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1.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1255-1259, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621972

RESUMO

The components with hypoglycemic activity in Plumeria rubra were isolated and purified by various column chromatography techniques and activity tracing methods. The physical and chemical properties of all the purified monomer compounds were characterized and analyzed, and a total of six compounds were isolated and identified, including 6″-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(1), 6-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(2), 2-hydroxy-6-methoxy-benzyl-benzoate-2-O-ß-D-glucoside(3), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(4), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(5), and 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-xyloside(6). Compounds 1 and 2 were new compounds, and compounds 3-6 were isolated from Plumeria for the first time. The α-glucosidase inhibitory activity of six identified compounds was tested. The results show that compounds 1-6 show certain inhibitory activity with an IC_(50) value ranging from 8.2 to 33.5 µmol·L~(-1).


Assuntos
Apocynaceae , Glucosídeos , Glucosídeos/química , Benzoatos
2.
Org Biomol Chem ; 21(17): 3547-3551, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37060142

RESUMO

A highly efficient Rh(II) catalyzed non-radical protocol to access NH-free C-3 bifunctional oxindoles, which possess 3-allyl and 3-amino simultaneously, was first achieved by employing an intermolecular [2,3]-sigmatropic rearrangement reaction between diazooxindoles and tertiary allylic amines. Utilizing readily available allylamines as the nitrogen and allyl source concurrently, a wide range of bio-active 3-allyl-3-(amino)oxindoles were obtained in excellent yields under very mild reaction conditions; meanwhile, the TON can be up to 90 000. Our study addresses a gap in the literature by investigating intermolecular rearrangements of ammonium ylides with diazoamides, which have been relatively understudied.

3.
BMC Pulm Med ; 22(1): 180, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524325

RESUMO

Allergic asthma is an allergic inflammatory disease of the airways, in which numerous cell types and cytokines have been shown to contribute to pathogenesis of the disease. Although increased expression of IL-9 has been shown to influence the activity of structural as well as eosinophils and mast cells in asthma, the influence of IL-9 on function of ILC2 and Th2 cells remains unclear. This study therefore aimed to elucidate the role of IL-9 on ILC2 and Th2 cells using a murine model of asthma. A murine model of asthma was established using wild type (WT) and IL-9-deficient (Il9-/-) transgenic mice sensitized to house dust mite (HDM). Bronchoalveolar lavage fluid (BALF) and lung tissues were collected, and analysed for inflammatory cells (eosinophils, mast cells, Th2 cells and ILC2 cells), histopathological changes, and several cytokines. HDM challenge significantly increased accumulation of ILC2 cells, Th2 cells and mast cells, as well as goblet cell hyperplasia, and the expression of cytokines IL-4, IL-5 and IL-13, but not IFN-γ, in WT mice compared to saline-challenged control group. In contrast, all pathological changes, including infiltration of ILC2 cells, Th2 cells and mast cells, were significantly attenuated in HDM-challenged Il9-/- mice. Furthermore, the number of Ki67+ILC2 cells, Ki67+Th2 cells and Ki67+mast cells were significantly reduced in the absence of IL-9 signalling. These data suggest that IL-9 promotes the proliferation and type 2 cytokine production of type 2 cells in the murine models of asthma, and therefore might be a potential therapeutic target for asthma treatment.


Assuntos
Asma , Hipersensibilidade , Interleucina-9 , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Imunidade Inata , Inflamação/metabolismo , Interleucina-9/metabolismo , Antígeno Ki-67/metabolismo , Pulmão/patologia , Linfócitos/metabolismo , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Pyroglyphidae , Células Th2
4.
Int J Mol Sci ; 23(4)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35216487

RESUMO

With the warming global climate, drought stress is considered to be the most important abiotic factor limiting plant growth and yield in the world. Drought stress has serious impacts on crop production. Many researchers have studied the influences of drought stress on crop production and plant physiology; however, few researchers have combined root exudates with root-associated microbiomes for their mutual effects under drought conditions. In this review, we systematically illustrate the impact of drought stress on root exudates and root-associated microbiomes, and then we discuss the mutual regulation of root-associated microbiomes and the host plant in helping the plant adapt to drought. Finally, we construct a framework for the mutual connections between the plant, root exudates, and the microbiome. We hope this review can provide some significant guidelines to promote the study of drought resistance in plants in association with the rhizosphere microbiota.


