bluuebunny/crossref_metadata_2025 huggingface dataset:
Empowering and Disempowering Motivational Climates, Mediating Psychological Processes, and Future Intentions of Sport Participation
Authors: Castillo-Jiménez Nallely , López-Walle Jeanette M. , Tomás Inés , Tristán José , Duda Joan L. , Balaguer Isabel
Published: January 2022

Based on the conceptual model of multidimensional and hierarchical motivational climate the objective of this study was to test two models. One model (M1) of total mediation, testing the mediating mechanisms that explain why the motivational climate affects intention of continuity or dropout. Specifically, we test the mediating role of satisfaction/frustration of basic psychological needs and self-determined motivation, in the relationship between the players’ perception of the empowering and disempowering climate created by the coach, and the intention of young soccer players to continue/dropout the sport practice. The second model (M2) of partial mediation, contributes to knowing the mechanisms that link the antecedent variables included in the model (perceived empowering and disempowering motivational climate) and the outcomes (intention of continuity or dropout in sport). A total of 381 young male soccer players between 12 and 14 years of age (M = 12.41, SD = 0.89), completed a questionnaire package tapping into the variables of interest: players’ perception of the motivational climate created by the coach (empowering and disempowering), satisfaction/thwarting of basic psychological needs, self-determined motivation and the intention to continue/dropout sports participation. The hypothesized model was tested using a structural equation model technique with latent variables. The results of the partial mediation model were satisfactory (χ2= 120.92; df = 68; RMSEA = 0.045; CFI = 0.968; TLI = 0.957) and showed that need satisfaction and self-determined motivation partially mediated the relationship between the perception of the empowering climate and the intention to continue. Moreover, need satisfaction showed a positive and significant relationship with the intention to continue sports participation. Additionally, need thwarting and self-determined motivation totally mediated the relationship between the perception of the disempowering climate and the intention to dropout. Furthermore, needs thwarting was positively and significantly related to the intention to dropout of sports participation. Findings point to the importance of fostering empowering climates and preventing the creation of disempowering climates in the grassroots football.
Returning Individual Tap Water Testing Results to Research Study Participants after a Wildfire Disaster
Authors: Von Behren Julie , Wong Michelle , Morales Daniela , Reynolds Peggy , English Paul B. , Solomon Gina
Published: January 2022

After the devastating wildfire that destroyed most of the town of Paradise, California in 2018, volatile organic compounds were found in water distribution pipes. Approximately 11 months after the fire, we collected tap water samples from 136 homes that were still standing and tested for over 100 chemicals. Each participant received a customized report showing the laboratory findings from their sample. Our goal was to communicate individual water results and chemical information rapidly in a way that was understandable, scientifically accurate, and useful to participants. On the basis of this process, we developed a framework to illustrate considerations and priorities that draw from best practices of previous environmental results return research and crisis communication, while also addressing challenges specific to the disaster context. We also conducted a follow-up survey on participants’ perceptions of the results return process. In general, participants found the results return communications to be understandable, and they felt less worried about their drinking water quality after receiving the information. Over one-third of the participants reported taking some kind of action around their water usage habits after receiving their results. Communication with participants is a critical element of environmental disaster research, and it is important to have a strategy to communicate results that achieves the goals of timeliness, clarity, and scientific accuracy, ultimately empowering people toward actions that can reduce exposure.
Risk of Mortality in Association with Pregnancy in Women Following Motor Vehicle Crashes: A Systematic Review and Meta-Analysis
Authors: Chang Ya-Hui , Cheng Ya-Yun , Hou Wen-Hsuan , Chien Yu-Wen , Chang Chiung-Hsin , Chen Ping-Ling , Lu Tsung-Hsueh , Yovita Hendrati Lucia , Li Chung-Yi , Foo Ning-Ping
Published: January 2022

The aim of the study was to provide a systematic review and meta-analysis of studies examining the association between mortality risk and motor vehicle crashes (MVCs) in pregnant women compared with nonpregnant women. We used relevant MeSH terms to identify epidemiological studies of mortality risk in relation to MVCs from PubMed, Embase, and MEDLINE databases. The Newcastle–Ottawa Scale (NOS) was used for quality assessment. For comparison of mortality from MVCs between pregnant and nonpregnant women, the pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. The eight studies selected met all inclusion criteria. These studies included 14,120 injured victims who were pregnant at the time of the incident and 207,935 victims who were not pregnant. Compared with nonpregnant women, pregnant women had a moderate but insignificant decrease in mortality risk (pooled OR = 0.68, 95% CI = 0.38–1.22, I2 = 88.71%). Subgroup analysis revealed that the pooled OR significantly increased at 1.64 (95% CI = 1.16–2.33, I2 < 0.01%) for two studies with a similar difference in the mean injury severity score (ISS) between pregnant and nonpregnant women. Future studies should further explore the risk factors associated with MVCs in pregnant women to reduce maternal mortality.
Knowledge and Use of Novel Psychoactive Substances in an Italian Sample with Substance Use Disorders
Authors: Dal Farra Deborah , Valdesalici Alice , Zecchinato Giancarlo , De Sandre Alfio , Saccon Diego , Simonato Pierluigi , Corazza Ornella , Martinotti Giovanni , Smith Andrew L. , Solmi Marco
Published: January 2022

