Search Results (20)

The BCS1L gene encodes a mitochondrial chaperone which inserts the Fe₂S₂ iron–sulfur Rieske protein into the nascent electron transfer complex III. Variants in the BCS1L gene are associated with a spectrum of mitochondrial disorders, ranging from mild to severe phenotypes. Björnstad syndrome, a milder condition, is characterized by sensorineural hearing loss (SNHL) and pili torti. More severe disorders include Complex III Deficiency, which leads to neuromuscular and metabolic dysfunctions with multi-systemic issues and Growth Retardation, Aminoaciduria, Cholestasis, Iron Overload, and Lactic Acidosis syndrome (GRACILE). The severity of these conditions varies depending on the specific BCS1L mutation and its impact on mitochondrial function. This study describes a 27-month-old child with SNHL, proximal renal tubular acidosis, woolly hypopigmented hair, developmental delay, and metabolic alterations. Genetic analysis revealed a homozygous BCS1L variant (c.38A>G, p.Asn13Ser), previously reported in a patient with a more severe phenotype that, however, was not functionally characterized. In this work, functional studies in a yeast model and patient-derived fibroblasts demonstrated that the variant impairs mitochondrial respiration, complex III activity (CIII), and also alters mitochondrial morphology in affected fibroblasts. Interestingly, we unveil a new possible mechanism of pathogenicity for BCS1L mutant protein. Since the interaction between BCS1L and CIII is increased, this suggests the formation of a BCS1L-containing nonfunctional preCIII unable to load RISP protein and complete CIII assembly. These findings support the pathogenicity of the BCS1L c.38A>G variant, suggesting altered interaction between the mutant BCS1L and CIII. Full article

Pulmonary artery endothelial cells (PAECs) are a major contributor to hypoxic pulmonary hypertension (PH) due to the possible roles of reactive oxygen species (ROS). However, the molecular mechanisms and functional roles of ROS in PAECs are not well established. In this study, we first used Amplex UltraRed reagent to assess hydrogen peroxide (H₂O₂) generation. The result indicated that hypoxic exposure resulted in a significant increase in Amplex UltraRed-derived fluorescence (i.e., H₂O₂ production) in human PAECs. To complement this result, we employed lucigenin as a probe to detect superoxide (O₂⁻) production. Our assays showed that hypoxia largely increased O₂⁻ production. Hypoxia also enhanced H₂O₂ production in the mitochondria from PAECs. Using the genetically encoded H₂O₂ sensor HyPer, we further revealed the hypoxic ROS production in PAECs, which was fully blocked by the mitochondrial inhibitor rotenone or myxothiazol. Interestingly, hypoxia caused an increase in the migration of PAECs, determined by scratch wound assay. In contrast, nicotine, a major cigarette or e-cigarette component, had no effect. Moreover, hypoxia and nicotine co-exposure further increased migration. Transfection of lentiviral shRNAs specific for the mitochondrial Rieske iron–sulfur protein (RISP), which knocked down its expression and associated ROS generation, inhibited the hypoxic migration of PAECs. Hypoxia largely increased the proliferation of PAECs, determined using Ki67 staining and direct cell number accounting. Similarly, nicotine caused a large increase in proliferation. Moreover, hypoxia/nicotine co-exposure elicited a further increase in cell proliferation. RISP knockdown inhibited the proliferation of PAECs following hypoxia, nicotine exposure, and hypoxia/nicotine co-exposure. Taken together, our data demonstrate that hypoxia increases RISP-mediated mitochondrial ROS production, migration, and proliferation in human PAECs; nicotine has no effect on migration, increases proliferation, and promotes hypoxic proliferation; the effects of nicotine are largely mediated by RISP-dependent mitochondrial ROS signaling. Conceivably, PAECs may contribute to PH via the RISP-mediated mitochondrial ROS. Full article

The study of the mechanisms underlying stem cell differentiation is under intensive research and includes the contribution of a metabolic switch from glycolytic to oxidative metabolism. While mitochondrial biogenesis has been previously demonstrated in number of differentiation models, it is only recently that the role of mitochondrial dynamics has started to be explored. The discovery of asymmetric distribution of mitochondria in stem cell progeny has strengthened the interest in the field. This review attempts to summarize the regulation of mitochondrial asymmetric apportioning by the mitochondrial fusion, fission, and mitophagy processes as well as emphasize how asymmetric mitochondrial apportioning in stem cells affects their metabolism, and thus epigenetics, and determines cell fate. Full article

