bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients with Prior Craniectomy or Craniotomy Have No Increased Risk of Acute Hemorrhage after Mild Traumatic Brain Injury
Authors: Binder Harald , Schallmeiner Daniel , Tiefenboeck Thomas M. , Payr Stephan , Winnisch Markus , Kdolsky Richard , Hajdu Stefan , Schwarz Gilbert Manuel , Hofbauer Marcus
Published: February 2022

The aim of this study was to retrospectively evaluate the risk of acute hemorrhagic complications in patients after either a decompressive craniectomy or a craniotomy sustaining a recurrent mild traumatic brain injury. Furthermore, we analyze whether there is a higher risk for acute hemorrhagic complications considering patients with anticoagulation compared with patients without anticoagulation in both groups. All patients with mild traumatic brain injuries after either decompressive craniectomy or craniotomy, treated between January 2005 and December 2020 at a single level 1 trauma center, were included in this retrospective analysis. Patients were screened for intracranial bleeding after mild traumatic brain injury with computed tomography. Additionally, the type of anticoagulation and its relationship concerning the clinical outcome were assessed. A total of 188 patients who had sustained a mild traumatic brain injury were included in the study. Overall, 22 patients (11.7%) presented intracranial lesions. A bony defect (decompressive craniectomy) was present in 31 patients (16.5%). In 157 patients (83.5%) who underwent decompressive craniectomy, the bony defect was closed during a second operation. There was no significant correlation between both groups on the occurrence of intracranial bleeding (p = 0.216). Furthermore, no difference was present between patients with and without anticoagulation (p = 0.794) concerning acute hemorrhagic complications after recurrent traumatic brain injury. Pre-existing bony defects after decompressive craniectomy showed no higher risk for acute hemorrhagic complications after recurrent mild traumatic brain injury compared with patients who primarily underwent craniotomy. Anticoagulation did not influence the occurrence of intracranial bleeding after mild traumatic brain injury in patients with decompressive craniectomy.
Slow-Wave EEG Activity Correlates with Impaired Inhibitory Control in Internet Addiction Disorder
Authors: Qi Yawei , Liu Yuting , Yan Ziyou , Hu Shiqi , Zhang Xinhe , Zhao Jia , Turel Ofir , He Qinghua
Published: February 2022

Impaired inhibitory control is a core feature of internet addiction disorder (IAD). It is therefore of interest to determine the neurophysiological markers associated with it. The present study aimed to find such biomarkers with a resting-state electroencephalogram (EEG). We specifically used scores on the Chinese Internet Addiction Scale revised edition (CIAS-R) to divide 46 participants into two groups: the IAD group (>53, n = 23) and control group (<46, n = 23). Both behavioral aspects (Go/NoGo responses and impulsivity) and EEG were measured in the lab. The results suggest that the IAD group presented a decreased slow-wave (1–8 Hz) absolute power across the whole brain. The slow-wave activities in the frontal areas were also correlated with the commission error rate in the Go/NoGo task in the IAD group. These results imply that the frontal slow-wave EEG activity may serve as a neurophysiological marker of IAD, helping to understand the underlying neural mechanisms of inhibitory control deficits in IAD and point to possible interventions.
Isolated Hypoglossal Nerve Palsy as an Early Symptom of a Granular Cell Tumor
Authors: Lemound Juliana , Papadimas Dimitrios , Skodda Sabine , Tannapfel Andrea , Alekseyev Anriy , Kunkel Martin
Published: February 2022

Background: Hypoglossal nerve palsy (HNP) is rather common as a neurological disease. However, as an isolated nerve palsy it is an exceedingly rare phenomenon and points at local pathologies along the peripheral course of the nerve. In this communication we report a granular cell tumor (GCT) arising in the submandibular segment of the hypoglossal nerve. Case-Report: Spontaneous isolated HNP was recognized in a female patient. First line MR-imaging identified a clivus-chordoma. However, involvement of the hypoglossal nerve was highly unlikely according to MR-findings. Finally, ultrasonographic investigation revealed a small submandibular mass which, at histological examination, turned out to be a granular cell tumor arising within the hypoglossal nerve. Conclusions: This is the report of an extremely rare GCT originating within the 12th cranial nerve. The case illustrates that isolated motoric cranial nerve palsy may result from this rare tumor entity. This report also points out the diagnostic value of a simple ultrasonographic investigation to depict pathologic lesions of the submandibular space.
Pain Neuroscience Education and Motor Control Exercises versus Core Stability Exercises on Pain, Disability, and Balance in Women with Chronic Low Back Pain
Authors: Gorji Sahar Modares , Mohammadi Nia Samakosh Hadi , Watt Peter , Henrique Marchetti Paulo , Oliveira Rafael
Published: February 2022

Background: Several interventions have been used to relieve chronic low back pain (CLBP). This study aimed to compare the effects of pain neuroscience education (PNE) followed by motor control exercises (MCEs) with core stability training (CST) on pain, disability, and balance in women with CLBP. Methods: Thirty-seven women with CLBP were randomly divided into two groups of PNE/MCE (n = 18, 55.2 ± 2.6 years) or CST (n = 19, 54.6 ± 2.4 years). Eight weeks of PNE/MCE or CST were prescribed for each group, independently. Pain intensity (VAS scale), disability (Roland Morris Disability Questionnaire), unipodal static balance, and dynamic balance (time up and go test) were measured at the beginning and 8 weeks after the intervention. Two-way mixed ANOVA was used to analyze the results with alpha of 5%. Results: After 8 weeks, there was a significant difference in VAS scale between groups (p = 0.024), with both PNE/MCE and CST showing 58% and 42% reductions, respectively. There were no differences for all other variables between groups. Regarding pre- to post-comparisons, both groups showed improvements in all dependent variables (p < 0.001). Conclusion: The treatment with PNE/MCE was more effective in improving pain disability and unipodal static and dynamic balance than treatment with CST. Even so, both treatments were shown to be valid and safe in improving all dependent variables analyzed in women with CLBP.
Association between Noise Annoyance and Mental Health Outcomes: A Systematic Review and Meta-Analysis
Authors: Gong Xiangpu , Fenech Benjamin , Blackmore Claire , Chen Yingxin , Rodgers Georgia , Gulliver John , Hansell Anna L.
Published: February 2022