Assuntos
Exsudatos e Transudatos/microbiologia , Microbiota/fisiologia , Raízes de Plantas/microbiologia , Raízes de Plantas/fisiologia , Plantas/microbiologia , Estresse Fisiológico/fisiologia , Produção Agrícola/métodos , Secas , Rizosfera , Microbiologia do Solo
5.
Psychol Res ; 85(6): 2186-2196, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32776258

RESUMO

This study investigated the relationship between numerical and spatial processing and reading direction, conducting conceptual replications of the Shaki et al. (Psychonomic Bulletin & Review 16(2): 328-331, 2009) parity task and the Mathieu et al. (Cognition 146: 229-239, 2016, Experiment 1) simple addition (e.g., 3 + 2) and subtraction (e.g., 3 - 2) task. Twenty-four left-to-right readers (LTR) and 24 right-to-left readers (RTL) were tested. The response time (RT) analysis of the parity task presented a robust spatial-numerical association of response codes (SNARC) effect (left-side response advantage for smaller numbers and right-side advantage for larger numbers) for LTR but not RTL readers. In the arithmetic task, the three problem elements (e.g., 3 + 4) were presented sequentially with the second operand displaced slightly to the left or right of fixation. RTL but not LTR readers presented a RT advantage for subtraction relative to addition with a right-shifted second operand compared to it being left-shifted. This is consistent with a spatial bias linked to native reading direction. For both reading-direction groups, effects of the left vs. right side manipulation in the arithmetic or parity task did not correspond to parallel effects in the other task. The results imply that the parity-based SNARC effects and side-related effects in cognitive arithmetic are not equivalent measures of space-related processes in cognitive number processing and likely reflect distinct mechanisms.


Assuntos
Leitura , Percepção Espacial , Humanos , Matemática , Tempo de Reação
6.
World J Surg Oncol ; 19(1): 128, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879180

RESUMO

BACKGROUND: Although the ACOSOG Z0011 study showed that axillary lymph node dissection (ALND) could be avoided in a specific population of sentinel lymph node-positive patients, it is not widely accepted by Chinese surgeons. We conducted a prospective single-arm study to confirm whether or not the results of Z0011 are applicable to Chinese patients. METHODS: Patients conforming to the Z0011 criteria were prospectively enrolled at the Peking University People's Hospital Breast Center from November 2014 to June 2019. The clinicopathological features of the study group were compared with those of the Z0011 study group. Lymphedema after surgery, the incidence of local-regional recurrence, and survival were analyzed. RESULTS: One hundred forty-two patients who met the Z0011 eligibility criteria were enrolled in this study; 115 underwent sentinel lymph node biopsy (SLNB) alone. Compared with the Z0011 trial, younger patients were included (median age, 52 [26-82] years vs 54 [25-90] years; P = 0.03). For clinical T stage, tumor histology, hormone status, lymphovascular invasion, and the number of positive sentinel lymph nodes (SLNs), no statistically significant differences were observed. More patients received adjuvant chemotherapy and endocrine therapy in this study (90.85% vs 58.0% and 80.99% vs 46.6% respectively, P <0.001). A similar percentage of patients received radiotherapy, but more nodal radiotherapy procedures were carried out in our study (54.5% vs 16.9%). After a median follow-up of 29 months, only 1 patient (0.9%) had ipsilateral breast tumor recurrence, and no regional recurrence occurred. CONCLUSION: Our study showed that it is achievable to avoid ALND in patients eligible for Z0011 in China. TRIAL REGISTRATION: ClinicalTrials.gov. Registration number NCT03606616 . Retrospectively registered on 31 July 2018.


