bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion of Isocyanide to Amine in The Presence of Water and Hg(II) Ions: Kinetics and Mechanism as Detected by Fluorescence Spectroscopy and Mass Spectrometry
Authors: Adamoczky Anita , Nagy Lajos , Nagy Miklós , Zsuga Miklós , Kéki Sándor
Published: August 2020

Aromatic isocyanides including isocyanonaphthalene derivatives have been proven to be very effective fluorescent sensors for the quantification of Hg(II) ions in water. Thus, the reaction of 1,5-isocyanoaminonaphthalene (1,5-ICAN), which is one of the most important members of this family, with water and HgCl2 as the oxidation agents, was studied by fluorescence spectroscopy and mass spectrometry in order to get deeper insight into the kinetics and mechanistic details of this complex reaction. The reactions of 1,5-ICAN with water and HgCl2 were performed in various water/co-solvent mixtures of different compositions. The co-solvents used in this study were both aprotic solvents including tetrahydrofuran, acetonitrile and N,N-dimethylformamide and protic solvents, such as ethanol and 2-propanol. It was found that in aprotic solvents the conversion of the isocyano group to amino moiety takes place, while in protic solvents the corresponding carbamate (urethane) group is formed in addition to the amino moiety. The variation of the resulting fluorescence intensities versus time curves were described using an irreversible, consecutive reaction model, in which the formation of isocyanate and carbamic acid intermediates, as well as diamino and carbamate (in the case of protic solvents) products were assumed. The formation of these intermediates and products was unambiguously confirmed by mass spectrometric measurements. Furthermore, by fitting the model to the experimental fluorescence versus time curves, the corresponding rate coefficients were determined. It was observed that the overall rate of transformation of the isocyano group to amino moiety increased with the water concentration and the polarity of the co-solvent. It was also supported that formation of diamino and carbamate derivatives in protic solvents takes place simultaneously and that the ratio of the amino to the carbamate function increased with the increasing water concentration. In addition, with an extension, the model presented herein proved to be capable of describing the kinetics of the transformation of 1,5-diisocyanonaphthalene (1,5-DIN) into 1,5-diaminonaphthalene (1,5-DAN) in the mixtures of water/aprotic solvents.
Uromodulin and microRNAs in Kidney Transplantation—Association with Kidney Graft Function
Authors: Borštnar Špela , Večerić-Haler Željka , Boštjančič Emanuela , Pipan Tkalec Živa , Kovač Damjan , Lindič Jelka , Kojc Nika
Published: August 2020

Uromodulin and microRNAs (miRNAs) have recently been investigated as potential biomarkers for kidney graft associated pathology and outcome, with a special focus on biomarkers indicating specific disease processes and kidney graft survival. The study’s aim was to determine whether expression of serum uromodulin concentration and selected miRNAs might be related to renal function in kidney transplant recipients (KTRs). The uromodulin concentration and expression of six selected miRNAs (miR-29c, miR-126, miR-146a, miR-150, miR-155, and miR-223) were determined in the serum of 100 KTRs with stable graft function and chronic kidney disease of all five stages. Kidney graft function was estimated with routine parameters (creatinine, urea, cystatin C, and Chronic Kidney Disease Epidemiology Collaboration study equations) and precisely measured using chromium-51 labelled ethylenediaminetetraacetic-acid clearance. The selected miRNAs were shown to be independent of kidney graft function, indicating their potential as biomarkers of associated kidney graft disease processes. In contrast, the serum uromodulin level depended entirely on kidney graft function and thus reflected functioning tubules rather than any specific kidney graft injury. However, decreased concentrations of serum uromodulin can be observed in the early course of tubulointerstitial injury, thereby suggesting its useful role as an accurate, noninvasive biomarker of early (subclinical) kidney graft injury.
Transcriptome Analysis and Expression of Selected Cationic Amino Acid Transporters in the Liver of Broiler Chicken Fed Diets with Varying Concentrations of Lysine
Authors: Khwatenge Collins N. , Kimathi Boniface M. , Nahashon Samuel N.
Published: August 2020

Amino acids are known to play a key role in gene expression regulation. Amino acid signaling is mediated via two pathways: the mammalian target of rapamycin complex 1 (mTORC1) and the amino acid responsive (AAR) pathways. Cationic amino acid transporters (CATs) are crucial in these pathways due to their sensing, signaling and transport functions. The availability of certain amino acids plays a key role in the intake of other amino acids, hence affecting growth in young birds. However, the specific mechanism for regulating lysine transport for growth is not clear. In this study, we analyze the transcriptome profiles and mRNA expression of selected cationic amino acid transporters in the livers of broilers fed low and high lysine diets. Birds consumed high-lysine (1.42% lysine) or low-lysine (0.85% lysine) diets while the control group consumed 1.14% lysine diet. These concentrations of lysine represent 125% (high lysine), 75% (low lysine) and 100% (control), respectively, of the National Research Council’s (NRC) recommendation for broiler chickens. After comparing the two groups, 210 differentially expressed genes (DEGs) were identified (fold change >1 and false discovery rate (FDR) <0.05). When comparing the high lysine and the low lysine treatments, there were 67 upregulated genes and 143 downregulated genes among these DEGs. Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) enrichment analysis show that cellular growth, lipid metabolism and lysine metabolism pathways were among the significantly enriched pathways. This study contributes to a better understanding of the potential molecular mechanisms underlying the correlation between lysine intake, body weight gain (BWG) and feed intake (FI) in broiler chickens. Moreover, the DEGs obtained in this study may be used as potential candidate genes for further investigation of broiler growth customized responses to individualized nutrients such as amino acids.
IDH2 Deficiency Is Critical in Myogenesis and Fatty Acid Metabolism in Mice Skeletal Muscle
Authors: Pan Jeong Hoon , Tang Jingsi , Kim Young Jun , Lee Jin Hyup , Shin Eui-Cheol , Zhao Jiangchao , Kim Kee-Hong , Hwang Kyung A. , Huang Yan , Kim Jae Kyeom
Published: August 2020

Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate with concurrent reduction of NADP+ to NADPH. However, it is not fully understood how IDH2 is intertwined with muscle development and fatty acid metabolism. Here, we examined the effects of IDH2 knockout (KO) on skeletal muscle energy homeostasis. Calf skeletal muscle samples from 10-week-old male IDH2 KO and wild-type (WT; C57BL/6N) mice were harvested, and the ratio of skeletal muscle weight to body and the ratio of mitochondrial to nucleic DNA were measured. In addition, genes involved in myogenesis, mitochondria biogenesis, adipogenesis, and thermogenesis were compared. Results showed that the ratio of skeletal muscle weight to body weight was lower in IDH2 KO mice than those in WT mice. Of note, a noticeable shift in fiber size distribution was found in IDH2 KO mice. Additionally, there was a trend of a decrease in mitochondrial content in IDH2 KO mice than in WT mice (p = 0.09). Further, mRNA expressions for myogenesis and mitochondrial biogenesis were either decreased or showed a trend of decrease in IDH2 KO mice. Moreover, genes for adipogenesis pathway (Pparg, Znf423, and Fat1) were downregulated in IDH2 KO mice. Interestingly, mRNA and protein expression of uncoupling protein 1 (UCP1), a hallmark of thermogenesis, were remarkably increased in IDH2 KO mice. In line with the UCP1 expression, IDH2 KO mice showed higher rectal temperature than WT mice under cold stress. Taken together, IDH2 deficiency may affect myogenesis, possibly due to impairments of muscle generation and abnormal fatty acid oxidation as well as thermogenesis in muscle via upregulation of UCP1.
Inclusion Formation and Toxicity of the ALS Protein RGNEF and Its Association with the Microtubule Network
Authors: Di Gregorio Sonja E. , Volkening Kathryn , Strong Michael J. , Duennwald Martin L.
Published: August 2020

The Rho guanine nucleotide exchange factor (RGNEF) protein encoded by the ARHGEF28 gene has been implicated in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Biochemical and pathological studies have shown that RGNEF is a component of the hallmark neuronal cytoplasmic inclusions in ALS-affected neurons. Additionally, a heterozygous mutation in ARHGEF28 has been identified in a number of familial ALS (fALS) cases that may give rise to one of two truncated variants of the protein. Little is known about the normal biological function of RGNEF or how it contributes to ALS pathogenesis. To further explore RGNEF biology we have established and characterized a yeast model and characterized RGNEF expression in several mammalian cell lines. We demonstrate that RGNEF is toxic when overexpressed and forms inclusions. We also found that the fALS-associated mutation in ARGHEF28 gives rise to an inclusion-forming and toxic protein. Additionally, through unbiased screening using the split-ubiquitin system, we have identified RGNEF-interacting proteins, including two ALS-associated proteins. Functional characterization of other RGNEF interactors identified in our screen suggest that RGNEF functions as a microtubule regulator. Our findings indicate that RGNEF misfolding and toxicity may cause impairment of the microtubule network and contribute to ALS pathogenesis.
Ostm1 from Mouse to Human: Insights into Osteoclast Maturation
Authors: Vacher Jean , Bruccoleri Michael , Pata Monica
Published: August 2020

The maintenance of bone mass is a dynamic process that requires a strict balance between bone formation and resorption. Bone formation is controlled by osteoblasts, while osteoclasts are responsible for resorption of the bone matrix. The opposite functions of these cell types have to be tightly regulated not only during normal bone development, but also during adult life, to maintain serum calcium homeostasis and sustain bone integrity to prevent bone fractures. Disruption of the control of bone synthesis or resorption can lead to an over accumulation of bone tissue in osteopetrosis or conversely to a net depletion of the bone mass in osteoporosis. Moreover, high levels of bone resorption with focal bone formation can cause Paget’s disease. Here, we summarize the steps toward isolation and characterization of the osteopetrosis associated trans-membrane protein 1 (Ostm1) gene and protein, essential for proper osteoclast maturation, and responsible when mutated for the most severe form of osteopetrosis in mice and humans.
l-Carnitine Supplementation during In Vitro Maturation and In Vitro Culture Does not Affect the Survival Rates after Vitrification and Warming but Alters Inf-T and ptgs2 Gene Expression
Authors: Carrillo-González Diego F. , Rodríguez-Osorio Nélida , Long Charles R. , Vásquez-Araque Neil A. , Maldonado-Estrada Juan G.
Published: August 2020

