bluuebunny/crossref_metadata_2025 huggingface dataset:
TEfinder: A Bioinformatics Pipeline for Detecting New Transposable Element Insertion Events in Next-Generation Sequencing Data
Authors: Sohrab Vista , López-Díaz Cristina , Di Pietro Antonio , Ma Li-Jun , Ayhan Dilay Hazal
Published: February 2021

Transposable elements (TEs) are mobile elements capable of introducing genetic changes rapidly. Their importance has been documented in many biological processes, such as introducing genetic instability, altering patterns of gene expression, and accelerating genome evolution. Increasing appreciation of TEs has resulted in a growing number of bioinformatics software to identify insertion events. However, the application of existing tools is limited by either narrow-focused design of the package, too many dependencies on other tools, or prior knowledge required as input files that may not be readily available to all users. Here, we reported a simple pipeline, TEfinder, developed for the detection of new TE insertions with minimal software and input file dependencies. The external software requirements are BEDTools, SAMtools, and Picard. Necessary input files include the reference genome sequence in FASTA format, an alignment file from paired-end reads, existing TEs in GTF format, and a text file of TE names. We tested TEfinder among several evolving populations of Fusarium oxysporum generated through a short-term adaptation study. Our results demonstrate that this easy-to-use tool can effectively detect new TE insertion events, making it accessible and practical for TE analysis.
The Genetic Basis of Tomato Aroma
Authors: Martina Matteo , Tikunov Yury , Portis Ezio , Bovy Arnaud G.
Published: February 2021

Tomato (Solanum lycopersicum L.) aroma is determined by the interaction of volatile compounds (VOCs) released by the tomato fruits with receptors in the nose, leading to a sensorial impression, such as “sweet”, “smoky”, or “fruity” aroma. Of the more than 400 VOCs released by tomato fruits, 21 have been reported as main contributors to the perceived tomato aroma. These VOCs can be grouped in five clusters, according to their biosynthetic origins. In the last decades, a vast array of scientific studies has investigated the genetic component of tomato aroma in modern tomato cultivars and their relatives. In this paper we aim to collect, compare, integrate and summarize the available literature on flavour-related QTLs in tomato. Three hundred and fifty nine (359) QTLs associated with tomato fruit VOCs were physically mapped on the genome and investigated for the presence of potential candidate genes. This review makes it possible to (i) pinpoint potential donors described in literature for specific traits, (ii) highlight important QTL regions by combining information from different populations, and (iii) pinpoint potential candidate genes. This overview aims to be a valuable resource for researchers aiming to elucidate the genetics underlying tomato flavour and for breeders who aim to improve tomato aroma.
Predicting and Interpreting Spatial Accidents through MDLSTM
Authors: Xiao Tianzheng , Lu Huapu , Wang Jianyu , Wang Katrina
Published: February 2021

Predicting and interpreting the spatial location and causes of traffic accidents is one of the current hot topics in traffic safety. This research purposed a multi-dimensional long-short term memory neural network model (MDLSTM) to fit the non-linear relationships between traffic accident characteristics and land use properties, which are further interpreted to form local and general rules. More variables are taken into account as the input land use properties and the output traffic accident characteristics. Five types of traffic accident characteristics are simultaneously predicted with higher accuracy, and three levels of interpretation, including the hidden factor-traffic potential, the potential-determine factors, which varies between grid cells, and the general rules across the whole study area are analyzed. Based on the model, some interesting insights were revealed including the division line in the potential traffic accidents in Shenyang (China). It is also purposed that the relationship between land use and accidents differ from previous researches in the neighboring and regional aspects. Neighboring grids have strong spatial connections so that the relationship of accidents in a continuous area is relatively similar. In a larger region, the spatial location is found to have a great influence on the traffic accident and has a strong directionality.
Zinc Based Metal-Organic Frameworks as Ofloxacin Adsorbents in Polluted Waters: ZIF-8 vs. Zn3(BTC)2
Authors: Capsoni Doretta , Guerra Giulia , Puscalau Constantin , Maraschi Federica , Bruni Giovanna , Monteforte Francesco , Profumo Antonella , Sturini Michela
Published: February 2021

Two different zinc-based metal-organic frameworks (MOFs) were investigated to remove one of the most used fluoroquinolone antibiotic, Ofloxacin (OFL), from polluted water. The most common zeolitic imidazolate framework-8 (ZIF-8) and the green Zn(II) and benzene-1,3,5-tri-carboxylate (Zn3(BTC)2) were prepared through a facile synthetic route and characterized by means of Fourier-Transform Infrared (FT-IR) Spectroscopy, X-ray Powder Diffraction (XRPD), and Scanning Electron Microscopy (SEM) analyses. The two MOFs were compared in terms of both adsorption and kinetic aspects under real conditions (tap water, natural pH). Results showed that OFL was adsorbed in remarkable amounts, 95 ± 10 and 25.3 ± 0.8 mg g−1 on ZIF-8 and Zn3(BTC)2, respectively, following different mechanisms. Specifically, a Langmuir model well described the ZIF-8 profile, while for Zn3(BTC)2, cooperative adsorption occurred. Moreover the kinetic results were quite different, pseudo-second-order and sigmoidal, respectively. The suitability of ZIF-8 and Zn3(BTC)2 as adsorbent phases for water depollution was tested on tap water samples spiked with OFL 10 µg L−1. The obtained removal efficiencies, of 88% for ZIF-8 and 72% for Zn3(BTC)2, make these materials promising candidates for removing fluoroquinolone antibiotics (FQs) from polluted waters, notwithstanding their limited reusability in tap water, as demonstrated by in-depth characterization of the two MOFs after usage.
Active Methodologies in Physical Education: Perception and Opinion of Students on the Pedagogical Model Used by Their Teachers
Authors: Crisol Moya Emilio , Caurcel Cara María Jesús
Published: February 2021