Assuntos
Neoplasias da Mama/cirurgia , Linfonodos/cirurgia , Mastectomia , Linfonodo Sentinela/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , China/epidemiologia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Prospectivos , Biópsia de Linfonodo Sentinela , Sociedades Médicas
7.
Int J Mol Sci ; 21(5)2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150945

RESUMO

Plants are associated with hundreds of thousands of microbes that are present outside on the surfaces or colonizing inside plant organs, such as leaves and roots. Plant-associated microbiota plays a vital role in regulating various biological processes and affects a wide range of traits involved in plant growth and development, as well as plant responses to adverse environmental conditions. An increasing number of studies have illustrated the important role of microbiota in crop plant growth and environmental stress resistance, which overall assists agricultural sustainability. Beneficial bacteria and fungi have been isolated and applied, which show potential applications in the improvement of agricultural technologies, as well as plant growth promotion and stress resistance, which all lead to enhanced crop yields. The symbioses of arbuscular mycorrhizal fungi, rhizobia and Frankia species with their host plants have been intensively studied to provide mechanistic insights into the mutual beneficial relationship of plant-microbe interactions. With the advances in second generation sequencing and omic technologies, a number of important mechanisms underlying plant-microbe interactions have been unraveled. However, the associations of microbes with their host plants are more complicated than expected, and many questions remain without proper answers. These include the influence of microbiota on the allelochemical effect caused by one plant upon another via the production of chemical compounds, or how the monoculture of crops influences their rhizosphere microbial community and diversity, which in turn affects the crop growth and responses to environmental stresses. In this review, first, we systematically illustrate the impacts of beneficial microbiota, particularly beneficial bacteria and fungi on crop plant growth and development and, then, discuss the correlations between the beneficial microbiota and their host plants. Finally, we provide some perspectives for future studies on plant-microbe interactions.


Assuntos
Bactérias/metabolismo , Produtos Agrícolas/microbiologia , Microbiota , Desenvolvimento Vegetal , Bactérias/classificação , Transdução de Sinais , Simbiose
8.
Proc Natl Acad Sci U S A ; 113(8): 2229-34, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26858444

RESUMO

Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriP-mediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection.


Assuntos
Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/metabolismo , Proteínas Ribossômicas/metabolismo , Linfócitos B/metabolismo , Linfócitos B/virologia , Linhagem Celular , DNA Viral/genética , DNA Viral/metabolismo , Antígenos Nucleares do Vírus Epstein-Barr/genética , Técnicas de Silenciamento de Genes , Genoma Viral , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Origem de Replicação , Proteínas Ribossômicas/antagonistas & inibidores , Proteínas Ribossômicas/genética , Ativação Transcricional , Nucleolina
9.
AIDS Care ; 29(6): 696-704, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27609532

RESUMO

People living with HIV/AIDS (PHA) often concurrently cope with mental health disorders that may greatly influence HIV and other health-related outcomes. The objective of this study was to examine the prevalence and correlates of self-reported mental health disorder diagnosis among a cohort of harder-to-reach HIV-positive individuals in British Columbia, Canada. Between 2007 and 2010, 1000 PHA who had initiated ART were enrolled in the Longitudinal Investigation into Supportive and Ancillary health services (LISA) study. Socio-demographic, behavioral, health-care utilization and psychosocial information was collected through interviewer-led questionnaires and linked to longitudinal clinical variables through the provincial Drug Treatment Program at the BC Centre for Excellence in HIV/AIDS. We identified the prevalence of all-type and specific mental health disorders among this population. Of the 916 participants included in this analysis, 494 (54%) reported ever having a mental health disorder diagnosis. Mood (85%) and anxiety (65%) disorders were the two most frequently reported mental health conditions. Self-reported all-type mental health disorder was independently associated with decreased overall functioning (adjusted odds ratio [AOR] = 0.90, 95% confidence interval [CI] = 0.83-0.98) and life satisfaction (AOR = 0.81, 95% CI = 0.74-0.89), and having higher stigma score (AOR = 1.11, 95%CI = 1.02-1.21). Participants reporting any mental health disorder were more likely to report a history of sexual assault (AOR = 2.45, 95% CI = 1.75-3.43) and to have used case management services (AOR = 1.63, 95%CI = 1.17-2.27). Our findings uncovered a high burden of mental health disorders among harder-to-reach PHA and suggest that PHA with at least one mental health disorder diagnosis are disproportionately impacted by sexual violence and stigma.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Colúmbia Britânica/epidemiologia , Administração de Caso , Comorbidade , Estudos Transversais , Feminino , Serviços de Saúde/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Transtornos Mentais/diagnóstico , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologia , Transtornos do Humor/psicologia , Razão de Chances , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Prevalência , Delitos Sexuais/psicologia , Delitos Sexuais/estatística & dados numéricos , Estigma Social , Inquéritos e Questionários
10.
Proc Natl Acad Sci U S A ; 111(1): 243-8, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24344309