Amid the COVID-19 pandemic’s significant impact on the dining-out industry, this study examined factors influencing consumers’ dining-out behavior changes using a unified theoretical framework based on the theory of planned behavior (TPB) and select components of the risk information seeking and processing (RISP) model. A quantitative research method was employed, analyzing 536 valid survey responses collected in South Korea in early 2021 using partial least squares structural equation modeling (PLS-SEM). Findings showed that consumer attitude, perceived control, and subjective norm positively influenced dining-out intention, supporting the TPB. However, risk information-seeking behavior discourages dining-out behavior without significantly affecting intention. Fear emerged as a determinant of dining-out intention, risk information-seeking behavior, and dining-out behavior, highlighting the importance of emotions over rational thinking. This study contributes to existing literature by incorporating dining-out intention, COVID-19-related information-seeking behavior, and fear as key antecedents of dining-out behavior during the pandemic, while validating formative indicators that constitute risk information-seeking behavior and dining-out behavior in the research model. Full article

The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with ¹²⁵I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 _D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either ¹²⁵I-RISP or [¹²⁵I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [¹²⁵I]I⁻ took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants. Full article

The “Remote Interactive Surgery Platform” (RISP) is an augmented reality (AR)-based platform for surgical telementoring. It builds upon recent advances of mixed reality head-mounted displays (MR-HMD) and associated immersive visualization technologies to assist the surgeon during an operation. It enables an interactive, real-time collaboration with a remote consultant by sharing the operating surgeon’s field of view through the Microsoft (MS) HoloLens2 (HL2). Development of the RISP started during the Medical Augmented Reality Summer School 2021 and is currently still ongoing. It currently includes features such as three-dimensional annotations, bidirectional voice communication and interactive windows to display radiographs within the sterile field. This manuscript provides an overview of the RISP and preliminary results regarding its annotation accuracy and user experience measured with ten participants. Full article

Adopting the model of risk information seeking and processing (RISP) as a theoretical framework, the objective of this study was to investigate the factors that prompted individuals’ information-seeking and -processing behaviors during the COVID-19 pandemic in Taiwan. There were two unique aspects in this study: one was to adopt specific emotions to investigate the impact of negative emotions, and the other was to examine the effect of informational subjective norms (ISNs) on information-seeking and -processing behavior. An online survey was conducted by a professional polling company, and a stratified random sampling method was employed, using gender, age, education, personal income, and residential areas as strata to select participants. This study obtained 1100 valid questionnaires. The results showed that (1) risk perception did not exert any significant impacts on respondents’ perceived information insufficiency; (2) risk perception exerted a powerful impact on respondents’ ISNs, which, in turn, positively affected their information insufficiency; (3) the respondents who experienced fear were found to have a high probability of using a systematic-processing mode, while the respondents who experienced anger were more likely to adopt a heuristic-processing mode to process information; and (4) the use of a systematic-processing mode was positively associated, while the use of a heuristic-processing mode was negatively associated, with information-seeking behavior. Full article

Sleep paralysis (SP) is a hypnagogic or hypnopompic state associated with the inability to move while conscious. Recurrent isolated sleep paralysis (RISP) is a type of REM parasomnia. Individuals experiencing anxiety disorders, PTSD, exposure to chronic stress, or shift work are at risk of developing this sleep disorder. This study aimed to assess: (1) the prevalence, frequency, and symptomatology of SP, and (2) the impact of the severity of anxiety symptoms, perceived stress, and lifestyle mode variables on the frequency and severity of SP in four professional groups at high risk of SP (n = 844): nurses and midwives (n = 172), policemen (n = 174), teachers (n = 107), and a group of mixed professions—“other professions” (n = 391). The study used a battery of online questionnaires: the Sociodemographic and Health Status Questionnaire, the SP-EPQ, the PCL -5, the STAI-T, the PSWQ and the PSS-10. The prevalence of SP was the lowest among policemen (15.5%) and the highest in the group of “other professions” (39.4%). The association of SP with symptoms of PTSD and anxiety was confirmed in the group of nurses and “other professions”. Among other factors modulating the incidence and severity of SP were: age, BMI, smoking, alcohol consumption, sleep duration, and perceived stress. This study indicates that there exist links between SP and psychological and lifestyle factors, suggesting a complex etiology for this sleep disorder. Due to the high prevalence of SP in the studied groups of occupations, further research is necessary to develop preventive and therapeutic methods for SP. Full article

