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1.
PLoS Genet ; 18(4): e1010144, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35404950

RESUMEN

Polyglutamylation is a dynamic posttranslational modification where glutamate residues are added to substrate proteins by 8 tubulin tyrosine ligase-like (TTLL) family members (writers) and removed by the 6 member Nna1/CCP family of carboxypeptidases (erasers). Genetic disruption of polyglutamylation leading to hyperglutamylation causes neurodegenerative phenotypes in humans and animal models; the best characterized being the Purkinje cell degeneration (pcd) mouse, a mutant of the gene encoding Nna1/CCP1, the prototypic eraser. Emphasizing the functional importance of the balance between glutamate addition and elimination, loss of TTLL1 prevents Purkinje cell degeneration in pcd. However, whether Ttll1 loss protects other vulnerable neurons in pcd, or if elimination of other TTLLs provides protection is largely unknown. Here using a mouse genetic rescue strategy, we characterized the contribution of Ttll1, 4, 5, 7, or 11 to the degenerative phenotypes in cerebellum, olfactory bulb and retinae of pcd mutants. Ttll1 deficiency attenuates Purkinje cell loss and function and reduces olfactory bulb mitral cell death and retinal photoreceptor degeneration. Moreover, degeneration of photoreceptors in pcd is preceded by impaired rhodopsin trafficking to the rod outer segment and likely represents the causal defect leading to degeneration as this too is rescued by elimination of TTLL1. Although TTLLs have similar catalytic properties on model substrates and several are highly expressed in Purkinje cells (e.g. TTLL5 and 7), besides TTLL1 only TTLL4 deficiency attenuated degeneration of Purkinje and mitral cells in pcd. Additionally, TTLL4 loss partially rescued photoreceptor degeneration and impaired rhodopsin trafficking. Despite their common properties, the polyglutamylation profile changes promoted by TTLL1 and TTLL4 deficiencies in pcd mice are very different. We also report that loss of anabolic TTLL5 synergizes with loss of catabolic Nna1/CCP1 to promote photoreceptor degeneration. Finally, male infertility in pcd is not rescued by loss of any Ttll. These data provide insight into the complexity of polyglutamate homeostasis and function in vivo and potential routes to ameliorate disorders caused by disrupted polyglutamylation.


Asunto(s)
Células de Purkinje , Degeneración Retiniana , Animales , Proteínas de Unión al GTP/genética , Ácido Glutámico/metabolismo , Masculino , Fenotipo , Células de Purkinje/metabolismo , Degeneración Retiniana/metabolismo , Rodopsina/genética
2.
J Biol Chem ; 299(7): 104923, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37321451

RESUMEN

Mammalian brain tubulins undergo a reversible posttranslational modification-polyglutamylation-which attaches a secondary polyglutamate chain to the primary sequence of proteins. Loss of its erasers can disrupt polyglutamylation homeostasis and cause neurodegeneration. Tubulin tyrosine ligase like 4 (TTLL4) and TTLL7 were known to modify tubulins, both with preference for the ß-isoform, but differently contribute to neurodegeneration. However, differences in their biochemical properties and functions remain largely unknown. Here, using an antibody-based method, we characterized the properties of a purified recombinant TTLL4 and confirmed its sole role as an initiator, unlike TTLL7, which both initiates and elongates the side chains. Unexpectedly, TTLL4 produced stronger glutamylation immunosignals for α-isoform than ß-isoform in brain tubulins. Contrarily, the recombinant TTLL7 raised comparable glutamylation immunoreactivity for two isoforms. Given the site selectivity of the glutamylation antibody, we analyzed modification sites of two enzymes. Tandem mass spectrometry analysis revealed their incompatible site selectivity on synthetic peptides mimicking carboxyl termini of α1- and ß2-tubulins and a recombinant tubulin. Particularly, in the recombinant α1A-tubulin, a novel region was found glutamylated by TTLL4 and TTLL7, that again at distinct sites. These results pinpoint different site specificities between two enzymes. Moreover, TTLL7 exhibits less efficiency to elongate microtubules premodified by TTLL4, suggesting possible regulation of TTLL7 elongation activity by TTLL4-initiated sites. Finally, we showed that kinesin behaves differentially on microtubules modified by two enzymes. This study underpins the different reactivity, site selectivity, and function of TTLL4 and TTLL7 on brain tubulins and sheds light on their distinct role in vivo.