The teaching of physical education today still incorporates innovative methodologies in order to create quality physical education. This article sets out to describe which pedagogical model is used in the initial training of physical education teachers at the University of Granada, from the perspective of the students. The study adopted an exploratory, descriptive and comparative research design, applying a survey to a sample of 303 physical education students. The students perceive that their teachers make use of different organising modalities, methodological strategies and assessment systems that favour the use of active methodologies. The structural equations model for analysing predictive relations between the three methodological components (organising modalities, methodological approaches and evaluation systems) was fitted correctly, obtaining positive relations between the three components. The model also showed positive and negative influences in the opinion of the students in the planning of the teaching–learning methodologies and some of the methodological components. The results indicate that the perception and opinion of the physical education students take on a special role in the development of student-centred methodologies.
Performance of the Hendrich Fall Risk Model II in Patients Discharged from Rehabilitation Wards. A Preliminary Study of Predictive Ability
Authors: Campanini Isabella , Bargellini Annalisa , Mastrangelo Stefano , Lombardi Francesco , Tolomelli Stefano , Lusuardi Mirco , Merlo Andrea
Published: February 2021

(1) Background: Falls are a dangerous adverse event in patients discharged from rehabilitation units, with the risk of falling being higher in the first weeks after discharge. In this study, we assessed the predictive performance of the Hendrich Fall Risk Model II tool (HIIFRM) when administered before discharging patients to their home from rehabilitative units in orthopedic (OR), neurologic (NR) and pulmonary (PR) rehabilitation wards. (2) Methods: Over a 6-month period, all adult patients who returned home after discharge were assessed by HIIFRM. At six months from discharge the occurrence of falls was obtained by performing a structured survey. The HIIFRM predictive performance was determined by the area under the ROC curve (AUC), sensitivity (Se) and specificity (Sp) for the whole sample and split by ward. (3) Results: 85 of 141 discharged patients were living at home and agreed to take part in the survey. Of these, 19 subjects fell, 6 suffered fractures or head traumas and 5 were hospitalized. The AUC was 0.809 (95% CI: 0.656–0.963), Se was 0.67 (0.30–0.93) and Sp was 0.79 (0.63–0.90) for OR patients. (4) Conclusions: Our preliminary results support the use of HIIFRM as a tool to be administered to OR patients at discharge and provides data for the design of a large study of predictive ability.
The Combined Effects of Fine Particulate Matter and Temperature on Preterm Birth in Seoul, 2010–2016
Authors: Kwag Youngrin , Kim Min-ho , Ye Shinhee , Oh Jongmin , Yim Gyeyoon , Kim Young Ju , Kim Eunji , Lee Semi , Koh Tai Kyung , Ha Eunhee
Published: February 2021

Background: Preterm birth contributes to the morbidity and mortality of newborns and infants. Recent studies have shown that maternal exposure to particulate matter and extreme temperatures results in immune dysfunction, which can induce preterm birth. This study aimed to evaluate the association between fine particulate matter (PM2.5) exposure, temperature, and preterm birth in Seoul, Republic of Korea. Methods: We used 2010–2016 birth data from Seoul, obtained from the Korea National Statistical Office Microdata. PM2.5 concentration data from Seoul were generated through the Community Multiscale Air Quality (CMAQ) model. Seoul temperature data were collected from the Korea Meteorological Administration (KMA). The exposure period of PM2.5 and temperature were divided into the first (TR1), second (TR2), and third (TR3) trimesters of pregnancy. The mean PM2.5 concentration was used in units of ×10 µg/m3 and the mean temperature was divided into four categories based on quartiles. Logistic regression analyses were performed to evaluate the association between PM2.5 exposure and preterm birth, as well as the combined effects of PM2.5 exposure and temperature on preterm birth. Result: In a model that includes three trimesters of PM2.5 and temperature data as exposures, which assumes an interaction between PM2.5 and temperature in each trimester, the risk of preterm birth was positively associated with TR1 PM2.5 exposure among pregnant women exposed to relatively low mean temperatures (<3.4 °C) during TR1 (OR 1.134, 95% CI 1.061–1.213, p < 0.001). Conclusions: When we assumed the interaction between PM2.5 exposure and temperature exposure, PM2.5 exposure during TR1 increased the risk of preterm birth among pregnant women exposed to low temperatures during TR1. Pregnant women should be aware of the risk associated with combined exposure to particulate matter and low temperatures during TR1 to prevent preterm birth.
An Egocentric Network Contact Tracing Experiment: Testing Different Procedures to Elicit Contacts and Places
Authors: Pilny Andrew , Huber C. Joseph
Published: February 2021

