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1.
Cell ; 187(2): 345-359.e16, 2024 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-38181787

RESUMEN

Cells self-organize molecules in space and time to generate complex behaviors, but we lack synthetic strategies for engineering spatiotemporal signaling. We present a programmable reaction-diffusion platform for designing protein oscillations, patterns, and circuits in mammalian cells using two bacterial proteins, MinD and MinE (MinDE). MinDE circuits act like "single-cell radios," emitting frequency-barcoded fluorescence signals that can be spectrally isolated and analyzed using digital signal processing tools. We define how to genetically program these signals and connect their spatiotemporal dynamics to cell biology using engineerable protein-protein interactions. This enabled us to construct sensitive reporter circuits that broadcast endogenous cell signaling dynamics on a frequency-barcoded imaging channel and to build control signal circuits that synthetically pattern activities in the cell, such as protein condensate assembly and actin filamentation. Our work establishes a paradigm for visualizing, probing, and engineering cellular activities at length and timescales critical for biological function.


Asunto(s)
Proteínas Bacterianas , Células Eucariotas , Transducción de Señal , Animales , Mamíferos , Biología Sintética/métodos , Células Eucariotas/metabolismo
2.
Brief Bioinform ; 24(4)2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37200156

RESUMEN

Multiple sequence alignment is widely used for sequence analysis, such as identifying important sites and phylogenetic analysis. Traditional methods, such as progressive alignment, are time-consuming. To address this issue, we introduce StarTree, a novel method to fast construct a guide tree by combining sequence clustering and hierarchical clustering. Furthermore, we develop a new heuristic similar region detection algorithm using the FM-index and apply the k-banded dynamic program to the profile alignment. We also introduce a win-win alignment algorithm that applies the central star strategy within the clusters to fast the alignment process, then uses the progressive strategy to align the central-aligned profiles, guaranteeing the final alignment's accuracy. We present WMSA 2 based on these improvements and compare the speed and accuracy with other popular methods. The results show that the guide tree made by the StarTree clustering method can lead to better accuracy than that of PartTree while consuming less time and memory than that of UPGMA and mBed methods on datasets with thousands of sequences. During the alignment of simulated data sets, WMSA 2 can consume less time and memory while ranking at the top of Q and TC scores. The WMSA 2 is still better at the time, and memory efficiency on the real datasets and ranks at the top on the average sum of pairs score. For the alignment of 1 million SARS-CoV-2 genomes, the win-win mode of WMSA 2 significantly decreased the consumption time than the former version. The source code and data are available at https://github.com/malabz/WMSA2.


Asunto(s)
COVID-19 , ARN , Humanos , Alineación de Secuencia , Filogenia , SARS-CoV-2/genética , Programas Informáticos , Algoritmos , ADN/genética
3.
J Cell Mol Med ; 28(2): e18034, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37942713

RESUMEN

Fulminant myocarditis (FM) is the most serious type of myocarditis. However, the molecular mechanism underlying the pathogenesis of FM has not been fully elucidated. Small extracellular vesicles (sEVs) play important roles in many diseases, but any potential role in paediatric FM has not been reported. Here, the differential signatures of lncRNAs in plasma sEVs were studied in FM children and healthy children using transcriptome sequencing followed by functional analysis. Then immune-related lncRNAs were screened to study their role in immune mechanisms, the levels and clinical relevance of core immune-related lncRNAs were verified by qRT-PCR in a large sample size. Sixty-eight lncRNAs had increased levels of plasma sEVs in children with FM and 11 had decreased levels. Functional analysis showed that the sEVs-lncRNAs with different levels were mainly related to immunity, apoptosis and protein efflux. Seventeen core immune-related sEVs-lncRNAs were screened, functional enrichment analysis showed that these lncRNAs were closely related to immune activation, immune cell migration and cytokine pathway signal transduction. The results of the study show that sEVs-lncRNAs may play an important role in the pathogenesis of fulminant myocarditis in children, especially in the mechanism of immune regulation.


