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1.
Plant Physiol ; 193(2): 1197-1212, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37335936

RESUMO

Domestication is the long and complex process underlying the evolution of crops, in which artificial directional selection transformed wild progenitors into the desired form, affecting genomic variation and leaving traces of selection at targeted loci. However, whether genes controlling important domestication traits follow the same evolutionary pattern expected under the standard selective sweep model remains unclear. With whole-genome resequencing of mungbean (Vigna radiata), we investigated this issue by resolving its global demographic history and targeted dissection of the molecular footprints of genes underlying 2 key traits representing different stages of domestication. Mungbean originated in Asia, and the Southeast Asian wild population migrated to Australia about 50 thousand generations ago. Later in Asia, the cultivated form diverged from the wild progenitor. We identified the gene associated with the pod shattering resistance trait, VrMYB26a, with lower expression across cultivars and reduced polymorphism in the promoter region, reflecting a hard selective sweep. On the other hand, the stem determinacy trait was associated with VrDet1. We found that 2 ancient haplotypes of this gene have lower gene expression and exhibited intermediate frequencies in cultivars, consistent with selection favoring independent haplotypes in a soft selective sweep. In mungbean, contrasting signatures of selection were identified from the detailed dissection of 2 important domestication traits. The results suggest complex genetic architecture underlying the seemingly simple process of directional artificial selection and highlight the limitations of genome-scan methods relying on hard selective sweeps.


Assuntos
Fabaceae , Vigna , Vigna/genética , Locos de Características Quantitativas , Domesticação , Fabaceae/genética , Demografia , Seleção Genética
2.
J Med Ethics ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527787

RESUMO

Respect for patient autonomy is paramount in resolving ethical tensions in end-of-life care. The concept of relational autonomy has contributed to this debate; however, scholars often use this concept in a fragmented manner. This leads to partial answers on ascertaining patients' true wishes, meaningfully engaging patients' significant others, balancing interests among patients and significant others, and determining clinicians' obligations to change patients' unconventional convictions to enhance patient autonomy. A satisfactory solution based on relational autonomy must incorporate patients' competence (apart from decisional capacity), authenticity (their true desires or beliefs) and the involvement level of their significant others. To that end, we argue that John Christman's procedural approach to relational autonomy provides critical insights, such as the diachronic or socio-historical personhood, sustained critical reflection and his recent explication of the nature of asymmetrical relationships and helpful interlocutors. This study reviews Christman's account, proposes minor modifications and advocates for an integrated three-dimensional model for medical decision-making. Clarifying the relationship among the three elements promotes an ethical framework with a coherent understanding of relational autonomy. This model not only provides a descriptive and normative framework for end-of-life care practice but also reconsiders the nature of the clinician-patient relationship and its normative implications. We further present a case study to illustrate the merits of our proposed model. Altogether, our proposal will help navigate complex medical decision-making, foster trust and negotiate shared values between patients and their significant others, particularly in end-of-life care.

3.
Am Nat ; 202(4): 558-570, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37792919

RESUMO

AbstractGenetic variation within species is crucial for sessile species to adapt to novel environments when facing dramatic climate changes. However, the debate continues whether standing ancestral variation adaptive to current environmental variability is sufficient to guarantee future suitability. Using wild banana Musa itinerans, we investigated the relative contribution of standing ancestral variation versus new mutations to environmental adaptation and inferred their future fate. On the continental island of Taiwan, local populations immigrated from the Southeast Asian continent during the ice age and have been isolated since then. This allows the classification of genetic variants into standing ancestral variation (polymorphic in Taiwan and the continent) and new mutations (polymorphic only in Taiwan). For temperature-related variables where Taiwan is mainly within the ancestral climatic range, standing ancestral variation had a slightly stronger association than new mutations. New mutations were more important for precipitation-related variables, where northeastern Taiwan had much more winter rainfall than most of continental Southeast Asia. Upon future climate change, new mutations showed higher genetic offset in regions of abrupt transition between allele frequency and local environments, suggesting their greater spatial heterogeneity of future vulnerability.