RESUMO

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for EBV episome maintenance, replication, and transcription. These effects are mediated by EBNA1 binding to cognate oriP DNA, which comprise 20 imperfect copies of a 30-bp dyad symmetry enhancer and an origin for DNA replication. To identify cell proteins essential for these EBNA1 functions, EBNA1 associated cell proteins were immune precipitated and analyzed by liquid chromatography-tandem mass spectrometry. Nucleolin (NCL) was identified to be EBNA1 associated. EBNA1's N-terminal 100 aa and NCL's RNA-binding domains were critical for EBNA1/NCL interaction. Lentivirus shRNA-mediated NCL depletion substantially reduced EBNA1 recruitment to oriP DNA, EBNA1-dependent transcription of an EBV oriP luciferase reporter, and EBV genome maintenance in lymphoblastoid cell lines. NCL RNA-binding domain K429 was critical for ATP and EBNA1 binding. NCL overexpression increased EBNA1 binding to oriP and transcription, whereas NCL K429A was deficient. Moreover, NCL silencing impaired lymphoblastoid cell line growth. These experiments reveal a surprisingly critical role for NCL K429 in EBNA1 episome maintenance and transcription, which may be a target for therapeutic intervention.


Assuntos
Antígenos Nucleares do Vírus Epstein-Barr/química , Antígenos Nucleares do Vírus Epstein-Barr/fisiologia , Fosfoproteínas/química , Fosfoproteínas/fisiologia , Plasmídeos/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/fisiologia , Transcrição Gênica , Trifosfato de Adenosina/química , Sítios de Ligação , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Cromatografia Líquida , Replicação do DNA , Epitopos/química , Regulação da Expressão Gênica , Inativação Gênica , Genoma , Proteínas de Fluorescência Verde/metabolismo , Humanos , Imunoprecipitação , Luciferases/metabolismo , Espectrometria de Massas , Microscopia Confocal , Ligação Proteica , Estrutura Terciária de Proteína , Origem de Replicação , Replicação Viral , Nucleolina
11.
Mem Cognit ; 44(8): 1288-1300, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27351881

RESUMO

In recent years, several researchers have proposed that skilled adults may solve single-digit addition problems (e.g., 3 + 1 = 4, 4 + 3 = 7) using a fast counting procedure. Practicing a procedure, however, often leads to transfer of learning to unpracticed items; consequently, the fast counting theory was potentially challenged by subsequent studies that found no generalization of practice for simple addition. In two experiments reported here (Ns = 48), we examined generalization in an alphabet arithmetic task (e.g., B + 5 = C D E F G) to determine that counting-based procedures do produce generalization. Both experiments showed robust generalization (i.e., faster response times relative to control problems) when a test problem's letter augend and answer letter sequence overlapped with practiced problems (e.g., practice B + 5 = C D E F G, test B + 3 = C D E ). In Experiment 2, test items with an unpracticed letter but whose answer was in a practiced letter sequence (e.g., practice C + 3 = DEF, test D + 2 = E F) also displayed generalization. Reanalysis of previously published addition generalization experiments (combined n = 172) found no evidence of facilitation when problems were preceded by problems with a matching augend and counting sequence. The clear presence of generalization in counting-based alphabet arithmetic, and the absence of generalization of practice effects in genuine addition, represent a challenge to fast counting theories of skilled adults' simple addition.


