bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Musical Stimulation and Mother’s Voice on the Early Development of Musical Abilities: A Neuropsychological Perspective
Authors: Poćwierz-Marciniak Ilona , Harciarek Michał
Published: August 2021

An infant’s early contact with music affects its future development in a broad sense, including the development of musical aptitude. Contact with the mother’s voice, both prenatally and after birth, is also extremely important for creating an emotional bond between the infant and the mother. This article discusses the role that auditory experience—both typically musical and that associated with the mother’s voice—plays in fetal, neonatal, and infant development, particularly in terms of musical aptitude. Attempts have also been made to elucidate the neuropsychological mechanisms underlying the positive effects that appropriate musical stimulation can have on a child’s development.
A Survey of Neonatal Nurses Perspectives on Voice Use and Auditory Needs with Premature Infants in the NICU
Authors: Smith Amy R. , Hanson-Abromeit Deanna , Heaton Ashley , Salley Brenda
Published: August 2021

Background: Exposure to the voice and language during the critical period of auditory development associated with the third trimester is thought to be an essential building block for language. Differences in the auditory experience associated with early life in the NICU may increase the risk of language delays for premature infants. NICU nurses are fundamental in the care of premature infants; how they use their voices may be important in understanding auditory experiences in the NICU. This study examined voice use behaviors of NICU nurses in the United States and their current knowledge of early auditory development. Method: An opt-in, online questionnaire. Results: Nurses reported using their voice more as the age of infants approached term gestation and speaking to infants was the most common type of voice use. Both infant and nurse factors influenced reported voice use decisions in the NICU. Nurses did not believe the NICU auditory environment to be sufficient to meet early auditory needs of premature infants but did believe that premature infants are exposed to adequate voice sounds. Conclusions: A gap in knowledge regarding the importance of early exposure to voice sounds may be a barrier to nurses using their voices to support early auditory development.
Indoor Air Quality Improvement Using Nature-Based Solutions: Design Proposals to Greener Cities
Authors: Mata Teresa M. , Oliveira Gisela M. , Monteiro Helena , Silva Gabriela Ventura , Caetano Nídia S. , Martins António A.
Published: August 2021

Low indoor air quality is an increasingly important problem due to the spread of urbanization. Because people spend most of their time inside, poor indoor air quality causes serious human health issues, resulting in significant economic losses. In this work, the current state of affairs is presented and analyzed, focusing on the current problems and the available solutions to improve the quality of indoor air, and the use of nature-based solutions. These involve the cultivation of microalgae in closed photobioreactors. In these systems, photosynthetic organisms can capture CO2 and other pollutants generated in indoor environments, which they use to grow and develop biomass. Several possible layouts for the implementation of microalgae-based indoor air cleaning systems are presented, taking into account the systems that are currently available at a commercial scale. A critical analysis of the microalgae indoor purification systems is presented, highlighting their advantages and disadvantages, and suggesting potential improvements and future lines of research and development in the area.
Long-Term Residential Exposure to Particulate Matter and Its Components, Nitrogen Dioxide and Ozone—A Northern Sweden Cohort Study on Mortality
Authors: Sommar Johan N. , Hvidtfeldt Ulla A. , Geels Camilla , Frohn Lise M. , Brandt Jørgen , Christensen Jesper H. , Raaschou-Nielsen Ole , Forsberg Bertil
Published: August 2021

This study aims to estimate the mortality risk associated with air pollution in a Swedish cohort with relatively low exposure. Air pollution models were used to estimate annual mean concentrations of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5), primary emitted carbonaceous particles (BC/pOC), sea salt, chemically formed particles grouped as secondary inorganic and organic aerosols (SIA and SOA) as well as ozone (O3) and nitrogen dioxide (NO2). The exposure, as a moving average was calculated based on home address for the time windows 1 year (lag 1), 1–5 years (lag 1–5) and 1–10 years (lag 1–10) preceding the death. During the study period, 1151 cases of natural mortality, 253 cases of cardiovascular disease (CVD) mortality and 113 cases of respiratory and lung cancer mortality were observed during 369,394 person-years of follow-up. Increased natural mortality was observed in association with NO2 (3% [95% CI −8–14%] per IQR) and PM2.5 (2% [95% CI −5–9%] for an IQR increase) and its components, except for SOA where a decreased risk was observed. Higher risk increases were observed for CVD mortality (e.g., 18% [95% CI 1–39%] per IQR for NO2). These findings at low exposure levels are relevant for future decisions concerning air quality policies.
Leveraging Strategic Foresight to Advance Worker Safety, Health, and Well-Being
Authors: Streit Jessica M. K. , Felknor Sarah A. , Edwards Nicole T. , Howard John
Published: August 2021

Attending to the ever-expanding list of factors impacting work, the workplace, and the workforce will require innovative methods and approaches for occupational safety and health (OSH) research and practice. This paper explores strategic foresight as a tool that can enhance OSH capacity to anticipate, and even shape, the future as it pertains to work. Equal parts science and art, strategic foresight includes the development and analysis of plausible alternative futures as inputs to strategic plans and actions. Here, we review several published foresight approaches and examples of work-related futures scenarios. We also present a working foresight framework tailored for OSH and offer recommendations for next steps to incorporate strategic foresight into research and practice in order to advance worker safety, health, and well-being.
Weight Gain Predicts Metabolic Syndrome among North Korean Refugees in South Korea
Authors: Kim Yoon Jung , Lee Yo Han , Lee Yun Jeong , Kim Kyeong Jin , Kim Sin Gon
Published: August 2021

