bluuebunny/crossref_metadata_2025 huggingface dataset:
Tropospheric Delay Calibration System Performance During the First Two BepiColombo Solar Conjunctions
Authors: Lasagni Manghi Riccardo , Bernacchia David , Gomez Casajus Luis , Zannoni Marco , Tortora Paolo , Martellucci Antonio , De Vicente Javier , Villalvilla Jose , Maschwitz Gerrit , Cappuccio Paolo , Iess Luciano
Published: January 2023

Media propagation delay and delay‐rate induced by the water vapor within the Earth's troposphere represent one of the main error sources for radiometric measurements in deep space. In preparation for the BepiColombo and JUICE missions, the European Space Agency has installed and operates the prototype of a tropospheric delay calibration system (TDCS) at the DSA‐3 ground station located in Malargüe, Argentina. An initial characterization of the TDCS performance was realized using two‐way Doppler measurements at X‐band to perform the orbit determination of the Gaia spacecraft. This work will further characterize the system by analyzing two‐way Doppler and range data at X‐ and Ka‐band for 31 tracking passes of the BepiColombo spacecraft, which were recorded between March 2021 and February 2022 during the first two solar conjunction experiments. The performance exceeds the expectations based on the previous analysis, with a reduction of the Doppler noise of 51% on average and up to 73% when using the TDCS measurements in place of standard calibrations based on global navigation satellite system data. Furthermore, the campaign serves as validation of the TDCS operations during superior solar conjunctions, with most of the tracking passes at low elongation now satisfying the Mercury orbiter radioscience experiment requirements on two‐way Doppler stability. These results, which are in line with those of similar instruments installed at other Deep Space Network antennas, are obtained using a commercial microwave radiometer with significantly lower installation and maintenance costs.
Euthyroid sick syndrome and its association with complications of type 1 diabetes mellitus onset
Authors: Marzuillo Pierluigi , Iafusco Dario , Guarino Stefano , Di Sessa Anna , Zanfardino Angela , Piscopo Alessia , Luongo Caterina , Capalbo Daniela , Verde Martina , Aiello Francesca , Festa Adalgisa , Miraglia del Giudice Emanuele , Grandone Anna
Published: January 2023

Objective

To evaluate (i) the prevalence and association of euthyroid sick syndrome (ESS) [decreased FT3 and/or FT4 and normal/decreased TSH] with severity indexes of type 1 diabetes mellitus (T1DM) onset such as diabetic ketoacidosis (DKA) and kidney damage [acute kidney injury (AKI) based on KDIGO criteria, acute tubular necrosis (ATN), renal tubular damage (RTD)], (ii) relationship between clinical/metabolic parameters at T1DM onset and thyroid hormones, and (iii) ESS as a prognostic indicator of delayed recovery from kidney damage.

Methods

A total of 161 children with T1DM onset were included. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin (NGAL) and/or tubular reabsorption of phosphate <85% and/or fractional excretion of Na>2%. ATN was defined by RTD+AKI.

Results

Of 161 participants, 60 (37.3%) presented ESS. It was more prevalent in case of more severe T1DM presentation both in terms of metabolic derangement (DKA) and kidney function impairment (AKI, RTD and ATN). Only ATN, however, was associated with ESS at adjusted analysis. FT3 inversely correlated with serum triglycerides and creatinine, and urinary calcium/creatinine ratio and NGAL. Participants with euthyroidism showed earlier recovery from AKI than those with ESS. ESS spontaneously disappeared.

Conclusions

ESS is associated with T1DM onset severity and spontaneously disappears. ESS delayed the recovery from AKI.

Impact

This is the first longitudinal study describing in detail the relationship between clinical/metabolic factors at type 1 diabetes mellitus (T1DM) onset and thyroid hormones, with particular attention to the relationship between diabetic ketoacidosis (DKA)-related kidney function impairment and euthyroid sick syndrome (ESS).

Participants with more severe T1DM onset presentation both in terms of metabolic derangement and kidney function impairment had an increased prevalence of ESS.

Children with ESS had a slower recovery from acute kidney injury compared with those without ESS.

ESS spontaneously disappeared in all participants.
High abundance of hydrocarbon-degrading Alcanivorax in plumes of hydrothermally active volcanoes in the South Pacific Ocean
Authors: Dede Bledina , Priest Taylor , Bach Wolfgang , Walter Maren , Amann Rudolf , Meyerdierks Anke
Published: January 2023

Species within the genus Alcanivorax are well known hydrocarbon-degraders that propagate quickly in oil spills and natural oil seepage. They are also inhabitants of the deep-sea and have been found in several hydrothermal plumes. However, an in-depth analysis of deep-sea Alcanivorax is currently lacking. In this study, we used multiple culture-independent techniques to analyze the microbial community composition of hydrothermal plumes in the Northern Tonga arc and Northeastern Lau Basin focusing on the autecology of Alcanivorax. The hydrothermal vents feeding the plumes are hosted in an arc volcano (Niua), a rear-arc caldera (Niuatahi) and the Northeast Lau Spreading Centre (Maka). Fluorescence in situ hybridization revealed that Alcanivorax dominated the community at two sites (1210–1565 mbsl), reaching up to 48% relative abundance (3.5 × 104 cells/ml). Through 16S rRNA gene and metagenome analyses, we identified that this pattern was driven by two Alcanivorax species in the plumes of Niuatahi and Maka. Despite no indication for hydrocarbon presence in the plumes of these areas, a high expression of genes involved in hydrocarbon-degradation was observed. We hypothesize that the high abundance and gene expression of Alcanivorax is likely due to yet undiscovered hydrocarbon seepage from the seafloor, potentially resulting from recent volcanic activity in the area. Chain-length and complexity of hydrocarbons, and water depth could be driving niche partitioning in Alcanivorax.
High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection
Authors: Normandin Erica , Rudy Melissa , Barkas Nikolaos , Schaffner Stephen F. , Levine Zoe , Padera Robert F. , Babadi Mehrtash , Mukerji Shibani S. , Park Daniel J. , MacInnis Bronwyn L. , Siddle Katherine J. , Sabeti Pardis C. , Solomon Isaac H.
Published: February 2023

