bluuebunny/crossref_metadata_2025 huggingface dataset:
Alteration of Electron Acceptor Preferences in the Oxidative Half-Reaction of Flavin-Dependent Oxidases and Dehydrogenases
Authors: Hiraka Kentaro , Tsugawa Wakako , Sode Koji
Published: May 2020

In this review, recent progress in the engineering of the oxidative half-reaction of flavin-dependent oxidases and dehydrogenases is discussed, considering their current and future applications in bioelectrochemical studies, such as for the development of biosensors and biofuel cells. There have been two approaches in the studies of oxidative half-reaction: engineering of the oxidative half-reaction with oxygen, and engineering of the preference for artificial electron acceptors. The challenges for engineering oxidative half-reactions with oxygen are further categorized into the following approaches: (1) mutation to the putative residues that compose the cavity where oxygen may be located, (2) investigation of the vicinities where the reaction with oxygen may take place, and (3) investigation of possible oxygen access routes to the isoalloxazine ring. Among these approaches, introducing a mutation at the oxygen access route to the isoalloxazine ring represents the most versatile and effective strategy. Studies to engineer the preference of artificial electron acceptors are categorized into three different approaches: (1) engineering of the charge at the residues around the substrate entrance, (2) engineering of a cavity in the vicinity of flavin, and (3) decreasing the glycosylation degree of enzymes. Among these approaches, altering the charge in the vicinity where the electron acceptor may be accessed will be most relevant.
Isolation of Human Small Extracellular Vesicles and Tracking of Their Uptake by Retinal Pigment Epithelial Cells In Vitro
Authors: Marcu Irene C. , Eberhard Naja , Yerly Anaïs , Balmer Verena , Hemphill Andrew , Mogel Helga , Gaschen Véronique , Stoffel Michael H. , Bluteau Jasmin
Published: May 2020

Small extracellular vesicles (EVs) are among the most frequently investigated EVs and play major roles in intercellular communication by delivering various cargo molecules to target cells. They could potentially represent an alternative delivery strategy to treat ocular toxoplasmosis, a parasitosis affecting the retinal pigment epithelium (RPE). To date, the uptake of human small EVs by RPE cells has never been reported. In this study, we report on the intracellular uptake of fluorescently labelled human urine and fibroblast-derived small EVs by human RPE cells. In summary, both dye-labelled urinary small EVs and small EVs obtained from fibroblasts stably expressing membrane-bound green fluorescent protein were successfully internalized by RPE cells as revealed by immunohistochemistry. In recipient ARPE19 cells, BODIPY-labelled small EVs were found in close vicinity to the parasite Toxoplasma gondii. Additionally, an ultrastructural method was enabled to distinguish between labelled exogenous and endogenous small EVs within target cells.
CRISPR/Cas9-Mediated Gene Correction to Understand ALS
Authors: Yun Yeomin , Ha Yoon
Published: May 2020

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the death of motor neurons in the spinal cord and brainstem. ALS has a diverse genetic origin; at least 20 genes have been shown to be related to ALS. Most familial and sporadic cases of ALS are caused by variants of the SOD1, C9orf72, FUS, and TARDBP genes. Genome editing using clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9 (CRISPR/Cas9) can provide insights into the underlying genetics and pathophysiology of ALS. By correcting common mutations associated with ALS in animal models and patient-derived induced pluripotent stem cells (iPSCs), CRISPR/Cas9 has been used to verify the effects of ALS-associated mutations and observe phenotype differences between patient-derived and gene-corrected iPSCs. This technology has also been used to create mutations to investigate the pathophysiology of ALS. Here, we review recent studies that have used CRISPR/Cas9 to understand the genetic underpinnings of ALS.
Molecular Research on Platelet Activity in Health and Disease
Authors: Catani Maria Valeria , Savini Isabella , Gasperi Valeria
Published: May 2020

This editorial summarizes and discusses the themes of eleven articles (five reviews and six original studies) published in the Special Issue “Molecular Research On Platelet Activity in Health and Disease”. They give an international picture of the up-to-date understanding of (i) platelet signalling under physiological and pathological conditions, (ii) novel technologies for monitoring platelet functions and (iii) clinical applications of platelet-based-therapy for management of pathological conditions, not directly related to haemostasis and thrombosis.
Association of A Novel Splice Site Mutation in P/Q-Type Calcium Channels with Childhood Epilepsy and Late-Onset Slowly Progressive Non-Episodic Cerebellar Ataxia
Authors: Stendel Claudia , D’Adamo Maria Cristina , Wiessner Manuela , Dusl Marina , Cenciarini Marta , Belia Silvia , Nematian-Ardestani Ehsan , Bauer Peter , Senderek Jan , Klopstock Thomas , Pessia Mauro
Published: May 2020

