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1.
EMBO J ; 42(24): e114054, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37933600

RESUMO

Cristae are high-curvature structures in the inner mitochondrial membrane (IMM) that are crucial for ATP production. While cristae-shaping proteins have been defined, analogous lipid-based mechanisms have yet to be elucidated. Here, we combine experimental lipidome dissection with multi-scale modeling to investigate how lipid interactions dictate IMM morphology and ATP generation. When modulating phospholipid (PL) saturation in engineered yeast strains, we observed a surprisingly abrupt breakpoint in IMM topology driven by a continuous loss of ATP synthase organization at cristae ridges. We found that cardiolipin (CL) specifically buffers the inner mitochondrial membrane against curvature loss, an effect that is independent of ATP synthase dimerization. To explain this interaction, we developed a continuum model for cristae tubule formation that integrates both lipid and protein-mediated curvatures. This model highlighted a snapthrough instability, which drives IMM collapse upon small changes in membrane properties. We also showed that cardiolipin is essential in low-oxygen conditions that promote PL saturation. These results demonstrate that the mechanical function of cardiolipin is dependent on the surrounding lipid and protein components of the IMM.


Assuntos
Cardiolipinas , Lipidômica , Cardiolipinas/metabolismo , Membranas Mitocondriais/metabolismo , Fosfolipídeos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Trifosfato de Adenosina/metabolismo
2.
Nature ; 596(7870): 68-73, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34349290

RESUMO

Key to our understanding of how electrons behave in crystalline solids is the band structure that connects the energy of electron waves to their wavenumber. Even in phases of matter with only short-range order (liquid or amorphous solid), the coherent part of electron waves still has a band structure. Theoretical models for the band structure of liquid metals were formulated more than five decades ago1-15, but, so far, band-structure renormalization and the pseudogap induced by resonance scattering have remained unobserved. Here we report the observation of the unusual band structure at the interface of a crystalline insulator (black phosphorus) and disordered dopants (alkali metals). We find that a conventional parabolic band structure of free electrons bends back towards zero wavenumber with a pseudogap of 30-240 millielectronvolts from the Fermi level. This is wavenumber renormalization caused by resonance scattering, leading to the formation of quasi-bound states in the scattering potential of alkali-metal ions. The depth of this potential tuned by different kinds of disordered alkali metal (sodium, potassium, rubidium and caesium) allows the classification of the pseudogap of p-wave and d-wave resonance. Our results may provide a clue to the puzzling spectrum of various crystalline insulators doped by disordered dopants16-20, such as the waterfall dispersion observed in copper oxides.

3.
Mol Cell ; 69(3): 398-411.e6, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29395062

RESUMO

The inflammatory response mediated by nuclear factor κB (NF-κB) signaling is essential for host defense against pathogens. Although the regulatory mechanism of NF-κB signaling has been well studied, the molecular basis for epigenetic regulation of the inflammatory response is poorly understood. Here we identify a new signaling axis of PKCα-LSD1-NF-κB, which is critical for activation and amplification of the inflammatory response. In response to excessive inflammatory stimuli, PKCα translocates to the nucleus and phosphorylates LSD1. LSD1 phosphorylation is required for p65 binding and facilitates p65 demethylation, leading to enhanced stability. In vivo genetic analysis using Lsd1SA/SA mice with ablation of LSD1 phosphorylation and chemical approaches in wild-type mice with inhibition of PKCα or LSD1 activity show attenuated sepsis-induced inflammatory lung injury and mortality. Together, we demonstrate that the PKCα-LSD1-NF-κB signaling cascade is crucial for epigenetic control of the inflammatory response, and targeting this signaling could be a powerful therapeutic strategy for systemic inflammatory diseases, including sepsis.


Assuntos
Histona Desmetilases/metabolismo , Proteína Quinase C/metabolismo , Animais , Núcleo Celular/metabolismo , Epigênese Genética/genética , Histona Desmetilases/genética , Inflamação/metabolismo , Metilação , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fosforilação , Proteína Quinase C/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
Nucleic Acids Res ; 52(7): 3794-3809, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38340339

