bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose and Blood Pressure-Dependent Pathways–The Progression of Diabetic Kidney Disease
Authors: Patel Devang M. , Bose Madhura , Cooper Mark E.
Published: March 2020

The major clinical associations with the progression of diabetic kidney disease (DKD) are glycemic control and systemic hypertension. Recent studies have continued to emphasize vasoactive hormone pathways including aldosterone and endothelin which suggest a key role for vasoconstrictor pathways in promoting renal damage in diabetes. The role of glucose per se remains difficult to define in DKD but appears to involve key intermediates including reactive oxygen species (ROS) and dicarbonyls such as methylglyoxal which activate intracellular pathways to promote fibrosis and inflammation in the kidney. Recent studies have identified a novel molecular interaction between hemodynamic and metabolic pathways which could lead to new treatments for DKD. This should lead to a further improvement in the outlook of DKD building on positive results from RAAS blockade and more recently newer classes of glucose-lowering agents such as SGLT2 inhibitors and GLP1 receptor agonists.
Type 1 FSHD with 6–10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention
Authors: Salort-Campana Emmanuelle , Fatehi Farzad , Beloribi-Djefaflia Sadia , Roche Stéphane , Nguyen Karine , Bernard Rafaelle , Cintas Pascal , Solé Guilhem , Bouhour Françoise , Ollagnon Elisabeth , Sacconi Sabrina , Echaniz-Laguna Andoni , Kuntzer Thierry , Levy Nicolas , Magdinier Frédérique , Attarian Shahram
Published: March 2020

Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study compared (1) the phenotype and severity of FSHD1 between patients carrying 6–8 vs. 9–10 RUs, (2) the amount of methylation in different D4Z4 regions between patients with FSHD1 with different clinical severity scores (CSS). This cross-sectional multicenter study was conducted to measure functional scales and for genetic analysis. Patients were classified into two categories according to RUs: Group 1, 6–8; Group 2, 9–10. Methylation analysis was performed in 27 patients. A total of 99 carriers of a contracted D4Z4 array were examined. No significant correlations between RUs and CSS (r = 0.04, p = 0.73) and any of the clinical outcome scales were observed between the two groups. Hypomethylation was significantly more pronounced in patients with high CSS (>3.5) than those with low CSS (<1.5) (in DR1 and 5P), indicating that the extent of hypomethylation might modulate disease severity. In Group 1, the disease severity is not strongly correlated with the allele size and is mostly correlated with the methylation of D4Z4 regions.
Recombination Pattern Characterization via Simulation Using Different Maize Populations
Authors: Ren Wei , Gong Xiaoping , Li Kun , Zhang Hongwei , Chen Fanjun , Pan Qingchun
Published: March 2020

Efficient recombination is critical to both plant breeding and gene cloning. However, almost all traditional recombination studies and genetic improvements require the slow and labor-intensive population construction process, and little is known about the recombination characteristics of populations of different types, generations, and origins. Here, we provide a simple and efficient simulation method for population construction based on doubled haploid (DH) and intermated B73 × Mo17 maize (IBM) populations to predict the recombination pattern. We found that the chromosomes had 0, 1, 2, and 3 recombination events that occurred at rates of 0.16, 0.30, 0.23, and 0.15, respectively, in the DH and the recombination rate of each chromosome in the IBM population ranged from 0 to 12.1 cM per 125 kb. Based on the observed recombination parameters, we estimated the number of recombination events and constructed the linkage maps of the simulated DH and recombination inbred line (RIL) populations. These simulated populations exhibited similar recombination patterns compared with the real populations, suggesting the feasibility of this simulation approach. We then compared the recombination rates of the simulated populations of different types (DH induced or self-crossed), generations, and origins (using the 8, 16, and 32 multiparent advanced generation intercross (MAGIC) populations), and suggested a rapid and cost-effective population construction procedure for breeders and geneticists, while maintaining an optimal recombination rate. This study offers a convenient method for optimizing the population construction process and has broader implications for other crop species, thereby facilitating future population studies and genetic improvement strategies.
Functional Analysis of Rice Long-Chain Acyl-CoA Synthetase 9 (OsLACS9) in the Chloroplast Envelope Membrane
Authors: Kitajima-Koga Aya , Baslam Marouane , Hamada Yuuki , Ito Namiko , Taniuchi Tomoko , Takamatsu Takeshi , Oikawa Kazusato , Kaneko Kentaro , Mitsui Toshiaki
Published: March 2020