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, which is often due to pulmonary hypertension (PH). The underlying molecular mechanisms are poorly understood, and current medications are neither specific nor always effective. In this review, we highlight the recent findings on the roles of altered mitochondrial bioenergetics in PH in COPD. We also discuss the central role of mitochondrial reactive oxygen species (ROS) generation mediated by Rieske iron–sulfur protein (RISP) and review the contributions of RISP-dependent DNA damage and NF-κB-associated inflammatory signaling. Finally, the potential importance of mitochondrial RISP and its associated molecules as novel therapeutic targets for PH in COPD are meticulously discussed. Full article

Mitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca²⁺ signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules leads to the development of pulmonary hypertension (PH), atherosclerosis, and other vascular diseases. Features of PH include vasoconstriction and pulmonary artery (PA) remodeling, which can result from abnormal proliferation, apoptosis, and migration of PA smooth muscle cells (PASMCs). These responses are mediated by increased Rieske iron–sulfur protein (RISP)-dependent mitochondrial ROS production and increased mitochondrial Ca²⁺ levels. Mitochondrial ROS and Ca²⁺ can both synergistically activate nuclear factor κB (NF-κB) to trigger inflammatory responses leading to PH, right ventricular failure, and death. Evidence suggests that increased mitochondrial ROS and Ca²⁺ signaling leads to abnormal synthesis of ketones, which play a critical role in the development of PH. In this review, we discuss some of the recent findings on the important interactive role and molecular mechanisms of mitochondrial ROS and Ca²⁺ in the development and progression of PH. We also address the contributions of NF-κB-dependent inflammatory responses and ketone-mediated oxidative stress due to abnormal regulation of mitochondrial ROS and Ca²⁺ signaling in PH. Full article

In 2011, the Chinese government launched a disaster mitigation and preparedness program called the Resettlement of South Shaanxi (RSS). Due to the wide geographical scope and complex interests, the possibility of conflicts was increased during and after resettlement. Efficient risk communication improves the supply of information about risks and meets the risk-related information needs of individuals. Using the risk information seeking and processing (RISP) model, this research applied a structural equation model and survey with a structured questionnaire to study ways to improve risk communication in disaster resettlement. A total of 616 valid questionnaires were provided by study respondents in resettlement sites in Ziyang County, Ankang City, Shaanxi Province. The results indicated the following: (1) the public’s information seeking behavior relies more on village committees and village officials than other channels. Emerging information channels, such as Weibo and WeChat (social media applications in China), do not play leading roles in disseminating risk information. (2) There are differences between the information channels used by residents and the channels that residents believe the most. (3) Relevant channel beliefs, information sufficiency, perceived hazard characteristics, and self-efficacy directly influence risk information seeking behavior. However, the capacity to gather information has non-significant direct influences on information seeking behavior. (4) Perceived hazard characteristics and self-efficacy drive risk information seeking behavior in both direct and indirect ways through information sufficiency. Full article

Murine fibroblasts deficient in mitochondria respiratory complexes III (CIII) and IV (CIV) produced by either the ablation of Uqcrfs1 (encoding for Rieske iron sulfur protein, RISP) or Cox10 (encoding for protoheme IX farnesyltransferase, COX10) genes, respectively, showed a pleiotropic effect in complex I (CI). Exposure to 1–5% oxygen increased the levels of CI in both RISP and COX10 KO fibroblasts. De novo assembly of the respiratory complexes occurred at a faster rate and to higher levels in 1% oxygen compared to normoxia in both RISP and COX10 KO fibroblasts. Hypoxia did not affect the levels of assembly of CIII in the COX10 KO fibroblasts nor abrogated the genetic defect impairing CIV assembly. Mitochondrial signaling involving reactive oxygen species (ROS) has been implicated as necessary for HIF-1α stabilization in hypoxia. We did not observe increased ROS production in hypoxia. Exposure to low oxygen levels stabilized HIF-1α and increased CI levels in RISP and COX10 KO fibroblasts. Knockdown of HIF-1α during hypoxic conditions abrogated the beneficial effect of hypoxia on the stability/assembly of CI. These findings demonstrate that oxygen and HIF-1α regulate the assembly of respiratory complexes. Full article

