bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA
Authors: Knorr Jakob , Sharafutdinov Irshad , Fiedler Florian , Soltan Esmaeili Delara , Rohde Manfred , Rottner Klemens , Backert Steffen , Tegtmeyer Nicole
Published: June 2021

Cortactin is a well-known regulatory protein of the host actin cytoskeleton and represents an attractive target of microbial pathogens like Helicobacter pylori. H. pylori manipulates cortactin’s phosphorylation status by type-IV secretion-dependent injection of its virulence protein CagA. Multiple host tyrosine kinases, like FAK, Src, and Abl, are activated during infection, but the pathway(s) involved is (are) not yet fully established. Among them, Src and Abl target CagA and stimulate tyrosine phosphorylation of the latter at its EPIYA-motifs. To investigate the role of cortactin in more detail, we generated a CRISPR/Cas9 knockout of cortactin in AGS gastric epithelial cells. Surprisingly, we found that FAK, Src, and Abl kinase activities were dramatically downregulated associated with widely diminished CagA phosphorylation in cortactin knockout cells compared to the parental control. Together, we report here a yet unrecognized cortactin-dependent signaling pathway involving FAK, Src, and Abl activation, and controlling efficient phosphorylation of injected CagA during infection. Thus, the cortactin status could serve as a potential new biomarker of gastric cancer development.
Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview
Authors: Lindberg Mattias F. , Meijer Laurent
Published: June 2021

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRK1A, 1B, 2-4) and cdc2-like kinases (CLK1-4) belong to the CMGC group of serine/threonine kinases. These protein kinases are involved in multiple cellular functions, including intracellular signaling, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine/methionine/folate regulation, body temperature regulation, endocytosis, neuronal development, synaptic plasticity, etc. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer’s disease and related diseases, tauopathies, dementia, Pick’s disease, Parkinson’s disease and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorder. DYRKs and CLKs are also involved in diabetes, abnormal folate/methionine metabolism, osteoarthritis, several solid cancers (glioblastoma, breast, and pancreatic cancers) and leukemias (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), as well as infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium). This variety of pathological implications calls for (1) a better understanding of the regulations and substrates of DYRKs and CLKs and (2) the development of potent and selective inhibitors of these kinases and their evaluation as therapeutic drugs. This article briefly reviews the current knowledge about DYRK/CLK kinases and their implications in human disease.
Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics
Authors: Danan Dor , Todder Doron , Zohar Joseph , Cohen Hagit
Published: June 2021

Previously, we found that basal corticosterone pulsatility significantly impacts the vulnerability for developing post-traumatic stress disorder (PTSD). Rats that exhibited PTSD-phenotype were characterized by blunted basal corticosterone pulsatility amplitude and a blunted corticosterone response to a stressor. This study sought to identify the mechanisms underlining both the loss of pulsatility and differences in downstream responses. Serial blood samples were collected manually via jugular vein cannula at 10-min intervals to evaluate suppression of corticosterone following methylprednisolone administration. The rats were exposed to predator scent stress (PSS) after 24 h, and behavioral responses were assessed 7 days post-exposure for retrospective classification into behavioral response groups. Brains were harvested for measurements of the glucocorticoid receptor, mineralocorticoid receptor, FK506-binding protein-51 and arginine vasopressin in specific brain regions to assess changes in hypothalamus–pituitary–adrenal axis (HPA) regulating factors. Methylprednisolone produced greater suppression of corticosterone in the PTSD-phenotype group. During the suppression, the PTSD-phenotype rats showed a significantly more pronounced pulsatile activity. In addition, the PTSD-phenotype group showed distinct changes in the ventral and dorsal CA1, dentate gyrus as well as in the paraventricular nucleus and supra-optic nucleus. These results demonstrate a pre-trauma vulnerability state that is characterized by an over-reactivity of the HPA and changes in its regulating factors.
Highly-Efficient Sulfonated UiO-66(Zr) Optical Fiber for Rapid Detection of Trace Levels of Pb2+
Authors: Nazari Marziyeh , Amini Abbas , Eden Nathan T. , Duke Mikel C. , Cheng Chun , Hill Matthew R.
Published: June 2021

