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1.
J Chem Theory Comput ; 20(12): 5337-5351, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38856971

RESUMO

Quantum mechanical (QM) treatments, when combined with molecular mechanical (MM) force fields, can effectively handle enzyme-catalyzed reactions without significantly increasing the computational cost. In this context, we present CHARMM-GUI QM/MM Interfacer, a web-based cyberinfrastructure designed to streamline the preparation of various QM/MM simulation inputs with ligand modification. The development of QM/MM Interfacer has been achieved through integration with existing CHARMM-GUI modules, such as PDB Reader and Manipulator, Solution Builder, and Membrane Builder. In addition, new functionalities have been developed to facilitate the one-stop preparation of QM/MM systems and enable interactive and intuitive ligand modifications and QM atom selections. QM/MM Interfacer offers support for a range of semiempirical QM methods, including AM1(+/d), PM3(+/PDDG), MNDO(+/d, +/PDDG), PM6, RM1, and SCC-DFTB, tailored for both AMBER and CHARMM. A nontrivial setup related to ligand modification, link-atom insertion, and charge distribution is automatized through intuitive user interfaces. To illustrate the robustness of QM/MM Interfacer, we conducted QM/MM simulations of three enzyme-substrate systems: dihydrofolate reductase, insulin receptor kinase, and oligosaccharyltransferase. In addition, we have created three tutorial videos about building these systems, which can be found at https://www.charmm-gui.org/demo/qmi. QM/MM Interfacer is expected to be a valuable and accessible web-based tool that simplifies and accelerates the setup process for hybrid QM/MM simulations.


Assuntos
Simulação de Dinâmica Molecular , Teoria Quântica , Software , Ligantes
2.
Plants (Basel) ; 13(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38891384

RESUMO

Rapeseed (Brassica napus L.) holds significant commercial value as one of the leading oil crops, with its agronomic features and oil quality being crucial determinants. In this investigation, 73,226 single nucleotide polymorphisms (SNPs) across 95 rapeseed mutant lines induced by gamma rays, alongside the original cultivar ('Tamra'), using genotyping-by-sequencing (GBS) analysis were examined. This study encompassed gene ontology (GO) analysis and a genomewide association study (GWAS), thereby concentrating on agronomic traits (e.g., plant height, ear length, thousand-seed weight, and seed yield) and oil traits (including fatty acid composition and crude fat content). The GO analysis unveiled a multitude of genes with SNP variations associated with cellular processes, intracellular anatomical structures, and organic cyclic compound binding. Through GWAS, we detected 320 significant SNPs linked to both agronomic (104 SNPs) and oil traits (216 SNPs). Notably, two novel candidate genes, Bna.A05p02350D (SFGH) and Bna.C02p22490D (MDN1), are implicated in thousand-seed weight regulation. Additionally, Bna.C03p14350D (EXO70) and Bna.A09p05630D (PI4Kα1) emerged as novel candidate genes associated with erucic acid and crude fat content, respectively. These findings carry implications for identifying superior genotypes for the development of new cultivars. Association studies offer a cost-effective means of screening mutants and selecting elite rapeseed breeding lines, thereby enhancing the commercial viability of this pivotal oil crop.

3.
J Neurol Sci ; 462: 123113, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38941706

RESUMO

BACKGROUND: Brain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or cortical volume to subcortical gray matter structure volumes are potential imaging markers for cognitive alterations in AD dementia and amnestic mild cognitive impairment (aMCI). METHODS: Seventy-seven subjects diagnosed with AD dementia or aMCI underwent baseline neuropsychological testing, 2-year follow-up cognitive assessments, and high-resolution T1-weighted MRI scans. Total brain/cortical volume and subcortical gray matter structure volumes were automatically segmented and measured. Univariate and multiple linear regression analyses were conducted to determine the associations between volumetric ratios and interval changes in cognitive scores. RESULTS: The ratio of cortical volume to caudate volume showed the most significant association with changes in MoCA (B = 0.132, SE = 0.042, p = 0.002), MMSE (B = 0.140, SE = 0.040, p = 0.001), and CDR-SOB (B = -0.013, SE = 0.005, p = 0.007) scores over the 2-year follow-up period. These associations remained significant after adjusting for various covariates. Similar associations were observed for the ratios of cortical volume to putamen and globus pallidum volumes. CONCLUSIONS: The cortex-to-caudate volume ratio is significantly associated with cognitive decline in AD dementia and aMCI. This ratio may serve as a useful biomarker for monitoring disease progression and predicting cognitive outcomes. Our findings highlight the importance of considering the relative atrophy of cortical and subcortical structures in understanding AD pathology.