SARS-CoV-2 distribution and circulation dynamics are not well understood due to challenges in assessing genomic data from tissue samples. We develop experimental and computational workflows for high-depth viral sequencing and high-resolution genomic analyses from formalin-fixed, paraffin-embedded tissues and apply them to 120 specimens from six subjects with fatal COVID-19. To varying degrees, viral RNA is present in extrapulmonary tissues from all subjects. The majority of the 180 viral variants identified within subjects are unique to individual tissue samples. We find more high-frequency (>10%) minor variants in subjects with a longer disease course, with one subject harboring ten such variants, exclusively in extrapulmonary tissues. One tissue-specific high-frequency variant was a nonsynonymous mutation in the furin-cleavage site of the spike protein. Our findings suggest adaptation and/or compartmentalized infection, illuminating the basis of extrapulmonary COVID-19 symptoms and potential for viral reservoirs, and have broad utility for investigating human pathogens.
Monitoring and modelling marine zooplankton in a changing climate
Authors: Ratnarajah Lavenia , Abu-Alhaija Rana , Atkinson Angus , Batten Sonia , Bax Nicholas J. , Bernard Kim S. , Canonico Gabrielle , Cornils Astrid , Everett Jason D. , Grigoratou Maria , Ishak Nurul Huda Ahmad , Johns David , Lombard Fabien , Muxagata Erik , Ostle Clare , Pitois Sophie , Richardson Anthony J. , Schmidt Katrin , Stemmann Lars , Swadling Kerrie M. , Yang Guang , Yebra Lidia
Published: February 2023

Zooplankton are major consumers of phytoplankton primary production in marine ecosystems. As such, they represent a critical link for energy and matter transfer between phytoplankton and bacterioplankton to higher trophic levels and play an important role in global biogeochemical cycles. In this Review, we discuss key responses of zooplankton to ocean warming, including shifts in phenology, range, and body size, and assess the implications to the biological carbon pump and interactions with higher trophic levels. Our synthesis highlights key knowledge gaps and geographic gaps in monitoring coverage that need to be urgently addressed. We also discuss an integrated sampling approach that combines traditional and novel techniques to improve zooplankton observation for the benefit of monitoring zooplankton populations and modelling future scenarios under global changes.
Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A
Authors: Li Fajin , Fang Jianhuo , Yu Yifan , Hao Sijia , Zou Qin , Zeng Qinglin , Yang Xuerui
Published: February 2023

The quickly accumulating ribosome profiling data is an insightful resource for studying the critical details of translation regulation under various biological contexts. Rocaglamide A (RocA), an antitumor heterotricyclic natural compound, has been shown to inhibit translation initiation of a large group of mRNA species by clamping eIF4A onto poly-purine motifs in the 5′ UTRs. However, reanalysis of previous ribosome profiling datasets reveals an unexpected shift of the ribosome occupancy pattern, upon RocA treatment in various types of cells, during early translation elongation for a specific group of mRNA transcripts without poly-purine motifs over-represented in their 5′ UTRs. Such perturbation of translation elongation dynamics can be attributed to the blockage of translating ribosomes due to the binding of eIF4A to the poly-purine sequence in coding regions. In summary, our study presents the complete dual modes of RocA in blocking translation initiation and elongation, which underlie the potent antitumor effect of RocA.
Glycoside hydrolase processing of the Pel polysaccharide alters biofilm biomechanics and Pseudomonas aeruginosa virulence
Authors: Razvi Erum , Whitfield Gregory B. , Reichhardt Courtney , Dreifus Julia E. , Willis Alexandra R. , Gluscencova Oxana B. , Gloag Erin S. , Awad Tarek S. , Rich Jacquelyn D. , da Silva Daniel Passos , Bond Whitney , Le Mauff François , Sheppard Donald C. , Hatton Benjamin D. , Stoodley Paul , Reinke Aaron W. , Boulianne Gabrielle L. , Wozniak Daniel J. , Harrison Joe J. , Parsek Matthew R. , Howell P. Lynne
Published: February 2023

