteoclasts and extend the therapeutic potential of OPTN in the aging process resulting from ROS-triggered oxidative stress, which is associated with PDB and many other degenerative diseases.
Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder
Authors: Song Xue Mei , Hu Xi-Wen , Li Zhe , Gao Yuan , Ju Xuan , Liu Dong-Yu , Wang Qian-Nan , Xue Chuang , Cai Yong-Chun , Bai Ruiliang , Tan Zhong-Lin , Northoff Georg
Published: April 2021

Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.
Nlp promotes autophagy through facilitating the interaction of Rab7 and FYCO1
Authors: Xiao Wenchang , Yeerken Danna , Li Jia , Li Zhangfu , Jiang Lanfang , Li Dan , Fu Ming , Ma Liying , Song Yongmei , Zhang Weimin , Zhan Qimin
Published: April 2021

Autophagy is the main degradation pathway to eliminate long-lived and aggregated proteins, aged or malfunctioning organelles, which is essential for the intracellular homeostasis and prevention of malignant transformation. Although the processes of autophagosome biogenesis have been well illuminated, the mechanism of autophagosome transport remains largely unclear. In this study, we demonstrated that the ninein-like protein (Nlp), a well-characterized centrosomal associated protein, was able to modulate autophagosome transport and facilitate autophagy. During autophagy, Nlp colocalized with autophagosomes and physically interacted with autophagosome marker LC3, autophagosome sorting protein Rab7 and its downstream effector FYCO1. Interestingly, Nlp enhanced the interaction between Rab7 and FYCO1, thus accelerated autophagic flux and the formation of autophagolysosomes. Furthermore, compared to the wild-type mice, NLP deficient mice treated with chemical agent DMBA were prone to increased incidence of hepatomegaly and liver cancer, which were tight associated with the hepatic autophagic defect. Taken together, our findings provide a new insight for the first time that the well-known centrosomal protein Nlp is also a new regulator of autophagy, which promotes the interaction of Rab7 and FYCO1 and facilitates the formation of autophagolysosome.
Azithromycin alleviates systemic lupus erythematosus via the promotion of M2 polarisation in lupus mice
Authors: Wang Jie , Chen Qian , Zhang Zhixiong , Wang Shangshang , Wang Yilun , Xiang Mengmeng , Liang Jun , Xu Jinhua
Published: April 2021

Our previous study demonstrated that azithromycin could promote alternatively activated (M2) macrophages under lupus conditions in vitro, which might be beneficial for lupus treatment. Thus, the aim of this study was to further confirm whether azithromycin can drive M2 polarisation in lupus and ultimately alleviate systemic lupus erythematosus (SLE) in vivo. Lymphocyte-derived DNA (ALD-DNA)-induced mice (induced lupus model) and MRL-Faslpr mice (spontaneous lupus model) were both used in the experiment. First, we observed symptoms of lupus by assessing the levels of serum anti-dsDNA antibodies and serum creatinine and renal pathology. We found that both murine models showed increased levels of serum anti-dsDNA antibodies and creatinine, enhanced glomerular fibrosis and cell infiltration, basement membrane thickening and elevated IgG deposition. After azithromycin treatment, all these medical indexes were alleviated, and kidney damage was effectively reversed. Next, macrophage polarisation was assessed in the spleen and kidneys. Macrophage infiltration in the spleen was notably decreased after azithromycin treatment in both murine models, with a remarkably elevated proportion of M2 macrophages. In addition, the expression of interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), CD86, toll-like receptor (TLR)2 and TLR4 was extremely downregulated, while the expression of transforming growth factor (TGF)-β, arginase-1 (Arg-1), chitinase-like 3 (Ym-1), found in inflammatory zone (Fizz-1) and mannose receptor (CD206) was significantly upregulated in the kidneys after azithromycin treatment. Taken together, our results indicated for the first time that azithromycin could alleviate lupus by promoting M2 polarisation in vivo. These findings exploited the newly discovered potential of azithromycin, a conventional drug with verified safety, affordability and global availability, which could be a novel treat-to-target strategy for SLE via macrophage modulation.
O-GlcNAcylation enhances sensitivity to RSL3-induced ferroptosis via the YAP/TFRC pathway in liver cancer
Authors: Zhu Guoqing , Murshed Abduh , Li Haojie , Ma Ji , Zhen Ni , Ding Miao , Zhu Jiabei , Mao Siwei , Tang Xiaochen , Liu Li , Sun Fenyong , Jin Lei , Pan Qiuhui
Published: April 2021

Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid hydroperoxides to lethal levels. YAP has been reported to play a pivotal role in controlling ferroptotic death, and the expression of YAP is enhanced and stabilized by O-GlcNAcylation. However, whether O-GlcNAcylation can increase the sensitivity of hepatocellular carcinoma (HCC) cells to ferroptosis remains unknown. In the present study, we found that O-GlcNAcylation increased the sensitivity of HCC cells to ferroptosis via YAP. Moreover, YAP increased the iron concentration in HCC cells through transcriptional elevation of TFRC via its O-GlcNAcylation. With YAP knockdown or YAP-T241 mutation, the increased sensitivity to ferroptosis induced by O-GlcNAcylation was abolished. In addition, the xenograft assay confirmed that O-GlcNAcylation increased ferroptosis sensitivity via TFRC in vivo. In summary, we are the first to find that O-GlcNAcylation can increase ferroptosis sensitivity in HCC cells via YAP/TFRC. Our work will provide a new basis for clinical therapeutic strategies for HCC patients.
Simple inheritance of color and pattern polymorphism in the steppe grasshopper Chorthippus dorsatus
Authors: Winter Gabe , Varma Mahendra , Schielzeth Holger
Published: April 2021

The green–brown polymorphism of grasshoppers and bush-crickets represents one of the most penetrant polymorphisms in any group of organisms. This poses the question of why the polymorphism is shared across species and how it is maintained. There is mixed evidence for whether and in which species it is environmentally or genetically determined in Orthoptera. We report breeding experiments with the steppe grasshopperChorthippus dorsatus, a polymorphic species for the presence and distribution of green body parts. Morph ratios did not differ between sexes, and we find no evidence that the rearing environment (crowding and habitat complexity) affected the polymorphism. However, we find strong evidence for genetic determination for the presence/absence of green and its distribution. Results are most parsimoniously explained by three autosomal loci with two alleles each and simple dominance effects: one locus influencing the ability to show green color, with a dominant allele for green; a locus with a recessive allele suppressing green on the dorsal side; and a locus with a recessive allele suppressing green on the lateral side. Our results contribute to the emerging contrast between the simple genetic inheritance of green–brown polymorphisms in the subfamily Gomphocerinae and environmental determination in other subfamilies of grasshoppers. In three out of four species of Gomphocerinae studied so far, the results suggest one or a few loci with a dominance of alleles allowing the occurrence of green. This supports the idea that brown individuals differ from green individuals by homozygosity for loss-of-function alleles preventing green pigment production or deposition.
Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response
Authors: Jia Qi , Sieburth Derek
Published: April 2021

Mitochondria play a pivotal role in the generation of signals coupling metabolism with neurotransmitter release, but a role for mitochondrial-produced ROS in regulating neurosecretion has not been described. Here we show that endogenously produced hydrogen peroxide originating from axonal mitochondria (mtH2O2) functions as a signaling cue to selectively regulate the secretion of a FMRFamide-related neuropeptide (FLP-1) from a pair of interneurons (AIY) in C. elegans. We show that pharmacological or genetic manipulations that increase mtH2O2 levels lead to increased FLP-1 secretion that is dependent upon ROS dismutation, mitochondrial calcium influx, and cysteine sulfenylation of the calcium-independent PKC family member PKC-1. mtH2O2-induced FLP-1 secretion activates the oxidative stress response transcription factor SKN-1/Nrf2 in distal tissues and protects animals from ROS-mediated toxicity. mtH2O2 levels in AIY neurons, FLP-1 secretion and SKN-1 activity are rapidly and reversibly regulated by exposing animals to different bacterial food sources. These results reveal a previously unreported role for mtH2O2 in linking diet-induced changes in mitochondrial homeostasis with neuropeptide secretion.
Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1
Authors: Vuorela A. , Freitag T. L. , Leskinen K. , Pessa H. , Härkönen T. , Stracenski I. , Kirjavainen T. , Olsen P. , Saarenpää-Heikkilä O. , Ilonen J. , Knip M. , Vaheri A. , Partinen M. , Saavalainen P. , Meri S. , Vaarala O.
Published: April 2021

Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175–189 (NA175–189) and nucleoprotein 214–228 (NP214–228), but also respond to a NA175–189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675–689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175–189 or POMT1675–689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.
Deletion of Mfsd2b impairs thrombotic functions of platelets
Authors: Chandrakanthan Madhuvanthi , Nguyen Toan Quoc , Hasan Zafrul , Muralidharan Sneha , Vu Thiet Minh , Li Aaron Wei Liang , Le Uyen Thanh Nha , Thi Thuy Ha Hoa , Baik Sang-Ha , Tan Sock Hwee , Foo Juat Chin , Wenk Markus R. , Cazenave-Gassiot Amaury , Torta Federico , Ong Wei Yi , Chan Mark Yan Yee , Nguyen Long N.
Published: April 2021

We recently discovered that Mfsd2b, which is the S1P exporter found in blood cells. Here, we report that Mfsd2b is critical for the release of all S1P species in both resting and activated platelets. We show that resting platelets store S1P in the cytoplasm. After activation, this S1P pool is delivered to the plasma membrane, where Mfsd2b is predominantly localized for export. Employing knockout mice of Mfsd2b, we reveal that platelets contribute a minor amount of plasma S1P. Nevertheless, Mfsd2b deletion in whole body or platelets impairs platelet morphology and functions. In particular, Mfsd2b knockout mice show significantly reduced thrombus formation. We show that loss of Mfsd2b affects intrinsic platelet functions as part of remarkable sphingolipid accumulation. These findings indicate that accumulation of sphingolipids including S1P by deletion of Mfsd2b strongly impairs platelet functions, which suggests that the transporter may be a target for the prevention of thrombotic disorders.
Experimental parameters defining ultra-low biomass bioaerosol analysis
Authors: Luhung Irvan , Uchida Akira , Lim Serene B. Y. , Gaultier Nicolas E. , Kee Carmon , Lau Kenny J. X. , Gusareva Elena S. , Heinle Cassie E. , Wong Anthony , Premkrishnan Balakrishnan N. V. , Purbojati Rikky W. , Acerbi Enzo , Kim Hie Lim , Junqueira Ana C. M. , Longford Sharon , Lohar Sachin R. , Yap Zhei Hwee , Panicker Deepa , Koh Yanqing , Kushwaha Kavita K. , Ang Poh Nee , Putra Alexander , Drautz-Moses Daniela I. , Schuster Stephan C.
Published: April 2021

Investigation of the microbial ecology of terrestrial, aquatic and atmospheric ecosystems requires specific sampling and analytical technologies, owing to vastly different biomass densities typically encountered. In particular, the ultra-low biomass nature of air presents an inherent analytical challenge that is confounded by temporal fluctuations in community structure. Our ultra-low biomass pipeline advances the field of bioaerosol research by significantly reducing sampling times from days/weeks/months to minutes/hours, while maintaining the ability to perform species-level identification through direct metagenomic sequencing. The study further addresses all experimental factors contributing to analysis outcome, such as amassment, storage and extraction, as well as factors that impact on nucleic acid analysis. Quantity and quality of nucleic acid extracts from each optimisation step are evaluated using fluorometry, qPCR and sequencing. Both metagenomics and marker gene amplification-based (16S and ITS) sequencing are assessed with regard to their taxonomic resolution and inter-comparability. The pipeline is robust across a wide range of climatic settings, ranging from arctic to desert to tropical environments. Ultimately, the pipeline can be adapted to environmental settings, such as dust and surfaces, which also require ultra-low biomass analytics.
TERT promoter hotspot mutations and gene amplification in metaplastic breast cancer
Authors: da Silva Edaise M. , Selenica Pier , Vahdatinia Mahsa , Pareja Fresia , Da Cruz Paula Arnaud , Ferrando Lorenzo , Gazzo Andrea M. , Dopeso Higinio , Ross Dara S. , Bakhteri Ariya , Riaz Nadeem , Chandarlapaty Sarat , Razavi Pedram , Norton Larry , Wen Hannah Y. , Brogi Edi , Weigelt Britta , Zhang Hong , Reis-Filho Jorge S.
Published: April 2021

Metaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according to their histologic subtype. TERT promoter hotspot mutations and gene amplification are rare in common forms of breast cancer, but present in a subset of phyllodes tumors. Here, we sought to determine the frequency of genetic alterations affecting TERT in a cohort of 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), and to compare the repertoire of genetic alterations of MBCs according to the presence of TERT promoter hotspot mutations or gene amplification. Forty-four MBCs were subjected to: whole-exome sequencing (WES; n = 27) or targeted sequencing of 341-468 cancer-related genes (n = 17); 16 MBCs were subjected to Sanger sequencing of the TERT promoter, TP53 and selected exons of PIK3CA, HRAS, and BRAF. TERT promoter hotspot mutations (n = 9) and TERT gene amplification (n = 1) were found in 10 of the 60 MBCs analyzed, respectively. These TERT alterations were less frequently found in MBCs with predominant chondroid differentiation than in other MBC subtypes (p = 0.01, Fisher’s exact test) and were mutually exclusive with TP53 mutations (p < 0.001, CoMEt). In addition, a comparative analysis of the MBCs subjected to WES or targeted cancer gene sequencing (n = 44) revealed that MBCs harboring TERT promoter hotspot mutations or gene amplification (n = 6) more frequently harbored PIK3CA than TERT wild-type MBCs (n = 38; p = 0.001; Fisher’s exact test). In conclusion, TERT somatic genetic alterations are found in a subset of TP53 wild-type MBCs with squamous/spindle differentiation, highlighting the genetic diversity of these cancers.
Machine learning augmented predictive and generative model for rupture life in ferritic and austenitic steels
Authors: Mamun Osman , Wenzlick Madison , Sathanur Arun , Hawk Jeffrey , Devanathan Ram
Published: April 2021

The Larson–Miller parameter (LMP) offers an efficient and fast scheme to estimate the creep rupture life of alloy materials for high-temperature applications; however, poor generalizability and dependence on the constant C often result in sub-optimal performance. In this work, we show that the direct rupture life parameterization without intermediate LMP parameterization, using a gradient boosting algorithm, can be used to train ML models for very accurate prediction of rupture life in a variety of alloys (Pearson correlation coefficient >0.9 for 9–12% Cr and >0.8 for austenitic stainless steels). In addition, the Shapley value was used to quantify feature importance, making the model interpretable by identifying the effect of various features on the model performance. Finally, a variational autoencoder-based generative model was built by conditioning on the experimental dataset to sample hypothetical synthetic candidate alloys from the learnt joint distribution not existing in both 9–12% Cr ferritic–martensitic alloys and austenitic stainless steel datasets.
mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents
Authors: Rauch Susanne , Roth Nicole , Schwendt Kim , Fotin-Mleczek Mariola , Mueller Stefan O. , Petsch Benjamin
Published: April 2021

mRNA technologies have recently proven clinical efficacy against coronavirus disease 2019 and are among the most promising technologies to address the current pandemic. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle-encapsulated mRNA vaccine that encodes full-length, pre-fusion stabilised severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. In contrast to previously published approaches, CVnCoV is exclusively composed of naturally occurring nucleotides. Immunisation with CVnCoV induced strong humoral responses with high titres of virus-neutralising antibodies and robust T-cell responses. CVnCoV vaccination protected hamsters from challenge with wild-type SARS-CoV-2, demonstrated by the absence of viral replication in the lungs. Hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication exhibited no evidence of vaccine-enhanced disease. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.
Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy
Authors: Giordano Giulia , Colaneri Marta , Di Filippo Alessandro , Blanchini Franco , Bolzern Paolo , De Nicolao Giuseppe , Sacchi Paolo , Colaneri Patrizio , Bruno Raffaele
Published: April 2021