Contact tracing is one of the oldest social network health interventions used to reduce the diffusion of various infectious diseases. However, some infectious diseases like COVID-19 amass at such a great scope that traditional methods of conducting contact tracing (e.g., face-to-face interviews) remain difficult to implement, pointing to the need to develop reliable and valid survey approaches. The purpose of this research is to test the effectiveness of three different egocentric survey methods for extracting contact tracing data: (1) a baseline approach, (2) a retrieval cue approach, and (3) a context-based approach. A sample of 397 college students were randomized into one condition each. They were prompted to anonymously provide contacts and populated places visited from the past four days depending on what condition they were given. After controlling for various demographic, social identity, psychological, and physiological variables, participants in the context-based condition were significantly more likely to recall more contacts (medium effect size) and places (large effect size) than the other two conditions. Theoretically, the research supports suggestions by field theory that assume network recall can be significantly improved by activating relevant activity foci. Practically, the research contributes to the development of innovative social network data collection methods for contract tracing survey instruments.
Smartphone Use and Willingness to Pay for HIV Treatment-Assisted Smartphone Applications among HIV-Positive Patients in Urban Clinics of Vietnam
Authors: Bui Thu Minh , Hoang Men Thi , Ngo Toan Van , Do Cuong Duy , Nghiem Son Hong , Byrnes Joshua , Phung Dung Tri , Nguyen Trang Huyen Thi , Vu Giang Thu , Do Hoa Thi , Latkin Carl A. , Ho Roger C.M. , Ho Cyrus S.H.
Published: February 2021

This study aimed to examine the effectiveness of Human Immunodeficiency Virus (HIV)-assisted smartphone applications in the treatment of HIV/AIDS patients in Vietnam. A cross-sectional study was performed in two urban outpatient clinics in Hanoi from May to December 2019. A simple random sampling method and a structured questionnaire were used to recruit 495 eligible participants and to collect data. Multivariable modified Poisson regression and multivariable linear regression models were employed to investigate the factors associated with the willingness to pay (WTP) and amount of money patients were willing to pay. Approximately 82.8% of respondents were willing to pay for the hypothetical applications, with the mean amount the participants were willing to pay of Vietnam Dong (VND) 72,100/month. Marital status (separate/divorced/widow: Odds ratio (OR) = 1.28, 95% confidence interval (CI) = (1.09; 1.50) and having spouse/partner: OR = 1.18, 95% CI = (1.03; 1.36)) and using health services (OR = 1.03, 95% CI = (1.01; 1.04)) were positively associated with nominating they would be WTP for the app, whereas the duration of antiretroviral treatment (ART) (OR = 0.98, 95% CI = (0.96; 0.99)) had a negative association. The frequency of using health services (β = 0.04, 95% CI = (−0.07; −0.01)) was negatively associated with the amount of WTP. High levels of WTP revealed the feasibility of implementing smartphone-based apps for HIV treatment. This study implied the necessity to consider a co-payment system to reach populations who were in need but where such applications may be unaffordable in lieu of other treatment-associated expenses. Developers also need to pay attention to privacy features to attract single people living with HIV/AIDS and additional measures to initiate people with a long duration on ART into using the applications.
Role of Mesh Pore Size in Dynamic Membrane Bioreactors
Authors: Vergine Pompilio , Salerno Carlo , Casale Barbara , Berardi Giovanni , Pollice Alfieri
Published: February 2021

Two identical bench-scale Self-Forming Dynamic Membrane BioReactors (SFD MBR) were set-up and operated for the treatment of real urban wastewater. The two bioreactors were equipped with meshes of different mesh pore size. Meshes having pore size values of 20 and 50 µm were tested under solid retention time (SRT) of 15 d, whereas meshes with 50 and 100 µm pore sizes were compared under SRT of 50 d. The results of long-term experiments showed very good overall performances by all systems at the steady state. High flux (in the range 61–71 L m−2 h−1) and very good effluent quality were obtained, with average suspended solids and chemical oxygen demanding values below 10 mg L−1 and 35 mg L−1, respectively. The mesh pore size did not have a major influence on the average cleaning frequency. However, the pore size affected the effluent quality in correspondence of two particular conditions: (i) immediately after mesh cleaning; and (ii) during operation under high suction pressures (mesh clogging not promptly removed through cleaning). Moreover, the mesh cleaning frequency was observed to be dependent on the SRT. In tests with 50 d SRT, the cleaning requirements were very low (one every five days), and this limited the influence of the mesh pore size on the effluent quality. In conclusion, in SFD MBR, the role of the mesh pore size on the effluent quality may be more or less relevant depending on the operating conditions that directly influence the Dynamic Membrane formation.
Ozone Concentration Levels in Urban Environments—Upper Silesia Region Case Study
Authors: Kobza Joanna , Geremek Mariusz , Dul Lechosław
Published: February 2021

