Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 198
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Proc Natl Acad Sci U S A ; 121(9): e2320276121, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38381789

RESUMEN

Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration trait in humans. We investigated the role of different NPS+ nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS+ neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS+ neurons are not important for sleep/wake modulation. Further, we found that a NPS+ nucleus in the central gray of the pons (CGPn) strongly promotes sleep. Fiber photometry recordings showed that NPS+ neurons are wake-active in the CGPn and wake/REM-sleep active in the PB and peri-LC. Blocking NPS-NPSR1 signaling or knockdown of Nps supported the function of the NPS-NPSR1 pathway in sleep/wake regulation. Together, these results reveal that NPS and NPS+ neurons play dichotomous roles in sleep/wake regulation at both the molecular and circuit levels.


Asunto(s)
Neuropéptidos , Sueño , Humanos , Sueño/fisiología , Puente/fisiología , Locus Coeruleus/fisiología , Neuronas/metabolismo , Neuropéptidos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(34): e2203266119, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-35901245

RESUMEN

Sleep is a necessity for our survival, but its regulation remains incompletely understood. Here, we used a human sleep duration gene to identify a population of cells in the peri-tegmental reticular nucleus (pTRNADRB1) that regulate sleep-wake, uncovering a role for a poorly understood brain area. Although initial ablation in mice led to increased wakefulness, further validation revealed that pTRNADRB1 neuron stimulation strongly promotes wakefulness, even after stimulation offset. Using combinatorial genetics, we found that excitatory pTRNADRB1 neurons promote wakefulness. pTRN neurons can be characterized as anterior- or posterior-projecting neurons based on multiplexed analysis of projections by sequencing (MAPseq) analysis. Finally, we found that pTRNADRB1 neurons promote wakefulness, in part, through projections to the lateral hypothalamus. Thus, human genetic information from a human sleep trait allowed us to identify a role for the pTRN in sleep-wake regulation.


Asunto(s)
Sueño , Tegmento Mesencefálico , Vigilia , Animales , Humanos , Área Hipotalámica Lateral/fisiología , Ratones , Neuronas/fisiología , Sueño/fisiología , Tegmento Mesencefálico/fisiología , Vigilia/fisiología
3.
Mol Biol Evol ; 40(10)2023 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-37791477

RESUMEN

Amphibians are ideal for studying visual system evolution because their biphasic (aquatic and terrestrial) life history and ecological diversity expose them to a broad range of visual conditions. Here, we evaluate signatures of selection on visual opsin genes across Neotropical anurans and focus on three diurnal clades that are well-known for the concurrence of conspicuous colors and chemical defense (i.e., aposematism): poison frogs (Dendrobatidae), Harlequin toads (Bufonidae: Atelopus), and pumpkin toadlets (Brachycephalidae: Brachycephalus). We found evidence of positive selection on 44 amino acid sites in LWS, SWS1, SWS2, and RH1 opsin genes, of which one in LWS and two in RH1 have been previously identified as spectral tuning sites in other vertebrates. Given that anurans have mostly nocturnal habits, the patterns of selection revealed new sites that might be important in spectral tuning for frogs, potentially for adaptation to diurnal habits and for color-based intraspecific communication. Furthermore, we provide evidence that SWS2, normally expressed in rod cells in frogs and some salamanders, has likely been lost in the ancestor of Dendrobatidae, suggesting that under low-light levels, dendrobatids have inferior wavelength discrimination compared to other frogs. This loss might follow the origin of diurnal activity in dendrobatids and could have implications for their behavior. Our analyses show that assessments of opsin diversification in across taxa could expand our understanding of the role of sensory system evolution in ecological adaptation.