Assuntos
Musa , Musa/genética , Mudança Climática , Frequência do Gene , Adaptação Fisiológica , Mutação
4.
Eur J Nutr ; 62(5): 2177-2194, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37024732

RESUMO

PURPOSE: Pu-erh tea can be classified into raw pu-erh tea and ripened pu-erh tea. Theabrownin (TB) is one of the major components of pu-erh tea. The difference of the anti-obesity activity between raw pu-erh tea TB (R-TB) and ripened pu-erh tea TB (F-TB) has not been comprehensively investigated yet. Therefore, this article aimed to systemically study the anti-obesity activity and the underlying mechanism of R-TB and F-TB. METHOD: High-fat diet (HFD)-induced C57BL/6J mice with obesity were gavaged with R-TB or F-TB to assess the effect of R-TB and F-TB on the amelioration of obesity, the expression of lipid metabolism-related genes, and the regulation of gut flora imbalance. RESULTS: Administration of both R-TB and F-TB could suppress body weight gain, improve insulin sensitivity and glucose homeostasis, regulate the lipid level and reduce the chronic inflammation in obese mice. The underlying anti-obesity mechanism of R-TB and F-TB might involve the regulation of lipogenesis and lipolysis, amelioration of the gut microbiota disorder and promotion of microbial metabolism. Interestingly, R-TB was more efficient in the regulation of blood glucose, reduction of inflammation and suppression of partial adipogenesis-related genes and protein, while F-TB was more effective in the inhibition of lipolysis-related genes and protein. In addition, F-TB might be more effective in adjusting the dysbacteria caused by HFD back to normal by promoting the proliferation of the beneficial microbiota, such as Lactobacillus and Lachnospiraceae_NK4A136_group. CONCLUSION: Taken together, both R-TB and F-TB had the potential to be developed as beneficial dietary supplements or functional foods for ameliorating obesity and obesity-related metabolic disorders, but their effects and the ability to regulate the intestinal flora varied.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Chá , Camundongos Endogâmicos C57BL , Obesidade , Inflamação
5.
Proc Natl Acad Sci U S A ; 117(25): 14543-14551, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32461376

RESUMO

The genetic architecture of quantitative traits is determined by both Mendelian and polygenic factors, yet classic examples of plant domestication focused on selective sweep of newly mutated Mendelian genes. Here we report the chromosome-level genome assembly and the genomic investigation of a nonclassic domestication example, bitter gourd (Momordica charantia), an important Asian vegetable and medicinal plant of the family Cucurbitaceae. Population resequencing revealed the divergence between wild and South Asian cultivars about 6,000 y ago, followed by the separation of the Southeast Asian cultivars about 800 y ago, with the latter exhibiting more extreme trait divergence from wild progenitors and stronger signs of selection on fruit traits. Unlike some crops where the largest phenotypic changes and traces of selection happened between wild and cultivar groups, in bitter gourd large differences exist between two regional cultivar groups, likely reflecting the distinct consumer preferences in different countries. Despite breeding efforts toward increasing female flower proportion, a gynoecy locus exhibits complex patterns of balanced polymorphism among haplogroups, with potential signs of selective sweep within haplogroups likely reflecting artificial selection and introgression from cultivars back to wild accessions. Our study highlights the importance to investigate such nonclassic example of domestication showing signs of balancing selection and polygenic trait architecture in addition to classic selective sweep in Mendelian factors.