Asunto(s)
Microtúbulos , Péptido Sintasas , Tubulina (Proteína) , Animales , Encéfalo/metabolismo , Microtúbulos/metabolismo , Ácido Poliglutámico/química , Isoformas de Proteínas/metabolismo , Procesamiento Proteico-Postraduccional , Tubulina (Proteína)/metabolismo , Péptido Sintasas/metabolismo
3.
BMC Biol ; 21(1): 124, 2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-37226238

RESUMEN

BACKGROUND: The axonemal microtubules of primary cilium undergo a conserved protein posttranslational modification (PTM) - polyglutamylation. This reversible procedure is processed by tubulin tyrosine ligase-like polyglutamylases to form secondary polyglutamate side chains, which are metabolized by the 6-member cytosolic carboxypeptidase (CCP) family. Although polyglutamylation modifying enzymes have been linked to ciliary architecture and motility, it was unknown whether they also play a role in ciliogenesis. RESULTS: In this study, we found that CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed. Overexpression of CCP5 inhibited ciliogenesis, suggesting that a transient downregulation of CCP5 expression is required for ciliation initiation. Interestingly, the inhibitory effect of CCP5 on ciliogenesis does not rely on its enzyme activity. Among other 3 CCP members tested, only CCP6 can similarly suppress ciliogenesis. Using CoIP-MS analysis, we identified a protein that potentially interacts with CCP - CP110, a known negative regulator of ciliogenesis, whose degradation at the distal end of mother centriole permits cilia assembly. We found that both CCP5 and CCP6 can modulate CP110 level. Particularly, CCP5 interacts with CP110 through its N-terminus. Loss of CCP5 or CCP6 led to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells. Co-depletion of CCP5 and CCP6 synergized this abnormal ciliation, suggesting their partially overlapped function in suppressing cilia formation in cycling cells. In contrast, co-depletion of the two enzymes did not further increase the length of cilia, although CCP5 and CCP6 differentially regulate polyglutamate side-chain length of ciliary axoneme and both contribute to limiting cilia length, suggesting that they may share a common pathway in cilia length control. Through inducing the overexpression of CCP5 or CCP6 at different stages of ciliogenesis, we further demonstrated that CCP5 or CCP6 inhibited cilia formation before ciliogenesis, while shortened the length of cilia after cilia formation. CONCLUSION: These findings reveal the dual role of CCP5 and CCP6. In addition to regulating cilia length, they also retain CP110 level to suppress cilia formation in cycling cells, pointing to a novel regulatory mechanism for ciliogenesis mediated by demodifying enzymes of a conserved ciliary PTM, polyglutamylation.


Asunto(s)
Carboxipeptidasas , Cilios , Proteínas Asociadas a Microtúbulos , Células HEK293 , Humanos , Carboxipeptidasas/fisiología , Proteínas Asociadas a Microtúbulos/fisiología , Cilios/fisiología , Microtúbulos
4.
Breast Cancer Res Treat ; 191(2): 319-326, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34725776

RESUMEN

PURPOSE: CYP4Z1 is a human cytochrome P450 enzyme involved in breast cancer progression and prognosis, but its functional role in these processes is not understood. In order to gain more insight into CYP4Z1's properties it was recombinantly expressed in a host animal that does not have an endogenous homologue. METHODS: We generated a transgenic mouse model that specifically expresses human CYP4Z1 in breast tissue under the control of the whey acidic protein promoter. Complementary experiments were done using cell lines derived from human breast cell. RESULTS: Induction of CYP4Z1 expression led to reduction of body weight, activity, and birth rates. Histological analysis revealed no evidence for tumor formation. However, a strong increase in estrogen receptor alpha was observed by immunohistochemistry; weaker but significantly increased immunoreactivity was also detected for collagen I and fibronectin. Overexpression of CYP4Z1 in the human breast cancer cell line MCF7 also led to increased ERα expression. Moreover, increased expression of both CYP4Z1 and ERα was observed in MCF-10A normal breast cells upon cocultivation with MCF-7 cells (with or without overexpression of CYP4Z1). CONCLUSION: These data suggest that CYP4Z1 facilitates breast cancer development by induction of ERα expression via an as yet undefined mechanism.