4.
Front Neurol ; 15: 1406443, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915802

RESUMO

Introduction: Women can experience various reproductive events, such as pregnancy, childbirth, lactation, and contraception, which cause long-term changes in female hormones. In middle-aged women, the prevalence of migraine is high, and a clear gender difference is evident. This study investigated the effects of factors associated with past reproductive events on the risk of new migraine in middle-aged premenopausal women. Methods: The influence of reproductive factors on migraine in middle-aged women was investigated using the Korean National Health Insurance Service (KNHIS) and Korean Health Examination (KHE) databases. The reproductive factors of interest were parity, breastfeeding, and oral contraceptive (OC) use. The study included 949,704 middle-aged premenopausal women 40-60 years of age. The study population was divided into two groups based on new diagnosis of migraine during the follow-up period (2009-2018). Results: The risk of new migraine tended to increase in the primiparous (hazard ratio, HR: 1.179; 95% confidence interval, CI: 1.137-1.221) and multiparous groups (HR: 1.181; 95% CI: 1.142-1.221) compared with the nulliparous group. The breastfeeding ≥12 months group (HR: 1.071; 95% CI: 1.052-1.091) showed a significantly increased risk of new migraine compared with the non-breastfeeding group. All women in the OC groups (< 1 year, HR: 1.048; 95% CI: 1.028-1.069 and ≥ 1 year, HR: 1.100; 95% CI: 1.067-1.134) showed a higher risk of new migraine than those in the non-OC group. Conclusion: The results of the current study indicate that childbirth, longer breastfeeding, and OC use may be associated with a higher risk of new migraine in middle-aged premenopausal women.

5.
Int J Mol Sci ; 25(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732049

RESUMO

In this study, the variability of major glucosinolates in the leaf lamina of 134 Chinese cabbage accessions was investigated using Acquity ultra-performance liquid chromatography (UPLC-ESI-MS/MS). A total of twenty glucosinolates were profiled, of which glucobrassicanapin and gluconapin were identified as the predominant glucosinolates within the germplasm. These two glucosinolates had mean concentration levels above 1000.00 µmol/kg DW. Based on the principal component analysis, accessions IT186728, IT120044, IT221789, IT100417, IT278620, IT221754, and IT344740 were separated from the rest in the score plot. These accessions exhibited a higher content of total glucosinolates. Based on the VIP values, 13 compounds were identified as the most influential and responsible for variation in the germplasm. Sinigrin (r = 0.73), gluconapin (r = 0.78), glucobrassicanapin (r = 0.70), epiprogoitrin (r = 0.73), progoitrin (r = 0.74), and gluconasturtiin (r = 0.67) all exhibited a strong positive correlation with total glucosinolate at p < 0.001. This indicates that each of these compounds had a significant influence on the overall glucosinolate content of the various accessions. This study contributes valuable insights into the metabolic diversity of glucosinolates in Chinese cabbage, providing potential for breeding varieties tailored to consumer preferences and nutritional demands.


Assuntos
Brassica rapa , Glucosinolatos , Espectrometria de Massas em Tandem , Glucosinolatos/análise , Glucosinolatos/metabolismo , Espectrometria de Massas em Tandem/métodos , Brassica rapa/genética , Brassica rapa/química , Brassica rapa/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Folhas de Planta/química , Folhas de Planta/metabolismo , Análise de Componente Principal
6.
Plants (Basel) ; 13(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38794361

