RESUMEN
Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder affecting millions globally. It encompasses both motor and non-motor symptoms, with a notable impact on patients' quality of life. Electroencephalogram (EEG) is a non-invasive tool that is increasingly utilized to investigate neural mechanisms in PD, identify early diagnostic markers, and assess therapeutic responses. Methods: The data were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database, focusing on publications related to EEG research in PD from 2004 to 2023. A comprehensive bibliometric analysis was conducted using CiteSpace and VOSviewer software. The analysis began with an evaluation of the selected publications, identifying leading countries, institutions, authors, and journals, as well as co-cited references, to summarize the current state of EEG research in PD. Keywords are employed to identify research topics that are currently of interest in this field through the analysis of high-frequency keyword co-occurrence and cluster analysis. Finally, burst keywords were identified to uncover emerging trends and research frontiers in the field, highlighting shifts in interest and identifying future research directions. Results: A total of 1,559 publications on EEG research in PD were identified. The United States, Germany, and England have made notable contributions to the field. The University of London is the leading institution in terms of publication output, with the University of California closely following. The most prolific authors are Brown P, Fuhr P, and Stam C In terms of total citations and per-article citations, Stam C has the highest number of citations, while Brown P has the highest H-index. In terms of the total number of publications, Clinical Neurophysiology is the leading journal, while Brain is the most highly cited. The most frequently cited articles pertain to software toolboxes for EEG analysis, neural oscillations, and PD pathophysiology. Through analyzing the keywords, four research hotspots were identified: research on the neural oscillations and connectivity, research on the innovations in EEG Analysis, impact of therapies on EEG, and research on cognitive and emotional assessments. Conclusion: This bibliometric analysis demonstrates a growing global interest in EEG research in PD. The investigation of neural oscillations and connectivity remains a primary focus of research. The application of machine learning, deep learning, and task analysis techniques offers promising avenues for future research in EEG and PD, suggesting the potential for advancements in this field. This study offers valuable insights into the major research trends, influential contributors, and evolving themes in this field, providing a roadmap for future exploration.
RESUMEN
Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1ß levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.
What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at −80°C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP.
Asunto(s)
Criopreservación , Plasma Rico en Plaquetas , Cicatrización de Heridas , Plasma Rico en Plaquetas/metabolismo , Humanos , Criopreservación/métodos , Proliferación Celular , Movimiento Celular , Fibroblastos/metabolismoRESUMEN
In brief: The impact of HVJ-E employed in mitochondrial replacement techniques (MRTs) on embryonic development remains uncertain. This study has exhibited the influence of HVJ-E utilized in MRTs on embryonic development and has devised a novel HVJ-E-induced fusion approach to curtail the amount of HVJ-E employed in MRTs. Abstract: Mitochondrial replacement techniques (MRTs) provide a viable option for women carrying pathogenic mitochondrial DNA (mtDNA) variants to conceive disease-free offspring with a genetic connection. In comparison to electrofusion, HVJ-E-induced fusion has been identified as the most promising approach for clinical translation of MRTs due to its absence of electrical interference. However, despite confirmation of the absence of RNA activity in HVJ-E, a reduction in blastocyst quality has been observed in various MRTs studies utilizing the HVJ-E-induced fusion scheme. Recent investigations have revealed a dose-dependent elevation of reactive oxygen species (ROS) levels in various cancer cells incubated with HVJ-E. However, the impact of HVJ-E as a sole determinant on embryonic development in MRTs remains unverified. This investigation establishes that the augmented concentration of HVJ-E utilized in the conventional HVJ-E fusion protocol is an autonomous variable that influences embryonic development in MRTs. This effect may be attributed to amplified DNA damage resulting from heightened levels of ROS in reconstructed embryos. To mitigate the presence of HVJ-E in reconstructed zygotes while maintaining optimal fusion efficiency in MRTs, a novel HVJ-E-induced fusion approach was devised, namely, press-assisted fusion. This technique offers potential advantages in reducing detrimental factors that impede embryo development in MRTs.