Previous cross-sectional studies showed that immigrants from low-income to high-income countries have higher risk of cardiovascular disease and type 2 diabetes mellitus. We investigated the association between weight gain during the resettlement in South Korea and risk of metabolic syndrome (MetS) among North Korean refugees (NKRs) in this cross-sectional study. In total, 932 NKRs aged 20–80 years in South Korea voluntarily underwent health examination from 2008 to 2017. We compared the risk of MetS and its components between the weight gain group (gained ≥5 kg) and the non-weight gain group (gained <5 kg, maintained or lost body weight) during resettlement in South Korea after defection from North Korea. Multiple logistic regression analysis predicted odds ratio of MetS on the basis of weight change, adjusting for covariates and current body mass index (BMI). We also evaluated the difference in body composition of NKRs between two groups. The prevalence of MetS in the weight gain group was 26%, compared to 10% in the non-weight gain group (p-value < 0.001). The weight gain group had a two-fold higher risk of MetS than the non-weight gain group after adjusting for current BMI (odds ratio 1.875, p-value = 0.045). The prevalence of central obesity, impaired fasting glucose, elevated blood pressure, and hypertriglyceridemia were higher in the weight gain group than the non-weight gain group (36% vs. 12%, p-value < 0.001; 32% vs. 19%, p-value < 0.001; 34 vs. 25%, p-value = 0.008; 19% vs. 13%, p-value = 0.025, respectively). The analysis of body composition showed that the percentage of body fat in the weight gain group was higher than in the non-weight gain group, indicating increased fat mass rather than muscle mass in the weight gain group as their body weight increased during resettlement (33.4 ± 6.53% vs. 28.88 ± 7.40%, p < 0.005). Excess weight gain after defection from North Korea increased the risk of MetS among NKRs in South Korea. It is necessary to monitor weight change among NKRs and their effect on their metabolic health in the long term.
Contextual Determinants in Alcohol, Tobacco and Cannabis Consumption, Mood and Bullying during Adolescence
Authors: Díaz-Geada Ainara , Obradors-Rial Núria , Baena Antoni , Teixidó-Compañó Ester , Colillas-Malet Ester , Mallah Narmeen , Moure-Rodríguez Lucía , Caamaño-Isorna Francisco , Barón-Garcia Tivy
Published: August 2021

The present study aimed to explore the differences in the consumption of alcohol, tobacco and cannabis, mood and bullying between adolescents. A cross-sectional study was carried out in five regions of Northern Spain (one in Galiza and four in central Catalonia) that share similar socioeconomic characteristics and encompass around 10,000 inhabitants each. Students living in Burela, Galiza (N = 71) were compared to those of Central Catalonia (N = 193). The independent variable was the municipality of residence. The dependent variables encompassed: weekly available pocket money, Family Affluence Scale, self-classified academic qualification, place of origin, alcohol consumption, tobacco and cannabis smoking, negative mood and bullying. The mean age and their 95% confidence intervals (95% CI) of participants were similar between the regions (Burela: 15.90 years (15.68–16.13) and Central Catalonia: 15.36 years (15.28–15.44)). More than half of the participants were females (Burela, Galiza (53.5%) and Catalonia (54.9%)). Prevalence ratios (PR) and their 95% CI were estimated using Poisson regression models. In comparison with adolescents from Burela (Galiza), those living in Central Catalonia had higher prevalence of diverse academic levels (adjusted PR = 3.92 (1.78–8.66)), tobacco consumption (adjusted PR = 2.41 (1.47–3.97)) and negative mood (adjusted PR = 5.97 (3.05–11.70)). Even when dealing with regions with similar socioeconomic characteristics and number of inhabitants, differences exist in terms of the socioeconomic level, tobacco consumption, mood and bullying, as reported by adolescents.
Traumatic Distress of COVID-19 and Depression in the General Population: Exploring the Role of Resilience, Anxiety, and Hope
Authors: Nearchou Finiki , Douglas Ellen
Published: August 2021

International evidence published so far shows that the COVID-19 pandemic has negatively impacted on global mental health. Specifically, there is some research suggesting that the psychological distress related to depression, anxiety and posttraumatic stress has impacted on the psychological well-being of the general population. Yet, there is limited evidence on the relational paths between COVID-19 traumatic distress and depression. Participants of this cross-sectional study were 456 adults 18 years old or older from the general population (Mean age = 41.2 years, SD = 11.7) who completed an online questionnaire including measures assessing depression, anxiety, resilience, hope and traumatic distress related to COVID-19. Structural equation modelling was applied to examine the proposed mediation model. The results confirmed the proposed model, with traumatic distress of COVID-19, resilience, anxiety and hope explaining a considerable amount of variance (59%) in depression scores. Traumatic distress of COVID-19 was a strong positive predictor of depression, while anxiety, hope and resilience were both joint and unique mediators of this relationship. Exposure to the COVID-19 pandemic is strongly associated with depression in adults of the general population. The co-occurrence of anxiety may negatively contribute to experiencing higher levels of depression, while resilience and hope may act as buffers against depression associated with the impact of this pandemic. Our findings suggest that wide community-based interventions designed to promote resilience, build hope and reduce anxiety may help mitigate depression associated with exposure to the COVID-19 pandemic.
Effects of a Physical Exercise Program on Physiological, Psychological, and Physical Function of Older Adults in Rural Areas
Authors: Kim Sunmi , Lee Eun-Jee , Kim Hyeon-Ok
Published: August 2021