RESUMO

Soybean, a major legume crop, has seen a decline in its production owing to challenges in seed germination and the development of seedlings. Thus, in this study, we systematically investigated the influence of various chitosan-S-nitrosoglutathione (chitosan-GSNO) nanoparticle (0, 25, 50, and 100 µM) and Si (0, 0.5, and 1 mM) priming concentrations on soybean seed germination and seedling growth over five different priming durations (range: 1-5 h at each concentration). Significant differences were observed in all parameters, except seedling diameter, with both treatments. Seed germination was significantly enhanced after 3 h of priming in both treatments. The final germination percentage (FGP), peak germination percentage (PGP), vigor index (VI), seedling biomass (SB), hypocotyl length (HL), and radical length (RL) of 100 µM chitosan-GSNO-nanoparticle-primed seeds increased by 20.3%, 41.3%, 78.9%, 25.2%, 15.7%, and 65.9%, respectively, compared with those of the control; however, the mean germination time (MGT) decreased by 18.43%. Si priming at 0.5 mM increased the FGP, PGP, VI, SB, HL, and RL by 13.9%, 55.17%, 39.2%, 6.5%, 22.5%, and 25.1%, respectively, but reduced the MGT by 12.29% compared with the control treatment. Chitosan-GSNO and Si treatment up-regulated the relative expression of gibberellic acid (GA)-related genes (GmGA3ox3 and GmGA2ox1) and down-regulated that of abscisic acid (ABA)-related genes (GmABA2, GmAAO3, and GmNCED5). Chitosan-GSNO and Si application increased bioactive GA4 levels and simultaneously reduced ABA content. Hence, the use of exogenous chitosan-GSNO nanoparticles and Si as priming agents had a beneficial effect on seed germination and seedling growth because of the up-regulation in the expression of GA and down-regulation in the expression of ABA. Additional research is needed to understand the combined impact of Si and chitosan-GSNO nanoparticles, including their effects on the expression levels of other hormones and genes even in the later growth stage of the crop.

7.
Soc Sci Med ; 348: 116796, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38603917

RESUMO

Health disparities by socioeconomic status (SES) are potentially shaped by how an individual's health status and work capacity are affected by the incidence of illness, and how these effects vary across SES groups. We examine the impact of illness on the dynamics of health status, work activity and income in older Singaporeans to gain new insights on how ill health shapes the socioeconomic health gradient. Our data comprise of 60 monthly waves (2015-2019) of panel survey data containing 445,464 person-observations from 11,827 unique respondents from Singapore. We apply a matched event-study difference-in-differences research design to track how older adults' health and work changes following the diagnosis of heart disease and cancer. Our focus is how the dynamics of health and work differ for different SES groups, which we measure by post-secondary education attainment. We find that the dynamics of how self-assessed health recovers following the diagnosis of a new heart disease or cancer do not vary significantly across SES groups. Work activity however varies significantly, with less well-educated males and females being significantly less likely to be in active employment and have income from work, and are marginally more likely to be in retirement following the onset of ill health. By contrast, more well-educated males work more, and earn more a year after the health shock than they did before they fell ill. Occupational differences likely played a role in how work activity of less well-educated men decline more after an acute health event compared with more well-educated men. Understanding the drivers of the socioeconomic health gradient necessitates a focus on individual-level factors, as well as system-level influences, that affect health and work.


Assuntos
Emprego , Disparidades nos Níveis de Saúde , Classe Social , Fatores Socioeconômicos , População do Sudeste Asiático , Humanos , Singapura/epidemiologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Emprego/estatística & dados numéricos , Nível de Saúde , Neoplasias/epidemiologia , Renda/estatística & dados numéricos
8.
Sci Rep ; 14(1): 8747, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627483

RESUMO

This study aimed to evaluate the incidence and likelihood of antibiotic-associated encephalopathy (AAE), comparing rates among the classes of antibiotics in monotherapy or in combination therapy. We also investigated the associations between the incidence of AAE and the glomerular filtration rate (GFR) and electroencephalogram features. Consecutive admissions that used any kind of antibiotics to treat infectious diseases were identified from six hospitals. We classified antibiotics according to three distinct pathophysiologic mechanisms and clinical subtypes. We searched for the incidence of AAE as the primary outcome. A total of 97,433 admission cases among 56,038 patients was identified. Cases that received type 1 antibiotics had significantly more frequent AAE compared to those that received type 2 antibiotics (adjusted odds ratio [OR], 2.62; 95% confidence interval [CI] 1.15-5.95; P = 0.021). Combined use of type 1 + 2 antibiotics was associated with a significantly higher incidence of AAE compared to the use of type 2 antibiotics alone (adjusted OR, 3.44; 95% CI 1.49-7.93; P = 0.004). Groups with GFR < 60 mL/min/1.73 m2 had significantly higher incidence rates of AAE compared to those with GFRs ≥ 90 mL/min/1.73 m2 among cases that received type 1 + 2 antibiotics. Detection of spike-and-wave or sharp-and-wave patterns on electroencephalogram was significantly more common in the combination therapy group. Combination use of antibiotics was associated with a higher incidence of AAE compared to monotherapy. The incidence of AAE significantly increased as renal function decreased, and epileptiform discharges were more likely to be detected in cases receiving combined antibiotics.