The long-chain acyl-CoA synthetases (LACSs) are involved in lipid synthesis, fatty acid catabolism, and the transport of fatty acids between subcellular compartments. These enzymes catalyze the critical reaction of fatty acyl chains to fatty acyl-CoAs for the triacylglycerol biosynthesis used as carbon and energy reserves. In Arabidopsis, LACSs are encoded by a family of nine genes, with LACS9 being the only member located in the chloroplast envelope membrane. However, the comprehensive role of LACS9 and its contribution to plant metabolism have not been explored thoroughly. In this study, we report on the identification and characterization of LACS9 mutants in rice plants. Our results indicate that the loss-of-function mutations in OsLACS9 affect the architecture of internodes resulting in dwarf plants with large starch granules in the chloroplast, showing the suppression of starch degradation. Moreover, the plastid localization of α-amylase I-1 (AmyI-1)—a key enzyme involved in starch breakdown in plastids—was suppressed in the lacs9 mutant line. Immunological and confocal laser scanning microscopy analyses showed that OsLACS9-GFP is located in the chloroplast envelope in green tissue. Microscopic analysis showed that OsLACS9s interact with each other in the plastid envelope membrane. Furthermore, OsLACS9 is also one of the proteins transported to plastids without a transit peptide or involvement of the Toc/Tic complex system. To identify the plastid-targeting signal of OsLACS9, the transient expression and localization of a series of N-terminal truncated OsLACS9-green fluorescent protein (GFP) fusion proteins were examined. Truncation analyses identified the N-terminal 30 amino acid residues to be required for OsLACS9 plastid localization. Overall, the data in this study provide an advanced understanding of the function of OsLACS9 and its role in starch degradation and plant growth.
Aromatase Inhibitors as Adjuvant Treatment for ER/PgR Positive Stage I Endometrial Carcinoma: A Retrospective Cohort Study
Authors: Paleari Laura , Rutigliani Mariangela , Siri Giacomo , Provinciali Nicoletta , Colombo Nicoletta , Decensi Andrea
Published: March 2020

Objective: Although endometrial cancer (EC) is a hormone dependent neoplasm, there are no recommendations for the determination of steroid hormone receptors in the tumor tissue and no hormone therapy has ever been assessed in the adjuvant setting. The purpose of this study was to explore the effect of adjuvant aromatase inhibitors (AIs) on progression-free survival (PFS) and overall survival (OS) in patients with early stage and steroid receptors-positive EC. Methods: We retrospectively analyzed clinical and pathological factors in 73 patients with high-risk (49.3%) or low-risk (50.7%) stage I (n = 71) or II (n = 2) endometrial cancer who received by their preference after counseling either no treatment (reference group) or AI. Prognostic factors were well balanced between groups. Expression of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 index was correlated with clinical outcomes. Results: Univariate and multivariate Cox proportional regression analyses, adjusted for age, grade, stage, depth of myometrial invasion, lymphovascular space invasion, BMI, ER, PgR and Ki-67 labeling index levels, showed that PFS and OS had a trend to be longer in patients receiving AI than in the reference group HR= 0.23 (95% CI; 0.04–1.27) for PFS and HR= 0.11 (95% CI; 0.01–1.36) for OS. Conclusion: Compared with no treatment, AI exhibited a trend toward a benefit on PFS and OS in patients with early stage hormone receptor-positive EC. Given the exploratory nature of our study, randomized clinical trials for ER/PgR positive EC patients are warranted to assess the clinical benefit of AI and the potential predictive role of steroid receptors and Ki-67.
MiRNAs in the Peri-Implantation Period: Contribution to Embryo–Maternal Communication in Pigs
Authors: Kaczmarek Monika M. , Najmula Joanna , Guzewska Maria M. , Przygrodzka Emilia
Published: March 2020

MicroRNAs (miRNAs) constitute a large family of noncoding RNAs, approximately 22 nucleotides long, which function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathophysiological processes in animals. To date, the regulatory roles of miRNAs in reproduction, such as fertilization, embryo development, implantation, and placenta formation, among others, have been demonstrated in numerous mammalian species, including domestic livestock such as pigs. Over the past years, it appeared that understanding the functions of miRNAs in mammalian reproduction can substantially improve our understanding of the biological challenges of successful reproductive performance. This review describes the current knowledge on miRNAs, specifically in relation to the peri-implantation period when the majority of embryonic mortality occurs in pigs. To present a broader picture of crucial peri-implantation events, we focus on the role of miRNA-processing machinery and miRNA–mRNA infarctions during the maternal recognition of pregnancy, leading to maintenance of the corpus luteum function and further embryo implantation. Furthermore, we summarize the current knowledge on cell-to-cell communication involving extracellular vesicles at the embryo–maternal interface in pigs. Finally, we discuss the potential of circulating miRNAs to serve as indicators of ongoing embryo–maternal crosstalk.
Fatty Acid Binding Protein 3 Enhances the Spreading and Toxicity of α-Synuclein in Mouse Brain
Authors: Yabuki Yasushi , Matsuo Kazuya , Kawahata Ichiro , Fukui Naoya , Mizobata Tomohiro , Kawata Yasushi , Owada Yuji , Shioda Norifumi , Fukunaga Kohji
Published: March 2020