Asunto(s)
Vesículas Extracelulares , Miocarditis , ARN Largo no Codificante , Humanos , Niño , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Miocarditis/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Transducción de Señal/genética , Citocinas
4.
Brief Bioinform ; 23(1)2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-34893794

RESUMEN

Multiple sequence alignment (MSA) is fundamental to many biological applications. But most classical MSA algorithms are difficult to handle large-scale multiple sequences, especially long sequences. Therefore, some recent aligners adopt an efficient divide-and-conquer strategy to divide long sequences into several short sub-sequences. Selecting the common segments (i.e. anchors) for division of sequences is very critical as it directly affects the accuracy and time cost. So, we proposed a novel algorithm, FMAlign, to improve the performance of multiple nucleotide sequence alignment. We use FM-index to extract long common segments at a low cost rather than using a space-consuming hash table. Moreover, after finding the longer optimal common segments, the sequences are divided by the longer common segments. FMAlign has been tested on virus and bacteria genome and human mitochondrial genome datasets, and compared with existing MSA methods such as MAFFT, HAlign and FAME. The experiments show that our method outperforms the existing methods in terms of running time, and has a high accuracy on long sequence sets. All the results demonstrate that our method is applicable to the large-scale nucleotide sequences in terms of sequence length and sequence number. The source code and related data are accessible in https://github.com/iliuh/FMAlign.


Asunto(s)
Secuencia de Bases , Alineación de Secuencia , Análisis de Secuencia de ADN/métodos , Algoritmos , Bases de Datos Factuales , Genoma Bacteriano , Genoma Humano , Humanos , Proyectos de Investigación , Programas Informáticos
5.
Rheumatology (Oxford) ; 63(4): 1093-1103, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-37432340

RESUMEN

OBJECTIVE: To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs). METHODS: Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. RESULTS: The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic. CONCLUSION: The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.


Asunto(s)
Artritis Psoriásica , COVID-19 , Endrín/análogos & derivados , Enfermedades Musculares , Enfermedades Musculoesqueléticas , Enfermedades Reumáticas , Adulto , Humanos , Analgésicos Opioides/uso terapéutico , Pandemias , COVID-19/epidemiología , Pautas de la Práctica en Medicina , Control de Enfermedades Transmisibles , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología
6.
J Comput Neurosci ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259462

RESUMEN

We demonstrate a model of chirp-velocity sensitivity in the inferior colliculus (IC) that retains the tuning to amplitude modulation (AM) that was established in earlier models. The mechanism of velocity sensitivity is sequence detection by octopus cells of the posteroventral cochlear nucleus, which have been proposed in physiological studies to respond preferentially to the order of arrival of cross-frequency inputs of different amplitudes. Model architecture is based on coincidence detection of a combination of excitatory and inhibitory inputs. Chirp-sensitivity of the IC output is largely controlled by the strength and timing of the chirp-sensitive octopus-cell inhibitory input. AM tuning is controlled by inhibition and excitation that are tuned to the same frequency. We present several example neurons that demonstrate the feasibility of the model in simulating realistic chirp-sensitivity and AM tuning for a wide range of characteristic frequencies. Additionally, we explore the systematic impact of varying parameters on model responses. The proposed model can be used to assess the contribution of IC chirp-velocity sensitivity to responses to complex sounds, such as speech.

7.
Mol Biol Rep ; 51(1): 961, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235637

RESUMEN

The high cost of producing conventional hybrid cotton seeds led to more research efforts on cotton male sterility systems. There is a lack of studies on cytology, histology, morphological variation, yield, and altered restorer backgrounds to identify and develop male sterility markers in cotton hybrids. Hybrid cotton can be efficiently produced by exploiting genetic male sterility. Among the 19 Genetic Male Sterility (GMS) genes discovered, the lines with ms5ms6 genes are mostly utilised to establish successful hybrid cotton in India. Molecular markers closely associated with the MS alleles are identified to facilitate the efficient and rapid backcrossing of male-sterility genes into elite lines or cultivars by marker-assisted backcrossing. The majority of the markers which are random DNA markers (RDMs), are probably lost, when recombination occurs. In contradiction, molecular markers (functional markers, or FMs) within the genic region can be identified and employed in crops for diverse traits, if prospective characteristic genes are known. In this review, the mechanism of male sterility, its gene expression level, and the need for functional markers for the male sterility trait in cotton have been put forward.