Assuntos
Domesticação , Genoma de Planta , Momordica charantia/genética , Seleção Genética , Especiação Genética , Herança Multifatorial , Filogenia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
6.
Am J Transplant ; 21(3): 1068-1079, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32860293

RESUMO

This study investigated how multiple family members co-construct the ethical significance of living donor liver transplantation (LDLT) and how the family structure and dynamics of donor-recipient-caregiver relationships shape the communication and decision-making process within the sociocultural context of Taiwan. We conducted in-depth interviews with 36 participants from 13 families at the Chang Gung Memorial Hospital from February to December 2019. Interviews were audio recorded, transcribed, and translated from Mandarin to English and analyzed utilizing grounded theory and thematic analysis. Our findings revealed that LDLT in Taiwan is not merely a personal choice of either donor or recipient but essentially a collaborative process of family-centered medical decision-making, intertwined with socioeconomic conditions, cultural and social norms, gender roles, and the division of labor in the household. The notion of reciprocity and indebtedness for family members is a central theme underlying the entire process of motivation, deliberation, and decision-making, thereby reinforcing the naturalness of LDLT. However, our study highlighted that donors from families with traditional gender hierarchy and power imbalance may experience psychological and social vulnerabilities. Conclusively, we suggest that healthcare professionals should be sensitive to the contextual and relational factors involved in family dynamics and provide appropriate support to the ambivalent donors.


Assuntos
Transplante de Fígado , Adulto , Comunicação , Família , Relações Familiares , Humanos , Doadores Vivos , Motivação , Taiwan
7.
Proc Biol Sci ; 288(1949): 20202472, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33878927

RESUMO

Differential local adaptation restricts gene flow between populations inhabiting distinct environments, resulting in isolation by adaptation. In addition to the statistical inferences of genotype-environment associations, an integrative approach is needed to investigate the effect of local adaptation on population divergence at the ecological, genetic and genomic scale. Here, we combine reciprocal transplant, genome-environment association and QTL mapping to investigate local adaptation in Boechera stricta (Drummond's rockcress). With reciprocal transplant experiment, we found local genetic groups exhibit phenotypic characteristics corresponding to the distinct selection forces from different water availability. At the genetic level, the local allele of a major fitness QTL confers higher and sturdier flowering stalks, maximizing the fecundity fitness component under sufficient water supply, and its genetic variation is associated with precipitation across the landscape. At the genomewide scale, we further showed that multiple loci associated with precipitation are highly differentiated between genetic groups, suggesting that local adaptation has a widespread effect on reducing gene flow. This study provides one of the few comprehensive examples demonstrating how local adaptation facilitates population divergence at the trait, gene and genome level.


Assuntos
Brassicaceae , Seleção Genética , Adaptação Fisiológica/genética , Brassicaceae/genética , Genômica , Locos de Características Quantitativas
8.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808261

RESUMO

In host-parasitoid interactions, antagonistic relationship drives parasitoids to vary in virulence in facing different hosts, which makes these systems excellent models for stress-induced evolutionary studies. Venom compositions varied between two strains of Tetrastichus brontispae, Tb-Bl and Tb-On. Tb-Bl targets Brontispa longissima pupae as hosts, and Tb-On is a sub-population of Tb-Bl, which has been experimentally adapted to a new host, Octodonta nipae. Aiming to examine variation in parasitoid virulence of the two strains toward two hosts, we used reciprocal injection experiments to compare effect of venom/ovarian fluids from the two strains on cytotoxicity, inhibition of immunity and fat body lysis of the two hosts. We found that Tb-Onvenom was more virulent towards plasmatocyte spreading, granulocyte function and phenoloxidase activity than Tb-Blvenom. Tb-Blovary was able to suppress encapsulation and phagocytosis in both hosts; however, Tb-Onovary inhibition targeted only B. longissima. Our data suggest that the venom undergoes rapid evolution when facing different hosts, and that the wasp has good evolutionary plasticity.