With the increase in the older population, there is a concern for health in older adults. This study aimed to develop a physical exercise program that combined walking and gymnastics for older adults residing in rural areas and to evaluate its effect on their physiological and psychological health and physical function. A quasi-experimental design was adopted. Participants were aged 65 years or older, with 94 and 130 participants in the experimental and control group, respectively. The program was implemented for seven months, from April–October 2016. Walking and gymnastics were performed once a week each, for about 60 and 50 min, respectively. Data were analyzed using the Chi-squared test, Fisher’s exact test, independent t-test, or Mann–Whitney U test. Results revealed that the experimental group participants displayed improved waist circumference (t = 1.70, p = 0.045), body mass index (U = 4691.00, p = 0.002), depressive symptoms (t = −2.94, p = 0.002), upper limb strength (t = 2.27, p = 0.012), and lower limb strength (t = 3.86, p < 0.001). Therefore, it can be presumed that the physical exercise program was effective and beneficial for older adults living in rural areas. This program is expected to contribute to maintaining and improving their health if implemented regularly in the future.
Physiotherapy Students’ Experiences about Ethical Situations Encountered in Clinical Practices
Authors: Aguilar-Rodríguez Marta , Kulju Kati , Hernández-Guillén David , Mármol-López María Isabel , Querol-Giner Felipe , Marques-Sule Elena
Published: August 2021

(1) Background: It is important to explore the ethical situations that physiotherapy students encountered in their clinical practices. (2) Methods: Qualitative, explorative, descriptive study. The participants included third-year physiotherapy students. They had to write five narratives about ethical situations encountered in their clinical practices. Krippendorff’s method for qualitative content analysis was used to cluster units within the data to identify emergent themes. The study protocol was approved by the authors’ University Ethic Committee of Human Research (H1515588244257). (3) Result: 280 narratives were reported by 64 students (23.34 ± 4.20 years, 59% women). Eight categories were identified from the qualitative analysis of the data: (a) professional responsibility, (b) professional competence, (c), beneficence, (d) equality and justice, (e) autonomy, (f) confidentiality, (g) respect for privacy, and (h) sincerity. All participants were informed and provided written informed consent. (4) Conclusions: Ethical principles were frequently violated in physiotherapy. Experiences of physiotherapy students must be examined to tailor educational interventions prior to their initiation into practice. Ethics education is needed in workplaces and should be increased in basic education. Facilitating the ethical awareness of future physiotherapists is a challenge for university teachers who provide ethical competence training.
A Step towards Understanding and Tackling Health Inequalities: The Use of Secondary Prevention Services and the Need for Health Promotion in a Rural Setting
Authors: Karasiewicz Monika , Chawłowska Ewelina , Lipiak Agnieszka , Więckowska Barbara
Published: August 2021

Poland has recently intensified its health promotion in an effort to extend healthy life expectancy and reduce health inequalities. Our aim was to reach a deprived rural population, increase its health literacy, and explore its use of and barriers to cancer screening and public health care. A CBPR study was conducted in one of the poorest districts in Wielkopolska region, Poland, among 122 beneficiaries of health education workshops. A self-developed questionnaire was used. The reported barriers to participation in cancer screening included: lack of time, lack of need, or feeling healthy (32.8%); long waiting times (17.2%); fear of costs (9%). Physicians seldom recommended screening to their patients. Only 7.4% of respondents had ever received dermatoscopy. Among women, 18.2% did not perform any breast exams and 25% had never had smear tests. Diagnostics was often financed out of pocket (thyroid ultrasound = 58.1%; smear test = 48.5%; breast ultrasound = 36.8%). The health system needs mentioned by participants included better access to physicians (65.6%), promotion of free screening tests (54.9%), and access to public health programmes (22.1%). There is an urgent need to translate national strategies into action. Health promotion and better access to care must become priorities in deprived areas, while primary care providers should become key figures in delivering these services.
Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome
Authors: Rooney Kathleen , Levy Michael A. , Haghshenas Sadegheh , Kerkhof Jennifer , Rogaia Daniela , Tedesco Maria Giovanna , Imperatore Valentina , Mencarelli Amedea , Squeo Gabriella Maria , Di Venere Eleonora , Di Cara Giuseppe , Verrotti Alberto , Merla Giuseppe , Tedder Matthew L. , DuPont Barbara R. , Sadikovic Bekim , Prontera Paolo
Published: August 2021