Oligomerization and/or aggregation of α-synuclein (α-Syn) triggers α-synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies. It is known that α-Syn can spread in the brain like prions; however, the mechanism remains unclear. We demonstrated that fatty acid binding protein 3 (FABP3) promotes propagation of α-Syn in mouse brain. Animals were injected with mouse or human α-Syn pre-formed fibrils (PFF) into the bilateral substantia nigra pars compacta (SNpc). Two weeks after injection of mouse α-Syn PFF, wild-type (WT) mice exhibited motor and cognitive deficits, whereas FABP3 knock-out (Fabp3−/−) mice did not. The number of phosphorylated α-Syn (Ser-129)-positive cells was significantly decreased in Fabp3−/− mouse brain compared to that in WT mice. The SNpc was unilaterally infected with AAV-GFP/FABP3 in Fabp3−/− mice to confirm the involvement of FABP3 in the development of α-Syn PFF toxicity. The number of tyrosine hydroxylase (TH)- and phosphorylated α-Syn (Ser-129)-positive cells following α-Syn PFF injection significantly decreased in Fabp3−/− mice and markedly increased by AAV-GFP/FABP3 infection. Finally, we confirmed that the novel FABP3 inhibitor MF1 significantly antagonized motor and cognitive impairments by preventing α-Syn spreading following α-Syn PFF injection. Overall, FABP3 enhances α-Syn spreading in the brain following α-Syn PFF injection, and the FABP3 ligand MF1 represents an attractive therapeutic candidate for α-synucleinopathy.
Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea
Authors: Sanz-Rubio David , Sanz Arianne , Varona Luis , Bolea Rosa , Forner Marta , Gil Ana V. , Cubero Pablo , Marin-Oto Marta , Martin-Burriel Inmaculada , Marin Jose M.
Published: March 2020

Background: Epigenetic changes in obstructive sleep apnea (OSA) have been proposed as a mechanism for end-organ vulnerability. In children with OSA, Forkhead Box P3 (FOXP3) DNA methylation were associated with inflammatory biomarkers; however, the methylation pattern and its effect in the expression of this gene have not been tested in adults with OSA. Methods: Plasma samples from subjects without comorbid conditions other than OSA were analyzed (the Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study: NCT02131610). In 16 patients with severe OSA (Apnea-Hypopnea Index—AHI- > 30 events/h) and seven matched controls (AHI < 5), methylation of FOXP3 gen was evaluated by PCR of the promoter and by pyrosequencing of the intron 1 Treg-specific demethylated region (TSDR). In another 74 patients with OSA (AHI > 10) and 31 controls, we quantified FOXP3 protein expression by ELISA and gene expression by quantitative real-time PCR. C-reactive protein (CRP) and plasma Treg cells were also evaluated. Results: Neither the levels of the promoter nor the TSDR demethylated region were different between controls and patients with OSA, whether they were grouped by normal or high CRP. FOXP3 protein and mRNA expression did not differ between groups. Conclusions: FOXP3 methylation or its expression is not altered in adults with OSA, whatever their inflammatory status.
Overcoming Shellfish Allergy: How Far Have We Come?
Authors: Wai Christine Y.Y. , Leung Nicki Y.H. , Chu Ka Hou , Leung Patrick S.C. , Leung Agnes S.Y. , Wong Gary W.K. , Leung Ting Fan
Published: March 2020

Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based skin prick test and specific IgE measurement while clinical management consists of food avoidance and as-needed use of adrenaline autoinjector should they develop severe allergic reactions. Such a standard of care is unsatisfactory to both patients and healthcare practitioners. There is a pressing need to introduce more specific diagnostic methods, as well as effective and safe therapies for patients with shellfish allergy. Knowledge gained on the identifications and defining the immuno-molecular features of different shellfish allergens over the past two decades have gradually translated into the design of new diagnostic and treatment options for shellfish allergy. In this review, we will discuss the epidemiology, the molecular identification of shellfish allergens, recent progress in various diagnostic methods, as well as current development in immunotherapeutic approaches including the use of unmodified allergens, hypoallergens, immunoregulatory peptides and DNA vaccines for the prevention and treatment of shellfish allergy. The prospect of a “cure “for shellfish allergy is within reach.
Synthesis, Anticancer Evaluation and Structure-Activity Analysis of Novel (E)- 5-(2-Arylvinyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamides
Authors: Szafrański Krzysztof , Sławiński Jarosław , Tomorowicz Łukasz , Kawiak Anna
Published: March 2020

To learn more about the structure–activity relationships of (E)-3-(5-styryl-1,3,4-oxadiazol-2-yl)benzenesulfonamide derivatives, which in our previous research displayed promising in vitro anticancer activity, we have synthesized a group of novel (E)-5-[(5-(2-arylvinyl)-1,3,4-oxadiazol-2-yl)]-4-chloro-2-R1-benzenesulfonamides 7–36 as well as (E)-4-[5-styryl1,3,4-oxadiazol-2-yl]benzenesulfonamides 47–50 and (E)-2-(2,4-dichlorophenyl)-5-(2-arylvinyl)-1,3,4-oxadiazols 51–55. All target derivatives were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. The obtained results were analyzed in order to explain the influence of a structure of the 2-aryl-vinyl substituent and benzenesulfonamide scaffold on the anti-tumor activity. Compound 31, bearing 5-nitrothiophene moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC50 values of 0.5, 4, and 4.5 µM, respectively. Analysis of structure-activity relationship showed significant differences in activity depending on the substituent in position 3 of the benzenesulfonamide ring and indicated as the optimal meta position of the sulfonamide moiety relative to the oxadizole ring. In the next stage, chemometric analysis was performed basing on a set of computed molecular descriptors. Hierarchical cluster analysis was used to examine the internal structure of the obtained data and the quantitative structure–activity relationship (QSAR) analysis with multiple linear regression (MLR) method allowed for finding statistically significant models for predicting activity towards all three cancer cell lines.
Enhancement of Neurite Outgrowth by Warming Biomaterial Ultrasound Treatment
Authors: Chen Jung-Chih , Su Chao-Ming , Chen Gin-Shin , Lai Chin-Chun , Chen Ching-Yun , Lin Kurt Ming-Chao , Lin Feng-Huei , Dong Guo-Chung
Published: March 2020