Asunto(s)
Gossypium , Infertilidad Vegetal , Gossypium/genética , Gossypium/fisiología , Infertilidad Vegetal/genética , Marcadores Genéticos , Genes de Plantas/genética , Fitomejoramiento/métodos , Semillas/genética , Regulación de la Expresión Génica de las Plantas/genética , Alelos , Hibridación Genética/genética
8.
J Phycol ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264835

RESUMEN

Due to global rises in temperature, recent studies predict marine species shifting toward higher latitudes. We investigated the impact of interacting abiotic drivers on the distribution potential of the temperate kelp Laminaria hyperborea. The ecosystem engineering species is widespread along European coasts but has not yet been observed in the High Arctic, although it can survive several months of low temperatures and darkness. To investigate its ability to extend northward in future, we conducted a long-term multifactorial experiment with sporophytes from Porsangerfjorden, Norway-close to the species' documented northernmost distribution margin. The samples were exposed to three different photoperiods (PolarDay, LongDay, and PolarNight) at 0°C, 5°C, and 10°C for 3 months. Optimum quantum yield of photosynthesis (Fv/Fm), dry weight, pigments, phlorotannins, and storage carbohydrates were monitored. Both physiological and biochemical parameters revealed that L. hyperborea was strongly influenced by the different photoperiods and their interaction with temperature, while temperature alone exerted only minor effects. The Fv/Fm data were integrated into a species distribution model to project a possible northward expansion of L. hyperborea. The combination of extended day lengths and low temperatures appeared to be the limiting reason for northward spread of L. hyperborea until recently. However, with water temperatures reaching 10°C in summer, this kelp will be able to thrive also in the High Arctic. Moreover, no evidence of stress to Arctic winter warming was observed. Consequently, L. hyperborea has a high potential for spreading northward with further warming which may significantly affect the structure and function of Arctic ecosystems.

9.
Biosci Biotechnol Biochem ; 88(2): 181-188, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-37968134

RESUMEN

Type I hypersensitivity is triggered by mast cell degranulation, a stimulus-induced exocytosis of preformed secretory granules (SGs) containing various inflammatory mediators. The degree of degranulation is generally expressed as a percentage of secretory granule markers (such as ß-hexosaminidase and histamine) released into the external solution, and considerable time and labor are required for the quantification of markers in both the supernatants and cell lysates. In this study, we developed a simple fluorimetry-based degranulation assay using rat basophilic leukemia (RBL-2H3) mast cells. During degranulation, the styryl dye FM1-43 in the external solution fluorescently labeled the newly exocytosed SGs, whose increase in intensity was successively measured using a fluorescence microplate reader. In addition to the rate of ß-hexosaminidase secretion, the cellular FM1-43 intensity successfully represented the degree and kinetics of degranulation under various conditions, suggesting that this method facilitates multi-sample and/or multi-time-point analyses required for screening substances regulating mast cell degranulation.


Asunto(s)
Degranulación de la Célula , Compuestos de Piridinio , Compuestos de Amonio Cuaternario , Ratas , Animales , Vesículas Secretoras/metabolismo , Mastocitos , beta-N-Acetilhexosaminidasas
10.
Neuropsychol Rehabil ; : 1-33, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38385531

RESUMEN

Fibromyalgia (FM) is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, and stiffness in muscles and joints. Traumatic life experiences and post-traumatic stress symptoms play a role in its development and persistence. Although previous research suggests that pain and FM symptoms decrease after eye movement desensitization and reprocessing (EMDR) therapy, its effectiveness has not been investigated in a controlled manner. The present study investigated the effectiveness of a six-session, 90-minute EMDR therapy using a multiple baseline single-case experimental design (SCED) across ten adult females with FM. The SCED involved a baseline, intervention, one- and three-month follow-up phase. The primary outcome was pain. Secondary outcomes included post-traumatic stress symptoms, other FM symptoms (fatigue, stiffness in muscles and joints), and the impact of FM on daily activities and sleep. Data were statistically analyzed by primarily testing means across phases on an individual and group level. Post-traumatic stress symptoms improved significantly in seven participants. Pain severity decreased significantly in six participants, with three of them maintaining significant improvement three months later. One participant showed clinically relevant change one month later. Furthermore, improvements were observed in secondary outcome measures. The findings support the efficacy of EMDR in reducing FM symptoms.

