bluuebunny/crossref_metadata_2025 huggingface dataset:
Competitive sgRNA Screen Identifies p38 MAPK as a Druggable Target to Improve HSPC Engraftment
Authors: Klatt Denise , Ha Teng-Cheong , Schinke Maximilian , Selich Anton , Lieske Anna , Dahlke Julia , Morgan Michael , Maetzig Tobias , Schambach Axel
Published: September 2020

Previous gene therapy trials for X-linked chronic granulomatous disease (X-CGD) lacked long-term engraftment of corrected hematopoietic stem and progenitor cells (HSPCs). Chronic inflammation and high levels of interleukin-1 beta (IL1B) might have caused aberrant cell cycling in X-CGD HSPCs with a concurrent loss of their long-term repopulating potential. Thus, we performed a targeted CRISPR-Cas9-based sgRNA screen to identify candidate genes that counteract the decreased repopulating capacity of HSPCs during gene therapy. The candidates were validated in a competitive transplantation assay and tested in a disease context using IL1B-challenged or X-CGD HSPCs. The sgRNA screen identified Mapk14 (p38) as a potential target to increase HSPC engraftment. Knockout of p38 prior to transplantation was sufficient to induce a selective advantage. Inhibition of p38 increased expression of the HSC homing factor CXCR4 and reduced apoptosis and proliferation in HSPCs. For potential clinical translation, treatment of IL1B-challenged or X-CGD HSPCs with a p38 inhibitor led to a 1.5-fold increase of donor cell engraftment. In summary, our findings demonstrate that p38 may serve as a potential druggable target to restore engraftment of HSPCs in the context of X-CGD gene therapy.
Hypoxia Promotes Mitochondrial Complex I Abundance via HIF-1α in Complex III and Complex IV Deficient Cells
Authors: Saldana-Caboverde Amy , Nissanka Nadee , Garcia Sofia , Lombès Anne , Diaz Francisca
Published: September 2020

Murine fibroblasts deficient in mitochondria respiratory complexes III (CIII) and IV (CIV) produced by either the ablation of Uqcrfs1 (encoding for Rieske iron sulfur protein, RISP) or Cox10 (encoding for protoheme IX farnesyltransferase, COX10) genes, respectively, showed a pleiotropic effect in complex I (CI). Exposure to 1–5% oxygen increased the levels of CI in both RISP and COX10 KO fibroblasts. De novo assembly of the respiratory complexes occurred at a faster rate and to higher levels in 1% oxygen compared to normoxia in both RISP and COX10 KO fibroblasts. Hypoxia did not affect the levels of assembly of CIII in the COX10 KO fibroblasts nor abrogated the genetic defect impairing CIV assembly. Mitochondrial signaling involving reactive oxygen species (ROS) has been implicated as necessary for HIF-1α stabilization in hypoxia. We did not observe increased ROS production in hypoxia. Exposure to low oxygen levels stabilized HIF-1α and increased CI levels in RISP and COX10 KO fibroblasts. Knockdown of HIF-1α during hypoxic conditions abrogated the beneficial effect of hypoxia on the stability/assembly of CI. These findings demonstrate that oxygen and HIF-1α regulate the assembly of respiratory complexes.
Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells
Authors: Montero-Montero Lucía , Renart Jaime , Ramírez Andrés , Ramos Carmen , Shamhood Mariam , Jarcovsky Rocío , Quintanilla Miguel , Martín-Villar Ester
Published: September 2020

Podoplanin and CD44 are transmembrane glycoproteins involved in inflammation and cancer. In this paper, we report that podoplanin is coordinately expressed with the CD44 standard (CD44s) and variant (CD44v) isoforms in vivo—in hyperplastic skin after a pro-inflammatory stimulus with 12-O-tetradecanoylphorbol-13-acetate (TPA)—and in vitro—in cell lines representative of different stages of mouse-skin chemical carcinogenesis, as well as in human squamous carcinoma cell (SCC) lines. Moreover, we identify CD44v10 in the mouse-skin carcinogenesis model as the only CD44 variant isoform expressed in highly aggressive spindle carcinoma cell lines together with CD44s and podoplanin. We also characterized CD44v3-10, CD44v6-10 and CD44v8-10 as the major variant isoforms co-expressed with CD44s and podoplanin in human SCC cell lines. Immunofluorescence confocal microscopy experiments show that these CD44v isoforms colocalize with podoplanin at plasma membrane protrusions and cell–cell contacts of SCC cells, as previously reported for CD44s. Furthermore, CD44v isoforms colocalize with podoplanin in chemically induced mouse-skin SCCs in vivo. Co-immunoprecipitation experiments indicate that podoplanin physically binds to CD44v3-10, CD44v6-10 and CD44v8-10 isoforms, as well as to CD44s. Podoplanin–CD44 interaction is mediated by the transmembrane and cytosolic regions and is negatively modulated by glycosylation of the extracellular domain. These results point to a functional interplay of podoplanin with both CD44v and CD44s isoforms in SCCs and give insight into the regulation of the podoplanin–CD44 association.
Effects of Inorganic ZnO Particle Doping on Crystalline Polymer Morphology and Space Charge Behavior
Authors: Yu Guang , Cheng Yujia
Published: September 2020