Although ozone (O3) plays a crucial role in screening the Earth’s surface and lower atmosphere layers from the ultraviolet radiation, troposphere ozone is proven to have negative health effects on the human body and is one of the greenhouse gases. The objective of this study was to perform a measurement-based assessment for determining whether the concentration of ozone is within admissible limits, or exceeded, in Silesia Province and does not pose a threat to the local population. The data provided by the Voivodship Inspectorate for Environmental Protection in Katowice were used in the analysis. The received data constitute the result of 8-h measurements of concentrations of ozone at selected air monitoring stations of the Silesian province. The locations of three monitoring stations were found to be useful for the aim of this research; one site is situated in a rural background area; another one is located in a medium-sized city and the Katowice station is representative for an urban background situation. We used cluster analysis, weighted pair group method using arithmetic averages (WPGMA) and Chebyshev distances to test the hypothesis and compare empirical distributions in the general population. The alarm level has not been exceeded in indicated measurements stations in Silesian Voivodship in the period 2015–2017 (averaging time 1 h: 240 µg/m3 for 3 h). The target level was exceeded in 2015 at all three measurements stations and in the following years at one station (in Zloty Potok, 2016, and in Katowice, 2017). Each year, the largest number of exceedances occurred in August. The results clearly indicate a lack of hazards for the general population’s health in terms of increased concentrations of ozone in the city centers and outside. The results confirm that environmental conditions (i.e., landform, the area surrounding monitoring station) have a significant influence on the ozone level.
Life Satisfaction during Forced Social Distancing and Home Confinement Derived from the COVID-19 Pandemic in Spain
Authors: Gonzalez-Bernal Jerónimo J , Rodríguez-Fernández Paula , Santamaría-Peláez Mirian , González-Santos Josefa , León-del-Barco Benito , Minguez Luis A. , Soto-Cámara Raúl
Published: February 2021

Life satisfaction is one of the main dimensions of well-being related to psychological factors, being essential for a person to adjust to difficult circumstances. The restrictive measures adopted to minimize the diffusion of the coronavirus disease (COVID-19) could alter the subjective dimension of well-being, so the objective of this study was to determine the factors related to life satisfaction of the Spanish population during forced home confinement derived from the COVID-19 pandemic. A cross-sectional study was designed, based on an online survey, and disseminated through the main social networks, which included the Satisfaction with Life Scale (SWLS) and sociodemographic and COVID-19-related variables. The possible relationships between the different variables were studied using univariate and multivariable regression analyses. A total of 3261 subjects participated in the study. Factors associated with greater personal life satisfaction were fewer days of home confinement (β = (−0.088); p ≤ 0.001), the perception of having received enough information (β = 0.076; p ≤ 0.001), having private access to the outside (β = 0.066; p ≤ 0.001), being employed (β = 0.063; p ≤ 0.001), being male (β = 0.057; p = 0.001) and not having been isolated (β = 0.043; p = 0.013). The results of this study provide novel information about the profiles of people related to greater well-being and life satisfaction during forced social distancing and home confinement, but more studies are needed to help to understand and complement these findings.
Transition to Multidisciplinary Pediatric Telerehabilitation during the COVID-19 Pandemic: Strategy Development and Implementation
Authors: Krasovsky Tal , Silberg Tamar , Barak Sharon , Eisenstein Etzyona , Erez Neta , Feldman Irit , Guttman Dafna , Liber Pnina , Patael Smadar Zohar , Sarna Hadar , Sadeh Yaara , Steinberg Pnina , Landa Jana
Published: February 2021

Telerehabilitation offers a unique solution for continuity of care in pediatric rehabilitation under physical distancing. The major aims of this study were to: (1) describe the development of telerehabilitation usage guidelines in a large hospital in Israel, and to (2) evaluate the implementation of telerehabilitation from the perspectives of healthcare practitioners and families. An expert focus group developed guidelines which were disseminated to multidisciplinary clinicians. Following sessions, clinicians filled The Clinician Evaluation of Telerehabilitation Service (CETS), a custom-built feedback questionnaire on telerehabilitation, and parents completed the client version of the Therapist Presence Inventory (TPI-C) and were asked to rate the effectiveness of sessions on an ordinal scale. Four goals of telerehabilitation sessions were defined: (1) maintenance of therapeutic alliance, (2) provision of parental coping strategies, (3) assistance in maintaining routine, and (4) preventing functional deterioration. Principal Components Analysis was used for the CETS questionnaire and the relationships of CETS and TPI-C with child’s age and the type of session were evaluated using Spearman’s correlations and the Kruskal–Wallis H test. In total, sixty-seven telerehabilitation sessions, with clients aged 11.31 ± 4.8 years, were documented by clinicians. Three components (child, session, parent) explained 71.3% of the variance in CETS. According to therapists, their ability to maintain the therapeutic alliance was generally higher than their ability to achieve other predefined goals (p < 0.01). With younger children, the ability to provide feedback to the child, grade treatment difficulty and provide coping strategies to the parents were diminished. Families perceived the therapist as being highly present in therapy regardless of treatment type. These results demonstrate a potential framework for the dissemination of telerehabilitation services in pediatric rehabilitation.
Readiness of Allied Professionals to Join the Mental Health Workforce: A Qualitative Evaluation of Trained Lay Trauma Counsellors’ Experiences When Refugee Youth Disclose Suicidal Ideation
Authors: Löfving Gupta Sandra , Wijk Katarina , Warner Georgina , Sarkadi Anna
Published: February 2021