Pel exopolysaccharide biosynthetic loci are phylogenetically widespread biofilm matrix determinants in bacteria. In Pseudomonas aeruginosa, Pel is crucial for cell-to-cell interactions and reducing susceptibility to antibiotic and mucolytic treatments. While genes encoding glycoside hydrolases have long been linked to biofilm exopolysaccharide biosynthesis, their physiological role in biofilm development is unclear. Here we demonstrate that the glycoside hydrolase activity of P. aeruginosa PelA decreases adherent biofilm biomass and is responsible for generating the low molecular weight secreted form of the Pel exopolysaccharide. We show that the generation of secreted Pel contributes to the biomechanical properties of the biofilm and decreases the virulence of P. aeruginosa in Caenorhabditis elegans and Drosophila melanogaster. Our results reveal that glycoside hydrolases found in exopolysaccharide biosynthetic systems can help shape the soft matter attributes of a biofilm and propose that secreted matrix components be referred to as matrix associated to better reflect their influence.
Biologically informed deep learning to query gene programs in single-cell atlases
Authors: Lotfollahi Mohammad , Rybakov Sergei , Hrovatin Karin , Hediyeh-zadeh Soroor , Talavera-López Carlos , Misharin Alexander V. , Theis Fabian J.
Published: February 2023

The increasing availability of large-scale single-cell atlases has enabled the detailed description of cell states. In parallel, advances in deep learning allow rapid analysis of newly generated query datasets by mapping them into reference atlases. However, existing data transformations learned to map query data are not easily explainable using biologically known concepts such as genes or pathways. Here we propose expiMap, a biologically informed deep-learning architecture that enables single-cell reference mapping. ExpiMap learns to map cells into biologically understandable components representing known ‘gene programs’. The activity of each cell for a gene program is learned while simultaneously refining them and learning de novo programs. We show that expiMap compares favourably to existing methods while bringing an additional layer of interpretability to integrative single-cell analysis. Furthermore, we demonstrate its applicability to analyse single-cell perturbation responses in different tissues and species and resolve responses of patients who have coronavirus disease 2019 to different treatments across cell types.
First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial
Authors: Song Yan , Zhang Bo , Xin Dao , Kou Xiaoge , Tan Zhenbo , Zhang Shu , Sun Meili , Zhou Jin , Fan Min , Zhang Ming , Song Yongxiang , Li Suyi , Yuan Yuan , Zhuang Wu , Zhang Jingdong , Zhang Li , Jiang Hao , Gu Kangsheng , Ye Huangyang , Ke Ying , Li Jing , Wang Qingyu , Zhu Jun , Huang Jing ,   The ASTRUM-007 investigators
Published: February 2023

First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m2) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m2) (on days 1 and 2), once every 2 weeks. The study met the primary endpoints. At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively; hazard ratio, 0.60; 95% confidence interval, 0.48–0.75; P < 0.0001). At the prespecified interim analysis of overall survival (OS), serplulimab plus chemotherapy also significantly prolonged OS compared with placebo plus chemotherapy (median OS of 15.3 months and 11.8 months, respectively; hazard ratio, 0.68; 95% confidence interval, 0.53–0.87; P = 0.0020). Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. This study is registered with ClinicalTrials.gov (NCT03958890).
Low thigh muscle strength in relation to myosteatosis in patients with type 2 diabetes mellitus
Authors: Huang Yilong , Yan Jun , Zhu Hongli , Zhang Zhenguang , Jiang Yuanming , Zhang Xuxiang , Wu Yiran , Lu Jiahang , Cun Hanxue , He Bo
Published: February 2023

This study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with muscle strength in patients with type 2 diabetes mellitus (T2DM). Seventy T2DM patients and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T MRI and isokinetic muscle strength measurements to obtain the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT) proton density fat fraction (PDFF), intramuscular fat (IMF) PDFF, peak torque (PT) and total work (TW) of knee extensors and flexors. The differences of measurements between T2DM patients and asymptomatic volunteers were compared. Multivariate regression analysis was used to determine significant predictors of thigh extension and flexion strength. The SMI, IMAT and IMF PDFF of thigh muscles in T2DM patients were higher than that in the control group (p < 0.001), while PT and TW were lower than those in the control subjects (p < 0.05). Both IMF and IMAT PDFF were negatively correlated with PT, TW in participants with T2DM (extensors: r = − 0.72, − 0.70, p < 0.001; r = − 0.62, − 0.56, p < 0.05. flexors: r = − 0.37, − 0.43, p < 0.05; r = − 0.39, − 0.46, p < 0.05). Moderate and strong correlations between HOMA-IR and muscle strength measurements, muscle PDFFs were observed in extensors and flexors. IMF PDFF and age were the statistically significant predictor of PT and TW of extensors of thigh in multivariate regression analysis. Therefore, the thigh muscle PDFF increased was associated with muscle strength decreased in T2DM patients beyond SMI. Age are also important factors influencing thigh muscle PDFF and strength in T2DM patients.
The human microbial exposome: expanding the Exposome-Explorer database with gut microbial metabolites
Authors: Neveu Vanessa , Nicolas Geneviève , Amara Adam , Salek Reza M. , Scalbert Augustin
Published: February 2023