To date, most studies of noise and mental health have focused on noise exposure rather than noise annoyance. The purpose of this systematic review and meta-analysis was to evaluate whether the available evidence supports an adverse association between noise annoyance and mental health problems in people. We carried out a literature search of Web of Science, PubMed, Scopus, PsycINFO, and conference proceedings published between 2000 and 2022. Thirteen papers met the inclusion criteria. We conducted meta-analyses of noise annoyance in relation to depression, anxiety, and general mental health. In the meta-analyses, we found that depression was approximately 1.23 times greater in those who were highly noise-annoyed (N = 8 studies). We found an approximately 55% higher risk of anxiety (N = 6) in highly noise-annoyed people. For general mental health (N = 5), highly annoyed participants had an almost 119% increased risk of mental health problems as assessed by Short Form (SF) or General Household Questionnaires (GHQ), but with high heterogeneity and risk of publication bias. In conclusion, findings are suggestive of a potential link between noise annoyance and poorer mental health based on a small number of studies. More evidence is needed to confirm these findings.
Emergency Use and Efficacy of an Asynchronous Teledermatology System as a Novel Tool for Early Diagnosis of Skin Cancer during the First Wave of COVID-19 Pandemic
Authors: Jobbágy Antal , Kiss Norbert , Meznerics Fanni Adél , Farkas Klára , Plázár Dóra , Bozsányi Szabolcs , Fésűs Luca , Bartha Áron , Szabó Endre , Lőrincz Kende , Sárdy Miklós , Wikonkál Norbert Miklós , Szoldán Péter , Bánvölgyi András
Published: February 2022

Background: After the outbreak of the corona virus disease-19 (COVID-19) pandemic, teledermatology was implemented in the Hungarian public healthcare system for the first time. Our objective was to assess aggregated diagnostic agreements and to determine the effectiveness of an asynchronous teledermatology system for skin cancer screening. Methods: This retrospective single-center study included cases submitted for teledermatology consultation during the first wave of the COVID-19 pandemic. Follow-up of the patients was performed to collect the results of any subsequent personal examination. Results: 749 patients with 779 lesions were involved. 15 malignant melanomas (9.9%), 78 basal cell carcinomas (51.3%), 21 squamous cell carcinomas (13.8%), 7 other malignancies (4.6%) and 31 actinic keratoses (20.4%) were confirmed. 87 malignancies were diagnosed in the high-urgency group (42.2%), 49 malignancies in the moderate-urgency group (21.6%) and 16 malignancies in the low-urgency group (4.6%) (p < 0.0001). Agreement of malignancies was substantial for primary (86.3%; κ = 0.647) and aggregated diagnoses (85.3%; κ = 0.644). Agreement of total lesions was also substantial for primary (81.2%; κ = 0.769) and aggregated diagnoses (87.9%; κ = 0.754). Conclusions: Our findings showed that asynchronous teledermatology using a mobile phone application served as an accurate skin cancer screening system during the first wave of the COVID-19 pandemic.
Emotional Dysregulation, Anxiety Symptoms and Insomnia in Individuals with Alcohol Use Disorder
Authors: Wołyńczyk-Gmaj Dorota , Jakubczyk Andrzej , Trucco Elisa M. , Kobyliński Paweł , Zaorska Justyna , Gmaj Bartłomiej , Kopera Maciej
Published: February 2022

Alcohol craving is associated with insomnia symptoms, and insomnia is often reported as a reason for alcohol relapse. The current study examined associations between emotional regulation, anxiety, and insomnia among a group of 338 patients with alcohol use disorder (AUD). Because insomnia most often develops after stressful experiences, it was expected that anxiety symptoms would mediate the association between emotional dysregulation and insomnia severity. It was also expected that an insomnia diagnosis would moderate the association between emotional dysregulation and anxiety symptoms, namely that higher anxiety levels would be found in individuals with insomnia than in those without insomnia. Insomnia severity was assessed with a total score based on the Athens Insomnia Scale (AIS). Additionally, an eight-point cut-off score on the AIS was used to classify participants as with (n = 107) or without (n = 231) an insomnia diagnosis. Moreover, participants completed the Emotion Regulation Scale (DERS; total score) and the Brief Symptoms Inventory (BSI; anxiety). Individuals with insomnia did not differ from those without insomnia in age (p = 0.86), duration of problematic alcohol use (p < 0.34), mean days of abstinence (p = 0.17), nor years of education (p = 0.41). Yet, individuals with insomnia endorsed higher anxiety (p < 0.001) and higher emotional dysregulation (p < 0.001). Anxiety symptoms fully mediated the association between emotional dysregulation and insomnia severity (p < 0.001). Furthermore, insomnia diagnosis positively moderated the association between emotional dysregulation and anxiety (p < 0.001). Our results suggest that emotional dysregulation can lead to insomnia via anxiety symptoms. Treating anxiety symptoms and emotional dysregulation could help to prevent or alleviate symptoms of insomnia in people with AUD. Moreover, treating insomnia in people with AUD may also have a positive effect on anxiety symptoms.
Sexual Addiction, Hypersexual Behavior and Relative Psychological Dynamics during the Period of Social Distancing and Stay-at-Home Policies Due to COVID-19
Authors: Caponnetto Pasquale , Maglia Marilena , Prezzavento Graziella Chiara , Pirrone Concetta
Published: February 2022

