bluuebunny/crossref_metadata_2025 huggingface dataset:
CPNE7-Induced Autophagy Restores the Physiological Function of Mature Odontoblasts
Authors: Park Yeoung-Hyun , Son Chul , Seo You-Mi , Lee Yoon Seon , Har Alix , Park Joo-Cheol
Published: April 2021

Dentin, which composes most of the tooth structure, is formed by odontoblasts, long-lived post-mitotic cells maintained throughout the entire life of the tooth. In mature odontoblasts, however, cellular activity is significantly weakened. Therefore, it is important to augment the cellular activity of mature odontoblasts to regenerate physiological dentin; however, no molecule regulating the cellular activity of mature odontoblasts has yet been identified. Here, we suggest that copine-7 (CPNE7) can reactivate the lost functions of mature odontoblasts by inducing autophagy. CPNE7 was observed to elevate the expression of microtubule-associated protein light chain 3-II (LC3-II), an autophagy marker, and autophagosome formation in the pre-odontoblast and mature odontoblast stages of human dental pulp cells. CPNE7-induced autophagy upregulated DSP and DMP-1, odontoblast differentiation and mineralization markers, and augmented dentin formation in mature odontoblasts. Furthermore, CPNE7 also upregulated NESTIN and TAU, which are expressed in the physiological odontoblast process, and stimulated the elongation of the odontoblast process by inducing autophagy. Moreover, lipofuscin, which progressively accumulates in long-lived post-mitotic cells and hinders their proper functions, was observed to be removed in recombinant CPNE7-treated mature odontoblasts. Thus, CPNE7-induced autophagy reactivated the function of mature odontoblasts and promoted the formation of physiological dentin in vivo. On the other hand, the well-known autophagy inducer, rapamycin, promoted odontoblast differentiation in pre-odontoblasts but did not properly reactivate the function of mature odontoblasts. These findings provide evidence that CPNE7 functionally reactivates mature odontoblasts and introduce its potential for dentinal loss-targeted clinical applications.
Using Biosensors to Study Protein–Protein Interaction in the Hippo Pathway
Authors: Pipchuk Alexander , Yang Xiaolong
Published: April 2021

The Hippo signaling network is dependent on protein–protein interactions (PPIs) as a mechanism of signal transduction to regulate organ size, cellular proliferation and differentiation, tumorigenesis, and other cellular processes. Current efforts aim to resolve the complex regulation of upstream Hippo components or focus on identifying targeted drugs for use in cancer therapy. Despite extensive characterization of the Hippo pathway interactome by affinity purification mass spectrometry (AP-MS) and other methodologies, previous research methods have not been sufficient to achieve these aims. In this review, we describe several recent studies that make use of luciferase-based biosensors as a new approach to study the Hippo Pathway. These biosensors serve as powerful tools with which to study PPIs both in vitro using purified biosensor proteins, and in real time in live cells. Notably, luciferase biosensors have excellent sensitivity and have been used to screen for upstream kinase regulators of the Hippo pathway. Furthermore, the high sensitivity and stability of these biosensors enables their application in high throughput screening for Hippo-targeted chemotherapeutics. Finally, we describe the strengths and weaknesses of this method relative to AP-MS and discuss potential future directions for using biosensors to study Hippo signaling.
Real-Time Imaging of Short-Wave Infrared Luminescence Lifetimes for Anti-counterfeiting Applications
Authors: Ziniuk Roman , Yakovliev Artem , Li Hui , Chen Guanying , Qu Junle , Ohulchanskyy Tymish Y.
Published: April 2021

Rare-earth doped nanoparticles (RENPs) have been widely used for anti-counterfeiting and security applications due to their light frequency conversion features: they are excited at one wavelength, and they display spectrally narrow and distinguished luminescence peaks either at shorter wavelengths (i.e., frequency/energy upconversion) or at longer wavelengths (frequency/energy downconversion). RENPs with a downconversion (DC) photoluminescence (PL) in short-wave infrared (SWIR) spectral range (~1,000–1,700 nm) have recently been introduced to anti-counterfeiting applications, allowing for multilevel protection based on PL imaging through opaque layers, due to a lesser scattering of SWIR PL emission. However, as the number and spectral positions of the discrete PL bands exhibited by rare-earth ions are well-known, it is feasible to replicate luminescence spectra from RENPs, which results in a limited anti-counterfeiting security. Alternatively, lifetime of PL from RENPs can be used for encoding, as it can be finely tuned in broad temporal range (i.e., from microseconds to milliseconds) by varying type of dopants and their content in RENPs, along with the nanoparticle morphology and size. Nevertheless, the current approach to decoding and imaging the RENP luminescence lifetimes requires multiple steps and is highly time-consuming, precluding practical applications of PL lifetime encoding for anti-counterfeiting. Herein, we report the use of a rapid lifetime determination (RLD) technique to overcome this issue and introduce real-time imaging of SWIR PL lifetime for anti-counterfeiting applications. NaYF4:20% Yb, x% Er (x = 0, 2, 20, 80)@NaYF4 core@shell RENPs were synthesized and characterized, revealing DC PL in SWIR region, with maximum at ~1,530 nm and PL lifetimes ranging from 3.2 to 6 ms. Imaging of the nanoparticles with different lifetimes was performed by the developed time-gated imaging system engaging RLD method and the precise manipulation of the delay between the excitation pulses and camera gating windows. Moreover, it is shown that imaging and decrypting can be performed at a high rate (3–4 fps) in a cyclic manner, thus allowing for real-time temporal decoding. We believe that the demonstrated RLD-based fast PL lifetime imaging approach can be employed in other applications of photoluminescent RENPs.
Nuclear Spin Relaxation of Longitudinal and Singlet Order in Liquid-CO2 Solutions
Authors: Moysiadi Aliki , Giustiniano Francesco , Hall Andrew M. R. , Cartlidge Topaz A. A. , Brown Lynda J. , Pileio Giuseppe
Published: April 2021