Ultrasound is a method for enhancing neurite outgrowth because of its thermal effect. In order to reach the working temperature to enhance neurite outgrowth, long-time treatment by ultrasound is necessary, while acknowledging that the treatment poses a high risk of damaging nerve cells. To overcome this problem, we developed a method that shortens the ultrasonic treatment time with a warming biomaterial. In this study, we used Fe3O4 nanoparticle-embedded polycaprolactone (PCL) as a sonosensitized biomaterial, which has an excellent heating rate due to its high acoustic attenuation. With this material, the ultrasonic treatment time for enhancing neurite outgrowth could be effectively shortened. Ultrasonic treatment could also increase neuronal function combined with the warming biomaterial, with more promoter neuronal function than only ultrasound. Moreover, the risk of overexposure can be avoided by the use of the warming biomaterial by reducing the ultrasonic treatment time, providing better effectiveness.
Analysis of the Activity and Expression of Cyclooxygenases COX1 and COX2 in THP-1 Monocytes and Macrophages Cultured with BiodentineTM Silicate Cement
Authors: Barczak Katarzyna , Palczewska-Komsa Mirona , Nowicka Alicja , Chlubek Dariusz , Buczkowska-Radlińska Jadwiga
Published: March 2020

BiodentineTM is a material based on hydrated calcium silicate with odontotropic properties. However, from the clinician’s perspective, every material used to fill a tooth—even those showing the optimal biochemical parameters—is in fact a foreign body introduced to the organism of the host. Therefore, apart from the chemical parameters of such materials, equally important is the so-called biocompatibility of such materials. The aim of the study was to investigate whether BiodentineTM, used in the regeneration of the pulp-dentine complex, may affect the expression of the enzymes cyclooxygenase 1 (COX1) and cyclooxygenase 2 (COX2) in THP-1 monocytes/macrophages and the amount of prostanoids synthesized by these enzymes-precursors of biologically active prostanoids such as prostaglandin E2 (PGE2) and thromboxane (TXB2) which are mediators of inflammation. An original aspect of this research is the use of the THP-1 monocyte/macrophage cell model and the use of biomaterial in direct contact with cells. In this way we tried to reflect the clinical conditions of regenerative pulp and periodontal tissue treatment using BiodentineTM. The results of our study showed a lack of macrophage activation (measured by flow cytometry) and a lack of stimulation of the expression of the studied cyclooxygenase enzymes (measured by Western blotting and fluorescent microscopy), as well as a lack of increase in the concentration (measured by ELISA method) of their inflammatory mediators (PGE2 and TXB2) in vitro incubated with BiodentineTM.
AMPK Regulates Developmental Plasticity through an Endogenous Small RNA Pathway in Caenorhabditis elegans
Authors: Wong Christopher , Roy Richard
Published: March 2020

Caenorhabditis elegans larvae can undergo developmental arrest upon entry into the dauer stage in response to suboptimal growth conditions. Dauer larvae can exit this stage in replete conditions with no reproductive consequence. During this diapause stage, the metabolic regulator AMP-activated protein kinase (AMPK) ensures that the germ line becomes quiescent to maintain germ cell integrity. Animals that lack all AMPK signalling undergo germline hyperplasia upon entering dauer, while those that recover from this stage become sterile. Neuronal AMPK expression in otherwise AMPK-deficient animals is sufficient for germline quiescence and germ cell integrity and its effects are likely mediated through an endogenous small RNA pathway. Upon impairing small RNA biosynthesis, the post-dauer fertility is restored in AMPK mutants. These data suggest that AMPK may function in neurons to relay a message through small RNAs to the germ cells to alter their quiescence in the dauer stage, thus challenging the permeability of the Weismann barrier.
Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy
Authors: Csobonyeiova Maria , Polak Stefan , Danisovic Lubos
Published: March 2020

Huntington’s disease (HD) is an inherited, autosomal dominant, degenerative disease characterized by involuntary movements, cognitive decline, and behavioral impairment ending in death. HD is caused by an expansion in the number of CAG repeats in the huntingtin gene on chromosome 4. To date, no effective therapy for preventing the onset or progression of the disease has been found, and many symptoms do not respond to pharmacologic treatment. However, recent results of pre-clinical trials suggest a beneficial effect of stem-cell-based therapy. Induced pluripotent stem cells (iPSCs) represent an unlimited cell source and are the most suitable among the various types of autologous stem cells due to their patient specificity and ability to differentiate into a variety of cell types both in vitro and in vivo. Furthermore, the cultivation of iPSC-derived neural cells offers the possibility of studying the etiopathology of neurodegenerative diseases, such as HD. Moreover, differentiated neural cells can organize into three-dimensional (3D) organoids, mimicking the complex architecture of the brain. In this article, we present a comprehensive review of recent HD models, the methods for differentiating HD–iPSCs into the desired neural cell types, and the progress in gene editing techniques leading toward stem-cell-based therapy.
Insights into Interactions of Flavanones with Target Human Respiratory Syncytial Virus M2-1 Protein from STD-NMR, Fluorescence Spectroscopy, and Computational Simulations
Authors: Piva Hêmily M. R. , Sá Jéssica M. , Miranda Artemiza S. , Tasic Ljubica , Fossey Marcelo A. , Souza Fátima P. , Caruso Ícaro P.
Published: March 2020