RESUMEN
Guided bone regeneration gathers significant interest in the realm of bone tissue engineering; however, the interplay between membrane thickness and permeability continues to pose a challenge that can be addressed by the water-collecting mechanism of spider silk, where water droplets efficiently move from smooth filaments to rough conical nodules. Inspired by the natural design of spider silk, an innovative silk fibroin membrane is developed featuring directional fluid transportation via harmoniously integrating a smooth, dense layer with a rough, loose layer; conical microchannels are engineered in the smooth and compact layer. Consequently, double-layered membranes with cone-shaped microporous passageways (CSMP-DSF membrane) are designed for in situ bone repair. Through extensive in vitro testing, it is noted that the CSMP-DSF membrane guides liquid flow from the compact layer's surface to the loose layer, enabling rapid diffusion. Remarkably, the CSMP-DSF membrane demonstrates superior mechanical properties and resistance to bacterial adhesion. When applied in vivo, the CSMP-DSF membrane achieves results on par with the commercial Bio-Gide collagen membranes. This innovative integration of a cross-thickness wetting gradient structure offers a novel solution, harmonizing the often-conflicting requirements of material transport, mechanical strength, and barrier effectiveness, while also addressing issues related to tissue engineering scaffold perfusion.
Asunto(s)
Fibroínas , Seda , Seda/química , Fibroínas/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Permeabilidad , AguaRESUMEN
This study aims to increase our understanding regarding the use of rituals as the prevention and management strategies for the external consequences resulting from sexual harassment in the workplace during the COVID-19 crisis. We conducted a qualitative study through semi-structured interviews (N = 30) with employees in five hospitals and analyzed the data with a grounded theory approach. The results indicated that rituals could positively influence reputation repair and legitimacy construction. Moreover, interaction patterns between organizations and stakeholders mediated the relationships between rituals and prevention and management results heterogeneously. Managerial perceptions, ritual factors and cultural factors influence rituals to achieve more effective results in terms of prevention and management. By presenting a process model illustrating rituals' unique capacity to prevent and manage the threats of workplace sexual harassment, we contribute to the literature on workplace sexual harassment and rituals in three ways. First, we extend the workplace sexual harassment literature by exploring prevention and management strategies for external consequence/reputation threats. Second, we present a process model to illustrate how rituals impact the results of sexual harassment prevention and management strategies. Third, we illustrate the mediating and moderating factors and their contributions toward developing better rituals that function in such prevention and management strategies.
RESUMEN
Mutations in mitochondrial DNA (mtDNA) contribute to a variety of serious multi-organ human diseases, which are strictly inherited from the maternal germline. However, there is currently no curative treatment. Attention has been focused on preventing the transmission of mitochondrial diseases through mitochondrial replacement (MR) therapy, but levels of mutant mtDNA can often unexpectedly undergo significant changes known as mitochondrial genetic drift. Here, we proposed a novel strategy to perform spindle-chromosomal complex transfer (SCCT) with maximal residue removal (MRR) in metaphase II (MII) oocytes, thus hopefully eliminated the transmission of mtDNA diseases. With the MRR procedure, we initially investigated the proportions of mtDNA copy numbers in isolated karyoplasts to those of individual oocytes. Spindle-chromosomal morphology and copy number variation (CNV) analysis also confirmed the safety of this method. Then, we reconstructed oocytes by MRR-SCCT, which well developed to blastocysts with minimal mtDNA residue and normal chromosomal copy numbers. Meanwhile, we optimized the manipulation order between intracytoplasmic sperm injection (ICSI) and SCC transfer and concluded that ICSI-then-transfer was conducive to avoid premature activation of reconstructed oocytes in favor of normal fertilization. Offspring of mice generated by embryos transplantation in vivo and embryonic stem cells derivation further presented evidences for competitive development competence and stable mtDNA carryover without genetic drift. Importantly, we also successfully accomplished SCCT in human MII oocytes resulting in tiny mtDNA residue and excellent embryo development through MRR manipulation. Taken together, our preclinical mouse and human models of the MRR-SCCT strategy not only demonstrated efficient residue removal but also high compatibility with normal embryo development, thus could potentially be served as a feasible clinical treatment to prevent the transmission of inherited mtDNA diseases.