The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS.
Serotonergic–Muscarinic Interaction within the Prefrontal Cortex as a Novel Target to Reverse Schizophrenia-Related Cognitive Symptoms
Authors: Cieślik Paulina , Radulska Adrianna , Burnat Grzegorz , Kalinowski Leszek , Wierońska Joanna M.
Published: August 2021

Recent studies revealed that the activation of serotonergic 5-HT1A and muscarinic M1, M4, or M5 receptors prevent MK-801-induced cognitive impairments in animal models. In the present study, the effectiveness of the simultaneous activation of 5-HT1A and muscarinic receptors at preventing MK-801-induced cognitive deficits in novel object recognition (NOR) or Y-maze tests was investigated. Activators of 5-HT1A (F15599), M1 (VU0357017), M4 (VU0152100), or M5 (VU0238429) receptors administered at top doses for seven days reversed MK-801-induced deficits in the NOR test, similar to the simultaneous administration of subeffective doses of F15599 (0.05 mg/kg) with VU0357017 (0.15 mg/kg), VU0152100 (0.05 mg/kg), or VU0238429 (1 mg/kg). The compounds did not prevent the MK-801-induced impairment when administered acutely. Their activity was less evident in the Y-maze. Pharmacokinetic studies revealed high brain penetration of F15599 (brain/plasma ratio 620%), which was detected in the frontal cortex (FC) up to 2 h after administration. Decreases in the brain penetration properties of the compounds were observed after acute administration of the combinations, which might have influenced behavioral responses. This negative effect on brain penetration was not observed when the compounds were administered repeatedly. Based on our results, prolonged administration of a 5-HT1A activator with muscarinic receptor ligands may be effective at reversing cognitive decline related to schizophrenia, and the FC may play a critical role in this interaction.
Identification of Potential Probiotics Producing Bacteriocins Active against Listeria monocytogenes by a Combination of Screening Tools
Authors: Desiderato Christian K. , Sachsenmaier Steffen , Ovchinnikov Kirill V. , Stohr Jonas , Jacksch Susanne , Desef Dominique N. , Crauwels Peter , Egert Markus , Diep Dzung B. , Goldbeck Oliver , Riedel Christian U.
Published: August 2021

Listeria monocytogenes is an important food-borne pathogen and a serious concern to food industries. Bacteriocins are antimicrobial peptides produced naturally by a wide range of bacteria mostly belonging to the group of lactic acid bacteria (LAB), which also comprises many strains used as starter cultures or probiotic supplements. Consequently, multifunctional strains that produce bacteriocins are an attractive approach to combine a green-label approach for food preservation with an important probiotic trait. Here, a collection of bacterial isolates from raw cow’s milk was typed by 16S rRNA gene sequencing and MALDI-Biotyping and supernatants were screened for the production of antimicrobial compounds. Screening was performed with live Listeria monocytogenes biosensors using a growth-dependent assay and pHluorin, a pH-dependent protein reporting membrane damage. Purification by cation exchange chromatography and further investigation of the active compounds in supernatants of two isolates belonging to the species Pediococcus acidilactici and Lactococcus garvieae suggest that their antimicrobial activity is related to heat-stable proteins/peptides that presumably belong to the class IIa bacteriocins. In conclusion, we present a pipeline of methods for high-throughput screening of strain libraries for potential starter cultures and probiotics producing antimicrobial compounds and their identification and analysis.
Live Cell Imaging of Enzymatic Turnover of an Adenosine 5′-Tetraphosphate Analog
Authors: Bhat Anayat , Li Shuang , Hammler Daniel , Winterhalder Martin J. , Marx Andreas , Zumbusch Andreas
Published: August 2021

The hydrolysis of nucleotides is of paramount importance as an energy source for cellular processes. In addition, the transfer of phosphates from nucleotides onto proteins is important as a post-translational protein modification. Monitoring the enzymatic turnover of nucleotides therefore offers great potential as a tool to follow enzymatic activity. While a number of fluorescence sensors are known, so far, there are no methods available for the real-time monitoring of ATP hydrolysis inside live cells. We present the synthesis and application of a novel fluorogenic adenosine 5′-tetraphosphate (Ap4) analog suited for this task. Upon enzymatic hydrolysis, the molecule displays an increase in fluorescence intensity, which provides a readout of its turnover. We demonstrate how this can be used for monitoring cellular processes involving Ap4 hydrolysis. To this end, we visualized the enzymatic activity in live cells using confocal fluorescence microscopy of the Ap4 analog. Our results demonstrate that the Ap4 analog is hydrolyzed in lysosomes. We show that this approach is suited to visualize the lysosome distribution profiles within the live cell and discuss how it can be employed to gather information regarding autophagic flux.
Identification of Two Early Folding Stage Prion Non-Local Contacts Suggested to Serve as Key Steps in Directing the Final Fold to Be Either Native or Pathogenic
Authors: Bergasa-Caceres Fernando , Rabitz Herschel A.
Published: August 2021