Lead detection for biological environments, aqueous resources, and medicinal compounds, rely mainly on either utilizing bulky lab equipment such as ICP-OES or ready-made sensors, which are based on colorimetry with some limitations including selectivity and low interference. Remote, rapid and efficient detection of heavy metals in aqueous solutions at ppm and sub-ppm levels have faced significant challenges that requires novel compounds with such ability. Here, a UiO-66(Zr) metal-organic framework (MOF) functionalized with SO3H group (SO3H-UiO-66(Zr)) is deposited on the end-face of an optical fiber to detect lead cations (Pb2+) in water at 25.2, 43.5 and 64.0 ppm levels. The SO3H-UiO-66(Zr) system provides a Fabry–Perot sensor by which the lead ions are detected rapidly (milliseconds) at 25.2 ppm aqueous solution reflecting in the wavelength shifts in interference spectrum. The proposed removal mechanism is based on the adsorption of [Pb(OH2)6]2+ in water on SO3H-UiO-66(Zr) due to a strong affinity between functionalized MOF and lead. This is the first work that advances a multi-purpose optical fiber-coated functional MOF as an on-site remote chemical sensor for rapid detection of lead cations at extremely low concentrations in an aqueous system.
Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity
Authors: Berrocal Maria , Saez Lucia , Mata Ana M.
Published: June 2021

Since dysregulation of intracellular calcium (Ca2+) levels is a common occurrence in neurodegenerative diseases, including Alzheimer’s disease (AD), the study of proteins that can correct neuronal Ca2+ dysregulation is of great interest. In previous work, we have shown that plasma membrane Ca2+-ATPase (PMCA), a high-affinity Ca2+ pump, is functionally impaired in AD and is inhibited by amyloid-β peptide (Aβ) and tau, two key components of pathological AD hallmarks. On the other hand, sorcin is a Ca2+-binding protein highly expressed in the brain, although its mechanism of action is far from being clear. Sorcin has been shown to interact with the intracellular sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), and other modulators of intracellular Ca2+ signaling, such as the ryanodine receptor or presenilin 2, which is closely associated with AD. The present work focuses on sorcin in search of new regulators of PMCA and antagonists of Aβ and tau toxicity. Results show sorcin as an activator of PMCA, which also prevents the inhibitory effects of Aβ and tau on the pump, and counteracts the neurotoxicity of Aβ and tau by interacting with them.
Reference Transcriptome Data in Silkworm Bombyx mori
Authors: Yokoi Kakeru , Tsubota Takuya , Jouraku Akiya , Sezutsu Hideki , Bono Hidemasa
Published: June 2021

Herein, we performed RNA-seq analysis of ten major tissues/subparts of silkworm larvae. The sequences were mapped onto the reference genome assembly and the reference transcriptome data were successfully constructed. The reference data provided a nearly complete sequence for sericin-1, a major silk gene with a complex structure. We also markedly improved the gene model for other genes. The transcriptomic expression was investigated in each tissue and a number of transcripts were identified that were exclusively expressed in tissues such as the testis. Transcripts strongly expressed in the midgut formed tight genomic clusters, suggesting that they originated from tandem gene duplication. Transcriptional factor genes expressed in specific tissues or the silk gland subparts were also identified. We successfully constructed reference transcriptome data in the silkworm and found that a number of transcripts showed unique expression profiles. These results will facilitate basic studies on the silkworm and accelerate its applications, which will contribute to further advances in lepidopteran and entomological research as well as the practical use of these insects.
Incidence, Risk, and Visual Outcomes after Repositioning of Acute Non-Traumatic Flap Dislocations Following Femtosecond-Assisted LASIK
Authors: Moshirfar Majid , West David G. , Miller Chase M , West William B. , McCabe Shannon E. , Shmunes Kathryn M. , Baker Preston A. , Ronquillo Yasmyne C. , Hoopes Phillip C.
Published: June 2021

Although the use of femtosecond lasers instead of mechanical devices has decreased the incidence of flap complications following laser-assisted in situ keratomileusis (LASIK), dislocations and striae still occur. Flap repositioning is an effective intervention to improve visual outcomes after acute flap complications in both microkeratome-assisted and femtosecond-assisted LASIK. This retrospective case series included patients undergoing flap repositioning secondary to acute flap dislocation and/or visually significant striae within the first two weeks following femtosecond LASIK (FS-LASIK) from 2015 to 2020 at a single institution. Preoperative, intraoperative, and postoperative de-identified data were analyzed for incidence, risk factors, and visual acuity outcomes. The incidence of flap repositioning was 0.35% in 21,536 eyes (n = 70). Indications for repositioning included acute flap dislocation (35.7%) and visually significant striae (64.3%). High myopia (OR = 3.04, p = 0.001) and patient age over 50 years (OR = 3.69, p = 0.001) were the strongest risk factors for these complications. Prior to flap repositioning, uncorrected distance visual acuity (UDVA) of 20/20 or better and 20/40 or better occurred in 19% and 57% of eyes, respectively. After repositioning, a final UDVA of 20/20 or better and 20/40 or better occurred in 78% and 98% of eyes, respectively. After repositioning, one line of UDVA was lost in two eyes (2.8%) and two lines were lost in one eye (1.4%). Risk factors for acute flap dislocation included high myopia and age over 50 years. Flap repositioning was effective in salvaging visual outcomes.
Monitoring of Changes in Masticatory Muscle Stiffness after Gum Chewing Using Shear Wave Elastography
Authors: Olchowy Cyprian , Grzech-Leśniak Kinga , Hadzik Jakub , Olchowy Anna , Łasecki Mateusz
Published: June 2021

