bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling LMNA Mutations in Metabolic Syndrome: Cellular Phenotype and Clinical Pitfalls
Authors: Desgrouas Camille , Varlet Alice-Anaïs , Dutour Anne , Galant Damien , Merono Françoise , Bonello-Palot Nathalie , Bourgeois Patrice , Lasbleiz Adèle , Petitjean Cathy , Ancel Patricia , Levy Nicolas , Badens Catherine , Gaborit Bénédicte
Published: January 2020

This study details the clinical and cellular phenotypes associated with two missense heterozygous mutations in LMNA, c.1745G>T p.(Arg582Leu), and c.1892G>A p.(Gly631Asp), in two patients with early onset of diabetes mellitus, hypertriglyceridemia and non-alcoholic fatty liver disease. In these two patients, subcutaneous adipose tissue was persistent, at least on the abdomen, and the serum leptin level remained in the normal range. Cellular studies showed elevated nuclear anomalies, an accelerated senescence rate and a decrease of replication capacity in patient cells. In cellular models, the overexpression of mutated prelamin A phenocopied misshapen nuclei, while the partial reduction of lamin A expression in patient cells significantly improved nuclear morphology. Altogether, these results suggest a link between lamin A mutant expression and senescence associated phenotypes. Transcriptome analysis of the whole subcutaneous adipose tissue from the two patients and three controls, paired for age and sex using RNA sequencing, showed the up regulation of genes implicated in immunity and the down regulation of genes involved in development and cell differentiation in patient adipose tissue. Therefore, our results suggest that some mutations in LMNA are associated with severe metabolic phenotypes without subcutaneous lipoatrophy, and are associated with nuclear misshaping.
Circadian rhythms, Neuroinflammation and Oxidative Stress in the Story of Parkinson’s Disease
Authors: Vallée Alexandre , Lecarpentier Yves , Guillevin Rémy , Vallée Jean-Noël
Published: January 2020

Parkinson’s disease (PD) is one of the main neurodegenerative disease characterized by a progressive degeneration of neurons constituted by dopamine in the substantia nigra pars compacta. The etiologies of PD remain unclear. Aging is the main risk factor for PD. Aging could dysregulate molecular pathways controlling cell homeostatic mechanisms. PD cells are the sites of several metabolic abnormalities including neuroinflammation and oxidative stress. Metabolic structures are driven by circadian rhythms. Biologic rhythms are complex systems interacting with the environment and controlling several physiological pathways. Recent findings have shown that the dysregulation of the circadian rhythms is correlated with PD and its metabolic dysregulations. This review is focused on the key role of circadian rhythms and their impact on neuroinflammation and oxidative stress in Parkinson’s disease.
Preclinical Comparison of Stem Cells Secretome and Levodopa Application in a 6-Hydroxydopamine Rat Model of Parkinson’s Disease
Authors: Teixeira Fábio G. , Vilaça-Faria Helena , Domingues Ana V. , Campos Jonas , Salgado António J.
Published: January 2020

Parkinson’s Disease (PD) is characterized by the massive loss of dopaminergic neurons, leading to the appearance of several motor impairments. Current pharmacological treatments, such as the use of levodopa, are yet unable to cure the disease. Therefore, there is a need for novel strategies, particularly those that can combine in an integrated manner neuroprotection and neuroregeneration properties. In vitro and in vivo models have recently revealed that the secretome of mesenchymal stem cells (MSCs) holds a promising potential for treating PD, given its effects on neural survival, proliferation, differentiation. In the present study, we aimed to access the impact of human bone marrow MSCs (hBM-MSCs) secretome in 6-hydroxydopamine (6-OHDA) PD model when compared to levodopa administration, by addressing animals’ motor performance, and substantia nigra (SN), and striatum (STR) histological parameters by tyrosine hydroxylase (TH) expression. Results revealed that hBM-MSCs secretome per se appears to be a modulator of the dopaminergic system, enhancing TH-positive cells expression (e.g., dopaminergic neurons) and terminals both in the SN and STR when compared to the untreated group 6-OHDA. Such finding was positively correlated with a significant amelioration of the motor outcomes of 6-OHDA PD animals (assessed by the staircase test). Thus, the present findings support hBM-MSCs secretome administration as a potential therapeutic tool in treating PD, and although we suggest candidate molecules (Trx1, SEMA7A, UCHL1, PEDF, BDNF, Clusterin, SDF-1, CypA, CypB, Cys C, VEGF, DJ-1, Gal-1, GDNF, CDH2, IL-6, HSP27, PRDX1, UBE3A, MMP-2, and GDN) and possible mechanisms of hBM-MSCs secretome-mediated effects, further detailed studies are needed to carefully and clearly define which players may be responsible for its therapeutic actions. By doing so, it will be reasonable to presume that potential treatments that can, per se, or in combination modulate or slow PD may lead to a rational design of new therapeutic or adjuvant strategies for its functional modeling and repair.
A Novel Simple Anti-Ice Aluminum Coating: Synthesis and In-Lab Comparison with a Superhydrophobic Hierarchical Surface
Authors: Balordi Marcella , Santucci de Magistris Giorgio , Chemelli Cristina
Published: January 2020