Episodic ataxia type 2 (EA2) is characterized by paroxysmal attacks of ataxia with typical onset in childhood or early adolescence. The disease is associated with mutations in the voltage-gated calcium channel alpha 1A subunit (Cav2.1) that is encoded by the CACNA1A gene. However, previously unrecognized atypical symptoms and the genetic overlap existing between EA2, spinocerebellar ataxia type 6, familial hemiplegic migraine type 1, and other neurological diseases blur the genotype/phenotype correlations, making a differential diagnosis difficult to formulate correctly and delaying early therapeutic intervention. Here we report a new clinical phenotype of a CACNA1A-associated disease characterized by absence epilepsy occurring during childhood. However, much later in life the patient displayed non-episodic, slowly progressive gait ataxia. Gene panel sequencing for hereditary ataxias led to the identification of a novel heterozygous CACNA1A mutation (c.1913 + 2T > G), altering the donor splice site of intron 14. This genetic defect was predicted to result in an in-frame deletion removing 44 amino acids from the voltage-gated calcium channel Cav2.1. An RT-PCR analysis of cDNA derived from patient skin fibroblasts confirmed the skipping of the entire exon 14. Furthermore, two-electrode voltage-clamp recordings performed from Xenopus laevis oocytes expressing a wild-type versus mutant channel showed that the genetic defect caused a complete loss of channel function. This represents the first description of distinct clinical manifestations that remarkably expand the genetic and phenotypic spectrum of CACNA1A-related diseases and should be considered for an early diagnosis and effective therapeutic intervention.
The FT-IR and Raman Spectroscopies as Tools for Biofilm Characterization Created by Cariogenic Streptococci
Authors: Gieroba Barbara , Krysa Mikolaj , Wojtowicz Kinga , Wiater Adrian , Pleszczyńska Małgorzata , Tomczyk Michał , Sroka-Bartnicka Anna
Published: May 2020

Fourier transform infrared (FT-IR) and Raman spectroscopy and mapping were applied to the analysis of biofilms produced by bacteria of the genus Streptococcus. Bacterial biofilm, also called dental plaque, is the main cause of periodontal disease and tooth decay. It consists of a complex microbial community embedded in an extracellular matrix composed of highly hydrated extracellular polymeric substances and is a combination of salivary and bacterial proteins, lipids, polysaccharides, nucleic acids, and inorganic ions. This study confirms the value of Raman and FT-IR spectroscopies in biology, medicine, and pharmacy as effective tools for bacterial product characterization.
Disruption of the Auxin Gradient in the Abscission Zone Area Evokes Asymmetrical Changes Leading to Flower Separation in Yellow Lupine
Authors: Kućko Agata , Wilmowicz Emilia , Pokora Wojciech , Alché Juan De Dios
Published: May 2020

How auxin transport regulates organ abscission is a long-standing and intriguing question. Polar auxin transport across the abscission zone (AZ) plays a more important role in the regulation of abscission than a local concentration of this hormone. We recently reported the existence of a spatiotemporal sequential pattern of the indole-3-acetic acid (IAA) localization in the area of the yellow lupine AZ, which is a place of flower detachment. In this study, we performed analyses of AZ following treatment with an inhibitor of polar auxin transport (2,3,5-triiodobenzoic acid (TIBA)). Once we applied TIBA directly onto the AZ, we observed a strong response as demonstrated by enhanced flower abscission. To elucidate the molecular events caused by the inhibition of auxin movement, we divided the AZ into the distal and proximal part. TIBA triggered the formation of the IAA gradient between these two parts. The AZ-marker genes, which encode the downstream molecular components of the inflorescence deficient in abscission (IDA)-signaling system executing the abscission, were expressed in the distal part. The accumulation of IAA in the proximal area accelerated the biosynthesis of abscisic acid and ethylene (stimulators of flower separation), which was also reflected at the transcriptional level. Accumulated IAA up-regulated reactive oxygen species (ROS) detoxification mechanisms. Collectively, we provide new information regarding auxin-regulated processes operating in specific areas of the AZ.
Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling
Authors: Annunziata Maria Carmela , Parisi Melania , Esposito Gabriella , Fabbrocini Gabriella , Ammendola Rosario , Cattaneo Fabio
Published: May 2020

FPR1, FPR2, and FPR3 are members of Formyl Peptides Receptors (FPRs) family belonging to the GPCR superfamily. FPR2 is a low affinity receptor for formyl peptides and it is considered the most promiscuous member of this family. Intracellular signaling cascades triggered by FPRs include the activation of different protein kinases and phosphatase, as well as tyrosine kinase receptors transactivation. Protein kinases and phosphatases act coordinately and any impairment of their activation or regulation represents one of the most common causes of several human diseases. Several phospho-sites has been identified in protein kinases and phosphatases, whose role may be to expand the repertoire of molecular mechanisms of regulation or may be necessary for fine-tuning of switch properties. We previously performed a phospho-proteomic analysis in FPR2-stimulated cells that revealed, among other things, not yet identified phospho-sites on six protein kinases and one protein phosphatase. Herein, we discuss on the selective phosphorylation of Serine/Threonine-protein kinase N2, Serine/Threonine-protein kinase PRP4 homolog, Serine/Threonine-protein kinase MARK2, Serine/Threonine-protein kinase PAK4, Serine/Threonine-protein kinase 10, Dual specificity mitogen-activated protein kinase kinase 2, and Protein phosphatase 1 regulatory subunit 14A, triggered by FPR2 stimulation. We also describe the putative FPR2-dependent signaling cascades upstream to these specific phospho-sites.
Human PSC-Derived Hepatocytes Express Low Levels of Viral Pathogen Recognition Receptors, but Are Capable of Mounting an Effective Innate Immune Response
Authors: Fischer Lena , Lucendo-Villarin Baltasar , Hay David C. , O’Farrelly Cliona
Published: May 2020

