bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Online Bodyweight High-Intensity Interval Training Intervention and Health Education on the Mental Health and Cognition of Sedentary Young Females
Authors: Zhang Yao , Zhang Beier , Gan Liaoyan , Ke Limei , Fu Yingyao , Di Qian , Ma Xindong
Published: January 2021

This study aimed to assess the effectiveness of an online high-intensity interval training (HIIT) intervention and health education on the behaviors, mental health, and cognitive function of sedentary young females. A single-blinded, six-week, randomized controlled pilot trial involving 70 sedentary young Chinese females, aged 18–30 years, was conducted. An intervention group (IG) (n = 33) underwent a HIIT intervention and health education, while a waitlist group (WG) (n = 37) only received health education. In pre-, mid-, and post-tests, both groups filled out questionnaires about physical activity, sedentary behavior, and mental health. Cognitive functions were assessed at the pre- and post-tests by computer-administered cognitive tests. A mixed-effect model with repeated measures was used to analyze outcomes of interest. The retention rate of the IG and WG was 100% and 78.38%, respectively. The IG were found to have significantly increased rates of moderate-to-vigorous physical activity (MVPA) (Mdiff = 940.61, p < 0.001, 95% confidence interval (95% CI): 576.67, 1304.55) from pre-test to post-test, while the WG demonstrated a more marked reduction in sedentary time (Mdiff = −73.02, p = 0.038, 95% CI: −141.90, −4.14) compared with the IG in the post-test. Moreover, anxiety and stress levels were shown to significantly reduce in the IG over the six-week period (Mdiff = −4.73, p = 0.002, 95% CI: −7.30, −2.15 and Mdiff = −5.09, p = 0.001, 95% CI: −8.29, −1.89, respectively). In addition, we observed a significant improvement in verbal ability (p = 0.008, ηp2 = 0.19) following the HIIT intervention and effects of the interaction with time on processing speed (p = 0.050, ηp2 = 0.10) and episodic memory (p = 0.048, ηp2 = 0.11). Moreover, the IG had better global cognitive performance than the WG in the post-test (Mdiff = 8.28, p = 0.003, 95% CI: 3.06, 13.50). In summary, both an online bodyweight HIIT intervention combined with health education, or health education alone, can effectively improve health-related behaviors, but the behavioral consequences may differ based on the emphasis of different intervention modalities. Furthermore, the “bodyweight HIIT plus health education” modality might be a more promising online intervention strategy to mitigate against negative emotions and improve cognitive function.
Regular Exercise and Depressive Symptoms in Korean Older Adults
Authors: Kim Young-Mee , Cho Sung-il
Published: January 2021

Prior studies have found that exercise has a positive effect on depressive symptoms in the general population. For older individuals, however, the association between exercise and depressive symptoms is conclusive. We examined whether regular exercise is related to depressive symptoms in 5379 Korean adults aged ≥55 years using data from a 2016 survey administered in the Korean Longitudinal Study of Aging. We used the 10-item Center for Epidemiological Studies–Depression scale to assess depressive symptoms. We performed a multivariate logistic regression analysis to investigate the relationship between regular exercise and depressive symptoms, adjusting for sociodemographic characteristics, self-rated health, number of chronic diseases, body mass index, hand-grip strength, physical disability, cognitive impairment, and health behavior. Interaction terms, including regular exercise and health-related factors, were also added. We found that a lack of regular exercise was significantly related to an increased frequency of depressive symptoms (OR = 1.18, 95% CI = 1.03–1.35). Moreover, hand-grip strength may increase the effect of regular exercise on depressive symptoms in individuals 65 years and older (OR = 1.01 vs. 1.70, 95% CI = 1.05–1.96). Our results suggest that it is important to encourage older individuals to exercise regularly as a means of relieving depressive symptoms.
Prevalence and Risk Factors of Latent Tuberculosis Infection (LTBI) in Patients with Type 2 Diabetes Mellitus (T2DM)
Authors: Ping Phan Ai , Zakaria Rosnani , Islam Md Asiful , Yaacob Lili Husniati , Muhamad Rosediani , Wan Mohamad Wan Mohamad Zahiruddin , Yusoff Harmy Mohamed
Published: January 2021

Type 2 diabetes mellitus (T2DM) and tuberculosis (TB) together impose a high disease burden in terms of both mortality and health economics worldwide. The objective of this study was to estimate the prevalence and risk factors of latent TB infection (LTBI) in patients with T2DM in Malaysia. A cross-sectional study was performed, and adult T2DM patients (n = 299) were included. Simple and multiple logistic regression analyses were performed to identify the LTBI-associated risk factors in patients with T2DM. Multiple logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) between T2DM and LTBI and was adjusted for potential confounders. The prevalence of LTBI in patients with T2DM was 11.4% (95% CI: 8.0–15.0%). There was no significant difference in the socio-demographic characteristics between LTBI and non-LTBI subjects. No significant difference in the smoking status, the duration of smoking, and the duration of T2DM, HbA1c, or treatments was observed. Interestingly, a higher level of education was observed to be associated with a lower prevalence of LTBI in T2DM patients (aOR: 0.08, 95% CI: 0.01–0.70, p = 0.02). Although the prevalence of LTBI in T2DM was low, it is important to screen for it in T2DM patients due to the risk of developing severe active TB.
The Related Risk Factors of Diabetic Retinopathy in Elderly Patients with Type 2 Diabetes Mellitus: A Hospital-Based Cohort Study in Taiwan
Authors: Chiu Tsai-Tung , Tsai Tien-Lung , Su Mei-Yin , Yang Tsan , Tseng Peng-Lin , Lee Yau-Jiunn , Lee Chao-Hsien
Published: January 2021