During the COVID-19 pandemic, increased stress factors affected people’s motivations to engage in potentially addictive behaviors. Sexuality, understood as one of the psychological aspects to be investigated to explore the level of psychological well-being of a person, has suffered considerable repercussions due to the pandemic. A growing body of evidence suggests an unprecedented increase in Internet use and online pornography consumption during the pandemic. Since March 2020, during the lockdown period, Pornhub has seen a worldwide increase in pornography use of 11.6% compared to the previous average days. This research was conducted with the aim of exploring the possible increasing use of pornographic material during the lockdown period, in order to assess whether dysfunctional behaviors, such as compulsive behaviors, and thoughts of sex-related obsessives can lead to hypersexual behavior or a more severe Sexual Addiction. The individuals who participated in our research were 18 years of age or older (mean 23.1, s.d. 5.8), and 48% male and 52% females and were recruited online to complete a self-report questionnaire in the period between April 2020 and April 2021. The questionnaires were delivered via main social networks. The tool used for our survey was the SAST (Sexual Addiction Screening Test), a questionnaire including socio-demographic data and data relating to sexual practices, such as sexual orientation and time spent on the Internet for sexual activities. The results revealed significant differences concerning the various factors investigated such as loss of control, addictive symptoms and hide score.
Association between Pre-Pregnancy BMI and Inflammatory Profile Trajectories during Pregnancy and Postpartum in Brazilian Women with Periodontitis: The IMPROVE Trial
Authors: Santana Danilo Dias , Kac Gilberto , dos Santos Pedro Paulo Teixeira , da Silva Thainá Castro , Benaim Camila , Cocate Paula Guedes , Trindade de Castro Maria Beatriz , Heitmann Berit Lilienthal , Adegboye Amanda Rodrigues Amorim
Published: February 2022

This study aimed to explore the association between pre-pregnancy BMI and longitudinal changes in inflammatory markers from the second trimester of pregnancy to 6–8 weeks postpartum in women with periodontitis. This is a secondary exploratory analysis of 68 women who took part in a feasibility clinical trial in Rio de Janeiro, Brazil. Inflammatory markers included C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and matrix metalloproteinase-9 (MMP-9) blood concentrations at 11–22 (T0) and 30–36 gestational weeks (T1), and 6–8 weeks postpartum (T3). Longitudinal generalised linear mixed-effects models were used to identify possible associations between pre-pregnancy BMI and changes in concentrations of inflammatory markers. Pre-pregnancy excess weight (β = 4.39; 95% CI, 2.12–6.65) was significantly associated with increased CRP levels from pregnancy to postpartum. There were no significant associations between pre-pregnancy BMI and longitudinal changes in IL-6, IL-10 and MMP-9. Our findings provide evidence that a higher pre-pregnancy BMI may lead to increases in CRP levels during pregnancy in women with periodontitis, irrespective of the severity of clinical periodontal parameters. Further studies need to investigate if predictors of changes in inflammatory markers can be used as prognostic factors for gestational outcomes.
How Do Master Weightlifters Train? A Transnational Study of Weightlifting Training Practices and Concurrent Training
Authors: Huebner Marianne , Faber Friedrich , Currie Katharine , Rieger Thomas
Published: February 2022

(1) Background: The wide range of preparedness, physical fitness, and capabilities of older athletes makes it challenging to recommend general training programs for this cohort ranging from ages 35 to 80 and older. Weightlifting has enjoyed an unprecedented growth in recent years, especially among women. The objectives of this study are to describe age and sex differences in self-reported training regimens and concurrent training for Masters weightlifters and investigate regional differences. (2) Methods: A total of 1051 Masters weightlifters from Australia, Canada, Europe, and the USA completed an online survey that included questions on sport history and training practices. (3) Results: A training session typically lasted 1.5 to 2 h for both sexes across all ages. Weightlifters engaged in concurrent training (66.9%), especially in endurance training (24.9%) and CrossFit (36.4%), but the proportions differed across geographic regions. Older females maintained training 4 days per week, while older males reduced this to 3 days per week. (4) Conclusions: Weightlifting training practice of Masters athletes was remarkably consistent across ages, but concurrent training differed between males and females and across regions. This study provides helpful information for athletes, coaches, and sport organizations about the variation in weightlifting training practices and concurrent training of older athletes.
An Internet-Based Multi-Approach Intervention Targeting University Students Suffering from Psychological Problems: Design, Implementation, and Evaluation
Authors: De Fabritiis Marlene , Trisolini Federica , Bertuletti Gloria , Fagadau Ionut Daniel , Ginelli Davide , Lalopa Katiuscia Pia , Peverelli Lisa , Pirola Alessia , Sala Gaia , Maisto Marta , Madeddu Fabio , Lopez-Castroman Jorge , Romano Daniele , Gabbiadini Alessandro , Preti Emanuele , Micucci Daniela , Calati Raffaella
Published: February 2022