Assuntos
Antibacterianos , Encefalopatias , Humanos , Antibacterianos/efeitos adversos , Incidência , Taxa de Filtração Glomerular , Encefalopatias/induzido quimicamente , Encefalopatias/epidemiologia , Encefalopatias/tratamento farmacológico , Hospitais
9.
Antioxidants (Basel) ; 13(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38539909

RESUMO

This study explored the glucosinolate (GSL) content in Brassica plants and utilized in silico analysis approach to assess their antioxidant capabilities. GSLs, present abundantly in Brassica vegetables, offer potential health advantages, including antioxidant effects. Employing Ultra-Performance Liquid Chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS), major GSLs were identified in 89 accessions from diverse species and subspecies. Statistical analysis and principal component analysis unveiled significant GSL variation and potential correlations among the Brassica germplasms. This study unveils the dominance of aliphatic GSLs over aromatic and indolyl compounds in all the accessions. Notably, Gluconapin (GNA) (33,049.23 µmol·kg-1 DW), Glucobrassicanapin (GBN) (9803.82 µmol·kg-1 DW), Progoitrin (PRO) (12,780.48 µmol·kg-1 DW) and Sinigrin (SIN) (14,872.93 µmol·kg-1 DW) were the most abundant compounds across the analyzed accessions. Moreover, in silico docking studies predicted promising antioxidant activity by evaluating the interactions of each GSL with antioxidant enzymes. Specifically, Sinigrin and Gluconapin exhibited a notably weaker influence on antioxidant enzymes. This provides key insights into the antioxidant potential of Brassica germplasm and highlights the importance of in silico analysis for evaluating bioactive properties. In general, the results of this study could be utilized in breeding programs to maximize GSL levels and antioxidant properties in Brassica crops and for developing functional foods with enhanced health benefits.

10.
Sensors (Basel) ; 24(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38474998

RESUMO

A fully integrated 24-GHz radar transceiver with one transmitter (TX) and two receivers (RXs) for compact frequency modulated continuous wave (FMCW) radar applications is here presented. The FMCW synthesizer was realized using a fractional-N phase-locked loop (PLL) and programmable chirp generator, which are completely integrated in the proposed transceiver. The measured output phase noise of the synthesizer is -80 dBc/Hz at 100 kHz offset. The TX consists of a three-bit bridged t-type attenuator for gain control, a two-stage drive amplifier (DA) and a one-stage power amplifier (PA). The TX chain provides an output power of 13 dBm while achieving <0.5 dB output power variation within the range of 24 to 24.25 GHz. The RX with a direct conversion I-Q structure is composed of a two-stage low noise amplifier (LNA), I-Q generator, mixer, transimpedance amplifier (TIA), a two-stage biquad band pass filter (BPF), and a differential-to-single (DTS) amplifier. The TIA and the BPF employ a DC offset cancellation (DCOC) circuit to suppress the strong reflection signal and TX-RX leakage. The RX chain exhibits an overall gain of 100 dB. The proposed radar transceiver is fabricated using a 65 nm CMOS technology. The transceiver consumes 220 mW from a 1 V supply voltage and has 4.84 mm2 die size including all pads. The prototype FMCW radar is realized with the proposed transceiver and Yagi antenna to verify the radar functionality, such as the distance and angle of targets.

11.
Plants (Basel) ; 13(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38256802

RESUMO

Kenaf (Hibiscus cannabinus L.), in the Malvaceae family, is an important crop for not only fiber production, but also various other industrial materials. We performed phylogenetic analysis and a genome-wide association study (GWAS) of seven agronomic traits: days to flowering, plant height, fresh weight, dry weight, flower color, stem color, and leaf shape, using 96 kenaf genotypes, including gamma-irradiation-derived mutant lines. Genotypes were determined by genotyping-by-sequencing (GBS) and a total of 49,241 single-nucleotide polymorphisms (SNPs) were used in the analysis. Days to flowering, plant height, fresh weight, and dry weight were positively correlated with each other, and stem color was also correlated with fresh weight and dry weight. The phylogenetic analysis divided the 96 lines into nine related groups within two independent groups, and the GWAS analysis detected a total of 49 SNPs for days to flowering, plant height, fresh weight, dry weight, flower color, stem color, and leaf shape with -log10(P) ≥ 4, of which 22 were located in genic regions. The detected SNPs were located in genes with homology ranging from 45% to 96% to plants of the Malvaceae and Betulaceae, and these genes were found to be involved in plant growth and development via various pathways. Our identification of SNP markers related to agronomic traits is expected to help improve the quality of selective breeding programs for kenaf.