Metabolites produced by the gut microbiota play an important role in the cross-talk with the human host. Many microbial metabolites are biologically active and can pass the gut barrier and make it into the systemic circulation, where they form the gut microbial exposome, i.e. the totality of gut microbial metabolites in body fluids or tissues of the host. A major difficulty faced when studying the microbial exposome and its role in health and diseases is to differentiate metabolites solely or partially derived from microbial metabolism from those produced by the host or coming from the diet. Our objective was to collect data from the scientific literature and build a database on gut microbial metabolites and on evidence of their microbial origin. Three types of evidence on the microbial origin of the gut microbial exposome were defined: (1) metabolites are produced in vitro by human faecal bacteria; (2) metabolites show reduced concentrations in humans or experimental animals upon treatment with antibiotics; (3) metabolites show reduced concentrations in germ-free animals when compared with conventional animals. Data was manually collected from peer-reviewed publications and inserted in the Exposome-Explorer database. Furthermore, to explore the chemical space of the microbial exposome and predict metabolites uniquely formed by the microbiota, genome-scale metabolic models (GSMMs) of gut bacterial strains and humans were compared. A total of 1848 records on one or more types of evidence on the gut microbial origin of 457 metabolites was collected in Exposome-Explorer. Data on their known precursors and concentrations in human blood, urine and faeces was also collected. About 66% of the predicted gut microbial metabolites (n = 1543) were found to be unique microbial metabolites not found in the human GSMM, neither in the list of 457 metabolites curated in Exposome-Explorer, and can be targets for new experimental studies. This new data on the gut microbial exposome, freely available in Exposome-Explorer (http://exposome-explorer.iarc.fr/), will help researchers to identify poorly studied microbial metabolites to be considered in future studies on the gut microbiota, and study their functionalities and role in health and diseases.
Transcriptome-wide analysis reveals the coregulation of RNA-binding proteins and alternative splicing genes in the development of atherosclerosis
Authors: Wang Runqing , Xu Jin , Tang Yuning , Wang Yongxiang , Zhao Jing , Ding Liqiong , Peng Yu , Zhang Zheng
Published: January 2023

RNA-binding proteins (RBPs) are involved in the regulation of RNA splicing, stability, and localization. How RBPs control the development of atherosclerosis, is not fully understood. To explore the relevant RNA-binding proteins (RBPs) and alternative splicing events (ASEs) in atherosclerosis. We made a comprehensive work to integrate analyses of differentially expressed genes, including differential RBPs, and variable splicing characteristics related to different stages of atherosclerosis in dataset GSE104140. A total of 3712 differentially expressed genes (DEGs) were identified, including 2921 upregulated genes and 791 downregulated genes. Further analysis screened out 54 RBP genes, and 434 AS genes overlapped DEGs. We selected high expression ten RBP genes (SAMHD1, DDX60 L, TLR7, RBM47, MYEF2, RNASE6, PARP12, APOBEC3G, SMAD9, and RNASE1) for co-expression analysis. Meanwhile, we found seven regulated alternative splicing genes (RASGs) (ABI1, FXR1, CHID1, PLEC, PRKACB, BNIP2, PPP3CB) that could be regulated by RBPs. The co-expression network was used to further elucidate the regulatory and interaction relationship between RBPs and AS genes. Apoptotic process and innate immune response, revealed by the functional enrichment analysis of RASGs regulated by RBPs were closely related to atherosclerosis. In addition, 26 of the 344 alternative splicing genes regulated by the above 10 RBPs were transcription factors (TFs), We selected high expression nine TFs (TFDP1, RBBP7, STAT2, CREB5, ERG, ELF1, HMGN3, BCLAF1, and ZEB2) for co-expression analysis. The target genes of these TFs were mainly enriched in inflammatory and immune response pathways that were associated with atherosclerosis. indicating that AS abnormalities of these TFs may have a function in atherosclerosis. Furthermore, the expression of differentially expressed RBPs and the alternative splicing events of AS genes was validated by qRT-PCR in umbilical vein endothelial cells (HUVEC). The results showed that RBM47 were remarkedly difference in HUVEC treated with ox-LDL and the splicing ratio of AS in BCLAF1which is regulated by RBM47 significantly changed. In conclusion, the differentially expressed RBPs identified in our analysis may play important roles in the development of atherosclerosis by regulating the AS of these TF genes.
Dynamics of aggregate-associated organic carbon after long-term cropland conversion in a karst region, southwest China
Authors: Wen Li , Li Dejun , Xiao Kongcao , Tang Haiming , Li Chao , Xiao Xiaoping
Published: January 2023

Cropland conversion has a major impact on soil C sequestration. However, it remains unclear about the changes in soil aggregate and their contribution to C accumulation following cropland conversion in a karst region, southwest China. In this study, three different cropland use types (sugarcane, mulberry and forage grass cultivation) were selected to replace maize-soybean cultivation. The soil was collected at a depth of 0 to 30 cm for analysis of soil aggregates and their OC content. Results showed that macro-aggregate was the predominant component underlying four cropland use types. Forage grass cultivation remarkably increased the OC stock and aggregate stability (MWD and GMD). OC content and stock associated with aggregate varied with cropland use types and soil depth, but were typically highest in forage grass fields. Macro-aggregates contained higher OC content and stock than other aggregate fractions, along with soil depth underlying four cropland use types. The increases in OC stock in forage grass field was mainly due to increased OC stocks within macro-aggregates, which is further attributed to the increase in OC content within macro-aggregates. Overall, forage grass cultivation replaced maize-soybean cultivation was suggested as an ecological restoration model to enhance soil C sequestration potential, owing to its role in increasing OC stock of aggregation and aggregate stability, in the karst region of southwest China.
Machine learning models development for shear strength prediction of reinforced concrete beam: a comparative study
Authors: Yaseen Zaher Mundher
Published: January 2023