The human Respiratory Syncytial Virus (hRSV) is the most frequent agent of respiratory infections in infants and children with no currently approved vaccine. The M2-1 protein is an important transcriptional antitermination factor and a potential target for viral replication inhibitor development. Hesperetin (HST) and hesperidin (HSD) are flavonoids from the flavanone group, naturally found in citrus and have, as one of their properties, antiviral activity. The present study reports on the interactions between hRSV M2-1 and these flavanones using experimental techniques in association with computational tools. STD-NMR results showed that HST and HSD bind to M2-1 by positioning their aromatic rings into the target protein binding site. Fluorescence quenching measurements revealed that HST had an interaction affinity greater than HSD towards M2-1. The thermodynamic analysis suggested that hydrogen bonds and van der Waals interactions are important for the molecular stabilization of the complexes. Computational simulations corroborated with the experimental results and indicated that the possible interaction region for the flavonoids is the AMP-binding site in M2-1. Therefore, these results point that HST and HSD bind stably to a critical region in M2-1, which is vital for its biological function, and thus might play a possible role antiviral against hRSV.
Sustained Release of Decoy Wnt Receptor (sLRP6E1E2)-Expressing Adenovirus Using Gel-Encapsulation for Scar Remodeling in Pig Model
Authors: Yang Chae-Eun , Choi Sewoon , Lee Ju Hee , Kang Eun Hye , Ahn Hyo Min , Roh Tai Suk , Yun Chae-Ok , Lee Won Jai
Published: March 2020

An adenoviral vector (Ad) expressing a Wnt decoy receptor (sLRP6E1E2) is known to induce an anti-fibrotic effect by inhibiting Wnt signaling. We evaluated its effects in vivo using pig models and attempted to introduce an alginate gel-matrix system to prolong the effect of the Ad. Transduction efficiency as to the biological activity of Ad in different forms was evaluated. Then, 50 days after the formation of full-thickness skin defects on the backs of Yorkshire pigs, scars were treated with each form of Ad. Therapeutic efficacy and various factors influencing scar formation and collagen rearrangement were analyzed. Inflammatory cell infiltration within the scar tissues was also evaluated. Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus treatment improved scar quality in a pig model. Loading this construct in alginate gel allows sustained virus release into local tissues and prolongs Ad activity, thus maintaining its therapeutic effect longer in vivo.
Transcriptome Analysis in Renal Transplant Biopsies Not Fulfilling Rejection Criteria
Authors: Moreso Francesc , Sellarès Joana , Soler María José , Serón Daniel
Published: March 2020

The clinical significance of renal transplant biopsies displaying borderline changes suspicious for T-cell mediated rejection (TCMR) or interstitial fibrosis and tubular atrophy (IFTA) with interstitial inflammation has not been well defined. Molecular profiling to evaluate renal transplant biopsies using microarrays has been shown to be an objective measurement that adds precision to conventional histology. We review the contribution of transcriptomic analysis in surveillance and indication biopsies with borderline changes and IFTA associated with variable degrees of inflammation. Transcriptome analysis applied to biopsies with borderline changes allows to distinguish patients with rejection from those in whom mild inflammation mainly represents a response to injury. Biopsies with IFTA and inflammation occurring in unscarred tissue display a molecular pattern similar to TCMR while biopsies with IFTA and inflammation in scarred tissue, apart from T-cell activation, also express B cell, immunoglobulin and mast cell-related genes. Additionally, patients at risk for IFTA progression can be identified by genes mainly reflecting fibroblast dysregulation and immune activation. At present, it is not well established whether the expression of rejection gene transcripts in patients with fibrosis and inflammation is the consequence of an alloimmune response, tissue damage or a combination of both.
Characterization, Expression Pattern and Antiviral Activities of Mx Gene in Chinese Giant Salamander, Andrias davidianus
Authors: Liu Yanan , Li Yiqun , Zhou Yongze , Jiang Nan , Fan Yuding , Zeng Lingbing
Published: March 2020

Mx, Myxovirus resistance is an important interferon-stimulated protein that mediates antiviral responses. In this study, the expression and activities of Chinese giant salamander, Andrias davidianus Mx gene, AdMx, were investigated. The AdMx cDNA sequence contains an open reading frame (ORF) of 2112 nucleotides, encoding a putative protein of 703 aa. Meanwhile, AdMx possesses the conserved tripartite GTP binding motif and a dynamin family signature. qRT-PCR analysis revealed a broad expression of AdMx in vivo, with the highest expression levels in brain, kidney and spleen. The AdMx expression level in kidney, spleen and muscle significantly increased at 6 h after Chinese giant salamander iridovirus (GSIV) infection and peaked at 48 h, while that in muscle cell line (GSM) was not noticeably up-regulated until 72 h post infection. Additionally, a plasmid expressing AdMx was constructed and transfected into the Chinese giant salamander GSM cells. The virus load and gene copies in AdMx over-expressed cells were significantly reduced compared with those in the control cells. Moreover, compared to the control cells, a lower level of virus major capsid protein (MCP) synthesis in AdMx over-expressed cells was confirmed by Western blot. These results collectively suggest that Mx plays an important antiviral role in the immune responses against GSIV in Chinese giant salamander.
Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages
Authors: Metryka Emilia , Kupnicka Patrycja , Kapczuk Patrycja , Simińska Donata , Tarnowski Maciej , Goschorska Marta , Gutowska Izabela , Chlubek Dariusz , Baranowska-Bosiacka Irena
Published: March 2020