Diabetic retinopathy (DR), caused by small vessel disease, is the main cause of blindness in persons with diabetes. Taiwan is one of the Asian countries with the highest prevalence rate of DR. The purpose was to investigate the related risk factors of DR in elderly patients with type 2 diabetes mellitus (T2DM), in Lee’s Endocrinology Clinic. 792 T2DM patients over 60 years old were invited to have an outpatient visit at least every three months, and all of them were asked to undergo a standardized interview and collect their blood samples. Significant factors were being female (adjusted hazard ratio (HR): 1.287; 95% CI, 1.082–1.531), higher glycated hemoglobin (HbA1c) (HR: 1.067; 95% CI: 1.016–1.119), higher mean low density of lipoprotein cholesterol (LDL-c) (HR: 1.004; 95% CI: 1.001–1.006), and chewing betel nut (HR: 1.788; 95% CI: 1.362–2.347). This study showed that gender, the behavior of chewing betel nut, HbA1c, and LDL-c are important factors for the development of DR in elderly patients with T2DM. It is suggested that patients should control their HbA1c and LDL-c and quit chewing betel nut to prevent DR. This suggestion applies especially to female patients.
Health Perceptions in Relation to Child Health and Mortality in a Rural Context, Sierra Leone: A Mixed Method Study
Authors: Midtgaard Eriksen Camilla , Lauridsen Kujabi Monica , Sulaiman Kanu Aminata , Gulis Gabriel
Published: January 2021

Child survival and wellbeing remain a global health challenge despite vast development within the area and a significant decline in mortality rates of children under five years of age. This study investigates the perceived causes of ill health and childhood mortality in the context of five villages located in the Tonkolili district of Sierra Leone. Mixed method methodology was applied in this study consisting of both quantitative and qualitative data contribution. The quantitative part consisted of a household survey on child health, where 341 households, equivalent to 50.6% of the total number of households in the five villages, participated with a response rate of 100%. The qualitative part consisted of six semi structured interviews—one with a health care worker and five with mothers from each village. The main perceived reason for child morbidity was inadequate care of children related to personal hygiene of the child, hygiene and safety in the environment, in-sufficient nutrition, inadequate supervision and poor healthcare seeking behavior. Additionally, reasons given for disease included supernatural forces such as witchcraft. In relation to the survey, the perceived causes of child mortality for ill children in the villages were mainly malaria (33.6%), diarrhea (11.6%), pneumonia (8.6%), and unknown (26%). The observed symptoms of illness among children were fever (43.7%), cough and difficulty breathing (10.7%), frequent watery stool (10.3%) and no symptoms (20.3%). The perception of ill health in children was mainly associated with the parent’s ability to cater for the child’s physical needs, but also associated with external factors such as witchcraft and “God’s will”. In addition, biomedical causes for disease and supernatural causes for disease were seen to coexist.
School Violence towards Peers and Teen Dating Violence: The Mediating Role of Personal Distress
Authors: Valdivia-Salas Sonsoles , Jiménez Teresa I. , Lombas Andrés S. , López-Crespo Ginesa
Published: January 2021

School violence towards peers and teen dating violence are two of the most relevant behaviour problems in adolescents. Although the relationship between the two types of violence is well established in the literature, few studies have focused on mediators that could explain this empirical relationship. We departed from the evidence that relates anger, emotional distress and impaired empathy to teen dating violence and juvenile sexual offending, to explore the role of personal distress, i.e., a self-focused, aversive affective reaction to another’s emotion associated with the desire to alleviate one’s own, but not the other’s distress; as a possible mechanism linking school violence towards peers and teen dating violence in a sample of Spanish adolescents. We also explored the prevalence of emotional and physical teen dating violence, both occasional and frequent, and the differences between boys and girls. A total of 1055 adolescents (49.2% boys and 50.8% girls) aged between 11 and 17 years (M = 14.06, SD = 1.34) who had had at least one romantic relationship within the last year, completed measures of school violence towards peers, teen dating violence, and personal distress. Statistical analyses revealed that occasional and frequent teen dating violence (both physical and emotional) was more frequent in girls than in boys, and that personal distress functioned as a partial mediator, with an overall model fit higher for boys than girls: in boys, partial mediation occurred for both physical and emotional teen dating violence; in girls, partial mediation occurred only for physical violence. The interpretation of the results is tentative given the novel nature of the study, and points to the evidence of the emotional costs of school violence and the importance of emotion and behavior regulation to undermine the social costs of personal distress.
Assessing the Impact of Street-View Greenery on Fear of Neighborhood Crime in Guangzhou, China
Authors: Jing Fengrui , Liu Lin , Zhou Suhong , Song Jiangyu , Wang Linsen , Zhou Hanlin , Wang Yiwen , Ma Ruofei
Published: January 2021