12.
J Clin Psychol ; 80(5): 1031-1049, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38294127

RESUMO

OBJECTIVE: Although life stress and adversity are well-known risk factors for mental health problems and cognitive impairment among older adults, limited research has comprehensively examined the impact of both childhood and adulthood adversity on psychiatric and cognitive impairment symptoms over a prolonged period. To address this issue, we investigated how lifetime adversity exposure is related to symptoms of depression, anxiety, and cognitive impairment in a nationally representative, longitudinal sample of older adults in the United States. METHOD: We analyzed data from the Health and Retirement Study (1992-2016). The sample included 3496 individuals (59.9% female), aged ≥64 years old (Mage = 76.0 ± 7.6 years in 2016). We used the individual-level panel data and ordinary least squares regressions to estimate associations between childhood and adulthood adversities, and later-life depression, anxiety, and cognitive impairment. RESULTS: Many participants experienced a significant early life (38%) or adulthood (79%) stressor. Moreover, experiencing one childhood adversity (vs. none) was associated with a 17.4% increased risk of adulthood adversity. Finally, as hypothesized, childhood adversity exposure was related to experiencing more depression and anxiety symptoms in later life, whereas adulthood stressor exposure predicted more cognitive impairment as well as more depression and anxiety symptoms. DISCUSSION: These findings demonstrate significant associations between lifetime adversity and symptoms of depression, anxiety, and cognitive impairment in older adults. Screening for lifetime stressors may thus help healthcare professionals and policymakers identify individuals who could potentially benefit from interventions designed to reduce stress and enhance resilience.


Assuntos
Disfunção Cognitiva , Depressão , Humanos , Feminino , Estados Unidos/epidemiologia , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Masculino , Depressão/epidemiologia , Transtornos de Ansiedade/psicologia , Ansiedade/epidemiologia , Estresse Psicológico , Disfunção Cognitiva/epidemiologia
13.
Foods ; 12(24)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38137307

RESUMO

In recent years, there has been a shift towards a greater demand for more nutritious and healthier foods, emphasizing the role of diets in human well-being. Edible Alliums, including common onions, garlic, chives and green onions, are staples in diverse cuisines worldwide and are valued specifically for their culinary versatility, distinct flavors and nutritional and medicinal properties. Green onions are widely cultivated and traded as a spicy vegetable. The mild, onion-like flavor makes the crop a pleasant addition to various dishes, serving as a staple ingredient in many world cuisines, particularly in Eastern Asian countries such as China, Japan and the Republic of Korea. The green pseudostems, leaves and non-developed bulbs of green onions are utilized in salads, stir-fries, garnishes and a myriad of culinary preparations. Additionally, green onions have a rich historical background in traditional medicine and diets, capturing the attention of chefs and the general public. The status of the crop as an important food, its culinary diversity and its nutraceutical and therapeutic value make it a subject of great interest in research. Therefore, the present review has examined the distribution, culinary, nutritional and therapeutic significance of green onions, highlighting the health benefits derived from the consumption of diets with this aromatic vegetable crop as a constituent.

14.
Nanomaterials (Basel) ; 13(21)2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37947748

RESUMO

We doped carbon into a TiZrN coating to reduce hydrogen permeability, and investigated the phase formation, bonding state, microstructure, and surface roughness of the carbon-doped TiZrN. The laser output for laser carburization was limited to a range of 20-50%. The grain size of the TiZrN coatings decreased from 26.49 nm before carburization to 18.31 nm after carburization. For XPS analysis, the sp2/sp3 ratio was 1.23 at 20% laser output, but it showed 2.64 at 40% laser output, which means that amorphous carbon was formed. As the grain size decreased with the formation of amorphous carbon, the surface microstructure of the carbon-doped TiZrN coatings transitioned to an intergranular structure, indicating the creation of amorphous carbon-embedded (Ti, Zr)(C, N) in the coating. The surface roughness (Ra) of the carbon-doped TiZrN coating was decreased to a maximum of 7.12 nm, and the hydrogen permeability correspondingly decreased by 78% at 573 K.