A simple process to obtain a slippery surface with anti-ice and ice-phobic properties has been developed and characterized in laboratory. The coating is realized by growing a nanostructured pseudo-boehmite on an aluminum substrate and applying an environmentally compatible final functionalization consisting of a fluorine-free oligomeric short-chain alkylfunctional silane. The resulting surface is conceptually similar to a slippery liquid infused porous surface (SLIP) material, but the porous infrastructure is inorganic and the process to generate it is very simple, rapid and economic. The coating performance in terms of hydrophobicity at room and low temperatures, ice nucleation temperature and ice adhesion forces were assessed in laboratory. Moreover, hydrophobicity persistence was tested after prolonged immersion in acid, basic and saline solutions while the durability of ice-phobic behavior was assessed by repeated shear stress tests. Results are compared with those of a superhydrophobic hierarchical aluminum surface obtained with a fluorinated siloxane. The novel coating shows very good anti-ice properties and relevant durability, with some differences from the fluorinated surface. The novel slippery coating process is promising for industrial applications, also taking into account its environmental compatibility, simplicity and low cost.
Phylogenetic Affinity of Genolopa (Digenea: Monorchiidae) with Descriptions of Two New Species
Authors: Panyi Apryle J. , Curran Stephen S. , Overstreet Robin M.
Published: January 2020

The validity of Genolopa Linton, 1910 has been controversial because the observation of presently recognized critical diagnostic morphological features (spines in the genital atrium and a bipartite, anteriorly spined terminal organ) were omitted from the original diagnosis, and these features were not universally appreciated as important diagnostic features until 2008. Modern taxonomists have been further challenged by inappropriate fixation techniques that have resulted in various interpretations of morphological features. Consequently, named species in the genus have fluctuated among other monorchiid genera depending on various interpretations by taxonomists, and a modern consensus on classifying these species is lacking. This study combines a molecular approach with modern conventional morphological techniques to investigate the validity of Genolopa as a lineage within the Monorchiidae. New morphology and molecular sequence data from the type-species of Genolopa were studied, and two new species in the genus were described, Genolopa vesca n. sp. and Genolopa minuscula n. sp. Interrelationships among the Monorchiidae were explored using Bayesian inference analysis of the partial 28S rDNA fragment, incorporating three species of Genolopa for the first time. The phylogenetic analysis revealed that the genus represents a natural lineage, supporting the presence of spines in the genital atrium in conjunction with a bipartite and anteriorly spined terminal organ as key features of the generic diagnosis. This study also provides for the first time partial 28S rDNA data for Postmonorchis orthopristis, Lasiotocus trachinoti, Lasiotocus glebulentus, and an unidentified species of Lasiotocus.
SRMM: A Social Relationship-Aware Human Mobility Model
Authors: Van Anh Duong Dat , Yoon Seokhoon
Published: January 2020

Since human movement patterns are important for validating the performance of wireless networks, several traces of human movements in real life have been collected. However, collecting data about human movements is costly and time-consuming. Moreover, multiple traces are demanded to test various network scenarios. As a result, a lot of synthetic models of human movement have been proposed. Nevertheless, most of the proposed models were often based on random generation, and cannot produce realistic human movements. Although there have been a few models that tried to capture the characteristics of human movement in real life (e.g., flights, inter-contact times, and pause times following the truncated power-law distribution), those models still cannot reflect realistic human movements due to a lack of consideration for social context among people. To address those limitations, in this paper, we propose a novel human mobility model called the social relationship–aware human mobility model (SRMM), which considers social context as well as the characteristics of human movement. SRMM partitions people into social groups by exploiting information from a social graph. Then, the movements of people are determined by considering the distances to places and social relationships. The proposed model is first evaluated by using a synthetic map, and then a real road map is considered. The results of SRMM are compared with a real trace and other synthetic mobility models. The obtained results indicate that SRMM is consistently better at reflecting both human movement characteristics and social relationships.
Advances in Occurrence, Importance, and Mycotoxin Control Strategies: Prevention and Detoxification in Foods
Authors: Agriopoulou Sofia , Stamatelopoulou Eygenia , Varzakas Theodoros
Published: January 2020

Mycotoxins are toxic substances that can infect many foods with carcinogenic, genotoxic, teratogenic, nephrotoxic, and hepatotoxic effects. Mycotoxin contamination of foodstuffs causes diseases worldwide. The major classes of mycotoxins that are of the greatest agroeconomic importance are aflatoxins, ochratoxins, fumonisins, trichothecenes, emerging Fusarium mycotoxins, enniatins, ergot alkaloids, Alternaria toxins, and patulin. Thus, in order to mitigate mycotoxin contamination of foods, many control approaches are used. Prevention, detoxification, and decontamination of mycotoxins can contribute in this purpose in the pre-harvest and post-harvest stages. Therefore, the purpose of the review is to elaborate on the recent advances regarding the occurrence of main mycotoxins in many types of important agricultural products, as well as the methods of inactivation and detoxification of foods from mycotoxins in order to reduce or fully eliminate them.
Novel Mutations Found in Individuals with Adult-Onset Pompe Disease
Authors: Aung-Htut May T. , Ham Kristin A. , Tchan Michel C. , Fletcher Sue , Wilton Steve D.
Published: January 2020