This study aimed to investigate if intensive exercise affects the stiffness of the masticatory muscles measured with shear-wave elastography. The study included a cohort of healthy adults (n = 40) aged 40 ± 11 years. In each individual, the stiffness of both the masseter and temporalis muscle was examined three times: at baseline, after 10 min of intensive exercise (chewing gum), and after 10 min of relaxation. Stiffness values (median (IQR)) of both the masseter and temporalis muscle were the lowest at the baseline (11.35 (9.7–12.65) and 10.1 (9.1–10.95)), increased significantly after the exercise (12.5 (11.1–13.25) and 10.3 (10.2–10.52)) and then dropped significantly after 10 min of relaxing (11.75 (9.95–12.6) and 10.2 (9.65–11.9)). The stiffness of the temporalis muscle was significantly lower than that of the masseter muscle. The values of the stiffness of the masseters correlated significantly with the values of the stiffness of the temporalis muscles. Shear wave elastography proved to be a sensitive method for showing changes in the stiffness of the muscles involved in the mastication occurring as a response to the effort, which increased the muscle stiffness. Further research is needed to broaden knowledge on the impact of eating habits and the occurrence of parafunctions on the development of temporomandibular disorders and the condition of masticatory muscles.
The Underestimated Prevalence of Neglected Chronic Pelvic Pain in Women, a Nationwide Cross-Sectional Study in France
Authors: Margueritte François , Fritel Xavier , Zins Marie , Goldberg Marcel , Panjo Henri , Fauconnier Arnaud , Ringa Virginie
Published: June 2021

Dysmenorrhoea, dyspareunia, and non-menstrual chronic pelvic pain (NMCPP) are symptoms that are probably underreported and neglected. This study aimed to assess the prevalence and overlapping relations between these symptoms among a general population of French women of reproductive age. A cross-sectional study among the nationwide CONSTANCES cohort study recruiting a representative sample of women within different French areas was constructed. Women aged 18–49 years (n = 21,287) who reported periods in the previous three months and experienced intercourse at least once were asked about prevalence of three types of chronic pelvic pain: mild, moderate and severe dysmenorrhea; dyspareunia assessed according to its frequency; NMCPP from a binary question. Between the start of 2012 through the end of 2017, 21,287 women were enrolled, 39.8% of them (95% confidence interval (CI), 39.2–40.5) reported moderate to severe dysmenorrhea; 20.3% (95% CI, 18.7–21.9) of the youngest group (18–24 years) reported severe dysmenorrhea. Dyspareunia was reported to happen often or always by 7.9% (95% CI, 7.5–8.2) and peaked among the youngest women at 12.8% (95% CI, 11.5–14.1). NMCPP was reported by 17.0% (95% CI, 16.5–17.5). Moreover, 7.5% (95% CI, 6.4–8.6) of the women reported two or more types of severe or frequent pain. More attention should be paid to this substantial proportion (7.5%) of French women of reproductive age who experience multiple, severe and frequent pelvic pain symptoms.
Recommendations for Diagnosis and Treatment of Lumbosacral Radicular Pain: A Systematic Review of Clinical Practice Guidelines
Authors: Khorami Ahmad Khoshal , Oliveira Crystian B. , Maher Christopher G. , Bindels Patrick J. E. , Machado Gustavo C. , Pinto Rafael Z. , Koes Bart W. , Chiarotto Alessandro
Published: June 2021

The management of patients with lumbosacral radicular pain (LRP) is of primary importance to healthcare professionals. This study aimed to: identify international clinical practice guidelines on LRP, assess their methodological quality, and summarize their diagnostic and therapeutic recommendations. A systematic search was performed (August 2019) in MEDLINE, PEDro, National Guideline Clearinghouse, National Institute for Health and Clinical Excellence (NICE), New Zealand Guidelines Group (NZGG), International Guideline Library, Guideline central, and Google Scholar. Guidelines presenting recommendations on diagnosis and/or treatment of adult patients with LRP were included. Two independent reviewers selected eligible guidelines, evaluated quality with Appraisal of Guidelines Research & Evaluation (AGREE) II, and extracted recommendations. Recommendations were classified into ‘should do’, ‘could do’, ‘do not do’, or ‘uncertain’; their consistency was labelled as ‘consistent’, ‘common’, or ‘inconsistent’. Twenty-three guidelines of varying quality (AGREE II overall assessment ranging from 17% to 92%) were included. Consistent recommendations regarding diagnosis are (‘should do’): Straight leg raise (SLR) test, crossed SLR test, mapping pain distribution, gait assessment, congruence of signs and symptoms. Routine use of imaging is consistently not recommended. The following therapeutic options are consistently recommended (‘should do’): educational care, physical activity, discectomy under specific circumstances (e.g., failure of conservative treatment). Referral to a specialist is recommended when conservative therapy fails or when steppage gait is present. These recommendations provide a clear overview of the management options in patients with LRP.
Study of the Physical Behavior of a New Composite Material Based on Fly Ash from the Combustion of Coal in an Ultra-Supercritical Thermal Power Plant
Authors: El Kanzaoui Mustapha , Ennawaoui Chouaib , Eladaoui Saleh , Hajjaji Abdelowahed , Guenbour Abdellah , Boussen Ratiba
Published: June 2021