Hyperpolarization techniques can enormously enhance the NMR signal thus allowing the exploitation of hyperpolarized substrates for in-vivo MRI applications. The short lifetime of hyperpolarized spin order poses significant limitations in such applications. Spin order storage can be prolonged through the use of long-lived spin states. Additionally, the storage of spin polarization–either in the form of longitudinal or singlet order–can be prolonged in low viscosity solutions. Here, we report the use of low viscosity liquid-CO2 solutions to store nuclear spin polarization in the form of longitudinal and singlet order for extended periods. Our results demonstrate that this storage time can be considerably sustained in liquid-CO2 solutions in comparison to other low viscosity solvents, opening up the possibility of new, exciting storage experiments in the future.
Utilization of Spent FCC Catalyst as Fine Aggregate in Non-sintered Brick: Alkali Activation and Environmental Risk Assessment
Authors: Zhang Dandan , Fang Shiping , Zhang Hongzhe , Liu Zhengwei , Zhang Zhiyuan , Zhang Shucai
Published: April 2021

This study focuses on the recycling of a spent fluid catalytic cracking (FCC) catalyst to produce catalyst-based non-sintered bricks (CN-bricks) for the recovery of its aluminosilicate components and the solidification of heavy metals. The effects of the content of cement (10–20%), the proportion of FCC (10–40%), and the type of an activator (NaOH/Na2SiO3/Na2SO4) on the performance of a CN-brick were investigated in terms of the mechanical strength and leaching behavior. The results show that an optimal binder system of 20% cement + Na2SO4 could promote the compressive strength up to 42.3 MPa; the proportion of an optimal spent FCC catalyst of 20% could achieve the lowest porosity and water absorption. The microscopic mechanism of a cementitious process was analyzed by x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), proving that C-S-H and ettringite (AFt) are the two main hydration products of a CN-brick. Na2SO4 is superior to NaOH or Na2SiO3 as an activator since Na2SO4 takes advantage of the aluminum-rich property of a spent FCC catalyst and specifically promote the formation of a needle-like AFt. Quantitative environmental risk assessment for the utilization of a CN-brick on roads was carried out based on the leaching test of a toxicity characteristic leaching procedure (TCLP), NEN 7371 maximum availability test, and the hazard Index (HI) identification, and a final HI 0.0045 (<1.0) indicates an acceptable risk for environment and nearby residents as CN-bricks are utilized on roads for 30 years.
An Ultrafast N-Glycoproteome Analysis Method Using Thermoresponsive Magnetic Fluid-Immobilized Enzymes
Authors: Fan Zhiya , Liu Tong , Zheng Fei , Qin Weijie , Qian Xiaohong
Published: April 2021

N-Glycosylation is one of the most common and important post-translational modification methods, and it plays a vital role in controlling many biological processes. Increasing discovery of abnormal alterations in N-linked glycans associated with many diseases leads to greater demands for rapid and efficient N-glycosylation profiling in large-scale clinical samples. In the workflow of global N-glycosylation analysis, enzymatic digestion is the main rate-limiting step, and it includes both protease digestion and peptide-N4–(N-acetyl-beta-glucosaminyl) asparagine amidase (PNGase) F deglycosylation. Prolonged incubation time is generally required because of the limited digestion efficiency of the conventional in-solution digestion method. Here, we propose novel thermoresponsive magnetic fluid (TMF)-immobilized enzymes (trypsin or PNGase F) for ultrafast and highly efficient proteome digestion and deglycosylation. Unlike other magnetic material-immobilized enzymes, TMF-immobilized enzymes display a unique temperature-triggered magnetic response behavior. At room temperature, a TMF-immobilized enzyme completely dissolves in an aqueous solution and forms a homogeneous system with a protein/peptide sample for efficient digestion but cannot be separated by magnetic force because of its excellent water dispersity. Above its lower critical solution temperature (LCST), thermoflocculation of a TMF-immobilized enzyme allows it to be easily recovered by increasing the temperature and magnetic force. Taking advantage of the unique homogeneous reaction of a TMF-immobilized enzyme, both protein digestion and glycopeptide deglycosylation can be finished within 3 min, and the whole sample processing time can be reduced by more than 20 times. The application of a TMF-immobilized enzyme in large-scale profiling of protein N-glycosylation in urine samples led to the successful identification of 2,197 N-glycopeptides and further demonstrated the potential of this strategy for fast and high-throughput analysis of N-glycoproteome in clinical samples.
Constraining the Moho Depth Below Bhutan With Global-Phase Seismic Interferometry
Authors: Obermann Anne , Ruigrok Elmer , Bianchi Irene , Hetényi György
Published: April 2021