Pompe disease, or glycogen storage disease II is a rare, progressive disease leading to skeletal muscle weakness due to deficiency of the acid α-1,4-glucosidase enzyme (GAA). The severity of disease and observed time of onset is subject to the various combinations of heterozygous GAA alleles. Here we have characterized two novel mutations: c.2074C>T and c.1910_1918del, and a previously reported c.1082C>G mutation of uncertain clinical significance. These mutations were found in three unrelated patients with adult-onset Pompe disease carrying the common c.-32-13T>G mutation. The c.2074 C>T nonsense mutation has obvious consequences on GAA expression but the c.1910_1918del (deletion of 3 amino acids) and c.1082C>G missense variants are more subtle DNA changes with catastrophic consequences on GAA activity. Molecular and clinical analyses from the three patients corresponded with the anticipated pathogenicity of each mutation.
Observational and Critical State Physics Descriptions of Long-Range Flow Structures
Authors: Malin Peter E. , Leary Peter C. , Cathles Lawrence M. , Barton Christopher C.
Published: January 2020

Using Fracture Seismic methods to map fluid-conducting fracture zones makes it important to understand fracture connectivity over distances greater 10–20 m in the Earth’s upper crust. The principles required for this understanding are developed here from the observations that (1) the spatial variations in crustal porosity are commonly associated with spatial variations in the magnitude of the natural logarithm of crustal permeability, and (2) many parameters, including permeability have a scale-invariant power law distribution in the crust. The first observation means that crustal permeability has a lognormal distribution that can be described as κ ≈ κ 0 exp ( α ( φ − φ 0 ) ) , where α is the ratio of the standard deviation of ln permeability from its mean to the standard deviation of porosity from its mean. The scale invariance of permeability indicates that αϕο = 3 to 4 and that the natural log of permeability has a 1/k pink noise spatial distribution. Combined, these conclusions mean that channelized flow in the upper crust is expected as the distance traversed by flow increases. Locating the most permeable channels using Seismic Fracture methods, while filling in the less permeable parts of the modeled volume with the correct pink noise spatial distribution of permeability, will produce much more realistic models of subsurface flow.
Physical Activity Promotion for Apprentices in Nursing Care and Automotive Mechatronics–Competence Counts More than Volume
Authors: Carl Johannes , Grüne Eva , Popp Johanna , Pfeifer Klaus
Published: January 2020

Apprentices in the area of nursing care and automotive mechatronics are exposed to increased health risks. In this context, the promotion of physical activity (PA) is considered an effective strategy for the assurance of work ability. The goal of the PArC-AVE study was therefore to better understand the role of PA for apprentices employed in these two sectors. In an exploratory study, 55 apprentices wore an ActiGraph accelerometer over seven consecutive days and were subject to activity analysis. The objective accelerometer data (18,979 ± 3780 steps/day; 471.00 ± 159.75 min of moderate-to-vigorous PA/week), complemented by questionnaire data, indicated that most met the volume-based PA recommendations. Subsequently, we conducted a multicenter study comprising 745 apprentices from six vocational education institutions. Path analyses showed that competencies for health-enhancing PA were significantly related to indicators of work ability (0.180 ≤ b ≤ 0.452) and psychophysical health (0.139 ≤ b ≤ 0.347), whereas mere volume of PA was not (−0.048 ≤ b ≤ 0.080). In summary, apprentices of nursing care and automotive mechatronics showed high levels of PA. However, the results highlight the importance of competencies for health-enhancing PA. The PAHCO model could provide a useful framework for the conceptualization of effective interventions.
Improving Environmental Capacities for Health Promotion in Support Settings for People with Intellectual Disabilities: Inclusive Design of the DIHASID Tool
Authors: Vlot-van Anrooij Kristel , Hilgenkamp Thessa I.M. , Leusink Geraline L. , van der Cruijsen Anneke , Jansen Henk , Naaldenberg Jenneken , van der Velden Koos
Published: January 2020

People with intellectual disabilities (ID) have unhealthier lifestyles than the general population. To sustainably improve their lifestyle and health status, a whole-system approach to creating healthy environments is crucial. To gain insight into how support for physical activity and healthy nutrition can be embedded in a setting, asset mapping can be helpful. Asset mapping involves creating a bottom–up overview of promoting and protective factors for health. However, there is no asset mapping tool available for ID support settings. This study aims to develop an asset mapping tool in collaboration with people with ID to gain insight into assets for healthy nutrition and physical activity in such settings. The tool is based on previous research and development continued in an iterative and inclusive process in order to create a clear, comprehensive, and usable tool. Expert interviews (n = 7), interviews with end-users (n = 7), and pilot testing (n = 16) were conducted to refine the tool. Pilot participants perceived the tool as helpful in pinpointing perceived assets and in prompting ideas on how to create inclusive environments with support for physical activity and healthy nutrition. This overview of assets can be helpful for mobilizing assets and building the health-promoting capacities of ID support settings.
Assessing the Contribution of Data Mining Methods to Avoid Aircraft Run-Off from the Runway to Increase the Safety and Reduce the Negative Environmental Impacts
Authors: Vorobyeva Olga , Bartok Juraj , Šišan Peter , Nechaj Pavol , Gera Martin , Kelemen Miroslav , Polishchuk Volodymyr , Gaál Ladislav
Published: January 2020