Hepatocytes are key players in the innate immune response to liver pathogens but are challenging to study because of inaccessibility and a short half-life. Recent advances in in vitro differentiation of hepatocyte-like cells (HLCs) facilitated studies of hepatocyte–pathogen interactions. Here, we aimed to define the anti-viral innate immune potential of human HLCs with a focus on pattern recognition receptor (PRR)-expression and the presence of a metabolic switch. We analysed cytoplasmic PRR and endosomal toll-like receptor (TLR)-expression, as well as activity and adaptation of HLCs to an inflammatory environment. We found that transcript levels of retinoic acid inducible gene I (RIG-I), melanoma differentiation antigen 5 (MDA5), and TLR3 became downregulated during differentiation, indicating the acquisition of a more tolerogenic phenotype, as expected in healthy hepatocytes. HLCs responded to activation of RIG-I by producing interferons (IFNs) and IFN-stimulated genes. Despite low-level levels of TLR3, receptor expression was upregulated in an inflammatory environment. TLR3 signalling induced expression of proinflammatory cytokines at the gene level, indicating that several PRRs need to interact for successful innate immune activation. The inflammatory responsiveness of HLCs was accompanied by the downregulation of cytochrome P450 3A and 1A2 activity and decreased serum protein production, showing that the metabolic switch seen in primary hepatocytes during anti-viral responses is also present in HLCs.
SAK3 Administration Improves Spine Abnormalities and Cognitive Deficits in AppNL-G-F/NL-G-F Knock-in Mice by Increasing Proteasome Activity through CaMKII/Rpt6 Signaling
Authors: Izumi Hisanao , Kawahata Ichiro , Shinoda Yasuharu , Helmstetter Fred J. , Fukunaga Kohji
Published: May 2020

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by neuropathological hallmarks consisting of accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFT). Recently, we have identified a new AD therapeutic candidate, ethyl-8′-methyl-2′,4-dioxo-2-(piperidin-1-yl)-2′H-spiro[cyclopentane-1,3′-imidazo [1,2-a] pyridin]-2-ene-3-carboxylate (SAK3), which ameliorates the AD-like pathology in AppNL-F/NL-F knock-in mice. However, the detailed mechanism underlying the therapeutic effects of SAK3 remains unclear. In this study, we found that SAK3 administration improved the reduced proteasome activity through the activation of CaMKII/Rpt6 signaling in AppNL-F/NL-F knock-in (NL-G-F) mice. Moreover, spine abnormalities observed in NL-G-F mice were significantly reversed by SAK3 administration. Along with this, cognitive impairments found in NL-G-F mice were markedly ameliorated by SAK3. In summary, our data suggest that SAK3 administration increases the activity of the proteasome via activation of the CaMKII/Rpt6 signaling pathway, contributing to improvements in spine abnormalities and cognitive deficits in NL-G-F mice. Overall, our findings suggest that SAK3 might be a new attractive drug candidate, representing a new mechanism for the treatment of AD pathology.
Functional Expression of Piezo1 in Dorsal Root Ganglion (DRG) Neurons
Authors: Roh Jueun , Hwang Sung-Min , Lee Sun-Ho , Lee Kihwan , Kim Yong Ho , Park Chul-Kyu
Published: May 2020

Piezo channels are mechanosensitive ion channels. Piezo1 is primarily expressed in nonsensory tissues, whereas Piezo2 is predominantly found in sensory tissues, including dorsal root ganglion (DRG) neurons. However, a recent study demonstrated the intracellular calcium response to Yoda1, a selective Piezo1 agonist, in trigeminal ganglion (TG) neurons. Herein, we investigate the expression of Piezo1 mRNA and protein in mouse and human DRG neurons and the activation of Piezo1 via calcium influx by Yoda1. Yoda1 induces inward currents mainly in small- (<25 μm) and medium-sized (25–35 μm) mouse DRG neurons. The Yoda1-induced Ca2+ response is inhibited by cationic channel blocker, ruthenium red and cationic mechanosensitive channel blocker, GsMTx4. To confirm the specific inhibition of Piezo1, we performed an adeno-associated virus serotype 2/5 (AAV2/5)-mediated delivery of short hairpin RNA (shRNA) into mouse DRG neurons. AAV2/5 transfection downregulates piezo1 mRNA expression and reduces Ca2+ response by Yoda1. Piezo1 also shows physiological functions with transient receptor potential vanilloid 1 (TRPV1) in the same DRG neurons and is regulated by the activation of TRPV1 in mouse DRG sensory neurons. Overall, we found that Piezo1 has physiological functions in DRG neurons and that TRPV1 activation inhibits an inward current induced by Yoda1.
miR-129-5p and miR-130a-3p Regulate VEGFR-2 Expression in Sensory and Motor Neurons during Development
Authors: Glaesel Kevin , May Caroline , Marcus Katrin , Matschke Veronika , Theiss Carsten , Theis Verena
Published: May 2020