We use a novel technique named global-phase seismic interferometry (GloPSI) to image the lithospheric structure, and in particular the Moho, below two parallel north-south transects belonging to the GANSSER network (2013–2014). The profiles cross the Himalayan orogenic wedge in Bhutan, a tectonically important area within the largest continent-continent collision zone on Earth that is still undergoing crustal thickening and represents a challenging imaging target for the GloPSI approach. GloPSI makes use of direct waves from distant earthquakes and receiver-side reverberations with near vertical incidence. Reflections are isolated from earthquake recordings by solving a correlation integral and are turned into a reflectivity image of the lithosphere below the arrays. Our results compare favorably with first-order features observed from a previous receiver function (RF) study. We show that a combined interpretation of GloPSI and RF results allows for a more in-depth understanding of the lithospheric structure across the orogenic wedge in Bhutan.
Vegetation Changes in Southeastern Siberia During the Late Pleistocene and the Holocene
Authors: Courtin Jérémy , Andreev Andrei A. , Raschke Elena , Bala Sarah , Biskaborn Boris K. , Liu Sisi , Zimmermann Heike , Diekmann Bernhard , Stoof-Leichsenring Kathleen R. , Pestryakova Luidmila A. , Herzschuh Ulrike
Published: April 2021

Relationships between climate, species composition, and species richness are of particular importance for understanding how boreal ecosystems will respond to ongoing climate change. This study aims to reconstruct changes in terrestrial vegetation composition and taxa richness during the glacial Late Pleistocene and the interglacial Holocene in the sparsely studied southeastern Yakutia (Siberia) by using pollen and sedimentary ancient DNA (sedaDNA) records. Pollen and sedaDNA metabarcoding data using the trnL g and h markers were obtained from a sediment core from Lake Bolshoe Toko. Both proxies were used to reconstruct the vegetation composition, while metabarcoding data were also used to investigate changes in plant taxa richness. The combination of pollen and sedaDNA approaches allows a robust estimation of regional and local past terrestrial vegetation composition around Bolshoe Toko during the last ∼35,000 years. Both proxies suggest that during the Late Pleistocene, southeastern Siberia was covered by open steppe-tundra dominated by graminoids and forbs with patches of shrubs, confirming that steppe-tundra extended far south in Siberia. Both proxies show disturbance at the transition between the Late Pleistocene and the Holocene suggesting a period with scarce vegetation, changes in the hydrochemical conditions in the lake, and in sedimentation rates. Both proxies document drastic changes in vegetation composition in the early Holocene with an increased number of trees and shrubs and the appearance of new tree taxa in the lake’s vicinity. The sedaDNA method suggests that the Late Pleistocene steppe-tundra vegetation supported a higher number of terrestrial plant taxa than the forested Holocene. This could be explained, for example, by the “keystone herbivore” hypothesis, which suggests that Late Pleistocene megaherbivores were able to maintain a high plant diversity. This is discussed in the light of the data with the broadly accepted species-area hypothesis as steppe-tundra covered such an extensive area during the Late Pleistocene.
A Recombinant BCG Vaccine Is Safe and Immunogenic in Neonatal Calves and Reduces the Clinical Disease Caused by the Respiratory Syncytial Virus
Authors: Díaz Fabián E. , Guerra-Maupome Mariana , McDonald Paiton O. , Rivera-Pérez Daniela , Kalergis Alexis M. , McGill Jodi L.
Published: April 2021

The human respiratory syncytial virus (hRSV) constitutes a major health burden, causing millions of hospitalizations in children under five years old worldwide due to acute lower respiratory tract infections. Despite decades of research, licensed vaccines to prevent hRSV are not available. Development of vaccines against hRSV targeting young infants requires ruling out potential vaccine-enhanced disease presentations. To achieve this goal, vaccine testing in proper animal models is essential. A recombinant BCG vaccine that expresses the Nucleoprotein of hRSV (rBCG-N-hRSV) protects mice against hRSV infection, eliciting humoral and cellular immune protection. Further, this vaccine was shown to be safe and immunogenic in human adult volunteers. Here, we evaluated the safety, immunogenicity, and protective efficacy of the rBCG-N-hRSV vaccine in a neonatal bovine RSV calf infection model. Newborn, colostrum-replete Holstein calves were either vaccinated with rBCG-N-hRSV, WT-BCG, or left unvaccinated, and then inoculatedviaaerosol challenge with bRSV strain 375. Vaccination with rBCG-N-hRSV was safe and well-tolerated, with no systemic adverse effects. There was no evidence of vaccine-enhanced disease following bRSV challenge of rBCG-N-hRSV vaccinated animals, suggesting that the vaccine is safe for use in neonates. Vaccination increased virus-specific IgA and virus-neutralization activity in nasal fluid and increased the proliferation of virus- and BCG-specific CD4+ and CD8+ T cells in PBMCs and lymph nodes at 7dpi. Furthermore, rBCG-N-hRSV vaccinated calves developed reduced clinical disease as compared to unvaccinated control calves, although neither pathology nor viral burden were significantly reduced in the lungs. These results suggest that the rBCG-N-hRSV vaccine is safe in neonatal calves and induces protective humoral and cellular immunity against this respiratory virus. These data from a newborn animal model provide further support to the notion that this vaccine approach could be considered as a candidate for infant immunization against RSV.
A Generic Methodology for Calculating Rescheduling Time for Multiple Unexpected Events in the Era of Zero Defect Manufacturing
Authors: Psarommatis Foivos , Martiriggiano Giacomo , Zheng Xiaochen , Kiritsis Dimitris
Published: April 2021