Asunto(s)
Opsinas , Venenos , Animales , Opsinas/genética , Filogenia , Opsinas de Bastones/genética
4.
Lupus ; 33(2): 121-128, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38320976

RESUMEN

OBJECTIVE: Through machine learning (ML) analysis of the radiomics features of ultrasound extracted from patients with lupus nephritis (LN), this attempt was made to non-invasively predict the chronicity index (CI)of LN. METHODS: A retrospective collection of 136 patients with LN who had renal biopsy was retrospectively collected, and the patients were randomly divided into training set and validation set according to 7:3. Radiomics features are extracted from ultrasound images, independent factors are obtained by using LASSO dimensionality reduction, and then seven ML models were used to establish predictive models. At the same time, a clinical model and an US model were established. The diagnostic efficacy of the model is evaluated by analysis of the receiver operating characteristics (ROC) curve, accuracy, specificity, and sensitivity. The performance of the seven machine learning models was compared with each other and with clinical and US models. RESULTS: A total of 1314 radiomics features are extracted from ultrasound images, and 5 features are finally screened out by LASSO for model construction, and the average ROC of the seven ML is 0.683, among which the Xgboost model performed the best, and the AUC in the test set is 0.826 (95% CI: 0.681-0.936). For the same test set, the AUC of clinical model constructed based on eGFR is 0.560 (95% CI: 0.357-0.761), and the AUC of US model constructed based on Ultrasound parameters is 0.679 (95% CI: 0.489-0.853). The Xgboost model is significantly more efficient than the clinical and US models. CONCLUSION: ML model based on ultrasound radiomics features can accurately predict the chronic degree of LN, which can provide a valuable reference for clinicians in the treatment strategy of LN patients.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Radiómica , Estudios Retrospectivos , Ultrasonografía
5.
Phys Rev Lett ; 131(3): 031601, 2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37540874

RESUMEN

Conformal field theory (CFT) plays a crucial role in the study of various critical phenomena. While much attention has been paid to the critical exponents of different universalities, which correspond to the conformal dimensions of CFT primary fields, other important and intricate data such as operator product expansion (OPE) coefficients governing the fusion of two primary fields, have remained largely unexplored, especially in dimensions higher than 2D (or equivalently, 1+1D). Motivated by the recently proposed fuzzy sphere regularization, we investigate the operator content of 3D Ising criticality from a microscopic perspective. We first outline the procedure for extracting OPE coefficients on the fuzzy sphere and then compute 13 OPE coefficients of low-lying CFT primary fields. Our results are highly accurate and in agreement with the numerical conformal bootstrap data of 3D Ising CFT. Moreover, we were able to obtain 4 OPE coefficients, including f_{T_{µν}T_{ρη}ε}, which were previously unknown, thus demonstrating the superior capabilities of our scheme. Expanding the horizon of the fuzzy sphere regularization from the state perspective to the operator perspective opens up new avenues for exploring a wealth of new physics.

6.
J Biomed Sci ; 30(1): 27, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37101169

RESUMEN

BACKGROUND: Amyotrophic lateral sclerosis (ALS) associated with TAR DNA-binding protein 43 (TDP-43) aggregation has been considered as a lethal and progressive motor neuron disease. Recent studies have shown that both C-terminal TDP-43 (C-TDP-43) aggregates and oligomers were neurotoxic and pathologic agents in ALS and frontotemporal lobar degeneration (FTLD). However, misfolding protein has long been considered as an undruggable target by applying conventional inhibitors, agonists, or antagonists. To provide this unmet medical need, we aim to degrade these misfolding proteins by designing a series of proteolysis targeting chimeras (PROTACs) against C-TDP-43. METHODS: By applying filter trap assay, western blotting, and microscopy imaging, the degradation efficiency of C-TDP-43 aggregates was studied in Neuro-2a cells overexpressing eGFP-C-TDP-43 or mCherry-C-TDP-43. The cell viability was characterized by alarmarBlue assay. The beneficial and disaggregating effects of TDP-43 PROTAC were examined with the YFP-C-TDP-43 transgenic C. elegans by motility assay and confocal microscopy. The impact of TDP-43 PROTAC on C-TDP-43 oligomeric intermediates was monitored by fluorescence lifetime imaging microscopy and size exclusion chromatography in the Neuro-2a cells co-expressing eGFP-C-TDP-43 and mCherry-C-TDP-43. RESULTS: Four PROTACs with different linker lengths were synthesized and characterized. Among these chimeras, PROTAC 2 decreased C-TDP-43 aggregates and relieved C-TDP-43-induced cytotoxicity in Neuro-2a cells without affecting endogenous TDP-43. We showed that PROTAC 2 bound to C-TDP-43 aggregates and E3 ligase to initiate ubiquitination and proteolytic degradation. By applying advanced microscopy, it was further shown that PROTAC 2 decreased the compactness and population of C-TDP-43 oligomers. In addition to cellular model, PROTAC 2 also improved the motility of transgenic C. elegans by reducing the C-TDP-43 aggregates in the nervous system. CONCLUSIONS: Our study demonstrated the dual-targeting capacity of the newly-designed PROTAC 2 against both C-TDP-43 aggregates and oligomers to reduce their neurotoxicity, which shed light on the potential drug development for ALS as well as other neurodegenerative diseases.