Asunto(s)
Neoplasias de la Mama , Receptor alfa de Estrógeno , Animales , Neoplasias de la Mama/genética , Línea Celular Tumoral , Familia 4 del Citocromo P450/genética , Familia 4 del Citocromo P450/metabolismo , Receptor alfa de Estrógeno/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Transgénicos , Regulación hacia Arriba
5.
Protein Expr Purif ; 197: 106112, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35598696

RESUMEN

CCP6 is a member of cytosolic carboxypeptidases (CCPs) family, an eraser of a reversible protein posttranslational modification - polyglutamylation, and represents a potential therapeutic target. Currently, production of CCPs mainly depends on eukaryotic expression system, which is time-consuming and costly. Here, we reported that mouse origin full-length CCP6 can be successfully expressed in the soluble fraction of bacteria ArcticExpress (DE3) strain. However, the recombinant mCCP6 was initially co-purified with Cpn60 in a stoichiometric ratio of roughly 1:7 and exhibited no enzyme activity. When coupled with a step to promote the release of the substrate protein from the chaperonins by treatment with ATP/Mg2+/K+, the recombinant CCP6 with deglutamylation activity was obtained, though still partially associated with Cpn60. This is the first report, to our knowledge, that the successful expression and purification of active recombinant mammalian CCPs using a bacterial system was achieved.


Asunto(s)
Carboxipeptidasas , Escherichia coli , Animales , Carboxipeptidasas/genética , Carboxipeptidasas/aislamiento & purificación , Carboxipeptidasas/metabolismo , Chaperonina 60/metabolismo , Escherichia coli/enzimología , Escherichia coli/genética , Escherichia coli/metabolismo , Mamíferos , Ratones , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo
6.
Analyst ; 146(8): 2484-2489, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33751010

RESUMEN

We reported here a naphthalimide-based fluorescent probe LysOBr that localizes in the lysosome in live cells. LysOBr exhibits excellent HOBr selectivity and desirable optical properties. It can quantitatively detect lysosomal HOBr at 0-20 µM, with a detection limit of 243 nM. The short (4 s) response time allows real-time HOBr detection and imaging, as shown with studies in live HeLa cancer cells. It is thus the most rapidly responsive HOBr probe to date, among the most selective ones, and the first probe that is lysosome-specific with a "turn-on" signal. The probe structure is modular, and convenient structural modification should lead to other organelle-specific probes.


Asunto(s)
Bromatos , Neoplasias , Colorantes Fluorescentes , Células HeLa , Humanos , Lisosomas , Naftalimidas/toxicidad , Imagen Óptica
7.
Biochem Biophys Res Commun ; 533(4): 1393-1399, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33092792

RESUMEN

Cytosolic carboxypeptidases (CCPs) comprise a unique subfamily of M14 carboxypeptidases and are erasers of the reversible protein posttranslational modification- polyglutamylation. Potent inhibitors for CCPs may serve as leading compounds targeting imbalanced polyglutamylation. However, no efficient CCP inhibitor has yet been reported. Here, we showed that 2-phosphonomethylpentanedioic acid (2-PMPA), a potent inhibitor of the distant M28 family member glutamate carboxypeptidase II (GCPII), rather than the typical M14 inhibitor 2-benzylsuccinic acid, could efficiently inhibit CCP activities. 2-PMPA inhibited the recombinant Nna1 (a.k.a. CCP1) for hydrolyzing a synthetic peptide in a mixed manner, with Ki and Ki' being 0.11 µM and 0.24 µM respectively. It inhibited Nna1 for deglutamylating tubulin, the best-known polyglutamylated protein, with an IC50 of 0.21 mM. Homology modeling predicted that the R-form of 2-PMPA is more favorable to bind Nna1, unlike that GCPII prefers to S-form. This work for the first time identified a potent inhibitor for CCP family.