The initial steps of the folding pathway of the C-terminal domain of the murine prion protein mPrP(90–231) are predicted based on the sequential collapse model (SCM). A non-local dominant contact is found to form between the connecting region between helix 1 and β-sheet 1 and the C-terminal region of helix 3. This non-local contact nucleates the most populated molten globule-like intermediate along the folding pathway. A less stable early non-local contact between segments 120–124 and 179–183, located in the middle of helix 2, promotes the formation of a less populated molten globule-like intermediate. The formation of the dominant non-local contact constitutes an example of the postulated Nature’s Shortcut to the prion protein collapse into the native structure. The possible role of the less populated molten globule-like intermediate is explored as the potential initiation point for the folding for three pathogenic mutants (T182A, I214V, and Q211P in mouse prion numbering) of the prion protein.
Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation
Authors: Hu Xiangqun , Zhang Lubo
Published: August 2021

Uteroplacental blood flow increases as pregnancy advances. Adequate supply of nutrients and oxygen carried by uteroplacental blood flow is essential for the well-being of the mother and growth/development of the fetus. The uteroplacental hemodynamic change is accomplished primarily through uterine vascular adaptation, involving hormonal regulation of myogenic tone, vasoreactivity, release of vasoactive factors and others, in addition to the remodeling of spiral arteries. In preeclampsia, hormonal and angiogenic imbalance, proinflammatory cytokines and autoantibodies cause dysfunction of both endothelium and vascular smooth muscle cells of the uteroplacental vasculature. Consequently, the vascular dysfunction leads to increased vascular resistance and reduced blood flow in the uteroplacental circulation. In this article, the (mal)adaptation of uteroplacental vascular function in normal pregnancy and preeclampsia and underlying mechanisms are reviewed.
Melatonin as a Potential Adjuvant Treatment for COVID-19 beyond Sleep Disorders
Authors: Wichniak Adam , Kania Aleksander , Siemiński Mariusz , Cubała Wiesław Jerzy
Published: August 2021

Melatonin is registered to treat circadian rhythm sleep–wake disorders and insomnia in patients aged 55 years and over. The essential role of the circadian sleep rhythm in the deterioration of sleep quality during COVID-19 confinement and the lack of an adverse effect of melatonin on respiratory drive indicate that melatonin has the potential to be a recommended treatment for sleep disturbances related to COVID-19. This review article describes the effects of melatonin additional to its sleep-related effects, which make this drug an attractive therapeutic option for treating patients with COVID-19. The preclinical data suggest that melatonin may inhibit COVID-19 progression. It may lower the risk of the entrance of the SARS-CoV-2 virus into cells, reduce uncontrolled hyper-inflammation and the activation of immune cells, limit the damage of tissues and multiorgan failure due to the action of free radicals, and reduce ventilator-induced lung injury and the risk of disability resulting from fibrotic changes within the lungs. Melatonin may also increase the efficacy of COVID-19 vaccination. The high safety profile of melatonin and its potential anti-SARS-CoV-2 effects make this molecule a preferable drug for treating sleep disturbances in COVID-19 patients. However, randomized clinical trials are needed to verify the clinical usefulness of melatonin in the treatment of COVID-19.
Rice OsWRKY50 Mediates ABA-Dependent Seed Germination and Seedling Growth, and ABA-Independent Salt Stress Tolerance
Authors: Huang Shuangzhan , Hu Lanjuan , Zhang Shihan , Zhang Mingxing , Jiang Wenzhu , Wu Tao , Du Xinglin
Published: August 2021

Plant WRKY transcription factors play crucial roles in plant growth and development, as well as plant responses to biotic and abiotic stresses. In this study, we identified and characterized a WRKY transcription factor in rice, OsWRKY50. OsWRKY50 functions as a transcriptional repressor in the nucleus. The transcription of OsWRKY50 was repressed under salt stress conditions, but activated after abscisic acid (ABA) treatment. OsWRKY50-overexpression (OsWRKY50-OX) plants displayed increased tolerance to salt stress compared to wild type and control plants. The expression of OsLEA3, OsRAB21, OsHKT1;5, and OsP5CS1 in OsWRKY50-OX were much higher than wild type and control plants under salt stress. Furthermore, OsWRKY50-OX displayed hyposensitivity to ABA-regulated seed germination and seedling establishment. The protoplast-based transient expression system and yeast hybrid assay demonstrated that OsWRKY50 directly binds to the promoter of OsNCED5, and thus further inhibits its transcription. Taken together, our results demonstrate that rice transcription repressor OsWRKY50 mediates ABA-dependent seed germination and seedling growth and enhances salt stress tolerance via an ABA-independent pathway.
The Oxoglutarate Binding Site and Regulatory Mechanism Are Conserved in Ammonium Transporter Inhibitors GlnKs from Methanococcales
Authors: Müller Marie-Caroline , Wagner Tristan
Published: August 2021