Given the amount of industrial waste produced and collected in the world today, a recycling and recovery process is needed. The study carried out on this subject focuses on the valorization of one of these industrial wastes, namely the fly ash produced by an ultra-supercritical coal power plant. This paper describes the use and recovery of fly ash as a high percentage reinforcement for the development of a new high-performance composite material for use in various fields. The raw material, fly ash, comes from the staged combustion of coal, which occurs in the furnace of an ultra-supercritical boiler of a coal-fired power plant. Mechanical compression, thermal conductivity, and erosion tests are used to study the mechanical, thermal, and erosion behavior of this new composite material. The mineralogical and textural analyses of samples were characterized using Scanning Electron Microscopy (SEM). SEM confirmed the formation of a new composite by a polymerization reaction. The results obtained are very remarkable, with a high Young’s modulus and a criterion of insulation, which approves the presence of a potential to be exploited in the different fields of materials. In conclusion, the composite material presented in this study has great potential for building material and could represent interesting candidates for the smart city.
Postprocessing for Skin Detection
Authors: Baldissera Diego , Nanni Loris , Brahnam Sheryl , Lumini Alessandra
Published: June 2021

Skin detectors play a crucial role in many applications: face localization, person tracking, objectionable content screening, etc. Skin detection is a complicated process that involves not only the development of apposite classifiers but also many ancillary methods, including techniques for data preprocessing and postprocessing. In this paper, a new postprocessing method is described that learns to select whether an image needs the application of various morphological sequences or a homogeneity function. The type of postprocessing method selected is learned based on categorizing the image into one of eleven predetermined classes. The novel postprocessing method presented here is evaluated on ten datasets recommended for fair comparisons that represent many skin detection applications. The results show that the new approach enhances the performance of the base classifiers and previous works based only on learning the most appropriate morphological sequences.
Service Life Prediction and Lateral Bearing Capacity Analysis of Piles Considering Coupled Corrosion-Temperature Deterioration Processes
Authors: Li Yue , Chen Youliang , Shao Wei , Zhang Juhui , Liao Shaoming , Fernandez-Steeger Tomas Manuel
Published: June 2021

High temperatures can enhance the chloride diffusion coefficient and this poses a threat to reinforced concrete (RC) piles. This study intends to propose predictive models that can evaluate the service life and lateral bearing behaviour of reinforced concrete piles subjected to marine environments and varying temperatures. The models show that temperature can accelerate the diffusion rate of chloride and increase the concentration of free chloride in concrete. The distribution law of chloride concentration is obtained by considering the ageing effect as well. Deterministic and probabilistic models are proposed to assess the time to corrosion initiation and propagation. The stiffness degradation coefficient is introduced in the analysis of the lateral bearing capacity of RC piles. The results show that high temperature can decrease the service life of piles and the life spans obtained from deterministic and probabilistic methods are similar; however, the predictions of the latter are more conservative. Temperature can enhance the current density and boost corrosion products, which leads to pile cracking. The rust appearing on the steel surface would make the stiffness degradation coefficient drop sharply. The lateral bearing capacity analysis is conducted from the perspectives of shear force, displacement and bearing moment of the piles.
Influence of Pile Diameter and Aspect Ratio on the Lateral Response of Monopiles in Sand with Different Relative Densities
Authors: Wang Huan , Wang Lizhong , Hong Yi , Askarinejad Amin , He Ben , Pan Hualin
Published: June 2021