Asunto(s)
Glutamato Carboxipeptidasa II/antagonistas & inhibidores , Compuestos Organofosforados/farmacología , Inhibidores de Proteasas/farmacología , Carboxipeptidasas/antagonistas & inhibidores , Carboxipeptidasas/genética , Carboxipeptidasas/metabolismo , Citosol/enzimología , Evaluación Preclínica de Medicamentos/métodos , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Glutamato Carboxipeptidasa II/química , Glutamato Carboxipeptidasa II/metabolismo , Glutaratos/farmacología , Cinética , Simulación del Acoplamiento Molecular , Compuestos Organofosforados/química , Inhibidores de Proteasas/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/genética , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/metabolismo , Ácido Succínico/farmacología
8.
J Biol Chem ; 290(2): 1222-32, 2015 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-25416787

RESUMEN

Nna1 (CCP1) defines a subfamily of M14 metallocarboxypeptidases (CCP1-6) and is mutated in pcd (Purkinje cell degeneration) mice. Nna1, CCP4, and CCP6 are involved in the post-translational process of polyglutamylation, where they catalyze the removal of polyglutamate side chains. However, it is unknown whether these three cytosolic carboxypeptidases share identical enzymatic properties and redundant biological functions. We show that like Nna1, purified recombinant CCP4 and CCP6 deglutamylate tubulin, but unlike Nna1, neither rescues Purkinje cell degeneration in pcd mice, indicating that they do not have identical functions. Using biotin-based synthetic substrates, we established that the three enzymes are distinguishable based upon individual preferences for glutamate chain length, the amino acid immediately adjacent to the glutamate chain, and whether their activity is enhanced by nearby acidic amino acids. Nna1 and CCP4 remove the C-terminal glutamate from substrates with two or more glutamates, whereas CCP6 requires four or more glutamates. CCP4 behaves as a promiscuous glutamase, with little preference for chain length or neighboring amino acid composition. Besides glutamate chain length dependence, Nna1 and CCP6 exhibit higher k(cat)/K(m) when substrates contain nearby acidic amino acids. All cytosolic carboxypeptidases exhibit a monoglutamase activity when aspartic acid precedes a single glutamate, which, together with their other individual preferences for flanking amino acids, greatly increases the potential substrates for these enzymes and the biological processes in which they act. Additionally, Nna1 metabolized substrates mimicking the C terminus of tubulin in a way suggesting that the tyrosinated form of tubulin will accumulate in pcd mice.


Asunto(s)
Carboxipeptidasas/genética , Proteínas de Unión al GTP/genética , Degeneración Nerviosa/metabolismo , Ácido Poliglutámico/metabolismo , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/genética , Secuencia de Aminoácidos , Animales , Carboxipeptidasas/química , Carboxipeptidasas/metabolismo , Proteínas de Unión al GTP/metabolismo , Ratones , Ratones Transgénicos , Degeneración Nerviosa/patología , Células de Purkinje/metabolismo , Células de Purkinje/patología , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/metabolismo , Especificidad por Sustrato , Tubulina (Proteína)/metabolismo
9.
Adv Mater ; 36(19): e2312148, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38314966

RESUMEN

Recently, utilizing the air breakdown effect in the charge excitation strategy proves as an efficient charge injection technique to increase the surface charge density of dielectric polymers for triboelectric nanogenerators (TENGs). However, quantitative characterization of the ability of dielectric polymers to trap reverse charges and the effect on the startup time of secondary self-charge excitation (SSCE) are essential for extensive applications. Here, an ultra-fast charge self-injection technique based on a self-charge excitation strategy is proposed, and a standard method to quantify the charge trapping and de-trapping abilities of 23 traditional tribo-materials is introduced. Further, the relationship among the distribution of dielectric intrinsic deep, shallow trap states, and transportation of trapped charges is systematically analyzed in this article. It shows that the de-trapping rate of charges directly determines the reactivation and failure of SSCE. Last, independent of TENG contact efficiency, an ultra-high charge density of 2.67 mC m-2 and an ultra-fast startup time of SSCE are obtained using a 15 µm poly(vinylidene fluoride-trifluoroethylene) film, breaking the historical record for material modification. As a standard for material selection, this work quantifies the charge trapping and de-trapping ability of the triboelectric dielectric series and provides insights for understanding the charge transport in dielectrics.