This study further investigated the synergistic effect of micro- and nanofiller doping on matrix material space charges and breakdown characteristics. Accordingly, low-density polyethylene (LDPE) was used as the matrix material, and spherical ZnO particles with sizes of 30 nm and 1 µm were used as additives. Micro-ZnO/LDPE, nano-ZnO/LDPE, and micro-nano-ZnO/LDPE composites were prepared through melt blending. The crystalline morphologies of the composites were observed via polarized light microscopy. The composite crystallinity and melting peak temperature were measured via differential scanning calorimetry, and the micro- and nanoparticle dispersions in the matrix were observed via scanning electron microscopy. The test results showed that the particles were uniformly dispersed in the polyethylene matrix. The filler acted as a heterogeneous nucleation agent in the matrix. The crystal size decreased, thereby increasing the crystal quantity. The doping of inorganic ZnO particles improved the composite crystallinity. The ZnO/LDPE composites were subjected to DC breakdown, space charge, and dielectric spectrum tests. When the crystal arrangement of the sample was loose and its size was large, the breakdown process developed along a shorter path, and the field strength of the composite breakdown decreased. The order of AC and DC breakdown field strengths of the samples was as follows: micro-ZnO/LDPE < pure LDPE < micro-nano-ZnO/LDPE < nano-ZnO/LDPE. The DC and AC breakdown field strengths of the micro- and nano-ZnO/LDPE were 4.7% and 3.2% higher than those of the pure LDPE, respectively. Moreover, the DC and AC breakdown field strengths of the nano-ZnO/LDPE were 11.02% and 15.8% higher than those of the pure LDPE, respectively. The doping of inorganic ZnO particles restrained the space charge accumulation, and the residual charges decreased after short-circuit treatment. The dielectric constant of all nanocomposites was lower than that of LDPE, and the dielectric loss of all composites was higher than that of LDPE.
On the Role of γ-Fe2O3 Nanoparticles and Reduced Graphene Oxide Nanosheets in Enhancing Self-Cleaning Properties of Composite TiO2 for Cultural Heritage Protection
Authors: Mokhtarifar Maryam , Kaveh Reyhaneh , Ormellese Marco , Bagherzadeh Mojtaba , Diamanti Maria , Pedeferri MariaPia
Published: September 2020

The durability of novel metallic artifacts and buildings is an open issue, and the role of smart protecting coatings in extending these artifacts’ lifetimes is crucial. In this paper, the role of γ-Fe2O3 nanoparticles and reduced graphene oxide (rGO) nanosheets on enhancing the self-cleaning properties of composite TiO2 films and reducing metal alterations due to contact with acid rain and pollutants is investigated. The photocatalytic assessment of the TiO2 based films indicates that there are optimum contents for γ-Fe2O3 and rGO, which confer the film lower bandgap and tune the TiO2 anatase/rutile ratio. By adding a proper content of γ-Fe2O3, wettability is reduced both in dark and under illumination, which could be related to higher roughness. γ-Fe2O3 overloading causes increasing crack density and eventually a fully cracked structure. Adding an appropriate amount of rGO causes a sharp increase in roughness, due to the stacking of rGO nanosheets, while simultaneously avoiding cracking. At higher contents of rGO, wettability further decreases due to higher amounts of hydroxyl groups bound onto rGO; also in this case, overloading causes film cracking. Evaluation of self-cleaning performance and discoloration resistance under soiling and acid rain simulated tests demonstrates that proper loadings of γ-Fe2O3 and rGO present higher efficiency thanks to higher superhydrophilic tendency and higher photocatalytic activities, as well as an efficient barrier effect.
SiO2-Based Nanostructured Superhydrophobic Film with High Optical Transmittance
Authors: Lazauskas Algirdas , Jucius Dalius , Puodžiukynas Linas , Guobienė Asta , Grigaliūnas Viktoras
Published: September 2020

Superhydrophobic and transparent films would be very useful in optoelectronic applications where non-wetting is desired. Herein, hexamethyldisilazane was used for functionalization of fumed SiO2 nanoparticles via silylation derivatization reaction. Modified fumed SiO2 nanoparticle dispersion was used for fabrication of SiO2-based nanostructured film via drop-casting method. This film exhibited a combination of high optical transmittance in the visible spectrum portion and superhydrophobicity (163° ± 1° and hysteresis as low as ~2°). This was possible to achieve due to the submicrometer-scale roughness (Rq = 252.7 nm) and branched network structure of the film surface with convenient surface chemistry of hydrophobic methyl groups. The method reported herein is not complicated, allows for obtaining large quantities of modified SiO2 nanoparticle dispersions and can be used in combination with other deposition methods.
Geometrical Phase Optical Components: Measuring Geometric Phase without Interferometry
Authors: Arteaga Oriol , Bendada Hana
Published: September 2020

Optical components that are based on Pancharatnam–Berry phase feature a polarization-dependent diffraction that can be used to fabricate lenses and gratings with unique properties. In recent years, the great progress made in the fabrication of the metasurfaces that are required for these optical components has lowered their cost and has made them widely available. One of the often-overlooked properties of optical components based on geometrical phases (GPs) is that, contrary to dynamical phases, their phase can be measured while using a polarimetric technique without the need to resort to interferometry methods. This is possible because the Pancharatnam–Berry phase is not controlled by an optical path difference; it results from a space variant polarization manipulation. In this work, we apply Mueller matrix microscopy in order to measure the geometrical phase of GP lenses and polarization gratings. We show that a single space resolved Mueller matrix measurement with micrometric resolution is enough to obtain a full characterization phase-profile of these GP-based optical components and evaluate their performance.
Entrepreneurship Education with Companies: Teachers Organizing School-Company Interaction
Authors: Sommarström Kaarina , Oikkonen Elena , Pihkala Timo
Published: September 2020