The large-diameter monopiles are the most preferred foundation used in offshore wind farms. However, the influence of pile diameter and aspect ratio on the lateral bearing behavior of monopiles in sand with different relative densities has not been systematically studied. This study presents a series of well-calibrated finite-element (FE) analyses using an advanced state dependent constitutive model. The FE model was first validated against the centrifuge tests on the large-diameter monopiles. Parametric studies were performed on rigid piles with different diameters (D = 4–10 m) and aspect ratios (L/D = 3–7.5) under a wide range of loading heights (e = 5–100 m) in sands with different relative densities (Dr = 40%, 65%, 80%). The API and PISA p-y models were systematically compared and evaluated against the FE simulation results. The numerical results revealed a rigid rotation failure mechanism of the rigid pile, which is independent of pile diameter and aspect ratio. The computed soil pressure coefficient (K = p/Dσ′v) of different diameter piles at same rotation is a function of z/L (z is depth) rather than z/D. The force–moment diagrams at different deflections were quantified in sands of different relative density. Based on the observed pile–soil interaction mechanism, a simple design model was proposed to calculate the combined capacity of rigid piles.
Use of Nanosilica for Increasing Dune Erosion Resistance during a Sea Storm
Authors: Leone Elisa , Kobayashi Nobuhisa , Francone Antonio , Bartolo Samuele De , Strafella Davide , D’Alessandro Felice , Tomasicchio Giuseppe Roberto
Published: June 2021

Dune recovery interventions that integrate natural, sustainable, and soft solutions have become increasingly popular in coastal communities. In the present study, the reliability of an innovative non-toxic colloidal silica-based solution for coastal sand dunes has been verified for the first time by means of laboratory experiments. An extensive experimental campaign aimed at studying the effectiveness of the use of nanosilica has been conducted in the 2D wave flume of the EUMER laboratory at the University of Salento (Italy). The study was first based on a horizontal seabed and then a cross-shore beach-dune profile was drawn similar to those generally observed in nature. Detailed measurements of wave characteristics and observed bed and cross-shore beach-dune profiles were analyzed for a wide range of wave conditions. In both cases, two sets of experiments were carried out. After the first set of experiments performed resembling the native conditions of the models composed with natural sand, the effects of the injection of the mineral colloidal silica-based grout were investigated. The observations show that mineral colloidal silica increases the mechanical strength of non-cohesive sediments reducing the volume of dune erosion, thus improving the resistance and longevity of the beach-dune system.
A Study of Wave-Induced Effects on Sea Surface Temperature Simulations during Typhoon Events
Authors: Sun Zhanfeng , Shao Weizeng , Yu Wupeng , Li Jun
Published: June 2021

In this work, we investigate sea surface temperature (SST) cooling under binary typhoon conditions. We particularly focus on parallel- and cross-type typhoon paths during four typhoon events: Tembin and Bolaven in 2012, and Typhoon Chan-hom and Linfa in 2015. Wave-induced effects were simulated using a third-generation numeric model, WAVEWATCH III (WW3), and were subsequently included in SST simulations using the Stony Brook Parallel Ocean Model (sbPOM). Four wave-induced effects were analyzed: breaking waves, nonbreaking waves, radiation stress, and Stokes drift. Comparison of WW3-simulated significant wave height (SWH) data with measurements from the Jason-2 altimeter showed that the root mean square error (RMSE) was less than 0.6 m with a correlation (COR) of 0.9. When the four typhoon-wave-induced effects were included in sbPOM simulations, the simulated SSTs had an RMSE of 1 °C with a COR of 0.99 as compared to the Argos data. This was better than the RMSE and COR recovered between the measured and simulated SSTs, which were 1.4 °C and 0.96, respectively, when the four terms were not included. In particular, our results show that the effects of Stokes drift, as well as of nonbreaking waves, were an important factor in SST reduction during binary typhoons. The horizontal profile of the sbPOM-simulated SST for parallel-type typhoon paths (Typhoons Tembin and Bolaven) suggested that the observed finger pattern of SST cooling (up to 2 °C) was probably caused by drag from typhoon Tembin. SST was reduced by up to 4 °C for cross-type typhoon paths (Typhoons Chan-hom and Linfa). In general, mixing significantly increased when the four wave-induced effects were included. The vertical profile of SST indicated that disturbance depth increased (up to 100 m) for cross-type typhoon paths because the mixing intensity was greater for cross-type typhoons than for parallel-type typhoons.
Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias
Authors: Haghighi Kobra , Gardner George , Vafiadaki Elizabeth , Kumar Mohit , Green Lisa C. , Ma Jianyong , Crocker Jeffrey S. , Koch Sheryl , Arvanitis Demetrios A. , Bidwell Phillip , Rubinstein Jack , van de Leur Rutger , Doevendans Pieter A. , Akar Fadi G. , Tranter Michael , Wang Hong-Sheng , Sadayappan Sakthivel , DeMazumder Deeptankar , Sanoudou Despina , Hajjar Roger J. , Stillitano Francesca , Kranias Evangelia G.
Published: June 2021