Assuntos
Besouros/parasitologia , Especificidade de Hospedeiro/genética , Interações Hospedeiro-Parasita/fisiologia , Animais , Evolução Molecular , Himenópteros/fisiologia , Fagocitose/fisiologia , Pupa/parasitologia , Virulência , Vespas/fisiologia
9.
Med Sci Monit ; 26: e924787, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32741960

RESUMO

BACKGROUND Rheumatoid arthritis (RA) is an inflammatory disorder that is present in approximately 1% of the world's population. This study was aimed to investigate the effect of retinoic acid-platinum (II) complex [RT-Pt(II)] on rheumatoid arthritis (RA) and to explore the mechanism involved. MATERIAL AND METHODS MH7A cell viability was determined by MTT assay and apoptosis was assessed using FACSCalibur flow cytometry. RT-PCR and Western blot assays were used for assessment of mRNA and proteins levels. RESULTS Treatment of rheumatoid arthritis with RT-Pt(II) significantly reduced the levels of IL­1ß, IL-6, IL-8, MMP-1, and MMP-13 in synovial fluid of mice in a dose-dependent manner. The expression of iNOS and COX-2 mRNA and protein in rheumatoid arthritis rats was also significantly inhibited by treatment with RT-Pt(II). The TNF-alpha-induced proliferation of MH7A cells was alleviated by RT-Pt(II) treatment in a concentration-dependent manner. Moreover, RT-Pt(II) treatment induced apoptosis and caused arrest of cell cycle in MH7A cells. The activation of MEK/NF-kappaB pathway was downregulated by RT-Pt(II) treatment in MH7A cells. CONCLUSIONS In summary, the present study demonstrated that RT-Pt(II) inhibits TNF-alpha-induced inflammatory response, suppresses cell viability, and induces apoptosis in rheumatoid arthritis synovial cells. Moreover, RT-Pt(II) exhibited its effect through targeting the MEK/NF-kappaB pathway. Therefore, RT-Pt(II) can be used for the development of treatments for rheumatoid arthritis.


Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Complexos de Coordenação/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , NF-kappa B/genética , Compostos de Platina/farmacologia , Animais , Antirreumáticos/síntese química , Apoptose/efeitos dos fármacos , Apoptose/genética , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Linhagem Celular , Complexos de Coordenação/síntese química , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/imunologia , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/imunologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Compostos de Platina/síntese química , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Líquido Sinovial/citologia , Líquido Sinovial/imunologia , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/imunologia , Sinoviócitos/patologia , Tretinoína/química , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia
10.
Int J Mol Sci ; 21(17)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882943

RESUMO

Calmodulin binding is a nearly universal property of gap junction proteins, imparting a calcium-dependent uncoupling behavior that can serve in an emergency to decouple a stressed cell from its neighbors. However, gap junctions that function as electrical synapses within networks of neurons routinely encounter large fluctuations in local cytoplasmic calcium concentration; frequent uncoupling would be impractical and counterproductive. We have studied the properties and functional consequences of calmodulin binding to the electrical synapse protein Connexin 35 (Cx35 or gjd2b), homologous to mammalian Connexin 36 (Cx36 or gjd2). We find that specializations in Cx35 calmodulin binding sites make it relatively impervious to moderately high levels of cytoplasmic calcium. Calmodulin binding to a site in the C-terminus causes uncoupling when calcium reaches low micromolar concentrations, a behavior prevented by mutations that eliminate calmodulin binding. However, milder stimuli promote calcium/calmodulin-dependent protein kinase II activity that potentiates coupling without interference from calmodulin binding. A second calmodulin binding site in the end of the Cx35 cytoplasmic loop, homologous to a calmodulin binding site present in many connexins, binds calmodulin with very low affinity and stoichiometry. Together, the calmodulin binding sites cause Cx35 to uncouple only at extreme levels of intracellular calcium.