The recent refugee crisis presented a huge challenge for the Swedish mental health workforce. Hence, innovative mental health workforce solutions were needed. Unaccompanied refugee minors (URM) are a particularly vulnerable refugee group. Teaching Recovery Techniques (TRT) was introduced as a community-based intervention utilising trained lay counsellors in a stepped model of care for refugee youth experiencing trauma symptoms. Professionals (e.g., teachers, social workers) can deliver the Cognitive Behavioural Therapy-based intervention after a brief training. A point of debate in this workforce solution is the readiness of trained lay counsellors to deal with potentially demanding situations like disclosure of suicidal ideation. This study aimed to explore the TRT trained lay counsellors’ experiences of procedures upon URM’s disclosure of suicidal ideation. Individual semi-structured interviews with TRT trained lay counsellors were conducted, then analysed using systemic text condensation. The analysis revealed four themes: “Importance of safety structures”, “Collaboration is key”, “Let sleeping dogs lie” and “Going the extra mile”. Dealing with suicidal ideation is challenging and feelings of helplessness occur. Adding adequate supervision and specific training on suicidal ideation using role play is recommended. Collaboration between agencies and key stakeholders is essential when targeting refugee mental health in a stepped care model.
The Effect of Dry Carbon Dioxide Bathing on Peripheral Blood Circulation Measured by Thermal Imaging among Patients with Risk Factors of PAD
Authors: Zbroja Hanna , Kowalski Mateusz , Lubkowska Anna
Published: February 2021

Peripheral artery disease (PAD) is becoming a serious health problem of present times. It appears crucial to explore therapies that might help to restore blood flow or increase tissue oxygenation. The most effective methods of detecting early-stage changes in blood circulation in the extremities need to be identified. The aim of this study was to identify the effect of carbon dioxide (CO2) bathing on peripheral blood circulation measured by thermal imaging among patients with risk factors of PAD and ankle–brachial index (ABI) in the normal range or ABI indicating some or moderate arterial disease (ABI > 0.5). The correlation between surface temperature change and PAD-relevant characteristics was also examined. Forty-six patients who were over 65 years old who had a minimum of two additional PAD risk factors were recruited. A series of ten dry CO2 baths was performed. Thermal images were taken before and after the intervention. The CO2 therapy caused a significant change in the body surface temperature of many body areas. Numerous moderate correlations between temperature change and health-related characteristics were identified. Therefore, patients with PAD risk factors could benefit from CO2 therapy. Improvements in blood flow change the body surface temperature, and these changes could be successfully detected by thermal imaging.
Long-Range PCR-Based NGS Applications to Diagnose Mendelian Retinal Diseases
Authors: Maggi Jordi , Koller Samuel , Bähr Luzy , Feil Silke , Kivrak Pfiffner Fatma , Hanson James V. M. , Maspoli Alessandro , Gerth-Kahlert Christina , Berger Wolfgang
Published: February 2021

The purpose of this study was to develop a flexible, cost-efficient, next-generation sequencing (NGS) protocol for genetic testing. Long-range polymerase chain reaction (PCR) amplicons of up to 20 kb in size were designed to amplify entire genomic regions for a panel (n = 35) of inherited retinal disease (IRD)-associated loci. Amplicons were pooled and sequenced by NGS. The analysis was applied to 227 probands diagnosed with IRD: (A) 108 previously molecularly diagnosed, (B) 94 without previous genetic testing, and (C) 25 undiagnosed after whole-exome sequencing (WES). The method was validated with 100% sensitivity on cohort A. Long-range PCR-based sequencing revealed likely causative variant(s) in 51% and 24% of proband from cohorts B and C, respectively. Breakpoints of 3 copy number variants (CNVs) could be characterized. Long-range PCR libraries spike-in extended coverage of WES. Read phasing confirmed compound heterozygosity in 5 probands. The proposed sequencing protocol provided deep coverage of the entire gene, including intronic and promoter regions. Our method can be used (i) as a first-tier assay to reduce genetic testing costs, (ii) to elucidate missing heritability cases, (iii) to characterize breakpoints of CNVs at nucleotide resolution, (iv) to extend WES data to non-coding regions by spiking-in long-range PCR libraries, and (v) to help with phasing of candidate variants.
Synthesis, Spectroscopy, Single-Crystal Structure Analysis and Antibacterial Activity of Two Novel Complexes of Silver(I) with Miconazole Drug
Authors: Stryjska Karolina , Korona-Glowniak Izabela , Chęcińska Lilianna , Kusz Joachim , Ochocki Justyn
Published: February 2021