RESUMO

Meiotic recombination is initiated by programmed double-strand breaks (DSBs). Studies in Saccharomyces cerevisiae have shown that, following rapid resection to generate 3' single-stranded DNA (ssDNA) tails, one DSB end engages a homolog partner chromatid and is extended by DNA synthesis, whereas the other end remains associated with its sister. Then, after regulated differentiation into crossover- and noncrossover-fated types, the second DSB end participates in the reaction by strand annealing with the extended first end, along both pathways. This second-end capture is dependent on Rad52, presumably via its known capacity to anneal two ssDNAs. Here, using physical analysis of DNA recombination, we demonstrate that this process is dependent on direct interaction of Rad52 with the ssDNA binding protein, replication protein A (RPA). Furthermore, the absence of this Rad52-RPA joint activity results in a cytologically-prominent RPA spike, which emerges from the homolog axes at sites of crossovers during the pachytene stage of the meiotic prophase. Our findings suggest that this spike represents the DSB end of a broken chromatid caused by either the displaced leading DSB end or the second DSB end, which has been unable to engage with the partner homolog-associated ssDNA. These and other results imply a close correspondence between Rad52-RPA roles in meiotic recombination and mitotic DSB repair.


Assuntos
Troca Genética , Quebras de DNA de Cadeia Dupla , Meiose , Proteína Rad52 de Recombinação e Reparo de DNA , Proteína de Replicação A , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Proteína de Replicação A/metabolismo , Proteína de Replicação A/genética , Meiose/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Recombinação Genética , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/genética , Recombinação Homóloga/genética
5.
Mol Psychiatry ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355784

RESUMO

Comparisons and linkage between multiple imaging scales are essential for neural circuit connectomics. Here, we report 20 new recombinant rabies virus (RV) vectors that we have developed for multi-scale and multi-modal neural circuit mapping tools. Our new RV tools for mesoscale imaging express a range of improved fluorescent proteins. Further refinements target specific neuronal subcellular locations of interest. We demonstrate the discovery power of these new tools including the detection of detailed microstructural changes of rabies-labeled neurons in aging and Alzheimer's disease mouse models, live imaging of neuronal activities using calcium indicators, and automated measurement of infected neurons. RVs that encode GFP and ferritin as electron microscopy (EM) and fluorescence microscopy reporters are used for dual EM and mesoscale imaging. These new viral variants significantly expand the scale and power of rabies virus-mediated neural labeling and circuit mapping across multiple imaging scales in health and disease.

6.
Cell ; 143(6): 924-37, 2010 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-21145459

RESUMO

Meiotic double-strand break (DSB)-initiated recombination must occur between homologous maternal and paternal chromosomes ("homolog bias"), even though sister chromatids are present. Through physical recombination analyses, we show that sister cohesion, normally mediated by meiotic cohesin Rec8, promotes "sister bias"; that meiosis-specific axis components Red1/Mek1kinase counteract this effect, thereby satisfying an essential precondition for homolog bias; and that other components, probably recombinosome-related, directly ensure homolog partner selection. Later, Rec8 acts positively to ensure maintenance of bias. These complexities mirror opposing dictates for global sister cohesion versus local separation and differentiation of sisters at recombination sites. Our findings support DSB formation within axis-tethered recombinosomes containing both sisters and ensuing programmed sequential release of "first" and "second" DSB ends. First-end release would create a homology-searching "tentacle." Rec8 and Red1/Mek1 also independently license recombinational progression and abundantly localize to different domains. These domains could comprise complementary environments that integrate inputs from DSB repair and mitotic chromosome morphogenesis into the complete meiotic program.


Assuntos
Troca Genética , Meiose , Saccharomyces cerevisiae/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos Fúngicos/metabolismo , Quebras de DNA de Cadeia Dupla , MAP Quinase Quinase 1/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Troca de Cromátide Irmã
7.
Mol Cell ; 65(5): 781-785, 2017 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-28257699

RESUMO

Autophagy is an evolutionarily conserved catabolic process. Although the components of autophagy in cytoplasm have been well-studied, the molecular basis for the epigenetic regulation of autophagy is poorly understood. It is becoming more important to propose a "whole-cell view" of autophagy embracing both cytoplasmic and nuclear events. Thus, it is great timing to summarize current status and discuss future direction.