Asunto(s)
Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Animales , Esclerosis Amiotrófica Lateral/metabolismo , Enfermedades Neurodegenerativas/genética , Proteolisis , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Unión al ADN/metabolismo , Animales Modificados Genéticamente
7.
Eur Radiol ; 33(10): 6872-6882, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37081299

RESUMEN

OBJECTIVES: The common practice is to remove symptomatic common bile duct (CBD) stones in patients. This study aimed to investigate the factors affecting the percutaneous transhepatic removal of CBD stones. METHODS: We retrospectively analyzed the data of 100 patients (66 men and 34 women; age: 25-105 years, mean 79.1 years) with symptomatic CBD stones who underwent percutaneous transhepatic stone removal (PTSR) from January 2010 through October 2019. After balloon dilation of the ampulla of Vater or bilioenteric anastomosis, the stones were pushed out of the CBD into the small bowel with a balloon catheter. If failed, basket lithotripsy was performed. Technical success was defined as complete clearance of the bile ducts on a cholangiogram. RESULTS: The technical success rate was 83%, and achieved 90.2% in patients with altered gastroduodenal/pancreatobiliary anatomy. Multivariable analysis revealed that CBD diameter (odds ratio [OR]: 506.460, p = 0.015), failed ERCP (OR: 16.509, p = 0.004), Tokyo guidelines TG18/TG13 severity (grade III; OR: 60.467, p = 0.006), and left-sided transhepatic approach (OR: 21.621, p = 0.012) were risk factors for technical failure. The appropriate cutoff CBD size was 15.5 mm (area under the curve: 0.91). CBD stone size, radiopacity of stones, and CBD angle between retroduodenal and pancreatic portion did not influence technical success. CONCLUSIONS: PTSR is effective for CBD stone removal in older adults and individuals with altered gastrointestinal tract anatomy. The aforementioned risk factors for technical failure should be considered in preoperative evaluation before PTSR to improve the success rate. KEY POINTS: • PTSR is effective in symptomatic CBD stone management among older adults and individuals with altered anatomy. Investigating clinical /anatomic factors can guide radiologists toward a more comprehensive preoperative evaluation to maximize the success rate. • Our data indicate that dilated CBD (diameter ≥ 15.5 mm) and left-sided PTBDs reduce the technical success rate by 506-fold and 22-fold, respectively. • Clinical factors such as previous failed ERCP for stone removal and higher severity of acute cholangitis lessen the technical success rate.


Asunto(s)
Coledocolitiasis , Cálculos Biliares , Masculino , Humanos , Femenino , Anciano , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Coledocolitiasis/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Cálculos Biliares/diagnóstico por imagen , Cálculos Biliares/cirugía , Conducto Colédoco/diagnóstico por imagen , Conducto Colédoco/cirugía , Colangiopancreatografia Retrógrada Endoscópica
8.
Angew Chem Int Ed Engl ; 61(2): e202113206, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-34636127