The Single Europe Sky Air Traffic Management Research (SESAR) program develops and implements innovative technological and operational solutions to modernize European air traffic management and to eliminate the negative environmental impacts of aviation activity. This article presents our developments within the SESAR Solution “Safety Support Tools for Avoiding Runway Excursions”. This SESAR Solution aims to mitigate the risk of runway excursion, to optimize airport operation management by decreasing the number of runway inspections, to make chemical treatment effective with respect to the environment, and to increase resilience, efficiency and safety in adverse weather situations. The proposed approach is based on the enhancement of runway surface condition awareness by integrating data from various sources. Dangerous windy conditions based on Lidar measurements are also discussed as another relevant factor in relation to runway excursions. The paper aims to explore four different data mining methods to obtain runway conditions from the available input data sources, examines their performance and discusses their pros and cons in comparison with a rule-based algorithm approach. The output of the SESAR Solution is developed in compliance with the new Global Reporting Format of the International Civil Aviation Organization for runway condition description to be valid from 2020. This standard is expected to provide concerned stakeholders with more precise information to enhance flight safety and environmental protection.
Reference Values for Fitness Level and Gross Motor Skills of 4–6-Year-Old Chilean Children
Authors: Godoy-Cumillaf Andrés , Bruneau-Chávez José , Fuentes-Merino Paola , Vásquez-Gómez Jaime , Sánchez-López Mairena , Alvárez-Bueno Celia , Cavero-Redondo Iván
Published: January 2020

In childhood, fitness level is considered an important indicator of health, while gross motor skills are the basis of future motor competence. So far, no reference values have been found for the Chilean population. Therefore, this study aims to provide fitness level and gross motor skill reference values by gender and age of Chilean children aged 4–6 years. A cross-sectional analysis was conducted that included 728 children between 4 and 6 years old from the La Araucanía region of Chile. To assess the fitness level, the 20-m shuttle run test, standing long jump, handgrip dynamometry, 4x10m shuttle run, and Sit and Reach tests were used. Gross motor skills were assessed by five tests including aiming and catching and balance motor tasks. For fitness level, boys have better values in the long jump and dynamometry test, while girls have better values in flexibility. For estimated maximum volume of oxygen, at 5 years old there are significant differences in favour of boys, while at 6 years old in favour of girls. No statistically significant differences in speed/agility by gender were found. For gross motor skills, boys obtain higher values for catching and aiming tests, and girls for balance. The reference values for fitness level and gross motor skills shown in this study could aid physical education and health professionals in identifying children with low reference values, as well as in establishing objectives that will help to improve their health.
Strengths Against Psychopathology in Adolescents: Ratifying the Robust Buffer Role of Trait Emotional Intelligence
Authors: Piqueras José A. , Salvador Maria do Céu , Soto-Sanz Victoria , Mira Francisco , Pérez-González Juan-Carlos
Published: January 2020

The aim of this study was to unravel the interrelated effects of trait emotional intelligence (Trait EI), mindfulness, and irrational beliefs on adolescent mental health. A random sample of students from three secondary schools in Spain and eight secondary schools in Portugal was recruited. We conducted four-step hierarchical regression analyses. We also conducted regression analyses to examine the role of mindfulness skills and catastrophizing as mediators of the link between emotional intelligence and psychosocial problems. Finally, the SPSS PROCESS computing tool was used to perform conditional process analysis (model 6). A total of 1370 adolescents from Spain (n = 591) and Portugal (n = 779) participated in this study (mean age = 14.97, SD = 1.50; range = 12–18). The mediation analyses confirmed that adolescent mental health was determined by Trait EI directly, and by mindfulness skills and catastrophizing thoughts in an indirect way. Together, the four variables explained 44% of psychopathology, with EI being the most powerful predictor, which ratify the robust buffer role and incremental validity of Trait EI against youth mental health. The identified pathways provide keys for emotional education interventions aimed at promoting adolescent mental health.
Physical Activity Promotion Tools in the Portuguese Primary Health Care: An Implementation Research
Authors: Mendes Romeu , Nunes Silva Marlene , Santos Silva Catarina , Marques Adilson , Godinho Cristina , Tomás Rita , Agostinho Marcos , Madeira Sara , Rebelo-Marques Alexandre , Martins Henrique , Teixeira Pedro J. , Cruz Diogo
Published: January 2020