Previous research into entrepreneurial learning has focused mainly on defining its aims; however, there seems to be little discussion on understanding the barriers or incentives involved when carrying out the pedagogical solutions that would enable entrepreneurial learning. In this study, we examine basic education level schools’ cooperation with outside partners, especially from the school principals’ and teachers’ viewpoints. The study aims to understand the perspectives of teachers and principals on planning and organizing school-company interaction. To do this, content analysis was used in this qualitative study. The data were collected via semi-structured interviews with school teachers and principals, involving a total of 35 people working in basic education. The findings of the study show that principals and teachers intentionally select long-term cooperation methods to meet the aims of entrepreneurial learning. On the other hand, teachers that have chosen to apply short-term school-company cooperation methods have highlighted the ease of these methods rather than learning. Finally, our findings suggest that planning and organizing entrepreneurial learning would benefit from school-level commitment where collaboration between teachers and between teachers and company representatives is valued. We believe that would lead to more satisfied teachers and longer-term school-company cooperation, and also believe that short-term school-company cooperation methods would better meet the aims of entrepreneurial learning.
Impact of Tolerances on the Cogging Torque of Tooth-Coil-Winding PMSMs with Modular Stator Core by Means of Efficient Superposition Technique
Authors: Madariaga Carlos , Jara Werner , Riquelme Danilo , Bramerdorfer Gerd , Tapia Juan A. , Riedemann Javier
Published: September 2020

This paper analyzes the impact of manufacturing tolerances on the cogging torque of a 24-slot 28-pole tooth-coil-winding permanent magnet synchronous machine with a modular stator core (TCW-MPMSM). Dimensional tolerances and asymmetries associated with the modular topology are studied by means of finite element simulations in order to identify key parameters that increase the cogging torque above the expected values of a faultless machine. Among five selected dimensional parameters, it was found that angular displacement, radial displacement, and tooth–tip width deviations of the stator segments have the most significant impact on the cogging torque. Considering these three key parameters, a full-range tolerance analysis is carried out by means of a proposed superposition-based approach, evaluating all possible combinations of typical deviation values. It is concluded that the cogging torque increment, generated by tolerances, is relatively independent of the faultless tooth–tip width of the stator segments and the arc-to-pole ratio. Robustness of the TCW-MPMSM, regarding cogging torque generation, depends on both the tightness of the tolerances handled in the manufacturing process and the rated cogging torque: the lower the cogging torque of the ideal machine, the less robust is the machine and, therefore, manufacturing imperfections will be required to be tightened.
Reduction of Unburned Carbon Release and NOx Emission from a Pulverized Wood Pellet Boiler Retrofitted for Fuel Switching from Coal
Authors: Lee Jiseok , Yu Seunghan , Park Jinje , Jo Hyunbin , Park Jongkeun , Ryu Changkook , Jeong Yeong-gap
Published: September 2020

For renewable electricity production, biomass can fully displace coal in an existing power plant with some equipment modifications. Recently, a 125 MWe power plant burning mainly anthracite in Korea was retrofitted for dedicated wood pellet combustion with a change of boiler configuration from arch firing to wall firing. However, this boiler suffers from operational problems caused by high unburned carbon (UBC) contents in the bottom ash. This study comprises an investigation of some methods to reduce the UBC release while achieving lower NOx emissions. The computational fluid dynamics approach was established and validated for typical operating data. Subsequently, it was applied to elucidate the particle combustion and flow characteristics leading to the high UBC content and to evaluate the operating variables for improving the boiler performance. It was found that the high UBC content in the bottom ash was a combined effect of the poor fuel grindability and low gas velocity in the wide burner zone originating from the arch-firing boiler. This prevented the operation with deeper air staging for lower NOx emissions. Reducing the particle size to <1.5 mm by modifying mills or pretreating the fuel using torrefaction was the only effective way of lowering the UBC and NOx emissions with deeper air staging while increasing the boiler efficiency.
Interior Permanent Magnet Synchronous Motor Design for Eddy Current Loss Reduction in Permanent Magnets to Prevent Irreversible Demagnetization
Authors: Jung Jae-Woo , Lee Byeong-Hwa , Kim Kyu-Seob , Kim Sung-Il
Published: September 2020

We designed and analyzed an interior permanent magnet synchronous motor (IPMSM) to prevent irreversible demagnetization of the permanent magnets (PMs). Irreversible demagnetization of NdFeB PMs mainly occurs due to high temperature, which should thus be minimized. Therefore, it is necessary to reduce the eddy current loss in the PM through optimal design. The shape of the rotor core was optimized using finite element analysis (FEA) and response surface methodology. Three-dimensional (3-D) FEA is required for accurate computation of the eddy current loss, but there is huge time, effort, and cost consumption. Therefore, a method is proposed for indirectly calculating the eddy current loss of PMs using 2-D FEA. A thermal equivalent circuit analysis was used to calculate the PM temperature of the optimized model. For the thermal analysis, the copper loss, core loss, and eddy current loss in PMs were estimated and applied as a heat source. Based on the results, we confirmed the stability of the optimum model in terms of the PM demagnetization.
A Survey of Defensive Measures for Digital Persecution in the Global South
Authors: Papa Louis Edward , Hayajneh Thaier
Published: September 2020