Fiber reinforced polymer (FPR) bars have been widely used as a substitutional material of steel reinforcement in reinforced concrete elements in corrosion areas. Shear resistance of FRP reinforced concrete element can be affected by concrete properties and transverse FRP stirrups. Hence, studying the shear strength (Vs) mechanism is one of the highly essential for pre-design procedure for reinforced concrete elements. This research examines the ability of three machine learning (ML) models called M5-Tree (M5), extreme learning machine (ELM), and random forest (RF) in predictingVsof 112 shear tests of FRP reinforced concrete beam with transverse reinforcement. For generating the prediction matrix of the developed ML models, statistical correlation analysis was conducted to generate the suitable inputs models forVsprediction. Statistical evaluation and graphical approaches were used to evaluate the efficiency of the proposed models. The results revealed that all the proposed models performed in general well for all the input combinations. However, ELM-M1 and M5-Tree-M5 models exhibited less accuracy performance in comparison with the other developed models. The study showed that the best prediction performance was revealed by M5 tree model using nine input parameters, with coefficient of determination (R2) and root mean square error (RMSE) equal to 0.9313 and 35.5083 KN, respectively. The comparison results also indicated that ELM and RF were performed significant results with a less slight performance than M5 model. The study outcome contributes to basic knowledge of investigating the impact of stirrups onVsof FRP reinforced concrete beam with the potential of applying different computer aid models.
Deep 3D reconstruction of synchrotron X-ray computed tomography for intact lungs
Authors: Shin Seungjoo , Kim Min Woo , Jin Kyong Hwan , Yi Kwang Moo , Kohmura Yoshiki , Ishikawa Tetsuya , Je Jung Ho , Park Jaesik
Published: January 2023

Synchrotron X-rays can be used to obtain highly detailed images of parts of the lung. However, micro-motion artifacts induced by such as cardiac motion impede quantitative visualization of the alveoli in the lungs. This paper proposes a method that applies a neural network for synchrotron X-ray Computed Tomography (CT) data to reconstruct the high-quality 3D structure of alveoli in intact mouse lungs at expiration, without needing ground-truth data. Our approach reconstructs the spatial sequence of CT images by using a deep-image prior with interpolated input latent variables, and in this way significantly enhances the images of alveolar structure compared with the prior art. The approach successfully visualizes 3D alveolar units of intact mouse lungs at expiration and enables us to measure the diameter of the alveoli. We believe that our approach helps to accurately visualize other living organs hampered by micro-motion.
Carbon black-containing self-healing adhesive hydrogels for endoscopic tattooing
Authors: Kwon Hyung Jun , Shin Hyun Ho , Hyun Da Han , Yoon Ghilsuk , Park Jun Seok , Ryu Ji Hyun
Published: February 2023

Endoscopic tattooing with India ink is a popular method for identifying colonic lesions during minimally invasive surgery because it is highly challenging to localize lesions during laparoscopy. However, there is a perceived unmet need for the injection of India ink and carbon particle suspension due to various complications and inconstant durability during the perioperative period. In this study, carbon black-containing self-healing adhesive alginate/polyvinyl alcohol composite hydrogels were synthesized as endoscopic tattooing inks. Alginate (Alg) conjugated with phenylboronic acid (PBA) groups in the backbone was crosslinked with polyvinyl alcohol (PVA) because of the dynamic bonds between the phenylboronic acid in alginate and the cis-diol groups of PVA. The carbon black-incorporated Alg-PBA/PVA hydrogels exhibited self-healing and re-shapable properties, indicating that improved intraoperative localization could be achieved. In addition, the adhesive tattooing hydrogels were stably immobilized on the target regions in the intraperitoneal spaces. These carbon black-containing self-healing adhesive hydrogels are expected to be useful in various surgical procedures, including endoscopic tattooing.
PRMT5 is a therapeutic target in choroidal neovascularization
Authors: Muniyandi Anbukkarasi , Martin Matthew , Sishtla Kamakshi , Motolani Aishat , Sun Mengyao , Jensen Nathan R. , Qi Xiaoping , Boulton Michael E. , Prabhu Lakshmi , Lu Tao , Corson Timothy W.
Published: January 2023

Ocular neovascular diseases including neovascular age-related macular degeneration (nvAMD) are widespread causes of blindness. Patients’ non-responsiveness to currently used biologics that target vascular endothelial growth factor (VEGF) poses an unmet need for novel therapies. Here, we identify protein arginine methyltransferase 5 (PRMT5) as a novel therapeutic target for nvAMD. PRMT5 is a well-known epigenetic enzyme. We previously showed that PRMT5 methylates and activates a proangiogenic and proinflammatory transcription factor, the nuclear factor kappa B (NF-κB), which has a master role in tumor progression, notably in pancreatic ductal adenocarcinoma and colorectal cancer. We identified a potent and specific small molecule inhibitor of PRMT5, PR5-LL-CM01, that dampens the methylation and activation of NF-κB. Here for the first time, we assessed the antiangiogenic activity of PR5-LL-CM01 in ocular cells. Immunostaining of human nvAMD sections revealed that PRMT5 is highly expressed in the retinal pigment epithelium (RPE)/choroid where neovascularization occurs, while mouse eyes with laser induced choroidal neovascularization (L-CNV) showed PRMT5 is overexpressed in the retinal ganglion cell layer and in the RPE/choroid. Importantly, inhibition of PRMT5 by PR5-LL-CM01 or shRNA knockdown of PRMT5 in human retinal endothelial cells (HRECs) and induced pluripotent stem cell (iPSC)-derived choroidal endothelial cells (iCEC2) reduced NF-κB activity and the expression of its target genes, such as tumor necrosis factor α (TNF-α) and VEGF-A. In addition to inhibiting angiogenic properties of proliferation and tube formation, PR5-LL-CM01 blocked cell cycle progression at G1/S-phase in a dose-dependent manner in these cells. Thus, we provide the first evidence that inhibition of PRMT5 impedes angiogenesis in ocular endothelial cells, suggesting PRMT5 as a potential therapeutic target to ameliorate ocular neovascularization.
Effects of wounds in the cell membrane on cell division
Authors: Tanvir Md. Istiaq Obaidi , Yumura Shigehiko
Published: February 2023