l-carnitine is a potent antioxidant used for in vitro culture systems. Controversial results have been reported using l-carnitine in culture medium at different stages of in vitro bovine embryo production. Cumulus-oocyte complexes (n = 843) were in vitro-fertilized and cultured and added (treatment group) or not added (control group) with l-carnitine. At day three of culture, each group was subdivided into two subgroups receiving no l-carnitine (group 1), 3.8 mM l-carnitine added during in vitro maturation (group 2), 1.5 mM added during the in vitro culture (group 3), and 3.8 mM and 1.5 mM added during the maturation and culture, respectively (group 4). At day 8, blastocyst embryos were examined for mitochondrial activity, the presence of lipid droplets, total cell number, gene expression, and cryotolerance by vitrification. The data were analyzed with a one-way analysis of variance. l-carnitine added in the late in vitro culture significantly reduced mitochondrial activity and lipid content, and upregulated ifn-τ and ptgs2 gene expression compared to controls (p < 0.05). l-carnitine supplementation did not significantly affect the embryo rate production or survival rate after vitrification and warming (p > 0.05). l-carnitine supplementation significantly improved embryo potential to develop viable pregnancies in agreement with a study reporting improved pregnancy rates.
In Vitro Determination of the Immunogenic Impact of Nanomaterials on Primary Peripheral Blood Mononuclear Cells
Authors: David Christopher A. W. , Barrow Michael , Murray Patricia , Rosseinsky Matthew J. , Owen Andrew , Liptrott Neill J.
Published: August 2020

Investigation of the potential for nanomaterials to generate immunogenic effects is a key aspect of a robust preclinical evaluation. In combination with physicochemical characterization, such assessments also provide context for how material attributes influence biological outcomes. Furthermore, appropriate models for these assessments allow accurate in vitro to in vivo extrapolation, which is vital for the mechanistic understanding of nanomaterial action. Here we have assessed the immunogenic impact of a small panel of commercially available and in-house prepared nanomaterials on primary human peripheral blood mononuclear cells (PBMCs). A diethylaminoethyl-dextran (DEAE-dex) functionalized superparamagnetic iron oxide nanoparticle (SPION) generated detectable quantities of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and IL-10, the only tested material to do so. The human leukemia monocytic cell line THP-1 was used to assess the potential for the nanomaterial panel to affect cellular oxidation-reduction (REDOX) via measurement of reactive oxygen species and reduced glutathione. Negatively charged sulfonate-functionalized polystyrene nanoparticles demonstrated a size-related trend for the inhibition of caspase-1, which was not observed for amine-functionalized polystyrene of similar sizes. Silica nanoparticles (310 nm) resulted in a 93% increase in proliferation compared to the untreated control (p < 0.01). No other nanomaterial treatments resulted in significant change from that of unstimulated PBMCs. Responses to the nanomaterials in the assays described demonstrate the utility of primary cells as ex vivo models for nanomaterial biological impact.
Hypoxia and HIF Signaling: One Axis with Divergent Effects
Authors: Corrado Chiara , Fontana Simona
Published: August 2020

The correct concentration of oxygen in all tissues is a hallmark of cellular wellness, and the negative regulation of oxygen homeostasis is able to affect the cells and tissues of the whole organism. The cellular response to hypoxia is characterized by the activation of multiple genes involved in many biological processes. Among them, hypoxia-inducible factor (HIF) represents the master regulator of the hypoxia response. The active heterodimeric complex HIF α/β, binding to hypoxia-responsive elements (HREs), determines the induction of at least 100 target genes to restore tissue homeostasis. A growing body of evidence demonstrates that hypoxia signaling can act by generating contrasting responses in cells and tissues. Here, this dual and controversial role of hypoxia and the HIF signaling pathway is discussed, with particular reference to the effects induced on the complex activities of the immune system and on mechanisms determining cell and tissue responses after an injury in both acute and chronic human diseases related to the heart, lung, liver, and kidney.
Age-Related Differences in the Time Course of Coagulation and Fibrinolytic Parameters in Patients with Traumatic Brain Injury
Authors: Nakae Ryuta , Fujiki Yu , Takayama Yasuhiro , Kanaya Takahiro , Igarashi Yutaka , Suzuki Go , Naoe Yasutaka , Yokobori Shoji
Published: August 2020

Coagulopathy and older age are common and well-recognized risk factors for poorer outcomes in traumatic brain injury (TBI) patients; however, the relationships between coagulopathy and age remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more pronounced in older patients and may be a factor in poorer outcomes. We retrospectively evaluated severe TBI cases in which fibrinogen and D-dimer were measured on arrival and 3–6 h after injury. Propensity score-matched analyses were performed to adjust baseline characteristics between older patients (the “elderly group,” aged ≥75 y) and younger patients (the “non-elderly group,” aged 16–74 y). A total of 1294 cases (elderly group: 395, non-elderly group: 899) were assessed, and propensity score matching created a matched cohort of 324 pairs. Fibrinogen on admission, the degree of reduction in fibrinogen between admission and 3–6 h post-injury, and D-dimer levels between admission and 3–6 h post-injury were significantly more abnormal in the elderly group than in the non-elderly group. On multivariate logistic regression analysis, independent risk factors for poor prognosis included low fibrinogen and high D-dimer levels on admission. Posttraumatic coagulation and fibrinolytic abnormalities are more severe in older patients, and fibrinogen and D-dimer abnormalities are negative predictive factors.
Development of CRISPR Interference (CRISPRi) Platform for Metabolic Engineering of Leuconostoc citreum and Its Application for Engineering Riboflavin Biosynthesis
Authors: Son Jaewoo , Jang Seung Hoon , Cha Ji Won , Jeong Ki Jun
Published: August 2020