11.
Nord J Psychiatry ; 78(5): 376-381, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38557370

RESUMEN

AIM: The diagnoses of Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are highly associated with fatigue and pain, respectively. Physiologically and clinically an effect of thyroid status on fatigue and pain is expected. There may be clinically relevant differences in thyroid hormone axes though within values of reference in both patients with normal thyroid hormones, or in patients with well-regulated thyroid disease. These potential differences are explored in this study. MATERIALS AND METHODS: In the present study, female patients with CFS (n = 49) and FM (n = 58) as well as female healthy controls (n = 53) were included. We explored plasma levels of TSH and FT4 between the groups using Kruskall-Wallis, and the relation between fatigue score and levels of TSH and FT4 by means of Spearman's rho. RESULTS: There were no group differences between CFS patients, FM patients, and healthy controls in levels of TSH and FT4. CONCLUSION: As one might clinically and physiologically expect an association between thyroid function and fatigue, which may be associated with clinical disorders such as CFS and FM, we suggest future studies to examine the field further by exploring the influence of thyroid receptors and responses of the thyroid hormone cascade.


Asunto(s)
Síndrome de Fatiga Crónica , Fibromialgia , Tirotropina , Tiroxina , Humanos , Síndrome de Fatiga Crónica/sangre , Síndrome de Fatiga Crónica/fisiopatología , Fibromialgia/sangre , Fibromialgia/fisiopatología , Femenino , Tirotropina/sangre , Adulto , Tiroxina/sangre , Persona de Mediana Edad , Fatiga/sangre , Fatiga/fisiopatología , Estudios de Casos y Controles
12.
New Phytol ; 237(1): 113-125, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36161283

RESUMEN

Singlet oxygen (1 O2 ) is a harmful species that functions also as a signaling molecule. In chloroplasts, 1 O2 is produced via charge recombination reactions in photosystem II, but which recombination pathway(s) produce triplet Chl and 1 O2 remains open. Furthermore, the role of 1 O2 in photoinhibition is not clear. We compared temperature dependences of 1 O2 production, photoinhibition, and recombination pathways. 1 O2 production by pumpkin thylakoids increased from -2 to +35°C, ruling out recombination of the primary charge pair as a main contributor. S2 QA - or S2 QB - recombination pathways, in turn, had too steep temperature dependences. Instead, the temperature dependence of 1 O2 production matched that of misses (failures of the oxygen (O2 ) evolving complex to advance an S-state). Photoinhibition in vitro and in vivo (also in Synechocystis), and in the presence or absence of O2 , had the same temperature dependence, but ultraviolet (UV)-radiation-caused photoinhibition showed a weaker temperature response. We suggest that the miss-associated recombination of P680 + QA - is the main producer of 1 O2 . Our results indicate three parallel photoinhibition mechanisms. The manganese mechanism dominates in UV radiation but also functions in white light. Mechanisms that depend on light absorption by Chls, having 1 O2 or long-lived P680 + as damaging agents, dominate in red light.


Asunto(s)
Complejo de Proteína del Fotosistema II , Tilacoides , Complejo de Proteína del Fotosistema II/metabolismo , Tilacoides/metabolismo , Oxígeno Singlete/metabolismo , Luz , Oxígeno/metabolismo
13.
Rheumatology (Oxford) ; 62(8): 2757-2764, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36573318