This paper examines the phenomenon of digital persecution in the Global South and evaluates tools that defend against it. First, the paper explains the nature of persecution and its digital incarnation. It then provides a contextual overview of real-world instances of digital persecution in seven Global South countries. The possible defensive technologies against censorship and surveillance are discussed. The article goes on to discuss barriers to technology adoption in the Global South, explains the security implication of these difficulties, and examines the role that human computer interaction (HCI) metrics could play in overcoming these challenges. Finally, the paper surveys the viability of sixteen security tools in a Global South context. The survey results were mixed, with 37.5% of the reviewed tools being deemed to be inviable for use in the Global South to defend against persecution. Prescriptive recommendations are provided for creating security tools that are universal, simple, and effective.
Flow Pressure Behavior Downstream of Ski Jumps
Authors: Lauria Agostino , Alfonsi Giancarlo , Tafarojnoruz Ali
Published: September 2020

Ski jump spillways are frequently implemented to dissipate energy from high-speed flows. The general feature of this structure is to transform the spillway flow into a free jet up to a location where the impact of the jet creates a plunge pool, representing an area for potential erosion phenomena. In the present investigation, several tests with different ski jump bucket angles are executed numerically by means of the OpenFOAM® digital library, taking advantage of the Reynolds-averaged Navier–Stokes equations (RANS) approach. The results are compared to those obtained experimentally by other authors as related to the jet length and shape, obtaining physical insights into the jet characteristics. Particular attention is given to the maximum pressure head at the tailwater. Simple equations are proposed to predict the maximum dynamic pressure head acting on the tailwater, as dependent upon the Froude number, and the maximum pressure head on the bucket. Results of this study provide useful suggestions for the design of ski jump spillways in dam construction.
Qualitative Factor-Based Comparison of NMR, Targeted and Untargeted GC-MS and LC-MS on the Metabolomic Profiles of Rioja and Priorat Red Wines
Authors: Kioroglou Dimitrios , Mas Albert , Portillo Maria C.
Published: September 2020

Wine origin and ageing are two factors related to wine quality which in turn is associated to wine metabolome. Currently, new metabolomic techniques and proper statistics procedures allow accurate profiling of wine metabolome. Thus, the main goal was to evaluate different metabolomic methodologies on their ability to provide patterns on the wine metabolome based on selected factors, such as ageing of barrel-aged wine (factor time), prior usage of the barrels (factor barrel-type), and differences between wine ageing in barrels or glass bottles (factor bottled-wine). In the current study, we implement NMR, targeted and untargeted GC-MS and LC-MS metabolomic analytical techniques so as to gain insights into the volatile and nonvolatile wine metabolome composition of red wines from two cellars located in the only two Spanish Qualified Appellations of Origin; DOQ Priorat and DOCa Rioja regions. Overall, 95 differentially significant metabolites were identified facilitating the evaluation of the analytical methodologies performance and finding common trends of those metabolites depending on the considered factor. The results did not favor NMR as an effective technique on the current dataset whereas suggested LC-MS as an adequate technique for revealing differences based on the factor time, targeted GC-MS on the factor barrel-type, and untargeted GC-MS on the factor bottled-wine. Thus, a combination of different metabolomic techniques is necessary for a complete overview of the metabolome changes. These results ease the selection of the correct methodology depending on the specific factor investigated.
Differences in Placental Imprinted Gene Expression across Preeclamptic and Non-Preeclamptic Pregnancies
Authors: Deyssenroth Maya A. , Li Qian , Escudero Carlos , Myatt Leslie , Chen Jia , Roberts James M.
Published: September 2020

Preeclampsia is a multi-systemic syndrome that presents in approximately 5% of pregnancies worldwide and is associated with a range of subsequent postpartum and postnatal outcomes, including fetal growth restriction. As the placenta plays a critical role in the development of preeclampsia, surveying genomic features of the placenta, including expression of imprinted genes, may reveal molecular markers that can further refine subtypes to aid targeted disease management. In this study, we conducted a comprehensive survey of placental imprinted gene expression across early and late onset preeclampsia cases and preterm and term normotensive controls. Placentas were collected at delivery from women recruited at the Magee-Womens Hospital prenatal clinics, and expression levels were profiled across 109 imprinted genes. We observed downregulation of placental Mesoderm-specific transcript (MEST) and Necdin (NDN) gene expression levels (false discovery rate (FDR) < 0.05) among early onset preeclampsia cases compared to preterm controls. No differences in placental imprinted gene expression were observed between late onset preeclampsia cases and term controls. While few studies have linked NDN to pregnancy complications, reductions in MEST expression levels, as observed in our study, are consistently reported in the literature in relation to various pregnancy complications, including fetal growth restriction, suggesting a potential role for placental MEST expression as a biosensor of an adverse in utero environment.
Multiple Isolated Transcription Factors Act as Switches and Contribute to Species Uniqueness
Authors: Zhao Xin-Wei , Kishino Hirohisa
Published: September 2020