Despite progress in clinical care for patients with coronavirus disease 2019 (COVID-19)1, population-wide interventions are still crucial to manage the pandemic, which has been aggravated by the emergence of new, highly transmissible variants. In this study, we combined the SIDARTHE model2, which predicts the spread of SARS-CoV-2 infections, with a new data-based model that projects new cases onto casualties and healthcare system costs. Based on the Italian case study, we outline several scenarios: mass vaccination campaigns with different paces, different transmission rates due to new variants and different enforced countermeasures, including the alternation of opening and closure phases. Our results demonstrate that non-pharmaceutical interventions (NPIs) have a higher effect on the epidemic evolution than vaccination alone, advocating for the need to keep NPIs in place during the first phase of the vaccination campaign. Our model predicts that, from April 2021 to January 2022, in a scenario with no vaccine rollout and weak NPIs ($${\cal{R}}_0$$

R

0

= 1.27), as many as 298,000 deaths associated with COVID-19 could occur. However, fast vaccination rollouts could reduce mortality to as few as 51,000 deaths. Implementation of restrictive NPIs ($${\cal{R}}_0$$

R

0

= 0.9) could reduce COVID-19 deaths to 30,000 without vaccinating the population and to 18,000 with a fast rollout of vaccines. We also show that, if intermittent open–close strategies are adopted, implementing a closing phase first could reduce deaths (from 47,000 to 27,000 with slow vaccine rollout) and healthcare system costs, without substantive aggravation of socioeconomic losses.
High spatial resolution global ocean metagenomes from Bio-GO-SHIP repeat hydrography transects
Authors: Larkin Alyse A. , Garcia Catherine A. , Garcia Nathan , Brock Melissa L. , Lee Jenna A. , Ustick Lucas J. , Barbero Leticia , Carter Brendan R. , Sonnerup Rolf E. , Talley Lynne D. , Tarran Glen A. , Volkov Denis L. , Martiny Adam C.
Published: April 2021

Detailed descriptions of microbial communities have lagged far behind physical and chemical measurements in the marine environment. Here, we present 971 globally distributed surface ocean metagenomes collected at high spatio-temporal resolution. Our low-cost metagenomic sequencing protocol produced 3.65 terabases of data, where the median number of base pairs per sample was 3.41 billion. The median distance between sampling stations was 26 km. The metagenomic libraries described here were collected as a part of a biological initiative for the Global Ocean Ship-based Hydrographic Investigations Program, or “Bio-GO-SHIP.” One of the primary aims of GO-SHIP is to produce high spatial and vertical resolution measurements of key state variables to directly quantify climate change impacts on ocean environments. By similarly collecting marine metagenomes at high spatiotemporal resolution, we expect that this dataset will help answer questions about the link between microbial communities and biogeochemical fluxes in a changing ocean.
Effect of perioperative bronchodilator therapy on postoperative pulmonary function among lung cancer patients with COPD
Authors: Shin Sun Hye , Shin Sumin , Im Yunjoo , Lee Genehee , Jeong Byeong-Ho , Lee Kyungjong , Um Sang-Won , Kim Hojoong , Kwon O. Jung , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Kim Jhingook , Zo Jae Ill , Shim Young Mog , Cho Juhee , Kang Danbee , Park Hye Yun
Published: April 2021

Chronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV1) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV1 (adjusted mean difference in FEV1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; − 161.1 mL [− 240.2, − 82.0], − 179.2 mL [− 252.1, − 106.3], − 128.8 mL [− 193.2, − 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC.
Molecular features of tumor-derived genetic alterations in circulating cell-free DNA in virtue of autopsy analysis
Authors: Koba Hayato , Kimura Hideharu , Yoneda Taro , Sone Takashi , Ohkura Noriyuki , Hara Johsuke , Hosomichi Kazuyoshi , Tajima Atsushi , Kasahara Kazuo
Published: April 2021