Background: This paper aims to discuss how physical activity (PA) brief assessment, brief counseling, and self-monitoring tools were designed and implemented in the Portuguese National Health Service (NHS), and to report on their current use by health professionals and citizens. Methods: Three digital tools to facilitate PA promotion in primary health care (PHC) were developed: 1) a PA brief assessment tool was incorporated in the electronic health record platform “SClínico Cuidados de Saúde Primários“; 2) a brief counseling tool was developed in the software “PEM—Prescrição Eletrónica Médica” (electronic medical prescription); and 3) a “Physical Activity Card” was incorporated in an official NHS smartphone app called “MySNS Carteira”. Results: From September 2017 to June 2019, 119,386 Portuguese patients had their PA assessed in PHC. Between December 2017 and June 2019, a total of 7957 patients received brief intervention for PA by a medical doctor. Regarding the app “MySNS Carteira”, 93,320 users activated the “Physical Activity Card”, between February 2018 and December 2018. Conclusions: These tools represent key actions to promote PA among Portuguese citizens using PHC as a priority setting. Further initiatives will follow, including proper assessment of their clinical impact and training programs for health care professionals on PA promotion.
Patient-Controlled Intravenous Morphine Analgesia Combined with Transcranial Direct Current Stimulation for Post-Thoracotomy Pain: A Cost-Effectiveness Study and A Feasibility for Its Future Implementation
Authors: Rancic Nemanja , Mladenovic Katarina , Ilic Nela V. , Dragojevic-Simic Viktorija , Karanikolas Menelaos , Ilic Tihomir V. , Stamenkovic Dusica M.
Published: January 2020

This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal analgesia after thoracotomy. Patients assigned to the active treatment group (a-tDCS, n = 27) received tDCS over the left primary motor cortex for five days, whereas patients assigned to the control group (sham-tDCS, n = 28) received sham tDCS stimulations. All patients received postoperative PCA-IV morphine. For cost-effectiveness analysis we used data about total amount of PCA-IV morphine and maximum visual analog pain scale with cough (VASP-Cmax). Direct costs of hospitalization were assumed as equal for both groups. Cost-effectiveness analysis was performed with the incremental cost-effectiveness ratio (ICER), expressed as the incremental cost (RSD or US$) per incremental gain in mm of VASP-Cmax reduction. Calculated ICER was 510.87 RSD per VASP-Cmax 1 mm reduction. Conversion on USA market (USA data 1.325 US$ for 1 mg of morphine) revealed ICER of 189.08 US$ or 18960.39 RSD/1 VASP-Cmax 1 mm reduction. Cost-effectiveness expressed through ICER showed significant reduction of PCA-IV morphine costs in the tDCS group. Further investigation of tDCS benefits with regards to reduction of postoperative pain treatment costs should also include the long-term benefits of reduced morphine use.
The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review
Authors: Webb Lauren M. , Phillips Kathryn E. , Ho Man Choi , Veldic Marin , Blacker Caren J.
Published: January 2020

Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current antidepressant medications are suboptimal, as most MDD patients fail to achieve complete remission from symptoms. At present, clinicians are unable to predict which antidepressant is most effective for a particular patient, exposing patients to multiple medication trials and side effects. Since MDD’s etiology includes interactions between genes and environment, the epigenome is of interest for predictive utility and treatment monitoring. Epigenetic mechanisms of antidepressant medications are incompletely understood. Differences in epigenetic profiles may impact treatment response. A systematic literature search yielded 24 studies reporting the interaction between antidepressants and eight genes (BDNF, MAOA, SLC6A2, SLC6A4, HTR1A, HTR1B, IL6, IL11) and whole genome methylation. Methylation of certain sites within BDNF, SLC6A4, HTR1A, HTR1B, IL11, and the whole genome was predictive of antidepressant response. Comparing DNA methylation in patients during depressive episodes, during treatment, in remission, and after antidepressant cessation would help clarify the influence of antidepressant medications on DNA methylation. Individuals’ unique methylation profiles may be used clinically for personalization of antidepressant choice in the future.
Region-Specific Sialylation Pattern of Prion Strains Provides Novel Insight into Prion Neurotropism
Authors: Makarava Natallia , Chang Jennifer Chen-Yu , Baskakov Ilia V.
Published: January 2020

Mammalian prions are unconventional infectious agents that invade and replicate in an organism by recruiting a normal form of a prion protein (PrPC) and converting it into misfolded, disease-associated state referred to as PrPSc. PrPC is posttranslationally modified with two N-linked glycans. Prion strains replicate by selecting substrates from a large pool of PrPC sialoglycoforms expressed by a host. Brain regions have different vulnerability to prion infection, however, molecular mechanisms underlying selective vulnerability is not well understood. Toward addressing this question, the current study looked into a possibility that sialylation of PrPSc might be involved in defining selective vulnerability of brain regions. The current work found that in 22L -infected animals, PrPSc is indeed sialylated in a region dependent manner. PrPSc in hippocampus and cortex was more sialylated than PrPSc from thalamus and stem. Similar trends were also observed in brain materials from RML- and ME7-infected animals. The current study established that PrPSc sialylation status is indeed region-specific. Together with previous studies demonstrating that low sialylation status accelerates prion replication, this work suggests that high vulnerability of certain brain region to prion infection could be attributed to their low sialylation status.
Circadian Clock, Time-Restricted Feeding and Reproduction
Authors: Pan Xiaoyue , Taylor Meredith J. , Cohen Emma , Hanna Nazeeh , Mota Samantha
Published: January 2020