Assuntos
Autofagia , Núcleo Celular/metabolismo , Cromatina/metabolismo , Epigênese Genética , Histonas/metabolismo , Acetilação , Animais , Autofagia/genética , Cromatina/genética , Montagem e Desmontagem da Cromatina , Humanos , Metilação , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas Metiltransferases/metabolismo
8.
Neuroimage ; 297: 120749, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033787

RESUMO

Differential diagnosis of acute loss of consciousness (LOC) is crucial due to the need for different therapeutic strategies despite similar clinical presentations among etiologies such as nonconvulsive status epilepticus, metabolic encephalopathy, and benzodiazepine intoxication. While altered functional connectivity (FC) plays a pivotal role in the pathophysiology of LOC, there has been a lack of efforts to develop differential diagnosis artificial intelligence (AI) models that feature the distinctive FC change patterns specific to each LOC cause. Three approaches were applied for extracting features for the AI models: three-dimensional FC adjacency matrices, vectorized FC values, and graph theoretical measurements. Deep learning using convolutional neural networks (CNN) and various machine learning algorithms were implemented to compare classification accuracy using electroencephalography (EEG) data with different epoch sizes. The CNN model using FC adjacency matrices achieved the highest accuracy with an AUC of 0.905, with 20-s epoch data being optimal for classifying the different LOC causes. The high accuracy of the CNN model was maintained in a prospective cohort. Key distinguishing features among the LOC causes were found in the delta and theta brain wave bands. This research advances the understanding of LOC's underlying mechanisms and shows promise for enhancing diagnosis and treatment selection. Moreover, the AI models can provide accurate LOC differentiation with a relatively small amount of EEG data in 20-s epochs, which may be clinically useful.

9.
Small ; 20(30): e2400828, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38693068

RESUMO

Efficient support materials are crucial for maximizing the efficacy of nanomaterials in various applications such as energy storage, drug delivery, catalysis, and environmental remediation. However, traditional supports often hinder nanomaterial performance due to their high weight ratio and limited manageability, leading to issues like tube blocking and secondary pollution. To address this, a novel grapefruit-inspired polymeric capsule (GPC) as a promising carrier platform is introduced. The millimeter-scale GPC features a hydrophilic shell and an internal hierarchical microstructure with 80% void volume, providing ample space for encapsulating diverse nanomaterials including metals, polymers, metal-organic frameworks, and silica. Through liquid-phase bottom-up methods, it is successfully loaded Fe2O3, SiO2, polyacrylic acid, and Prussian blue nanomaterials onto the GPC, achieving high mass ratio (1776, 488, 898, and 634 wt.%, respectively). The GPC shell prevents nanomaterial leakage and the influx of suspended solids, while its internal framework enhances structural stability and mass transfer rates. With long-term storage stability, high carrying capacity, and versatile applicability, the GPC significantly enhances the field applicability of nanomaterials.

10.
J Clin Microbiol ; 62(7): e0020724, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38888305

RESUMO

The Panbio COVID-19/Flu A&B Panel (Abbott) is an in vitro diagnostic rapid test designed for the qualitative detection of nucleocapsid proteins SARS-CoV-2 and nucleoprotein influenza A and B antigens in nasal mid-turbinate (NMT) swab specimens from symptomatic individuals meeting COVID-19 and influenza clinical and/or epidemiological criteria. This study, the largest global one to date using fresh samples, aimed to assess the diagnostic sensitivity and specificity of the Panbio COVID-19/Flu A&B Panel in freshly collected NMT swab specimens from individuals suspected of respiratory viral infection consistent with COVID-19 and/or influenza within the first 5 days of symptom onset compared with results obtained with the cobas SARS-CoV-2 and influenza A/B qualitative assay (cobas 6800/8800 systems), which were tested using nasopharyngeal swab samples. A total of 512 evaluable subjects were enrolled in the COVID-19 cohort across 18 sites, and 1,148 evaluable subjects were enrolled in the influenza cohort across 22 sites in the Asia-Pacific, Europe, and the USA. The Panbio COVID-19/Flu A&B Panel demonstrated a sensitivity of 80.4% and a specificity of 99.7% for COVID-19. For influenza A, the sensitivity and specificity rates were 80.6% and 99.3%, respectively. Likewise, for influenza B, the sensitivity and specificity rates were 80.8% and 99.4%, respectively. In conclusion, the Panbio COVID-19/Flu A&B Panel emerges as a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.4% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B. IMPORTANCE: The Panbio COVID-19/Flu A&B Panel is a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.0% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B.