RESUMEN

Multiple resonance (MR) emitters are promising for highly efficient organic light-emitting diodes (OLEDs) with narrowband emission; however, they still face intractable challenges with concentration-caused emission quenching, exciton annihilation, and spectral broadening. In this study, sterically wrapped MR dopants with a fluorescent MR core sandwiched by bulk substituents were developed to address the intractable challenges by reducing intermolecular interactions. Consequently, high photo-luminance quantum yields of ≥90 % and small full width at half maximums (FWHMs) of ≤25 nm over a wide range of dopant concentrations (1-20 wt %) were recorded. In addition, we demonstrated that the sandwiched MR emitter can effectively suppress Dexter interaction when doped in a thermally activated delayed fluorescence sensitizer, eliminating exciton loss through dopant triplet. Within the above dopant concentration range, the optimal emitter realizes remarkably high maximum external quantum efficiencies of 36.3-37.2 %, identical small FWHMs of 24 nm, and alleviated efficiency roll-offs in OLEDs.

9.
Angew Chem Int Ed Engl ; 61(52): e202213585, 2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36281782

RESUMEN

A novel macrocycle of B/N-doped calix[4]arene (C-BN) was synthesized by a one-shot double boronation. Owing to the structural tension and electron-donating properties of the nitrogen atoms in the macrocycle, reaction selectively proceeds between the adjacent benzene rings outside the macrocycle. C-BN shows a highly centrosymmetric structure with two multiple resonance (MR) fragments bridged by tertiary amine groups at the 1,3 positions of the benzene ring. Benefiting from the large intermolecular distance (>4.6 Å) between adjacent MR-emitting cores, C-BN also exhibits excellent narrowband emitting features against aggregation-induced quenching and spectrum broadening. Optimized organic light-emitting diode devices based on C-BN exhibit high maximum external quantum efficiencies of 24.7-26.6 % and small full width at half maximums of 25-28 nm over a wide doping range of 1-12 wt %.

10.
Angew Chem Int Ed Engl ; 61(40): e202207293, 2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-35749578

RESUMEN

Despite the remarkable multiple resonance (MR) optoelectronic properties of organic nanographenes with boron and nitrogen atoms disposed para to each other, the synthetic procedures are sophisticated with low yields and the molecular skeletons are limited. Here, a new paradigm of easy-to-access MR emitter is constructed by simplifying the multiborylation through amine-directed formation of B-N bonds while introducing an additional para-positioned nitrogen atom to trigger the MR effect. The proof-of-concept molecules exhibit narrowband emissions at 480 and 490 nm, with full width at half maxima (FWHMs) of only 29 and 34 nm. The devices based on them showed external quantum efficiencies (EQE) of >33.0 %, which remained above 24.0 % even at a high brightness of 5000 cd m-2 . This is the first example of MR emitters with a B-N covalent bond, not only decreasing the synthesis difficulty but also increasing the diversity of MR skeletons for emerging new optoelectronic properties.

11.
BMC Bioinformatics ; 22(1): 605, 2021 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-34930116

RESUMEN

BACKGROUND: Upon environmental stimuli, ribosomes are surmised to undergo compositional rearrangements due to abundance changes among proteins assembled into the complex, leading to modulated structural and functional characteristics. Here, we present the ComplexOme-Structural Network Interpreter ([Formula: see text]), a computational method to allow testing whether ribosomal proteins (rProteins) that exhibit abundance changes under specific conditions are spatially confined to particular regions within the large ribosomal complex. RESULTS: [Formula: see text] translates experimentally determined structures into graphs, with nodes representing proteins and edges the spatial proximity between them. In its first implementation, [Formula: see text] considers rProteins and ignores rRNA and other objects. Spatial regions are defined using a random walk with restart methodology, followed by a procedure to obtain a minimum set of regions that cover all proteins in the complex. Structural coherence is achieved by applying weights to the edges reflecting the physical proximity between purportedly contacting proteins. The weighting probabilistically guides the random-walk path trajectory. Parameter tuning during region selection provides the option to tailor the method to specific biological questions by yielding regions of different sizes with minimum overlaps. In addition, other graph community detection algorithms may be used for the [Formula: see text] workflow, considering that they yield different sized, non-overlapping regions. All tested algorithms result in the same node kernels under equivalent regions. Based on the defined regions, available abundance change information of proteins is mapped onto the graph and subsequently tested for enrichment in any of the defined spatial regions. We applied [Formula: see text] to the cytosolic ribosome structures of Saccharomyces cerevisiae, Oryctolagus cuniculus, and Triticum aestivum using datasets with available quantitative protein abundance change information. We found that in yeast, substoichiometric rProteins depleted from translating polysomes are significantly constrained to a ribosomal region close to the tRNA entry and exit sites. CONCLUSIONS: [Formula: see text] offers a computational method to partition multi-protein complexes into structural regions and a statistical approach to test for spatial enrichments of any given subsets of proteins. [Formula: see text] is applicable to any multi-protein complex given appropriate structural and abundance-change data. [Formula: see text] is publicly available as a GitHub repository https://github.com/MSeidelFed/COSNet_i and can be installed using the python installer pip.