The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.
Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood
Authors: Weiß Elisa , Berger Hannah M. , Brandl Waltraud T. , Strutz Jasmin , Hirschmugl Birgit , Simovic Violeta , Tam-Ammersdorfer Carmen , Cvitic Silvija , Hiden Ursula
Published: January 2020

Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring’s health for developing cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (−39.9%, p < 0.05), protein (−42.5%, p = 0.02), and MME release from fpEC (−64.7%, p = 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (r = −0.42, p = 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.
RPGR-Associated Dystrophies: Clinical, Genetic, and Histopathological Features
Authors: Nguyen Xuan-Thanh-An , Talib Mays , van Schooneveld Mary J. , Brinks Joost , ten Brink Jacoline , Florijn Ralph J. , Wijnholds Jan , Verdijk Robert M. , Bergen Arthur A. , Boon Camiel J.F.
Published: January 2020

This study describes the clinical, genetic, and histopathological features in patients with RPGR-associated retinal dystrophies. Nine male patients from eight unrelated families underwent a comprehensive ophthalmic examination. Additionally, the histopathology of the right eye from a patient with an end-stage cone-rod-dystrophy (CRD)/sector retinitis pigmentosa (RP) phenotype was examined. All RPGR mutations causing a CRD phenotype were situated in exon ORF15. The mean best-corrected visual acuity (BCVA, decimals) was 0.58 (standard deviation (SD)): 0.34; range: 0.05–1.13); and the mean spherical refractive error was −4.1 D (SD: 2.11; range: −1.38 to −8.19). Hyperautofluorescent rings were observed in six patients. Full-field electroretinography responses were absent in all patients. The visual field defects ranged from peripheral constriction to central islands. The mean macular sensitivity on microperimetry was 11.6 dB (SD: 7.8; range: 1.6–24.4) and correlated significantly with BCVA (r = 0.907; p = 0.001). A histological examination of the donor eye showed disruption of retinal topology and stratification, with a more severe loss found in the peripheral regions. Reactive gliosis was seen in the inner layers of all regions. Our study demonstrates the highly variable phenotype found in RPGR-associated retinal dystrophies. Therapies should be applied at the earliest signs of photoreceptor degeneration, prior to the remodeling of the inner retina.
Alpha-1 Antitrypsin—A Target for MicroRNA-Based Therapeutic Development for Cystic Fibrosis
Authors: Hunt Alison M.D. , Glasgow Arlene M.A. , Humphreys Hilary , Greene Catherine M.
Published: January 2020

Cystic fibrosis (CF) is an autosomal recessive genetic disorder arising from mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Disruption to normal ion homeostasis in the airway results in impaired mucociliary clearance, leaving the lung more vulnerable to recurrent and chronic bacterial infections. The CF lung endures an excess of neutrophilic inflammation, and whilst neutrophil serine proteases are a crucial part of the innate host defence to infection, a surplus of neutrophil elastase (NE) is understood to create a net destructive effect. Alpha-1 antitrypsin (A1AT) is a key antiprotease in the control of NE protease activity but is ineffective in the CF lung due to the huge imbalance of NE levels. Therapeutic strategies to boost levels of protective antiproteases such as A1AT in the lung remain an attractive research strategy to limit the damage from excess protease activity. microRNAs are small non-coding RNA molecules that bind specific cognate sequences to inhibit expression of target mRNAs. The inhibition of miRNAs which target the SERPINA1 (A1AT-encoding gene) mRNA represents a novel therapeutic approach for CF inflammation. This could involve the delivery of antagomirs that bind and sequester the target miRNA, or target site blockers that bind miRNA recognition elements within the target mRNA to prevent miRNA interaction. Therefore, miRNA targeted therapies offer an alternative strategy to drive endogenous A1AT production and thus supplement the antiprotease shield of the CF lung.
Zinc Transporter-3 Knockout Mice Demonstrate Age-Dependent Alterations in the Metalloproteome
Authors: Hancock Sara M. , Portbury Stuart D. , Gunn Adam P. , Roberts Blaine R. , Bush Ashley I. , Adlard Paul A.
Published: January 2020

Metals are critical cellular elements that are involved in a variety of cellular processes, with recent literature demonstrating that zinc, and the synaptic zinc transporter (ZnT3), are specifically involved in learning and memory and may also be key players in age-related neurodegenerative disorders such as Alzheimer’s disease. Whilst the cellular content and location of metals is critical, recent data has demonstrated that the metalation state of proteins is a determinant of protein function and potential toxicity. As we have previously reported that ZnT3 knockout (KO) mice have deficits in total zinc levels at both 3 and 6 months of age, we were interested in whether there might be changes in the metalloproteomic profile in these animals. To do this, we utilised size exclusion chromatography-inductively coupled plasma mass spectrometry (SEC-ICP-MS) and examined hippocampal homogenates from ZnT3 KO and age-matched wild-type mice at 3, 6 and 18 months of age. Our data suggest that there are alterations in specific metal binding proteins, for zinc, copper and iron all being modulated in the ZnT3 KO mice compared to wild-type (WT). These data suggest that ZnT3 KO mice may have impairments in the levels or localisation of multiple transition metals, and that copper- and iron-dependent cellular pathways may also be impacted in these mice.
MicroRNAs and Neutrophil Activation Markers Predict Venous Thrombosis in Pancreatic Ductal Adenocarcinoma and Distal Extrahepatic Cholangiocarcinoma
Authors: Oto Julia , Navarro Silvia , Larsen Anders C. , Solmoirago María José , Plana Emma , Hervás David , Fernández-Pardo Álvaro , España Francisco , Kristensen Søren R. , Thorlacius-Ussing Ole , Medina Pilar
Published: January 2020

Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited tools are available to identify high risk patients. Upon activation, neutrophils release their content through different mechanisms, thereby prompting thrombosis. We explored plasma microRNAs (miRNAs) and neutrophil activation markers to predict VTE in pancreatic ductal adenocarcinoma (PDAC) and distal extrahepatic cholangiocarcinoma (DECC). Twenty-six PDAC and 6 DECC patients recruited at cancer diagnosis, were examined for deep vein thrombosis and pulmonary embolisms, and were then followed-up with clinical examinations, blood collections, and biCUS. Ten patients developed VTE and were compared with 22 age- and sex-matched controls. miRNA expression levels were measured at diagnosis and right before VTE, and neutrophil activation markers (cell-free DNA, nucleosomes, calprotectin, and myeloperoxidase) were measured in every sample obtained during follow-up. We obtained a profile of 7 miRNAs able to estimate the risk of future VTE at diagnosis (AUC = 0.95; 95% Confidence Interval (CI) (0.987, 1)) with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. Seven miRNAs were up- or down-regulated before VTE compared with diagnosis. We obtained a predictive model of VTE with calprotectin as predictor (AUC = 0.77; 95% CI (0.57, 0.95)). This is the first study that addresses the ability of plasma miRNAs and neutrophil activation markers to predict VTE in PDAC and DECC.
Nitrogen-Doped Carbon Nanotube/Polypropylene Composites with Negative Seebeck Coefficient
Authors: Krause Beate , Konidakis Ioannis , Arjmand Mohammad , Sundararaj Uttandaraman , Fuge Robert , Liebscher Marco , Hampel Silke , Klaus Maxim , Serpetzoglou Efthymis , Stratakis Emmanuel , Pötschke Petra
Published: January 2020

This study describes the application of multi-walled carbon nanotubes that were nitrogen-doped during their synthesis (N-MWCNTs) in melt-mixed polypropylene (PP) composites. Different types of N-MWCNTs, synthesized using different methods, were used and compared. Four of the five MWCNT grades showed negative Seebeck coefficients (S), indicating n-type charge carrier behavior. All prepared composites (with a concentration between 2 and 7.5 wt% N-MWCNTs) also showed negative S values, which in most cases had a higher negative value than the corresponding nanotubes. The S values achieved were between 1.0 μV/K and −13.8 μV/K for the N-MWCNT buckypapers or powders and between −4.7 μV/K and −22.8 μV/K for the corresponding composites. With a higher content of N-MWCNTs, the increase in electrical conductivity led to increasing values of the power factor (PF) despite the unstable behavior of the Seebeck coefficient. The highest power factor was achieved with 4 wt% N-MWCNT, where a suitable combination of high electrical conductivity and acceptable Seebeck coefficient led to a PF value of 6.1 × 10−3 µW/(m·K2). First experiments have shown that transient absorption spectroscopy (TAS) is a useful tool to study the carrier transfer process in CNTs in composites and to correlate it with the Seebeck coefficient.
Influence of Glass Additions on Illitic Clay Ceramics
Authors: Shishkin Andrei , Baronins Janis , Mironovs Viktors , Lukáč František , Štubňa Igor , Ozolins Jurijs
Published: January 2020

A mixture of an illitic clay and waste glass was prepared and studied during the sintering process. The illitic clay, from the Liepa deposit (Latvia), and green glass waste (GW) were disintegrated to obtain a homogeneous mixture. The addition of disintegrated GW (5–15 wt% in the mixture) led to a reduction in the intensive sintering temperature, from 900 to 860 °C, due to a significant decrease in the glass viscosity. The addition of GW slightly decreased the intensities of the endo- and exothermic reactions in the temperature range from 20 to 1000 °C due to the reduced concentration of clay minerals. GW reduced the plasticity of the clay and reduced the risk of structural breakage. The increase in sintering temperature from 700 to 1000 °C decreased the apparent porosity and water uptake capacity of the ceramics from 35% and 22%, down to 24% and 13%, respectively. The apparent porosities of all the sintered mixtures showed a decrease of between 6% to 9% after the addition of GW with concentrations from 5 up to 15 wt% respectively, while the water uptake capacities decreased from between 4% and 10%. The addition of GW led to an increase in the apparent density of the ceramic materials, up to 2.2 g/cm3. Furthermore, the compressive strength increased by more than two times, reaching a highest value of 240 MPa after the sintering of the 15 wt% GW-containing mixture at 1000 °C.
Additive Manufactured Large Zr-Based Bulk Metallic Glass Composites with Desired Deformation Ability and Corrosion Resistance
Authors: Luo Yu , Xing Leilei , Jiang Yidong , Li Ruiwen , Lu Chao , Zeng Rongguang , Luo Jinru , Zhang Pengcheng , Liu Wei
Published: January 2020