The aim of this study was to assess the influence of lead (Pb) at low concentrations (imitating Pb levels in human blood in chronic environmental exposure to this metal) on interleukin 1β (IL-1β) and interleukin 6 (IL-6) concentrations and the activity and expression of COX-1 and COX-2 in THP-1 macrophages. Macrophages were cultured in vitro in the presence of Pb at concentrations of: 1.25 μg/dL; 2.5 μg/dL; 5 μg/dL; 10 μg/dL. The first two concentrations of Pb were selected on the basis of our earlier study, which showed that Pb concentration in whole blood (PbB) of young women living in the northern regions of Poland and in the cord blood of their newborn children was within this range (a dose imitating environmental exposure). Concentrations of 5 μg/dL and 10 μg/dL correspond to the previously permissible PbB concentrations in children or pregnant women, and adults. Our results indicate that even low concentrations of Pb cause an increase in production of inflammatory interleukins (IL-1β and IL-6), increases expression of COX-1 and COX-2, and increases thromboxane B2 and prostaglandin E2 concentration in macrophages. This clearly suggests that the development of inflammation is associated not only with COX-2 but also with COX-1, which, until recently, had only been attributed constitutive expression. It can be concluded that environmental Pb concentrations are able to activate the monocytes/macrophages similarly to the manner observed during inflammation.
LncRNAs in HCV Infection and HCV-Related Liver Disease
Authors: Unfried Juan P. , Fortes P.
Published: March 2020

Long non-coding RNAs (lncRNAs) are transcripts with poor coding capacity that may interact with proteins, DNA, or other RNAs to perform structural and regulatory functions. The lncRNA transcriptome changes significantly in most diseases, including cancer and viral infections. In this review, we summarize the functional implications of lncRNA-deregulation after infection with hepatitis C virus (HCV). HCV leads to chronic infection in many patients that may progress to liver cirrhosis and hepatocellular carcinoma (HCC). Most lncRNAs deregulated in infected cells that have been described function to potentiate or block the antiviral response and, therefore, they have a great impact on HCV viral replication. In addition, several lncRNAs upregulated by the infection contribute to viral release. Finally, many lncRNAs have been described as deregulated in HCV-related HCC that function to enhance cell survival, proliferation, and tumor progression by different mechanisms. Interestingly, some HCV-related HCC lncRNAs can be detected in bodily fluids, and there is great hope that they could be used as biomarkers to predict cancer initiation, progression, tumor burden, response to treatment, resistance to therapy, or tumor recurrence. Finally, there is high confidence that lncRNAs could also be used to improve the suboptimal long-term outcomes of current HCC treatment options.
The Respiratory Phenotype of Pompe Disease Mouse Models
Authors: Fusco Anna F. , McCall Angela L. , Dhindsa Justin S. , Zheng Lucy , Bailey Aidan , Kahn Amanda F. , ElMallah Mai K.
Published: March 2020

Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA), a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease mouse models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts that characterize the respiratory phenotype of Pompe mouse models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease mouse models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, higher-order respiratory control centers, phrenic and hypoglossal motor nuclei, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.
Iron Metabolism in Cancer Progression
Authors: Forciniti Stefania , Greco Luana , Grizzi Fabio , Malesci Alberto , Laghi Luigi
Published: March 2020

Iron is indispensable for cell metabolism of both normal and cancer cells. In the latter, several disruptions of its metabolism occur at the steps of tumor initiation, progression and metastasis. Noticeably, cancer cells require a large amount of iron, and exhibit a strong dependence on it for their proliferation. Numerous iron metabolism-related proteins and signaling pathways are altered by iron in malignancies, displaying the pivotal role of iron in cancer. Iron homeostasis is regulated at several levels, from absorption by enterocytes to recycling by macrophages and storage in hepatocytes. Mutations in HFE gene alter iron homeostasis leading to hereditary hemochromatosis and to an increased cancer risk because the accumulation of iron induces oxidative DNA damage and free radical activity. Additionally, the iron capability to modulate immune responses is pivotal in cancer progression. Macrophages show an iron release phenotype and potentially deliver iron to cancer cells, resulting in tumor promotion. Overall, alterations in iron metabolism are among the metabolic and immunological hallmarks of cancer, and further studies are required to dissect how perturbations of this element relate to tumor development and progression.
In Which Patients with Sarcoidosis Is FDG PET/CT Indicated?
Authors: Keijsers Ruth G.M. , Grutters Jan C.
Published: March 2020