Assuntos
Antígenos Virais , COVID-19 , Vírus da Influenza A , Vírus da Influenza B , Influenza Humana , SARS-CoV-2 , Sensibilidade e Especificidade , Humanos , COVID-19/diagnóstico , Influenza Humana/diagnóstico , Influenza Humana/virologia , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza B/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Adulto , Pessoa de Meia-Idade , Feminino , Masculino , Antígenos Virais/análise , Antígenos Virais/imunologia , Adulto Jovem , Adolescente , Idoso , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/imunologia , Criança , Pré-Escolar , Nasofaringe/virologia , Teste para COVID-19/métodos , Lactente , Idoso de 80 Anos ou mais
11.
BMC Cancer ; 24(1): 397, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553680

RESUMO

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Estudos Multicêntricos como Assunto , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Fluoruracila/uso terapêutico
12.
Aging Male ; 27(1): 2317165, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38389408

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is linked to various health complications, including erectile dysfunction (ED), which is more prevalent in individuals with OSA. This study explored ED in Korean OSA patients and assessed the impact of continuous positive airway pressure (CPAP) therapy on ED. METHODS: A total of 87 male patients with OSA from four different sleep centers underwent physical measurements and completed sleep and mental health (MH) questionnaires, including the Korean version of the International index of erectile function (IIEF), before and three months after initiating CPAP therapy. RESULTS: After three months of CPAP therapy, the patients demonstrated a significant improvement in ED as measured on the IIEF. However, the study found no significant correlation between the duration of CPAP use and the improvement in IIEF score. It did identify the SF36 quality of life assessment as a significant factor influencing ED improvement after CPAP. CONCLUSIONS: ED is a prevalent issue that escalates with age and is associated with OSA. CPAP therapy has shown potential in alleviating ED symptoms, particularly in those with underlying psychological conditions, although further research is required to confirm these findings and understand the underlying mechanisms.


Assuntos
Disfunção Erétil , Apneia Obstrutiva do Sono , Masculino , Humanos , Disfunção Erétil/etiologia , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Qualidade de Vida/psicologia , Polissonografia/efeitos adversos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/diagnóstico
13.
BMC Neurol ; 24(1): 89, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448803

RESUMO

BACKGROUND: Neuropsychiatric symptoms and delusions are highly prevalent among people with dementia. However, multiple roots of neurobiological bases and shared neural basis of delusion and cognitive function remain to be characterized. By utilizing a fine-grained multivariable approach, we investigated distinct neuroanatomical correlates of delusion symptoms across a large population of dementing illnesses. METHODS: In this study, 750 older adults with mild cognitive impairment and Alzheimer's disease completed brain structural imaging and neuropsychological assessment. We utilized principal component analysis followed by varimax rotation to identify the distinct multivariate correlates of cortical thinning patterns. Five of the cognitive domains were assessed whether the general cognitive abilities mediate the association between cortical thickness and delusion. RESULTS: The result showed that distributed thickness patterns of temporal and ventral insular cortex (component 2), inferior and lateral prefrontal cortex (component 1), and somatosensory-visual cortex (component 5) showed negative correlations with delusions. Subsequent mediation analysis showed that component 1 and 2, which comprises inferior frontal, anterior insula, and superior temporal regional thickness accounted for delusion largely through lower cognitive functions. Specifically, executive control function assessed with the Trail Making Test mediated the relationship between two cortical thickness patterns and delusions. DISCUSSION: Our findings suggest that multiple distinct subsets of brain regions underlie the delusions among older adults with cognitive impairment. Moreover, a neural loss may affect the occurrence of delusion in dementia largely due to impaired general cognitive abilities.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Delusões , Disfunção Cognitiva/diagnóstico por imagem , Cognição , Encéfalo/diagnóstico por imagem
14.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469788

RESUMO

BACKGROUND: There is little data about the performance of multiplex rapid antigen tests (RATs) on the detection of SARS-CoV-2, influenza A (Flu A), and influenza B (Flu B). This study is to evaluate the performance of Panbio COVID-19/Flu A&B rapid panel (Abbott Diagnostics, Korea) and analyze the factors influencing its sensitivity. METHODS: Nasopharyngeal swabs were collected and stored at the Korea University Anam hospital. In total, 400 residual samples from nasopharyngeal swabs were examined. The diagnostic accuracy of RAT was compared to that of RT-qPCR using the Allplex SARS-CoV-2/FluA/FluB/RSV Assay (Seegene, Seoul, South Korea). RESULTS: Panbio COVID-19/Flu A&B rapid panel showed the sensitivities of 88.0%, 92.0%, and 100% for SARS-CoV-2, Flu A, and Flu B, respectively, and specificities of 100% for all. The agreements with previously licensed single-plex RATs were shown to be high. In the analysis of variables affecting sensitivity, inappropriate sampling time after symptom onset (STASO) and high cycle threshold (Ct value) were shown to negatively affect the sensi-tivity. CONCLUSIONS: In conclusion, the multiplex RAT is useful for diagnosing SARS-CoV-2 and Flu A/B, but more clinical studies are needed.