Assuntos
Generalização Psicológica/fisiologia , Conceitos Matemáticos , Prática Psicológica , Resolução de Problemas/fisiologia , Transferência de Experiência/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
12.
Biochem Biophys Res Commun ; 459(4): 617-22, 2015 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-25749344

RESUMO

Despite the effectiveness of the anti-CD20 chimeric antibody (mAb), rituximab, in treating B-cell lymphomas, its efficacy remains variable and often modest. Hu8E4 is an anti-CD20 humanized antibody which exhibits markedly higher antitumor activity compared with rituximab. Previous studies have indicated that rituximab and almost all known anti-CD20 murine mAbs recognize the A170/P172 motif within the large extracellular loop of CD20. In this study, we demonstrated that hu8E4 also recognized the A170/P172 motif, suggesting that the epitopes recognized by rituximab and hu8E4 are very similar. Based on this, three single mutations (D57E, Y102K and Y102T) at the heavy chain variable region that can improve the affinity of rituximab were transferred to hu8E4. The results showed that D57E and Y102T but not Y102K successfully enhanced the binding of hu8E4 to CD20. Out of these hu8E4 mutants, hu8E4D57E exhibited the highest affinity. The in vitro and in vivo antitumor activity of hu8E4D57E was further investigated. Our data indicated that hu8E4D57E was as effective as hu8E4 in mediating CDC and inducing apoptosis in B-lymphoma cells, but it was more potent in ADCC than hu8E4. Importantly, hu8E4D57E was shown to be significantly more effective than Hu8E4 in prolonging the survival of SCID mice bearing disseminated B-lymphoma cells, suggesting that it might be a promising therapeutic agent for B-cell lymphomas. Moreover, this study also suggests that the mutations that can improve the affinity of rituximab may be transferred to other anti-CD20 murine mAbs to enhance their binding to CD20.


Assuntos
Anticorpos Monoclonais Humanizados/imunologia , Antígenos CD20/imunologia , Epitopos/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais Humanizados/genética , Citotoxicidade Celular Dependente de Anticorpos , Apoptose , Epitopos/química , Humanos , Camundongos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Homologia de Sequência de Aminoácidos
13.
Mem Cognit ; 43(4): 672-80, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25392192

RESUMO

This research investigated retrieval-induced interference between counterpart multiplication (2 × 3 = 6) and addition facts (2 + 3 = 5). Adults (N =72) repeatedly solved either a set of simple addition (0 + 2, 1 + 5, 2 + 3) or multiplication problems (0 × 2, 1 × 5, 2 × 3) during a practice phase and then switched operations during a test phase that included counterparts to the practiced problems and control problems. The paradigm afforded measurement in response time both of inter-operation retrieval-induced forgetting (RIF) and generalization of practice across different problems within operations. The experiment demonstrated generalization of practice for the rule-based 0 + N = N problems (e.g., practicing 0 + 2 facilitated performance on 0 + 7) as well as for problems governed by the multiplicative identity principle (1 × N = N) and zero-product principle (0 × N = 0), but not the fact-based 1 + N problems. The experiment also demonstrated for the first time inter-operation RIF of fact-based multiplication, which was as large as the effect observed for fact-based addition. The 0 × N, 0 + N, and 1 + N problems did not present item-specific RIF from practice of cross-operation counterparts, but 1 × N problems did, despite the generalization-of-practice evidence that 1 × N problems were solved using an item-general procedure. The item-specific RIF for 1 × N = N must reflect item-specific interference rather than item-level competitor inhibition given that there is no item-level representation of 1 × N = N facts in long-term memory.