Despite the widespread prevalence of mental health problems, most psychological distress remains untreated. Internet-based psychological interventions can be an essential tool for increasing treatment availability and accessibility. The main objective of the MindBlooming project is to design and implement an innovative Internet-based multi-approach treatment for university students suffering from psychological or physical problems. The intervention will focus on symptoms of depression, anxiety, sleep problems, self-destructive thoughts, job- and study-related stress and burnout, and chronic pain. It will be based on different approaches, primarily psychoeducation, Cognitive-Behavioral Treatment (CBT), and third-wave CBT. At the end of the treatment, user satisfaction and usability will be assessed. In addition, two further aims will be evaluating the treatment efficacy through a randomized controlled trial and tuning a predictive model through Machine Learning techniques. The intervention consists of a 7-week treatment on two problematic areas according to each students’ personal needs, identified through an initial assessment. Besides the treatment assigned following the initial screening, participants will also be assigned to a different module to improve their relational skills. The treatment, which can be accessed through a mobile app, consists of psychoeducational videos followed by related exercises. We expect MindBlooming to be a remarkable tool for promoting the mental health of university students.
Impact on Sleep Quality, Mood, Anxiety, and Personal Satisfaction of Doctors Assigned to COVID-19 Units
Authors: Andrés-Olivera Pilar , García-Aparicio Judit , Lozano López María Teresa , Benito Sánchez José Antonio , Martín Carmen , Maciá-Casas Ana , González-Sánchez Armando , Marcos Miguel , Roncero Carlos
Published: February 2022

The SARS-CoV-2 health emergency has led to a restructuring of health care systems and the reassignment of medical specialists from their usual duties to attend COVID-19 patients. The aim of this paper is to describe the levels of insomnia, anxiety, depression, and the impact on quality of life of doctors who were on the frontline of COVID-19 during the first two waves of the pandemic. Self-report surveys were conducted on said physicians during both waves, with 83 and 61 responses in the first and second waves, respectively. The reported presence of insomnia was frequent (71.8%), although it decreased in the second survey. Anxiety was moderate, decreasing from 57.1% to 43.1% between measurements. Overall, depression rates decreased between the two surveys. Substance use was found to have an indirect correlation with personal and professional satisfaction. In the light of the unforeseeable evolution of the pandemic and the medium- to long-term repercussions on professionals, we believe the adaptation of health resources is crucial to meet the new unpredictable mental health needs of this group.
Effect of Intrinsic and Extrinsic Motivations on Service Performance after Parental Leave
Authors: Lee Yerim , Kim Haeok Liz , Hyun Sunghyup Sean
Published: February 2022

This study was conducted to empirically investigate the effects of intrinsic and extrinsic motivation on job satisfaction perceived by married female flight attendants after reinstatement, the effect of job satisfaction on service performance after reinstatement, and the moderating effect of the marriage period on the relationship between intrinsic and extrinsic motivation. A questionnaire survey was conducted to collate data from 248 married female flight attendants who had been reinstated after parental leave. The data was analyzed quantitatively, and the main results and implications of this study were as follows. First, intrinsic motivation related to job, aptitude significantly affected job satisfaction, whereas self-realization did not. Second, extrinsic motivation, lay over, salary, and external recognition had significant positive effects on job satisfaction, while welfare did not affect job satisfaction. Third, job satisfaction perceived by married female flight attendants had a significant effect on their service performance after reinstatement. This demonstrates that there is a need to support married women to induce high job satisfaction and for them to reach a level of service performance similar to or better than before they took leave. Fourth, an analysis of the moderating effect of the marriage period on the relationship between intrinsic and extrinsic motivation demonstrated that the marriage period only significantly moderated the relationship between salary and job satisfaction. The study is related to the quality of life and subjective well-being including mental health of service workers in tourism and hospitality. The results of this study can be widely used as reference materials for successful reinstatement, job re-adjustment, job satisfaction, and commitment of all married female employees, especially flight attendants.
Multi-Resolution Transformer Network for Building and Road Segmentation of Remote Sensing Image
Authors: Sun Zhongyu , Zhou Wangping , Ding Chen , Xia Min
Published: February 2022

Extracting buildings and roads from remote sensing images is very important in the area of land cover monitoring, which is of great help to urban planning. Currently, a deep learning method is used by the majority of building and road extraction algorithms. However, for existing semantic segmentation, it has a limitation on the receptive field of high-resolution remote sensing images, which means that it can not show the long-distance scene well during pixel classification, and the image features is compressed during down-sampling, meaning that the detailed information is lost. In order to address these issues, Hybrid Multi-resolution and Transformer semantic extraction Network (HMRT) is proposed in this paper, by which a global receptive field for each pixel can be provided, a small receptive field of convolutional neural networks (CNN) can be overcome, and the ability of scene understanding can be enhanced well. Firstly, we blend the features by branches of different resolutions to keep the high-resolution and multi-resolution during down-sampling and fully retain feature information. Secondly, we introduce the Transformer sequence feature extraction network and use encoding and decoding to realize that each pixel has the global receptive field. The recall, F1, OA and MIoU of HMPR obtain 85.32%, 84.88%, 85.99% and 74.19%, respectively, in the main experiment and reach 91.29%, 90.41%, 91.32% and 84.00%, respectively, in the generalization experiment, which prove that the method proposed is better than existing methods.
Investigation of the Molecular Details of the Interactions of Selenoglycosides and Human Galectin-3
Authors: Raics Mária , Balogh Álex Kálmán , Kishor Chandan , Timári István , Medrano Francisco J. , Romero Antonio , Go Rob Marc , Blanchard Helen , Szilágyi László , E. Kövér Katalin , Fehér Krisztina
Published: February 2022