Asunto(s)
Variaciones en el Número de Copia de ADN , Enfermedades Mitocondriales , Masculino , Humanos , Animales , Ratones , Variaciones en el Número de Copia de ADN/genética , Semen , Mitocondrias/genética , ADN Mitocondrial/genética , ADN Mitocondrial/análisis , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/prevención & control , OocitosRESUMEN
The second polar body (PB2) transfer in assisted reproductive technology is regarded as the most promising mitochondrial replacement scheme for preventing the mitochondrial disease inheritance owing to its less mitochondrial carryover and stronger operability. However, the mitochondrial carryover was still detectable in the reconstructed oocyte in conventional second polar body transfer scheme. Moreover, the delayed operating time would increase the second polar body DNA damage. In this study, we established a spindle-protrusion-retained second polar body separation technique, which allowed us to perform earlier second polar body transfer to avoid DNA damage accumulation. We could also locate the fusion site after the transfer through the spindle protrusion. Then, we further eliminated the mitochondrial carryover in the reconstructed oocytes through a physically based residue removal method. The results showed that our scheme could produce a nearly normal proportion of normal-karyotype blastocysts with further reduced mitochondrial carryover, both in mice and humans. Additionally, we also obtained mouse embryonic stem cells and healthy live-born mice with almost undetectable mitochondrial carryover. These findings indicate that our improvement in the second polar body transfer is conducive to the development and further mitochondria carryover elimination of reconstructed embryos, which provides a valuable choice for future clinical applications of mitochondrial replacement.
RESUMEN
BACKGROUND: Patients with anomic aphasia experience difficulties in narrative processing. General discourse measures are time consuming and require necessary skills. Core lexicon analysis has been proposed as an effort-saving approach but has not been developed in Mandarin discourse. AIMS: This exploratory study was aimed (1) to apply core lexicon analysis in Mandarin patients with anomic aphasia at the discourse level and (2) to verify the problems with core words among people with anomic aphasia. METHODS & PROCEDURE: The core nouns and verbs were extracted from narrative language samples from 88 healthy participants. The production of core words for 12 anomic aphasia and 12 age- and education-matched controls were then calculated and compared. The correlation between the percentages and the Aphasia Quotients of the revised Western Aphasia Battery was analyzed as well. OUTCOMES & RESULTS: The core nouns and verbs were successfully extracted. Patients with anomic aphasia produced fewer core words than healthy people, and the percentages differed significantly in different tasks as well as word classes. There was no correlation between the core lexicon use and the severity of aphasia in patients with anomic aphasia. CONCLUSIONS & IMPLICATIONS: Core lexicon analysis may potentially serve as a clinician-friendly manner of quantifying core words produced at the discourse level in Mandarin patients with anomic aphasia. WHAT THIS PAPER ADDS: What is already known on the subject Discourse analyses in aphasia assessment and treatment have increasingly garnered attention. Core lexicon analysis based on English AphasiaBank has been reported in recent years. It is correlated with microlinguistic and macrolinguistic measures in aphasia narratives. Nevertheless, the application based on Mandarin AphasiaBank is still under development in healthy individuals and patients with anomic aphasia. What this paper adds to existing knowledge A Mandarin core lexicon set was developed for different tasks. The feasibility of core lexicon analysis to evaluate the corpus of patients with anomic aphasia was preliminarily discussed and the speech performance of patients and healthy people was then compared to provide a reference for the evaluation and treatment of clinical aphasia corpus. What are the potential or actual clinical implications of this work? The purpose of this exploratory study was to consider the potential use of core lexicon analysis to evaluate core word production in narrative discourse. Moreover, normative and aphasia data were provided for comparison to develop clinical use for Mandarin patients with anomic aphasia.
Asunto(s)
Anomia , Afasia , Humanos , Anomia/diagnóstico , Afasia/diagnóstico , Afasia/terapia , Lenguaje , Habla , Pruebas del LenguajeRESUMEN
The gut microbiota, as a 'new organ' of humans, has been identified to affect many biological processes, including immunity, inflammatory response, gut-brain neural circuits, and energy metabolism. Profound dysbiosis of the gut microbiome could change the metabolic pattern, aggravate systemic inflammation and insulin resistance, and exacerbate metabolic disturbance and the progression of type 2 diabetes (T2D). The aim of this review is to focus on the potential roles and functional mechanisms of gut microbiota in the antidiabetic therapy. In general, antidiabetic drugs (α-glucosidase inhibitor, biguanides, incretin-based agents, and traditional Chinese medicine) induce the alteration of microbial diversity and composition, and the levels of bacterial component and derived metabolites, such as lipopolysaccharide (LPS), short chain fatty acids (SCFAs), bile acids and indoles. The altered microbial metabolites are involved in the regulation of gut barrier, inflammation response, insulin resistance and glucose homeostasis. Furthermore, we summarize the new strategies for antidiabetic treatment based on microbial regulation, such as pro/prebiotics administration and fecal microbiota transplantation, and discuss the need for more basic and clinical researches to evaluate the feasibility and efficacy of the new therapies for diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Microbiota , Humanos , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , InflamaciónRESUMEN
Mechanical forces are the indispensable constituent of environmental cues, such as gravity, barometric pressure, vibration, and contact with bodies, which are involved in pattern and organogenesis, providing mechanical input to tissues and determining the ultimate fate of cells. Extracellular matrix (ECM) stiffness, the slow elastic force, carries the external physical force load onto the cell or outputs the internal force exerted by the cell and its neighbors into the environment. Accumulating evidence illustrates the pivotal role of ECM stiffness in the regulation of organogenesis, maintenance of tissue homeostasis, and the development of multiple diseases, which is largely fulfilled through its systematical impact on cellular metabolism. This review summarizes the establishment and regulation of ECM stiffness, the mechanisms underlying how ECM stiffness is sensed by cells and signals to modulate diverse cell metabolic pathways, and the physiological and pathological significance of the ECM stiffness-cell metabolism axis.