The wide-ranging influence of vascular endothelial growth factor (VEGF) within the central (CNS) and peripheral nervous system (PNS), for example through effects on axonal growth or neuronal cell survival, is mainly mediated by VEGF receptor 2 (VEGFR-2). However, the regulation of VEGFR-2 expression during development is not yet well understood. As microRNAs are considered to be key players during neuronal maturation and regenerative processes, we identified the two microRNAs (miRNAs)—miR-129-5p and miR-130a-3p—that may have an impact on VEGFR-2 expression in young and mature sensory and lower motor neurons. The expression level of VEGFR-2 was analyzed by using in situ hybridization, RT-qPCR, Western blot, and immunohistochemistry in developing rats. microRNAs were validated within the spinal cord and dorsal root ganglia. To unveil the molecular impact of our candidate microRNAs, dissociated cell cultures of sensory and lower motor neurons were transfected with mimics and inhibitors. We depicted age-dependent VEGFR-2 expression in sensory and lower motor neurons. In detail, in lower motor neurons, VEGFR-2 expression was significantly reduced during maturation, in conjunction with an increased level of miR-129-5p. In sensory dorsal root ganglia, VEGFR-2 expression increased during maturation and was accompanied by an overexpression of miR-130a-3p. In a second step, the functional significance of these microRNAs with respect to VEGFR-2 expression was proven. Whereas miR-129-5p seems to decrease VEGFR-2 expression in a direct manner in the CNS, miR-130a-3p might indirectly control VEGFR-2 expression in the PNS. A detailed understanding of genetic VEGFR-2 expression control might promote new strategies for the treatment of severe neurological diseases like ischemia or peripheral nerve injury.
Broad-Spectrum Coronavirus Fusion Inhibitors to Combat COVID-19 and Other Emerging Coronavirus Diseases
Authors: Wang Xinling , Xia Shuai , Wang Qian , Xu Wei , Li Weihua , Lu Lu , Jiang Shibo
Published: May 2020

In the past 17 years, three novel coronaviruses have caused severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the coronavirus disease 2019 (COVID-19). As emerging infectious diseases, they were characterized by their novel pathogens and transmissibility without available clinical drugs or vaccines. This is especially true for the newly identified COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) for which, to date, no specific antiviral drugs or vaccines have been approved. Similar to SARS and MERS, the lag time in the development of therapeutics is likely to take months to years. These facts call for the development of broad-spectrum anti-coronavirus drugs targeting a conserved target site. This review will systematically describe potential broad-spectrum coronavirus fusion inhibitors, including antibodies, protease inhibitors, and peptide fusion inhibitors, along with a discussion of their advantages and disadvantages.
Implications of Skeletal Muscle Extracellular Matrix Remodeling in Metabolic Disorders: Diabetes Perspective
Authors: Ahmad Khurshid , Choi Inho , Lee Yong-Ho
Published: May 2020

The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Skeletal muscle ECM is a complex network comprising collagens, proteoglycans, glycoproteins, and elastin. Recent therapeutic approaches targeting ECM remodeling have been extensively deliberated. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. Skeletal muscle ECM remodeling is thought to be a feature of the pathogenic milieu allied with metabolic dysregulation, obesity, and eventual diabetes. This narrative review explores the current understanding of key components of skeletal muscle ECM and their specific roles in the regulation of metabolic diseases. Additionally, we discuss muscle-specific integrins and their role in the regulation of insulin sensitivity. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.
Riboflavin Deficiency—Implications for General Human Health and Inborn Errors of Metabolism
Authors: Mosegaard Signe , Dipace Graziana , Bross Peter , Carlsen Jasper , Gregersen Niels , Olsen Rikke Katrine Jentoft
Published: May 2020

As an essential vitamin, the role of riboflavin in human diet and health is increasingly being highlighted. Insufficient dietary intake of riboflavin is often reported in nutritional surveys and population studies, even in non-developing countries with abundant sources of riboflavin-rich dietary products. A latent subclinical riboflavin deficiency can result in a significant clinical phenotype when combined with inborn genetic disturbances or environmental and physiological factors like infections, exercise, diet, aging and pregnancy. Riboflavin, and more importantly its derivatives, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), play a crucial role in essential cellular processes including mitochondrial energy metabolism, stress responses, vitamin and cofactor biogenesis, where they function as cofactors to ensure the catalytic activity and folding/stability of flavoenzymes. Numerous inborn errors of flavin metabolism and flavoenzyme function have been described, and supplementation with riboflavin has in many cases been shown to be lifesaving or to mitigate symptoms. This review discusses the environmental, physiological and genetic factors that affect cellular riboflavin status. We describe the crucial role of riboflavin for general human health, and the clear benefits of riboflavin treatment in patients with inborn errors of metabolism.
HRness in Breast and Ovarian Cancers
Authors: Santana dos Santos Elizabeth , Lallemand François , Petitalot Ambre , Caputo Sandrine M. , Rouleau Etienne
Published: May 2020