In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)2NO3 (1)] and [Ag(MCZ)2ClO4 (2)] in HepG2 tumor cells compared to the corresponding salts of silver, miconazole and cisplatin. Here, we present the synthesis of two silver(I) complexes of miconazole containing two new counter ions in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = BF4− (3), SbF6− (4)). The novel silver(I) complexes were characterized by elemental analysis, 1H NMR, 13C NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry and X-ray-crystallography. In the present study, the antimicrobial activity of all obtained silver(I) complexes of miconazole against six strains of Gram-positive bacteria, five strains of Gram-negative bacteria and yeasts was evaluated. The results were compared with those of a silver sulfadiazine drug, the corresponding silver salts and the free ligand. Silver(I) complexes exhibited significant activity against Gram-positive bacteria, which was much better than that of silver sulfadiazine and silver salts. The highest antimicrobial activity was observed for the complex containing the nitrate counter ion. All Ag(I) complexes of miconazole resulted in much better inhibition of yeast growth than silver sulfadiazine, silver salts and miconazole. Moreover, the synthesized silver(I) complexes showed good or moderate activity against Gram-negative bacteria compared to the free ligand.
Resolvin D1 Decreases Severity of Streptozotocin-Induced Type 1 Diabetes Mellitus by Enhancing BDNF Levels, Reducing Oxidative Stress, and Suppressing Inflammation
Authors: Bathina Siresha , Das Undurti N.
Published: February 2021

Type 1 diabetes mellitus is an autoimmune disease characterized by increased production of pro-inflammatory cytokines secreted by infiltrating macrophages and T cells that destroy pancreatic β cells in a free radical-dependent manner that causes decrease or absence of insulin secretion and consequent hyperglycemia. Hence, suppression of pro-inflammatory cytokines and oxidative stress may ameliorate or decrease the severity of diabetes mellitus. To investigate the effect and mechanism(s) of action of RVD1, an anti-inflammatory metabolite derived from docosahexaenoic acid (DHA), on STZ-induced type 1 DM in male Wistar rats, type 1 diabetes was induced by single intraperitoneal (i.p) streptozotocin (STZ-65 mg/kg) injection. RVD1 (60 ng/mL, given intraperitoneally) was administered from day 1 along with STZ for five consecutive days. Plasma glucose, IL-6, TNF-α, BDNF (brain-derived neurotrophic factor that has anti-diabetic actions), LXA4 (lipoxin A4), and RVD1 levels and BDNF concentrations in the pancreas, liver, and brain tissues were measured. Apoptotic (Bcl2/Bax), inflammatory (COX-1/COX-2/Nf-κb/iNOS/PPAR-γ) genes and downstream insulin signaling proteins (Gsk-3β/Foxo1) were measured in the pancreatic tissue along with concentrations of various antioxidants and lipid peroxides. RVD1 decreased severity of STZ-induced type 1 DM by restoring altered plasma levels of TNF-α, IL-6, and BDNF (p < 0.001); expression of pancreatic COX-1/COX-2/PPAR-γ genes and downstream insulin signaling proteins (Gsk-3β/Foxo1) and the concentrations of antioxidants and lipid peroxides to near normal. RVD1 treatment restored expression of Bcl2/Pdx genes, plasma LXA4 (p < 0.001) and RVD1 levels and increased brain, pancreatic, intestine, and liver BDNF levels to near normal. The results of the present study suggest that RVD1 can prevent STZ-induced type 1 diabetes by its anti-apoptotic, anti-inflammatory, and antioxidant actions and by activating the Pdx gene that is needed for pancreatic β cell proliferation.
Disruption of the Complex between GAPDH and Hsp70 Sensitizes C6 Glioblastoma Cells to Hypoxic Stress
Authors: Mikeladze Marina A. , Dutysheva Elizaveta A. , Kartsev Victor G. , Margulis Boris A. , Guzhova Irina V. , Lazarev Vladimir F.
Published: February 2021

Hypoxia, which commonly accompanies tumor growth, depending on its strength may cause the enhancement of tumorigenicity of cancer cells or their death. One of the proteins targeted by hypoxia is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and we demonstrated here that hypoxia mimicked by treating C6 rat glioblastoma cells with cobalt chloride caused an up-regulation of the enzyme expression, while further elevation of hypoxic stress caused the enzyme aggregation concomitantly with cell death. Reduction or elevation of GAPDH performed with the aid of specific shRNAs resulted in the augmentation of the tumorigenicity of C6 cells or their sensitization to hypoxic stress. Another hypoxia-regulated protein, Hsp70 chaperone, was shown to prevent the aggregation of oxidized GAPDH and to reduce hypoxia-mediated cell death. In order to release the enzyme molecules from the chaperone, we employed its inhibitor, derivative of colchicine. The compound was found to substantially increase aggregation of GAPDH and to sensitize C6 cells to hypoxia both in vitro and in animals bearing tumors with distinct levels of the enzyme expression. In conclusion, blocking the chaperonic activity of Hsp70 and its interaction with GAPDH may become a promising strategy to overcome tumor resistance to multiple environmental stresses and enhance existing therapeutic tools.
Multiomics Integration in Skin Diseases with Alterations in Notch Signaling Pathway: PlatOMICs Phase 1 Deployment
Authors: Brandão Lucas André Cavalcanti , Tricarico Paola Maura , Gratton Rossella , Agrelli Almerinda , Zupin Luisa , Abou-Saleh Haissam , Moura Ronald , Crovella Sergio
Published: February 2021