Protein inhibition is a natural regulatory process to control cellular metabolic fluxes. PII-family signal-transducing effectors are in this matter key regulators of the nitrogen metabolism. Their interaction with their various targets is governed by the cellular nitrogen level and the energy charge. Structural studies on GlnK, a PII-family inhibitor of the ammonium transporters (Amt), showed that the T-loops responsible for channel obstruction are displaced upon the binding of 2-oxoglutarate, magnesium and ATP in a conserved cleft. However, GlnK from Methanocaldococcus jannaschii was shown to bind 2-oxoglutarate on the tip of its T-loop, causing a moderate disruption to GlnK–Amt interaction, raising the question if methanogenic archaea use a singular adaptive strategy. Here we show that membrane fractions of Methanothermococcus thermolithotrophicus released GlnKs only in the presence of Mg-ATP and 2-oxoglutarate. This observation led us to structurally characterize the two GlnK isoforms apo or in complex with ligands. Together, our results show that the 2-oxoglutarate binding interface is conserved in GlnKs from Methanococcales, including Methanocaldococcus jannaschii, emphasizing the importance of a free carboxy-terminal group to facilitate ligand binding and to provoke the shift of the T-loop positions.
Epidermal PPARγ Is a Key Homeostatic Regulator of Cutaneous Inflammation and Barrier Function in Mouse Skin
Authors: Konger Raymond L. , Derr-Yellin Ethel , Zimmers Teresa A. , Katona Terrence , Xuei Xiaoling , Liu Yunlong , Zhou Hong-Ming , Simpson Ed Ronald , Turner Matthew J.
Published: August 2021

Both agonist studies and loss-of-function models indicate that PPARγ plays an important role in cutaneous biology. Since PPARγ has a high level of basal activity, we hypothesized that epidermal PPARγ would regulate normal homeostatic processes within the epidermis. In this current study, we performed mRNA sequencing and differential expression analysis of epidermal scrapings from knockout mice and wildtype littermates. Pparg-/-epi mice exhibited a 1.5-fold or greater change in the expression of 11.8% of 14,482 identified transcripts. Up-regulated transcripts included those for a large number of cytokines/chemokines and their receptors, as well as genes associated with inflammasome activation and keratinization. Several of the most dramatically up-regulated pro-inflammatory genes in Pparg-/-epi mouse skin included Igfl3, 2610528A11Rik, and Il1f6. RT-PCR was performed from RNA obtained from non-lesional full-thickness skin and verified a marked increase in these transcripts, as well as transcripts for Igflr1, which encodes the receptor for Igfl3, and the 2610528A11Rik receptor (Gpr15). Transcripts for Il4 were detected in Pparg-/-epi mouse skin, but transcripts for Il17 and Il22 were not detected. Down-regulated transcripts included sebaceous gland markers and a number of genes associated with lipid barrier formation. The change in these transcripts correlates with an asebia phenotype, increased transepidermal water loss, alopecia, dandruff, and the appearance of spontaneous inflammatory skin lesions. Histologically, non-lesional skin showed hyperkeratosis, while inflammatory lesions were characterized by dermal inflammation and epidermal acanthosis, spongiosis, and parakeratosis. In conclusion, loss of epidermal Pparg alters a substantial set of genes that are associated with cutaneous inflammation, keratinization, and sebaceous gland function. The data indicate that epidermal PPARγ plays an important role in homeostatic epidermal function, particularly epidermal differentiation, barrier function, sebaceous gland development and function, and inflammatory signaling.
Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns
Authors: Frederick Rosanne E. , Bearden Robert , Jovanovic Aleksa , Jacobson Nasreen , Sood Rajiv , Dhall Sandeep
Published: August 2021

Clostridium collagenase has provided superior clinical results in achieving digestion of immediate and accumulating devitalized collagen tissue. Recent studies suggest that debridement via Clostridium collagenase modulates a cellular response to foster an anti-inflammatory microenvironment milieu, allowing for a more coordinated healing response. In an effort to better understand its role in burn wounds, we evaluated Clostridium collagenase’s ability to effectively minimize burn progression using the classic burn comb model in pigs. Following burn injury, wounds were treated with Clostridium collagenase or control vehicle daily and biopsied at various time points. Biopsies were evaluated for factors associated with progressing necrosis as well as inflammatory response associated with treatment. Data presented herein showed that Clostridium collagenase treatment prevented destruction of dermal collagen. Additionally, treatment with collagenase reduced necrosis (HMGB1) and apoptosis (CC3a) early in burn injuries, allowing for increased infiltration of cells and protecting tissue from conversion. Furthermore, early epidermal separation and epidermal loss with a clearly defined basement membrane was observed in the treated wounds. We also show that collagenase treatment provided an early and improved inflammatory response followed by faster resolution in neutrophils. In assessing the inflammatory response, collagenase-treated wounds exhibited significantly greater neutrophil influx at day 1, with macrophage recruitment throughout days 2 and 4. In further evaluation, macrophage polarization to MHC II and vascular network maintenance were significantly increased in collagenase-treated wounds, indicative of a pro-resolving macrophage environment. Taken together, these data validate the impact of clostridial collagenases in the pathophysiology of burn wounds and that they complement patient outcomes in the clinical scenario.
Glycosphingolipids with Very Long-Chain Fatty Acids Accumulate in Fibroblasts from Adrenoleukodystrophy Patients
Authors: Fujiwara Yuko , Hama Kotaro , Shimozawa Nobuyuki , Yokoyama Kazuaki
Published: August 2021