Cells are consistently subjected to wounding by physical or chemical damages from the external environment. We previously showed that a local wound of the cell membrane modulates the polarity of cell migration and the wounded cells escape from the wound site in Dictyostelium. Here, we examined effects of wounds on dividing cells. When the cell membrane at the cleavage furrow during cytokinesis was locally wounded using laserporation, furrow constriction was significantly accelerated. Neither myosin II nor cortexillins contributed to the acceleration, because the acceleration was not hindered in mutant cells deficient in these proteins. When the cell membrane outside the furrow was wounded, the furrow constriction was not accelerated. Instead, the wounded-daughter half became smaller and the unwounded half became larger, resulting in an asymmetrical cell division. These phenomena occurred independently of wound repair. When cells in anaphase were wounded at the presumptive polar region, about 30% of the wounded cells changed the orientation of the division axis. From these observations, we concluded that dividing cells also escape from the wound site. The wound experiments on dividing cells also provide new insights into the mechanism of cytokinesis and cell polarity establishment.
Analysis of Himalayan marmot distribution and plague risk in Qinghai province of China using the “3S” technology
Authors: Wu Hailian , Wu Haisheng , Wang Yongshun , Li Hongying , Tian Fuzhang , Zhou Kuizhang , Qi Zhizhen , Zhang Yiquan , Zhang Qingwen , Zhang Xuefei
Published: February 2023

To provide guidance for plague surveillance and a reliable basis for plague prevention and control, we analyzed the habitat characteristics of Himalayan marmots, developed Himalayan marmot information collection system V3.0 based on global navigation satellite system (GNSS), remote sensing, and geographic information system (“3S”) technology, and drew a predictive spatial distribution map of Himalayan marmots in Qinghai Province. Field survey data of 352 marmot plague sites in Qinghai Province were collected in 2014, and the data from 80 sample sites were included. The Himalayan marmot habitat characteristics were analyzed based on “3S” technology using five environment variables (elevation, slope, aspect, vegetation cover, and grass type) and the geographical coordinates. Himalayan marmot information collection system V3.0, which has been approved by the National Copyright Administration of the People’s Republic of China (No.00764743), was used to draw a predictive spatial distribution map of Himalayan marmots in Qinghai province. Moreover, from 2015 to 2017, positioning data of the plague-foci and plague-free areas in Qinghai Province were collected using GNSS receptor for field validations to verify the accuracy of the marmot predictive spatial distribution map. Elevation, slope, vegetation cover, and grassland type were identified as important environmental factors that determine the spatial distribution of Himalayan marmots. The suitable range of environmental features was 3400–4600 m elevation, 5°–20° slope, 0.60–1.00 vegetation cover, and alpine meadows. The Himalayan marmot predictive spatial distribution map in Qinghai Province based on “3S” technology and marmot information collection system V3.0 had a spatial resolution of 30 m. Field validation in areas of Qinghai Province revealed a prediction accuracy and mean absolute error of 0.8669 and 0.1331, respectively, which indicated excellent prediction accuracy. This study greatly improved the work efficiency of plague surveillance and effectively reduced the work intensity of researchers. Application of “3S” technology and marmot information collection system V3.0 has improved the data collection efficiency, provided new technical means for plague investigation and research, and provided a reference for development of plague surveillance programs. The research results will play a positive role in promoting the improvement and perfection of plague prevention and control strategies in Qinghai province and even in China.
Combined space stressors induce independent behavioral deficits predicted by early peripheral blood monocytes
Authors: Rienecker Kira D. A. , Grue Katherine , Paladini Maria Serena , Frias Elma S. , Frattini Valentina , Borlongan Mia C. , Chou Austin , Torres-Espin Abel , Krukowski Karen , Ferguson Adam R. , Rosi Susanna
Published: January 2023

Interplanetary space travel poses many hazards to the human body. To protect astronaut health and performance on critical missions, there is first a need to understand the effects of deep space hazards, including ionizing radiation, confinement, and altered gravity. Previous studies of rodents exposed to a single such stressor document significant deficits, but our study is the first to investigate possible cumulative and synergistic impacts of simultaneous ionizing radiation, confinement, and altered gravity on behavior and cognition. Our cohort was divided between 6-month-old female and male mice in group, social isolation, or hindlimb unloading housing, exposed to 0 or 50 cGy of 5 ion simplified simulated galactic cosmic radiation (GCRsim). We report interactions and independent effects of GCRsim exposure and housing conditions on behavioral and cognitive performance. Exposure to GCRsim drove changes in immune cell populations in peripheral blood collected early after irradiation, while housing conditions drove changes in blood collected at a later point. Female mice were largely resilient to deficits observed in male mice. Finally, we used principal component analysis to represent total deficits as principal component scores, which were predicted by general linear models using GCR exposure, housing condition, and early blood biomarkers.
Rapid clonal identification of biallelic CRISPR/Cas9 knock-ins using SNEAK PEEC
Authors: Singh Sameer , Banerjee Anoosha , Vanden Broeck Arnaud , Klinge Sebastian
Published: January 2023