This study aims to determine prevalence and frequency of use of novel psychoactive substances (NPS) and to identify the factors associated with NPS use in an Italian sample of patients diagnosed with substance use disorder (SUD). Prevalence and correlates of NPS knowledge and use were assessed in 185 patients with SUD in three addiction services (Padova, Belluno, Feltre) in the Veneto region with an ad-hoc designed survey. Two thirds of the samples reported knowing NPS and one third reported using them. NPS were considered by them less dangerous than “regular” substances of abuse (t = 6.06 mean 0.78, p < 0.001). Factors associated with NPS use were youth (OR = 4.81; p < 0.001), studentship (OR = 4.99; p = 0.004), subsequent mental disorders diagnosis (OR = 2.49; p = 0.027), suicide attempt history (OR = 11.67; p < 0.001), home detention (OR = 2.30; p = 0.040), residential care (OR = 5.66; p = 0.002), and polysubstance abuse (t = 8.99 mean 2.65 p < 0.001). NPS use in patients with SUD is highly prevalent, particularly in the youngest age group, and associated with psychiatric comorbidity and worse prognosis. It is crucial to systematically assess NPS use and inform addiction service users with SUD of the toxic and potentially lethal side effects. Mental healthcare professionals working in addiction services should receive education and training. Cohort and longitudinal studies are needed.
Achieving Human Resource Management Sustainability in Universities
Authors: Mohiuddin Muhammad , Hosseini Elahe , Faradonbeh Sedigheh Bagheri , Sabokro Mehdi
Published: January 2022

The sustainability of human resource management (HRM) is the basis for an organization’s future growth and success. This study aims to investigate achieving HRM sustainability in universities. We use a quantitative research method design to investigate the factors that affect HRM sustainability at universities. The study was conducted during the spring and summer of 2020 at Iranian state universities. As the study’s statistical population included 2543 employees, a sample size of 334 employees was calculated using the Cochran formula. A questionnaire with 32 statements based on a 5-point Likert scale was used to collect the data, which were analyzed using PLS3 software. The findings show that human resource practices, social factors, psychological factors, employer branding, and economic factors have positive and significant effects on HRM sustainability at universities. Findings indicate that it is essential to consider the implementation of adequate HRM practices and related socio-economic and psychological supports for HRM sustainability in universities that can lead to the competitiveness of the higher education institutions such as universities.
Building Environmental Health and Genomics Literacy among Healthcare Providers Serving Vulnerable Communities: An Innovative Educational Framework
Authors: Vandiver Kathleen Mead , Erdei Esther , Mayer Amanda G. , Ricciardi Catherine , O’Leary Marcia , Burke Kathleen , Zelikoff Judith T.
Published: January 2022

This study addresses healthcare providers’ knowledge deficits in environmental health and genetics, and primarily focuses on student nurses and nurses serving marginalized, low-income communities frequently exposed to environmental toxicants. Our approach to improve public health is unique, combining hands-on modeling exercises with case-based lessons in addition to three targeted 40 min lectures on toxicology. These lectures included the team’s community-based environmental health research among Indigenous peoples of the U.S. The hands-on approach employed DNA and protein molecular models designed to demonstrate normal and dysfunctional molecules, as well as genetic variants in world populations. The models provided learners with visuals and an experience of “learning by doing.” Increased awareness of the effects of environmental toxicants is the first step toward improving health care for exposed communities. We measured knowledge gains by pre- and post-tests among student nurses and nurses serving Native Americans living both in urban and rural areas of the U.S. (n = 116). The modeling lessons illustrated genetic variants in liver proteins common in Native peoples and their resulting health vulnerabilities. Participants were engaged and enthusiastic; and pre- and post-test results reported substantial knowledge gains and a greater understanding of genetic susceptibility (p < 0.0001). Our study demonstrates the utility of this framework across diverse populations and remote communities.
Lipoprotein Profile in Populations from Regions of the Russian Federation: ESSE-RF Study
Authors: Metelskaya Victoria A. , Shalnova Svetlana A. , Yarovaya Elena B. , Kutsenko Vladimir A. , Boytsov Sergey A. , Shlyakhto Eugeny V. , Drapkina Oxana M.
Published: January 2022

This study aimed to describe the dyslipidemia prevalence and pattern among adult populations from different regions (n = 13) of the Russian Federation (RF). Randomly selected samples (n = 22,258, aged 25–64) were studied according to the ESSE-RF protocol. Lipoprotein parameters were estimated by routine methods. Statistical analyses were performed using R software (v.3.5.1). The overall dyslipidemia prevalence was 76.1% (76.9/75.3% for men/women). In women, total cholesterol (TC) and low-density lipoprotein (LDL)-C levels gradually increased with age (from 4.72 to 5.93 and from 2.76 to 3.79 mmol/L, respectively); in men, they reached a maximum by 45–54 (5.55 and 3.55 mmol/L, respectively) and then decreased. No differences in high-density lipoprotein (HDL)-C in men of different ages were found, but slight decreases in HDL-C and apo AI were observed in women by 55–64 years. No pronounced associations between education and lipid levels in men were observed; higher-educated women showed significantly better lipoprotein profiles. Similar associations between lipids and income level were detected. Women from rural areas had higher TC and triglycerides than urban residents. Regardless of sex, rural residents had higher HDL-C and apo AI, and reduced apo B/apo AI. Conclusion: Information on the peculiarities of dyslipidemia prevalence and lipoprotein profile depending on sex, age, residential place, and socioeconomic status is useful for assessing the global ASCVD risk, and for risk modeling based on national data.
How Does Social Class Affect Need for Structure during the COVID-19 Pandemic? A Moderated Mediating Model Analysis
Authors: Rao Ting-Ting , Yang Shen-Long , Zhu Xiaowen
Published: January 2022