Nowadays, the manufacturing industry is constantly changing. Production systems must operate in a highly dynamic environment where unexpected events could occur and create disruption, making rescheduling inevitable for manufacturing companies. Rescheduling models are fundamental to the robustness of production processes. This paper proposes a model to address rescheduling caused by unexpected events, aiming to achieve the zero-defect manufacturing (ZDM) concept. The goal of the model is to incorporate traditional and ZDM–oriented events into one methodology to calculate when the next rescheduling will be performed to effectively react to unexpected events. The methodology relies on the definition of two key time parameters for each event type: event response time (RT) and event delay response time (DRT). Based on these parameters, an event management algorithm is designed to identify the optimal rescheduling solution. The DRT parameter is calculated based on a multi-parametric dynamic formula to capture the dynamics of production. Moreover, ANOM, and ANOVA methods are used to analyse the behaviour of the developed method and to assess the level of robustness of the proposed approach. Finally, a case study based on real production scenarios is conducted, a series of simulation experiments are performed, and comparisons with other rescheduling policies are presented. The results demonstrate the effectiveness of the proposed event management algorithm for managing rescheduling.
Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature
Authors: Eriksson Per , Mölne Johan , Wirestam Lina , Sjöwall Christopher
Published: April 2021

Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.
Apatinib-Induced Hand–Foot Skin Reaction in Chinese Patients With Liver Cancer
Authors: Xia Hui , Zhou Cheng , Luo Zhaoxia , Zhang Ping , Zhu Liping , Gong Zhao
Published: April 2021

Apatinib, an anti-tumor drug selectively targeting VEGFR2 (Vascular Endothelia Growth Factor Recpetor-2), has been proven effective in Chinese patients with liver cancer. Generally, treatment with apatinib achieves 16.1% of the overall objective remission rate (ORR) and 55.83% of the disease control rate (DCR) in Chinese patients with liver cancer. However, the prevalence of apatinib-induced hand–foot skin reaction (AI-HFSR) is noticeably high. The incidence of AI-HFSR is about 50.5%, of which Grades 1/2 and 3 are 38.8 and 11.6%, respectively. In addition, potential molecular mechanisms underlying the development of AI-HFSR are poorly understood and urgently needed to be investigated histologically. In this review, we summarize and review the current efficacy of apatinib and the prevalence of AI-HFSR in Chinese patients with liver cancer. Besides, we postulate the potential mechanisms underlying the development of AI-HFSR and discuss the optimal clinical management for this unwanted cutaneous side effect.
Clinicopathological Analysis of 34 Cases of Primary Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Chinese Children
Authors: Wu Jingyi , Pei Yuxin , Rong Liping , Zhuang Hongjie , Zeng Shuhan , Chen Lizhi , Jiang Xiaoyun
Published: April 2021

Background: This study aimed to summarize the clinicopathological features and prognostic risk factors of primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in children.

Methods: Clinical and prognostic data for children admitted to our center with AAV between September 2003 and September 2020 were studied retrospectively. The incidence and risk factors of end-stage renal disease (ESRD) were calculated and analyzed.

Results: Thirty-four children were enrolled; 28 were female, with a median onset age of 10 years. Except for one case negative for ANCA, the other 33 patients were diagnosed with microscopic polyangiitis (MPA). The most frequently involved organ was the kidney (100.0%), followed by the lungs (58.8%) and heart (50.0%). Twenty children (58.8%) progressed to ESRD with a median course of 3 months, and they were more likely to present respiratory and cardiovascular system involvement than were the non-ESRD group (P < 0.05). Patients in the ESRD group also had a higher serum creatinine level, 24-h protein excretion, Pediatric Vasculitis Activity Score (PVAS), and a lower level of estimated glomerular filtration rate (eGFR), hemoglobin, and complement C3 than had those in the non-ESRD group (P < 0.05). The main pathological manifestations were crescentic and sclerotic classes in the ESRD group and focal class in the non-ESRD group. After 6 months of induction therapy, 90.0% of cases achieved complete or partial remission. The multivariate logistic regression model showed that baseline eGFR < 60 ml/min/1.73 m2 was an independent risk factor for progressing to ESRD (OR = 0.016, 95% CI = 0.001~0.412, P = 0.012).

Conclusions: AAV in children usually occurs in teenage girls, and the most commonly involved organ is the kidney, of which hematuria is the most common symptom, followed by proteinuria, abnormal renal function (eGFR < 90 ml/min/1.73 m2), etc. The primary type of AAV is MPA. Nearly 60% of patients progressed to ESRD with a median course of 3 months. Baseline eGFR < 60 ml/min/1.73 m2 is an independent risk factor for ESRD progression in AAV children.
Dexmedetomidine Protects Against Septic Liver Injury by Enhancing Autophagy Through Activation of the AMPK/SIRT1 Signaling Pathway
Authors: Yu Qing , Zou Liying , Yuan Xiu , Fang Fang , Xu Feng
Published: April 2021

Background: Liver injury is one of the serious complications of sepsis. Previous studies suggested that dexmedetomidine (DEX) could alleviate cecal ligation and puncture (CLP)-induced liver injury. However, it is unclear whether the protective effect of DEX on sepsis-induced liver injury is related to autophagy.