The high volume of information produced in the age of omics was and still is an important step to understanding several pathological processes, providing the enlightenment of complex molecular networks and the identification of molecular targets associated with many diseases. Despite these remarkable scientific advances, the majority of the results are disconnected and divergent, making their use limited. Skin diseases with alterations in the Notch signaling pathway were extensively studied during the omics era. In the GWAS Catalog, considering only studies on genomics association (GWAS), several works were deposited, some of which with divergent results. In addition, there are thousands of scientific articles available about these skin diseases. In our study, we focused our attention on skin diseases characterized by the impairment of Notch signaling, this pathway being of pivotal importance in the context of epithelial disorders. We considered the pathologies of five human skin diseases, Hidradenitis Suppurativa, Dowling Degos Disease, Adams–Oliver Syndrome, Psoriasis, and Atopic Dermatitis, in which the molecular alterations in the Notch signaling pathway have been reported. To this end, we started developing a new multiomics platform, PlatOMICs, to integrate and re-analyze omics information, searching for the molecular interactions involved in the pathogenesis of skin diseases with alterations in the Notch signaling pathway.
The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease
Authors: Huang Chunling , Bian Ji , Cao Qinghua , Chen Xin-Ming , Pollock Carol A.
Published: February 2021

Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.
In Vivo Transcutaneous Monitoring of Hemoglobin Derivatives Using a Red-Green-Blue Camera-Based Spectral Imaging Technique
Authors: Khatun Fahima , Aizu Yoshihisa , Nishidate Izumi
Published: February 2021

Cyanosis is a pathological condition that is characterized by a bluish discoloration of the skin or mucous membranes. It may result from a number of medical conditions, including disorders of the respiratory system and central nervous system, cardiovascular diseases, peripheral vascular diseases, deep vein thrombosis, and regional ischemia. Cyanosis can also be elicited from methemoglobin. Therefore, a simple, rapid, and simultaneous monitoring of changes in oxygenated hemoglobin and deoxygenated hemoglobin is useful for protective strategies against organ ischemic injury. We previously developed a red-green-blue camera-based spectral imaging method for the measurements of melanin concentration, oxygenated hemoglobin concentration (CHbO), deoxygenated hemoglobin concentration (CHbR), total hemoglobin concentration (CHbT) and tissue oxygen saturation (StO2) in skin tissues. We leveraged this approach in this study and extended it to the simultaneous quantifications of methemoglobin concentration (CmetHb), CHbO, CHbR, and StO2. The aim of the study was to confirm the feasibility of the method to monitor CmetHb, CHbO, CHbR, CHbT, and StO2. We performed in vivo experiments using rat dorsal skin during methemoglobinemia induced by the administration of sodium nitrite (NaNO2) and changing the fraction of inspired oxygen (FiO2), including normoxia, hypoxia, and anoxia. Spectral diffuse reflectance images were estimated from an RGB image by the Wiener estimation method. Multiple regression analysis based on Monte Carlo simulations of light transport was used to estimate CHbO, CHbR, CmetHb, CHbT, and StO2. CmetHb rapidly increased with a half-maximum time of less than 30 min and reached maximal values nearly 60 min after the administration of NaNO2, whereas StO2 dramatically dropped after the administration of NaNO2, indicating the temporary production of methemoglobin and severe hypoxemia during methemoglobinemia. Time courses of CHbT and StO2, while changing the FiO2, coincided with well-known physiological responses to hyperoxia, normoxia, and hypoxia. The results indicated the potential of this method to evaluate changes in skin hemodynamics due to loss of tissue viability and vitality.
Pneumoviral Phosphoprotein, a Multidomain Adaptor-Like Protein of Apparent Low Structural Complexity and High Conformational Versatility
Authors: Cardone Christophe , Caseau Claire-Marie , Pereira Nelson , Sizun Christina
Published: February 2021

Mononegavirales phosphoproteins (P) are essential co-factors of the viral polymerase by serving as a linchpin between the catalytic subunit and the ribonucleoprotein template. They have highly diverged, but their overall architecture is conserved. They are multidomain proteins, which all possess an oligomerization domain that separates N- and C-terminal domains. Large intrinsically disordered regions constitute their hallmark. Here, we exemplify their structural features and interaction potential, based on the Pneumoviridae P proteins. These P proteins are rather small, and their oligomerization domain is the only part with a defined 3D structure, owing to a quaternary arrangement. All other parts are either flexible or form short-lived secondary structure elements that transiently associate with the rest of the protein. Pneumoviridae P proteins interact with several viral and cellular proteins that are essential for viral transcription and replication. The combination of intrinsic disorder and tetrameric organization enables them to structurally adapt to different partners and to act as adaptor-like platforms to bring the latter close in space. Transient structures are stabilized in complex with protein partners. This class of proteins gives an insight into the structural versatility of non-globular intrinsically disordered protein domains.
Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly
Authors: De Sanctis Paola , Filardo Giuseppe , Abruzzo Provvidenza Maria , Astolfi Annalisa , Bolotta Alessandra , Indio Valentina , Di Martino Alessandro , Hofer Christian , Kern Helmut , Löfler Stefan , Marcacci Maurilio , Marini Marina , Zampieri Sandra , Zucchini Cinzia
Published: February 2021

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared—the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.
The Chemistry of DPPH· Free Radical and Congeners
Authors: Ionita Petre
Published: February 2021