Assuntos
Calmodulina/metabolismo , Conexinas/metabolismo , Sinapses Elétricas/fisiologia , Junções Comunicantes/fisiologia , Sinalização do Cálcio , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Calmodulina/genética , Conexinas/genética , Células HeLa , Humanos , Mutação , Fosforilação , Ligação Proteica , Transporte Proteico , Proteína delta-2 de Junções Comunicantes
11.
BMC Evol Biol ; 18(1): 187, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30526493

RESUMO

BACKGROUND: Adaptive evolution is one of the crucial mechanisms for organisms to survive and thrive in new environments. Recent studies suggest that adaptive evolution could rapidly occur in species to respond to novel environments or environmental challenges during range expansion. However, for environmental adaptation, many studies successfully detected phenotypic features associated with local environments, but did not provide ample genetic evidence on microevolutionary dynamics. It is therefore crucial to thoroughly investigate the genetic basis of rapid microevolution in response to environmental changes, in particular on what genes and associated variation are responsible for environmental challenges. Here, we genotyped genome-wide gene-associated microsatellites to detect genetic signatures of rapid microevolution of a marine tunicate invader, Ciona robusta, during recent range expansion to the harsh environment in the Red Sea. RESULTS: The Red Sea population was significantly differentiated from the other global populations. The genome-wide scan, as well as multiple analytical methods, successfully identified a set of adaptive genes. Interestingly, the allele frequency largely varied at several adaptive loci in the Red Sea population, and we found significant correlations between allele frequency and local environmental factors at these adaptive loci. Furthermore, a set of genes were annotated to get involved in local temperature and salinity adaptation, and the identified adaptive genes may largely contribute to the invasion success to harsh environments. CONCLUSIONS: All the evidence obtained in this study clearly showed that environment-driven selection had left detectable signatures in the genome of Ciona robusta within a few generations. Such a rapid microevolutionary process is largely responsible for the harsh environmental adaptation and therefore contributes to invasion success in different aquatic ecosystems with largely varied environmental factors.


Assuntos
Evolução Biológica , Ciona intestinalis/genética , Ecossistema , Adaptação Fisiológica/genética , Animais , Teorema de Bayes , Ciona intestinalis/fisiologia , Frequência do Gene/genética , Ontologia Genética , Loci Gênicos , Variação Genética , Genética Populacional , Genoma , Repetições de Microssatélites/genética , Anotação de Sequência Molecular , Seleção Genética
13.
J Cell Sci ; 128(21): 3888-97, 2015 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-26359298

RESUMO

Gap junctions formed of connexin 36 (Cx36, also known as Gjd2) show tremendous functional plasticity on several time scales. Changes in connexin phosphorylation modify coupling in minutes through an order of magnitude, but recent studies also imply involvement of connexin turnover in regulating cell-cell communication. We utilized Cx36 with an internal HaloTag to study Cx36 turnover and trafficking in cultured cells. Irreversible, covalent pulse-chase labeling with fluorescent HaloTag ligands allowed clear discrimination of newly formed and pre-existing Cx36. Cx36 in junctional plaques turned over with a half-life of 3.1 h, and the turnover rate was unchanged by manipulations of protein kinase A (PKA) activity. In contrast, changes in PKA activity altered coupling within 20 min. New Cx36 in cargo vesicles was added directly to existing gap junctions and newly made Cx36 was not confined to points of addition, but diffused throughout existing gap junctions. Existing connexins also diffused into photobleached areas with a half-time of less than 2 s. In conclusion, studies of Cx36-HaloTag revealed novel features of connexin trafficking and demonstrated that phosphorylation-based changes in coupling occur on a different time scale than turnover.


Assuntos
Conexinas/metabolismo , Junções Comunicantes/metabolismo , Animais , Brefeldina A/farmacologia , Bovinos , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/fisiologia , Linhagem Celular , Recuperação de Fluorescência Após Fotodegradação , Junções Comunicantes/efeitos dos fármacos , Células HeLa , Humanos , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Proteína delta-2 de Junções Comunicantes
14.
Artigo em Inglês | MEDLINE | ID: mdl-28990217