10.
FASEB J ; 26(11): 4468-80, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22835831

RESUMEN

The axotomy-inducible enzyme Nna1 defines a subfamily of M14 metallocarboxypeptidases, and its mutation underlies the Purkinje cell degeneration (pcd) mouse. However, the relationship among its catalytic activity, substrate specificities, and the critical processes of neurodegeneration/axon regeneration is incompletely understood. Here we used a transgenic rescue strategy targeting expression of modified forms of Nna1 to Purkinje cells in pcd mice to determine structure-activity relationships for neuronal survival and in parallel characterized the enzymatic properties of purified recombinant Nna1. The Nna1 subfamily uniquely shares conserved substrate-determining residues with aspartoacylase that, when mutated, cause Canavan disease. Homologous mutations (D1007E and R1078E) inactivate Nna1 in vivo, as does mutation of its catalytic glutamate (E1094A), which implies that metabolism of acidic substrates is essential for neuronal survival. Consistent with reports that Nna1 is a tubulin glutamylase, recombinant Nna1-but not the catalytic mutants-removes glutamate from tubulin. Recombinant Nna1 metabolizes synthetic substrates with 2 or more C-terminal glutamate (but not aspartate) residues (V(max) for 3 glutamates is ∼7-fold higher than 2 glutamates although K(M) is similar). Catalysis is not ATP/GTP dependent, and mutating the ATP/GTP binding site of Nna1 has no effect in vivo. Nna1 is a monomeric enzyme essential for neuronal survival through hydrolysis of polyglutamate-containing substrates.


Asunto(s)
Proteínas de Unión al GTP/química , Proteínas de Unión al GTP/metabolismo , Células de Purkinje/fisiología , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/química , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/metabolismo , Adenosina Trifosfato/metabolismo , Secuencia de Aminoácidos , Animales , Dominio Catalítico , Quelantes/farmacología , Proteínas de Unión al GTP/genética , Regulación de la Expresión Génica , Guanosina Trifosfato/metabolismo , Células HEK293 , Humanos , Ratones , Ratones Endogámicos , Ratones Transgénicos , Datos de Secuencia Molecular , Mutación , Neuronas/citología , Neuronas/fisiología , Conformación Proteica , Células de Purkinje/citología , Células de Purkinje/patología , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/genética , Relación Estructura-Actividad , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Zinc/farmacología
11.
Cytoskeleton (Hoboken) ; 80(9-10): 382-392, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37098731

RESUMEN

Microtubule-associated proteins (MAPs) regulate assembly and stability of microtubules (MTs) during cell cytokinesis, cell migration, neuronal growth, axon guidance, and synapse formation. Using data mining of the Human Protein Atlas database and experimental screening, we identified nucleosome assembly protein 1 like 1 (NAP1L1) as a new MAP. The Human Protein Atlas and PubMed database screening identified 99 potential new MAPs. Twenty candidate proteins that highly co-localized with MTs were exogenously expressed with green fluorescent protein (GFP) or hemagglutinin (HA) tags in tissue culture cells and MTs were co-stained for immunofluorescent microscopy. We found that NAP1L1 is mainly localized in the cytosol with MTs during interphase. Using bacterially expressed recombinant NAP1L1 fragments and purified MTs, we biochemically mapped the MT-binding site on the N-terminal region (1-72aa) and the central region (164-269aa) of NAP1L1. NAP1L1 dimerizes through the long helix region (73-163aa), and full-length NAP1L1 induces the formation of thick MTs, indicating that NAP1L1 has the ability to bundle MTs in cells. Analysis of publicly available RNA-seq data of NAP1L1 depleted cells suggested that NAP1L1 is involved in cell adhesion and migration in agreement with the function of NAP1L1 as a MAP.