Assuntos
Generalização Psicológica/fisiologia , Conceitos Matemáticos , Rememoração Mental/fisiologia , Resolução de Problemas/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
14.
PLoS Pathog ; 8(12): e1003084, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23271972

RESUMO

Epstein-Barr Virus (EBV) is an oncogenic γ-herpesvirus that capably establishes both latent and lytic modes of infection in host cells and causes malignant diseases in humans. Nuclear antigen 2 (EBNA2)-mediated transcription of both cellular and viral genes is essential for the establishment and maintenance of the EBV latency program in B lymphocytes. Here, we employed a protein affinity pull-down and LC-MS/MS analysis to identify nucleophosmin (NPM1) as one of the cellular proteins bound to EBNA2. Additionally, the specific domains that are responsible for protein-protein interactions were characterized as EBNA2 residues 300 to 360 and the oligomerization domain (OD) of NPM1. As in c-MYC, dramatic NPM1 expression was induced in EBV positively infected B cells after three days of viral infection, and both EBNA2 and EBNALP were implicated in the transactivation of the NPM1 promoter. Depletion of NPM1 with the lentivirus-expressed short-hairpin RNAs (shRNAs) effectively abrogated EBNA2-dependent transcription and transformation outgrowth of lymphoblastoid cells. Notably, the ATP-bound state of NPM1 was required to induce assembly of a protein complex containing EBNA2, RBP-Jκ, and NPM1 by stabilizing the interaction of EBNA2 with RBP-Jκ. In a NPM1-knockdown cell line, we demonstrated that an EBNA2-mediated transcription defect was fully restored by the ectopic expression of NPM1. Our findings highlight the essential role of NPM1 in chaperoning EBNA2 onto the latency-associated membrane protein 1 (LMP1) promoters, which is coordinated with the subsequent activation of transcriptional cascades through RBP-Jκ during EBV infection. These data advance our understanding of EBV pathology and further imply that NPM1 can be exploited as a therapeutic target for EBV-associated diseases.


Assuntos
Linfócitos B/metabolismo , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/fisiologia , Chaperonas Moleculares/metabolismo , Proteínas Nucleares/metabolismo , Transcrição Gênica , Proteínas Virais/metabolismo , Latência Viral/fisiologia , Linfócitos B/virologia , Linhagem Celular Tumoral , Antígenos Nucleares do Vírus Epstein-Barr/genética , Humanos , Chaperonas Moleculares/genética , Proteínas Nucleares/genética , Nucleofosmina , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-myc , Proteínas da Matriz Viral/biossíntese , Proteínas da Matriz Viral/genética , Proteínas Virais/genética , Montagem de Vírus/fisiologia
15.
Sex Transm Infect ; 90(5): 408-12, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24695989

RESUMO

OBJECTIVES: We examined sexual decision making type among couples in HIV sero-discordant partnerships in Uganda, and investigated how sexual decision making type changed over time and its effect on condom use. METHODS: Data were drawn from a longitudinal cohort of HIV sero-discordant couples, recruited through the AIDS Support Organisation in Jinja, Uganda. Sexual decision making was measured using the Sexual Relationship Power Scale, and couples' individual self-report answers were matched to assess agreement for decision making type and condom use. Generalised linear mixed effects modelling was used to assess statistically significant differences in time trend of sexual decision making type, and to investigate the independent association of decision making type on condom use status over time. RESULTS: Of the 533 couples included in this analysis, 345 (65%) reported using condoms at last sex at study enrolment. In the time trend analysis of decision making, the proportion of couples who decided together increased over time while the proportions of couples who reported that one partner decided or no one decided/did not use condoms, decreased over time (overall p<0.001). Compared with couples who decided together, those who disagreed (adjusted OR=0.42, 95% CI 0.28 to 0.64) and those where one partner decided (adjusted OR=0.20, 95% CI 0.12 to 0.34) had significantly lower odds of condom use at last sex, even after controlling for confounders. CONCLUSIONS: Couples who disagreed on decision making, or agreed that one partner decides alone, had significantly lower odds of reporting condom use compared with couples who decided together. HIV counselling interventions that encourage joint sexual decision making may improve condom use within this population.