RESUMEN

OBJECTIVES: Coexistence of FM represents a challenge in the evaluation of enthesitis in patients with axial spondyloarthritis (axSpA) due to a possible overlap between the tender points (TP) due to enthesitis and those of FM. The objective was to assess the agreement between the MASES enthesitis score and the tender points of the ACR 1990 criteria in patients with axSpA. METHODS: This was a cross-sectional ancillary analysis of the Predict-SpA study (NCT03039088). Patients had a diagnosis of axSpA according to their rheumatologist and an indication to start a TNFα blocker. All patients were screened for FM according to the FiRST questionnaire. A physician was asked to assess 31 anatomically described sites in a random order without knowing to which instrument the site belonged (i.e. the 18 ACR 1990 TP and the 13 MASES sites). Agreement between the MASES and the ACR 1990 TPs by the intraclass correlation coefficient (ICC), also stratified by the presence/absence of concomitant FM according to the FiRST. RESULTS: Among the 526 patients, 53% were men and 202 (38%) had FM. Radiographic sacroiliitis and MRI sacroiliitis were present in 56% and 68% patients, respectively. Patients were mostly men (53.4%) with radiographic and MRI sacroiliitis in 56% and 68% patients, respectively. Mean number of ACR 1990 TP was 5.4 (s.d. 4.6) and mean MASES was 4.2 (s.d. 3.6). ICC between both scores was 0.7 [95% CI (0.6, 0.8)]. ICC between both scores was 0.6 [95% CI (0.3, 0.8)] and 0.7 [95% CI (0.6, 0.7)] for patients with and without FM, respectively. CONCLUSION: These results suggest a significant overlap between both scores in patients with axSpA, including in those without concomitant FM. TRIAL REGISTRATION: clinicaltrials.gov, https://clinicaltrials.gov, NCT03039088.


Asunto(s)
Espondiloartritis Axial , Entesopatía , Fibromialgia , Sacroileítis , Espondiloartritis , Masculino , Humanos , Femenino , Fibromialgia/diagnóstico , Fibromialgia/complicaciones , Sacroileítis/diagnóstico por imagen , Sacroileítis/complicaciones , Estudios Transversales , Entesopatía/diagnóstico por imagen , Entesopatía/complicaciones , Espondiloartritis/complicaciones , Espondiloartritis/diagnóstico
14.
J Exp Bot ; 74(18): 5458-5471, 2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37410874

RESUMEN

Photosystem II (PSII) uses solar energy to oxidize water and delivers electrons to fix CO2. Although the structure at atomic resolution and the basic photophysical and photochemical functions of PSII are well understood, many important questions remain. The activity of PSII in vitro and in vivo is routinely monitored by recording the induction kinetics of chlorophyll a fluorescence (ChlF). According to the 'mainstream' model, the rise from the minimum level (Fo) to the maximum (Fm) of ChlF of dark-adapted PSII reflects the closure of all functionally active reaction centers, and the Fv/Fm ratio is equated with the maximum photochemical quantum yield of PSII (where Fv=Fm-Fo). However, this model has never been free of controversies. Recent experimental data from a number of studies have confirmed that the first single-turnover saturating flash (STSF), which generates the closed state (PSIIC), produces F1

15.
Mol Pharm ; 20(1): 419-426, 2023 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-36538346

RESUMEN

The contribution ratio of metabolic enzymes such as cytochrome P450 to in vivo clearance (fraction metabolized: fm) is a pharmacokinetic index that is particularly important for the quantitative evaluation of drug-drug interactions. Since obtaining experimental in vivo fm values is challenging, those derived from in vitro experiments have often been used alternatively. This study aimed to explore the possibility of constructing machine learning models for predicting in vivo fm using chemical structure information alone. We collected in vivo fm values and chemical structures of 319 compounds from a public database with careful manual curation and constructed predictive models using several machine learning methods. The results showed that in vivo fm values can be obtained from structural information alone with a performance comparable to that based on in vitro experimental values and that the prediction accuracy for the compounds involved in CYP induction or inhibition is significantly higher than that by using in vitro values. Our new approach to predicting in vivo fm values in the early stages of drug discovery should help improve the efficiency of the drug optimization process.


Asunto(s)
Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450 , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Interacciones Farmacológicas , Área Bajo la Curva , Descubrimiento de Drogas/métodos
16.
Crit Rev Food Sci Nutr ; : 1-18, 2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37440689