Mammals have variable numbers (1300–2000) of transcription factors (TFs), but the reasons for this large variation are unclear. To investigate general TF patterns, we de novo identified 156,906 TFs from 96 mammalian species. We identified more than 500 human isolated TFs that are rarely reported in human TF-to-TF networks. Mutations in the genes of these TFs were less lethal than those of connected TFs. Consequently, these isolated TFs are more tolerant of changes and have become unique during speciation. They may also serve as a source of variation for TF evolution. Reconciliation of TF-family phylogenetic trees with a mammalian species tree revealed an average of 37.8% TF gains and 15.0% TF losses over 177 million years, which implies that isolated TFs are pervasive in mammals. Compared with non-TF interacting genes, TF-interacting genes have unique TF profiles and have higher expression levels in mice than in humans. Different expression levels of the same TF-interacting gene contribute to species-specific phenotypes. Formation and loss of isolated TFs enabling unique TF profiles may provide variable switches that adjust divergent expression profiles of target genes to generate species-specific phenotypes, thereby making species unique.
Instrumental Activities of Daily Living—A Good Tool to Prospectively Assess Disability after a Second Contralateral Hip Fracture?
Authors: Dubljanin Raspopovic Emilija , Marković Denić Ljiljana , Tomanović Vujadinović Sanja , Kadija Marko , Nedeljković Una , Ilić Nela , Milovanović Darko
Published: September 2020

The aim of this study was to determine the outcome for patients who sustain a second hip fracture compared with those who sustain a first fracture, and to define the optimal measure to evaluate functional outcome after second hip fracture. Methods: 343 patients with acute hip fractures who presented during a 12 month period were included in the study. Patients with a first (318 patients, 78.10 +/− 7.53 years) and second (25 patients, 78.96 +/− 6.02) hip fracture were compared regarding all baseline variables. Regression analysis was also performed to assess the independent relationship between the presence of a second hip fracture and observed outcome variables at discharge (physical disability, complications, length of stay, and mortality) and one-year after surgery (physical disability and mortality). Results: Disability when performing instrumentalized activities of daily living (IADL) at one-year follow-up is independently related to the presence of a second hip fracture. There were no other statistically significant relationships between the presence of a second hip fracture and other observed outcome variables. Conclusions: Patients with a second hip fracture showed worse functional outcome at one-year follow-up when measured with the IADL scale. No increased short-nor long-term mortality rates were found in patients with a secondary hip fracture. IADL is a good tool to assess disability after a second hip fracture and could be thus a more reliable outcome measure when investigating differences in functional recovery in patients with a second hip fracture compared to conventionally used ADL scales.
Groundwater Arsenic Distribution in India by Machine Learning Geospatial Modeling
Authors: Podgorski Joel , Wu Ruohan , Chakravorty Biswajit , Polya David A.
Published: September 2020

Groundwater is a critical resource in India for the supply of drinking water and for irrigation. Its usage is limited not only by its quantity but also by its quality. Among the most important contaminants of groundwater in India is arsenic, which naturally accumulates in some aquifers. In this study we create a random forest model with over 145,000 arsenic concentration measurements and over two dozen predictor variables of surface environmental parameters to produce hazard and exposure maps of the areas and populations potentially exposed to high arsenic concentrations (>10 µg/L) in groundwater. Statistical relationships found between the predictor variables and arsenic measurements are broadly consistent with major geochemical processes known to mobilize arsenic in aquifers. In addition to known high arsenic areas, such as along the Ganges and Brahmaputra rivers, we have identified several other areas around the country that have hitherto not been identified as potential arsenic hotspots. Based on recent reported rates of household groundwater use for rural and urban areas, we estimate that between about 18–30 million people in India are currently at risk of high exposure to arsenic through their drinking water supply. The hazard models here can be used to inform prioritization of groundwater quality testing and environmental public health tracking programs.
Relationship between Quality of Life and the Complexity of Default Mode Network in Resting State Functional Magnetic Resonance Image in Down Syndrome
Authors: Carbó-Carreté Maria , Cañete-Massé Cristina , Figueroa-Jiménez María D. , Peró-Cebollero Maribel , Guàrdia-Olmos Joan
Published: September 2020

Background: The study of the Default Mode Network (DMN) has been shown to be sensitive for the recognition of connectivity patterns between the brain areas involved in this network. It has been hypothesized that the connectivity patterns in this network are related to different cognitive states. Purpose: In this study, we explored the relationship that can be estimated between these functional connectivity patterns of the DMN with the Quality-of-Life levels in people with Down syndrome, since no relevant data has been provided for this population. Methods: 22 young people with Down syndrome were evaluated; they were given a large evaluation battery that included the Spanish adaptation of the Personal Outcome Scale (POS). Likewise, fMRI sequences were obtained on a 3T resonator. For each subject, the DMN functional connectivity network was studied by estimating the indicators of complexity networks. The variability obtained in the Down syndrome group was studied by taking into account the Quality-of-Life distribution. Results: There is a negative correlation between the complexity of the connectivity networks and the Quality-of-Life values. Conclusions: The results are interpreted as evidence that, even at rest, connectivity levels are detected as already shown in the community population and that less intense connectivity levels correlate with higher levels of Quality of Life in people with Down syndrome.
Reluctancy towards Help-Seeking for Mental Health Concerns at Secondary School among Students in the COMPASS Study
Authors: Doan Natalie , Patte Karen A. , Ferro Mark A. , Leatherdale Scott T.
Published: September 2020