Sarcoidosis is a granulomatous disease of which the etiology remains unknown. The diverse clinical manifestations may challenge clinicians, particularly when conventional markers are inconclusive. From various studies, it has become clear that fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT aids in sarcoidosis care. In this article, an update on FDG PET/CT in sarcoidosis is provided. The use of FDG PET/CT in the diagnostic process of sarcoidosis is explained, especially in determining treatable inflammatory lesions in symptomatic patients with indecisive conventional tests. Furthermore, FDG PET/CT for evaluating the potential benefit of additional inflammatory treatment is described and its use in cardiac sarcoidosis is highlighted.
An Overview of the Expected Shoreline Impact of the Marine Energy Farms Operating in Different Coastal Environments
Authors: Raileanu Alina , Onea Florin , Rusu Eugen
Published: March 2020

The aim of the present work is to provide an overview of the possible implications involving the influence of a generic marine energy farm on the nearshore processes. Several case studies covering various European coastal areas are considered for illustration purposes. These include different nearshore areas, such as the Portuguese coast, Sardinia Island or a coastal sector close to the Danube Delta in the Black Sea. For the case studies related to the Portuguese coast, it is noted that a marine energy farm may reduce the velocity of the longshore currents, with a complete attenuation of the current velocity for some case studies in the coastal area from Leixoes region being observed. For the area located close to the Danube Delta, it is estimated that in the proposed configuration, a marine energy farm would provide an efficient protection against the wave action, but it will have a relatively negligible impact on the longshore currents. Summarizing the results, we can conclude that a marine energy farm seems to be beneficial for coastal protection, even in the case of the enclosed areas, such as the Mediterranean or Black seas, where the erosion generated by the wave action represents a real problem.
Variable-Speed Engines on Wind Farm Support Vessels
Authors: Holmefjord Kristian Eikeland , Husdal Lars , de Jongh Martijn , Torben Sverre
Published: March 2020

We examine the fuel savings of Edda Passat, a newly constructed wind farm support vessel that utilizes a common direct current (DC) grid. This enables its diesel engines to operate at variable speeds by using frequency converter technology. A detailed investigation of these benefits has been performed based on real-life measurements from three months of operations in the Race Bank wind farm off the east coast of England. The calculated fuel savings of Edda Passat achieved via its variable-speed engines are 21% lower compared to using a conventional alternating current (AC) grid with a fixed frequency. This paper will explain the technology, measurements, and results in detail.
Early Detection and Identification of Fatigue Damage in Thrust Ball Bearings by an Acoustic Emission Technique
Authors: Hase Alan
Published: March 2020

As rolling bearings are widely used in various machines, there is a strong need to detect any problems as early as possible. Although vibration analysis is commonly used in the diagnosis of rolling bearings, it is possible that the failure of such bearings might be detected earlier by an acoustic emission (AE) technique. Methods for detecting potential fatigue damage in a thrust ball bearing by AE signal analysis and by vibration analysis were compared. For the AE signal analysis, the maximum amplitude and the frequency spectrum were used to detect and identify fatigue damage in the bearing. Features of AE signals detected when a defect was artificially formed on the raceway surface of a bearing by using a Vickers hardness tester were also examined. The AE technique detected initial cracks due to fatigue damage earlier than the vibration technique. Additionally, AE signals were always detected during bearing fatigue tests, but the AE signals detected during the running-in process, crack initiation, crack propagation, and flaking all contained different frequency components. Furthermore, the correlation map between the frequency spectra of AE signals and deformation and fracture phenomena (friction and wear modes) was updated by adding the new findings of this study.
Influence of Cu Content on Structure and Magnetic Properties in Fe86-xCuxB14 Alloys
Authors: Warski Tymon , Wlodarczyk Patryk , Polak Marcin , Zackiewicz Przemyslaw , Radon Adrian , Wojcik Anna , Szlezynger Maciej , Kolano-Burian Aleksandra , Hawelek Lukasz
Published: March 2020

Influence of Cu content on thermodynamic parameters (configurational entropy, Gibbs free energy of mixing, Gibbs free energy of amorphous phase formation), crystallization kinetics, structure and magnetic properties of Fe86-xCuxB14 (x = 0, 0.4, 0.55, 0.7, 1) alloys is investigated. The chemical composition has been optimized using a thermodynamic approach to obtain a minimum of Gibbs free energy of amorphous phase formation (minimum at 0.55 at.% of Cu). By using differential scanning calorimetry method the crystallization kinetics of amorphous melt-spun ribbons was analyzed. It was found that the average activation energy of α-Fe phase crystallization is in the range from 201.8 to 228.74 kJ/mol for studied samples. In order to obtain the lowest power core loss values, the isothermal annealing process was optimized in the temperature range from 260 °C to 400 °C. Materials annealed at optimal temperature had power core losses at 1 T/50 Hz—0.13–0.25 W/kg, magnetic saturation—1.47–1.6 T and coercivity—9.71–13.1 A/m. These samples were characterized by the amorphous structure with small amount of α-Fe nanocrystallites. The studies of complex permeability allowed to determine a minimum of both permeability values at 0.55 at.% of Cu. At the end of this work a correlation between thermodynamic parameters and kinetics, structure and magnetic properties were described.
Ridge Augmentation Using β-Tricalcium Phosphate and Biphasic Calcium Phosphate Sphere with Collagen Membrane in Chronic Pathologic Extraction Sockets with Dehiscence Defect: A Pilot Study in Beagle Dogs
Authors: Lee Jungwon , Lee Yong-Moo , Lim Young-Jun , Kim Bongju
Published: March 2020