Assuntos
Preservativos/estatística & dados numéricos , Tomada de Decisões , Aconselhamento Diretivo , Características da Família , Soronegatividade para HIV , Soropositividade para HIV/epidemiologia , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais , Adulto , Feminino , Soropositividade para HIV/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Autorrelato , Comportamento Sexual/psicologia , Parceiros Sexuais/psicologia , Uganda/epidemiologia
16.
AIDS Behav ; 18(11): 2240-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24781638

RESUMO

Treatment interruptions (TIs) limit the therapeutic success of combination antiretroviral therapy and are associated with higher morbidity and mortality. HIV-positive individuals dealing with concurrent health issues, access challenges and competing life demands are hypothesized to be more likely to interrupt treatment. Individuals were included if they initiated cART ≥1 year prior to interview date and had a CD4 cell count and initial regimen recorded at initiation. Using pharmacy recording, a TI was defined as a patient-initiated gap in treatment ≥90 consecutive days during the 12 months preceding or following the study interview. 117 (15.2 %) of 768 participants included in this study had a TI during the study window. 76.0 % of participants were male, 27.5 % were of Aboriginal ancestry and the median age was 46 (interquartile range 40-52). In multivariable logistic regression, TIs were significantly associated with current illicit drug use (adjusted odds ratio [aOR] 1.68, 95 % confidence interval [CI] 1.05-2.68); <95 % adherence in the first year of treatment (aOR 2.68, 95 % CI 1.67-4.12); living with at least one person (aOR 1.95; 95 % CI 1.22-3.14) or living on the street (aOR 5.08, 95 % CI 1.72-14.99) compared to living alone; poor perception of overall health (aOR 1.64 95 % CI 1.05-2.55); being unemployed (aOR: 2.22, 95 % CI 1.16-4.23); and younger age at interview (aOR 0.57, 95 % CI 0.44-0.75, per 10 year increase). Addressing socioeconomic barriers to treatment retention is vital for supporting the continuous engagement of patients in care.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Fatores Etários , Colúmbia Britânica/epidemiologia , Contagem de Linfócito CD4/estatística & dados numéricos , Feminino , Infecções por HIV/psicologia , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos
17.
Contemp Nurse ; 46(2): 214-24, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24787255

RESUMO

The aim of the study was to develop and test the psychometric properties of an instrument which measures clinical teaching competencies of nursing preceptors. It is necessary to investigate what kinds of teaching competencies are required in modern, more student-centered higher education teaching contexts. Nurses need to possess teaching competence to perform the role of preceptor properly. However, empirical studies exploring teaching competence are rare. Psychometric testing was conducted on a sample of 389 clinical nursing preceptors from three hospitals in 2010. Exploratory factor analysis and reliability testing were conducted on the 53-item Clinical Teaching Competencies Scale. Results indicated that principal axis factoring extraction identified four factors through a promax rotation: Student evaluation, goal setting and individual teaching, teaching strategies, and demonstration of organized knowledge. The Cronbach's α values for the four factors ranged from 0.82-0.87. The Clinical Teaching Competence Inventory was found to have adequate construct validity and internal consistency of reliability for clinical nursing preceptors to assess clinical teaching behaviors in practice settings.


Assuntos
Competência Clínica/normas , Bacharelado em Enfermagem/normas , Avaliação Educacional/métodos , Docentes/normas , Recursos Humanos de Enfermagem/normas , Preceptoria/normas , Adulto , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Estudantes de Enfermagem , Taiwan , Adulto Jovem
18.
Sci China Life Sci ; 67(1): 161-174, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37837530

RESUMO

N6-methyladenosine (m6A) is the most abundant eukaryotic mRNA modification and is involved in various biological processes. Increasing evidence has implicated that m6A modification is an important anti-viral defense mechanism in mammals and plants, but it is largely unknown how m6A regulates viral infection in plants. Here we report the dynamic changes and functional anatomy of m6A in Nicotiana benthamiana and Solanum lycopersicum during Pepino mosaic virus (PepMV) infection. m6A modification in the PepMV RNA genome is conserved in these two species. Overexpression of the m6A writers, mRNA adenosine methylase A (MTA), and HAKAI inhibit the PepMV RNA accumulation accompanied by increased viral m6A modifications, whereas deficiency of these writers decreases the viral RNA m6A levels but enhances virus infection. Further study reveals that the cytoplasmic YTH-domain family protein NbECT2A/2B/2C as m6A readers are involved in anti-viral immunity. Protein-protein interactions indicate that NbECT2A/2B/2C interact with nonsense-mediated mRNA decay (NMD)-related proteins, including NbUPF3 and NbSMG7, but not with NbUPF1. m6A modification-mediated restriction to PepMV infection is dependent on NMD-related factors. These findings provide new insights into the functionality of m6A anti-viral activity and reveal a distinct immune response that NMD factors recognize the m6A readers-viral m6A RNA complex for viral RNA degradation to limit virus infection in plants.