Previous literature has examined the relationship between the amount of green space and perceived safety in urban areas, but little is known about the effect of street-view neighborhood greenery on perceived neighborhood safety. Using a deep learning approach, we derived greenery from a massive set of street view images in central Guangzhou. We further tested the relationships and mechanisms between street-view greenery and fear of crime in the neighborhood. Results demonstrated that a higher level of neighborhood street-view greenery was associated with a lower fear of crime, and its relationship was mediated by perceived physical incivilities. While increasing street greenery of the micro-environment may reduce fear of crime, this paper also suggests that social factors should be considered when designing ameliorative programs.
The Relationship between Dynamic Balance and Jumping Tests among Adolescent Amateur Rugby Players. A Preliminary Study
Authors: Wilczyński Bartosz , Hinca Jakub , Ślęzak Daniel , Zorena Katarzyna
Published: January 2021

Rugby is a demanding contact sport. In light of research, poor balance, reduced jumping ability, muscle strength, and incorrect landing patterns might contribute to the increased risk of injury in athletes. Investigating the relationship between tests assessing these abilities might not only allow for the skillful programming of preventive training but also helps in assessing the risk of injury to athletes. Thus, the main purpose of this study was to investigate the relationship between dynamic balance, vertical and horizontal jumps, and jump-landings movement patterns. Thirty-one healthy amateur adolescent rugby players (age: 14.3 ± 1.6 years, height 171.4 ± 9.7 cm, body mass 80 ± 26 kg) participated in the study. Data were collected by the Y-balance Test (YBT), Counter Movement Jump (CMJ), Single Leg Hop for Distance (SLHD), and Landing Error Score System (LESS). Significant positive correlations were found between SLHD both legs (SLHDb) and YBT Composite both legs (COMb) (r = 0.51, p = 0.0037) and between SLHDb and CMJ (r = 0.72, p < 0.0001). A relationship was also observed between the CMJ and YBT COMb test (r = 0.51, p = 0.006). Moderate positive correlations were found between the dominant legs in SLHD and the posterolateral (r = 0.40, p = 0.027), posteromedial (r = 0.43, p = 0.014), and composite (r = 0.48, p = 0.006) directions of the YBT. These results indicate that variables that are dependent on each other can support in the assessment of injury-risk and in enhancing sports performance of young athletes.
The Effects of Government Bonds on Liquidity Risk and Bank Profitability in Cape Verde
Authors: Teixeira José Carlos , Vieira Carlos , Ferreira Paulo
Published: January 2021

To analyze the effects of government debt securities on the liquidity risk and profitability of banks in Cape Verde, this research employs an unbalanced panel dataset from 2000 to 2017 on the activity of all commercial banks operating at the end of 2017 (seven in total). The study employs models with lagged regressors, estimated by the ordinary least squares estimation method. The results show that government debt securities have no effect on bank liquidity risks, but they have an effect on bank profitability, with government debt securities having a positive impact on assets’ profitability, in the long run. When government debt securities include Consolidated Securities of Financial Mobilization, the effects on profitability are negative both in the short and the long run. The study concludes that banks’ strategy to hold the more conventional government debt securities as safe assets and risk-free alternative for the domestic application of liquidity surpluses is appropriate and a viable way to gain profitability in the long run. These results show the negative effect of government debt securities when the Consolidated Securities of Financial Mobilization are included, which helps to explain the low average profitability rates of Cape Verde’s banks, when compared to other similar sub-Saharan African countries, like Mauritius or Seychelles.
Epigenetics of Aging and Aging-Associated Diseases
Authors: Saul Dominik , Kosinsky Robyn Laura
Published: January 2021

Aging represents the multifactorial decline in physiological function of every living organism. Over the past decades, several hallmarks of aging have been defined, including epigenetic deregulation. Indeed, multiple epigenetic events were found altered across different species during aging. Epigenetic changes directly contributing to aging and aging-related diseases include the accumulation of histone variants, changes in chromatin accessibility, loss of histones and heterochromatin, aberrant histone modifications, and deregulated expression/activity of miRNAs. As a consequence, cellular processes are affected, which results in the development or progression of several human pathologies, including cancer, diabetes, osteoporosis, and neurodegenerative disorders. In this review, we focus on epigenetic mechanisms underlying aging-related processes in various species and describe how these deregulations contribute to human diseases.
Localization and Dynamics of the Methionine Sulfoxide Reductases MsrB1 and MsrB2 in Beech Seeds
Authors: Wojciechowska Natalia , Bagniewska-Zadworna Agnieszka , Minicka Julia , Michalak Kornel M. , Kalemba Ewa M.
Published: January 2021