Asunto(s)
Matriz Extracelular , Transducción de Señal , Humanos , Matriz Extracelular/metabolismo , Mecanotransducción Celular/fisiologíaRESUMEN
Despite optimal medical therapy, many patients with diabetic kidney disease (DKD) progress to end-stage renal disease. The identification of new biomarkers and drug targets for DKD is required for the development of more effective therapies. The apoptosis of renal tubular epithelial cells is a key feature of the pathogenicity associated with DKD. SIK2, a salt-inducible kinase, regulates important biological processes, such as energy metabolism, cell cycle progression and cellular apoptosis. In our current study, a notable decrease in the expression of SIK2 was detected in the renal tubules of DKD patients and murine models. Functional experiments demonstrated that deficiency or inactivity of SIK2 aggravates tubular injury and interstitial fibrosis in diabetic mice. Based on transcriptome sequencing, molecular mechanism exploration revealed that SIK2 overexpression reduces endoplasmic reticulum (ER) stress-mediated tubular epithelial apoptosis by inhibiting the histone acetyltransferase activity of p300 to activate HSF1/Hsp70. Furthermore, the specific restoration of SIK2 in tubules blunts tubular and interstitial impairments in diabetic and vancomycin-induced kidney disease mice. Together, these findings indicate that SIK2 protects against renal tubular injury and the progression of kidney disease, and make a compelling case for targeting SIK2 for therapy in DKD.
Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Fallo Renal Crónico , Animales , Ratones , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Riñón/metabolismo , Fallo Renal Crónico/metabolismo , Túbulos Renales/metabolismo , HumanosRESUMEN
Optical feedback exists in most laser configurations and strongly affects laser performances depending on the feedback strength, length, and phase. In this paper, we investigate the frequency comb behaviour of a semiconductor quantum cascade laser emitting around 4.2 THz with external optical feedback. A periodic evolution of the laser inter-mode beatnote from single-line to multiple-line structures is experimentally observed with a minor change of optical feedback length (phase) on the wavelength scale. The comb stability of the laser with feedback is also measured and compared with the same laser without feedback. Furthermore, our simulations reveal that the dynamical oscillations invoked by optical feedback are responsible for the measured multiple-line beatnotes. It is found that the characteristic feedback period is determined by the half wavelength of the laser, while the comb operation is maintained at most feedback length positions. Therefore, terahertz quantum cascade laser combs are robust against the minor position vibration of the feedback mirror in practice, owing to the much smaller feedback phase change than that of common near-infrared laser diodes.
RESUMEN
Radiation-induced oral mucositis is the most common complication for patients who receive head/neck radiotherapy. Nicotinamide adenine dinucleotide (NAD+) is vital for DNA damage repair under ionizing radiation, through functioning as either the substrate for protein poly(ADP-ribosyl)ation at DNA break sites or the cofactor for multiple DNA repair-related enzymes, which therefore can result in a significant consumption of cellular NAD+ during DNA repair. Mammalian cells produce NAD+ mainly by recycling nicotinamide via the salvage pathway, in which the rate-limiting step is governed by nicotinamide phosphoribosyltransferase (NAMPT). However, whether NAMPT is co-opted under ionizing radiation to timely fine-tune NAD+ homeostasis remains elusive. Here we show that ionizing radiation evokes NAMPT activation within 30 min without apparent changes in its protein expression. AMPK rapidly phosphorylates NAMPT at S314 under ionizing radiation, which reinforces the enzymatic activity of NAMPT by increasing NAMPT binding with its substrate phosphoribosyl pyrophosphate (PRPP). AMPK-mediated NAMPT S314 phosphorylation substantially restores NAD+ level in the irradiated cells and facilitates DNA repair and cell viability. Our findings demonstrate a new post-translational modification-based signalling route, by which cells can rapidly orchestrate NAD+ metabolism to support DNA repair, thereby highlighting NAMPT as a potential target for the prevention of ionizing radiation-induced injuries.