One of the challenges faced by current CRISPR/Cas9 editing strategies is the difficulty in rapidly selecting clonal populations of biallelically edited cells. Here we present Surface engiNeered fluorEscence Assisted Kit with Protein Epitope Enhanced Capture (SNEAK PEEC), a platform that combines human genome editing with cell-surface display, which enables the direct identification of biallelically edited clones with minimal screening.
Changes in pupil dilation and P300 amplitude indicate the possible involvement of the locus coeruleus-norepinephrine (LC-NE) system in psychological flow
Authors: Lu Hairong , van der Linden Dimitri , Bakker Arnold B.
Published: February 2023

Psychological flow is a state of full task immersion. The present study was conducted to test the hypothesis that psychological flow is positively related to activity of the phasic locus coeruleus-norepinephrine (LC-NE) system, which supports decisions on whether to engage in or disengage from the current activity. Subjective flow was assessed among 36 participants who engaged in a gamified version of the n-back task with various difficulty levels (0, 1, 2, and 3 back). During the tasks, continuous pupil diameter and EEG were recorded. We found that psychological flow and two presumed indicators of the phasic LC-NE activity (pupil dilation and EEG P300 amplitude) fit inverted U-shapes with increasing subjective task difficulty. Moreover, a positive linear relationship between psychological flow and pupil dilation (not with P300) was found. In conclusion, this study indicates the involvement of the LC-NE system in the peak experience of flow.
Adaptation of Glycyrrhiza glabra L. to water deficiency based on carbohydrate and fatty acid quantity and quality
Authors: Haghighi Tahereh Movahhed , Saharkhiz Mohammad Jamal , Kavoosi Gholamreza , Zarei Mehdi
Published: January 2023

Water deficit affects agricultural systems negatively globally. This research objective was to mitigate drought’s detrimental effects on plants metabolite profiling by utilizing biofertilizers and mineral nutrition. The carbohydrate content and fatty acid profile of Licorice (Glycyrrhiza glabra) were assessed under Silicon (Si) nutrition, Claroiedoglomus etunicatum inoculation (F), and drought stress (100, 80, 60, 40, and 20% of field capacity (FC)). Results showed that Si application increased total sugar content under severe drought levels (20 and 40% FC) and made it reach 12.41 and 12.63 g/100 g DW, respectively. Sucrose, as the predominant sugar of licorice, was at its highest level (13.1 g/100 g DW) in response to integrated values of F and Si (60% FC). Gas chromatography–mass spectrometry showed that the majority of fatty acid components in plants were 9-Octadecenoic acid (8.72–71.27%), 9,12-Octadecadienoic acid (0.1–56.43%), Hexadecanoic acid (12.84–30.59%), Octadecanoic acid (6.9–15.3%), Docosanoic acid (0.57–2.77%), Eicosanoic acid (1.07–2.64%), and 7-Hexadecenoic acid (0.26–2.62%). Since a lower omega6/omega3 ratio represents a healthier product, the lowest ratio (0.25%) was observed in well-watered inoculated plants. Also, severe drought-treated plants under integrated Si and F applications showed a low omega6/omega3 ratio (1.88%). In conclusion, Si and F improved synergistically the carbohydrate content and fatty acid profile in plants, despite the drought stress.
Ultrastructural changes in esophageal tissue undergoing stretch tests with possible impact on tissue engineering and long gap esophageal repairs performed under tension
Authors: Biro Ede , Sommer Gerhard , Leitinger Gerd , Abraham Hajnalka , Kardos Daniel J. , Oberritter Zsolt , Saxena Amulya K.
Published: January 2023

Esophageal biomechanical studies are being performed to understand structural changes resulting from stretches during repair of esophageal atresias as well as to obtain biomechanical values for tissue-engineered esophagus. The present study offers insights into ultrastructural changes after stretching of the ovine esophagus using uniaxial stretch tests. In vitro uniaxial stretching was performed on esophagi (n = 16) obtained from the abattoir within 4–6 h of 1-month-old lambs. Esophagi were divided into 4 groups (4 esophagi/group): control, Group1 (G1), Group2 (G2), Group3 (G3) stretched to 20%, 30% and 40% of their original length respectively. Force and lengthening were measured with 5 cycles performed on every specimen. Transmission electron microscopic (TEM) studies were performed on the 4 groups. During observational TEM study of the control group there were no significant differences in muscle cell structure or extracellular matrix. In all stretched groups varying degrees of alterations were identified. The degree of damage correlated linearly with the increasing level of stretch. Distance between the cells showed significant difference between the groups (control (μ = 0.41 μm, SD = 0.26), G1 (μ = 1.36 μm, SD = 1.21), G2 (μ = 2.8 μm, SD = 1.83), and G3 (μ = 3.01 μm, SD = 2.06). The diameter of the cells (control μ = 19.87 μm, SD = 3.81; G1 μ = 20.38 μm, SD = 4.45; G2 μ = 21.7 μm, SD = 6.58; G3 μ = 24.48 μm, SD = 6.69) and the distance between myofibrils (control μ = 0.23 μm, SD = 0.08; G1 μ = 0.27 μm, SD = 0.08; G2 μ = 0.4 μm, SD = 0.15; G3 μ = 0.61 μm, SD = 0.2) were significantly different as well (p < 0.05 was considered to be significant). Esophageal stretching > 30% alters the regular intracellular and extracellular structure of the esophageal muscle and leads to disruption of intra- and extracellular bonds. These findings could provide valuable insights into alterations in the microscopic structure of the esophagus in esophageal atresias repaired under tension as well as the basis for mechanical characterization for tissue engineering of the esophagus.
In vivo and in vitro toxicity profile of tetrabutylammonium bromide and alcohol-based deep eutectic solvents
Authors: Inayat Shamaila , Ahmad Sajid Rashid , Awan Sana Javaid , Nawshad Muhammad , Ali Qurban
Published: January 2023