Beech seeds are produced irregularly, and there is a need for long-term storage of these seeds for forest management practices. Accumulated reactive oxygen species broadly oxidize molecules, including amino acids, such as methionine, thereby contributing to decreased seed viability. Methionine oxidation can be reversed by the activity of methionine sulfoxide reductases (Msrs), which are enzymes involved in the regulation of many developmental processes and stress responses. Two types of Msrs, MsrB1 and MsrB2, were investigated in beech seeds to determine their abundance and localization. MsrB1 and MsrB2 were detected in the cortical cells and the outer area of the vascular cylinder of the embryonic axes as well as in the epidermis and parenchyma cells of cotyledons. The abundances of MsrB1 and MsrB2 decreased during long-term storage. Ultrastructural analyses have demonstrated the accumulation of these proteins in protein storage vacuoles and in the cytoplasm, especially in close proximity to the cell membrane. In silico predictions of possible Msr interactions supported our findings. In this study, we investigate the contribution of MsrB1 and MsrB2 locations in the regulation of seed viability and suggest that MsrB2 is linked with the longevity of beech seeds via association with proper utilization of storage material.
Risperidone Exacerbates Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Renal Impairment in Obese Mice
Authors: Tsai Hsiao-Pei , Hou Po-Hsun , Mao Frank-Chiahung , Chang Chia-Chia , Yang Wei-Cheng , Wu Ching-Feng , Liao Huei-Jyuan , Lin Tzu-Chun , Chou Lan-Szu , Hsiao Li-Wei , Chang Geng-Ruei
Published: January 2021

Risperidone, a second-generation antipsychotic drug used for schizophrenia treatment with less-severe side effects, has recently been applied in major depressive disorder treatment. The mechanism underlying risperidone-associated metabolic disturbances and liver and renal adverse effects warrants further exploration. This research explores how risperidone influences weight, glucose homeostasis, fatty liver scores, liver damage, and renal impairment in high-fat diet (HFD)-administered C57BL6/J mice. Compared with HFD control mice, risperidone-treated obese mice exhibited increases in body, liver, kidney, and retroperitoneal and epididymal fat pad weights, daily food efficiency, serum triglyceride, blood urea nitrogen, creatinine, hepatic triglyceride, and aspartate aminotransferase, and alanine aminotransferase levels, and hepatic fatty acid regulation marker expression. They also exhibited increased insulin resistance and glucose intolerance but decreased serum insulin levels, Akt phosphorylation, and glucose transporter 4 expression. Moreover, their fatty liver score and liver damage demonstrated considerable increases, corresponding to increases in sterol regulatory element-binding protein 1 mRNA, fatty acid-binding protein 4 mRNA, and patatin-like phospholipid domain containing protein 3 expression. Finally, these mice demonstrated renal impairment, associated with decreases in glutathione peroxidase, superoxide dismutase, and catalase levels. In conclusion, long-term administration of risperidone may exacerbate diabetes syndrome, nonalcoholic fatty liver disease, and kidney injury.
Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome
Authors: Ha Byung Geun , Heo Jung-Yoon , Jang Yu-Jin , Park Tae-Shin , Choi Ju-Yeon , Jang Woo Young , Jeong Sung-Jin
Published: January 2021

Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).
Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis
Authors: Nedoszytko Boguslaw , Arock Michel , Lyons Jonathan , Bachelot Guillaume , Schwartz Lawrence , Reiter Andreas , Jawhar Mohamad , Schwaab Juliana , Lange Magdalena , Greiner Georg , Hoermann Gregor , Niedoszytko Marek , Metcalfe Dean , Valent Peter
Published: January 2021

Mastocytosis is a rare and complex disease characterized by expansion of clonal mast cells (MC) in skin and/or various internal organ systems. Involvement of internal organs leads to the diagnosis of systemic mastocytosis (SM). The WHO classification divides SM into indolent SM, smoldering SM and advanced SM variants, including SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia. Historically, genetic analysis of individuals with pure cutaneous mastocytosis (CM) and SM have focused primarily on cohort studies of inherited single nucleotide variants and acquired pathogenic variants. The most prevalent pathogenic variant (mutation) in patients with SM is KIT p.D816V, which is detectable in most adult patients. Other somatic mutations have also been identified—especially in advanced SM—in TET2, SRSF2, ASXL1, RUNX1, CBL and JAK2, and shown to impact clinical and cellular phenotypes. Although only small patient cohorts have been analyzed, disease associations have also been identified in several germline variants within genes encoding certain cytokines or their receptors (IL13, IL6, IL6R, IL31, IL4R) and toll-like receptors. More recently, an increased prevalence of hereditary alpha-tryptasemia (HαT) caused by increased TPSAB1 copy number encoding alpha-tryptase has been described in patients with SM. Whereas HαT is found in 3–6% of general Western populations, it is identified in up to 17% of patients with SM. In the current manuscript we review the prevalence, functional role and clinical impact of various germline and somatic genetic variants in patients with mastocytosis.
TUNEL Assay: A Powerful Tool for Kidney Injury Evaluation
Authors: Moore Christopher L. , Savenka Alena V. , Basnakian Alexei G.
Published: January 2021

Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay is a long-established assay used to detect cell death-associated DNA fragmentation (3’-OH DNA termini) by endonucleases. Because these enzymes are particularly active in the kidney, TUNEL is widely used to identify and quantify DNA fragmentation and cell death in cultured kidney cells and animal and human kidneys resulting from toxic or hypoxic injury. The early characterization of TUNEL as an apoptotic assay has led to numerous misinterpretations of the mechanisms of kidney cell injury. Nevertheless, TUNEL is becoming increasingly popular for kidney injury assessment because it can be used universally in cultured and tissue cells and for all mechanisms of cell death. Furthermore, it is sensitive, accurate, quantitative, easily linked to particular cells or tissue compartments, and can be combined with immunohistochemistry to allow reliable identification of cell types or likely mechanisms of cell death. Traditionally, TUNEL analysis has been limited to the presence or absence of a TUNEL signal. However, additional information on the mechanism of cell death can be obtained from the analysis of TUNEL patterns.
GH/IGF-1 Abnormalities and Muscle Impairment: From Basic Research to Clinical Practice
Authors: Biagetti Betina , Simó Rafael
Published: January 2021

The impairment of skeletal muscle function is one of the most debilitating least understood co-morbidity that accompanies acromegaly (ACRO). Despite being one of the major determinants of these patients’ poor quality of life, there is limited evidence related to the underlying mechanisms and treatment options. Although growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels are associated, albeit not indisputable, with the presence and severity of ACRO myopathies the precise effects attributed to increased GH or IGF-1 levels are still unclear. Yet, cell lines and animal models can help us bridge these gaps. This review aims to describe the evidence regarding the role of GH and IGF-1 in muscle anabolism, from the basic to the clinical setting with special emphasis on ACRO. We also pinpoint future perspectives and research lines that should be considered for improving our knowledge in the field.
Gender Differences in Low-Molecular-Mass-Induced Acute Lung Inflammation in Mice
Authors: Xie Yifang , Xie Dehui , Li Bin , Zhao Hang
Published: January 2021

Gender differences in pulmonary inflammation have been well documented. Although low molecular mass hyaluronan (LMMHA) is known to trigger pulmonary lung inflammation, sex differences in susceptibility to LMMHA are still unknown. In this study, we test the hypothesis that mice may display sex-specific differences after LMMHA administration. After LMMHA administration, male mice have higher neutrophil, cytokine, and chemokine counts compared to that of their female counterparts. Additionally, Ovariectomized (OVX) mice show greater LMMHA-induced inflammation compared to that of mice with intact ovaries. Injections of OVX mice with 17β-estradiol can decrease inflammatory responses in the OVX mice. These results show that ovarian hormones regulate LMMHA induced lung inflammation.
DAP3 Is Involved in Modulation of Cellular Radiation Response by RIG-I-Like Receptor Agonist in Human Lung Adenocarcinoma Cells
Authors: Sato Yoshiaki , Yoshino Hironori , Kashiwakura Ikuo , Tsuruga Eichi
Published: January 2021

Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) mediate anti-viral response through mitochondria. In addition, RLR activation induces anti-tumor effects on various cancers. We previously reported that the RLR agonist Poly(I:C)-HMW/LyoVec™ (Poly(I:C)) enhanced radiosensitivity and that cotreatment with Poly(I:C) and ionizing radiation (IR) more than additively increased cell death in lung adenocarcinoma cells, indicating that Poly(I:C) modulates the cellular radiation response. However, it remains unclear how mitochondria are involved in the modulation of this response. Here, we investigated the involvement of mitochondrial dynamics and mitochondrial ribosome protein death-associated protein 3 (DAP3) in the modulation of cellular radiation response by Poly(I:C) in A549 and H1299 human lung adenocarcinoma cell lines. Western blotting revealed that Poly(I:C) decreased the expression of mitochondrial dynamics-related proteins and DAP3. In addition, siRNA experiments showed that DAP3, and not mitochondrial dynamics, is involved in the resistance of lung adenocarcinoma cells to IR-induced cell death. Finally, we revealed that a more-than-additive effect of cotreatment with Poly(I:C) and IR on increasing cell death was diluted by DAP3-knockdown because of an increase in cell death induced by IR alone. Together, our findings suggest that RLR agonist Poly(I:C) modulates the cellular radiation response of lung adenocarcinoma cells by downregulating DAP3 expression.
Metformin Preserves β-Cell Compensation in Insulin Secretion and Mass Expansion in Prediabetic Nile Rats
Authors: Huang Hui , Lorenz Bradi R. , Zelmanovitz Paula Horn , Chan Catherine B.
Published: January 2021