In cancer patients, circulating cell-free DNA (cfDNA) includes tumor-derived DNA (tDNA). cfDNA has been used clinically for non-invasive gene mutation testing. The aim of this study was to characterize the features of the genetic alterations detected in cfDNA. This study included 6 patients with primary lung cancer who died due to cancer progression. Tumors were biopsied at autopsy. Genetic alteration profiles were obtained using next generation sequencing. The features of the tDNA genetic alterations detected in cfDNA included a higher frequency of being present in multiple tumors (67% truncal mutations, 36% shared mutations, and 4% individual mutations) and a higher variant allele frequency (VAF; 47.6% versus 4.1% for tDNA alterations detected in cfDNA versus not detected in cfDNA, respectively). The data revealed that the tumor-derived genetic alterations most easily detected in cfDNA were truncal mutations with a high VAF. These results showed that essential genetic alterations enriched in cfDNA could help to characterize cancer cells and that genetic testing using cfDNA has advantages in the detection of fundamental regulatory aberrations occurring during tumorigenesis.
Optimisation of the coalescent hyperbolic embedding of complex networks
Authors: Kovács Bianka , Palla Gergely
Published: April 2021

Several observations indicate the existence of a latent hyperbolic space behind real networks that makes their structure very intuitive in the sense that the probability for a connection is decreasing with the hyperbolic distance between the nodes. A remarkable network model generating random graphs along this line is the popularity-similarity optimisation (PSO) model, offering a scale-free degree distribution, high clustering and the small-world property at the same time. These results provide a strong motivation for the development of hyperbolic embedding algorithms, that tackle the problem of finding the optimal hyperbolic coordinates of the nodes based on the network structure. A very promising recent approach for hyperbolic embedding is provided by the noncentered minimum curvilinear embedding (ncMCE) method, belonging to the family of coalescent embedding algorithms. This approach offers a high-quality embedding at a low running time. In the present work we propose a further optimisation of the angular coordinates in this framework that seems to reduce the logarithmic loss and increase the greedy routing score of the embedding compared to the original version, thereby adding an extra improvement to the quality of the inferred hyperbolic coordinates.
Low serum iron is associated with anemia in CKD stage 1–4 patients with normal transferrin saturations
Authors: Yu Pei-Hua , Lin Ming-Yen , Chiu Yi-Wen , Lee Jia-Jung , Hwang Shang-Jyh , Hung Chi-Chih , Chen Hung-Chun
Published: April 2021

Low transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1–4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 μg/dL in men, 60 μg/dL in women). Our results confirmed low TIBC (< 200 μg/dL) was associated with hypoalbuminemia and high C-reactive protein. In fully-adjusted logistic regression, both “normal TSAT low iron” and “low TSAT low iron” groups were associated with baseline anemia (hemoglobin < 11 g/dL) (odds ratios (OR) 1.56; 95% confidence interval (CI) 1.13–2.16 and OR 2.36; 95% CI 1.76–3.18, respectively) compared with the reference group (normal TSAT normal iron). Sensitivity tests with different cutoffs for TSAT and iron also showed similar results. In patients without anemia, both groups were associated with anemia after 1 year (OR 1.69; 95% CI 1.00–2.83 and OR 1.94; 95% CI 1.11–3.40, respectively). In conclusion, CKD stage 1–4 patients with normal TSAT but low serum iron are still at risk for anemia.
The non-indigenous Oithona davisae in a Mediterranean transitional environment: coexistence patterns with competing species
Authors: Pansera Marco , Camatti Elisa , Schroeder Anna , Zagami Giacomo , Bergamasco Alessandro
Published: April 2021