RESUMO

A typical characteristic of the insect innate immune system is the activation of the serine protease cascade in the hemolymph. As being the terminal component of the extracellular serine protease cascade in the prophenoloxidase (proPO) activating system, proPO-activating factors (PPAFs) activated by the upstream cascade may generate active phenoloxidase, which then induces downstream melanization. In the present study, we reported three PPAFs from the nipa palm hispid beetle Octodonta nipae (Maulik) (designated as OnPPAF1, OnPPAF2, OnPPAF3). All three OnPPAFs contained a single clip domain at the amino-terminus followed by a trypsin-like serine protease domain at the carboxyl-terminus, except the Ser in the active sites of OnPPAF2 and OnPPAF3 was substituted with Gly. Transcript expression analysis revealed that all OnPPAFs were highly expressed in hemolymph, whereas OnPPAF2 showed an extremely low mRNA abundance compared with that of OnPPAF1 and OnPPAF3, and that the abundance of all three OnPPAFs was dramatically increased upon bacterial challenge. Knockdown of OnPPAF1 or OnPPAF3 resulted in a reduction of hemolymph phenoloxidase activity and an inhibition of hemolymph melanization, whereas the knockdown of OnPPAF2 did not affect the proPO cascade. Our work thus implies that the three OnPPAFs may have different functions and regulation during immune responses in O. nipae.


Assuntos
Catecol Oxidase/metabolismo , Besouros/metabolismo , Precursores Enzimáticos/metabolismo , Serina Endopeptidases/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Besouros/genética , Besouros/imunologia , Expressão Gênica , Hemolinfa/enzimologia , Imunidade Inata , Proteínas de Insetos/metabolismo , Melaninas/metabolismo , Filogenia , Interferência de RNA , Serina Endopeptidases/genética , Serina Proteases/metabolismo
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(4): 380-388, 2017 Apr 28.
Artigo em Zh | MEDLINE | ID: mdl-28490694

RESUMO

OBJECTIVE: To observe effect of acupuncture combined with hypothermia therapy on MAPK/ERK pathway and apoptosis related factorsin rats suffered cerebral ischemia reperfusion and to explore underlying mechanisms.
 Methods: Middle cerebral artery ischemia model were established.Ninety SD rats were randomly assigned into a blank group, a control group, a model group, an acupuncture group, a mild hypothermia group, and an acupuncture with hypothermia group. After 72 h treatment, nerve function defect scores were observed, and infarction area percent was detected by 2, 3, 5-triphenyl-2H-tetrazolium chloride (TTC) staining; expressions of Bcl-2 and Bax were examined by immunohistochemistry; apoptotic cells were detected by TUNEL assay; and expression levels of phospho-mitogen-activated protein kinase(p-MEK2) and phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2) in the rats' hippocampus ischemic side were determined by Western blot.
 Results: In the rats of the model group, the neural function defect scores, the infarction area percent, the expression level of Bax, and apoptotic cells increased, while the level of Bcl-2 decreased significantly. The level of p-MEK2 and p-ERK1/2 increased obviously compared with the blank and control groups (P<0.05 or P<0.01). After treatment with acupuncture and hypothermia, the neural function defect scores, infarction area percent, and the level of Bax, apoptotic cells and the levels of p-MEK2 and p-ERK1/2 were significantly decreased, while the level of Bcl-2 in the treatment group was significantly elevated (P<0.05 or P<0.01) compared with the model group. Compared with the acupuncture group or the hypothermia group, the neural function defect scores and the levels of p-MEK2 and p-ERK1/2 in the acupuncture combined with hypothermia group were significantly reduced (P<0.05 or P<0.01).
 Conclusion: Acupuncture and hypothermia therapy can improve cerebral function, and reduce the cerebral injury through down-regulation of Bax level, and up-regulation of Bcl-2 level, which is related to reducing the levels of p-MEK2 and p-ERK1/2. The therapeutic effects on cerebral ischemia reperfusion injury for combination of acupuncture with hypothermia are better than those with single application of acupuncture or hypothermia.