12.
Adv Mater ; 35(7): e2209657, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36398558

RESUMEN

To enhance the durability of triboelectric nanogenerator (TENG), liquid lubrication has been used to reduce mechanical abrasion. However, as the charge transportation behavior in dielectric liquid is not clearly understood, the output energy is still low although some improvements have been reported. Herein, the charge transportation behaviors in dielectric liquid by self-excited liquid suspension triboelectric nanogenerator (LS-TENG) are systematically investigated. The important role of solid-liquid triboelectrification effect, charge-liquid transmission and dissipation effect, and the homogeneous dielectric induction effect in promoting its output performance is found. The LS-TENG with a dual dielectric tribolayer has advantages of slight driving force and long lifetime for harvesting micro energy. The output of LS-TENG remains almost constant for more than 234 k operating cycles. A high charge density of 704 µC m-2 is obtained, 2.7 times as much as that of the current highest record in non-contact TENG. Additionally, the rotary LS-TENG lights up 4200 LEDs and continuously powers a variety of wireless sensors by harvesting wind energy at low wind speed. This work provides an important insight toward the charge transportation mechanism in dielectric liquid, and a prospective strategy for achieving highly robust TENG in micro energy harvesting for practical applications.

13.
Adv Mater ; 35(40): e2302954, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37354126

RESUMEN

Improving the output energy and durability of triboelectric nanogenerators (TENGs) remains a considerable challenge for their practical applications. Owing to the interface effect of triboelectrification and electrostatic induction, thinner films with higher dielectric constants yield a higher output; however, they are not durable for practical applications. Herein, the dielectric surface effect is changed into a volume effect by adopting a millimeter-thick dielectric film with an inner porous network structure so that charges can hop in the surface state of the network. Charge migration inside the dielectric film is the key factor affecting the output of the triboelectric nanogenerator (TENG) with a thick film, based on which each working stage follows the energy-maximization principle in the voltage-charge plot. The maximum peak and average power densities of the TENG with polyurethane foam film in 1 mm thickness reach 40.9 and 20.7 W m-2  Hz-1 , respectively, under environmental conditions, and the output charge density is 5.14 times that of TENGs with a poly(tetrafluoroethylene) film of the same thickness. Superdurability is achieved in the rotary-mode TENG after 200 000 operation cycles. This study identifies the physical mechanism of the thick dielectric film used in TENGs and provides a new approach to promote the output and durability of TENGs.

14.
Transl Cancer Res ; 11(11): 4148-4158, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36523321

RESUMEN

Background: Mindfulness-based stress reduction (MBSR) has become an alternative intervention for cancer patients, but its impact on depression and quality of life (QOL) of breast cancer patients remains controversial. The aim of this study was to evaluate the effects of MBSR vs. standard or usual care to relieve psychological stress in patients with breast cancer. Methods: According to the PICOS principles, databases [PubMed, Cochrane Database, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), and Wanfang Database] were searched for randomized controlled trials (RCTs) on the evaluation of MBSR vs. standard or usual care for patients with breast cancer, the outcome variables included depression, stress, anxiety, fatigue, sleep and QOL. Review Manager 5.4 was used to evaluate the effects of the results among selected articles. Forest plots and funnel plots were also performed. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Results: The final analysis included 14 studies with a total of 2,224 patients (1,138 in the MBSR group and 1,086 in the control group). The overall results of risk of bias assessment showed that the reporting bias among articles was high, and other bias was relatively moderate. Funnel plots and Egger's tests showed that there was no significant publication bias. Compared with standard or usual care, MBSR effectively relieved the psychological stress [mean difference (MD), -1.72; 95% confidence interval (CI): (-2.53, -0.92); P<0.0001] and anxiety [standardized mean difference (SMD), -1.36; 95% CI: (-2.13, -0.60); P=0.0005] of breast cancer patients, and improved depression [SMD, -0.62; 95% CI: (-1.20, -0.03); P=0.04] and sleep status [MD, -0.42; 95% CI: (-0.73, -0.10), P=0.009]. However, it had no significant effect on fatigue [SMD, -0.97; 95% CI: (-2.24, 0.31); P=0.14] or QOL [MD, 1.95; 95% CI: (-3.15, 7.05); P=0.45]. Conclusions: MBSR was better than standard or usual care for relieving psychological stress, anxiety, depression, and sleep in patients with breast cancer. Considering the limitations of this article, such as high risk of bias and high heterogeneity of included studies, the interpretation of this conclusion should be cautious.