RESUMEN

In today's world, non-nutritive sweeteners (NNSs) are recognized as substitutes for sugar or other high-calorie sweeteners, and their consumption is increasing dramatically. However, there is ongoing debate regarding the impact of NNSs on anthropometric indices. To fill this gap in knowledge, the current GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of artificial- and stevia-based sweeteners consumption on anthropometric indices and serum leptin level which is known as an appetite-regulating hormone. A comprehensive search was conducted on the Scopus, PubMed, and Embase databases up to November 2022 to identify randomized controlled trials (RCTs) investigating the effects of NNSs on anthropometric indices and serum leptin levels. Data extraction from qualified studies was performed independently by two researchers. A random- or fixed-effects model was used to estimate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for anthropometric indices such as body weight (BW), body mass index (BMI), fat mass (FM), fat-free mass (FFM), waist circumference (WC) and serum leptin level. Heterogeneity between studies was assessed using Cochran's Q test and quantified using the I2 statistic. From a pool of 3212 studies initially identified, 20 studies with a total sample size of 2158 subjects were included in the analysis. Results of the pooled analysis showed that NNSs consumption had a significant reducing effect on BW (WMD: -1.02, 95% CI: -1.57, -0.46 Kg), FM (WMD: -1.09, 95% CI: -1.90, -0.29), and FFM (WMD: -0.83, 95% CI: -1.42, -0.23), but did not have any significant effect on BMI (WMD: -0.16, 95% CI: -0.35, 0.02), WC (WMD: -1.03, 95% CI: -2.77, 0.72), or serum leptin level (WMD: -2.17, 95% CI: -4.98, 0.65). The findings of this study indicate that the consumption of artificial- and stevia-based sweeteners may lead to a reduction in body weight, fat mass, and free fat mass.

17.
Cell Mol Life Sci ; 79(6): 286, 2022 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-35534740

RESUMEN

Endocytosis is controlled by a well-orchestrated molecular machinery, where the individual players as well as their precise interactions are not fully understood. We now show that syndapin I/PACSIN 1 is expressed in pancreatic ß cells and that its knockdown abrogates ß cell endocytosis leading to disturbed plasma membrane protein homeostasis, as exemplified by an elevated density of L-type Ca2+ channels. Intriguingly, inositol hexakisphosphate (InsP6) activates casein kinase 2 (CK2) that phosphorylates syndapin I/PACSIN 1, thereby promoting interactions between syndapin I/PACSIN 1 and neural Wiskott-Aldrich syndrome protein (N-WASP) and driving ß cell endocytosis. Dominant-negative interference with endogenous syndapin I/PACSIN 1 protein complexes, by overexpression of the syndapin I/PACSIN 1 SH3 domain, decreases InsP6-stimulated endocytosis. InsP6 thus promotes syndapin I/PACSIN 1 priming by CK2-dependent phosphorylation, which endows the syndapin I/PACSIN 1 SH3 domain with the capability to interact with the endocytic machinery and thereby initiate endocytosis, as exemplified in ß cells.


Asunto(s)
Proteínas del Citoesqueleto , Ácido Fítico , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Proteínas del Citoesqueleto/metabolismo , Endocitosis/fisiología , Fosforilación
18.
Ecotoxicol Environ Saf ; 257: 114930, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37080135

RESUMEN

The reduction of Cd and Pb accumulation in wheat grains grown on Cd and Pb contaminated alkaline soils is a pressing issue that needs to be solved. In this study, ferromanganese functionalized biochar (FM-BC) was used to remediate Cd and Pb contaminated alkaline soils and mitigate Cd and Pb accumulation in wheat grains. The immobilization capacity and mechanism of FM-BC were investigated by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) characterization and chemical analysis. Fe and Mn loaded on FM-BC improved the removal efficiencies of DTPA-Cd and DTPA-Pb in soil with DTPA-Cd removal of 22.99%- 52.04% (JM22) and 25.54%- 53.32 (AK58) and DTPA-Pb removal of 11.39%- 22.36% (JM22) and 5.38%- 13.00% (AK58). The FT-IR and XRD results indicated that the complexation and precipitation of Cd and Pb with the Fe-Mn oxides and the oxygen-containing functional groups on biochar surface stabilized the Cd and Pb in soil for the observation of Cd2Mn3O8, PbHPO4, CdCO3, and PbO2 on FM-BC isolated from contaminated soils. FM-BC with excellent adsorption capacity reduced the available Cd and Pb in the soil, therefore, thereby inhibiting the Cd and Pb accumulation in wheat. In the 3% FM-BC treatment, Cd and Pb contents in wheat grains were lower than 0.10 mg/kg and 0.20 mg/kg, respectively, reaching the national safety standards. And FM-BC increased the Fe, Mn, Na and Zn contents in wheat grains, and improved the growth and yield of wheat. These findings suggest that FM-BC can be considered a prospective and effective material for remediation of alkaline soils contaminated with Cd and Pb.