The inherited mutation (R14del) in the calcium regulatory protein phospholamban (PLN) is linked to malignant ventricular arrhythmia with poor prognosis starting at adolescence. However, the underlying early mechanisms that may serve as prognostic factors remain elusive. This study generated humanized mice in which the endogenous gene was replaced with either human wild type or R14del-PLN and addressed the early molecular and cellular pathogenic mechanisms. R14del-PLN mice exhibited stress-induced impairment of atrioventricular conduction, and prolongation of both ventricular activation and repolarization times in association with ventricular tachyarrhythmia, originating from the right ventricle (RV). Most of these distinct electrocardiographic features were remarkably similar to those in R14del-PLN patients. Studies in isolated cardiomyocytes revealed RV-specific calcium defects, including prolonged action potential duration, depressed calcium kinetics and contractile parameters, and elevated diastolic Ca-levels. Ca-sparks were also higher although SR Ca-load was reduced. Accordingly, stress conditions induced after contractions, and inclusion of the CaMKII inhibitor KN93 reversed this proarrhythmic parameter. Compensatory responses included altered expression of key genes associated with Ca-cycling. These data suggest that R14del-PLN cardiomyopathy originates with RV-specific impairment of Ca-cycling and point to the urgent need to improve risk stratification in asymptomatic carriers to prevent fatal arrhythmias and delay cardiomyopathy onset.
Olfactory Bulb Proteomics Reveals Widespread Proteostatic Disturbances in Mixed Dementia and Guides for Potential Serum Biomarkers to Discriminate Alzheimer Disease and Mixed Dementia Phenotypes
Authors: Lachén-Montes Mercedes , Íñigo-Marco Ignacio , Cartas-Cejudo Paz , Fernández-Irigoyen Joaquín , Santamaría Enrique
Published: June 2021

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer’s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related dementias, little is known about the impact of this sensorial impairment in MixD at the molecular level. To address this gap in knowledge, we assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n = 6) respect to neurologically intact controls (n = 7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolism, and neuron projection regeneration. In addition, network-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT, and the PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, also being deregulated across different tauopathies, synucleinopathies, and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phenotypes.
Improved Models of Human Endometrial Organoids Based on Hydrogels from Decellularized Endometrium
Authors: Francés-Herrero Emilio , Juárez-Barber Elena , Campo Hannes , López-Martínez Sara , de Miguel-Gómez Lucía , Faus Amparo , Pellicer Antonio , Ferrero Hortensia , Cervelló Irene
Published: June 2021

Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoECM (0.01 mg/mL) as a soluble additive. We characterized the resultant organoids to verify their epithelial origin, long-term chromosomal stability, and stemness properties. Lastly, we determined their proliferation potential under different culture conditions using proliferation rates and immunohistochemical methods. Our results demonstrate the importance of a bioactive environment for the maintenance and proliferation of human endometrial organoids.
Association of Matrix Metalloproteinases with Coronary Artery Calcification in Patients with CHD
Authors: Polonskaya Yana V. , Kashtanova Elena V. , Murashov Ivan S. , Striukova Evgenia V. , Kurguzov Alexey V. , Stakhneva Ekaterina M. , Shramko Viktoria S. , Maslatsov Nikolay A. , Chernyavsky Aleksandr M. , Ragino Yulia I.
Published: June 2021

This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.
A Study on the Factors Influencing Users’ Online Knowledge Paying-Behavior Based on the UTAUT Model
Authors: Yu Liying , Chen Zixuan , Yao Pinbo , Liu Hongda
Published: June 2021

With the explosive growth of information and the increase of people’s fragmented time, the knowledge payment industry’s market size is growing. However, the heterogeneity between online knowledge payment behavior and traditional consumption gradually comes to the fore. It is of great practical significance to analyze the factors influencing users’ online knowledge payment behavior and clarify users’ online knowledge payment mechanism. Based on UTAUT theory, this study uses statistics, structural equation modeling, and mediating effect analysis to construct a theoretical model of the influencing factors of users’ payment behavior of knowledge payment platform from the user level, knowledge-provider level, and platform level. The findings show that content quality, peer influence, KOL influence, perceived interaction, effort expectation, and perceived trust significantly affect users’ willingness-to-pay and have an indirect effect on users’ paying behavior through their willingness-to-pay. Perceived cost, perceived interaction, content quality, peer influence, performance expectation, and effort expectation directly and significantly affect user paying behavior. By regulating the above elements, the improvement of customer attraction ability of online knowledge platforms can be realized.
In Vitro Observations of the Interactions between Pholiota carbonaria and Polytrichum commune and Its Potential Environmental Relevance
Authors: Raudabaugh Daniel B. , Wells Daniel G. , Matheny Patrick B. , Hughes Karen W. , Sargent Malcolm , Iturriaga Teresa , Miller Andrew N.
Published: June 2021