15.
Front Plant Sci ; 13: 905202, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35812944

RESUMEN

Polyploids generated by the replication of a single genome (autopolyploid) or synthesis of two or more distinct genomes (allopolyploid) usually show significant advantages over their diploid progenitors in biological characteristics, including growth and development, nutrient accumulation, and plant resistance. Whereas, the impacts of genomic replication on transcription regulation and chromatin structure in pak choi have not been explored fully. In this study, we observed the transcriptional and genomic structural alterations between diploid B. rapa (AA) and artificial autotetraploid B. rapa (AAAA) using RNA-seq and Hi-C. RNA-seq revealed 1,786 differentially expressed genes (DEGs) between the diploids and autotetraploids, including 717 down-regulated and 1,069 up-regulated genes in autotetraploids. Of all the 1,786 DEGs, 23 DEGs (10 down-regulated DEGs in autotetraploids) were involved in Compartment A-B shifts, while 28 DEGs (20 up-regulated DEGs in autotetraploids) participated in Compartment B-A shifts. Moreover, there were 15 DEGs in activated topologically associating domains (TADs) (9 up-regulated DEGs in diploids) and 80 DEGs in repressed TADs (49 down-regulated DEGs in diploids). Subsequently, eight DEGs with genomic structural variants were selected as potential candidate genes, including four DEGs involved in photosynthesis (BraA01003143, BraA09002798, BraA04002224, and BraA08000594), three DEGs related to chloroplast (BraA05002974, BraA05001662, and BraA04001148), and one DEG associated with disease resistance (BraA09004451), which all showed high expression in autotetraploids. Overall, our results demonstrated that integrative RNA-seq and Hi-C analysis can identify related genes to phenotypic traits and also provided new insights into the molecular mechanism of the growth advantage of polyploids.

16.
Genes (Basel) ; 13(7)2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35885992

RESUMEN

TFIIIA is a zinc-finger transcription factor that is involved in post-transcriptional regulation during development. Here, the BcTFIIIA gene was isolated from pak choi. Sequence analysis showed that BcTFIIIA encodes 383 amino acids (aa) with an open reading frame (ORF) of 1152 base pairs (bp). We investigated the subcellular location of BcTFIIIA and found the localized protein in the nucleus. BcTFIIIA was suppressed when the pak choi was infected by the turnip mosaic virus (TuMV). The BcTFIIIA mRNA expression level in a resistant variety was higher than that in a sensitive variety, as determined by qRT-PCR analysis. Yeast two hybrid (Y2H) assay and bimolecular fluorescence complementation (BiFC) suggested that BcTFIIIA interacts with TuMV CP and VPg in vivo, respectively, and in vitro. A virus-induced gene silencing (VIGS) experiment showed that the silencing of BcTFIIIA gene expression in pak choi promoted the accumulation of TuMV. These results suggest that BcTFIIIA negatively regulates viral infection through the interaction with TuMV CP and VPg.


Asunto(s)
Brassica , Potyvirus , Brassica/metabolismo , Factores de Transcripción/metabolismo
17.
Research (Wash D C) ; 2022: 9812865, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35909938

RESUMEN

Triboelectric nanogenerator (TENG) is a promising strategy for harvesting low frequency mechanical energy. However, the bottlenecks of limited electric output by air/dielectric breakdown and poor durability by material abrasion seriously restrict its further improvement. Herein, we propose a liquid lubrication promoted sliding mode TENG to address both issues. Liquid lubrication greatly reduces interface material abrasion, and its high breakdown strength and charge transmission effect further enhance device charge density. Besides, the potential decentralization design by the voltage balance bar effectively suppresses the dielectric breakdown. In this way, the average power density up to 87.26 W·m-2·Hz-1, energy conversion efficiency of 48%, and retention output of 90% after 500,000 operation cycles are achieved, which is the highest average power density and durability currently. Finally, a cell phone is charged to turn on by a palm-sized TENG device at 2 Hz within 25 s. This work has a significance for the commercialization of TENG-based self-powered systems.