Adrenoleukodystrophy (X-ALD) is an X-linked genetic disorder caused by mutation of the ATP-binding cassette subfamily D member 1 gene, which encodes the peroxisomal membrane protein, adrenoleukodystrophy protein (ALDP). ALDP is associated with the transport of very-long-chain fatty acids (VLCFAs; carbon chain length ≥ 24) into peroxisomes. Defective ALDP leads to the accumulation of saturated VLCFAs in plasma and tissues, which results in damage to myelin and the adrenal glands. Here, we profiled the glycosphingolipid (GSL) species in fibroblasts from X-ALD patients. Quantitative analysis was performed using liquid chromatography–electrospray ionization–tandem mass spectrometry with a chiral column in multiple reaction monitoring (MRM) mode. MRM transitions were designed to scan for precursor ions of long-chain bases to detect GSLs, neutral loss of hexose to detect hexosylceramide (HexCer), and precursor ions of phosphorylcholine to detect sphingomyelin (SM). Our results reveal that levels of C25 and C26-containing HexCer, Hex2Cer, NeuAc-Hex2Cer, NeuAc-HexNAc-Hex2Cer, Hex3Cer, HexNAc-Hex3Cer, and SM were elevated in fibroblasts from X-ALD patients. In conclusion, we precisely quantified SM and various GSLs in fibroblasts from X-ALD patients and determined structural information of the elevated VLCFA-containing GSLs.
Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells
Authors: Fejes Zsolt , Pócsi Marianna , Takai Jun , Erdei Judit , Tóth Andrea , Balogh Enikő , Rusznyák Ágnes , Fenyvesi Ferenc , Nagy Andrea , Kappelmayer János , Jeney Viktória , Nagy Béla
Published: August 2021

Following an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF) samples obtained from Grade-III and Grade-IV preterm IVH infants (IVH-III and IVH-IV, respectively) at multiple time points between days 0–60 after the onset of IVH. Furthermore, human choroid plexus epithelial cells (HCPEpiCs) were incubated with IVH and non-IVH CSF (10 v/v %) for 24 h in vitro to investigate the IVH-induced inflammatory response that was investigated via: (i) HMOX1, IL8, VCAM1, and ICAM1 mRNAs as well as miR-155, miR-223, and miR-181b levels by RT-qPCR; (ii) nuclear translocation of the NF-κB p65 subunit by fluorescence microscopy; and (iii) reactive oxygen species (ROS) measurement. We found a time-dependent alteration of heme, IL-8, and adhesion molecules which revealed a prolonged elevation in IVH-IV vs. IVH-III with higher miR-155 and miR-181b expression at days 41–60. Exposure of HCPEpiCs to IVH CSF samples induced HMOX1, IL8, and ICAM1 mRNA levels along with increased ROS production via the NF-κB pathway activation but without cell death, as confirmed by the cell viability assay. Additionally, the enhanced intracellular miR-155 level was accompanied by lower miR-223 and miR-181b expression in HCPEpiCs after CSF treatment. Overall, choroid plexus epithelial cells exhibit an abnormal cell phenotype after interaction with pro-inflammatory CSF of IVH origin which may contribute to the development of later clinical complications in preterm IVH.
Identification and Characterization of the Masculinizing Function of the Helicoverpa armigera Masc Gene
Authors: Deng Zhongyuan , Zhang Yakun , Li Yalu , Huang Kaiyuan , Chen Xuewei , Zhang Min , Huang Jinyong , Ni Xinzhi , Li Xianchun
Published: August 2021

The Masculinizer (Masc) gene has been known to control sex development and dosage compensation in lepidopterans. However, it remains unclear whether its ortholog exists and plays the same roles in distantly related lepidopterans such as Helicoverpa armigera. To address this question, we cloned Masc from H. armigera (HaMasc), which contains all essential functional domains of BmMasc, albeit with less than 30% amino acid sequence identity with BmMasc. Genomic PCR and qPCR analyses showed that HaMasc is a Z chromosome-linked gene since its genomic content in males (ZZ) was two times greater than that in females (ZW). RT-PCR and RT-qPCR analyses revealed that HaMasc expression was sex- and stage-biased, with significantly more transcripts in males and eggs than in females and other stages. Transfection of a mixture of three siRNAs of HaMasc into a male embryonic cell line of H. armigera led to the appearance of female-specific mRNA splicing isoforms of H. armigeradoublesex (Hadsx), a downstream target gene of HaMasc in the H. armigera sex determination pathway. The knockdown of HaMasc, starting from the third instar larvae resulted in a shift of Hadsx splicing from male to female isoforms, smaller male pupa and testes, fewer but larger/longer spermatocytes and sperm bundles, delayed pupation and internal fusion of the testes and follicles. These data demonstrate that HaMasc functions as a masculinizing gene in the H. armigera sex-determination cascade.
Newborn Screening for 5q Spinal Muscular Atrophy: Comparisons between Real-Time PCR Methodologies and Cost Estimations for Future Implementation Programs
Authors: Romanelli Tavares Vanessa Luiza , Monfardini Frederico , Lourenço Naila Cristina Vilaça , da Rocha Katia Maria , Weinmann Karina , Pavanello Rita , Zatz Mayana
Published: August 2021