Human galectin-3 (hGal-3) is involved in a variety of biological processes and is implicated in wide range of diseases. As a result, targeting hGal-3 for clinical applications has become an intense area of research. As a step towards the development of novel hGal-3 inhibitors, we describe a study of the binding of two Se-containing hGal-3 inhibitors, specifically that of di(β-D-galactopyranosyl)selenide (SeDG), in which two galactose rings are linked by one Se atom and a di(β-D-galactopyranosyl)diselenide (DSeDG) analogue with a diseleno bond between the two sugar units. The binding affinities of these derivatives to hGal-3 were determined by 15N-1H HSQC NMR spectroscopy and fluorescence anisotropy titrations in solution, indicating a slight decrease in the strength of interaction for SeDG compared to thiodigalactoside (TDG), a well-known inhibitor of hGal-3, while DSeDG displayed a much weaker interaction strength. NMR and FA measurements showed that both seleno derivatives bind to the canonical S face site of hGal-3 and stack against the conserved W181 residue also confirmed by X-ray crystallography, revealing canonical properties of the interaction. The interaction with DSeDG revealed two distinct binding modes in the crystal structure which are in fast exchange on the NMR time scale in solution, explaining a weaker interaction with hGal-3 than SeDG. Using molecular dynamics simulations, we have found that energetic contributions to the binding enthalpies mainly differ in the electrostatic interactions and in polar solvation terms and are responsible for weaker binding of DSeDG compared to SeDG. Selenium-containing carbohydrate inhibitors of hGal-3 showing canonical binding modes offer the potential of becoming novel hydrolytically stable scaffolds for a new class of hGal-3 inhibitors.
Nst1, Densely Associated to P-Body in the Post-Exponential Phases of Saccharomyces cerevisiae, Shows an Intrinsic Potential of Producing Liquid-Like Condensates of P-Body Components in Cells
Authors: Choi Yoon-Jeong , Song Kiwon
Published: February 2022

Membrane-less biomolecular compartmentalization is a core phenomenon involved in many physiological activities that occur ubiquitously in cells. Condensates, such as promyelocytic leukemia (PML) bodies, stress granules, and P-bodies (PBs), have been investigated to understand the process of membrane-less cellular compartmentalization. In budding yeast, PBs dispersed in the cytoplasm of exponentially growing cells rapidly accumulate in response to various stresses such as osmotic stress, glucose deficiency, and heat stress. In addition, cells start to accumulate PBs chronically in post-exponential phases. Specific protein–protein interactions are involved in accelerating PB accumulation in each circumstance, and discovering the regulatory mechanism for each is the key to understanding cellular condensation. Here, we demonstrate that Nst1 of budding yeast Saccharomyces cerevisiae is far more densely associated with PBs in post-exponentially growing phases from the diauxic shift to the stationary phase than during glucose deprivation of exponentially growing cells, while the PB marker Dcp2 exhibits a similar degree of condensation under these conditions. Similar to Edc3, ectopic Nst1 overexpression induces self-condensation and the condensation of other PB components, such as Dcp2 and Dhh1, which exhibit liquid-like properties. Altogether, these results suggest that Nst1 has the intrinsic potential for self-condensation and the condensation of other PB components, specifically in post-exponential phases.
Monitoring TRPC7 Conformational Changes by BRET Following GPCR Activation
Authors: Pétigny Cécile , Dumont Audrey-Ann , Giguère Hugo , Collette Audrey , Holleran Brian J. , Iftinca Mircea , Altier Christophe , Besserer-Offroy Élie , Auger-Messier Mannix , Leduc Richard
Published: February 2022

Transient receptor potential canonical (TRPC) channels are membrane proteins involved in regulating Ca2+ homeostasis, and whose functions are modulated by G protein-coupled receptors (GPCR). In this study, we developed bioluminescent resonance energy transfer (BRET) biosensors to better study channel conformational changes following receptor activation. For this study, two intramolecular biosensors, GFP10-TRPC7-RLucII and RLucII-TRPC7-GFP10, were constructed and were assessed following the activation of various GPCRs. We first transiently expressed receptors and the biosensors in HEK293 cells, and BRET levels were measured following agonist stimulation of GPCRs. The activation of GPCRs that engage Gαq led to a Gαq-dependent BRET response of the functional TRPC7 biosensor. Focusing on the Angiotensin II type-1 receptor (AT1R), GFP10-TRPC7-RLucII was tested in rat neonatal cardiac fibroblasts, expressing endogenous AT1R and TRPC7. We detected similar BRET responses in these cells, thus validating the use of the biosensor in physiological conditions. Taken together, our results suggest that activation of Gαq-coupled receptors induce conformational changes in a novel and functional TRPC7 BRET biosensor.
Identification and Quantitation of Bioactive and Taste-Related Dipeptides in Low-Salt Dry-Cured Ham
Authors: Heres Alejandro , Gallego Marta , Mora Leticia , Toldrá Fidel
Published: February 2022