Asunto(s)
Ribosomas , Animales , Conejos , Ribosomas/genética
12.
Eur Radiol ; 31(10): 7464-7475, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33765160

RESUMEN

OBJECTIVE: To evaluate whether parenchyma-to-lipiodol ratio (PLR) and lesion-to-lipiodol ratio (LLR) on C-arm cone-beam computed tomography (CBCT) can predict 1-year tumor response in patients with hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (cTACE). METHODS: This retrospective analysis included 221 HCC target lesions within up-to-seven criteria in 80 patients who underwent cTACE with arterial-phase CBCT and unenhanced CBCT after cTACE from 2015 to 2018. PLR and LLR of every tumor slice were obtained through mean density division of liver parenchyma and tumor enhancement with intratumoral lipiodol deposition. The cutoff values (COVs) of maximal PLR and LLR of every tumor were analyzed using Youden's index. The reliability of COV, correlations between the related parameters, and 1-year progression were assessed through interobserver agreement and multivariate analysis. COV validity was verified using the chi-square test and Cramer's V coefficient (V) in the validation cohort. RESULTS: Standard COVs of PLR and LLR were 0.149 and 1.4872, respectively. Interobserver agreement of COV for PLR and LLR was near perfect (kappa > 0.9). Multivariate analysis suggested that COV of PLR is an independent predictor (odds ratio = 1.23532×1014, p = 4.37×10-7). COV of PLR showed strong consistency, correlation with 1-year progression in prediction model (V = 0.829-0.776; p < 0.0001), and presented as an effective predictor in the validation cohort (V = 0.766; p < 0.0001). CONCLUSION: The COV of PLR (0.149) assessed through immediate post-embolization CBCT is an objective, effective, and approachable predictor of 1-year HCC progression after cTACE. KEY POINTS: • The maximal PLR value indicates the least lipiodol-distributed region in an HCC tumor. The maximal LLR value indicates the least lipiodol-deposited region in the tumor due to incomplete lipiodol delivery. PLR and LLR are concepts like signal-to-noise ratio to characterize the lipiodol retention pattern objectively to predict 1-year tumor progression immediately without any quantification software for 3D image analysis immediately after cTACE treatment. • COV of PLR can facilitate the early prediction of tumor progression/recurrence and indicate the section of embolized HCC, providing the operator's good targets for sequential cTACE or combined ablation. • The validation cohort in our study verified standard COVs of PLR and LLR. The validation process was more convincing and delicate than that of previous retrospective studies.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Tomografía Computarizada de Haz Cónico , Aceite Etiodizado , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Resultado del Tratamiento
13.
Environ Toxicol ; 36(5): 764-772, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33347704