Leuconostoccitreum, a hetero-fermentative type of lactic acid bacteria, is a crucial probiotic candidate because of its ability to promote human health. However, inefficient gene manipulation tools limit its utilization in bioindustries. We report, for the first time, the development of a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) interference (CRISPRi) system for engineering L. citreum. For reliable expression, the expression system of synthetic single guide RNA (sgRNA) and the deactivated Cas9 of Streptococcus pyogenes (SpdCas9) were constructed in a bicistronic design (BCD) platform using a high-copy-number plasmid. The expression of SpdCas9 and sgRNA was optimized by examining the combination of two synthetic promoters and Shine–Dalgarno sequences; the strong expression of sgRNA and the weak expression of SpdCas9 exhibited the most significant downregulation (20-fold decrease) of the target gene (sfGFP), without cell growth retardation caused by SpdCas9 overexpression. The feasibility of the optimized CRISPRi system was demonstrated by modulating the biosynthesis of riboflavin. Using the CRISPRi system, the expression of ribF and folE genes was downregulated (3.3-fold and 5.6-fold decreases, respectively), thereby improving riboflavin production. In addition, the co-expression of the rib operon was introduced and the production of riboflavin was further increased up to 1.7 mg/L, which was 1.53 times higher than that of the wild-type strain.
Aminopeptidases in Cardiovascular and Renal Function. Role as Predictive Renal Injury Biomarkers
Authors: Vargas Félix , Wangesteen Rosemary , Rodríguez-Gómez Isabel , García-Estañ Joaquín
Published: August 2020

Aminopeptidases (APs) are metalloenzymes that hydrolyze peptides and polypeptides by scission of the N-terminus amino acid and that also participate in the intracellular final digestion of proteins. APs play an important role in protein maturation, signal transduction, and cell-cycle control, among other processes. These enzymes are especially relevant in the control of cardiovascular and renal functions. APs participate in the regulation of the systemic and local renin–angiotensin system and also modulate the activity of neuropeptides, kinins, immunomodulatory peptides, and cytokines, even contributing to cholesterol uptake and angiogenesis. This review focuses on the role of four key APs, aspartyl-, alanyl-, glutamyl-, and leucyl-cystinyl-aminopeptidases, in the control of blood pressure (BP) and renal function and on their association with different cardiovascular and renal diseases. In this context, the effects of AP inhibitors are analyzed as therapeutic tools for BP control and renal diseases. Their role as urinary biomarkers of renal injury is also explored. The enzymatic activities of urinary APs, which act as hydrolyzing peptides on the luminal surface of the renal tubule, have emerged as early predictive renal injury biomarkers in both acute and chronic renal nephropathies, including those induced by nephrotoxic agents, obesity, hypertension, or diabetes. Hence, the analysis of urinary AP appears to be a promising diagnostic and prognostic approach to renal disease in both research and clinical settings.
The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California
Authors: Tang Hao , Matteson Jamie , Rinaldo Piero , Tortorelli Silvia , Currier Robert , Sciortino Stanley
Published: August 2020

Since the start of X-linked adrenoleukodystrophy (ALD) newborn screening in California, more than half of the diagnosed cases were found to have an ATP binding cassette subfamily D member 1 (ABCD1) gene variant of uncertain significance (VUS). To determine retrospectively the likelihood that these were true positive cases, we used a web-based post-analytical tool in Collaborative Laboratory Integrated Reports (CLIR). Confirmatory plasma very long-chain fatty-acids (VLCFA) profiles for ALD screen positive infant boys were run through the CLIR ALD tool. We compared the distribution by ABCD1 variant classification (pathogenic, likely pathogenic, VUS, and no variant) with the CLIR tool score interpretation (non-informative, possibly ALD, likely ALD, and very likely ALD) and the current case diagnosis. The study showed that CLIR tool positive interpretations were consistent with 100% of the pathogenic and likely pathogenic variants on the ABCD1 gene if a more conservative guideline was used. The tool interpretations were also consistent with screened cases that were determined to not have disease (our no-disorder group). The CLIR tool identified 19 diagnosed ALD cases with VUS to be potential false positives, representing a 40% reduction among all diagnosed ALD cases with VUS. The reduction could be extended to 65% if a more aggressive threshold was used. Identifying such preventable false positives could alleviate the follow-up burden for patients, their families, and California Special Care Centers.
Review of Enzyme-Induced Calcite Precipitation as a Ground-Improvement Technique
Authors: Putra Heriansyah , Yasuhara Hideaki , Erizal  , Sutoyo  , Fauzan Muhammad
Published: August 2020