Asunto(s)
Cadmio , Contaminantes del Suelo , Cadmio/análisis , Triticum , Plomo/análisis , Espectroscopía Infrarroja por Transformada de Fourier , Estudios Prospectivos , Contaminantes del Suelo/análisis , Carbón Orgánico/química , Suelo/química , Ácido Pentético
19.
Ecotoxicol Environ Saf ; 254: 114764, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36907097

RESUMEN

A field study was conducted to compare FM-1 inoculation by irrigation and spraying for promoting Bidens pilosa L. phytoremediation of cadmium (Cd)-contaminated soil. Cascading relationships between bacterial inoculation by irrigation and spraying and soil properties, plant growth-promoting traits, plant biomass and Cd concentrations in Bidens pilosa L. were explored based on the partial least squares path model (PLS-PM). The results indicated that inoculation with FM-1 not only improved the rhizosphere soil environment of B. pilosa L. but also increased the Cd extracted from the soil. Moreover, Fe and P in leaves play vital roles in promoting plant growth when FM-1 is inoculated by irrigation, while Fe in leaves and stems plays a vital role in promoting plant growth when FM-1 is inoculated by spraying. In addition, FM-1 inoculation decreased the soil pH by affecting soil dehydrogenase and oxalic acid in cases with irrigation and Fe in roots in cases with spraying. Thus, the soil bioavailable Cd content increased and promoted Cd uptake by Bidens pilosa L. To address Cd-induced oxidative stress, Fe in leaves helped to convert GSH into PCs, which played a vital role in ROS scavenging when FM-1 was inoculated by irrigation. The soil urease content effectively increased the POD and APX activities in the leaves of Bidens pilosa L., which helped alleviate Cd-induced oxidative stress when FM-1 was inoculated by spraying. This study compares and illustrates the potential mechanism by which FM-1 inoculation can improve the phytoremediation of Cd-contaminated soil by Bidens pilosa L., suggesting that FM-1 inoculation by irrigation and spraying is useful in the phytoremediation of Cd-contaminated sites.


Asunto(s)
Bidens , Contaminantes del Suelo , Cadmio/análisis , Biodegradación Ambiental , Contaminantes del Suelo/análisis , Suelo/química , Raíces de Plantas
20.
BMC Med Educ ; 23(1): 183, 2023 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-36964563

RESUMEN

BACKGROUND: Medical educators in academia have faced challenges incorporating leadership training into curricula while minimizing redundancy and assuring value and relevance for all learners. This study aims to assess the status of leadership training as perceived by family medicine residents in Riyadh to advise the development of a formal leadership training curriculum. METHOD: The research is cross-sectional and quantitative. Participants were asked via an electronic questionnaire about their leadership attitudes, perceived degree of training in various leadership domains, and where they could find additional training. RESULTS: The survey was completed by 270 family medicine residents in Riyadh. Residents rated the importance of physician leadership in their communities as high (6 out of 7 on a Likert scale). In contrast, agreement with the statement 'I am a leader' obtained the lowest grade (4.4 of 7 on a Likert scale). Overall, most of the residents participating in the study (50% or more) voiced a desire for more training in all leadership domains. Over 50% of residents indicated that leadership electives or selective lectures, workshops, or seminars as well as WADAs (Weekly Academic Day Activities), leadership mentors or coaches teaching junior learners (with training), and leadership courses could be incorporated into the curriculum to foster leadership skills. CONCLUSION: Residents were enthusiastic about family physicians being leaders, aligning with the current educational philosophy but requiring formal training. They also indicated areas where leadership training might be improved and developed in the current curriculum. This poll's results could be used to help residents build leadership skills by incorporating them into a formal leadership curriculum.


Asunto(s)
Internado y Residencia , Humanos , Estudios Transversales , Medicina Familiar y Comunitaria/educación , Liderazgo , Curriculum
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