15.
Materials (Basel) ; 16(22)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38005169

RESUMO

MnO2 and CeO2 were doped to improve the corrosion resistance of CSZ (calcia-stabilized zirconia), and we studied the phase formation, mechanical properties, and corrosion resistance by molten mold flux. The volume fraction of the monoclinic phase gradually decreased as the amount of MnO2 doping increased. The splitting phenomenon of the t(101) peak was observed in 2Mn_CSZ, and in 4Mn_CSZ, it was completely split, forming a cubic phase. The relative density increased and the monoclinic phase decreased as the doping amount increased, leading to an increase in Vickers hardness and flexural strength. However, in 3Mn_CSZ and 4Mn_CSZ, where cubic phase formation occurred, the tetragonal phase decreased, leading to a reduction in these properties. MnO2-doped CSZ exhibited a larger fraction of the monoclinic phase compared to the original CSZ after the corrosion test, indicating worsened corrosion resistance. These results are attributed to the predominant presence of Mn3+ and Mn2+ forms, rather than the Mn4+ form, which has a smaller basicity difference with SiO2, and due to the low melting point. The monoclinic phase fraction decreased as the doping amount of CeO2 increased in CeO2-doped CSZ, but the rate of decrease was lower compared to MnO2-doped CSZ. The monoclinic phase decreased as the doping amount increased, but the Vickers hardness and flexural strength showed a decreasing trend due to the low relative density. The destabilization behavior of Ca in SEM-EDS images before and after corrosion was difficult to identify due to the presence of Ca in the slag, and the destabilization behavior of Ce due to slag after corrosion was not observed. In the XRD data of the specimen surface after the corrosion test, the fraction of the monoclinic phase increased compared to before the test but showed a lower monoclinic phase fraction compared to CSZ. It is believed that CeO2 has superior corrosion resistance compared to CaO because Ce predominantly exists in the form of Ce4+, which has a smaller difference in basicity within the zirconia lattice.

16.
Chem Sci ; 14(45): 13014-13024, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38023530

RESUMO

Membrane proteins play essential roles in a number of biological processes, and their structures are important in elucidating such processes at the molecular level and also for rational drug design and development. Membrane protein structure determination is notoriously challenging compared to that of soluble proteins, due largely to the inherent instability of their structures in non-lipid environments. Micelles formed by conventional detergents have been widely used for membrane protein manipulation, but they are suboptimal for long-term stability of membrane proteins, making downstream characterization difficult. Hence, there is an unmet need for the development of new amphipathic agents with enhanced efficacy for membrane protein stabilization. In this study, we designed and synthesized a set of glucoside amphiphiles with a melamine core, denoted melamine-cored glucosides (MGs). When evaluated with four membrane proteins (two transporters and two G protein-coupled receptors), MG-C11 conferred notably enhanced stability compared to the commonly used detergents, DDM and LMNG. These promising findings are mainly attributed to a unique feature of the MGs, i.e., the ability to form dynamic water-mediated hydrogen-bond networks between detergent molecules, as supported by molecular dynamics simulations. Thus, MG-C11 is the first example of a non-peptide amphiphile capable of forming intermolecular hydrogen bonds within a protein-detergent complex environment. Detergent micelles formed via a hydrogen-bond network could represent the next generation of highly effective membrane-mimetic systems useful for membrane protein structural studies.

17.
Neuropsychiatr Dis Treat ; 19: 2081-2091, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37810949

RESUMO

Purpose: Patients with epilepsy frequently experience autonomic dysfunction, closely related to sudden unexplained death in epilepsy (SUDEP). SUDEP occurs most often at night or during sleep, and frequent nocturnal seizures are an established risk factor. This study investigated the influence of nocturnal seizures on autonomic dysfunction in epilepsy. Patients and Methods: This retrospective study enrolled frontal lobe epilepsy (FLE) patients who performed 24-hour EEG monitoring. All participants were divided into nocturnal FLE (NFLE, > 90% of seizures occurring during sleep) or diurnal FLE (DFLE) groups. EEG and ECG signals were simultaneously obtained during waking and sleep stages. EEG current density source and connectivity analysis of the autonomic network were performed. ECG was analyzed across time and frequency domains heart rate variability (HRV) analysis method was used. The obtained parameters were compared between the NFLE and DFLE groups. Results: Fifteen NFLE and 16 DFLE patients were enrolled with no significant difference in age, sex, disease duration, seizure frequency, or the number of anti-seizure medications between the two groups. During sleep, a decrease in HRV parameters and an increase of the beta-1 (13-22 Hz) current source density power in the bilateral paracentral lobule (BA4,5,6), precuneus (BA7), and cingulate (BA31) were observed in the NFLE group compared to DFLE group. The NFLE group also showed hyperconnectivity in the central autonomic (12 edges distributed over 10 nodes), sympathetic (2 edges distributed over 3 nodes), and parasympathetic (4 edges distributed over 6 nodes) beta-1 frequency band networks during sleep. During wakefulness, central and cardiac autonomic variables were not significantly different between the NFLE and DFLE groups. Conclusion: Interictal cardiac and central autonomic dysfunction occurred simultaneously and can be attributed to the brain-heart autonomic axis. Our findings suggest that nocturnal seizures may contribute to interictal autonomic dysfunction during sleep in people with epilepsy.