Calcite-induced precipitation methods (CIPMs) have recently become potential techniques in geotechnical engineering for improving the shear strength of sandy soil. One of the most promising methods among them is enzyme-induced calcite precipitation (EICP). In this technique, a mixed solution composed of reagents and the urease enzyme, which produces calcite, is utilized as the grouting material. The precipitated calcite in granular soil provides ties among the grains of soil and limits their mobility, thus promoting an improvement in strength and stiffness and also a reduction in the hydraulic conductivity of sandy soil. This paper discusses the potential increase in the strength and stiffness of the soil, the additional materials for grouting, the effect of these materials on the treatment process, and the engineering properties of the soil. The possible sources of the urease enzyme and the applicability of the EICP method to other soil types are also discussed in this paper. The environmental and economic impacts of the application of EICP are also presented. The envisioned plans for application, potential advantages, and limitations of EICP for soil stabilization are discussed. Finally, the primary challenges and opportunities for development in future research are briefly addressed.
Association between Proinflammatory Markers, Leukocyte–Endothelium Interactions, and Carotid Intima–Media Thickness in Type 2 Diabetes: Role of Glycemic Control
Authors: de Marañón Aranzazu Martinez , Iannantuoni Francesca , Abad-Jiménez Zaida , Canet Francisco , Díaz-Pozo Pedro , López-Domènech Sandra , Roldán-Torres Ildefonso , Morillas Carlos , Rocha Milagros , Víctor Víctor M.
Published: August 2020

Glycated hemoglobin monitorization could be a tool for maintaining type 2 diabetes (T2D) under control and delaying the appearance of cardiovascular events. This cross-sectional study was designed to assess the role of glycemic control in modulating early-stage markers of cardiovascular complications. One hundred and eight healthy controls and 161 type 2 diabetic patients were recruited and distributed according to their glycemic control, setting the threshold at 6.5% (good control). Biochemical and anthropometrical parameters were registered during the initial visit, and peripheral blood was extracted to obtain polymorphonuclear cells and analyze inflammatory markers, adhesion molecules, leukocyte–endothelium interactions, and carotid intima–media thickness. Correlations between these parameters were explored. We found that inflammatory markers and adhesion molecules were augmented in type 2 diabetic subjects with poor glycemic control. Polymorphonuclear leukocytes interacted more with the endothelium in the diabetic population, and even more significantly in the poorly controlled subjects. In parallel, carotid intima–media thickness was also increased in the diabetic population, and the difference was greater among poorly controlled subjects. Finally, correlation measurement revealed that carotid intima–media thickness was related to glycemic control and lipid metabolism in diabetic patients. Our results suggest that glycemic control delays the onset of cardiovascular comorbidities in diabetic subjects.
Exhaled Biomarkers in Idiopathic Pulmonary Fibrosis—A Six-Month Follow-up Study in Patients Treated with Pirfenidone
Authors: Jaskiewicz Kaja , Mycroft Katarzyna , Maskey-Warzechowska Marta , Paralusz Karolina , Siemiez Natalia , Nejman-Gryz Patrycja , Barnas Malgorzata , Krenke Rafal , Gorska Katarzyna
Published: August 2020

The mechanism of action of pirfenidone in idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. To offer additional insight, we evaluated the change in the cytokine profile in exhaled breath condensate (EBC) following a six-month treatment with pirfenidone in patients with IPF. EBC concentrations of interleukin (IL)-6, IL-8, IL-15, TNF-α and VEGF-A were assessed with ELISA and compared at baseline and after six months of pirfenidone treatment. Twenty-nine patients with IPF and 13 controls were evaluated at baseline. With the exception of IL-8 concentration, which was lower in patients with IPF when compared to controls (p = 0.005), the cytokine levels did not differ between the groups. Despite the use of a high sensitivity assay, IL-8 reached detectable values only in 24% of IPF patients. EBC analysis after six months of treatment with pirfenidone did not reveal any differences in the cytokine levels. The change in EBC vascular endothelial growth factor A (VEGF-A) correlated with the change in the 6 min walk distance (r = 0.54, p = 0.045). We conclude that a six-month treatment with pirfenidone did not significantly change the EBC cytokine profile. Our findings support the potential usefulness of VEGF-A as a marker in IPF. The low EBC IL-8 level in patients with IPF is a novel finding which needs confirmation in larger studies.
Characterization of Left Ventricular Non-Compaction Cardiomyopathy
Authors: Lorca Rebeca , Martín María , Pascual Isaac , Astudillo Aurora , Díaz Molina Beatriz , Cigarrán Helena , Cuesta-Llavona Elías , Avanzas Pablo , Rodríguez Reguero José Julían , Coto Eliecer , Morís César , Gómez Juan
Published: August 2020