Assuntos
Terapia por Acupuntura , Hipotermia Induzida , Sistema de Sinalização das MAP Quinases/fisiologia , Animais , Apoptose/fisiologia , Infarto Encefálico/terapia , Lesões Encefálicas/terapia , Isquemia Encefálica/terapia , Regulação para Baixo , MAP Quinase Quinase 2/fisiologia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/terapia , Regulação para Cima
16.
Biochim Biophys Acta ; 1854(12): 1842-1852, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26275807

RESUMO

Acetylene (HCCH) has a long history as a mechanism-based enzyme inhibitor and is considered an active-site probe of the particulate methane monooxygenase (pMMO). Here, we report how HCCH inactivates pMMO in Methylococcus capsulatus (Bath) by using high-resolution mass spectrometry and computational simulation. High-resolution MALDI-TOF MS of intact pMMO complexes has allowed us to confirm that the enzyme oxidizes HCCH to the ketene (C2H2O) intermediate, which then forms an acetylation adduct with the transmembrane PmoC subunit. LC-MS/MS analysis of the peptides derived from in-gel proteolytic digestion of the protein subunit identifies K196 of PmoC as the site of acetylation. No evidence is obtained for chemical modification of the PmoA or PmoB subunit. The inactivation of pMMO by a single adduct in the transmembrane PmoC domain is intriguing given the complexity of the structural fold of this large membrane-protein complex as well as the complicated roles played by the various metal cofactors in the enzyme catalysis. Computational studies suggest that the entry of hydrophobic substrates to, and migration of products from, the catalytic site of pMMO are controlled tightly within the transmembrane domain. Support of these conclusions is provided by parallel experiments with two related alkynes: propyne (CH3CCH) and trifluoropropyne (CF3CCH). Finally, we discuss the implication of these findings to the location of the catalytic site in pMMO.


Assuntos
Acetileno/metabolismo , Methylococcus capsulatus/metabolismo , Oxigenases/metabolismo , Cromatografia Líquida , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
17.
Zhongguo Zhong Yao Za Zhi ; 39(14): 2646-52, 2014 Jul.
Artigo em Zh | MEDLINE | ID: mdl-25272489

RESUMO

OBJECTIVE: To establish the analytical method for the release kinetic (RK) of Aconitum Brachypodum gel based on the nonlinear mixed effect model (NLMEM), in order to rationally evaluate the drug release process and explain the release mechanism. METHOD: The zero-order kinetic model containing for non-corroded drug system with the random effect was taken as the base model. The fixed effect and random effect factors impacting the drug release were analyzed by PROC NLMIXED of SAS to establish the final typical model. Subsequently, 10 training subsets were randomly extracted from the primary data to respectively their RK models, calculate the corresponding predicted root-mean-square error and average relative error, and evaluate the model stability and prediction accuracy. RESULT: The burst effect F0 had a very significant effect on the RK model. Among the component factors, carbopol 940 showed an obvious effect on the inherence release speed constant k0 and the concentration gradient change constant a, with different variations on the basis of dosage range. The random effect factors of k0 and a had a significant impact. The final RK model was proved to be stable, effective and reliable in the cross validation. CONCLUSION: The drug release kinetic analysis method could be used to rationally evaluate the drug release process and explain the release mechanisms.


Assuntos
Aconitum/química , Medicamentos de Ervas Chinesas/química , Dinâmica não Linear , Géis , Cinética , Método de Monte Carlo
18.
J Eval Clin Pract ; 30(2): 174-183, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37723854