The Venice lagoon (VL) has been recognized as a hot spot of introduction of non-indigenous species (NIS), due to several anthropogenic factors and environmental stressors that combined may facilitate NIS invasions. In the last decades an increasing number of zooplankton NIS have been observed in the VL. This work aims to provide a picture of the annual cycle and distribution of the recently recorded non-indigenous copepod Oithona davisae, considering the coexistence patterns with the congeneric resident Oithona nana. Therefore, zooplankton samplings were carried out monthly from August 2016 to July 2017 at five Long-Term Ecological Research LTER stations in the VL. Oithona davisae showed a persistent occurrence throughout the year with the highest abundances in the warm season and in the inner areas, while the congeneric O. nana, showing a different distribution pattern, resulted more abundant near the inlets of the Lagoon, where O. davisae reached the minimum density. Oithona davisae seems to find local conditions that promote its settlement and distribution, especially in the inner and more trophic lagoon sites. In other European coastal embayments or transitional waters, O. davisae occupied the niche left by the indigenous O. nana or can replace this congeneric species through competitive exclusion mechanisms. Our data indicate that, for now, such species replacement has not occurred in the VL. One of the causes is the extreme variety of habitats and niches offered by this environment allowing a balanced coexistence with O. nana and in general with the resident copepod community.
Clinical presentations and long term prognosis of childhood onset polyarteritis nodosa in single centre of Korea
Authors: Lee Jeong-Seon , Kim Joong-Gon , Lee Soyoung
Published: April 2021

Childhood-onset polyarteritis nodosa (PAN) is a rare and systemic necrotising vasculitis in children affecting small- to medium-sized arteries. To date, there have been only a few reports because of its rarity. Thus, we aimed to investigate the clinical manifestations, laboratory findings, treatment, and long-term outcomes in patients with childhood-onset PAN and to evaluate the usefulness of the paediatric vasculitis activity score (PVAS). We retrospectively analysed the data of nine patients with childhood-onset PAN from March 2003 to February 2020. The median ages at symptom onset, diagnosis, and follow-up duration were 7.6 (3–17.5), 7.7 (3.5–17.6), and 7.0 (1.6–16.3) years, respectively. All patients had constitutional symptoms and skin manifestations, while five exhibited Raynaud’s phenomenon. Organ involvement was observed in one patient. The median PVAS at diagnosis was 7 (range: 2–32). Prednisolone was initially used for induction in all patients, and other drugs were added in cases refractory to prednisolone. All patients survived, but three patients with high PVAS at diagnosis experienced irreversible sequelae, including intracranial haemorrhage and digital amputation. In conclusion, early diagnosis and treatment may minimise sequelae in patients with childhood-onset PAN. This study suggests that high PVAS score at diagnosis may be associated with poor prognosis.
Reconcile the debate over protective effects of BCG vaccine against COVID-19
Authors: Fu Wei , Ho Pei-Chuan , Liu Chia-Lun , Tzeng Kai-Teh , Nayeem Nawar , Moore Jonni S. , Wang Li-San , Chou Shin-Yi
Published: April 2021

While awaiting the COVID-19 vaccines, researchers have been actively exploring the effectiveness of existing vaccines against the new virus, among which the BCG vaccine (Bacillus Calmette-Guérin) receives the most attention. While many reports suggest a potential role for BCG immunization in ameliorating SARS-CoV-2 infection, these findings remain controversial. With country-level COVID-19 outbreak data from Johns Hopkins University Coronavirus Resource Center, and BCG program data from World Atlas of BCG Policies and Practices and WHO/UNICE, we estimated a dynamic model to investigate the effect of BCG vaccination across time during the pandemic. Our results reconcile these varying reports regarding protection by BCG against COVID-19 in a variety of clinical scenarios and model specifications. We observe a notable protective effect of the BCG vaccine during the early stage of the pandemic. However, we do not see any strong evidence for protection during the later stages. We also see that a higher proportion of vaccinated young population may confer some level of communal protection against the virus in the early pandemic period, even when the proportion of vaccination in the older population is low. Our results highlight that while BCG may offer some protection against COVID-19, we should be cautious in interpreting the estimated effectiveness as it may vary over time and depend on the age structure of the vaccinated population.
Subgenomic flavivirus RNA (sfRNA) associated with Asian lineage Zika virus identified in three species of Ugandan bats (family Pteropodidae)
Authors: Fagre Anna C. , Lewis Juliette , Miller Megan R. , Mossel Eric C. , Lutwama Julius J. , Nyakarahuka Luke , Nakayiki Teddy , Kityo Robert , Nalikka Betty , Towner Jonathan S. , Amman Brian R. , Sealy Tara K. , Foy Brian , Schountz Tony , Anderson John , Kading Rebekah C.
Published: April 2021