Methods: Mice (n = 105) were randomly divided into the following groups: (i) CON group (Sham); (ii) CLP group (CLP-induced liver injury + saline); (iii) CLP + DEX group (CLP-induced liver injury + DEX). Mouse models of sepsis-induced liver injury were established using CLP. DEX or normal saline was administered by intraperitoneal injection at 0, 2, and 4 h after CLP surgery. The mortality rate within 120 h was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and inflammatory cytokines were measured at 6, 12, and 24 h in each group. Hematoxylin and eosin staining assay was carried out to detect the morphological changes of mouse liver cells in each group. The levels of autophagy-associated proteins LC3II, Beclin-1, p62, and LAMP-2 were detected in three groups of mice using western blotting. The expression of LC3II was detected using immunofluorescence. Transmission electron microscopy (TEM) of liver tissue was used to observe autophagosomes and autophagosome–lysosomes. Lastly, the effect of DEX on the AMPK/SIRT1 pathway-associated protein levels were detected using western blotting. Meanwhile, we used L0-2 cells infected with mRFP-GFP-LC3 adenovirus to further analyze the role of SIRT1 in DEX-induced autophagy in liver injury model in vitro.

Results: DEX significantly improved the survival rate of septic mice at the early stage and ameliorated the pathology of sepsis-induced liver injury. The level of autophagy-associated proteins, phosphorylated (p)-AMPK/AMPK, and SIRT1 in the liver of CLP-induced sepsis mice peaked at 12 h post-CLP and decreased significantly at 24 h. In the CLP + DEX group, the levels of autophagy-associated proteins, p-AMPK/AMPK, and SIRT1 increased, whereas inflammatory cytokines decreased at 24 h. The autophagosome structure was clearly observed at different time points in the CLP + DEX group. In the in vitro hepatocyte injury model, the SIRT1 inhibitor significantly increased intracellular ROS levels and reversed the effect of DEX on autophagy flux.

Conclusion: We demonstrated a novel mechanism in which DEX protects against CLP-induced liver injury. DEX enhances autophagy, which alleviates the inflammatory responses in CLP-induced liver injury by regulating the SIRT1/AMPK pathway.
Computational and Phantom-Based Feasibility Study of 3D dcNCI With Ultra-Low-Field MRI
Authors: Höfner Nora , Storm Jan-Hendrik , Hömmen Peter , Cassarà Antonino Mario , Körber Rainer
Published: April 2021

The possibility to directly and non-invasively localize neuronal activities in the human brain, as for instance by performing neuronal current imaging (NCI) via magnetic resonance imaging (MRI), would be a breakthrough in neuroscience. In order to assess the feasibility of 3-dimensional (3D) NCI, comprehensive computational and physical phantom experiments using low-noise ultra-low-field (ULF) MRI technology were performed using two different source models within spherical phantoms. The source models, consisting of a single dipole and an extended dipole grid, were calibrated enabling the quantitative emulation of a long-lasting neuronal activity by the application of known current waveforms. The dcNCI experiments were also simulated by solving the Bloch equations using the calculated internal magnetic field distributions of the phantoms and idealized MRI fields. The simulations were then validated by physical phantom experiments using a moderate polarization field of 17 mT. A focal activity with an equivalent current dipole of about 150 nAm and a physiologically relevant depth of 35 mm could be resolved with an isotropic voxel size of 25 mm. The simulation tool enabled the optimization of the imaging parameters for sustained neuronal activities in order to predict maximum sensitivity.
The Maximal Lactate Steady State Workload Determines Individual Swimming Performance
Authors: Hering Gernot O. , Stepan Jens
Published: April 2021

The lactate threshold (LT) and the strongly related maximal lactate steady state workload (MLSSW) are critical for physical endurance capacity and therefore of major interest in numerous sports. However, their relevance to individual swimming performance is not well understood. We used a custom-made visual light pacer for real-time speed modulation during front crawl to determine the LT and MLSSW in a single-exercise test. When approaching the LT, we found that minute variations in swimming speed had considerable effects on blood lactate concentration ([La−]). The LT was characterized by a sudden increase in [La−], while the MLSSW occurred after a subsequent workload reduction, as indicated by a rapid cessation of blood lactate accumulation. Determination of the MLSSW by this so-called “individual lactate threshold” (ILT)-test was highly reproducible and valid in a constant speed test. Mean swimming speed in 800 and 1,500 m competition (S-Comp) was 3.4% above MLSSW level and S-Comp, and the difference between S-Comp and the MLSSW (Δ S-Comp/MLSSW) were higher for long-distance swimmers (800–1,500 m) than for short- and middle-distance swimmers (50–400 m). Moreover, Δ S-Comp/MLSSW varied significantly between subjects and had a strong influence on overall swimming performance. Our results demonstrate that the MLSSW determines individual swimming performance, reflects endurance capacity in the sub- to supra-threshold range, and is therefore appropriate to adjust training intensity in moderate to severe domains of exercise.
Breastfeeding Duration Is Associated With Domain-Specific Improvements in Cognitive Performance in 9–10-Year-Old Children
Authors: Lopez Daniel A. , Foxe John J. , Mao Yunjiao , Thompson Wesley K. , Martin Hayley J. , Freedman Edward G.
Published: April 2021