Wildfires play a critical role in maintaining biodiversity and shaping ecosystem structure in fire-prone regions, and successional patterns involving numerous plant and fungal species in post-fire events have been elucidated. Evidence is growing to support the idea that some post-fire fungi can form endophytic/endolichenic relationships with plants and lichens. However, no direct observations of fire-associated fungal–moss interactions have been visualized to date. Therefore, physical interactions between a post-fire fungus, Pholiota carbonaria, and a moss, Polytrichum commune, were visually examined under laboratory conditions. Fungal appressoria were visualized on germinating spores and living protonemata within two weeks of inoculation in most growth chambers. Appressoria were pigmented, reddish gold to braun, and with a penetration peg. Pigmented, reddish gold to braun fungal hyphae were associated with living tissue, and numerous mature rhizoids contained fungal hyphae at six months. Inter-rhizoidal hyphae were pigmented and reddish gold to braun, but no structures were visualized on mature gametophyte leaf or stem tissues. Based on our visual evidence and previous work, we provide additional support for P. carbonaria having multiple strategies in how it obtains nutrients from the environment, and provide the first visual documentation of these structures in vitro.
Analysis of the Sequence Characteristics of Antifreeze Protein
Authors: Zhang Yu-Hang , Li Zhandong , Lu Lin , Zeng Tao , Chen Lei , Li Hao , Huang Tao , Cai Yu-Dong
Published: June 2021

Antifreeze protein (AFP) is a proteinaceous compound with improved antifreeze ability and binding ability to ice to prevent its growth. As a surface-active material, a small number of AFPs have a tremendous influence on the growth of ice. Therefore, identifying novel AFPs is important to understand protein–ice interactions and create novel ice-binding domains. To date, predicting AFPs is difficult due to their low sequence similarity for the ice-binding domain and the lack of common features among different AFPs. Here, a computational engine was developed to predict the features of AFPs and reveal the most important 39 features for AFP identification, such as antifreeze-like/N-acetylneuraminic acid synthase C-terminal, insect AFP motif, C-type lectin-like, and EGF-like domain. With this newly presented computational method, a group of previously confirmed functional AFP motifs was screened out. This study has identified some potential new AFP motifs and contributes to understanding biological antifreeze mechanisms.
Altered Bone Status in Rett Syndrome
Authors: Pecorelli Alessandra , Cordone Valeria , Schiavone Maria Lucia , Caffarelli Carla , Cervellati Carlo , Cerbone Gaetana , Gonnelli Stefano , Hayek Joussef , Valacchi Giuseppe
Published: June 2021

Rett syndrome (RTT) is a monogenic neurodevelopmental disorder primarily caused by mutations in X-linked MECP2 gene, encoding for methyl-CpG binding protein 2 (MeCP2), a multifaceted modulator of gene expression and chromatin organization. Based on the type of mutation, RTT patients exhibit a broad spectrum of clinical phenotypes with various degrees of severity. In addition, as a complex multisystem disease, RTT shows several clinical manifestations ranging from neurological to non-neurological symptoms. The most common non-neurological comorbidities include, among others, orthopedic complications, mainly scoliosis but also early osteopenia/osteoporosis and a high frequency of fractures. A characteristic low bone mineral density dependent on a slow rate of bone formation due to dysfunctional osteoblast activity rather than an increase in bone resorption is at the root of these complications. Evidence from human and animal studies supports the idea that MECP2 mutation could be associated with altered epigenetic regulation of bone-related factors and signaling pathways, including SFRP4/WNT/β-catenin axis and RANKL/RANK/OPG system. More research is needed to better understand the role of MeCP2 in bone homeostasis. Indeed, uncovering the molecular mechanisms underlying RTT bone problems could reveal new potential pharmacological targets for the treatment of these complications that adversely affect the quality of life of RTT patients for whom the only therapeutic approaches currently available include bisphosphonates, dietary supplements, and physical activity.
Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer
Authors: Liu Dehua , Sun Chenyu , Kim Nahyun , Bhan Chandur , Tuason John Pocholo Whitaker , Chen Yue , Ma Shaodi , Huang Yuting , Cheng Ce , Zhou Qin , Zhang Kaiguang
Published: June 2021

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.
Loss of Function of OsARG Resulted in Pepper-Shaped Husk in Indica Rice
Authors: Zheng Yan , Mwamburi Mjomba Fredrick , Liu Huaqing , Wang Feng
Published: June 2021