Youth populations represent a key population for addressing mental health, yet many youths express reluctance towards help seeking. Considering the volume of time that almost all youth spend at school during the school year, it is important to assess the role of the school environment in relation to students’ attitudes toward help-seeking. Data from 47,290 grade 9 to 12 students and 116 Canadian secondary schools that participated in the 2018-19 wave of the COMPASS (Cannabis, Obesity, Mental health, Physical activity, Alcohol, Smoking, Sedentary behaviour) study were analyzed using GEE models to assess the student and school characteristics associated with attitudes regarding seeking help for mental health concerns from an adult at school. Overall, 58% of students reported being reluctant to seek help for mental health concerns at school. Students who reported lower self-rated mental health (aOR = 1.76, 95% CI = 1.65, 1.87), emotion regulation (aOR = 1.08, 95% CI = 1.07, 1.09), family support (aOR = 2.31, 95% CI = 2.16, 2.47), peer support (aOR = 1.20, 95% CI = 1.13, 1.31), and school connectedness (aOR = 0.93, 95% CI = 0.92, 0.93) scores were more likely to be reluctant towards help-seeking at school than students with more favourable scores on these variables. Students with higher flourishing scores were less likely than students who were languishing to report reluctance to help-seeking at school (aOR = 0.96, 95% CI = 0.96, 0.97). Students attending schools in areas with lower population densities and median household incomes between $50,000–75,000 were less likely to be reluctant to help-seeking relative to students attending schools in areas with higher density (aOR = 0.85, 95% CI = 0.79, 0.93) and median household incomes (aOR = 1.20, 95% CI = 1.13, 1.31), respectively. The availability of school mental health services and specialists were not associated with student help-seeking reluctance. High levels of resistance towards help-seeking among youth remain a significant barrier, particularly among youth at highest risk (i.e., with lower support and poorer mental health). The student and school characteristics identified in the current study can help inform strategies to promote greater acceptance of help seeking among students in schools.
Experiences of Mothers Facing the Prognosis of Their Children with Complex Congenital Heart Disease
Authors: Lee Sunhee , Ahn Jeong-Ah
Published: September 2020

Mothers of children with complex congenital heart disease face unique challenges and emotional burdens, while their children go through physical and psychological difficulties during disease progression. In this study, we aimed to explore the in-depth experiences and feelings of mothers facing the prognosis of their children with complex congenital heart disease that was surgically corrected. This is a descriptive qualitative study. We conducted semi-structured, face-to-face interviews with 12 mothers of children with complex congenital heart disease at a tertiary hospital in Seoul, Korea. The interview data were analyzed by content analysis. Participants were mothers aged between 40–58 years whose children were diagnosed with complex congenital heart disease which was surgically corrected. Based on the content analysis, the mothers’ experiences and feelings were categorized as immense suffering and adapting to a new life. Under the main categories, the concepts included feeling of abandonment, anxiety with potentially losing their children, having hope, seeking reassurance, being encouraged, and trying to embrace the situation. Mothers who cared for their children with complex congenital heart disease expressed emotions that changed sequentially alongside physical and psychosocial changes in the children. The results of this study are valuable for understanding the experiences and emotions of mothers facing the prognosis of their children with complex congenital heart disease in order to aid in the development of programs that support these mothers.
Radiation Exposure Predicts Reported Vaccine Adverse Effects in Veterans with Gulf War Illness
Authors: Golomb Beatrice A. , Nguyen Emily , Dinkeloo Eero
Published: September 2020

Most people have no problems when administered vaccines; however, as with all drugs, reported adverse effects (rAEs) do occur. There is a need to better understand the potential predictors of reported vaccine AEs (rVaxAEs), including modifiable (environmental) predictors. Gulf War Veterans (GWV) who have Gulf War illness (GWI) report increased experiences of drug and chemical rAEs, extending to rVaxAEs. GWV provide an opportunity to examine the relationship between their reported exposures and rAEs. Forty one GWV with GWI and 40 healthy controls reported exposure and rAEs to exposure, including for 14 vaccines. Individual and summed vaccine exposures, rVaxAEs, and reported Vaccine AE Propensity (summed rVaxAEs/summed vaccines exposures) were compared in cases vs. controls. Exposure–outcome assessments focused on GWV, using a multivariable regression with robust standard error. More designated vaccines were reported in cases than in controls: 9.0 (2.3) vs. 3.8 (2.3), p < 0.0001. The fraction of vaccines received that led to rAEs was ten-fold higher in cases: 0.24 (0.21), vs. 0.023 (0.081), p < 0.0001. Multivariable assessment confirmed that radiation and pesticides remained significant statistical predictors of reported Vaccine AE Propensity. Exposure tied to excess rVaxAEs in GWV may contribute to, or underlie, the reported link between rVaxAEs in GWV and later ill health.
Markers Specific to Bacteroides fragilis Group Bacteria as Indicators of Anthropogenic Pollution of Surface Waters
Authors: Niestępski Sebastian , Harnisz Monika , Korzeniewska Ewa , Osińska Adriana
Published: September 2020