Significant immunological, physical and neurological benefits of breastfeeding in infancy are well-established, but to what extent these gains persist into later childhood remain uncertain. This study examines the association between breastfeeding duration and subsequent domain-specific cognitive performance in a diverse sample of 9–10-year-olds enrolled in the Adolescent Brain Cognitive Development (ABCD) Study®. The analyses included 9,116 children that attended baseline with their biological mother and had complete neurocognitive and breastfeeding data. Principal component analysis was conducted on data from an extensive battery of neurocognitive tests using varimax-rotation to extract a three-component model encompassing General Ability, Executive Functioning, and Memory. Propensity score weighting using generalized boosted modeling was applied to balance the distribution of observed covariates for children breastfed for 0, 1–6, 7–12, and more than 12 months. Propensity score-adjusted linear regression models revealed significant association between breastfeeding duration and performance on neurocognitive tests representing General Ability, but no evidence of a strong association with Executive Function or Memory. Benefits on General Ability ranged from a 0.109 (1–6 months) to 0.301 (>12 months) standardized beta coefficient difference compared to those not breastfed. Results indicate clear cognitive benefits of breastfeeding but that these do not generalize to all measured domains, with implications for public health policy as it pertains to nutrition during infancy.
Overview of Control Programs for Twenty-Four Infectious Cattle Diseases in Italy
Authors: Tamba Marco , Pallante Ivana , Petrini Stefano , Feliziani Francesco , Iscaro Carmen , Arrigoni Norma , Di Sabatino Daria , Barberio Antonio , Cibin Veronica , Santi Annalisa , Ianniello Marco , Ruocco Luigi , Pozzato Nicola
Published: April 2021

The cattle industry is a major driving force for the Italian agricultural sector totalling about 5. 6 million heads for dairy and meat production together. It is particularly developed in the northern part of the country, where 70% of the whole Italian cattle population is reared. The cattle industry development in the rest of the country is hampered by the hard orography of the territories and a variety of socioeconomic features leading to the persistence of the traditional rural farming systems. The differences in the farming systems (industrial vs. traditional) also affect the health status of the farms. Whereas, Enzootic Bovine Leukosis (EBL) is almost eradicated across the whole country, in Southern Italy where Bovine Tuberculosis and Brucellosis are still present and Bluetongue is endemic due to the presence of the competent vector (Culicoides imicola), less investments are aimed at controlling diseases with economic impact or at improving farm biosecurity. On the other hand, with the eradication of these diseases in most part of the country, the need has emerged for reducing the economic burden of non-regulated endemic disease and control programs (CPs) for specific diseases have been implemented at regional level, based on the needs of each territory (for instance common grazing or trading with neighboring countries). This explains the coexistence of different types of programs in force throughout the country. Nowadays in Italy, among cattle diseases with little or no EU regulations only three are regulated by a national CP: Enzootic Bovine Leukosis, Bluetongue and Paratuberculosis, while Bovine Genital Campylobacteriosis and Trichomonosis are nationwide controlled only in breeding bulls. For some of the remaining diseases (Infectious Bovine Rhinotracheitis, Bovine Viral Diarrhea, Streptococcus agalactiae) specific CPs have been implemented by the regional Authorities, but for most of them a CP does not exist at all. However, there is a growing awareness among farmers and public health authorities that animal diseases have a major impact not only on the farm profitability but also on animal welfare and on the use of antibiotics in livestock. It is probable that in the near future other CPs will be implemented.
Zebrafish as a Useful Model to Study Oxidative Stress-Linked Disorders: Focus on Flavonoids
Authors: Abbate Francesco , Maugeri Alessandro , Laurà Rosaria , Levanti Maria , Navarra Michele , Cirmi Santa , Germanà Antonino
Published: April 2021

The zebrafish is considered one of the most versatile experimental animal models. The transparency of the embryos, the small size, the rapid development and the homology with higher vertebrates have made the zebrafish a valuable model also for drug screening. Its use is closely related for the determination of bioactivity, toxicity and off-target side effects of novel drug candidates, which also allows a thorough evaluation of new targets; thus, it may represent a suitable model for drug screening and the optimization of novel candidates. Flavonoids are polyphenolic compounds widely present in fruits, vegetables and cereals. Polyphenols are important for both plants and humans, considering their involvement in defense mechanisms, particularly against oxidative stress. They protect plants from biotic and abiotic stressors and prevent or treat oxidative-based human diseases. For these reasons, polyphenols are used as nutraceuticals, functional foods and supplements by the pharmaceutical industry. Therefore, the most relevant findings on zebrafish as a useful experimental model to study oxidative stress-linked disorders, focusing on the biological activities of flavonoids, are here summarized and reviewed.
Nanotechnology for Natural Medicine: Formulation of Neem Oil Loaded Phospholipid Vesicles Modified with Argan Oil as a Strategy to Protect the Skin from Oxidative Stress and Promote Wound Healing
Authors: Manca Maria Letizia , Manconi Maria , Meloni Maria Cristina , Marongiu Francesca , Allaw Mohamad , Usach Iris , Peris Josè Esteban , Escribano-Ferrer Elvira , Tuberoso Carlo Ignazio Giovanni , Gutierrez Gemma , Matos Maria , Ghavam Mansureh
Published: April 2021