The reduction of salt in meat products influences the natural mechanisms of proteolysis occurring in their processing, and could affect the final characteristics of the product in terms of texture and flavor due to its effect on the activity of enzymes. In the present study, the quantitation of dipeptides PA, GA, VG, EE, ES, DA, and DG in low-salt Spanish dry-cured ham was carried out using a triple quadrupole mass spectrometry instrument. The developed methodology demonstrated the advantages of hydrophilic interaction liquid chromatography in the removal of salt as a clean-up/separation step before ionization. This resulted in a value of 44.88 μg/g dry-cured ham for GA dipeptide, and values ranging from 2 to 8 μg/g dry-cured ham for VG, EE, ES, DA, and DG dipeptides. PA showed the lowest concentration with a value of 0.18 μg/g dry-cured ham. These outcomes prove the remarkable activity of muscular dipeptidyl peptidases during dry-curing as well as confirming the presence of these dipeptides which are related to certain taste attributes (e.g., ‘bitter’ or ‘umami’). Such dipeptides have also been confirmed as anti-inflammatory and potential cardiovascular protectors using in vitro assays, with the advantage of dipeptides small size increases their chance to resist both gastrointestinal digestion and intestinal/bloodstream transport without being degraded or modified.
Micro-Current Stimulation Suppresses Inflammatory Responses in Peptidoglycan-Treated Raw 264.7 Macrophages and Propionibacterium acnes-Induced Skin Inflammation via TLR2/NF-κB Signaling Pathway
Authors: Lee Hana , Hwang Donghyun , Lee Minjoo , Lee Jinho , Cho Seungkwan , Kim Tack-Joong , Kim Han Sung
Published: February 2022

Acne is a common inflammatory disorder of the human skin and a multifactorial disease caused by the sebaceous gland and Propionibacterium acnes (P. acnes). This study aimed to evaluate the anti-inflammatory effect of micro-current stimulation (MC) on peptidoglycan (PGN)-treated raw 264.7 macrophages and P. acnes-induced skin inflammation. To specify the intensity with anti-inflammatory effects, nitric oxide (NO) production was compared according to various levels of MC. As the lowest NO production was shown at an intensity of 50 μA, subsequent experiments used this intensity. The changes of expression of the proteins related to TLR2/NF-κB signaling were examined by immunoblotting. Also, immunofluorescence analysis was performed for observing NF-κB p65 localization. All of the expression levels of proteins regarding TLR2/NF−κB signaling were decreased by the application of MC. Moreover, the application of MC to PGN−treated raw 264.7 cells showed a significant decrease in the amount of nuclear p65−protein. In the case of animal models with P. acnes−induced skin inflammation, various pro−inflammatory cytokines and mediators significantly decreased in MC−applied mice. In particular, the concentration of IL−1β in serum decreased, and the area of acne lesions, decreased from the histological analysis. We suggest for the first time that MC can be a novel treatment for acne.
Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-β-D-Glucan, but Is Attenuated by Lacticaseibacillus rhamnosus L34
Authors: Tungsanga Somkanya , Panpetch Wimonrat , Bhunyakarnjanarat Thansita , Udompornpitak Kanyarat , Katavetin Pisut , Chancharoenthana Wiwat , Chatthanathon Piraya , Somboonna Naraporn , Tungsanga Kriang , Tumwasorn Somying , Leelahavanichkul Asada
Published: February 2022

A chronic kidney disease (CKD) causes uremic toxin accumulation and gut dysbiosis, which further induces gut leakage and worsening CKD. Lipopolysaccharide (LPS) of Gram-negative bacteria and (1➔3)-β-D-glucan (BG) of fungi are the two most abundant gut microbial molecules. Due to limited data on the impact of intestinal fungi in CKD mouse models, the influences of gut fungi and Lacticaseibacillus rhamnosus L34 (L34) on CKD were investigated using oral C. albicans-administered 5/6 nephrectomy (5/6Nx) mice. At 16 weeks post-5/6Nx, Candida-5/6Nx mice demonstrated an increase in proteinuria, serum BG, serum cytokines (tumor necrotic factor-α; TNF-α and interleukin-6), alanine transaminase (ALT), and level of fecal dysbiosis (Proteobacteria on fecal microbiome) when compared to non-Candida-5/6Nx. However, serum creatinine, renal fibrosis, or gut barrier defect (FITC-dextran assay and endotoxemia) remained comparable between Candida- versus non-Candida-5/6Nx. The probiotics L34 attenuated several parameters in Candida-5/6Nx mice, including fecal dysbiosis (Proteobacteria and Bacteroides), gut leakage (fluorescein isothiocyanate (FITC)-dextran), gut-derived uremic toxin (trimethylamine-N-oxide; TMAO) and indoxyl sulfate; IS), cytokines, and ALT. In vitro, IS combined with LPS with or without BG enhanced the injury on Caco-2 enterocytes (transepithelial electrical resistance and FITC-dextran permeability) and bone marrow-derived macrophages (supernatant cytokines (TNF-α and interleukin-1 β; IL-1β) and inflammatory genes (TNF-α, IL-1β, aryl hydrocarbon receptor, and nuclear factor-κB)), compared with non-IS activation. These injuries were attenuated by the probiotics condition media. In conclusion, Candida administration worsens kidney damage in 5/6Nx mice through systemic inflammation, partly from gut dysbiosis-induced uremic toxins, which were attenuated by the probiotics. The additive effects on cell injury from uremic toxin (IS) and microbial molecules (LPS and BG) on enterocytes and macrophages might be an important underlying mechanism.
Targeted Analysis of Sphingolipids in Turkeys Fed Fusariotoxins: First Evidence of Key Changes That Could Help Explain Their Relative Resistance to Fumonisin Toxicity
Authors: Guerre Philippe , Travel Angelique , Tardieu Didier
Published: February 2022