Zr-based bulk metallic glasses have been attracting tremendous interest of researchers because of their unique combination of mechanical and chemical properties. However, their application is limited as large-scale production is difficult due to the limitation of cooling rate. Recently, additive manufacturing technology has been proposed as a new solution for fabricating bulk metallic glasses without size limitation. In this study, selective laser melting technology was used to prepare Zr60Fe10Cu20Al10 bulk metallic glass. The laser parameters for fabricating full dense amorphous specimens were investigated. The mechanical and corrosion resistance properties of the prepared samples were measured by micro-compression and electrochemical corrosion testing, respectively. Lastly, Zr60Fe10Cu20Al10 bulk metallic glass (BMG) with dispersed nano-crystals was made, and good deformation ability was revealed during micro-compression test. The corrosion resistance decreased a bit due to the crystalline phases. The results provide a promising route for manufacturing large and complex bulk metallic glasses with better mechanical property and acceptable corrosion resistance.
Modelling the Mechanical Attributes (Roughness, Strength, and Hardness) of Al-alloy A356 during Sand Casting
Authors: Ishfaq Kashif , Ali Muhammad Asad , Ahmad Naveed , Zahoor Sadaf , Al-Ahmari Abdulrahman M. , Hafeez Faisal
Published: January 2020

Sand-casting is a well established primary process for manufacturing various parts of A356 alloy. However, the quality of the casting is adversely affected by the change in the magnitude of the control variables. For instance, a larger magnitude of pouring velocity induces a drop effect and a lower velocity increases the likelihood of cold-shut and mis-run types of defects. Similarly, a high pouring temperature causes the formation of hot tears, whereas a low temperature is a source of premature solidification. Likewise, a higher moisture content yields microcracks (due to gas shrinkages) in the casting and a lower moisture content results in the poor strength of the mold. Therefore, the appropriate selection of control variables is essential to ensure quality manufactured products. The empirical relations could provide valuable guidance in this regard. Additionally, although the casting process was optimized for A356 alloy, it was mostly done for a single response. Therefore, this paper aimed to formulate empirical relations for the contradictory responses, i.e., hardness, ultimate tensile strength and surface roughness, using the response surface methodology. The experimental results were comprehensively analyzed using statistical and scanning electron microscopic analyses. Optimized parameters were proposed and validated to achieve castings with high hardness (84.5 HB) and strength (153.5 MPa) with minimum roughness (5.8 µm).
Robust Finite-Time Tracking Control for Robotic Manipulators with Time Delay Estimation
Authors: Zhang Tie , Zhang Aimin
Published: January 2020

In this study, a robust H∞ finite-time tracking controller is proposed for robotic manipulators based on time delay estimation. In this controller, there is no need to know the dynamics of robots, so it is quite simple. The high-gain observer is employed to estimate the joint velocities, which makes it much lower in cost. The theorem proof shows that the closed-loop system is finite-time stable and has a L2 gain that is less than or equal to γ, which shows high accuracy and strong robustness to estimation errors and external disturbances. Simulations on a two-link robot illustrate the effectiveness and advantages of the proposed controllers.
Haematococcus pluvialis-Derived Astaxanthin Is a Potential Neuroprotective Agent against Optic Nerve Ischemia
Authors: Lin Wei-Ning , Kapupara Kishan , Wen Yao-Tseng , Chen Yi-Hsun , Pan I-Hong , Tsai Rong-Kung
Published: January 2020

Astaxanthin, a xanthophyll belonging to the family of carotenoids, is a potent antioxidant. However, much less is known about its protective effects on the oxidative stress of ischemic optic nerve. We hypothesized that astaxanthin treatment could protect retinal ganglion cells (RGCs) from death via anti-oxidative and anti-apoptotic responses. Adult male Wistar rats were fed astaxanthin (100 mg/kg/day) by daily gavage for seven consecutive days, either before or after inducing oxidative stress in the retina by photodynamic treatment. The visual function, RGC apoptosis, macrophage infiltration in the optic nerve, expression of p-Akt, p-mTOR, SGK1, pS6K, Nrf2, p62, TNFα, Il1β in retinas were investigated. The visual function and the RGC densities were significantly higher in both pre- and post-treatment groups. The numbers of apoptotic RGCs and extrinsic macrophage infiltration in the optic nerve were significantly decreased in both astaxanthin-treated groups. Furthermore, pre- and post-treatment of astaxanthin showed a higher expression of p-Akt, p-mTOR, Nrf2 and superoxide dismutase activity, and a lower expression of cleaved caspase-3, suggesting anti-apoptotic and anti-oxidative roles. Our findings indicate that astaxanthin can preserve visual function and reduce RGC apoptosis after ischemic insults. Including astaxanthin in daily diet as a supplement may be beneficiary for ischemic optic neuropathy.