Neem oil, a plant-derived product rich in bioactives, has been incorporated in liposomes and hyalurosomes modified by adding argan oil and so called argan-liposomes and argan-hyalurosomes. Argan oil has also been added to the vesicles because of its regenerative and protective effects on skin. In the light of this, vesicles were specifically tailored to protect the skin from oxidative stress and treat lesions. Argan-liposomes were the smallest vesicles (~113 nm); the addition of sodium hyaluronate led to an increase in vesicle size (~143 nm) but it significantly improved vesicle stability during storage. In vitro studies confirmed the free radical scavenging activity of formulations, irrespective of their composition. Moreover, rheological investigation confirmed the higher viscosity of argan-hyalurosomes, which avoid formulation leakage after application. In vitro studies performed by using the most representative cells of the skin (i.e., keratinocytes and fibroblasts) underlined the ability of vesicles, especially argan-liposomes and argan-hyalurosomes, to counteract oxidative stress induced in these cells by using hydrogen peroxide and to improve the proliferation and migration of cells ensuring the more rapid and even complete closure of the wound (scratch assay).
Hydrogen Permeability of Epoxy Composites as Liners in Lined Rock Caverns—Experimental Study
Authors: Gajda Dawid , Lutyński Marcin
Published: April 2021

Energy production from renewable energy sources is not stable and any fluctuations in energy productions need to be eliminated with underground energy storage. Demand of underground gas storage will be increasing, due to the switching to green energy, while the availability of underground storage sites, especially salt caverns suitable for hydrogen storage, is limited. The purpose of this paper is to compare the hydrogen permeability of different materials and select a proper liner material for hydrogen storage in Liner Rock Caverns or post mine workings. A variety of materials, like concrete, polymer concrete, epoxy resin, salt rock, and mudstone, were tested for gas permeability/hydrogen diffusion, using the combined Steady-State Flow/Carrier Gas methods. Results are shown in different units, providing the opportunity to compare the results with literature data. The permeability value of investigated epoxy resin is comparable to the salt rock (after creep process), which makes the epoxy resin a promising sealing liner for hydrogen and potential substitution of stainless-steel in Lined Rock Cavern (LRC) gas storage.
Fractal-Stereometric Correlation of Nanoscale Spatial Patterns of GdMnO3 Thin Films Deposited by Spin Coating
Authors: Romaguera-Barcelay Yonny , Ţălu Ştefan , Matos Robert Saraiva , Oliveira Rosane Maria Pessoa Betânio , Moreira Joaquim Agostinho , de Cruz Javier Perez , da Fonseca Filho Henrique Duarte
Published: April 2021

Multiferroic systems are of great interest for technological applications. To improve the fabrication of thin films, stereometric and fractal analysis of surface morphology have been extensively performed to understand the influence of physical parameters on the quality of spatial patterns. In this work, GaMnO3 was synthesized and thin films were deposited on Pt(111)/TiO2/SiO2/Si substrates using a spin coating apparatus to study the correlation between their stereometric and fractal parameters. All films were studied by X-ray diffraction (XRD), where the structure and microstructure of the film sintered at 850 °C was investigated by Rietveld refinement. Topographic maps of the films were obtained using an atomic force microscope (AFM) in tapping mode. The results show that the film sintered at 850 °C exhibited a clear formation of a GdMnO3 orthorhombic structure with crystallite size of ~14 nm and a microstrain higher than other values reported in the literature. Its surface morphology presented a rougher topography, which was confirmed by the height parameters. Topographic differences due to different asymmetries and shapes of the height distributions between the films were observed. Specific stereometric parameters also showed differences in the morphology and microtexture of the films. Qualitative rendering obtained by commercial image processing software revealed substantial differences between the microtextures of the films. Fractal and advanced fractal parameters showed that the film sintered at 850 °C had greater spatial complexity, which was due to their higher topographic roughness, lower surface percolation and greater topographic uniformity, being dominated by low dominant special frequencies. Our combination of stereometric and fractal measurements can be useful to improve the fabrication process by optimizing spatial patterns as a function of the sintering temperature of the film.
Torque Prediction Model of a CI Engine for Agricultural Purposes Based on Exhaust Gas Temperatures and CFD-FVM Methodologies Validated with Experimental Tests
Authors: Bietresato Marco , Selmo Francesco , Renzi Massimiliano , Mazzetto Fabrizio
Published: April 2021