The effects of fumonisins on sphingolipids in turkeys are unknown, except for the increased sphinganine to sphingosine ratio (Sa:So) used as a biomarker. Fumonisins fed at 20.2 mg/kg for 14 days were responsible for a 4.4 fold increase in the Sa:So ratio and a decrease of 33% and 36% in C14-C16 ceramides and C14-C16 sphingomyelins, respectively, whereas C18-C26 ceramides and C18-C26 sphingomyelins remained unaffected or were increased. Glucosyl- and lactosyl-ceramides paralleled the concentrations of ceramides. Fumonisins also increased dihydroceramides but had no effect on deoxysphinganine. A partial least squfares discriminant analysis revealed that all changes in sphingolipids were important in explaining the effect of fumonisins. Because deoxynivalenol and zearalenone are often found in feed, their effects on sphingolipids alone and in combination with fumonisins were investigated. Feeding 5.12 mg deoxynivalenol/kg reduced dihydroceramides in the liver. Zearalenone fed at 0.47 mg/kg had no effect on sphingolipids. When fusariotoxins were fed simultaneously, the effects on sphingolipids were similar to those observed in turkeys fed fumonisins alone. The concentration of fumonisin B1 in the liver of turkeys fed fumonisins was 0.06 µmol/kg. Changes in sphingolipid concentrations differed but were consistent with the IC50 of fumonisin B1 measured in mammals; these changes could explain the relative resistance of turkeys to fumonisins.
Impact of Two Neuronal Sigma-1 Receptor Modulators, PRE084 and DMT, on Neurogenesis and Neuroinflammation in an Aβ1–42-Injected, Wild-Type Mouse Model of AD
Authors: Borbély Emőke , Varga Viktória , Szögi Titanilla , Schuster Ildikó , Bozsó Zsolt , Penke Botond , Fülöp Lívia
Published: February 2022

Alzheimer’s disease (AD) is the most common form of dementia characterized by cognitive dysfunctions. Pharmacological interventions to slow the progression of AD are intensively studied. A potential direction targets neuronal sigma-1 receptors (S1Rs). S1R ligands are recognized as promising therapeutic agents that may alleviate symptom severity of AD, possibly via preventing amyloid-β-(Aβ-) induced neurotoxicity on the endoplasmic reticulum stress-associated pathways. Furthermore, S1Rs may also modulate adult neurogenesis, and the impairment of this process is reported to be associated with AD. We aimed to investigate the effects of two S1R agonists, dimethyltryptamine (DMT) and PRE084, in an Aβ-induced in vivo mouse model characterizing neurogenic and anti-neuroinflammatory symptoms of AD, and the modulatory effects of S1R agonists were analyzed by immunohistochemical methods and western blotting. DMT, binding moderately to S1R but with high affinity to 5-HT receptors, negatively influenced neurogenesis, possibly as a result of activating both receptors differently. In contrast, the highly selective S1R agonist PRE084 stimulated hippocampal cell proliferation and differentiation. Regarding neuroinflammation, DMT and PRE084 significantly reduced Aβ1–42-induced astrogliosis, but neither had remarkable effects on microglial activation. In summary, the highly selective S1R agonist PRE084 may be a promising therapeutic agent for AD. Further studies are required to clarify the multifaceted neurogenic and anti-neuroinflammatory roles of these agonists.
Plant Peroxisome-Targeting Effector MoPtep1 Is Required for the Virulence of Magnaporthe oryzae
Authors: Ning Na , Xie Xin , Yu Haiyue , Mei Jie , Li Qianqian , Zuo Shimin , Wu Hanxiang , Liu Wende , Li Zhiqiang
Published: February 2022

Rice blast caused by Magnaporthe oryzae is one of the most serious fungous diseases in rice. In the past decades, studies have reported that numerous M. oryzae effectors were secreted into plant cells to facilitate inoculation. Effectors target host proteins to assist the virulence of pathogens via the localization of specific organelles, such as the nucleus, endoplasmic reticulum, chloroplast, etc. However, studies on the pathogenesis of peroxisome-targeting effectors are still limited. In our previous study, we analyzed the subcellular localization of candidate effectors from M. oryzae using the agrobacterium-mediated transient expression system in tobacco and found that MoPtep1 (peroxisomes-targeted effector protein 1) localized in plant peroxisomes. Here, we proved that MoPtep1 was induced in the early stage of the M. oryzae infection and positively regulated the pathogenicity, while it did not affect the vegetative growth of mycelia. Subcellular localization results showed that MoPtep1 was localized in the plant peroxisomes with a signal peptide and a cupredoxin domain. Sequence analysis indicated that the homologous protein of MoPtep1 in plant-pathogenic fungi was evolutionarily conserved. Furthermore, MoPtep1 could suppress INF1-induced cell death in tobacco, and the targeting host proteins were identified using the Y2H system. Our results suggested that MoPtep1 is an important pathogenic effector in rice blast.
Epstein-Barr Virus Enhances Cancer-Specific Aberrant Splicing of TSG101 Pre-mRNA
Authors: Chua Huey-Huey , Kameyama Toshiki , Mayeda Akila , Yeh Te-Huei
Published: February 2022