This study was conducted to comparatively examine spontaneous healing versus ridge augmentation, in surgically-created dehiscence defects, associated with chronic pathology in dogs. Mandibular second, third and fourth premolars (P2, P3 and P4) were hemi-sectioned, and a dehiscence defect was created at the mesial root, while a groove was made on the buccal area from the top of the teeth to the bottom of the defect, exposing the dental pulp. The mesial roots of P2, P3 and P4 were extracted 1 month after the induction of the dehiscence defect with chronic pathology. Three teeth were randomly allocated to these experimental groups: (i) spontaneous healing without any bone graft (Control group: C); (ii) ridge augmentation with β-tricalcium phosphate (β-TCP) granules (Test 1 group: T1); and (iii) ridge augmentation with 60% hydroxyapatite (HA) and 40% β-TCP microspheres (Test 2 group: T2). Postmortem histopathologic examination showed significant between-group differences in C and T1 and C and T2 in bone volume/tissue volume in qualitative micro-computed tomography (CT) analysis, as well as significant intergroup differences in the coronal area at 4 and 12 weeks. The composition of connective tissue and mineralized bone in C and T1 were higher than in T2 at 4 weeks of healing, whereas the composition of mineralized bone was higher in T2 than in T1 at 12 weeks of healing. Biphasic calcium phosphate, composed of 60% HA and 40% β-TCP microsphere (i) potentially prevented marked osteoclastic resorption and (ii) promoted ridge preservation in the extraction socket with the dehiscence defect and chronic pathology.
Editorial-Special Issue “Macromolecular Self-Assembly Materials: From Modeling to Advanced Applications”
Authors: Magazù Salvatore , Lombardo Domenico
Published: March 2020

Materials self-assembly represents a key strategy for the design and fabrication of nanostructured systems and has become a fundamental approach for the construction of advanced nanomaterials [...]
Requirements and Variability Affecting the Durability of Bonded Joints
Authors: Jones Rhys , Peng Daren , Michopoulos John G. , Kinloch Anthony J.
Published: March 2020

This paper firstly reveals that when assessing if a bonded joint meets the certification requirements inherent in MIL-STD-1530D and the US Joint Services Standard JSSG2006 it is necessary to ensure that: (a) There is no yielding at all in the adhesive layer at 115% of design limit load (DLL), and (b) that the joint must be able to withstand design ultimate load (DUL). Secondly, it is revealed that fatigue crack growth in both nano-reinforced epoxies, and structural adhesives can be captured using the Hartman–Schijve crack growth equation, and that the scatter in crack growth in adhesives can be modelled by allowing for variability in the fatigue threshold. Thirdly, a methodology was established for estimating a valid upper-bound curve, for cohesive failure in the adhesive, which encompasses all the experimental data and provides a conservative fatigue crack growth curve. Finally, it is shown that this upper-bound curve can be used to (a) compare and characterise structural adhesives, (b) determine/assess a “no growth” design (if required), (c) assess if a disbond in an in-service aircraft will grow and (d) to design and life in-service adhesively-bonded joints in accordance with the slow-growth approach contained in the United States Air Force (USAF) certification standard MIL-STD-1530D.
Growth and Characterization of Cu2Zn1−xFexSnS4 Thin Films for Photovoltaic Applications
Authors: Trifiletti Vanira , Tseberlidis Giorgio , Colombo Marco , Spinardi Alberto , Luong Sally , Danilson Mati , Grossberg Maarja , Fenwick Oliver , Binetti Simona
Published: March 2020

Photovoltaics is a promising technology to produce sustainable energy, thanks to the high amount of energy emitted by the sun. One way of having solar cells with low production costs is to apply thin-film technology and with earth-abundant raw materials. A keen interest is arising in kesterite compounds, which are chalcogenides composed of abundant and non-toxic elements. They have already achieved excellent performance at the laboratory level. Here, we report the synthesis and characterization of mixed chalcogenides based on copper, zinc, iron, and tin. Solutions have been studied with different zinc and iron ratios. The distortion of the elementary cell of kesterite increases with the addition of iron until a phase transition to stannite occurs. The process of synthesis and deposition proposed herein is cheap and straightforward, based on the sol-gel technique. These thin films are particularly attractive for use in cheap and easily processable solar cells. The synthesized layers have been characterized by X-ray diffraction, UV-Vis absorption, and Raman, X-ray photoelectron, and energy-dispersive X-ray spectroscopy measurements.
Using Different Qualitative Scales in a Multi-Criteria Decision-Making Procedure
Authors: González del Pozo Raquel , Dias Luis C. , García-Lapresta José Luis
Published: March 2020

Many decision problems manage linguistic information assessed through several ordered qualitative scales. In these contexts, the main problem arising is how to aggregate this qualitative information. In this paper, we present a multi-criteria decision-making procedure that ranks a set of alternatives assessed by means of a specific ordered qualitative scale for each criterion. These ordered qualitative scales can be non-uniform and be formed by a different number of linguistic terms. The proposed procedure follows an ordinal approach by means of the notion of ordinal proximity measure that assigns an ordinal degree of proximity to each pair of linguistic terms of the qualitative scales. To manage the ordinal degree of proximity from different ordered qualitative scales, we provide a homogenization process. We also introduce a stochastic approach to assess the robustness of the conclusions.