Serological cross-reactivity among flaviviruses makes determining the prior arbovirus exposure of animals challenging in areas where multiple flavivirus strains are circulating. We hypothesized that prior infection with ZIKV could be confirmed through the presence of subgenomic flavivirus RNA (sfRNA) of the 3′ untranslated region (UTR), which persists in tissues due to XRN-1 stalling during RNA decay. We amplified ZIKV sfRNA but not NS5 from three experimentally-infected Jamaican fruit bats, supporting the hypothesis of sfRNA tissue persistence. Applying this approach to 198 field samples from Uganda, we confirmed presence of ZIKV sfRNA, but not NS5, in four bats representing three species: Eidolon helvum (n = 2), Epomophorus labiatus (n = 1), and Rousettus aegyptiacus (n = 1). Amplified sequence was most closely related to Asian lineage ZIKV. Our results support the use of sfRNA as a means of identifying previous flavivirus infection and describe the first detection of ZIKV RNA in East African bats.
Electrically turning periodic structures in cholesteric layer with conical–planar boundary conditions
Authors: Prishchepa Oxana , Krakhalev Mikhail , Rudyak Vladimir , Sutormin Vitaly , Zyryanov Victor
Published: April 2021

Electro-optical cell based on the cholesteric liquid crystal is studied with unique combination of the boundary conditions: conical anchoring on the one substrate and planar anchoring on another one. Periodic structures in cholesteric layer and their transformation under applied electric field are considered by polarizing optical microscopy, the experimental findings are supported by the data of the calculations performed using the extended Frank elastic continuum approach. Such structures are the set of alternating over- and under-twisted defect lines whose azimuthal director angles differ by $$180^\circ$$

180
∘

. The $$U^+$$

U
+

and $$U^-$$

U
-

-defects of periodicity, which are the smooth transition between the defect lines, are observed at the edge of electrode area. The growth direction of defect lines forming a diffraction grating can be controlled by applying a voltage in the range of $$0\le \, V \le 1.3$$

0
≤

V
≤
1.3

 V during the process. Resulting orientation and distance between the lines don’t change under voltage. However, at $$V>1.3$$

V
>
1.3

 V $$U^+$$

U
+

-defects move along the defect lines away from the electrode edges, and, finally, the grating lines collapse at the cell’s center. These results open a way for the use of such cholesteric material in applications with periodic defect structures where a periodicity, orientation, and configuration of defects should be adjusted.
ILDR2 stabilization is regulated by its interaction with GRP78
Authors: Watanabe Kazuhisa , Nakayama Kazuhiro , Ohta Satoshi , Matsumoto Ayumi , Tsuda Hidetoshi , Iwamoto Sadahiko
Published: April 2021

Ildr2 was initially identified as a genetic modifier of diabetes susceptibility in B6.DBA Lepob congenic mice, and was associated with decreased β-cell replication rates, reduced β-cell mass, and persistent mild hypoinsulinemic hyperglycemia. However, the molecular mechanisms of how the ILDR2 protein is involved in these effects are largely unknown. We sought to identify ILDR2-interacting proteins to further elucidate the molecular mechanisms underpinning ILDR2 function in pancreatic β-cells. Using TAP tag technology, we purified proteins interacting with ILDR2 in the pancreatic β-cell line MIN6, and identified the endoplasmic reticulum resident chaperones, GRP78 and PDIA1, as novel proteins interacting with ILDR2. We demonstrated that GRP78 interacted with ILDR2 and was possibly involved in ILDR2 stabilization by inhibiting ubiquitin–proteasome degradation. Additionally, adenoviral ILDR2 knockdown led to reduced glucose-responsive insulin secretion in MIN6 β-cells, suggesting ILDR2 may be implicated in a new pathway in hypoinsulinemic hyperglycemia. These data provide evidence for a novel association between GRP78 and ILDR2, and suggest GPR78-ILDR2 may a novel target for diabetic therapeutic modulation in decreased insulin secretion.