Deep eutectic solvents (DESs) have emerged as new promising solvents in the field of “green chemistry,” which possess a broad range of potential applications. However, the ecotoxicological profile of these solvents is still poorly known. In this study, ammonium-based deep eutectic solutions with glycerol (2:2), ethylene glycol (1:2), and diethylene glycol (1:2) as hydrogen bond donors in 1:2 proportion were evaluated for their interaction with various biological systems, including gram-positive and negative bacteria, fungi, fish, and human fibroblast cell lines. The DES synthesis was confirmed by Fourier transform infrared spectroscopy analysis, which analyses the interactions between DES precursors for their synthesis. The antimicrobial activity of tetrabutylammonium bromide: ethylene glycol was the most potent, while tetrabutylammonium bromide: diethylene glycol had a higher LC50 against C. carpio fish. Tetrabutylammonium bromide: glycerol was supposed to be the most suitable DES in terms of cell viability percentage (118%) and 2,2-diphenyl-1-picrylhydrazyl scavenging activity (93%). Finally, tetrabutylammonium bromide in glycerol can be considered an eco-friendly solvent due to its lower toxicity in both in vivo and in vitro environments.
Fully automated immunoassay for cholesterol uptake capacity to assess high-density lipoprotein function and cardiovascular disease risk
Authors: Murakami Katsuhiro , Harada Amane , Toh Ryuji , Kubo Takuya , Miwa Keiko , Kim Jeeeun , Kiriyama Maria , Iino Takuya , Nishikawa Youichi , Uno Shin-Nosuke , Akatsuchi Kohei , Nagao Manabu , Ishida Tatsuro , Hirata Ken-ichi
Published: February 2023

High-density lipoprotein (HDL) cholesterol efflux capacity (CEC), which is a conventional metric of HDL function, has been associated with coronary heart disease risk. However, the CEC assay requires cultured cells and takes several days to perform. We previously established a cell-free assay to evaluate cholesterol uptake capacity (CUC) as a novel measure of HDL functionality and demonstrated its utility in coronary risk stratification. To apply this concept clinically, we developed a rapid and sensitive assay system based on a chemiluminescent magnetic particle immunoassay. The system is fully automated, providing high reproducibility. Measurement of CUC in serum is completed within 20 min per sample without HDL isolation, a notably higher throughput than that of the conventional CEC assay. CUC decreased with myeloperoxidase-mediated oxidation of HDL or in the presence of N-ethylmaleimide, an inhibitor of lecithin: cholesterol acyltransferase (LCAT), whereas CUC was enhanced by the addition of recombinant LCAT. Furthermore, CUC correlated with CEC even after being normalized by ApoA1 concentration and was significantly associated with the requirement for revascularization due to the recurrence of coronary lesions. Therefore, our new assay system shows potential for the accurate measurement of CUC in serum and permits assessing cardiovascular health.
A highly sensitive NanoLuc-based protease biosensor for detecting apoptosis and SARS-CoV-2 infection
Authors: Arakawa Masashi , Yoshida Akiho , Okamura Shinya , Ebina Hirotaka , Morita Eiji
Published: January 2023

Proteases play critical roles in various biological processes, including apoptosis and viral infection. Several protease biosensors have been developed; however, obtaining a reliable signal from a very low level of endogenous protease activity remains a challenge. In this study, we developed a highly sensitive protease biosensor, named FlipNanoLuc, based on the Oplophorus gracilirostris NanoLuc luciferase. The flipped β-strand was restored by protease activation and cleavage, resulting in the reconstitution of luciferase and enzymatic activity. By making several modifications, such as introducing NanoBiT technology and CL1-PEST1 degradation tag, the FlipNanoLuc-based protease biosensor system achieved more than 500-fold luminescence increase in the corresponding protease-overexpressing cells. We demonstrated that the FlipNanoLuc-based caspase sensor can be utilized for the detection of staurosporine-induced apoptosis with sixfold increase in luminescence. Furthermore, we also demonstrated that the FlipNanoLuc-based coronavirus 3CL-protease sensor can be used to detect human coronavirus OC43 with tenfold increase in luminescence and severe acute respiratory syndrome-coronavirus-2 infections with 20-fold increase in luminescence by introducing the stem-loop 1 sequence to prevent the virus inducing global translational shutdown.