Prediabetes is a high-risk condition for type 2 diabetes (T2D). Pancreatic β-cells adapt to impaired glucose regulation in prediabetes by increasing insulin secretion and β-cell mass expansion. In people with prediabetes, metformin has been shown to prevent prediabetes conversion to diabetes. However, emerging evidence indicates that metformin has negative effects on β-cell function and survival. Our previous study established the Nile rat (NR) as a model for prediabetes, recapitulating characteristics of human β-cell compensation in function and mass expansion. In this study, we investigated the action of metformin on β-cells in vivo and in vitro. A 7-week metformin treatment improved glucose tolerance by reducing hepatic glucose output and enhancing insulin secretion. Although high-dose metformin inhibited β-cell glucose-stimulated insulin secretion in vitro, stimulation of β-cell insulin secretion was preserved in metformin-treated NRs via an indirect mechanism. Moreover, β-cells in NRs receiving metformin exhibited increased endoplasmic reticulum (ER) chaperones and alleviated apoptotic unfold protein response (UPR) without changes in the expression of cell identity genes. Additionally, metformin did not suppress β-cell mass compensation or proliferation. Taken together, despite the conflicting role indicated by in vitro studies, administration of metformin does not exert a negative effect on β-cell function or cell mass and, instead, early metformin treatment may help protect β-cells from exhaustion and decompensation.
The p24 Complex Contributes to Specify Arf1 for COPI Coat Selection
Authors: Sabido-Bozo Susana , Perez-Linero Ana , Manzano-Lopez Javier , Rodriguez-Gallardo Sofia , Aguilera-Romero Auxiliadora , Cortes-Gomez Alejandro , Lopez Sergio , Wellinger Ralf , Muñiz Manuel
Published: January 2021

Golgi trafficking depends on the small GTPase Arf1 which, upon activation, drives the assembly of different coats onto budding vesicles. Two related types of guanine nucleotide exchange factors (GEFs) activate Arf1 at different Golgi sites. In yeast, Gea1 in the cis-Golgi and Gea2 in the medial-Golgi activate Arf1 to form COPI-­coated vesicles for retrograde cargo sorting, whereas Sec7 generates clathrin/adaptor­-coated vesicles at the trans-Golgi network (TGN) for forward cargo transport. A central question is how the same activated Arf1 protein manages to assemble different coats depending on the donor Golgi compartment. A previous study has postulated that the interaction between Gea1 and COPI would channel Arf1 activation for COPI vesicle budding. Here, we found that the p24 complex, a major COPI vesicle cargo, promotes the binding of Gea1 with COPI by increasing the COPI association to the membrane independently of Arf1 activation. Furthermore, the p24 complex also facilitates the interaction of Arf1 with its COPI effector. Therefore, our study supports a mechanism by which the p24 complex contributes to program Arf1 activation by Gea1 for selective COPI coat assembly at the cis-Golgi compartment.
Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity
Authors: Avram Vlad F. , Chamkha Imen , Åsander-Frostner Eleonor , Ehinger Johannes K. , Timar Romulus Z. , Hansson Magnus J. , Muntean Danina M. , Elmér Eskil
Published: January 2021

Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings.
Switching from Apoptosis to Pyroptosis: Gasdermin-Elicited Inflammation and Antitumor Immunity
Authors: Tsuchiya Kohsuke
Published: January 2021

Pyroptosis is a necrotic form of regulated cell death. Gasdermines (GSDMs) are a family of intracellular proteins that execute pyroptosis. While GSDMs are expressed as inactive forms, certain proteases proteolytically activate them. The N-terminal fragments of GSDMs form pores in the plasma membrane, leading to osmotic cell lysis. Pyroptotic cells release pro-inflammatory molecules into the extracellular milieu, thereby eliciting inflammation and immune responses. Recent studies have significantly advanced our knowledge of the mechanisms and physiological roles of pyroptosis. GSDMs are activated by caspases and granzymes, most of which can also induce apoptosis in different situations, for example where the expression of GSDMs is too low to cause pyroptosis; that is, caspase/granzyme-induced apoptosis can be switched to pyroptosis by the expression of GSDMs. Pyroptosis appears to facilitate the killing of tumor cells by cytotoxic lymphocytes, and it may also reprogram the tumor microenvironment to an immunostimulatory state. Understanding pyroptosis may help the development of cancer immunotherapy. In this review article, recent findings on the mechanisms and roles of pyroptosis are introduced. The effectiveness and limitations of pyroptosis in inducing antitumor immunity are also discussed.
Microemulsion Synthesis of Superparamagnetic Nanoparticles for Bioapplications
Authors: Salvador María , Gutiérrez Gemma , Noriega Sara , Moyano Amanda , Blanco-López María Carmen , Matos María
Published: January 2021