Asunto(s)
Proteínas Quinasas Activadas por AMP , NAD , Nicotinamida Fosforribosiltransferasa , Radiación Ionizante , Proteínas Quinasas Activadas por AMP/metabolismo , Citocinas/metabolismo , Homeostasis , Humanos , NAD/metabolismo , Niacinamida , Nicotinamida Fosforribosiltransferasa/genética , Nicotinamida Fosforribosiltransferasa/metabolismo , Fosforribosil PirofosfatoRESUMEN
Background: In recent years, temporal leadership has gradually attracted academic attention. Purpose: This paper discussed the impact of temporal leadership on team innovation performance. Methodology: Through the sample analysis of 385 team members in 98 teams. The measurements of temporal leadership, team innovation performance, transactive memory system, and team reflection were used to measure the relationships between temporal leadership, transactive memory systems and team innovation performance. Findings/Results: It is found that temporal leadership has a positive impact on team innovation performance, which is transmitted through the credibility dimension and coordination dimension of transactive memory systems. Positive team reflection regulates the relationship between temporal leadership and transactive memory systems. Value: This paper reveals the specific impact mechanism of temporal leadership on team innovation performance and provides a new perspective on how to improve team innovation performance in limited time resources.
RESUMEN
Higher contact resistance not only increases power consumption and temperature rise but also causes undesirable interconnectivity between electrode materials, which further influences the electrical lifespan and reliability of switching devices. However, relevant studies on the relationship between contact resistance and load force, and on the reduction of contact resistance by controlling the micro-structure of rough surfaces, especially for electrode materials with larger Sq (root mean square) values, are very limited. In this study, the contact resistance calculation method, based on classical Holm theory in combination with the elastic and plastic deformation, was reviewed. Then, typical curves of measured contact resistance and load force were analyzed and compared with the calculation results for smooth surfaces. Furthermore, experimental results for electrodes with bright and matt surfaces were compared. It was found that the average contact resistance of samples with matt surfaces was 0.162 mΩ for a load force of 5 N, which decreased by 18.52% compared to that of the bright surface. The standard deviation of the contact resistance greatly decreased to 0.008 mΩ for samples with matt surfaces, which indicated that the matt electrode surface could effectively produce low and stable contact resistance. In addition, the influences of the numbers and sizes of contact a-spots on the relationship between contact resistance and load force were investigated. It was found that denser asperities with smaller curvature radii for the matt surface were beneficial for lower contact resistance, even for the electrode material with larger Sq values. Finally, an empirical model of the contact resistance with error bands based on the experimental results was established and verified.
RESUMEN
OBJECTIVE: To investigate the correlation between the left arcuate fasciculus (AF) segments and acute/subacute post-stroke aphasia (PSA). METHODS: Twenty-six patients underwent language assessment and MRI scanning. The integrity of the AF based on a three-segment model was evaluated using diffusion tensor imaging. All patients were classified into three groups according to the reconstruction of the left AF: completely reconstructed (group A, 8 cases), non-reconstructed (group B, 6 cases), and partially reconstructed (group C, 12 cases). The correlations and intergroup differences in language performance and diffusion indices were comprehensively estimated. RESULTS: A correlation analyses showed that the lesion load of the language areas and diffusion indices on the left AF posterior and long segments was significantly related to some language subsets, respectively. When controlled lesion load was variable, significant correlations between diffusion indices on the posterior and long segments and comprehension, repetition, naming, and aphasia quotient were retained. Multiple comparison tests revealed intergroup differences in diffusion indices on the left AF posterior and long segments, as well as these language subsets. No significant correlation was found between the anterior segment and language performance. CONCLUSIONS: The integrity of the left AF segments, particularly the posterior segment, is crucial for the residual comprehension and repetition abilities in individuals with acute/subacute PSA, and lesion load in cortical language areas is an important factor that should be taken into account when illustrating the contributions of damage to special fiber tracts to language impairments.