RESUMO

RATIONALE: Previous studies have explored shared decision making (SDM) implementation to determine the renal replacement therapy modality; however, the SDM approach for dialysis initiation, especially when patients refuse physician suggestions for long-term dialysis, remains unclear. AIMS AND OBJECTIVES: This study aimed to explore physicians' responses towards patients' refusal of long-term dialysis during the SDM process and the thinking processes of both physicians and patients regarding dialysis refusal. METHOD: We conducted in-depth semi-structured interviews with 10 patients diagnosed with end-stage renal disease, each of whom refused long-term dialysis after physicians employed the SDM framework, and nine nephrologists at the Chang Gung Memorial Hospital, Taiwan, from March to May 2020. Interviews were audio-recorded, transcribed, and translated from Mandarin to English. They were then thematically analysed. RESULTS: Three main themes on dialysis initiation SDM implementation and the differences between physician and patient perceptions on patient treatment refusal were yielded. While the SDM approach for dialysis initiation developed by nephrologists in Taiwan respects patient decisions, physicians often actively persuade patients to undergo dialysis in case of treatment refusal. The motivation behind this approach is to promote the patient's best medical interests, particularly post-dialysis life quality, and to ensure a 'rational' medical decision is made. However, patients' perceptions of treatment refusal differ significantly from those of physicians, and their decision-making process is often iterative and based on comprehensive evaluation of immediate concerns beyond biomedical factors. CONCLUSIONS: Findings suggest that the current physician-led SDM approach for dialysis initiation characterises active persuasion with physicians' perspectives predominating the clinical encounter. To improve SDM implementation, we propose that physicians should acknowledge and understand patients' reasoning for dialysis refusal and the distinction between objective health and subjective well-being during the decision-making process.


Assuntos
Tomada de Decisão Compartilhada , Médicos , Humanos , Diálise Renal , Tomada de Decisões , Taiwan , Participação do Paciente , Relações Médico-Paciente
19.
Front Microbiol ; 15: 1408885, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846563

RESUMO

The introduction of plant pathogens can quickly reshape disease dynamics in island agro-ecologies, representing a continuous challenge for local crop management strategies. Xanthomonas pathogens causing tomato bacterial spot were probably introduced in Taiwan several decades ago, creating a unique opportunity to study the genetic makeup and adaptive response of this alien population. We examined the phenotypic and genotypic identity of 669 pathogen entries collected across different regions of Taiwan in the last three decades. The analysis detected a major population shift, where X. euvesicatoria and X. vesicatoria races T1 and T2 were replaced by new races of X. perforans. After its introduction, race T4 quickly became dominant in all tomato-growing areas of the island. The genomic analysis of 317 global genomes indicates that the Xanthomonas population in Taiwan has a narrow genetic background, most likely resulting from a small number of colonization events. However, despite the apparent genetic uniformity, X. perforans race T4 shows multiple phenotypic responses in tomato lines. Additionally, an in-depth analysis of effector composition suggests diversification in response to local adaptation. These include unique mutations on avrXv3 which might allow the pathogen to overcome Xv3/Rx4 resistance gene. The findings underscore the dynamic evolution of a pathogen when introduced in a semi-isolated environment and provide insights into the potential management strategies for this important disease of tomato.

20.
J Neurosci ; 32(37): 12797-807, 2012 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-22973003

RESUMO

Unlike many other vertebrates, a healthy mammalian retina does not grow throughout life and lacks a ciliary margin zone capable of actively generating new neurons. The isolation of stem-like cells from the ciliary epithelium has led to speculation that the mammalian retina and/or surrounding tissues may retain neurogenic potential capable of responding to retinal damage. Using genetically altered mouse lines with varying degrees of retinal ganglion cell loss, we show that the retinal margin responds to ganglion cell loss by prolonging specific neurogenic activity, as characterized by increased numbers of Atoh7(LacZ)-expressing cells. The extent of neurogenic activity correlated with the degree of ganglion cell deficiency. In the pars plana, but not the retinal margin, cells remain proliferative into adulthood, marking the junction of pars plana and retinal margin as a niche capable of producing proliferative cells in the mammalian retina and a potential cellular source for retinal regeneration.


Assuntos
Corioide/citologia , Corioide/fisiologia , Neurogênese/fisiologia , Células Fotorreceptoras de Vertebrados/citologia , Células Fotorreceptoras de Vertebrados/fisiologia , Retina/citologia , Retina/fisiologia , Animais , Diferenciação Celular , Camundongos , Camundongos Knockout , Camundongos Transgênicos
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