Superparamagnetic nanoparticles have seen increased potential in medical and environmental applications. Their preparation is traditionally made by the coprecipitation method, with limited control over the particle size distribution. Microemulsion methods could be advantageous due to the efficient control of the size, shape, and composition of the nanoparticles obtained. Water-in-oil (W/O) microemulsions consist of aqueous microdomains dispersed in a continuous oil phase, stabilized by surfactant molecules. These work as nanoreactors where the synthesis of the desired nanoparticles takes place through a co-precipitation chemical reaction. In this work, superparamagnetic magnetite nanoparticles with average diameters between 5.4 and 7.2 nm and large monodispersity have been synthesized through precipitation in a W/O microemulsion, with Cetyl Trimethyl Ammonium Bromide (CTAB) as a main surfactant, 1-butanol as a cosurfactant, and with 1-hexanol as the continuous oily phase. The optimization of the corresponding washing protocol has also been established since a strict control is required when using these materials for bioapplications. Their applicability in those has been proved by their encapsulation in liposomes, being tested as signal enhancers for lateral flow immunoassays by using the affinity neutravidin-biotin model system. Due to their magnetic behaviour, they were also tested for magnetic separation. These novel materials have been found to be useful for analytical applications requiring high sensitivity and the removal of interferences.
Salinity Effects on Guard Cell Proteome in Chenopodium quinoa
Authors: Rasouli Fatemeh , Kiani-Pouya Ali , Shabala Lana , Li Leiting , Tahir Ayesha , Yu Min , Hedrich Rainer , Chen Zhonghua , Wilson Richard , Zhang Heng , Shabala Sergey
Published: January 2021

Epidermal fragments enriched in guard cells (GCs) were isolated from the halophyte quinoa (Chenopodium quinoa Wild.) species, and the response at the proteome level was studied after salinity treatment of 300 mM NaCl for 3 weeks. In total, 2147 proteins were identified, of which 36% were differentially expressed in response to salinity stress in GCs. Up and downregulated proteins included signaling molecules, enzyme modulators, transcription factors and oxidoreductases. The most abundant proteins induced by salt treatment were desiccation-responsive protein 29B (50-fold), osmotin-like protein OSML13 (13-fold), polycystin-1, lipoxygenase, alpha-toxin, and triacylglycerol lipase (PLAT) domain-containing protein 3-like (eight-fold), and dehydrin early responsive to dehydration (ERD14) (eight-fold). Ten proteins related to the gene ontology term “response to ABA” were upregulated in quinoa GC; this included aspartic protease, phospholipase D and plastid-lipid-associated protein. Additionally, seven proteins in the sucrose–starch pathway were upregulated in the GC in response to salinity stress, and accumulation of tryptophan synthase and L-methionine synthase (enzymes involved in the amino acid biosynthesis) was observed. Exogenous application of sucrose and tryptophan, L-methionine resulted in reduction in stomatal aperture and conductance, which could be advantageous for plants under salt stress. Eight aspartic proteinase proteins were highly upregulated in GCs of quinoa, and exogenous application of pepstatin A (an inhibitor of aspartic proteinase) was accompanied by higher oxidative stress and extremely low stomatal aperture and conductance, suggesting a possible role of aspartic proteinase in mitigating oxidative stress induced by saline conditions.
Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach
Authors: Bini Luca , Schvartz Domitille , Carnemolla Chiara , Besio Roberta , Garibaldi Nadia , Sanchez Jean-Charles , Forlino Antonella , Bianchi Laura
Published: January 2021

Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.
Mass Spectrometric Identification of Proteins Enhanced by the Atomic Force Microscopy Immobilization Surface
Authors: Kaysheva Anna L. , Frantsuzov Pavel A. , Kopylov Arthur T. , Pleshakova Tatyana O. , Stepanov Alexander A. , Malsagova Kristina A. , Archakov Alexander I. , Ivanov Yurii D.
Published: January 2021

An approach to highly-sensitive mass spectrometry detection of proteins after surface-enhanced concentrating has been elaborated. The approach is based on a combination of mass spectrometry and atomic force microscopy to detect target proteins. (1) Background: For this purpose, a technique for preliminary preparation of molecular relief surfaces formed as a result of a chemical or biospecific concentration of proteins from solution was developed and tested on several types of chip surfaces. (2) Methods: mass spectrometric identification of proteins using trailing detectors: ion trap, time of flight, orbital trap, and triple quadrupole. We used the electrospray type of ionization and matrix-assisted laser desorption/ionization. (3) Results: It is shown that when using locally functionalized atomically smooth surfaces, the sensitivity of the mass spectrometric method increases by two orders of magnitude as compared with measurements in solution. Conclusions: It has been demonstrated that the effective concentration of target proteins on specially prepared surfaces increases the concentration sensitivity of mass spectrometric detectors—time-of-flight, ion trap, triple quadrupole, and orbital ion trap in the concentration range from up to 10−15 M.
Facilitating Workers’ Task Proficiency with Subtle Decay of Contextual AR-Based Assistance Derived from Unconscious Memory Structures
Authors: Neumann Alexander , Strenge Benjamin , Schalkwijk Lars , Essig Kai , Schack Thomas
Published: January 2021