Since the approval of modifying therapies for Spinal Muscular Atrophy (SMA), several protocols aiming to screen SMN1 homozygous deletion in a neonatal context have been published. However, no work has compared different methodologies along with detailed implementation costs for centers where the neonatal screening of SMA has not yet been implemented. Therefore, our work compared different qualitative real-time PCR approaches for SMA screening and the estimated costs of test implementation. Using Brazilian blood samples, the presence and absence (P/A) and melt curve protocols were analyzed. MLPA was used as a confirmatory test. The costs were calculated for the simplex and multiplex tests plus equipment. The test workflow was based on the present experience and literature report. The accuracy of the P/A protocol was 1 (95% CI 0.8677−1) using dried blood spots (DBS). The melt curve protocol also achieved 100% concordance. The consumable costs ranged from USD 1.68 to 4.42 and from USD 2.04 to 12.76 per reaction, for the simplex and multiplex tests, respectively. The equipment acquisition costs ranged from USD 44,817.07 to 467,253.10, with several factors influencing this value presented. Our work presents a framework for decision-making, with a project demonstration of the different assays that will be useful in dealing with the issues of cost and availability of reagents. Moreover, we present a literature review and discussion of important concerns regarding treatment policies. We take the first step towards a future SMA NBS pilot program where it is not yet a reality.
Personality Traits Affecting Opinion Leadership Propensity in Social Media: An Empirical Examination in Saudi Arabia
Authors: Dukhaykh Suad
Published: August 2021

Few studies have examined the personality traits that may predict opinion leadership behavior in social media. This study aims to examine the personality traits of individuals who use social media platforms and engage in social networking in Saudi Arabia. This study investigates the extent to which innovativeness, competence in interpersonal relationships, and extraversion affect the opinion leadership propensity in social media. The data were collected via an online structured questionnaire which was completed by a sample of 321 social media users. The results of this study show that people with a high level of innovativeness and interpersonal relationship competency are more likely to be opinion leaders on social media. However, the personality trait of extraversion does not affect the propensity to be an opinion leader. The results indicate that the effect of innovativeness on opinion leadership propensity is lower for Generation Y than Generation X.
Study of Morphological Features in Pre-Imaginal Honey Bee Impaired by Varroa destructor by Means of Computer Tomography
Authors: Sipos Tamás , Donkó Tamás , Jócsák Ildikó , Keszthelyi Sándor
Published: August 2021

The honey bee (Apis mellifera L. 1778) is an essential element in maintaining the diversity of the biosphere and food production. One of its most important parasites is Varroa destructor, Anderson and Trueman, 2000, which plays a role in the vectoring of deformed wing virus (DWV) in honey bee colonies. Our aim was to measure the potential morphometric changes in the pre-imaginal stage of A. mellifera caused by varroosis by means of computed tomography, hence supplying evidence for the presumable role that V. destructor plays as a virus vector. Based on our results, the developmental disorders in honey bees that ensued during the pre-imaginal stages were evident. The total-body length and abdomen length of parasitized specimens were shorter than those of their intact companions. In addition, the calculated quotients of the total-body/abdomen, head/thorax, and head/abdomen in parasitized samples were significantly altered upon infestation. In our view, these phenotypical disorders can also be traced to viral infection mediated by parasitism, which was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Capitalizing on a non-destructive method, our study reveals the deformation of the honey bee due to mite parasitism and the intermediary role this pest plays in viral infection, inside the brood cell.
Risk Factors Associated with 30-Day Mortality in Older Patients with Influenza
Authors: Guesneau Charles , Boureau Anne Sophie , Bourigault Céline , Berrut Gilles , Lepelletier Didier , de Decker Laure , Chapelet Guillaume
Published: August 2021

Background: Influenza is a common viral condition, but factors related to short-term mortality have not been fully studied in older adults. Our objective was to determine whether there is an association between geriatric factors and 30-day mortality. Methods: This was a retrospective cohort design. All patients aged 75 years and over, with a diagnosis of influenza confirmed by a positive RT-PCR, were included. The primary endpoint was death within the 30 days after diagnosis. Results: 114 patients were included; 14 (12.3%) patients died within 30 days. In multivariate analysis these patients were older (OR: 1.37 95% CI (1.05, 1.79), p = 0.021), and had a lower ADL score (OR: 0.36 95% CI (0, 17; 0.75), p = 0.006), and a higher SOFA score (OR: 2.30 95% CI (1.07, 4.94), p = 0.03). Oseltamivir treatment, initiated within the first 48 h, was independently associated with survival (OR: 0.04 95% CI (0.002, 0.78), p = 0.034). Conclusions: Identification of mortality risk factors makes it possible to consider specific secondary prevention measures such as the rapid introduction of antiviral treatment. Combined with primary prevention, these measures could help to limit the mortality associated with influenza in older patients.
A Generalized and Modular Framework for Digital Generation of Composite Microstructures
Authors: Cecen Ahmet , Yucel Berkay , Kalidindi Surya R.
Published: August 2021

This paper presents a generalized framework for the digital generation of composite microstructures using filter-based approaches that can devise and utilize a wide variety of cost functions reflecting the desired targets on geometrical and statistical measures. The use of filter-based approaches leads to remarkable computational advantages compared to the conventional approaches used currently for microstructure generation. The framework provides a highly modular and flexible approach to generate stochastic ensembles of microstructures meeting user-defined microstructural characteristics. The proposed framework is illustrated in this paper through selected case studies.