RESUMEN

Genistein (GEN) has been shown to induce apoptotic cell death in various human cancer cells. L-asparaginase (Asp), a clinical drug for leukemia, has been shown to induce cell apoptosis in leukemia cells. No available information concerning GEN combined with Asp increased the cell apoptosis compared to GEN or Asp treatment alone. The objective of this study is to evaluate the anti-leukemia activity of GEN combined with Asp on human leukemia HL-60 cells in vitro. The cell viability, the distribution of cell cycle, apoptotic cell death, and the level of ΔΨm were examined by flow cytometric assay. The expressions of apoptosis-associated proteins were measured by western blotting. GEN combined with Asp revealed a more significant decrease in total viable cells and induced a higher percentage of G2/M phase arrest, DNA damage, and cell apoptosis than that of GEN or Asp treatment only in HL-60 cells. Furthermore, the combined treatments (GEN and Asp) showed a higher decrease in the level of ΔΨm than that of GEN or Asp treatment only. These results indicated that GEN combined with Asp induced mitochondria dysfunction by disrupting the mitochondrial membrane potential. The results from western blotting demonstrated that the treatment of GEN combined with Asp showed a higher increase in the levels of Bax and Bak (pro-apoptotic proteins) and an active form of caspase-3 and a higher decrease in Bcl-2 (anti-apoptotic protein) than that of GEN or Asp treatment alone. GEN significantly enhances the efficiency of Asp on cytotoxic effects (the induction of apoptosis) in HL-60 cells.


Asunto(s)
Genisteína , Leucemia , Apoptosis , Asparaginasa , Genisteína/farmacología , Células HL-60 , Humanos
14.
Int J Mol Sci ; 22(9)2021 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-33922264

RESUMEN

The genes influencing cancer patient mortality have been studied by survival analysis for many years. However, most studies utilized them only to support their findings associated with patient prognosis: their roles in carcinogenesis have not yet been revealed. Herein, we applied an in silico approach, integrating the Cox regression model with effect size estimated by the Monte Carlo algorithm, to screen survival-influential genes in more than 6000 tumor samples across 16 cancer types. We observed that the survival-influential genes had cancer-dependent properties. Moreover, the functional modules formed by the harmful genes were consistently associated with cell cycle in 12 out of the 16 cancer types and pan-cancer, showing that dysregulation of the cell cycle could harm patient prognosis in cancer. The functional modules formed by the protective genes are more diverse in cancers; the most prevalent functions are relevant for immune response, implying that patients with different cancer types might develop different mechanisms against carcinogenesis. We also identified a harmful set of 10 genes, with potential as prognostic biomarkers in pan-cancer. Briefly, our results demonstrated that the survival-influential genes could reveal underlying mechanisms in carcinogenesis and might provide clues for developing therapeutic targets for cancers.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinogénesis/patología , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Neoplasias/mortalidad , Transcriptoma , Carcinogénesis/genética , Carcinogénesis/metabolismo , Biología Computacional , Perfilación de la Expresión Génica , Humanos , Neoplasias/genética , Neoplasias/patología , Pronóstico , Tasa de Supervivencia
15.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34200446

RESUMEN

Ribosome biogenesis is essential for plants to successfully acclimate to low temperature. Without dedicated steps supervising the 60S large subunits (LSUs) maturation in the cytosol, e.g., Rei-like (REIL) factors, plants fail to accumulate dry weight and fail to grow at suboptimal low temperatures. Around REIL, the final 60S cytosolic maturation steps include proofreading and assembly of functional ribosomal centers such as the polypeptide exit tunnel and the P-Stalk, respectively. In consequence, these ribosomal substructures and their assembly, especially during low temperatures, might be changed and provoke the need for dedicated quality controls. To test this, we blocked ribosome maturation during cold acclimation using two independent reil double mutant genotypes and tested changes in their ribosomal proteomes. Additionally, we normalized our mutant datasets using as a blank the cold responsiveness of a wild-type Arabidopsis genotype. This allowed us to neglect any reil-specific effects that may happen due to the presence or absence of the factor during LSU cytosolic maturation, thus allowing us to test for cold-induced changes that happen in the early nucleolar biogenesis. As a result, we report that cold acclimation triggers a reprogramming in the structural ribosomal proteome. The reprogramming alters the abundance of specific RP families and/or paralogs in non-translational LSU and translational polysome fractions, a phenomenon known as substoichiometry. Next, we tested whether the cold-substoichiometry was spatially confined to specific regions of the complex. In terms of RP proteoforms, we report that remodeling of ribosomes after a cold stimulus is significantly constrained to the polypeptide exit tunnel (PET), i.e., REIL factor binding and functional site. In terms of RP transcripts, cold acclimation induces changes in RP families or paralogs that are significantly constrained to the P-Stalk and the ribosomal head. The three modulated substructures represent possible targets of mechanisms that may constrain translation by controlled ribosome heterogeneity. We propose that non-random ribosome heterogeneity controlled by specialized biogenesis mechanisms may contribute to a preferential or ultimately even rigorous selection of transcripts needed for rapid proteome shifts and successful acclimation.