Grain shape is one of the most important and complex traits determining the grain yield in rice. In this study, we discovered two rice mutants with defective shape spikelets, designated as psh1-1/2 (pepper-shaped husk 1-1/2), which were both isolated from the tissue-culture-regenerated plants of indica cultivar Minghui 86. The two mutants showed the same mutant phenotypes, containing pepper-shaped spikelets; shorter, smaller and compact panicles; very low seed-setting rate; high percentage of split grains; and lower grain width. Genetic analysis indicated that the mutant phenotypes were controlled by a recessive gene. Gene mapping indicated that the target gene PSH1 was located on the short arm of chromosome 4. Sequencing analysis revealed that the two mutants each had a different nonsense mutation in OsARG, confirming that the target gene is OsARG. Compared with the previously reported OsARG mutant nglf-1, psh1-1/2 possessed some distinct mutant phenotypes, probably because of the influence of different genetic background, suggesting that OsARG may function differently under different genetic backgrounds.
Nanometer-Sized Boron Loaded Liposomes Containing Fe3O4 Magnetic Nanoparticles and Tributyl Borate and Anti-Albumin from Bovine Serum Antibody for Thermal Neutron Detection
Authors: Zhang Wei , Wang Kaikai , Hu Xiaodan , Zhang Xiaohong , Chang Shuquan , Zhang Haiqian
Published: June 2021

A shortage in the supply of 3He used for thermal neutron detector makes researchers to find 3He alternatives for developing new neutron detectors. Here, we prepared a neutron-sensitive composite liposome with tributyl borate and encapsulating with Fe3O4@oleic acid nanoparticles (Fe3O4@OA NPs), methylene blue (MB), or anti-albumin from bovine serum (anti-BSA). The tributyl borate compound was characterized by Fourier transform infrared spectroscopy (FT-IR). In addition, the morphology, element compositions, and magnetic properties of the composite liposome were investigated with transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), and vibrating sample magnetometer (VSM), respectively. The results indicated that a typical ellipsoidal magnetic liposome structure was obtained, and the lengths of the minor axis and major axis were 49 ± 1 nm and 87 ± 3 nm, respectively. Under thermal neutron irradiation, the structure of composite liposome was destroyed, and encapsulated reporter molecules were released, which was detected by ultraviolet–visible (UV–vis) spectroscopy and surface plasmon resonance (SPR) technology. The response of this sensor based on a destructive assay shows a good correlation with neutron doses. Besides, the sensor has a neutron to gamma-ray rejection ratio of 1568 at a thermal neutron flux rate of 135.6 n/cm2·s, which makes it a promising alternative to 3He.
Theoretical Predictions of the Structural and Mechanical Properties of Tungsten–Rare Earth Element Alloys
Authors: Wu Mingyu , Wang Zhihang , Zhang Ningning , Ge Changchun , Zhang Yujuan
Published: June 2021

Tungsten (W) is considered as the potential plasma facing material of the divertor and the first wall material in fusion. To further improve the ductility of W, the structural and mechanical properties of W–M (M = rare earth element Y, La, Ce and Lu) alloys are systematically investigated by first-principles calculations. Our results reveal that all the W1−xMx (x = 0.0625, 0.125, 0.1875, 0.25) alloys can form binary solid solution at the atomic level, and the alloys keep bcc lattice structures until the concentration of M increases to a certain value. Although the moduli of the alloys are reduced compared to that of pure W metal, the characteristic B/G ratio and Poisson’s ratio significantly increase, implying all the four rare earth elements can efficiently improve the ductility of W metal. Considering both factors of mechanical strength and ductility, La and Ce are better alloying elements than Y and Lu.
Hybrid Polymer Composites Used in the Arms Industry: A Review
Authors: Czech Kamil , Oliwa Rafał , Krajewski Dariusz , Bulanda Katarzyna , Oleksy Mariusz , Budzik Grzegorz , Mazurkow Aleksander
Published: June 2021

Polymer fiber composites are increasingly being used in many industries, including the defense industry. However, for protective applications, in addition to high specific strength and stiffness, polymer composites are also required to have a high energy absorption capacity. To improve the performance of fiber-reinforced composites, many researchers have modified them using multiple methods, such as the introduction of nanofillers into the polymer matrix, the modification of fibers with nanofillers, the impregnation of fabrics using a shear thickening fluid (STF) or a shear thickening gel (STG), or a combination of these techniques. In addition, the physical structures of composites have been modified through reinforcement hybridization; the appropriate design of roving, weave, and cross-orientation of fabric layers; and the development of 3D structures. This review focuses on the effects of modifying composites on their impact energy absorption capacity and other mechanical properties. It highlights the technologies used and their effectiveness for the three main fiber types: glass, carbon, and aramid. In addition, basic design considerations related to fabric selection and orientation are indicated. Evaluation of the literature data showed that the highest energy absorption capacities are obtained by using an STF or STG and an appropriate fiber reinforcement structure, while modifications using nanomaterials allow other strength parameters to be improved, such as flexural strength, tensile strength, or shear strength.