Left ventricle non-compaction cardiomyopathy (LVNC) has gained great interest in recent years, being one of the most controversial cardiomyopathies. There are several open debates, not only about its genetic heterogeneity, or about the possibility to be an acquired cardiomyopathy, but also about its possible overdiagnosis based on imaging techniques. In order to better understand this entity, we identified 38 LVNC patients diagnosed by cardiac MRI (CMRI) or anatomopathological study that could underwent NGS-sequencing and clinical study. Anatomopathological exam was performed in eight available LVNC hearts. The genetic yield was 34.2%. Patients with negative genetic testing had better left ventricular ejection fraction (LVEF) or it showed a tendency to improve in follow-up, and a possible trigger factor for LVNC was identified in 1/3 of them. Nonetheless, cerebrovascular accidents occurred in similar proportions in both groups. We conclude that in LVNC there seem to be different ways to achieve the same final phenotype. Genetic testing has a good genetic yield and provides valuable information. LVNC without an underlying genetic cause may have a better prognosis in terms of LVEF evolution. However, anticoagulation to prevent cerebrovascular accident (CVA) should be carefully evaluated in all patients. Larger series with pathologic examination are needed to help better understand this entity.
Using Genetics in Periodontal Disease to Justify Implant Failure in Down Syndrome Patients
Authors: Baus-Domínguez Maria , Gómez-Díaz Raquel , Corcuera-Flores Jose-Ramón , Torres-Lagares Daniel , Ruiz-Villandiego José-Cruz , Machuca-Portillo Guillermo , Gutiérrez-Pérez José-Luis , Serrera-Figallo María-Angeles
Published: August 2020

Peri-implant bone loss leading to dental implant failure does not develop in the same way across subjects who apparently present the same condition—specifically, in the case of Down syndrome patients with the same genetic disorder—given that they do not necessarily develop immune–inflammatory disorders to the same extent. Methods: This retrospective case-control study was aimed at identifying the possible genes involved in implant failure in Down syndrome patients by matching the periodontal disease variable by means of a retrospective case-control study. This process involved using the functional analysis of gene expression software Transcriptome Analysis Console (TAC, Affymetrix, Thermo Fisher Scientific, Waltham, MA, USA) and a search for the possible candidate genes involved. Focus was placed on the 92 genes related to the inflammation identified from the TaqMan™ Array Plate Human Inflammation Kit (Thermo Fisher Scientific, Waltham, MA, USA). Results: Six genes showed statistically significant results (p < 0.05) in our comparison. Three of them—PLCG2 (p = 0.0333), ALOX5 (p = 0.03) and LTAH4 (p = 0.0081)—were overexpressed in the implant reject group, and the following three were down-regulated: VCAM1 (p = 0.0182), PLA2G2A (p = 0.0034) and PLA2G10 (p = 0.047). Conclusion: Statistically significant differences exist in the gene expression involved in osteoclastogenesis, inflammatory response and host defensive response.
Autonomic Phenotypes in Chronic Fatigue Syndrome (CFS) Are Associated with Illness Severity: A Cluster Analysis
Authors: Słomko Joanna , Estévez-López Fernando , Kujawski Sławomir , Zawadka-Kunikowska Monika , Tafil-Klawe Małgorzata , Klawe Jacek J. , Morten Karl J. , Szrajda Justyna , Murovska Modra , Newton Julia L. , Zalewski Paweł
Published: August 2020

In this study we set out to define the characteristics of autonomic subgroups of patients with Chronic Fatigue Syndrome (CFS). The study included 131 patients with CFS (Fukuda criteria). Participants completed the following screening symptom assessment tools: Chalder Fatigue Scale, Fatigue Impact Scale, Fatigue Severity Scale, Epworth Sleepiness Scales, the self-reported Composite Autonomic Symptom Scale. Autonomic parameters were measured at rest with a Task Force Monitor (CNS Systems) and arterial stiffness using an Arteriograph (TensioMed Kft.). Principal axis factor analysis yielded four factors: fatigue, subjective and objective autonomic dysfunction and arterial stiffness. Using cluster analyses, these factors were grouped in four autonomic profiles: 34% of patients had sympathetic symptoms with dysautonomia, 5% sympathetic alone, 21% parasympathetic and 40% had issues with sympathovagal balance. Those with a sympathetic-dysautonomia phenotype were associated with more severe disease, reported greater subjective autonomic symptoms with sympathetic over-modulation and had the lowest quality of life. The highest quality of life was observed in the balance subtype where subjects were the youngest, had lower levels of fatigue and the lowest values for arterial stiffness. Future studies will aim to design autonomic profile-specific treatment interventions to determine links between autonomic phenotypes CFS and a specific treatment.
Could Evening Dietary Protein Intake Play a Role in Nocturnal Polyuria?
Authors: Alwis Upeksha S. , Delanghe Joris , Dossche Lien , Walle Johan Vande , Van Camp John , Monaghan Thomas F. , Roggeman Saskia , Everaert Karel
Published: August 2020

Urea is the most abundant and the largest contributing factor for urine osmolality. Urinary urea excretion is highly interrelated with dietary protein intake. Accordingly, an increase of urinary urea excretion due to high protein diet may lead to urea-induced osmotic diuresis. This study aims to explore the association between nocturnal polyuria (NP) and urea. This is a post hoc analysis of a prospective observational study of subjects who completed a renal function profile between October 2011 and February 2015 (n = 170). Each subject underwent a 24 h urine collection, which included 8 urine samples collected at 3 h intervals. Urine volume, osmolality, creatinine, urea and sodium were determined. Urinary urea excretion was used to estimate dietary protein intake. Compared to the control group, subjects with NP exhibited significantly higher nighttime urea and sodium excretion. Estimated evening dietary protein intake was correspondingly significantly higher amongst the NP subgroup. Nighttime diuresis rate was positively associated with age and nighttime free water clearance, creatinine clearance, sodium excretion, and urea excretion in NP subjects. Therefore, increased nocturnal urinary urea excretion may reflect an additional important mediator of nocturia owing to excess nocturnal urine production.
Practical Camera Sensor Spectral Response and Uncertainty Estimation
Authors: Toivonen Mikko E. , Klami Arto
Published: August 2020