High sea ice production (SIP) generates high-salinity water, thus, influencing the global thermohaline circulation. Estimation from passive microwave data and heat flux models have indicated that the Ross Ice Shelf polynya (RISP) may be the highest SIP region in the Southern Oceans. However, the coarse spatial resolution of passive microwave data limited the accuracy of these estimates. The Sentinel-1 Synthetic Aperture Radar dataset with high spatial and temporal resolution provides an unprecedented opportunity to more accurately distinguish both polynya area/extent and occurrence. In this study, the SIPs of RISP and McMurdo Sound polynya (MSP) from 1 March–30 November 2017 and 2018 are calculated based on Sentinel-1 SAR data (for area/extent) and AMSR2 data (for ice thickness). The results show that the wind-driven polynyas in these two years occurred from the middle of March to the middle of November, and the occurrence frequency in 2017 was 90, less than 114 in 2018. However, the annual mean cumulative SIP area and volume in 2017 were similar to (or slightly larger than) those in 2018. The average annual cumulative polynya area and ice volume of these two years were 1,040,213 km² and 184 km³ for the RSIP, and 90,505 km² and 16 km³ for the MSP, respectively. This annual cumulative SIP (volume) is only 1/3–2/3 of those obtained using the previous methods, implying that ice production in the Ross Sea might have been significantly overestimated in the past and deserves further investigations. Full article

This paper presents interdisciplinary research focusing on the municipality of Braunsbach in the German state of Baden-Württemberg, where, in May 2016, a flash flood attracted media attention and scientific scrutiny that highlighted the fact that certain aspects of flood risk were overlooked during earlier assessments conducted by the municipality, such as sediment transport. Using a network analysis and a focus-group discussion, we traced the flow of knowledge through the reported interactions between governmental, private, and academic actors in the two and a half years after the event. From our analysis, we learned that the extreme event attracted scientists to the formal and informal assessment of the hazard and the associated damages. Most importantly, we found conditions under which scientific scrutiny is not detached from but becomes integrated in a governance setting. While it is through this process that sediment transport has become an integral part of flood-risk management in Baden-Württemberg, with an evident impact on the measures already implemented, the impact of morphological changes, as well as large wood and sediment transport, have not been factored into the risk assessment as of yet. These variations in scientific impact on the assessment can be explained by decision biases that can occur when decision makers are under pressure to tackle vulnerabilities and thus lack the time to deliberate in a way that uses all the available evidence. Full article

Consumers’ food safety risk information-seeking behavior plays a vital role in improving their food quality and safety awareness and preventing food safety risks. Based on the Risk Information Seeking and Processing Model (RISP), this paper empirically analyzes the food safety risk information-seeking intention of consumers in WeChat and influencing factors under the impact of food safety incidents. We use data from 774 WeChat users and apply the Structural Equation Modeling (SEM) approach. We also conduct multigroup analysis with demographic characteristics as moderating variables. The results demonstrated that: (1) Risk perception (p ≤ 0.01) has direct significant positive effects on consumers’ intention to seek food safety information. Besides, higher risk perception (p ≤ 0.01) regarding food safety risks will make people feel more anxious and threatened, and then expand the gap between the information they need and the relevant knowledge they actually have (p ≤ 0.1), which will further stimulate them to seek more information (p ≤ 0.05). (2) Informational subjective norms (p ≤ 0.01) can not only directly affect consumers’ information-seeking about food safety, but also indirectly affect consumers’ intention through information insufficiency (p ≤ 0.01). (3) The more consumers trust the relevant channels (p ≤ 0.01), the stronger their intention to search for food safety risk information. Moreover, the multiple-group analysis also shows that the effects of consumers’ gender, age, educational background, and average monthly earnings are different among different groups. Furthermore, implications are put forward for food safety risk communication efforts in China. Full article