A truly universal system to optimize consumptions, monitor operation and predict maintenance interventions for internal combustion engines must be independent of onboard systems, if present. One of the least invasive methods of detecting engine performance involves the measurement of the exhaust gas temperature (EGT), which can be related to the instant torque through thermodynamic relations. The practical implementation of such a system requires great care since its torque-predictive capabilities are strongly influenced by the position chosen for the temperature-detection point(s) along the exhaust line, specific for each engine, the type of installation for the thermocouples, and the thermal characteristics of the interposed materials. After performing some preliminary tests at the dynamometric brake on a compression-ignition engine for agricultural purposes equipped with three thermocouples at different points in the exhaust duct, a novel procedure was developed to: (1) tune a CFD-FVM-model of the exhaust pipe and determine many unknown thermodynamic parameters concerning the engine (including the real EGT at the exhaust valve outlet in some engine operative conditions), (2) use the CFD-FVM results to considerably increase the predictive capability of an indirect torque-detection strategy based on the EGT. The joint use of the CFD-FVM software, Response Surface Method, and specific optimization algorithms was fundamental to these aims and granted the experimenters a full mastery of systems’ non-linearity and a maximum relative error on the torque estimations of 2.9%.
Information, Thermodynamics and Life: A Narrative Review
Authors: Lambrou George I. , Zaravinos Apostolos , Ioannidou Penelope , Koutsouris Dimitrios
Published: April 2021

Information is probably one of the most difficult physical quantities to comprehend. This applies not only to the very definition of information, but also to the physical entity of information, meaning how can it be quantified and measured. In recent years, information theory and its function in systems has been an intense field of study, due to the large increase of available information technology, where the notion of bit dominated the information discipline. Information theory also expanded from the “simple” “bit” to the quantal “qubit”, which added more variables for consideration. One of the main applications of information theory could be considered the field of “autonomy”, which is the main characteristic of living organisms in nature since they all have self-sustainability, motion and self-protection. These traits, along with the ability to be aware of existence, make it difficult and complex to simulate in artificial constructs. There are many approaches to the concept of simulating autonomous behavior, yet there is no conclusive approach to a definite solution to this problem. Recent experimental results have shown that the interaction between machines and neural cells is possible and it consists of a significant tool for the study of complex systems. The present work tries to review the question on the interactions between information and life. It attempts to build a connection between information and thermodynamics in terms of energy consumption and work production, as well as present some possible applications of these physical quantities.
The Effect of Selected Herbal Extracts on Lactic Acid Bacteria Activity
Authors: Ziarno Małgorzata , Kozłowska Mariola , Ścibisz Iwona , Kowalczyk Mariusz , Pawelec Sylwia , Stochmal Anna , Szleszyński Bartłomiej
Published: April 2021

This study aimed to investigate the effect of plant extracts (valerian Valeriana officinalis L., sage Salvia officinalis L., chamomile Matricaria chamomilla L., cistus Cistus L., linden blossom Tilia L., ribwort plantain Plantago lanceolata L., marshmallow Althaea L.) on the activity and growth of lactic acid bacteria (LAB) during the fermentation and passage of milk through a digestive system model. The tested extracts were also characterized in terms of their content of polyphenolic compounds and antioxidant activity. It was observed that the addition of the tested herbal extracts did not inhibit the growth of LAB in fermented milk drinks, such as yogurts. However, they can gradually inhibit fermentation when added at concentrations above 2% by weight, and hence should be used in limited amounts. The microflora of yogurts containing the tested herbal extracts did not die during digestion in model digestive juices, and no stimulating effect of the added plant extracts was noted either. Nevertheless, due to the antioxidant properties, a slight addition of the herbal extracts containing polyphenols to different kinds of food products can increase the nutritional quality, thus making them functional foods.
Tight Junction Protein Claudin-12 Is Involved in Cell Migration during Metastasis
Authors: Kolchakova Desislava , Moten Dzhemal , Batsalova Tsvetelina , Dzhambazov Balik
Published: April 2021

Claudins are important components of the tight junctions determining barrier properties, cell polarity, and paracellular permeability. Although many functions of claudins in cancer cells have not been elucidated, recent studies have shown that claudins play an important role in cell migration and metastasis. Loss of epithelial/endothelial integrity, disruption of tight junctions, and increased paracellular leakage are often observed during metastasis. The aim of our study was to investigate the involvement of claudin-12 in the process of cell migration as well as to evaluate the possibility of using this protein as a specific target for the regulation of tumorigenesis. We have performed immunocytochemistry assays to detect the expression of claudin-12 in different epithelial/endothelial human cell lines, and selected three (A549, LS180, and HeLa) for further experiments. Using transwell chamber migration assays, we found that anti-claudin-12 antibodies inhibited both the migration and proliferation of claudin-12 expressing cells (A549 and LS180), inducing apoptosis, as well as the migration capacity of Jurkat cells through the monolayers formed from A549 or LS180 cells. In addition, co-cultures of Jurkat cells on monolayers from A549 or LS180 cells, in the presence of synthetic claudin-12 peptides representing the extracellular domains of the claudin-12 protein, also reduced the number of migrated Jurkat cells. Two of the tested peptides (p5 and p6) almost completely blocked the migration of Jurkat cells. All migrated Jurkat cells expressed LFA-1 and CD62L, but not CD44. Thus, claudin-12 is a suitable biomarker for tumor progression and metastasis and an attractive target for antitumor therapy. Anti-claudin-12 antibodies and competitive inhibitory peptides could be useful in the therapeutic approach applied to cancer metastasis in tissues expressing claudin-12.