18.
Nanomicro Lett ; 14(1): 155, 2022 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-35916998

RESUMEN

Triboelectric nanogenerator (TENG) is regarded as an effective strategy to convert environment mechanical energy into electricity to meet the distributed energy demand of large number of sensors in the Internet of Things (IoTs). Although TENG based on the coupling of triboelectrification and air-breakdown achieves a large direct current (DC) output, material abrasion is a bottleneck for its applications. Here, inspired by primary cell and its DC signal output characteristics, we propose a novel primary cell structure TENG (PC-TENG) based on contact electrification and electrostatic induction, which has multiple working modes, including contact separation mode, freestanding mode and rotation mode. The PC-TENG produces DC output and operates at low surface contact force. It has an ideal effective charge density (1.02 mC m-2). Meanwhile, the PC-TENG shows a superior durability with 99% initial output after 100,000 operating cycles. Due to its excellent output performance and durability, a variety of commercial electronic devices are powered by PC-TENG via harvesting wind energy. This work offers a facile and ideal scheme for enhancing the electrical output performance of DC-TENG at low surface contact force and shows a great potential for the energy harvesting applications in IoTs.

19.
Adv Mater ; 34(13): e2109918, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35081267

RESUMEN

Boosting output charge density is top priority for achieving high-performance triboelectric nanogenerators (TENGs). The charge-excitation strategy is demonstrated to be a superior approach to acquire high output charge density. Meanwhile, the molecular charge behaviors in the dielectric under a strong electric field from high charge density bring new physics that are worth exploring. Here, a rapid self-polarization effect of a polar dielectric material by the superhigh electric field in a charge-excitation TENG is reported, by which the permittivity of the polar dielectric material realizes self-increase to a saturation, and thus enhances the output charge density. Consequently, an ultrahigh charge density of 3.53 mC m-2 is obtained with 7 µm homemade lead zirconate titanate-poly(vinylidene fluoride) composite film in the atmosphere with 5% relative humidity, which is the highest charge density for TENGs with high durability currently. This work provides new guidance for dielectric material optimization under charge excitation to boost the output performance of TENGs toward practical applications.

20.
Plants (Basel) ; 10(4)2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33919922

RESUMEN

Chinese cabbage is a leafy vegetable, and its leaves are the main edible organs. The formation of trichomes on the leaves can significantly affect its taste, so studying this phenomenon is of great significance for improving the quality of Chinese cabbage. In this study, two varieties of Chinese cabbage, W30 with trichome leaves and 082 with glabrous leaves, were crossed to generate F1 and F1 plants, which were self-fertilized to develop segregating populations with trichome or glabrous morphotypes. The two bulks of the different segregating populations were used to conduct bulked segregant analysis (BSA). A total of 293.4 M clean reads were generated from the samples, and plants from the trichome leaves (AL) bulk and glabrous leaves (GL) bulk were identified. Between the two DNA pools generated from the trichome and glabrous plants, 55,048 SNPs and 272 indels were generated. In this study, three regions (on chromosomes 6, 10 and scaffold000100) were identified, and the annotation revealed three candidate genes that may participate in the formation of leaf trichomes. These findings suggest that the three genes-Bra025087 encoding a cyclin family protein, Bra035000 encoding an ATP-binding protein/kinase/protein kinase/protein serine/threonine kinase and Bra033370 encoding a WD-40 repeat family protein-influence the formation of trichomes by participating in trichome morphogenesis (GO: 0010090). These results demonstrate that BSA can be used to map genes associated with traits and provide new insights into the molecular mechanism of leafy trichome formation in Chinese cabbage.

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