RESUMEN
Hypoxia is a physiological stress that frequently occurs in solid tissues. Autophagy, a ubiquitous degradation/recycling system in eukaryotic cells, renders cells tolerant to multiple stressors. However, the mechanisms underlying autophagy initiation upon hypoxia remains unclear. Here we show that protein arginine methyltransferase 5 (PRMT5) catalyzes symmetrical dimethylation of the autophagy initiation protein ULK1 at arginine 170 (R170me2s), a modification removed by lysine demethylase 5C (KDM5C). Despite unchanged PRMT5-mediated methylation, low oxygen levels decrease KDM5C activity and cause accumulation of ULK1 R170me2s. Dimethylation of ULK1 promotes autophosphorylation at T180, a prerequisite for ULK1 activation, subsequently causing phosphorylation of Atg13 and Beclin 1, autophagosome formation, mitochondrial clearance and reduced oxygen consumption. Further, expression of a ULK1 R170K mutant impaired cell proliferation under hypoxia. This study identifies an oxygen-sensitive methylation of ULK1 with an important role in hypoxic stress adaptation by promoting autophagy induction.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Oxígeno , Autofagia/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Proteínas Relacionadas con la Autofagia/metabolismo , Humanos , Hipoxia/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Metilación , Fosforilación , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismoRESUMEN
Exposure to radiation causes DNA damage; hence, continuous surveillance and timely DNA repair are important for genome stability. Epigenetic modifications alter the chromatin architecture, thereby affecting the efficiency of DNA repair. However, how epigenetic modifiers coordinate with the DNA repair machinery to modulate cellular radiosensitivity is relatively unknown. Here, we report that loss of the demethylase ribosomal oxygenase 1 (RIOX1) restores cell proliferation and reduces cell death after exposure to ionizing radiation. Furthermore, RIOX1 depletion enhances homologous recombination (HR) repair but not nonhomologous end-joining (NHEJ) repair in irradiated bone marrow cells and oral mucosal epithelial cells. Mechanistic study demonstrates that RIOX1 removes monomethylation at K491 of cyclic GMP-AMP synthase (cGAS) to release cGAS from its interaction with the methyl-lysine reader protein SAGA complex-associated factor 29 (SGF29), which subsequently enables cGAS to interact with poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase 1 (PARP1) at DNA break sites, thereby blocking PARP1-mediated recruitment of Timeless. High expression of RIOX1 maintains cGAS K491me at a low level, which impedes HR repair and reduces cellular tolerance to ionizing radiation. This study highlights a novel RIOX1-dependent mechanism involved in the non-immune function of cGAS that is essential for the regulation of ionizing radiation-elicited HR repair.
RESUMEN
In the terahertz frequency range, the quantum cascade laser (QCL) is a suitable platform for the frequency comb and dual-comb operation. Improved comb performances have been always much in demand. In this work, by employing a symmetric thermal dissipation scheme, we report an improved frequency comb and dual-comb operation of terahertz QCLs. Two configurations of cold fingers, i.e., type A and B with asymmetric and symmetric thermal dissipation schemes, respectively, are investigated here. A finite-element thermal analysis is carried out to study the parametric effects on the thermal management of the terahertz QCL. The modeling reveals that the symmetric thermal dissipation (type B) results in a more uniform thermal conduction and lower maximum temperature in the active region of the laser, compared to the traditional asymmetric thermal dissipation scheme (type A). To verify the simulation, experiments are further performed by measuring laser performance and comb characteristics of terahertz QCLs emitting around 4.2 THz mounted on type A and type B cold fingers. The experimental results show that the symmetric thermal dissipation approach (type B) is effective for improving the comb and dual-comb operation of terahertz QCLs, which can be further widely adopted for spectroscopy, imaging, and near-field applications.
RESUMEN
Epigenetic modification is a fundamental biological process in living organisms, which has significant impact on health and behavior. Metabolism refers to a set of life-sustaining chemical reactions, including the uptake of nutrients, the subsequent conversion of nutrients into energy or building blocks for organism growth, and finally the clearance of redundant or toxic substances. It is well established that epigenetic modifications govern the metabolic profile of a cell by modulating the expression of metabolic enzymes. Strikingly, almost all the epigenetic modifications require substrates produced by cellular metabolism, and a large proportion of metabolic enzymes can transfer into nucleus to locally produce substrates for epigenetic modification, thereby providing an alternative link between metabolism, epigenetic modification and gene expression. Here, we summarize the recent literature pertinent to metabolic enzymes functioning as epigenetic modulators in the regulation of chromatin architecture and gene expression.