The aim of this study was to evaluate the applicability of markers specific to Bacteroides fragilis group (BFG) bacteria as indicators of anthropogenic pollution of surface waters. In addition, the impact of wastewater treatment plants (WWTPs) on the spread of genes specific to fecal indicator bacteria and genes encoding antimicrobial resistance in water bodies was also determined. Samples of hospital wastewater (HWW), untreated wastewater (UWW), and treated wastewater (TWW) evacuated from a WWTP were collected, and samples of river water were taken upstream (URW) and downstream (DRW) from the wastewater discharge point to determine, by qPCR, the presence of genes specific to BFG, Escherichia coli and Enterococcus faecalis, and the abundance of 11 antibiotic resistance genes (ARGs) and two integrase genes. The total number of bacterial cells (TCN) in the examined samples was determined by fluorescence in situ hybridization (FISH). Genes specific to BFG predominated among the analyzed indicator microorganisms in HWW, and their copy numbers were similar to those of genes specific to E. coli and E. faecalis in the remaining samples. The abundance of genes specific to BFG was highly correlated with the abundance of genes characteristic of E. coli and E. faecalis, all analyzed ARGs and intI genes. The results of this study indicate that genes specific to BFG can be used in analyses of human fecal pollution, and as indicators of environmental contamination with ARGs. A significant increase in the copy numbers of genes specific to BFG, E. coli, and seven out of the 11 analyzed ARGs was noted in samples of river water collected downstream from the wastewater discharge point, which suggests that WWTPs are an important source of these genes in riparian environments.
Estimating Soil Erosion Rate Changes in Areas Affected by Wildfires
Authors: Depountis Nikolaos , Michalopoulou Maria , Kavoura Katerina , Nikolakopoulos Konstantinos , Sabatakakis Nikolaos
Published: September 2020

In recent decades, wildfires have become a serious threat worldwide, producing disasters in the natural and anthropogenic environment as well as serious economic losses. One of wildfire’s major impacts is soil erosion, as it may cause major problems in both the physical and anthropogenic environment and seriously affect the landscape. This study investigates the soil erosion rate changes in areas affected by wildfires and uses, as a pilot area, the drainage basin of the Pinios earth-filled dam located in the Ilia Regional Unit, western Greece, which has suffered serious erosion changes after a wildfire event. For this purpose, the Revised Universal Soil Loss Equation (RUSLE) is applied in GIS software, and the soil erosion rate changes in the selected investigation area are estimated at different time intervals. Specifically, soil erosion rate changes are calculated by importing the factors from the RUSLE equation in the GIS software and uses as a dependent variable the cover management factor C, which is strongly influenced by large destructive fires. The models that are produced are compared with each other by collating average annual soil erosion maps and rates before the fire, immediately after the fire and for the existing conditions occurring in the pilot area.
Monitoring Wildfires in the Northeastern Peruvian Amazon Using Landsat-8 and Sentinel-2 Imagery in the GEE Platform
Authors: Barboza Castillo Elgar , Turpo Cayo Efrain , de Almeida Cláudia , Salas López Rolando , Rojas Briceño Nilton , Silva López Jhonsy , Barrena Gurbillón Miguel , Oliva Manuel , Espinoza-Villar Raul
Published: September 2020

During the latest decades, the Amazon has experienced a great loss of vegetation cover, in many cases as a direct consequence of wildfires, which became a problem at local, national, and global scales, leading to economic, social, and environmental impacts. Hence, this study is committed to developing a routine for monitoring fires in the vegetation cover relying on recent multitemporal data (2017–2019) of Landsat-8 and Sentinel-2 imagery using the cloud-based Google Earth Engine (GEE) platform. In order to assess the burnt areas (BA), spectral indices were employed, such as the Normalized Burn Ratio (NBR), Normalized Burn Ratio 2 (NBR2), and Mid-Infrared Burn Index (MIRBI). All these indices were applied for BA assessment according to appropriate thresholds. Additionally, to reduce confusion between burnt areas and other land cover classes, further indices were used, like those considering the temporal differences between pre and post-fire conditions: differential Mid-Infrared Burn Index (dMIRBI), differential Normalized Burn Ratio (dNBR), differential Normalized Burn Ratio 2 (dNBR2), and differential Near-Infrared (dNIR). The calculated BA by Sentinel-2 was larger during the three-year investigation span (16.55, 78.50, and 67.19 km2) and of greater detail (detected small areas) than the BA extracted by Landsat-8 (16.39, 6.24, and 32.93 km2). The routine for monitoring wildfires presented in this work is based on a sequence of decision rules. This enables the detection and monitoring of burnt vegetation cover and has been originally applied to an experiment in the northeastern Peruvian Amazon. The results obtained by the two satellites imagery are compared in terms of accuracy metrics and level of detail (size of BA patches). The accuracy for Landsat-8 and Sentinel-2 in 2017, 2018, and 2019 varied from 82.7–91.4% to 94.5–98.5%, respectively.
The Commensal Microbiota Enhances ADP-Triggered Integrin αIIbβ3 Activation and von Willebrand Factor-Mediated Platelet Deposition to Type I Collagen
Authors: Kiouptsi Klytaimnistra , Jäckel Sven , Wilms Eivor , Pontarollo Giulia , Winterstein Jana , Karwot Cornelia , Groß Kathrin , Jurk Kerstin , Reinhardt Christoph
Published: September 2020

The commensal microbiota is a recognized enhancer of arterial thrombus growth. While several studies have demonstrated the prothrombotic role of the gut microbiota, the molecular mechanisms promoting arterial thrombus growth are still under debate. Here, we demonstrate that germ-free (GF) mice, which from birth lack colonization with a gut microbiota, show diminished static deposition of washed platelets to type I collagen compared with their conventionally raised (CONV-R) counterparts. Flow cytometry experiments revealed that platelets from GF mice show diminished activation of the integrin αIIbβ3 (glycoprotein IIbIIIa) when activated by the platelet agonist adenosine diphosphate (ADP). Furthermore, washed platelets from Toll-like receptor-2 (Tlr2)-deficient mice likewise showed impaired static deposition to the subendothelial matrix component type I collagen compared with wild-type (WT) controls, a process that was unaffected by GPIbα-blockade but influenced by von Willebrand factor (VWF) plasma levels. Collectively, our results indicate that microbiota-triggered steady-state activation of innate immune pathways via TLR2 enhances platelet deposition to subendothelial matrix molecules. Our results link host colonization status with the ADP-triggered activation of integrin αIIbβ3, a pathway promoting platelet deposition to the growing thrombus.
Effects of Ketamine on Rodent Fear Memory
Authors: Choi Kwang H. , Berman Rina Y. , Zhang Michael , Spencer Haley F. , Radford Kennett D.
Published: September 2020

Ketamine, a multimodal anesthetic drug, has become increasingly popular in the treatment of pain following traumatic injury as well as treatment-resistant major depressive disorders. However, the psychological impact of this dissociative medication on the development of stress-related disorders such as post-traumatic stress disorder (PTSD) remains controversial. To address these concerns, preclinical studies have investigated the effects of ketamine administration on fear memory and stress-related behaviors in laboratory animals. Despite a well-documented line of research examining the effects of ketamine on fear memory, there is a lack of literature reviews on this important topic. Therefore, this review article summarizes the current preclinical literature on ketamine and fear memory with a particular emphasis on the route, dose, and timing of ketamine administration in rodent fear conditioning studies. Additionally, this review describes the molecular mechanisms by which ketamine may impact fear memory and stress-related behaviors. Overall, findings from previous studies are inconsistent in that fear memory may be increased, decreased, or unaltered following ketamine administration in rodents. These conflicting results can be explained by factors such as the route, dose, and timing of ketamine administration; the interaction between ketamine and stress; and individual variability in the rodent response to ketamine. This review also recommends that future preclinical studies utilize a clinically relevant route of administration and account for biological sex differences to improve translation between preclinical and clinical investigations.
Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases
Authors: Luo Fang , Sandhu Aaron F. , Rungratanawanich Wiramon , Williams George E. , Akbar Mohammed , Zhou Shuanhu , Song Byoung-Joon , Wang Xin
Published: September 2020

With aging, the nervous system gradually undergoes degeneration. Increased oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and cell death are considered to be common pathophysiological mechanisms of various neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), organophosphate-induced delayed neuropathy (OPIDN), and amyotrophic lateral sclerosis (ALS). Autophagy is a cellular basic metabolic process that degrades the aggregated or misfolded proteins and abnormal organelles in cells. The abnormal regulation of neuronal autophagy is accompanied by the accumulation and deposition of irregular proteins, leading to changes in neuron homeostasis and neurodegeneration. Autophagy exhibits both a protective mechanism and a damage pathway related to programmed cell death. Because of its “double-edged sword”, autophagy plays an important role in neurological damage and NDDs including AD, PD, HD, OPIDN, and ALS. Melatonin is a neuroendocrine hormone mainly synthesized in the pineal gland and exhibits a wide range of biological functions, such as sleep control, regulating circadian rhythm, immune enhancement, metabolism regulation, antioxidant, anti-aging, and anti-tumor effects. It can prevent cell death, reduce inflammation, block calcium channels, etc. In this review, we briefly discuss the neuroprotective role of melatonin against various NDDs via regulating autophagy, which could be a new field for future translational research and clinical studies to discover preventive or therapeutic agents for many NDDs.
The Down-Regulation of Clusterin Expression Enhances the αSynuclein Aggregation Process
Authors: Lenzi Chiara , Ramazzina Ileana , Russo Isabella , Filippini Alice , Bettuzzi Saverio , Rizzi Federica
Published: September 2020

Parkinson’s Disease (PD) is a progressive neurodegenerative disease characterized by the presence of proteinaceous aggregates of αSynuclein (αSyn) in the dopaminergic neurons. Chaperones are key components of the proteostasis network that are able to counteract αSyn’s aggregation, as well as its toxic effects. Clusterin (CLU), a molecular chaperone, was consistently found to interfere with Aβ aggregation in Alzheimer’s Disease (AD). However, its role in PD pathogenesis has yet to be extensively investigated. In this study, we assessed the involvement of CLU in the αSyn aggregation process by using SH-SY5Y cells stably overexpressing αSyn (SH-Syn). First, we showed that αSyn overexpression caused a strong increase in CLU expression without affecting levels of Hsp27, Hsp70, and Hsp90, which are the chaperones widely recognized to counteract αSyn burden. Then, we demonstrated that αSyn aggregation, induced by proteasome inhibition, determines a strong increase of CLU in insoluble aggregates. Remarkably, we revealed that CLU down-regulation results in an increase of αSyn aggregates in SH-Syn without significantly affecting cell viability and the Unfolded Protein Response (UPR). Furthermore, we demonstrated the direct molecular interaction between CLU and αSyn via a co-immunoprecipitation (co-IP) assay. All together, these findings provide incontrovertible evidence that CLU is an important player in the response orchestrated by the cell to cope with αSyn burden.