Knowledge of the spectral response of a camera is important in many applications such as illumination estimation, spectrum estimation in multi-spectral camera systems, and color consistency correction for computer vision. We present a practical method for estimating the camera sensor spectral response and uncertainty, consisting of an imaging method and an algorithm. We use only 15 images (four diffraction images and 11 images of color patches of known spectra to obtain high-resolution spectral response estimates) and obtain uncertainty estimates by training an ensemble of response estimation models. The algorithm does not assume any strict priors that would limit the possible spectral response estimates and is thus applicable to any camera sensor, at least in the visible range. The estimates have low errors for estimating color channel values from known spectra, and are consistent with previously reported spectral response estimates.
Consequences of a Storm Surge for Aeolian Sand Transport on a Low-Gradient Beach
Authors: Tuijnman Jorn T. , Donker Jasper J. A. , Schwarz Christian S. , Ruessink Gerben
Published: August 2020

Wind-blown beach sand is the primary source for the volume growth of the most seaward dune, the foredune. Strong wind events can potentially dominate long-term aeolian supply but in reality do not contribute considerably because they often coincide with a storm surge. The aim of this paper is to further our understanding of how a storm surge prevents or severely restricts aeolian supply. Using field data collected on the 1:50 sloping Egmond beach (Netherlands) in the aftermath of a 1-m storm surge, we show that the ground water in the upper beach rose to well above normal levels during the surge, which resulted in the development of a seepage face during falling tide and hence persistent saturation of the emerging beach. Using a fetch-based model, we predicted aeolian supply during the 2-day surge period to be about 66% of the potential supply. Fetch limitations imposed by the surge-induced inundation and the continuous saturation of the sand on the emerging beach both contributed to the predicted supply limitation. Our results quantitatively support earlier studies that suggested surges to be the primary condition that causes predictions of long-term potential foredune growth to overestimate measured growth.
Dynamic Coastal-Shelf Seascapes to Support Marine Policies Using Operational Coastal Oceanography: The French Example
Authors: Tew-Kai Emilie , Quilfen Victor , Cachera Marie , Boutet Martial
Published: August 2020

In the context of maritime spatial planning and the implementation of spatialized Good Environmental Status indicators in the Marine Strategy Framework Directive (MSFD), the definition of a mosaic composed of coherent and standardised spatial units is necessary. We propose here a characterization of seascapes in time and space within the specific framework of the MSFD in the English Channel and the Bay of Biscay areas. A spatio-temporal classification of coastal-shelf water masses is carried out using twelve essential oceanographic and derived variables from operational coastal oceanography using the HYCOM model. Partitioning is computed using a multivariate hybrid two-step clustering process defining a time series of categorical maps representing hydrographical patch classes. Main patch occurrence is analyzed to understand their spatio-temporal dynamics and their oceanographic characteristics. Finally, patch classes are combined with MSFD marine sub-region delimitations to build seascapes, including ecosystem approach management and marine policy considerations.
Cyber–Physical Systems Forensics: Today and Tomorrow
Authors: Mohamed Nader , Al-Jaroodi Jameela , Jawhar Imad
Published: August 2020

Cyber–Physical Systems (CPS) connect the physical world (systems, environments, and humans) with the cyber world (software, data, etc.) to intelligently enhance the operational environment they serve. CPS are distributed software and hardware components embedded in the physical world and possibly attached to humans. They offer smart features, such as enhancing and optimizing the reliability, quality, safety, health, security, efficiency, operational costs, sustainability, and maintainability of physical systems. CPS are also very vulnerable to security attacks and criminal activities. In addition, they are very complex and have a direct impact on their environment. Therefore, it is hard to detect and investigate security attacks, while such attacks may have a catastrophic impact on the physical world. As a result, CPS must incorporate security measures in addition to suitable and effective forensics capabilities. When the security measures fail and an attack occurs, it becomes imperative to perform thorough forensics analysis. Adding effective forensics tools and capabilities will support the investigations of incidents. This paper defines the field of CPS forensics and its dimensions: Technical, Organizational, and Legal. Then, it reviews examples of current research efforts in the field and the types of tools and methods they propose for CPS forensics. In addition, it discusses the issues and challenges in the field that need to be addressed by researchers and developers of CPS. The paper then uses the review outcomes to discuss future research directions to address challenges and create a more effective, efficient, and safe forensics tools and for CPS. This discussion aims to create a starting point for researchers where they can identify the gaps and challenges and create suitable solutions through their research in CPS forensics.
Determination of Farmers’ Willingness to Pay for Sustainable Agricultural Land Use in the GAP-Harran Plain of Turkey
Authors: Aydoğdu Mustafa Hakkı , Sevinç Mehmet Reşit , Cançelik Mehmet , Doğan Hatice Parlakçı , Şahin Zeliha
Published: August 2020