Assuntos
COVID-19 , Vírus da Influenza A , Influenza Humana , Humanos , Influenza Humana/diagnóstico , SARS-CoV-2 , Vírus da Influenza B/genética , COVID-19/diagnóstico , Nasofaringe , Sensibilidade e Especificidade
15.
Cryobiology ; 115: 104869, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38412911

RESUMO

We investigated methods for cryopreserving sperm from the endangered gudgeon, Microphysogobio rapidus, by examining the effects of cryoprotective agent (CPA) concentration, diluent, and dilution ratio on post-thaw sperm quality. The quality of frozen sperm was evaluated in terms of motility and kinematic parameters, viability, DNA damage, and fertilization rate. We evaluated methanol, glycerol, dimethyl sulfoxide (DMSO), and ethylene glycol as CPAs. Sperm motility, velocity, and viability were significantly higher when methanol was used as the CPA (p < 0.05). The diluents tested were Ringer's solution, Kurokura's Extender, Common Carp Sperm Extender (CCSE), and buffered sperm motility-inhibiting saline solution (BSMIS); post-thaw motility was highest when Ringer's solution was used as the diluent. Next, various quantities of methanol were combined with Ringer's solution to identify the optimal dose of methanol. The dilution ratios tested ranged from 1:1 to 1:7. Cryopreserved sperm was thawed at 20 °C for 15 s. The use of 10% methanol with Ringer's solution at a dilution ratio of 1:5 resulted in the highest post-thaw sperm motility, viability, and velocity including VAP, VCL, and VSL. Post-thaw sperm showed significantly greater DNA damage than the control (fresh sperm) (p < 0.05). The fertilization rate was highest with fresh sperm (p < 0.05), followed by sperm frozen with 10% methanol + Ringer's solution. We recommend that the best way to preserve sperm in the studied species is to use a combination of Ringer's solution and 10% methanol at a 1:5 dilution ratio. Our findings will facilitate the artificial fertilization of M. rapidus.


Assuntos
Criopreservação , Crioprotetores , Cyprinidae , Dimetil Sulfóxido , Metanol , Preservação do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Animais , Masculino , Criopreservação/métodos , Criopreservação/veterinária , Crioprotetores/farmacologia , Preservação do Sêmen/métodos , Preservação do Sêmen/veterinária , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Cyprinidae/fisiologia , Metanol/farmacologia , Dimetil Sulfóxido/farmacologia , Glicerol/farmacologia , Etilenoglicol/farmacologia , Dano ao DNA/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino
16.
Nucleic Acids Res ; 50(14): 7856-7872, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35821310

RESUMO

Autophagy is a catabolic pathway that maintains cellular homeostasis under various stress conditions, including conditions of nutrient deprivation. To elevate autophagic flux to a sufficient level under stress conditions, transcriptional activation of autophagy genes occurs to replenish autophagy components. Thus, the transcriptional and epigenetic control of the genes regulating autophagy is essential for cellular homeostasis. Here, we applied integrated transcriptomic and epigenomic profiling to reveal the roles of plant homeodomain finger protein 20 (PHF20), which is an epigenetic reader possessing methyl binding activity, in controlling the expression of autophagy genes. Phf20 deficiency led to impaired autophagic flux and autophagy gene expression under glucose starvation. Interestingly, the genome-wide characterization of chromatin states by Assay for Transposase-Accessible Chromatin (ATAC)-sequencing revealed that the PHF20-dependent chromatin remodelling occurs in enhancers that are co-occupied by dimethylated lysine 36 on histone H3 (H3K36me2). Importantly, the recognition of H3K36me2 by PHF20 was found to be highly correlated with increased levels of H3K4me1/2 at the enhancer regions. Collectively, these results indicate that PHF20 regulates autophagy genes through enhancer activation via H3K36me2 recognition as an epigenetic reader. Our findings emphasize the importance of nuclear events in the regulation of autophagy.