Assuntos
Vírus de Plantas , Viroses , Humanos , Degradação do RNAm Mediada por Códon sem Sentido , Vírus de Plantas/genética , RNA , RNA Mensageiro/genética
19.
Bioengineering (Basel) ; 11(6)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38927867

RESUMO

Fatigue is believed to increase the risk of anterior cruciate ligament (ACL) injury by directly promoting high-risk biomechanics in the lower limbs. Studies have shown that dynamic taping can help normalize inadequate biomechanics during landings. This study aims to examine the effects of dynamic taping on landing biomechanics in fatigued football athletes. Twenty-seven high-school football athletes were recruited and randomly allocated to groups of either active taping or sham taping, with a crossover allocation two weeks later. In each group, the participants underwent a functional agility short-term fatigue protocol and were evaluated using the landing error scoring system before and after the fatigue protocol. The landing error scoring system (LESS) scores in the sham taping group increased from 4.24 ± 1.83 to 5.36 ± 2.00 (t = -2.07, p = 0.04, effect size = 0.61). In contrast, the pre-post difference did not reach statistical significance in the active taping group (from 4.24 ± 1.69 to 4.52 ± 1.69, t = -1.50, p = 0.15, effect size 0.46). Furthermore, the pre-post changes between the sham and active taping groups were statistically significant (sham taping: 1.12 ± 1.20; active taping: 0.28 ± 0.94, p = 0.007). Dynamic taping, particularly using the spiral technique, appeared to mitigate faulty landing biomechanics in the fatigued athletes by reducing hip and knee flexion and increasing hip internal rotation during landing. These results suggest that dynamic taping can potentially offer protective benefits in landing mechanics, which could further be applied to prevent ACL injuries in fatigued athletes.

20.
Diabetes Res Clin Pract ; 207: 111033, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38049037

RESUMO

AIMS: The prevalence of Type 2 Diabetes Mellitus (T2DM) is projected to be 7 % in 2030. Despite its need for long-term diabetes care, the adherence rate of injectable medications such as insulin is around 60 %, lower than the acceptable threshold of 80 %. This study aims to create classification models to predict insulin adherence among adult T2DM naïve insulin users. METHODS: Clinical data were extracted from Taipei Medical University Clinical Research Database (TMUCRD) from January 1st, 2004 to December 30th, 2020. A patient was regarded as adherent if his/her medication possession ratio (MPR) was at least 80 %. Seven domains of predictors were created, including demographics, baseline medications, baseline comorbidities, baseline laboratory data, healthcare resource utilization, index insulins, and the concomitant non-insulin T2DM medications. We built two Xgboost models for internal and external testing respectively. RESULTS: Using a cohort of 4134 patients from Taiwan, our model achieved the Area Under the curve of the Receiver Operating Characteristic (AUROC) of the internal test was 0.782 and the AUROC of the external test was 0.771. the SHAP (SHapley Additive exPlanations) value showed that the number of prescribed medications, the number of outpatient visits, and laboratory data were predictive of future insulin adherence. CONCLUSIONS: This is the first study to predict adherence among adult naïve insulin users. The developed model is a potential clinical decision support tool to identify possible non-adherent patients for healthcare providers to design individualized education plans.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Adulto , Masculino , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Insulina/uso terapêutico , Estudos de Coortes , Adesão à Medicação , Insulina Regular Humana/uso terapêutico , Aprendizado de Máquina , Estudos Retrospectivos
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