Contemporary assistance systems support a broad variety of tasks. When they provide information or instruction, the way they do it has an implicit and often not directly graspable impact on the user. System design often forces static roles onto the user, which can have negative side effects when system errors occur or unique and previously unknown situations need to be tackled. We propose an adjustable augmented reality-based assistance infrastructure that adapts to the user’s individual cognitive task proficiency and dynamically reduces its active intervention in a subtle, not consciously noticeable way over time to spare attentional resources and facilitate independent task execution. We also introduce multi-modal mechanisms to provide context-sensitive assistance and argue why system architectures that provide explainability of concealed automated processes can improve user trust and acceptance.
Influence of Substituents in Terephthalate Linker on the Structure of MOFs Obtained from Presynthesized Heterometallic Complex
Authors: Barsukova Marina , Dudko Evgeny , Samsonenko Denis , Kovalenko Konstantin , Ryadun Alexey , Sapianik Aleksandr , Fedin Vladimir
Published: January 2021

The synthesis of new porous materials with desired properties is a challenging task. It becomes especially difficult if you need to combine several metals in one framework to obtain a heterometallic node. The use of presynthesized complexes for obtaining of new heterometallic metal–organic frameworks could be essential to solve the problem of tailored synthesis. In our study we use presynthesized heterometallic pivalate complex [Li2Zn2(piv)6(py)2] to obtain new MOFs with heterometallic core as a node of the framework. We are managed to obtain four new heterometallic MOFs: [H2N(CH3)2]2[Li2Zn2(bdc)4]·CH3CN·DMF (1), [Li2Zn2(H2Br2-bdc)(Br2-bdc)3]·2DMF (2), [H2N(CH3)2][LiZn2(ndc)3]·CH3CN (3) and [{Li2Zn2(dmf)(py)2}{LiZn(dmf)2}2 (NO2-bdc)6]·5DMF (4). Moreover three of them contain starting tetranuclear core {Li2Zn2} and saves its geometry. We also demonstrate the influence of substituent in terephthalate ring on preservation of tetranuclear core. For compound 1 it was shown that luminescence of the framework could be quenched when nitrobenzene is included in the pores.
Large-Scale Monitoring of Resistance to Coumaphos, Amitraz, and Pyrethroids in Varroa destructor
Authors: Hernández-Rodríguez Carmen Sara , Marín Óscar , Calatayud Fernando , Mahiques María José , Mompó Ana , Segura Inmaculada , Simó Enrique , González-Cabrera Joel
Published: January 2021

Varroa destructor is an ectoparasitic mite causing devastating damages to honey bee colonies around the world. Its impact is considered a major factor contributing to the significant seasonal losses of colonies recorded every year. Beekeepers usually rely on a reduced set of acaricides to manage the parasite, usually the pyrethroids tau-fluvalinate or flumethrin, the organophosphate coumaphos, and the formamidine amitraz. However, the evolution of resistance in the mite populations is leading to an unsustainable scenario with almost no alternatives to reach an adequate control of the mite. Here, we present the results from the first large-scale and extensive monitoring of the susceptibility to acaricides in the Comunitat Valenciana, one of the most prominent apicultural regions in Spain. Our ultimate goal is to provide beekeepers with timely information to help them decide what would be the best alternative for a long-term control of the mites in their apiaries. Our data show that there is a significant variation in the expected efficacy of coumaphos and pyrethroids across the region, indicating the presence of a different ratio of resistant individuals to these acaricides in each population. On the other hand, the expected efficacy of amitraz was more consistent, though slightly below the expected efficacy according to the label.
Reproductive Performance Following Hysteroscopic Surgery for Uterine Septum: Results from a Single Surgeon Data
Authors: Saridogan Ertan , Salman Mona , Direk Lerzan Sinem , Alchami Ali
Published: January 2021

Uterine septum can negatively affect reproductive outcomes in women. Based on evidence from retrospective observational studies, hysteroscopic incision has been considered a solution to improve reproductive performance, however there has been recent controversy on the need for surgery for uterine septum. High quality evidence from prospective studies is still lacking, and until it is available, experts are encouraged to publish their data. We are therefore presenting our data that involves analysis of the patient characteristics, surgical approach and long-term reproductive outcomes of women who received treatment for uterine septum under the care of a single surgeon. This includes all women (99) who underwent hysteroscopic surgery for uterine septum between January 2001 and December 2019. Of those 99 women treated for intrauterine septum who were trying to conceive, 91.4% (64/70) achieved pregnancy, 78.6% (55/70) had live births and 8.6% (6/70) had miscarriages. No statistically significant difference was found in the live birth rates when data was analyzed in subgroups based on age, reason for referral/aetiology and severity of pathology. Our study results support the view that surgical treatment of uterine septa is beneficial in improving reproductive outcomes.