Tumor viruses gain control of cellular functions when they infect and transform host cells. Alternative splicing is one of the cellular processes exploited by tumor viruses to benefit viral replication and support oncogenesis. Epstein-Barr virus (EBV) participates in a number of cancers, as reported mostly in nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). Using RT-nested-PCR and Northern blot analysis in NPC and BL cells, here we demonstrate that EBV promotes specific alternative splicing of TSG101 pre-mRNA, which generates the TSG101∆154-1054 variant though the agency of its viral proteins, such as EBNA-1, Zta and Rta. The level of TSG101∆154-1054 is particularly enhanced upon EBV entry into the lytic cycle, increasing protein stability of TSG101 and causing the cumulative synthesis of EBV late lytic proteins, such as VCA and gp350/220. TSG101∆154-1054-mediated production of VCA and gp350/220 is blocked by the overexpression of a translational mutant of TSG101∆154-1054 or by the depletion of full-length TSG101, which is consistent with the known role of the TSG101∆154-1054 protein in stabilizing the TSG101 protein. NPC patients whose tumor tissues express TSG101∆154-1054 have high serum levels of anti-VCA antibodies and high levels of viral DNA in their tumors. Our findings highlight the functional importance of TSG101∆154-1054 in allowing full completion of the EBV lytic cycle to produce viral particles. We propose that targeting EBV-induced TSG101 alternative splicing has broad potential as a therapeutic to treat EBV-associated malignancies.
The Splicing of the Mitochondrial Calcium Uniporter Genuine Activator MICU1 Is Driven by RBFOX2 Splicing Factor during Myogenic Differentiation
Authors: Vecellio Reane Denis , Cerqua Cristina , Sacconi Sabrina , Salviati Leonardo , Trevisson Eva , Raffaello Anna
Published: February 2022

Alternative splicing, the process by which exons within a pre-mRNA transcript are differentially joined or skipped, is crucial in skeletal muscle since it is required both during myogenesis and in post-natal life to reprogram the transcripts of contractile proteins, metabolic enzymes, and transcription factors in functionally distinct muscle fiber types. The importance of such events is underlined by the numerosity of pathological conditions caused by alternative splicing aberrations. Importantly, many skeletal muscle Ca2+ homeostasis genes are also regulated by alternative splicing mechanisms, among which is the Mitochondrial Ca2+ Uniporter (MCU) genuine activator MICU1 which regulates MCU opening upon cell stimulation. We have previously shown that murine skeletal muscle MICU1 is subjected to alternative splicing, thereby generating a splice variant—which was named MICU1.1—that confers unique properties to the mitochondrial Ca2+ uptake and ensuring sufficient ATP production for muscle contraction. Here we extended the analysis of MICU1 alternative splicing to human tissues, finding two additional splicing variants that were characterized by their ability to regulate mitochondrial Ca2+ uptake. Furthermore, we found that MICU1 alternative splicing is induced during myogenesis by the splicing factor RBFOX2. These results highlight the complexity of the alternative splicing mechanisms in skeletal muscle and the regulation of mitochondrial Ca2+ among tissues.
Drug-Resistant Stem Cells: Novel Approach for Colon Cancer Therapy
Authors: Telang Nitin
Published: February 2022

Background: Next to breast cancer, advanced stage metastatic colon cancer represents a major cause for mortality in women. Germline or somatic mutations in tumor suppressor genes or in DNA mismatch repair genes represent risk factors for genetic predisposition of colon cancer that are also detectable in sporadic colon cancer. Conventional chemotherapy for colon cancer includes combination of 5-fluoro-uracil with oxaliplatin and irinotecan or targeted therapy with non-steroid anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors. Major limitations of these therapeutic interventions are associated with systemic toxicity, acquired tumor resistance and the emergence of drug resistant stem cells that favor initiation, progression and metastasis of therapy-resistant disease. These limitations emphasize an unmet need to identify tumor stem cell selective testable alternatives. Drug-resistant stem cell models facilitate the identification of new testable alternatives from natural phytochemicals and herbal formulations. The goal of this review is to provide an overview relevant to the current status of conventional/targeted therapy, the role of cancer stem cells and the status of testable alternatives for therapy-resistant colon cancer. Experimental models: Hyper-proliferative and tumorigenic cell lines from genetically predisposed colonic tissues of female mice represent experimental models. Chemotherapeutic agents select drug-resistant phenotypes that exhibit upregulated expressions of cellular and molecular stem cell markers. Mechanistically distinct natural phytochemicals effectively inhibit stem cell growth and downregulate the expressions of stem cell markers. Conclusions: The present review discusses the status of colon cancer therapy and inherent limitations, cancer stem cell biology, potential lead compounds and their advantages over chemotherapy. The present experimental approaches will facilitate the identification of pharmacological and naturally-occurring agents as lead compounds for stem cell targeted therapy of colon cancer.
Processing of D1 Protein: A Mysterious Process Carried Out in Thylakoid Lumen
Authors: Inagaki Noritoshi
Published: February 2022

In oxygenic photosynthetic organisms, D1 protein, a core subunit of photosystem II (PSII), displays a rapid turnover in the light, in which D1 proteins are distinctively damaged and immediately removed from the PSII. In parallel, as a repair process, D1 proteins are synthesized and simultaneously assembled into the PSII. On this flow, the D1 protein is synthesized as a precursor with a carboxyl-terminal extension, and the D1 processing is defined as a step for proteolytic removal of the extension by a specific protease, CtpA. The D1 processing plays a crucial role in appearance of water-oxidizing capacity of PSII, because the main chain carboxyl group at carboxyl-terminus of the D1 protein, exposed by the D1 processing, ligates a manganese and a calcium atom in the Mn4CaO5-cluster, a special equipment for water-oxidizing chemistry of PSII. This review focuses on the D1 processing and discusses it from four angles: (i) Discovery of the D1 processing and recognition of its importance: (ii) Enzyme involved in the D1 processing: (iii) Efforts for understanding significance of the D1 processing: (iv) Remaining mysteries in the D1 processing. Through the review, I summarize the current status of our knowledge on and around the D1 processing.