Since the discovery in 1922 of 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl stable free radical (DPPH·), the chemistry of such open-shell compounds has developed continuously, allowing for both theoretical and practical advances in the free radical chemistry area. This review presents the important, general and modern aspects of the chemistry of hydrazyl free radicals and the science behind it.
MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells
Authors: Arisan Elif Damla , Rencuzogullari Ozge , Cieza-Borrella Clara , Miralles Arenas Francesc , Dwek Miriam , Lange Sigrun , Uysal-Onganer Pinar
Published: February 2021

Breast cancer (BCa) is one of the leading health problems among women. Although significant achievements have led to advanced therapeutic success with targeted therapy options, more efforts are required for different subtypes of tumors and according to genomic, transcriptomic, and proteomic alterations. This study underlines the role of microRNA-21 (miR-21) in metastatic MDA-MB-231 breast cancer cells. Following the knockout of miR-21 from MDA-MB-231 cells, which have the highest miR-21 expression levels compared to MCF-7 and SK-BR-3 BCa cells, a decrease in epithelial-mesenchymal transition (EMT) via downregulation of mesenchymal markers was observed. Wnt-11 was a critical target for miR-21, and the Wnt-11 related signaling axis was altered in the stable miR-21 knockout cells. miR-21 expression was associated with a significant increase in mesenchymal markers in MDA-MB-231 BCa cells. Furthermore, the release of extracellular vesicles (EVs) was significantly reduced in the miR-21 KO cells, alongside a significant reduction in relative miR-21 export in EV cargo, compared with control cells. We conclude that miR-21 is a leading factor involved in mesenchymal transition in MDA-MB-231 BCa. Future therapeutic strategies could focus on its role in the treatment of metastatic breast cancer.
Identifying Wild Versus Cultivated Gene-Alleles Conferring Seed Coat Color and Days to Flowering in Soybean
Authors: Liu Cheng , Chen Xianlian , Wang Wubin , Hu Xinyang , Han Wei , He Qingyuan , Yang Hongyan , Xiang Shihua , Gai Junyi
Published: February 2021

Annual wild soybean (G. soja) is the ancestor of the cultivated soybean (G. max). To reveal the genetic changes from soja to max, an improved wild soybean chromosome segment substitution line (CSSL) population, SojaCSSLP5, composed of 177 CSSLs with 182 SSR markers (SSR-map), was developed based on SojaCSSLP1 generated from NN1138-2(max)×N24852(soja). The SojaCSSLP5 was genotyped further through whole-genome resequencing, resulting in a physical map with 1366 SNPLDBs (SNP linkage-disequilibrium blocks), which are composed of more markers/segments, shorter marker length and more recombination breakpoints than the SSR-map and caused 721 new wild substituted segments. Using the SNPLDB-map, two loci co-segregating with seed-coat color (SCC) and six loci for days to flowering (DTF) with 88.02% phenotypic contribution were identified. Integrated with parental RNA-seq and DNA-resequencing, two SCC and six DTF candidate genes, including three previously cloned (G, E2 and GmPRR3B) and five newly detected ones, were predicted and verified at nucleotide mutant level, and then demonstrated with the consistency between gene-alleles and their phenotypes in SojaCSSLP5. In total, six of the eight genes were identified with the parental allele-pairs coincided to those in 303 germplasm accessions, then were further demonstrated by the consistency between gene-alleles and germplasm phenotypes. Accordingly, the CSSL population integrated with parental DNA and RNA sequencing data was demonstrated to be an efficient platform in identifying candidate wild vs. cultivated gene-alleles.
Interaction of TLR4 and TLR8 in the Innate Immune Response against Mycobacterium Tuberculosis
Authors: Thada Shruthi , Horvath Gabor L. , Müller Mario M. , Dittrich Nickel , Conrad Melanie L. , Sur Saubashya , Hussain Abid , Pelka Karin , Gaddam Suman Latha , Latz Eicke , Slevogt Hortense , Schumann Ralf R. , Burkert Sanne
Published: February 2021

The interaction and crosstalk of Toll-like receptors (TLRs) is an established pathway in which the innate immune system recognises and fights pathogens. In a single nucleotide polymorphisms (SNP) analysis of an Indian cohort, we found evidence for both TLR4-399T and TRL8-1A conveying increased susceptibility towards tuberculosis (TB) in an interdependent manner, even though there is no established TLR4 ligand present in Mycobacterium tuberculosis (Mtb), which is the causative pathogen of TB. Docking studies revealed that TLR4 and TLR8 can build a heterodimer, allowing interaction with TLR8 ligands. The conformational change of TLR4-399T might impair this interaction. With immunoprecipitation and mass spectrometry, we precipitated TLR4 with TLR8-targeted antibodies, indicating heterodimerisation. Confocal microscopy confirmed a high co-localisation frequency of TLR4 and TLR8 that further increased upon TLR8 stimulation. The heterodimerisation of TLR4 and TLR8 led to an induction of IL12p40, NF-κB, and IRF3. TLR4-399T in interaction with TLR8 induced an increased NF-κB response as compared to TLR4-399C, which was potentially caused by an alteration of subsequent immunological pathways involving type I IFNs. In summary, we present evidence that the heterodimerisation of TLR4 and TLR8 at the endosome is involved in Mtb recognition via TLR8 ligands, such as microbial RNA, which induces a Th1 response. These findings may lead to novel targets for therapeutic interventions and vaccine development regarding TB.