There is a risk of salinity and degradation in soil structure due to excessive irrigation in the GAP-Harran Plain. The purpose of the research is to determine farmers’ willingness to pay (WTP) for applications of sustainable agricultural land usage practices to avoid salinization in soil based on irrigation problems related to the demands of the farmers’, their needs, and which factors affect their willingness to accept payment. The basic material of the research was obtained through face-to-face questionnaires from farmers who were selected by a method of simple random sampling in 2018. Heckman’s two-stage model was used in the analysis of the data in Stata. According to the results obtained from the research, 27.85% of the participants indicated WTP and the average amount was USD 16.2/hectare. The average WTP is calculated as USD 4.43/hectare for all participants and 735.38 thousand USD/year for the whole plain. The agricultural income, household size, farming experience, land amount, non-agricultural income, education level, working in the non-agricultural sector, and membership of farmers’ union were determined as statistically effective factors. It is necessary to raise the awareness of farmers through extension services. As awareness increases, both WTP and the adoption of applications will increase. The results supply useful data for people working on this subject for the planning and implementation of sustainable usage of resources in Turkey and to regions with similar socio–economic characteristics. This study is the first of its kind in GAP-Harran, Turkey.
Entrepreneurs and Territorial Diversity: Success and Failure in Andalusia 2007–2015
Authors: Cejudo García Eugenio , Cañete Pérez José Antonio , Navarro Valverde Francisco , Ruiz Moya Noelia
Published: August 2020

Rural Europe today cannot be understood without considering the impact of the EU’s Liaisons Entre Actions de Developpement de l’Economie Rurale (LEADER) rural development programme. Although in general it has had a positive impact, research has also revealed spatial and social disparities in the distribution of funds. Our primary source was the files for all the LEADER projects processed in Andalusia between 2007 and 2015. In addition to successfully executed projects, we also focused on “unfunded” projects, those in which, although promoters had initiated the application procedure, a grant was never ultimately obtained. Project failure must be studied so as to avoid biased findings. We then classified these projects within the different types of rural area and analysed the behaviour of the different promoters in these areas. Relevant findings include: project success or failure varies according to the different types of rural area, as does the behaviour of the different promoters; the degree of rurality can hinder project success; young and female entrepreneurs were more likely to fail; the type of promoter is strongly influenced by the distance to cities in that companies and Individual Entrepreneurs tend to invest in periurban spaces, while public sector promoters such as Local Councils are more prominent in remote rural areas.
A Scientometrics Review on Farmland Abandonment Research
Authors: Huang Yingqian , Li Fengqin , Xie Hualin
Published: August 2020

Using the Web of Science database, 1498 research articles published between 1900 and 2019 on the subject of farmland abandonment were retrieved. With the help of the SciMAT tool, a theme strategic diagram, overlay map and evolution map represented by keywords were constructed, and the strategic coordinate analysis and data flow analysis methods were used to analyze the research themes, evolutionary states and paths of farmland abandonment in different research time periods. The results show the following: (1) Research on farmland abandonment has rapidly grown in the past ten years, the development of studies on farmland abandonment has become more mature, and the research topics and content have tended to solidify; (2) The research topics of studies on farmland abandonment are mostly centered on forests, patterns, landscapes, land use changes, climate change, etc. The research topics have had strong continuity and few new research hotspots; (3) The study of the ecological environment effect of farmland abandonment is the basic research direction in the field of farmland abandonment and will continue to become a research hotspot; (4) Farmland abandonment has become an important part of the research on land use change and ecosystem processes; (5) The driving force of farmland abandonment includes natural, social and economic factors, among which the socioeconomic factors are the most important driving force, and will continue to be a research hotspot. Finally, this study concludes that the research directions on farmland abandonment in future should strengthen the quantitative assessment of environmental effects of farmland abandonment, information extraction and multiscale simulation monitoring, trend prediction and risk assessment.
An Another Protocol to Make Sulfur Embedded Ultrathin Sections of Extraterrestrial Small Samples
Authors: Noguchi Takaaki , Takase Minako , Matsumoto Rikako , Kebukawa Yoko , Suga Hiroki , Kondo Masashi , Takahashi Yoshio , Takeichi Yasuo , Yabuta Hikaru
Published: August 2020

Another protocol to make sulfur embedded ultrathin sections was developed for STXM–XANES, AFM–IR and TEM analyses of organic materials in small extraterrestrial samples. Polymerized liquid sulfur—instead of low-viscosity liquid sulfur—is the embedding media in this protocol. Due to high viscosity of the polymerized sulfur, the embedded samples stay near the surface of polymerized liquid sulfur, which facilitates trimming of glassy sulfur and ultramicrotomy of tiny embedded samples. In addition, well-continued ribbons of ultramicrotomed sections can be obtained, which are suitable for the above mentioned analyses. Because there is no remarkable difference in Carbon XANES spectra of Murchison IOM prepared by this protocol and by the conventional protocol, this protocol gives another alternative to prepare sulfur embedded ultramicrotomed sections.