The COVID-19 pandemic is profoundly affecting the minds and behaviors of people worldwide. This study investigated the differences in the need for structure among people from different social classes and the psychological mechanisms underlying this need, as well as the moderating effect of the threat posed by the pandemic. Using data collected from non-student adults in China, we found that the lower an individual’s social class, the lower their need for structure, and this effect was based on the mediating role of perceived control. However, the mediating effect was moderated by pandemic threat, and the above relationship existed only when this threat was low. When the level of pandemic threat was higher, neither the effect of social class nor of perceived control on the need for structure were significant. Specifically, in higher-threat situations, the need for structure among individuals from higher social classes and who had a higher sense of control increased significantly, meaning the mediating effect was no longer significant. This finding showed that under the threat of a pandemic, individuals who have a lower need for structure will still pursue and prefer structure and order. The theoretical and practical implications of the research are also discussed.
A New Story on the Multidimensionality of the MSPSS: Validity of the Internal Structure through Bifactor ESEM
Authors: Merino-Soto César , Boluarte Carbajal Alicia , Toledano-Toledano Filiberto , Nabors Laura A. , Núñez-Benítez Miguel Ángel
Published: January 2022

The internal structure of the Multidimensional Scale of Perceived Social Support (MSPSS) in adolescents has been evaluated with some factorial analysis methodologies but not with bifactor exploratory structural equation modeling (ESEM), and possibly the inconsistency in the internal structure was dependent on these approaches. The objective of the study was to update evidence regarding its internal structure of MSPSS, by means of a detailed examination of its multidimensionality The participants were 460 adolescents from an educational institution in the Callao region, Lima, Peru. The structure was modeled using unidimensional, three-factor and bifactor models with confirmatory factor analysis (CFA) and ESEM approaches. The models showed good levels of fit, with the exception of the unidimensional model; however, the multidimensionality indicators supported the superiority of the bifactor ESEM. In contrast, the general factor was not strong enough, and the interfactorial correlations were substantially lower. It is concluded that the MSPSS can be interpreted by independent but moderately correlated factors, and there is possible systematic variance that potentially prevented the identification of a general factor.
Long and Short-Term Coastal Changes Assessment Using Earth Observation Data and GIS Analysis: The Case of Sperchios River Delta
Authors: Psomiadis Emmanouil
Published: January 2022

The present study provides information about the evolution of the Sperchios River deltaic area over the last 6500 years. Coastal changes, due to natural phenomena and anthropogenic activities, were analyzed utilizing a variety of geospatial data such as historic records, topographic maps, aerial photos, and satellite images, covering a period from 4500 BC to 2020. A qualitative approach for the period, from 4500 BC to 1852, and a quantitative analysis, from 1852 to the present day, were employed. Considering their scale and overall quality, the data were processed and georeferenced in detail based on the very high-resolution orthophoto datasets of the area. Then, the multitemporal shorelines were delineated in a geographical information system platform. Two different methods were utilized for the estimation of the shoreline changes and trends, namely the coastal change area method and the cross-section analysis, by implementing the digital shoreline analysis system with two statistical approaches, the end point rate and the linear regression rate. Significant river flow and coastline changes were observed with the overall increase in the delta area throughout the study period reaching 135 km2 (mean annual growth of 0.02 km2/yr) and the higher accretion rates to be detected during the periods 1805–1852, 1908–1945 and 1960–1986, especially at the central and north part of the gulf. During the last three decades, the coastline has remained relatively stable with a decreasing tendency, which, along with the expected sea-level rise due to climate change, can infer significant threats for the coastal zone in the near future.
Spatial Variability of the ‘Airbnb Effect’: A Spatially Explicit Analysis of Airbnb’s Impact on Housing Prices in Sydney
Authors: Thackway William Thomas , Ng Matthew Kok Ming , Lee Chyi-Lin , Shi Vivien , Pettit Christopher James
Published: January 2022