18.
Nat Methods ; 20(10): 1581-1592, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37723246

RESUMO

Here we report SUPPORT (statistically unbiased prediction utilizing spatiotemporal information in imaging data), a self-supervised learning method for removing Poisson-Gaussian noise in voltage imaging data. SUPPORT is based on the insight that a pixel value in voltage imaging data is highly dependent on its spatiotemporal neighboring pixels, even when its temporally adjacent frames alone do not provide useful information for statistical prediction. Such dependency is captured and used by a convolutional neural network with a spatiotemporal blind spot to accurately denoise voltage imaging data in which the existence of the action potential in a time frame cannot be inferred by the information in other frames. Through simulations and experiments, we show that SUPPORT enables precise denoising of voltage imaging data and other types of microscopy image while preserving the underlying dynamics within the scene.


Assuntos
Microscopia , Redes Neurais de Computação , Razão Sinal-Ruído , Distribuição Normal , Processamento de Imagem Assistida por Computador/métodos
19.
Plants (Basel) ; 12(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37687325

RESUMO

Soybean (Glycine max) is a crucial legume crop known for its nutritional value, as its seeds provide large amounts of plant protein and oil. To ensure maximum productivity in soybean farming, it is essential to carefully choose high-quality seeds that possess desirable characteristics, such as the appropriate size, shape, color, and absence of any damage. By studying the relationship between seed shape and other traits, we can effectively identify different genotypes and improve breeding strategies to develop high-yielding soybean seeds. This study focused on the analysis of seed traits using a Python algorithm. The seed length, width, projected area, and aspect ratio were measured, and the total number of seeds was calculated. The OpenCV library along with the contour detection function were used to measure the seed traits. The seed traits obtained through the algorithm were compared with the values obtained manually and from two software applications (SmartGrain and WinDIAS). The algorithm-derived measurements for the seed length, width, and projected area showed a strong correlation with the measurements obtained using various methods, with R-square values greater than 0.95 (p < 0.0001). Similarly, the error metrics, including the residual standard error, root mean square error, and mean absolute error, were all below 0.5% when comparing the seed length, width, and aspect ratio across different measurement methods. For the projected area, the error was less than 4% when compared with different measurement methods. Furthermore, the algorithm used to count the number of seeds present in the acquired images was highly accurate, and only a few errors were observed. This was a preliminary study that investigated only some morphological traits, and further research is needed to explore more seed attributes.

20.
Plants (Basel) ; 12(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37765458

RESUMO

Onion (Allium cepa L.) is recognized globally as a crucial vegetable crop, prized not only for its culinary applications but also for its numerous health-promoting properties. With climate change relentlessly exerting mounting challenges to agriculture, the preservation and deployment of onion germplasm has become critical to ensuring sustainable agriculture and safeguarding food security. Global onion germplasm collections function as repositories of genetic diversity, holding within them an extensive array of valuable traits or genes. These can be harnessed to develop varieties resilient to climate adversities. Therefore, detailed information concerning onion germplasm collections from various geographical regions can bolster their utility. Furthermore, an amplified understanding of the importance of fostering international and inter-institutional collaborations becomes essential. Sharing and making use of onion genetic resources can provide viable solutions to the looming agricultural challenges of the future. In this review, we have discussed the preservation and worldwide distribution of onion germplasm, along with its implications for agricultural sustainability. We have also underscored the importance of international and interinstitutional collaboration in onion germplasm collecting and conservation for agricultural sustainability.

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