Ovarian and breast cancers are currently defined by the main pathways involved in the tumorigenesis. The majority are carcinomas, originating from epithelial cells that are in constant division and subjected to cyclical variations of the estrogen stimulus during the female hormonal cycle, therefore being vulnerable to DNA damage. A portion of breast and ovarian carcinomas arises in the context of DNA repair defects, in which genetic instability is the backdrop for cancer initiation and progression. For these tumors, DNA repair deficiency is now increasingly recognized as a target for therapeutics. In hereditary breast/ovarian cancers (HBOC), tumors with BRCA1/2 mutations present an impairment of DNA repair by homologous recombination (HR). For many years, BRCA1/2 mutations were only screened on germline DNA, but now they are also searched at the tumor level to personalize treatment. The reason of the inactivation of this pathway remains uncertain for most cases, even in the presence of a HR-deficient signature. Evidence indicates that identifying the mechanism of HR inactivation should improve both genetic counseling and therapeutic response, since they can be useful as new biomarkers of response.
CopomuS—Ranking Compensatory Mutations to Guide RNA-RNA Interaction Verification Experiments
Authors: Raden Martin , Gutmann Fabio , Uhl Michael , Backofen Rolf
Published: May 2020

In silico RNA-RNA interaction prediction is widely applied to identify putative interaction partners and to assess interaction details in base pair resolution. To verify specific interactions, in vitro evidence can be obtained via compensatory mutation experiments. Unfortunately, the selection of compensatory mutations is non-trivial and typically based on subjective ad hoc decisions. To support the decision process, we introduce our COmPensatOry MUtation Selector CopomuS. CopomuS evaluates the effects of mutations on RNA-RNA interaction formation using a set of objective criteria, and outputs a reliable ranking of compensatory mutation candidates. For RNA-RNA interaction assessment, the state-of-the-art IntaRNA prediction tool is applied. We investigate characteristics of successfully verified RNA-RNA interactions from the literature, which guided the design of CopomuS. Finally, we evaluate its performance based on experimentally validated compensatory mutations of prokaryotic sRNAs and their target mRNAs. CopomuS predictions highly agree with known results, making it a valuable tool to support the design of verification experiments for RNA-RNA interactions. It is part of the IntaRNA package and available as stand-alone webserver for ad hoc application.
Contact Effect Contribution to the High Efficiency of Lithium Chloride Against the Mite Parasite of the Honey Bee
Authors: Kolics Éva , Mátyás Kinga , Taller János , Specziár András , Kolics Balázs
Published: May 2020

Lithium chemicals have been proven to be very effective in eradicating Varroa destructor, the detrimental parasite of the honey bee; however, little is known about the side effects on brood and long term consequences on the colony. Earlier, it was proposed that the action mechanisms of lithium chloride do not include the contact mode. Here, we investigate this question using a paper strip test to demonstrate the concentration-dependent effectiveness of lithium in the contact mode of action, confirming that it is also a contact agent against the Varroa mite. According to our knowledge, this is the first report on the high varroicidal effect of lithium in the contact mode of action. Our findings may open up possibilities for novel ways of treatment (e.g., the use of lithiated strips) in the event that lithium salts become legal for use in apiculture.
Microstructure and Texture Variations in High Temperature Titanium Alloy Ti65 Sheets with Different Rolling Modes and Heat Treatments
Authors: Zhao Ding , Fan Jiangkun , Zhang Zhixin , Liu Xudong , Wang Qingjiang , Chen Zhiyong , Tang Bin , Kou Hongchao , Jia Shuanxiao , Li Jinshan
Published: May 2020

Ti65 alloy (Ti-5.8Al-4.0Sn-3.5Zr-0.5Mo-0.4Si-0.3Nb-1.0Ta-0.8W-0.05C) is the newly developed high temperature titanium alloy optimized from Ti60 alloys. The long-term service temperature of the alloy is as high as 650 °C, which is unattainable with the previous high temperature titanium alloy. It has excellent strength and excellent creep resistance, and has great application prospects in the aerospace industry. In the current study, the evolution of microstructure and texture of Ti65 alloy sheets developed by unidirectional rolling (UDR) and cross rolling (CR) followed by solution and aging treatment was investigated. The microstructure of the UDR sample consists of equiaxed α p , lamellar α s and few elongated α p , and the texture is the combination of minor B-type and major T-type texture, with the main component of basal {0001} fiber texture and { 01 1 ¯ 0 } < 2 1 ¯ 1 ¯ 0 > , respectively. Due to more active slip system resulted by transformed direction, the microstructure of the CR sample consists of more elongated α p , and the { 01 1 ¯ 0 } <0001> texture characterized as R-type texture forms in addition to B/T-type texture. With aging temperature increasing, the microstructures for both transform to duplex microstructure, and the thicknesses of lamellar α s increase. B-type texture becomes stronger, while T/R-type texture are weakened, which is caused by the combination of recrystallization, spheroidization, and variant selection. An abnormal increasing of T/R-type texture but constant B-type texture happens in the CR-600 sample, which is related to high recrystallization fraction. It is expected that the research results can provide useful references for the rolling of high temperature titanium alloy sheets and the precise control of microstructure/texture.
Selenium Deficiency Is Widespread and Spatially Dependent in Ethiopia
Authors: Belay Adamu , Joy Edward J. M. , Chagumaira Christopher , Zerfu Dilnesaw , Ander E. Louise , Young Scott D. , Bailey Elizabeth H. , Lark R. Murray , Broadley Martin R. , Gashu Dawd
Published: May 2020

Selenium (Se) is an essential element for human health and livestock productivity. Globally, human Se status is highly variable, mainly due to the influence of soil types on the Se content of crops, suggesting the need to identify areas of deficiency to design targeted interventions. In sub-Saharan Africa, including Ethiopia, data on population Se status are largely unavailable, although previous studies indicated the potential for widespread Se deficiency. Serum Se concentration of a nationally representative sample of the Ethiopian population was determined, and these observed values were combined with a spatial statistical model to predict and map the Se status of populations across the country. The study used archived serum samples (n = 3269) from the 2015 Ethiopian National Micronutrient Survey (ENMS). The ENMS was a cross-sectional survey of young and school-age children, women and men. Serum Se concentration was measured using inductively coupled plasma mass spectrometry (ICPMS). The national median (Q1, Q3) serum Se concentration was 87.7 (56.7, 123.0) μg L−1. Serum Se concentration differed between regions, ranging from a median (Q1, Q3) of 54.6 (43.1, 66.3) µg L−1 in the Benishangul-Gumuz Region to 122.0 (105, 141) µg L−1 in the Southern Nations, Nationalities, and Peoples’ Region and the Afar Region. Overall, 35.5% of the population were Se deficient, defined as serum Se < 70 µg L−1. A geostatistical analysis showed that there was marked spatial dependence in Se status, with serum concentrations greatest among those living in North-East and Eastern Ethiopia and along the Rift Valley, while serum Se concentrations were lower among those living in North-West and Western Ethiopia. Selenium deficiency in Ethiopia is widespread, but the risk of Se deficiency is highly spatially dependent. Policies to enhance Se nutrition should target populations in North-West and Western Ethiopia.
Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma
Authors: Uchida Daisuke , Takaki Akinobu , Oyama Atsushi , Adachi Takuya , Wada Nozomu , Onishi Hideki , Okada Hiroyuki
Published: May 2020

Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients’ disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis.
Bifidobacterium longum Subspecies infantis (B. infantis) in Pediatric Nutrition: Current State of Knowledge
Authors: Chichlowski Maciej , Shah Neil , Wampler Jennifer L. , Wu Steven S. , Vanderhoof Jon A.
Published: May 2020

Since originally isolated in 1899, the genus Bifidobacterium has been demonstrated to predominate in the gut microbiota of breastfed infants and to benefit the host by accelerating maturation of the immune response, balancing the immune system to suppress inflammation, improving intestinal barrier function, and increasing acetate production. In particular, Bifidobacterium longum subspecies infantis (B. infantis) is well adapted to the infant gut and has co-evolved with the mother-infant dyad and gut microbiome, in part due to its ability to consume complex carbohydrates found in human milk. B. infantis and its human host have a symbiotic relationship that protects the preterm or term neonate and nourishes a healthy gut microbiota prior to weaning. To provide benefits associated with B. infantis to all infants, a number of commercialized strains have been developed over the past decades. As new ingredients become available, safety and suitability must be assessed in preclinical and clinical studies. Consideration of the full clinical evidence for B. infantis use in pediatric nutrition is critical to better understand its potential impacts on infant health and development. Herein we summarize the recent clinical studies utilizing select strains of commercialized B. infantis.
A Snapshot of the Prevalence and Molecular Diversity of Legionella pneumophila in the Water Systems of Israeli Hotels
Authors: Yakunin Eugenia , Kostyal Eszter , Agmon Vered , Grotto Itamar , Valinsky Lea , Moran-Gilad Jacob
Published: May 2020

Exposure to Legionella spp. contaminated aerosols in hotel settings confers risk for travel-associated Legionnaire’s disease (TALD). In this study, we investigated the prevalence of Legionella contamination and its molecular diversity in hotels and resorts across Israel. The study was comprised of a convenience sample of water systems from 168 hotels and resorts countrywide, routinely inspected between March 2015 and February 2017. Isolation and quantitation of Legionella were performed in a water laboratory using the ISO 11731 method. The distribution of Legionella isolates was analyzed according to geography and source. The genetic diversity of a subset of isolates was analyzed by sequence-based typing (SBT) at the National Reference Laboratory for Legionella and compared to the national database. Out of 2830 samples tested, 470 (17%) obtained from 102 different premises (60% of hotels) were positive for Legionella spp. In 230 samples (49% of all positive, 8% of total samples), accounting for 37% of hotels, Legionella spp. counts exceeded the regulatory threshold of 1000 CFU/L. The most frequently contaminated water sources were cooling towers (38%), followed by faucets, hot tubs, water lines, and storage tanks (14–17% each). Furthermore, 32% and 17% of samples obtained from cooling towers and hot tubs, respectively, exceeded the regulatory thresholds. SBT was performed on 78 strains and revealed 27 different sequence types (STs), including two novel STs. The most prevalent STs found were ST1 (26%), ST87 (10%), ST93 (6%), and ST461 and ST1516 (5% each). Several L. pneumophila STs were found to be limited to certain geographical regions. This is the first study to investigate the prevalence and diversity of Legionella in hotels and resorts in Israel during non-outbreak environmental inspections. These findings will inform risk assessment, surveillance, and control measures of TALD.
Surface Plasmon Resonance (SPR)-Based Biosensors as Instruments with High Versatility and Sensitivity
Authors: Shpacovitch Victoria , Hergenröder Roland
Published: May 2020

Surface plasmon resonance (SPR), as a physical phenomenon, is not restricted only to events occurring in thin planar metal films [...]
Gamma Radiation Imaging System via Variable and Time-Multiplexed Pinhole Arrays
Authors: Schwarz Ariel , Shemer Amir , Danan Yossef , Bar-Shalom Rachel , Avraham Hemy , Zlotnik Alex , Zalevsky Zeev
Published: May 2020

Biomedical planar imaging using gamma radiation is a very important screening tool for medical diagnostics. Since lens imaging is not available in gamma imaging, the current methods use lead collimator or pinhole techniques to perform imaging. However, due to ineffective utilization of the gamma radiation emitted from the patient’s body and the radioactive dose limit in patients, poor image signal to noise ratio (SNR) and long image capturing time are evident. Furthermore, the resolution is related to the pinhole diameter, thus there is a tradeoff between SNR and resolution. Our objectives are to reduce the radioactive dose given to the patient and to preserve or improve SNR, resolution and capturing time while incorporating three-dimensional capabilities in existing gamma imaging systems. The proposed imaging system is based on super-resolved time-multiplexing methods using both variable and moving pinhole arrays. Simulations were performed both in MATLAB and GEANT4, and gamma single photon emission computed tomography (SPECT) experiments were conducted to support theory and simulations. The proposed method is able to reduce the radioactive dose and image capturing time and to improve SNR and resolution. The results and method enhance the gamma imaging capabilities that exist in current systems, while providing three-dimensional data on the object.
Numerical and Experimental UAV Structure Investigation by Pre-Flight Load Test
Authors: Kurnyta Artur , Zielinski Wojciech , Reymer Piotr , Dragan Krzysztof , Dziendzikowski Michal
Published: May 2020

This paper presents the preparation and execution of on-ground static and engine load tests for the composite unmanned aerial vehicle (UAV). The test was conducted for pre-flight structural strength verification of the remotely piloted aerial target named HORNET, after introducing some structural modifications. The ground tests were performed before the flight test campaign, to ensure the strength and operational safety of the modified structure. The panel method and Computer Aided Design (CAD) modelling were adopted for numerical evaluation of aerodynamic and inertial forces’ distribution to simulate loading scenarios for launch, flight and parachute deploying conditions during the static test. Then, the multi-stage airframe static test was prepared and executed with the use of a designed modular test rig, artificial masses, as well as a wireless strain measurement system to perform structure verification. The UAV was investigated with 150% of the typical load spectrum. Furthermore, an engine test was also conducted on a ground test stand to verify strain and vibration levels in correspondence to engine speed, as well as the reliability of data link and the lack of its interferences with wireless control and telemetry. In the article, data achieved from the numerical and experimental parts of the test are discussed, as well as post-test remarks are given.
Gamma Radiation-Induced Effects over an Optical Fiber Laser: Towards New Sensing Applications
Authors: Perez-Herrera Rosa Ana , Stancalie Andrei , Cabezudo Pablo , Sporea Dan , Neguţ Daniel , Lopez-Amo Manuel
Published: May 2020

In the present work, the effect of gamma radiation on the performance of different types of erbium-doped fibers (EDFs) when they are used in a fiber ring cavity (FRC) configuration is studied. Several pieces of commercial EDF are gamma-ray irradiated with different doses to evaluate the output power variations over time. The influence of different doses, from 150 Gy to 1000 Gy, over the output power level measurement and their amplified spontaneous emission (ASE) are experimentally evaluated both in the C and L bands. By using an FRC configuration we can detect the presence of gamma radiation. We can also estimate the irradiation doses applied to EDFs by measuring the slope of the short-term emission power.
Performance of a Low-Cost Sensor Community Air Monitoring Network in Imperial County, CA
Authors: English Paul , Amato Heather , Bejarano Esther , Carvlin Graeme , Lugo Humberto , Jerrett Michael , King Galatea , Madrigal Daniel , Meltzer Dan , Northcross Amanda , Olmedo Luis , Seto Edmund , Torres Christian , Wilkie Alexa , Wong Michelle
Published: May 2020

Air monitoring networks developed by communities have potential to reduce exposures and affect environmental health policy, yet there have been few performance evaluations of networks of these sensors in the field. We developed a network of over 40 air sensors in Imperial County, CA, which is delivering real-time data to local communities on levels of particulate matter. We report here on the performance of the Network to date by comparing the low-cost sensor readings to regulatory monitors for 4 years of operation (2015–2018) on a network-wide basis. Annual mean levels of PM10 did not differ statistically from regulatory annual means, but did for PM2.5 for two out of the 4 years. R2s from ordinary least square regression results ranged from 0.16 to 0.67 for PM10, and increased each year of operation. Sensor variability was higher among the Network monitors than the regulatory monitors. The Network identified a larger number of pollution episodes and identified under-reporting by the regulatory monitors. The participatory approach of the project resulted in increased engagement from local and state agencies and increased local knowledge about air quality, data interpretation, and health impacts. Community air monitoring networks have the potential to provide real-time reliable data to local populations.
Background Point Filtering of Low-Channel Infrastructure-Based LiDAR Data Using a Slice-Based Projection Filtering Algorithm
Authors: Lin Ciyun , Liu Hui , Wu Dayong , Gong Bowen
Published: May 2020

A light detection and ranging (LiDAR) sensor can obtain richer and more detailed traffic flow information than traditional traffic detectors, which could be valuable data input for various novel intelligent transportation applications. However, the point cloud generated by LiDAR scanning not only includes road user points but also other surrounding object points. It is necessary to remove the worthless points from the point cloud by using a suitable background filtering algorithm to accelerate the micro-level traffic data extraction. This paper presents a background point filtering algorithm using a slice-based projection filtering (SPF) method. First, a 3-D point cloud is projected to 2-D polar coordinates to reduce the point data dimensions and improve the processing efficiency. Then, the point cloud is classified into four categories in a slice unit: Valuable object points (VOPs), worthless object points (WOPs), abnormal ground points (AGPs), and normal ground points (NGPs). Based on the point cloud classification results, the traffic objects (pedestrians and vehicles) and their surrounding information can be easily identified from an individual frame of the point cloud. We proposed an artificial neuron network (ANN)-based model to improve the adaptability of the algorithm in dealing with the road gradient and LiDAR-employing inclination. The experimental results showed that the algorithm of this paper successfully extracted the valuable points, such as road users and curbstones. Compared to the random sample consensus (RANSAC) algorithm and 3-D density-statistic-filtering (3-D-DSF) algorithm, the proposed algorithm in this paper demonstrated better performance in terms of the run-time and background filtering accuracy.
Gloxinia—An Open-Source Sensing Platform to Monitor the Dynamic Responses of Plants
Authors: Pieters Olivier , De Swaef Tom , Lootens Peter , Stock Michiel , Roldán-Ruiz Isabel , wyffels Francis
Published: May 2020

The study of the dynamic responses of plants to short-term environmental changes is becoming increasingly important in basic plant science, phenotyping, breeding, crop management, and modelling. These short-term variations are crucial in plant adaptation to new environments and, consequently, in plant fitness and productivity. Scalable, versatile, accurate, and low-cost data-logging solutions are necessary to advance these fields and complement existing sensing platforms such as high-throughput phenotyping. However, current data logging and sensing platforms do not meet the requirements to monitor these responses. Therefore, a new modular data logging platform was designed, named Gloxinia. Different sensor boards are interconnected depending upon the needs, with the potential to scale to hundreds of sensors in a distributed sensor system. To demonstrate the architecture, two sensor boards were designed—one for single-ended measurements and one for lock-in amplifier based measurements, named Sylvatica and Planalta, respectively. To evaluate the performance of the system in small setups, a small-scale trial was conducted in a growth chamber. Expected plant dynamics were successfully captured, indicating proper operation of the system. Though a large scale trial was not performed, we expect the system to scale very well to larger setups. Additionally, the platform is open-source, enabling other users to easily build upon our work and perform application-specific optimisations.
A Cognitive Method for Automatically Retrieving Complex Information on a Large Scale
Authors: Wang Yongyue , Yao Beitong , Wang Tianbo , Xia Chunhe , Zhao Xianghui
Published: May 2020

Modern retrieval systems tend to deteriorate because of their large output of useless and even misleading information, especially for complex search requests on a large scale. Complex information retrieval (IR) tasks requiring multi-hop reasoning need to fuse multiple scattered text across two or more documents. However, there are two challenges for multi-hop retrieval. To be specific, the first challenge is that since some important supporting facts have little lexical or semantic relationship with the retrieval query, the retriever often omits them; the second challenge is that once a retriever chooses misinformation related to the query as the entities of cognitive graphs, the retriever will fail. In this study, in order to improve the performance of retrievers in complex tasks, an intelligent sensor technique was proposed based on a sub-scope with cognitive reasoning (2SCR-IR), a novel method of retrieving reasoning paths over the cognitive graph to provide users with verified multi-hop reasoning chains. Inspired by the users’ process of step-by-step searching online, 2SCR-IR includes a dynamic fusion layer that starts from the entities mentioned in the given query, explores the cognitive graph dynamically built from the query and contexts, gradually finds relevant supporting entities mentioned in the given documents, and verifies the rationality of the retrieval facts. Our experimental results show that 2SCR-IR achieves competitive results on the HotpotQA full wiki and distractor settings, and outperforms the previous state-of-the-art methods by a more than two points absolute gain on the full wiki setting.