Assuntos
Epigenômica , Inanição , Autofagia/genética , Cromatina/genética , Proteínas de Ligação a DNA/genética , Epigênese Genética , Proteínas de Homeodomínio/genética , Humanos , Inanição/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
J Korean Med Sci ; 39(17): e157, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711319

RESUMO

This study assessed the performance of the BioFire Blood Culture Identification 2 (BCID2) panel in identifying microorganisms and antimicrobial resistance (AMR) profiles in positive blood cultures (BCs) and its influence on turnaround time (TAT) compared with conventional culture methods. We obtained 117 positive BCs, of these, 102 (87.2%) were correctly identified using BCID2. The discordance was due to off-panel pathogens detected by culture (n = 13), and additional pathogens identified by BCID2 (n = 2). On-panel pathogen concordance between the conventional culture and BCID2 methods was 98.1% (102/104). The conventional method detected 19 carbapenemase-producing organisms, 14 extended-spectrum beta-lactamase-producing Enterobacterales, 18 methicillin-resistant Staphylococcus spp., and four vancomycin-resistant Enterococcus faecium. BCID2 correctly predicted 53 (96.4%) of 55 phenotypic resistance patterns by detecting AMR genes. The TAT for BCID2 was significantly lower than that for the conventional method. BCID2 rapidly identifies pathogens and AMR genes in positive BCs.


Assuntos
Hemocultura , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase Multiplex/métodos , Humanos , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética , Proteínas de Bactérias/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterococcus faecium/genética , Enterococcus faecium/isolamento & purificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/genética , Enterococos Resistentes à Vancomicina/isolamento & purificação , Bacteriemia/microbiologia , Bacteriemia/diagnóstico
18.
Nano Lett ; 23(17): 7927-7933, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37647420

RESUMO

Transition metal dichalcogenides (TMDs) benefit electrical devices with spin-orbit coupling and valley- and topology-related properties. However, TMD-based devices suffer from traps arising from defect sites inside the channel and the gate oxide interface. Deactivating them requires independent treatments, because the origins are dissimilar. This study introduces a single treatment to passivate defects in a multilayer MoS2 FET. By applying back-gate bias, protons from an H-TFSI droplet are injected into the MoS2, penetrating deeply enough to reach the SiO2 gate oxide. The characterizations employing low-temperature transport and deep-level transient spectroscopy (DLTS) studies reveal that the trap density of S vacancies in MoS2 drops to the lowest detection level. The temperature-dependent mobility plot on the SiO2 substrate resembles that of the h-BN substrate, implying that dangling bonds in SiO2 are passivated. The carrier mobility on the SiO2 substrate is enhanced by approximately 2200% after the injection.

19.
Int J Mol Sci ; 25(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38612732

RESUMO

Yellow catfish Tachysurus fulvidraco is an important commercial fish species in South Korea. However, due to their current declines in its distribution area and population size, it is being released from hatchery populations into wild populations. Hatchery populations also produced from wild broodstocks are used for its captive breeding. We reported 15 new microsatellite DNA markers of T. fulvidraco to identify the genetic diversity and structure of its hatchery and wild populations, providing baseline data for useful resource development strategies. The observed heterozygosity of the hatchery populations ranged from 0.816 to 0.873, and that of the wild populations ranged from 0.771 to 0.840. Their inbreeding coefficient ranged from -0.078 to 0.024. All populations experienced a bottleneck (p < 0.05), with effective population sizes ranging from 21 to infinity. Their gene structure was divided into two groups with STRUCTURE results of K = 2. It was confirmed that each hatchery population originated from a different wild population. This study provides genetic information necessary for the future development and conservation of fishery resources for T. fulvidraco.


Assuntos
Peixes-Gato , Animais , Peixes-Gato/genética , República da Coreia , Densidade Demográfica , Pesqueiros , Repetições de Microssatélites/genética
20.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892434

RESUMO

Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.


Assuntos
Receptores ErbB , Proteínas Proto-Oncogênicas c-bcl-2 , Pontos Quânticos , RNA Interferente Pequeno , Pontos Quânticos/química , Animais , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , RNA Interferente Pequeno/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Camundongos , Linhagem Celular Tumoral , Nanopartículas/química , Lipídeos/química , Nanomedicina Teranóstica/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Micelas
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