Asunto(s)
Aclimatación , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Frío , Proteoma/metabolismo , Proteínas Ribosómicas/metabolismo , Ribosomas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteoma/análisis , Proteínas Ribosómicas/genética , Ribosomas/genética
16.
BMC Nurs ; 20(1): 238, 2021 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-34823511

RESUMEN

BACKGROUND: The essence and workload of nursing can easily lead to burdens associated with female nurses' menstrual symptoms, and consequently, result in decreased working performance. Without effective support this can lead to resignation due to maladaptation. This study adopted Q methodology to explore the experience of working stressors and coping strategies associated with menstrual symptoms among nurses with shifting schedules. METHODS: Data were collected in two stages. First, in-depth interviews were conducted to collect nurses' experiences. Sentences that best fit the study's purpose were extracted for the construction of Q statements. Second, nurses were allowed to subjectively rank these Q statements by using Q-sorts. A total of 90 participants ranked the designed Q statements. The Q factor analysis revealed a five-factor solution that accounted for 48.90% of the total variance. RESULTS: The five evident factors included: menstrual symptoms interfering in collaboration with colleagues, deficiency of professional function and stress due to symptoms burden, diverse experiences without a clear pattern, adapted self-management with and without medication use, and stress due to symptoms burden and using medication for self-management. CONCLUSIONS: The identification of these five groups may facilitate the development of responsive strategies to meet nurses' preferences. Furthermore, identifying workplace factors that are associated with the adverse effects of menstrual symptoms on nurses will be helpful for nursing supervisors and hospital managers. Additionally, strategies that can be implemented to create supportive work environments are discussed.

17.
Angew Chem Int Ed Engl ; 60(44): 23771-23776, 2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34405502

RESUMEN

Thermally activated delayed fluorescence (TADF) materials with through-space charge transfers (CT) have attracted particularly interest recently. However, the slow reverse intersystem crossing (RISC) and radiative decay always limit their electroluminescence performances. Herein, TADF molecules with ortho-linked multiple donors-acceptor (ortho-Dn -A) motif are developed to create near-degenerate excited states for the reinforcement of spin-orbit coupling. The incorporation of both through-bond and through-space CT enlarges oscillator strength. The optimal ortho-D3 -A compound exhibits a photoluminescence quantum yield of ca. 100 %, a high RISC rate of 2.57×106  s-1 and a high radiative decay rate of 1.00×107  s-1 simultaneously. With this compound as the sensitizer, a TADF-sensitized-fluorescent organic light-emitting diode shows a maximum external quantum efficiency of 31.6 % with an ultrapure green Commission Internationale de L'Eclairage y coordinate value of 0.69.

18.
Phys Rev Lett ; 124(10): 100605, 2020 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-32216397

RESUMEN

A powerful perspective in understanding nonequilibrium quantum dynamics is through the time evolution of its entanglement content. Yet apart from a few guiding principles for the entanglement entropy, to date, much less is known about the refined characteristics of entanglement propagation. Here, we unveil signatures of the entanglement evolving and information propagating out of equilibrium, from the view of the entanglement Hamiltonian. We investigate quantum quench dynamics of prototypical Bose-Hubbard model using state-of-the-art numerical technique combined with conformal field theory. Before reaching equilibrium, it is found that a current operator emerges in the entanglement Hamiltonian, implying that entanglement spreading is carried by particle flow. In the long-time limit the subsystem enters a steady phase, evidenced by the dynamic convergence of the entanglement Hamiltonian to the expectation of a thermal ensemble. Importantly, the entanglement temperature in steady state is spatially independent, which provides an intuitive trait of equilibrium. These findings not only provide crucial information on how equilibrium statistical mechanics emerges in many-body dynamics, but also add a tool to exploring quantum dynamics from the perspective of the entanglement Hamiltonian.