Over the last decade, the emergence and significant growth of home-sharing platforms, such as Airbnb, has coincided with rising housing unaffordability in many global cities. It is in this context that we look to empirically assess the impact of Airbnb on housing prices in Sydney—one of the least affordable cities in the world. Employing a hedonic property valuation model, our results indicate that Airbnb’s overall effect is positive. A 1% increase in Airbnb density is associated with approximately a 2% increase in property sales price. However, recognizing that Airbnb’s effect is geographically uneven and given the fragmented nature of Sydney’s housing market, we also employ a GWR to account for the spatial variation in Airbnb activity. The findings confirm that Airbnb’s influence on housing prices is varied across the city. Sydney’s northern beaches and parts of western Sydney experience a statistically significant value uplift attributable to Airbnb activity. However, traditional tourist locations focused around Sydney’s CBD and the eastern suburbs experience insignificant or negative property price impacts. The results highlight the need for policymakers to consider local Airbnb and housing market contexts when deciding the appropriate level and design of Airbnb regulation.
Emerging Advances of Detection Strategies for Tumor-Derived Exosomes
Authors: Cheng Huijuan , Yang Qian , Wang Rongrong , Luo Ruhua , Zhu Shanshan , Li Minhui , Li Wenqi , Chen Cheng , Zou Yuqing , Huang Zhihua , Xie Tian , Wang Shuling , Zhang Honghua , Tian Qingchang
Published: January 2022

Exosomes derived from tumor cells contain various molecular components, such as proteins, RNA, DNA, lipids, and carbohydrates. These components play a crucial role in all stages of tumorigenesis and development. Moreover, they reflect the physiological and pathological status of parental tumor cells. Recently, tumor-derived exosomes have become popular biomarkers for non-invasive liquid biopsy and the diagnosis of numerous cancers. The interdisciplinary significance of exosomes research has also attracted growing enthusiasm. However, the intrinsic nature of tumor-derived exosomes requires advanced methods to detect and evaluate the complex biofluid. This review analyzes the relationship between exosomes and tumors. It also summarizes the exosomal biological origin, composition, and application of molecular markers in clinical cancer diagnosis. Remarkably, this paper constitutes a comprehensive summary of the innovative research on numerous detection strategies for tumor-derived exosomes with the intent of providing a theoretical basis and reference for early diagnosis and clinical treatment of cancer.
Supported Lipid Bilayer Platform for Characterizing the Membrane-Disruptive Behaviors of Triton X-100 and Potential Detergent Replacements
Authors: Gooran Negin , Yoon Bo Kyeong , Jackman Joshua A.
Published: January 2022

Triton X-100 (TX-100) is a widely used detergent to prevent viral contamination of manufactured biologicals and biopharmaceuticals, and acts by disrupting membrane-enveloped virus particles. However, environmental concerns about ecotoxic byproducts are leading to TX-100 phase out and there is an outstanding need to identify functionally equivalent detergents that can potentially replace TX-100. To date, a few detergent candidates have been identified based on viral inactivation studies, while direct mechanistic comparison of TX-100 and potential replacements from a biophysical interaction perspective is warranted. Herein, we employed a supported lipid bilayer (SLB) platform to comparatively evaluate the membrane-disruptive properties of TX-100 and a potential replacement, Simulsol SL 11W (SL-11W), and identified key mechanistic differences in terms of how the two detergents interact with phospholipid membranes. Quartz crystal microbalance-dissipation (QCM-D) measurements revealed that TX-100 was more potent and induced rapid, irreversible, and complete membrane solubilization, whereas SL-11W caused more gradual, reversible membrane budding and did not induce extensive membrane solubilization. The results further demonstrated that TX-100 and SL-11W both exhibit concentration-dependent interaction behaviors and were only active at or above their respective critical micelle concentration (CMC) values. Collectively, our findings demonstrate that TX-100 and SL-11W have distinct membrane-disruptive effects in terms of potency, mechanism of action, and interaction kinetics, and the SLB platform approach can support the development of biophysical assays to efficiently test potential TX-100 replacements.
Subcellular Remodeling in Filamin C Deficient Mouse Hearts Impairs Myocyte Tension Development during Progression of Dilated Cardiomyopathy
Authors: Powers Joseph D. , Kirkland Natalie J. , Liu Canzhao , Razu Swithin S. , Fang Xi , Engler Adam J. , Chen Ju , McCulloch Andrew D.
Published: January 2022

Dilated cardiomyopathy (DCM) is a life-threatening form of heart disease that is typically characterized by progressive thinning of the ventricular walls, chamber dilation, and systolic dysfunction. Multiple mutations in the gene encoding filamin C (FLNC), an actin-binding cytoskeletal protein in cardiomyocytes, have been found in patients with DCM. However, the mechanisms that lead to contractile impairment and DCM in patients with FLNC variants are poorly understood. To determine how FLNC regulates systolic force transmission and DCM remodeling, we used an inducible, cardiac-specific FLNC-knockout (icKO) model to produce a rapid onset of DCM in adult mice. Loss of FLNC reduced systolic force development in single cardiomyocytes and isolated papillary muscles but did not affect twitch kinetics or calcium transients. Electron and immunofluorescence microscopy showed significant defects in Z-disk alignment in icKO mice and altered myofilament lattice geometry. Moreover, a loss of FLNC induces a softening myocyte cortex and structural adaptations at the subcellular level that contribute to disrupted longitudinal force production during contraction. Spatially explicit computational models showed that these structural defects could be explained by a loss of inter-myofibril elastic coupling at the Z-disk. Our work identifies FLNC as a key regulator of the multiscale ultrastructure of cardiomyocytes and therefore plays an important role in maintaining systolic mechanotransmission pathways, the dysfunction of which may be key in driving progressive DCM.
Transcriptome Analysis of an Aedes albopictus Cell Line Single- and Dual-Infected with Lammi Virus and WNV
Authors: Öhlund Pontus , Delhomme Nicolas , Hayer Juliette , Hesson Jenny C. , Blomström Anne-Lie
Published: January 2022

Understanding the flavivirus infection process in mosquito hosts is important and fundamental in the search for novel control strategies that target the mosquitoes’ ability to carry and transmit pathogenic arboviruses. A group of viruses known as insect-specific viruses (ISVs) has been shown to interfere with the infection and replication of a secondary arbovirus infection in mosquitoes and mosquito-derived cell lines. However, the molecular mechanisms behind this interference are unknown. Therefore, in the present study, we infected the Aedes albopictus cell line U4.4 with either the West Nile virus (WNV), the insect-specific Lammi virus (LamV) or an infection scheme whereby cells were pre-infected with LamV 24 h prior to WNV challenge. The qPCR analysis showed that the dual-infected U4.4 cells had a reduced number of WNV RNA copies compared to WNV-only infected cells. The transcriptome profiles of the different infection groups showed a variety of genes with altered expression. WNV-infected cells had an up-regulation of a broad range of immune-related genes, while in LamV-infected cells, many genes related to stress, such as different heat-shock proteins, were up-regulated. The transcriptome profile of the dual-infected cells was a mix of up- and down-regulated genes triggered by both viruses. Furthermore, we observed an up-regulation of signal peptidase complex (SPC) proteins in all infection groups. These SPC proteins have shown importance for flavivirus assembly and secretion and could be potential targets for gene modification in strategies for the interruption of flavivirus transmission by mosquitoes.
High-Accuracy Relative Biological Effectiveness Values Following Low-Dose Thermal Neutron Exposures Support Bimodal Quality Factor Response with Neutron Energy
Authors: Paterson Laura C. , Festarini Amy , Stuart Marilyne , Ali Fawaz , Costello Christie , Boyer Chad , Rogge Ronald , Ybarra Norma , Kildea John , Richardson Richard B.
Published: January 2022

Theoretical evaluations indicate the radiation weighting factor for thermal neutrons differs from the current International Commission on Radiological Protection (ICRP) recommended value of 2.5, which has radiation protection implications for high-energy radiotherapy, inside spacecraft, on the lunar or Martian surface, and in nuclear reactor workplaces. We examined the relative biological effectiveness (RBE) of DNA damage generated by thermal neutrons compared to gamma radiation. Whole blood was irradiated by 64 meV thermal neutrons from the National Research Universal reactor. DNA damage and erroneous DNA double-strand break repair was evaluated by dicentric chromosome assay (DCA) and cytokinesis-block micronucleus (CBMN) assay with low doses ranging 6–85 mGy. Linear dose responses were observed. Significant DNA aberration clustering was found indicative of high ionizing density radiation. When the dose contribution of both the 14N(n,p)14C and 1H(n,γ)2H capture reactions were considered, the DCA and the CBMN assays generated similar maximum RBE values of 11.3 ± 1.6 and 9.0 ± 1.1, respectively. Consequently, thermal neutron RBE is approximately four times higher than the current ICRP radiation weighting factor value of 2.5. This lends support to bimodal peaks in the quality factor for RBE neutron energy response, underlining the importance of radiological protection against thermal neutron exposures.
Activation of Notch3 in Renal Tubular Cells Leads to Progressive Cystic Kidney Disease
Authors: Djudjaj Sonja , Kavvadas Panagiotis , Prakoura Niki , Bülow Roman D. , Migeon Tiffany , Placier Sandrine , Chadjichristos Christos E. , Boor Peter , Chatziantoniou Christos
Published: January 2022

Background: Polycystic kidney disease (PKD) is a genetic disorder affecting millions of people worldwide that is characterized by fluid-filled cysts and leads to end-stage renal disease (ESRD). The hallmarks of PKD are proliferation and dedifferentiation of tubular epithelial cells, cellular processes known to be regulated by Notch signaling. Methods: We found increased Notch3 expression in human PKD and renal cell carcinoma biopsies. To obtain insight into the underlying mechanisms and the functional consequences of this abnormal expression, we developed a transgenic mouse model with conditional overexpression of the intracellular Notch3 (ICN3) domain specifically in renal tubules. We evaluated the alterations in renal function (creatininemia, BUN) and structure (cysts, fibrosis, inflammation) and measured the expression of several genes involved in Notch signaling and the mechanisms of inflammation, proliferation, dedifferentiation, fibrosis, injury, apoptosis and regeneration. Results: After one month of ICN3 overexpression, kidneys were larger with tubules grossly enlarged in diameter, with cell hypertrophy and hyperplasia, exclusively in the outer stripe of the outer medulla. After three months, mice developed numerous cysts in proximal and distal tubules. The cysts had variable sizes and were lined with a single- or multilayered, flattened, cuboid or columnar epithelium. This resulted in epithelial hyperplasia, which was observed as protrusions into the cystic lumen in some of the renal cysts. The pre-cystic and cystic epithelium showed increased expression of cytoskeletal filaments and markers of epithelial injury and dedifferentiation. Additionally, the epithelium showed increased proliferation with an aberrant orientation of the mitotic spindle. These phenotypic tubular alterations led to progressive interstitial inflammation and fibrosis. Conclusions: In summary, Notch3 signaling promoted tubular cell proliferation, the alignment of cell division, dedifferentiation and hyperplasia, leading to cystic kidney diseases and pre-neoplastic lesions.
A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome
Authors: Skalníková Magdalena , Staňo Kozubík Kateřina , Trizuljak Jakub , Vrzalová Zuzana , Radová Lenka , Réblová Kamila , Holbová Radka , Kurucová Terézia , Svozilová Hana , Štika Jiří , Blaháková Ivona , Dvořáčková Barbara , Prudková Marie , Stehlíková Olga , Šmída Michal , Křen Leoš , Smejkal Petr , Pospíšilová Šárka , Doubek Michael
Published: January 2022

Bernard-Soulier syndrome (BSS) is a rare inherited disorder characterized by unusually large platelets, low platelet count, and prolonged bleeding time. BSS is usually inherited in an autosomal recessive (AR) mode of inheritance due to a deficiency of the GPIb-IX-V complex also known as the von Willebrand factor (VWF) receptor. We investigated a family with macrothrombocytopenia, a mild bleeding tendency, slightly lowered platelet aggregation tests, and suspected autosomal dominant (AD) inheritance. We have detected a heterozygous GP1BA likely pathogenic variant, causing monoallelic BSS. A germline GP1BA gene variant (NM_000173:c.98G > A:p.C33Y), segregating with the macrothrombocytopenia, was detected by whole-exome sequencing. In silico analysis of the protein structure of the novel GPIbα variant revealed a potential structural defect, which could impact proper protein folding and subsequent binding to VWF. Flow cytometry, immunoblot, and electron microscopy demonstrated further differences between p.C33Y GP1BA carriers and healthy controls. Here, we provide a detailed insight into its clinical presentation and phenotype. Moreover, the here described case first presents an mBSS patient with two previous ischemic strokes.
The Effect of Ethanol on Disassembly of Amyloid-β1-42 Pentamer Revealed by Atomic Force Microscopy and Gel Electrophoresis
Authors: Matsui Atsuya , Bellier Jean-Pierre , Kanai Takeshi , Satooka Hiroki , Nakanishi Akio , Terada Tsukasa , Ishibe Takafumi , Nakamura Yoshiaki , Taguchi Hiroyasu , Naruse Nobuyasu , Mera Yutaka
Published: January 2022

The most common type of dementia, Alzheimer’s disease, is associated with senile plaques formed by the filamentous aggregation of hydrophobic amyloid-β (Aβ) in the brains of patients. Small oligomeric assemblies also occur and drugs and chemical compounds that can interact with such assemblies have attracted much attention. However, these compounds need to be solubilized in appropriate solvents, such as ethanol, which may also destabilize their protein structures. As the impact of ethanol on oligomeric Aβ assembly is unknown, we investigated the effect of various concentrations of ethanol (0 to 7.2 M) on Aβ pentameric assemblies (Aβp) by combining blue native-PAGE (BN-PAGE) and ambient air atomic force microscopy (AFM). This approach was proven to be very convenient and reliable for the quantitative analysis of Aβ assembly. The Gaussian analysis of the height histogram obtained from the AFM images was correlated with band intensity on BN-PAGE for the quantitative estimation of Aβp. Our observations indicated up to 1.4 M (8.3%) of added ethanol can be used as a solvent/vehicle without quantitatively affecting Aβ pentamer stability. Higher concentration induced significant destabilization of Aβp and eventually resulted in the complete disassembly of Aβp.
Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis
Authors: Riewruja Kanyakorn , Phakham Suphattra , Sompolpong Patlapa , Reantragoon Rangsima , Tanavalee Aree , Ngarmukos Srihatach , Udomsinprasert Wanvisa , Suantawee Tanyawan , Dechsupa Sinsuda , Honsawek Sittisak
Published: January 2022

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient’s quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1β were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery.
XRCC1 Prevents Replication Fork Instability during Misincorporation of the DNA Demethylation Bases 5-Hydroxymethyl-2′-Deoxycytidine and 5-Hydroxymethyl-2′-Deoxyuridine
Authors: Peña-Gómez María José , Suárez-Pizarro Marina , Rosado Iván V.
Published: January 2022

Whilst avoidance of chemical modifications of DNA bases is essential to maintain genome stability, during evolution eukaryotic cells have evolved a chemically reversible modification of the cytosine base. These dynamic methylation and demethylation reactions on carbon-5 of cytosine regulate several cellular and developmental processes such as embryonic stem cell pluripotency, cell identity, differentiation or tumourgenesis. Whereas these physiological processes are well characterized, very little is known about the toxicity of these cytosine analogues when they incorporate during replication. Here, we report a role of the base excision repair factor XRCC1 in protecting replication fork upon incorporation of 5-hydroxymethyl-2′-deoxycytosine (5hmC) and its deamination product 5-hydroxymethyl-2′-deoxyuridine (5hmU) during DNA synthesis. In the absence of XRCC1, 5hmC exposure leads to increased genomic instability, replication fork impairment and cell lethality. Moreover, the 5hmC deamination product 5hmU recapitulated the genomic instability phenotypes observed by 5hmC exposure, suggesting that 5hmU accounts for the observed by 5hmC exposure. Remarkably, 5hmC-dependent genomic instability and replication fork impairment seen in Xrcc1−/− cells were exacerbated by the trapping of Parp1 on chromatin, indicating that XRCC1 maintains replication fork stability during processing of 5hmC and 5hmU by the base excision repair pathway. Our findings uncover natural epigenetic DNA bases 5hmC and 5hmU as genotoxic nucleosides that threaten replication dynamics and genome integrity in the absence of XRCC1.
The Small GTPase FgRab1 Plays Indispensable Roles in the Vegetative Growth, Vesicle Fusion, Autophagy and Pathogenicity of Fusarium graminearum
Authors: Yuan Yanping , Zhang Meiru , Li Jingjing , Yang Chengdong , Abubakar Yakubu Saddeeq , Chen Xin , Zheng Wenhui , Wang Zonghua , Zheng Huawei , Zhou Jie
Published: January 2022

Rab GTPases are key regulators of membrane and intracellular vesicle transports. However, the biological functions of FgRab1 are still unclear in the devastating wheat pathogen Fusarium graminearum. In this study, we generated constitutively active (CA) and dominant-negative (DN) forms of FgRAB1 from the wild-type PH-1 background for functional analyses. Phenotypic analyses of these mutants showed that FgRab1 is important for vegetative growth, cell wall integrity and hyphal branching. Compared to the PH-1 strain, the number of spores produced by the Fgrab1DN strain was significantly reduced, with obviously abnormal conidial morphology. The number of septa in the conidia of the Fgrab1DN mutant was fewer than that observed in the PH-1 conidia. Fgrab1DN was dramatically reduced in its ability to cause Fusarium head blight symptoms on wheat heads. GFP-FgRab1 was observed to partly localize to the Golgi apparatus, endoplasmic reticulum and Spitzenkörper. Furthermore, we found that FgRab1 inactivation blocks not only the transport of the v-SNARE protein FgSnc1 from the Golgi to the plasma membrane but also the fusion of endocytic vesicles with their target membranes and general autophagy. In summary, our results indicate that FgRab1 plays vital roles in vegetative growth, conidiogenesis, pathogenicity, autophagy, vesicle fusion and trafficking in F. graminearum.
Effects of Endurance Training on the Coenzyme Q Redox State in Rat Heart, Liver, and Brain at the Tissue and Mitochondrial Levels: Implications for Reactive Oxygen Species Formation and Respiratory Chain Remodeling
Authors: Dominiak Karolina , Galganski Lukasz , Budzinska Adrianna , Woyda-Ploszczyca Andrzej , Zoladz Jerzy A. , Jarmuszkiewicz Wieslawa
Published: January 2022

Sixteen adult, 4-month-old male Wistar rats were randomly assigned to the training group (n = 8) or the control group (n = 8). We elucidated the effects of 8 weeks of endurance training on coenzyme Q (Q) content and the formation of reactive oxygen species (ROS) at the tissue level and in isolated mitochondria of the rat heart, liver and brain. We demonstrated that endurance training enhanced mitochondrial biogenesis in all tested organs, while a significant increase in the Q redox state was observed in the heart and brain, indicating an elevated level of QH2 as an antioxidant. Moreover, endurance training increased the mQH2 antioxidant pool in the mitochondria of the heart and liver, but not in the brain. At the tissue and isolated mitochondria level, an increase in ROS formation was only observed in the heart. ROS formation observed in the mitochondria of individual rat tissues after training may be associated with changes in the activity/amount of individual components of the oxidative phosphorylation system and its molecular organization, as well as with the size of the oxidized pool of mitochondrial Q acting as an electron carrier in the respiratory chain. Our results indicate that tissue-dependent changes induced by endurance training in the cellular and mitochondrial QH2 pool acting as an antioxidant and in the mitochondrial Q pool serving the respiratory chain may serve important roles in energy metabolism, redox homeostasis and the level of oxidative stress.
Thymoquinone-Loaded Chitosan Nanoparticles as Natural Preservative Agent in Cosmetic Products
Authors: Mondéjar-López María , López-Jiménez Alberto José , Martínez Joaquín C. García , Ahrazem Oussama , Gómez-Gómez Lourdes , Niza Enrique
Published: January 2022

The current status of controversy regarding the use of certain preservatives in cosmetic products makes it necessary to seek new ecological alternatives that are free of adverse effects on users. In our study, the natural terpene thymoquinone was encapsulated in chitosan nanoparticles. The nanoparticles were characterized by DLS and TEM, showing a particle size of 20 nm. The chemical structure, thermal properties, and release profile of thymoquinone were evaluated and showed a successful stabilization and sustained release of terpenes. The antimicrobial properties of the nanoparticles were evaluated against typical microbial contaminants found in cosmetic products, showing high antimicrobial properties. Furthermore, natural moisturizing cream inoculated with the aforementioned microorganisms was formulated with thymoquinone-chitosan nanoparticles to evaluate the preservative efficiency, indicating its promising use as a preservative in cosmetics.
Serum Amyloid A3 Promoter-Driven Luciferase Activity Enables Visualization of Diabetic Kidney Disease
Authors: Saliu Tolulope Peter , Yazawa Nao , Hashimoto Kotaro , Miyata Kenshu , Kudo Ayane , Horii Mayu , Kamesawa Mion , Kumrungsee Thanutchaporn , Yanaka Noriyuki
Published: January 2022

The early detection of diabetic nephropathy (DN) in mice is necessary for the development of drugs and functional foods. The purpose of this study was to identify genes that are significantly upregulated in the early stage of DN progression and develop a novel model to non-invasively monitor disease progression within living animals using in vivo imaging technology. Streptozotocin (STZ) treatment has been widely used as a DN model; however, it also exhibits direct cytotoxicity to the kidneys. As it is important to distinguish between DN-related and STZ-induced nephropathy, in this study, we compared renal responses induced by the diabetic milieu with two types of STZ models: multiple low-dose STZ injections with a high-fat diet and two moderate-dose STZ injections to induce DN. We found 221 genes whose expression was significantly altered during DN development in both models and identified serum amyloid A3 (Saa3) as a candidate gene. Next, we applied the Saa3 promoter-driven luciferase reporter (Saa3-promoter luc mice) to these two STZ models and performed in vivo bioluminescent imaging to monitor the progression of renal pathology. In this study, to further exclude the possibility that the in vivo bioluminescence signal is related to renal cytotoxicity by STZ treatment, we injected insulin into Saa3-promoter luc mice and showed that insulin treatment could downregulate renal inflammatory responses with a decreased signal intensity of in vivo bioluminescence imaging. These results strongly suggest that Saa3 promoter activity is a potent non-invasive indicator that can be used to monitor DN progression and explore therapeutic agents and functional foods.
Discovery of microRNA-like Small RNAs in Pathogenic Plant Fungus Verticillium nonalfalfae Using High-Throughput Sequencing and qPCR and RLM-RACE Validation
Authors: Jeseničnik Taja , Štajner Nataša , Radišek Sebastjan , Mishra Ajay Kumar , Košmelj Katarina , Kunej Urban , Jakše Jernej
Published: January 2022

Verticillium nonalfalfae (V. nonalfalfae) is one of the most problematic hop (Humulus lupulus L.) pathogens, as the highly virulent fungal pathotypes cause severe annual yield losses due to infections of entire hop fields. In recent years, the RNA interference (RNAi) mechanism has become one of the main areas of focus in plant—fungal pathogen interaction studies and has been implicated as one of the major contributors to fungal pathogenicity. MicroRNA-like RNAs (milRNAs) have been identified in several important plant pathogenic fungi; however, to date, no milRNA has been reported in the V. nonalfalfae species. In the present study, using a high-throughput sequencing approach and extensive bioinformatics analysis, a total of 156 milRNA precursors were identified in the annotated V. nonalfalfae genome, and 27 of these milRNA precursors were selected as true milRNA candidates, with appropriate microRNA hairpin secondary structures. The stem-loop RT-qPCR assay was used for milRNA validation; a total of nine V. nonalfalfae milRNAs were detected, and their expression was confirmed. The milRNA expression patterns, determined by the absolute quantification approach, imply that milRNAs play an important role in the pathogenicity of highly virulent V. nonalfalfae pathotypes. Computational analysis predicted milRNA targets in the V. nonalfalfae genome and in the host hop transcriptome, and the activity of milRNA-mediated RNAi target cleavage was subsequently confirmed for two selected endogenous fungal target gene models using the 5′ RLM-RACE approach.
Suppressing Effect of Na+/Ca2+ Exchanger (NCX) Inhibitors on the Growth of Melanoma Cells
Authors: Liu Zikai , Cheng Qing , Ma Xiaoli , Song Mingke
Published: January 2022

The role of calcium ion (Ca2+) signaling in tumorigenicity has received increasing attention in melanoma research. Previous Ca2+ signaling studies focused on Ca2+ entry routes, but rarely explored the role of Ca2+ extrusion. Functioning of the Na+/Ca2+ exchanger (NCX) on the plasma membrane is the major way of Ca2+ extrusion, but very few associations between NCX and melanoma have been reported. Here, we explored whether pharmacological modulation of the NCX could suppress melanoma and promise new therapeutic strategies. Methods included cell viability assay, Ca2+ imaging, immunoblotting, and cell death analysis. The NCX inhibitors SN-6 and YM-244769 were used to selectively block reverse operation of the NCX. Bepridil, KB-R7943, and CB-DMB blocked either reverse or forward NCX operation. We found that blocking the reverse NCX with SN-6 or YM-244769 (5–100 μM) did not affect melanoma cells or increase cytosolic Ca2+. Bepridil, KB-R7943, and CB-DMB all significantly suppressed melanoma cells with IC50 values of 3–20 μM. Bepridil and KB-R7943 elevated intracellular Ca2+ level of melanoma. Bepridil-induced melanoma cell death came from cell cycle arrest and enhanced apoptosis, which were all attenuated by the Ca2+ chelator BAPTA-AM. As compared with melanoma, normal melanocytes had lower NCX1 expression and were less sensitive to the cytotoxicity of bepridil. In conclusion, blockade of the forward but not the reverse NCX leads to Ca2+-related cell death in melanoma and the NCX is a potential drug target for cancer therapy.