19.
BMC Cancer ; 20(1): 1023, 2020 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-33092589

RESUMEN

BACKGROUND: This study proposes a prediction model for the automatic assessment of lung cancer risk based on an artificial neural network (ANN) with a data-driven approach to the low-dose computed tomography (LDCT) standardized structure report. METHODS: This comparative validation study analysed a prospective cohort from Chiayi Chang Gung Memorial Hospital, Taiwan. In total, 836 asymptomatic patients who had undergone LDCT scans between February 2017 and August 2018 were included, comprising 27 lung cancer cases and 809 controls. A derivation cohort of 602 participants (19 lung cancer cases and 583 controls) was collected to construct the ANN prediction model. A comparative validation of the ANN and Lung-RADS was conducted with a prospective cohort of 234 participants (8 lung cancer cases and 226 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. RESULTS: At the cut-off of category 3, the Lung-RADS had a sensitivity of 12.5%, specificity of 96.0%, positive predictive value of 10.0%, and negative predictive value of 96.9%. At its optimal cut-off value, the ANN had a sensitivity of 75.0%, specificity of 85.0%, positive predictive value of 15.0%, and negative predictive value of 99.0%. The area under the ROC curve was 0.764 for the Lung-RADS and 0.873 for the ANN (P = 0.01). The two most important predictors used by the ANN for predicting lung cancer were the documented sizes of partially solid nodules and ground-glass nodules. CONCLUSIONS: Compared to the Lung-RADS, the ANN provided better sensitivity for the detection of lung cancer in an Asian population. In addition, the ANN provided a more refined discriminative ability than the Lung-RADS for lung cancer risk stratification with population-specific demographic characteristics. When lung nodules are detected and documented in a standardized structured report, ANNs may better provide important insights for lung cancer prediction than conventional rule-based criteria.


Asunto(s)
Neoplasias Pulmonares/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Área Bajo la Curva , Estudios de Casos y Controles , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Redes Neurales de la Computación , Estudios Prospectivos , Sensibilidad y Especificidad
20.
Cryobiology ; 93: 109-114, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32032586

RESUMEN

Embryo cryopreservation is an important tool to preserve endangered species. As a cryoprotectant for mouse oocytes, antifreeze protein from Anatolica polita (ApAFP914) has demonstrated utility. In the present study, the effects of controlled slow freezing and vitrification methods on the survival rate of sheep oocytes fertilized in vitro after freezing-thawing were compared. Different ApAFP914 concentrations were added to the vitrification liquid for exploring the effect of antifreeze protein on the warmed embryos. The results showed that the survival and hatching rates of in vitro derived embryos were significantly higher than that of the slow freezing method. Furthermore, among the cryopreserved embryos at different developmental stages, the survival and hatching rates of the expanded blastocyst were significantly higher than those of the blastocysts, early blastocysts and morula. The survival and the hatching rates of the fast-growing embryos were both significantly higher than that of the slow-growing embryos. Additionally, treatment of ApAFP914 (5-30 µg/mL) did not increase the freezing efficiency of the 6-6.5 d embryos. However, addition of 10 µg/mL of ApAFP914 significantly increased the hatching rate of slow-growing embryos. In conclusion, our study suggests that the vitrification is better than the slow freezing method for the conservation of in vitro sheep embryos, and supplementation of ApAFP914 (10 µg/mL) significantly increased the hatching rate of slow-growing embryos after cryopreservation.


Asunto(s)
Proteínas Anticongelantes/farmacología , Criopreservación/métodos , Embrión de Mamíferos , Proteínas de Insectos/farmacología , Vitrificación , Animales , Blastocisto/efectos de los fármacos , Escarabajos , Desarrollo Embrionario/efectos de los fármacos , Femenino , Congelación , Mórula/efectos de los fármacos , Ovinos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA