Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 136
Filtrar
1.
Nature ; 585(7824): 256-260, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32848244

RESUMO

Temperature controls plant growth and development, and climate change has already altered the phenology of wild plants and crops1. However, the mechanisms by which plants sense temperature are not well understood. The evening complex is a major signalling hub and a core component of the plant circadian clock2,3. The evening complex acts as a temperature-responsive transcriptional repressor, providing rhythmicity and temperature responsiveness to growth through unknown mechanisms2,4-6. The evening complex consists of EARLY FLOWERING 3 (ELF3)4,7, a large scaffold protein and key component of temperature sensing; ELF4, a small α-helical protein; and LUX ARRYTHMO (LUX), a DNA-binding protein required to recruit the evening complex to transcriptional targets. ELF3 contains a polyglutamine (polyQ) repeat8-10, embedded within a predicted prion domain (PrD). Here we find that the length of the polyQ repeat correlates with thermal responsiveness. We show that ELF3 proteins in plants from hotter climates, with no detectable PrD, are active at high temperatures, and lack thermal responsiveness. The temperature sensitivity of ELF3 is also modulated by the levels of ELF4, indicating that ELF4 can stabilize the function of ELF3. In both Arabidopsis and a heterologous system, ELF3 fused with green fluorescent protein forms speckles within minutes in response to higher temperatures, in a PrD-dependent manner. A purified fragment encompassing the ELF3 PrD reversibly forms liquid droplets in response to increasing temperatures in vitro, indicating that these properties reflect a direct biophysical response conferred by the PrD. The ability of temperature to rapidly shift ELF3 between active and inactive states via phase transition represents a previously unknown thermosensory mechanism.


Assuntos
Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas Priônicas/química , Temperatura , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Aclimatação/fisiologia , Arabidopsis/química , Temperatura Alta , Modelos Moleculares , Peptídeos/metabolismo , Transição de Fase , Domínios Proteicos , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo
2.
Proc Natl Acad Sci U S A ; 118(17)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33875591

RESUMO

Long-term potentiation (LTP) is a cellular mechanism of learning and memory that results in a sustained increase in the probability of vesicular release of neurotransmitter. However, previous work in hippocampal area CA1 of the adult rat revealed that the total number of vesicles per synapse decreases following LTP, seemingly inconsistent with the elevated release probability. Here, electron-microscopic tomography (EMT) was used to assess whether changes in vesicle density or structure of vesicle tethering filaments at the active zone might explain the enhanced release probability following LTP. The spatial relationship of vesicles to the active zone varies with functional status. Tightly docked vesicles contact the presynaptic membrane, have partially formed SNARE complexes, and are primed for release of neurotransmitter upon the next action potential. Loosely docked vesicles are located within 8 nm of the presynaptic membrane where SNARE complexes begin to form. Nondocked vesicles comprise recycling and reserve pools. Vesicles are tethered to the active zone via filaments composed of molecules engaged in docking and release processes. The density of tightly docked vesicles was increased 2 h following LTP compared to control stimulation, whereas the densities of loosely docked or nondocked vesicles congregating within 45 nm above the active zones were unchanged. The tethering filaments on all vesicles were shorter and their attachment sites shifted closer to the active zone. These findings suggest that tethering filaments stabilize more vesicles in the primed state. Such changes would facilitate the long-lasting increase in release probability following LTP.


Assuntos
Hipocampo/fisiologia , Potenciação de Longa Duração/fisiologia , Vesículas Sinápticas/ultraestrutura , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Citoesqueleto , Tomografia com Microscopia Eletrônica/métodos , Hipocampo/metabolismo , Potenciação de Longa Duração/genética , Masculino , Neurotransmissores , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/fisiologia , Ratos , Ratos Long-Evans , Sinapses/fisiologia , Membranas Sinápticas/fisiologia , Membranas Sinápticas/ultraestrutura , Vesículas Sinápticas/fisiologia
3.
Int J Mol Sci ; 25(2)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38256100

RESUMO

In this study, a novel film of poly(vinyl alcohol) (PVA)/pullulan (PULL) with improved surface characteristics was prepared from poly(vinyl acetate) (PVAc)/PULL blend films with various mass ratios after the saponification treatment in a heterogeneous medium. According to proton nuclear magnetic resonance (1H-NMR), Fourier transform infrared, and X-ray diffraction results, it was established that the successful fabrication of saponified PVA/PULL (100/0, 90/10, and 80/20) films could be obtained from PVAc/PULL (100/0, 90/10, and 80/20) films, respectively, after 72 h saponification at 50 °C. The degree of saponification calculated from 1H-NMR analysis results showed that fully saponified PVA was obtained from all studied films. Improved hydrophilic characteristics of the saponified films were revealed by a water contact angle test. Moreover, the saponified films showed improved mechanical behavior, and the micrographs of saponified films showed higher surface roughness than the unsaponified films. This kind of saponified film can be widely used for biomedical applications. Moreover, the reported saponified film dressing extended the lifespan of dressing as determined by its self-healing capacity and considerably advanced in vivo wound-healing development, which was attributed to its multifunctional characteristics, meaning that saponified film dressings are promising candidates for full-thickness skin wound healing.


Assuntos
Etanol , Álcool de Polivinil , Glucanos , Bandagens , Poli A , Cloreto de Polivinila
4.
Proc Natl Acad Sci U S A ; 117(12): 6901-6909, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32165537

RESUMO

The Evening Complex (EC), composed of the DNA binding protein LUX ARRHYTHMO (LUX) and two additional proteins EARLY FLOWERING 3 (ELF3) and ELF4, is a transcriptional repressor complex and a core component of the plant circadian clock. In addition to maintaining oscillations in clock gene expression, the EC also participates in temperature and light entrainment, acting as an important environmental sensor and conveying this information to growth and developmental pathways. However, the molecular basis for EC DNA binding specificity and temperature-dependent activity were not known. Here, we solved the structure of the DNA binding domain of LUX in complex with DNA. Residues critical for high-affinity binding and direct base readout were determined and tested via site-directed mutagenesis in vitro and in vivo. Using extensive in vitro DNA binding assays of LUX alone and in complex with ELF3 and ELF4, we demonstrate that, while LUX alone binds DNA with high affinity, the LUX-ELF3 complex is a relatively poor binder of DNA. ELF4 restores binding to the complex. In vitro, the full EC is able to act as a direct thermosensor, with stronger DNA binding at 4 °C and weaker binding at 27 °C. In addition, an excess of ELF4 is able to restore EC binding even at 27 °C. Taken together, these data suggest that ELF4 is a key modulator of thermosensitive EC activity.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Ritmo Circadiano , DNA de Plantas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica de Plantas , Arabidopsis/genética , Proteínas de Arabidopsis/genética , DNA de Plantas/genética , Proteínas de Ligação a DNA/genética
5.
J Pediatr Orthop ; 43(5): e363-e369, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36914261

RESUMO

BACKGROUND: Treatment protocols for macrodactyly have not been elucidated due to its rarity and variety of clinical manifestations. This study aims to share our long-term clinical results of epiphysiodesis in children with macrodactyly. METHODS: A retrospective chart review was performed for 17 patients with isolated macrodactyly treated with epiphysiodesis over 20 years. Length and width of each phalanx in both the affected finger and the corresponding unaffected finger in the contralateral hand were measured. Results were presented in ratios of the affected to unaffected side for each phalanx. Measuring of length and width of phalanx was performed preoperatively and postoperatively at 6, 12, and 24 months, and the last follow-up session. Postoperative satisfaction scoring was done with visual analogue scale. RESULTS: The mean follow-up period was 7 years and 2 months. In the proximal phalanx, length ratio significantly decreased compared with preoperative state at after more than 24 months, in the middle phalanx after 6 months, in the distal phalanx after 12 months. When classified by the growth patterns, the progressive type showed significant decrease in length ratio at after 6 months, and the static type after 12 months. Patients were overall satisfied with the results. CONCLUSION: Epiphysiodesis effectively regulated longitudinal growth with different degree of control for different phalanges in the long-term follow-up.


Assuntos
Falanges dos Dedos da Mão , Deformidades Congênitas dos Membros , Humanos , Criança , Estudos Retrospectivos , Dedos/cirurgia , Falanges dos Dedos da Mão/diagnóstico por imagem , Falanges dos Dedos da Mão/cirurgia
6.
Bioorg Med Chem Lett ; 55: 128451, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34774741

RESUMO

JAK inhibitors have been considered as useful targets for the treatment of related diseases. However, first-generation JAK inhibitors have side effects such as anemia, thrombocytopenia, neutropenia and headaches which have been suggested to result from high JAK2 inhibition. Second-generation JAK inhibitors with more specific JAK isozyme inhibition have been studied to eliminate these adverse effects. In this study, novel 4-(1,5- or 2,5-triazole)-pyrrolopyrimidine derivatives with aromatic moieties were synthesized as JAK1 inhibitors, and an in vitro enzyme assay was used to evaluate the JAK inhibitory effects. Among these JAK1 inhibitors, the compound 23a showed an IC50 level of 72 nM, as well as being selective against other JAKs by 12 times or more: the results of molecular docking studies suggested that the high JAK1 selectivity resulted from a key interaction between the iodine atom of compound 23a and His-885 of hJAK1.


Assuntos
Janus Quinase 1/antagonistas & inibidores , Inibidores de Janus Quinases/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Triazóis/farmacologia , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Janus Quinase 1/metabolismo , Inibidores de Janus Quinases/síntese química , Inibidores de Janus Quinases/química , Modelos Moleculares , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Pirróis/síntese química , Pirróis/química , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
7.
Drug Dev Res ; 83(7): 1600-1612, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36124859

RESUMO

µ-Opioid receptor (MOR) Gi-biased agonists with no recruitment of ß-arrestin were introduced as a new analgesic strategy to overcome the conventional undesirable side effects of opioid receptor-targeted drugs, such as tolerance, addiction, respiratory depression, and constipation. For the development of novel Gi-biased MOR agonists, the design, synthesis, and structure-activity relationship (SAR) analysis of the aminopyrazole core skeleton were conducted according to the current SAR data of PZM21 (2a) and its derivatives. New derivatives were biologically evaluated for their agonistic effects on cyclic adenosine monophosphate (cAMP) levels for the Gi pathway and ß-arrestin recruitment in MOR/κ-opioid receptor/δ opioid receptor. An optimized selective Gi-biased agonist, Compound 17a, was discovered with potent cAMP inhibitory activities, with a 50% efficacy concentration value of 87.1 nM and no activity in the MOR ß-arrestin pathway and other subtypes. The in vivo pain relief efficacy of Compound 17a was confirmed in a dose-dependent manner with spinal nerve ligation and cisplatin-induced peripheral neuropathy rodent neuropathic pain models.


Assuntos
Neuralgia , Receptores Opioides mu , Humanos , Receptores Opioides mu/agonistas , Analgésicos Opioides/farmacologia , beta-Arrestinas/metabolismo , Receptores Opioides/metabolismo , Pirazóis
8.
Plant Cell ; 29(11): 2817-2830, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29070509

RESUMO

Stomata are epidermal openings that facilitate plant-atmosphere gas exchange during photosynthesis, respiration, and water evaporation. Stomatal differentiation and patterning are spatially and temporally regulated by the master regulators SPEECHLESS (SPCH), MUTE, and FAMA, which constitute a central gene regulatory network along with Inducer of CBF Expression (ICE) transcription factors for this developmental process. Stomatal development is also profoundly influenced by environmental conditions, such as light, temperature, and humidity. Light induces stomatal development, and various photoreceptors modulate this response. However, it is unknown how light is functionally linked with the master regulatory network. Here, we demonstrate that, under dark conditions, the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) degrades ICE proteins through ubiquitination pathways in leaf abaxial epidermal cells in Arabidopsis thaliana Accordingly, the ICE proteins accumulate in the nuclei of leaf abaxial epidermal cells in COP1-defective mutants, which constitutively produce stomata. Notably, light in the blue, red, and far-red wavelength ranges suppresses the COP1-mediated degradation of the ICE proteins to induce stomatal development. These observations indicate that light is directly linked with the ICE-directed signaling module, via the COP1-mediated protein surveillance system, in the modulation of stomatal development.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Luz , Estômatos de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Estômatos de Plantas/genética , Estômatos de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Proteólise/efeitos da radiação , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Fatores de Transcrição/genética , Ubiquitina-Proteína Ligases/genética
9.
BMC Ophthalmol ; 20(1): 16, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914958

RESUMO

BACKGROUD: To determine whether diffuse retinal nerve fiber layer (RNFL) defects, identified on red-free fundus photographs, could be identified on optical coherence tomography (OCT) en face structural images and to evaluate which factors are related to the different recognition patterns on en face images. METHODS: This retrospective, cross-sectional study included open-angle glaucoma eyes with diffuse RNFL defects in the inferior hemifield, identified in red-free photographs. The corresponding OCT en face structural images were divided into 3 groups: (1) no defect, (2) localized defect, and (3) diffuse defect. We compared the demographic and clinical ocular characteristics among the groups. RESULTS: A total of 209 eyes from 157 patients were included. The distribution of OCT en face images was: no defect, 25 eyes (11.96%); localized defect, 106 eyes (50.72%); diffuse defect, 78 eyes (37.32%). Logistic regression analysis revealed that eyes with greater mean deviation (P = 0.004) and thicker inferior RNFL (P = 0.008) would be included in the no defect and localized defect groups based on OCT en face images, rather than in the diffuse defect group. CONCLUSION: Around half of diffuse RNFL defects identified in the red-free photographs appeared as localized defects in OCT en face images. Mild glaucomatous damage was related to no defect and localized defect groups, classified based on the OCT en face images, in eyes with diffuse photographic RNFL defects. OCT en face images may be helpful in further assessing diffuse RNFL defects seen in red-free photographs in eyes with open-angle glaucoma.


Assuntos
Glaucoma de Ângulo Aberto/diagnóstico , Fibras Nervosas/patologia , Fotografação/métodos , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Angiofluoresceinografia , Gonioscopia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tonometria Ocular , Acuidade Visual/fisiologia
10.
Gynecol Obstet Invest ; 85(3): 252-258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32268326

RESUMO

BACKGROUND/OBJECTIVES: Mechanical micro-vibration remains insufficient for improving embryo culture conditions in human immature oocytes. This study compared the clinical outcomes and embryo development between germinal vesicle (GV) oocytes with the micro-vibration culture (MVC) system in in vitro maturation (IVM) cycles and in vivo-matured oocytes in controlled ovarian hyperstimulation (COH) cycles in polycystic ovarian syndrome (PCOS) patients. METHODS: This study investigated 152 PCOS patients who underwent 159 fresh embryo transfer cycles, including IVM cycles with embryos derived from GV oocytes and the COH cycles with embryos derived from in vivo-matured oocytes. The IVM cycles were divided into groups according to the culture system used: static culture (SC) and MVC: In the IVM-S group (n = 47), SC was applied during both IVM and in vitro culture (IVC), whereas in the IVM-MV group (n = 44), MVC was applied during both IVM and IVC. For the COH cycles, in the COH-S group (n = 68), SC was applied during IVC. RESULTS: The number of in vitro-matured oocytes was similar in the IVM-S and IVM-MV groups, but the good-quality embryo (GQE; ≥6-cells) rate was significantly higher in the IVM-MV group (p < 0.01). The GQE rate and clinical outcomes of the COH-S group were significantly better than those of the IVM-S group (p < 0.05) but similar to those of the IVM-MV group. CONCLUSION: Compared with the SC system, the MVC system in IVM cycles improves the embryonic quality of GV oocytes and clinical outcomes, resulting in development of potential equivalent to in vivo-matured oocytes.


Assuntos
Desenvolvimento Embrionário/fisiologia , Técnicas de Maturação in Vitro de Oócitos/métodos , Oócitos/fisiologia , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Transferência Embrionária , Feminino , Humanos , Gravidez , Resultado do Tratamento , Vibração
11.
Ann Plast Surg ; 84(6): 638-643, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31800563

RESUMO

BACKGROUND: Complications after 2-stage tissue expander/implant breast reconstruction have been studied as outcomes of a single procedure. We separately evaluated complications after the second stage and assessed factors associated with the outcomes of the second stage of breast reconstruction. METHODS: Patients who underwent immediate 2-stage breast reconstruction between February 2010 and April 2017 were retrospectively reviewed. Patient demographics, surgical factors of the first stage of breast reconstruction, and complications and number of revision surgeries after the second stage were recorded. Factors associated with postoperative complications were analyzed, and a risk-scoring system was devised. RESULTS: We analyzed 619 patients who underwent 653 immediate 2-stage breast reconstructions. Multivariate analysis showed that complications were associated independently with smoking history, radiotherapy, and a final inflation volume of 450 mL or greater. Each factor contributed 1 point in the creation of a risk-scoring system. The overall complication rate was increased as the risk score increased (1.2%, 4.7%, and 16.0% for 0, 1, and 2 risk scores, respectively, P < 0.001). Revision operation rate was also significantly different across the 3 groups (0.2%, 1.6%, and 12.0% for 0, 1, and 2 risk scores, respectively, P < 0.001). The area under the receiver operating characteristic curve was 0.732 and 0.731 for the logistic regression model and risk-scoring system, respectively (P = 0.975). CONCLUSIONS: In the second stage of immediate 2-stage tissue expander/implant breast reconstruction, the rate of complication and revision surgery can be predicted by a novel risk-scoring system. Greater attention and preventive measures for complications are needed for high-risk patients.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Implante Mamário/efeitos adversos , Implantes de Mama/efeitos adversos , Neoplasias da Mama/cirurgia , Humanos , Mamoplastia/efeitos adversos , Mastectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Reoperação , Estudos Retrospectivos , Dispositivos para Expansão de Tecidos/efeitos adversos
12.
Rheumatol Int ; 39(3): 453-460, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30617512

RESUMO

The objective of this study was to identify optimal magnetic resonance imaging (MRI) parameters and their cutoff values for diagnosing adhesive capsulitis (AC). One hundred shoulder MRI images with stage 2 AC (AC group) and 100 MRI images without AC (control group) were randomly reviewed by two experienced shoulder specialists. They were asked whether MRI findings were compatible with AC and measurement of MRI parameters. Sensitivity, specificity, and accuracy were calculated. Correlation between MRI parameters and the range of motions was also analyzed. The mean capsular thickness in the axillary recess (AR) (5.9 mm in the AC group vs. 3.6 mm in the control group) on coronal oblique T2-weighted images and the rotator interval (RI) (7.2 mm vs. 4.8 mm, respectively) on oblique sagittal proton-density images were significantly greater in the AC group than in the control group, whereas the width of RI showed no significant difference between two groups. The highest diagnostic cutoff values were 4.5 mm for the AR and 6 mm for the RI, with sensitivity (91% and 88%, respectively), specificity (90% and 90%), and accuracy (90% and 89%). Capsular thickness in the AR and RI was significantly correlated with external rotation (P = 0.047) and internal rotation (P = 0.023). On conventional MRI, capsular thickness greater than 4.5 mm in the AR or 6 mm in the RI can be an optimal criterion for diagnosing AC. Capsular thickness in the AR and RI was correlated with the range of rotational motion.


Assuntos
Bursite/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Bursite/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Índice de Gravidade de Doença
13.
Proc Natl Acad Sci U S A ; 113(8): E1098-107, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26858418

RESUMO

The priming of a docked synaptic vesicle determines the probability of its membrane (VM) fusing with the presynaptic membrane (PM) when a nerve impulse arrives. To gain insight into the nature of priming, we searched by electron tomography for structural relationships correlated with fusion probability at active zones of axon terminals at frog neuromuscular junctions. For terminals fixed at rest, the contact area between the VM of docked vesicles and PM varied >10-fold with a normal distribution. There was no merging of the membranes. For terminals fixed during repetitive evoked synaptic transmission, the normal distribution of contact areas was shifted to the left, due in part to a decreased number of large contact areas, and there was a subpopulation of large contact areas where the membranes were hemifused, an intermediate preceding complete fusion. Thus, fusion probability of a docked vesicle is related to the extent of its VM-PM contact area. For terminals fixed 1 h after activity, the distribution of contact areas recovered to that at rest, indicating the extent of a VM-PM contact area is dynamic and in equilibrium. The extent of VM-PM contact areas in resting terminals correlated with eccentricity in vesicle shape caused by force toward the PM and with shortness of active zone material macromolecules linking vesicles to PM components, some thought to include Ca(2+) channels. We propose that priming is a variable continuum of events imposing variable fusion probability on each vesicle and is regulated by force-generating shortening of active zone material macromolecules in dynamic equilibrium.


Assuntos
Canais de Cálcio/metabolismo , Tomografia com Microscopia Eletrônica , Membranas Sinápticas , Vesículas Sinápticas , Animais , Rana pipiens , Membranas Sinápticas/metabolismo , Membranas Sinápticas/ultraestrutura , Vesículas Sinápticas/metabolismo , Vesículas Sinápticas/ultraestrutura
14.
Phytother Res ; 33(4): 939-948, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30632220

RESUMO

Valerian root is the most commonly used herbal supplement for sedation and anxiolysis, but it is unknown whether it may affect functional brain connectivity. Our goal was to use electroencephalography (EEG) to investigate whether valerian root extract (VRE) affects resting-state connectivity changes and whether such changes are associated with clinical symptoms. This 4-week, double-blinded, randomized, placebo-controlled clinical trial was conducted with 64 nonclinical volunteers suffering psychological stress. The participants received VRE (100 mg) or a placebo thrice daily. We examined VRE's therapeutic effects on anxiety and stress-related psychological constructs. Functional brain connectivity changes were measured as EEG coherence in the alpha and theta frequency bands. The VRE and placebo groups both exhibited significant postintervention improvements on all clinical scales, but no significant between-group differences in these changes were noted. Compared with the placebo group, the VRE group exhibited significantly greater increases in frontal brain region alpha coherence across four electrode pairs, and these changes were significantly correlated with anxiolysis. The VRE group also exhibited significantly greater decreases in theta coherence across another four electrodes pairs. Our findings indicate that VRE alters functional brain connectivity in relation to anxiety. Further EEG studies are needed to confirm VRE's neurophysiological effects.


Assuntos
Ansiolíticos/farmacologia , Encéfalo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Valeriana , Adulto , Encéfalo/fisiologia , Método Duplo-Cego , Eletroencefalografia/efeitos dos fármacos , Feminino , Humanos , Hipnóticos e Sedativos/farmacologia , Masculino , Pessoa de Meia-Idade , Estresse Fisiológico/efeitos dos fármacos , Valeriana/química
15.
Int J Mol Sci ; 20(11)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31159267

RESUMO

Synaptic vesicles dock on the presynaptic plasma membrane of axon terminals and become ready to fuse with the presynaptic membrane or primed. Fusion of the vesicle membrane and presynaptic membrane results in the formation of a pore between the membranes, through which the vesicle's neurotransmitter is released into the synaptic cleft. A recent electron tomography study on frog neuromuscular junctions fixed at rest showed that there is no discernible gap between or merging of the membrane of docked synaptic vesicles with the presynaptic membrane, however, the extent of the contact area between the membrane of docked synaptic vesicles and the presynaptic membrane varies 10-fold with a normal distribution. The study also showed that when the neuromuscular junctions are fixed during repetitive electrical nerve stimulation, the portion of large contact areas in the distribution is reduced compared to the portion of small contact areas, suggesting that docked synaptic vesicles with the largest contact areas are greatly primed to fuse with the membrane. Furthermore, the finding of several hemifused synaptic vesicles among the docked vesicles was briefly reported. Here, the spatial relationship of 81 synaptic vesicles with the presynaptic membrane at active zones of the neuromuscular junctions fixed during stimulation is described in detail. For the most of the vesicles, the combined thickness of each of their contact sites was not different from the sum of the membrane thicknesses of the vesicle membrane and presynaptic membrane, similar to the docked vesicles at active zones of the resting neuromuscular junctions. However, the combined membrane thickness of a small portion of the vesicles was considerably less than the sum of the membrane thicknesses, indicating that the membranes at their contact sites were fixed in a state of hemifusion. Moreover, the hemifused vesicles were found to have large contact areas with the presynaptic membrane. These findings support the recently proposed hypothesis that, at frog neuromuscular junctions, docked synaptic vesicles with the largest contact areas are most primed for fusion with the presynaptic membrane, and that hemifusion is a fusion intermediate step of the vesicle membrane with the presynaptic membrane for synaptic transmission.


Assuntos
Junção Neuromuscular/metabolismo , Membranas Sinápticas/metabolismo , Transmissão Sináptica , Vesículas Sinápticas/metabolismo , Animais , Anuros , Modelos Biológicos , Junção Neuromuscular/ultraestrutura , Membranas Sinápticas/ultraestrutura , Vesículas Sinápticas/ultraestrutura
16.
Foot Ankle Surg ; 25(2): 113-118, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29409297

RESUMO

BackgroundRecently, distraction osteogenesis has been widely used to treat brachymetatarsia. However, few papers have compared complications associated with this treatment. The purpose of the present study was to compare the complications between the first and fourth brachymetatarsia treated by distraction osteogenesis. MethodsWe performed distraction osteogenesis to 83 metatarsals in 41 patients between 1999 and 2012. A total of 30 metatarsals received treatment for the first metatarsal (Group A) while 53 metatarsals received treatment with the fourth metatarsal (Group B). ResultsThe complication rate in Group A (40%) was higher than that in Group B (18.9%). Those who had high percentage of lengthening gain were more likely to have complications. A cut-off value for lengthening gain developing complication was 41.3%. ConclusionComplication incidence after distraction osteogenesis was increased when lengthening gain was more than 41.3% for brachymetatarsia. In the 1st metatarsal lengthening, the most common complication was stiffness. In contrast, complications of the 4th metatarsal lengthening were pin-track infection and angular deformity.


Assuntos
Deformidades Congênitas do Pé/cirurgia , Ossos do Metatarso/anormalidades , Osteogênese por Distração/efeitos adversos , Complicações Pós-Operatórias , Adolescente , Adulto , Criança , Feminino , Deformidades Congênitas do Pé/diagnóstico por imagem , Humanos , Masculino , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Plant J ; 89(1): 128-140, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27607358

RESUMO

The circadian clock control of CONSTANS (CO) transcription and the light-mediated stabilization of its encoded protein coordinately adjust photoperiodic flowering by triggering rhythmic expression of the floral integrator flowering locus T (FT). Diurnal accumulation of CO is modulated sequentially by distinct E3 ubiquitin ligases, allowing peak CO to occur in the late afternoon under long days. Here we show that CO abundance is not simply targeted by E3 enzymes but is also actively self-adjusted through dynamic interactions between two CO isoforms. Alternative splicing of CO produces two protein variants, the full-size COα and the truncated COß lacking DNA-binding affinity. Notably, COß, which is resistant to E3 enzymes, induces the interaction of COα with CO-destabilizing E3 enzymes but inhibits the association of COα with CO-stabilizing E3 ligase. These observations demonstrate that CO plays an active role in sustaining its diurnal accumulation dynamics during Arabidopsis photoperiodic flowering.


Assuntos
Processamento Alternativo , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Proteínas de Ligação a DNA/genética , Flores/genética , Fotoperíodo , Fatores de Transcrição/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Ritmo Circadiano , Proteínas de Ligação a DNA/metabolismo , Flores/crescimento & desenvolvimento , Flores/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Luz , Plantas Geneticamente Modificadas , Ligação Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
18.
Am J Otolaryngol ; 38(1): 108-111, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27751620

RESUMO

We report an extremely rare case of hearing aid silicone impression material as a foreign body in the middle ear. Symptoms of the patient were otorrhea and vertigo after taking of a mold impression on his only hearing ear, and the symptoms mimicked chronic otitis media. A temporal bone CT scan revealed foreign body material in the middle ear and Eustachian tube. An intact canal wall mastoidectomy with a facial recess approach and type IV tympanoplasty was performed to remove the silicone impression material. In addition to the case report, we review the literature regarding impression material foreign bodies.


Assuntos
Orelha Média/cirurgia , Tuba Auditiva/cirurgia , Corpos Estranhos/cirurgia , Imageamento Tridimensional , Procedimentos Cirúrgicos Otológicos/métodos , Silicones/efeitos adversos , Otorreia de Líquido Cefalorraquidiano/diagnóstico , Otorreia de Líquido Cefalorraquidiano/etiologia , Orelha Média/diagnóstico por imagem , Seguimentos , Corpos Estranhos/diagnóstico por imagem , Auxiliares de Audição/efeitos adversos , Humanos , Masculino , Desenho de Prótese , Doenças Raras , Medição de Risco , Silicones/farmacologia , Resultado do Tratamento , Timpanoplastia/métodos , Vertigem/diagnóstico , Vertigem/etiologia
19.
J Shoulder Elbow Surg ; 26(5): 804-808, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27914840

RESUMO

BACKGROUND: The purpose of this study was to evaluate the radiologic and clinical outcomes of coracoclavicular (CC) stabilization using a suture button device for Neer type IIB lateral clavicle fractures. METHODS: Eighteen consecutive patients with Neer type IIB fractures were treated with CC stabilization using a TightRope device (Arthrex, Naples, FL, USA). The mean follow-up period was 46.6 months (range, 24-75 months). Radiologic outcomes were assessed using serial plain radiographs. Clinical outcomes were evaluated using the visual analog scale pain score; University of California, Los Angeles score; American Shoulder and Elbow Surgeons score; and subjective shoulder value. Intraoperative and postoperative complications were also evaluated. RESULTS: Of the 18 cases, 17 (94.4%) showed complete bony union. The mean final visual analog scale pain score was 1.1; University of California, Los Angeles score, 31.3; American Shoulder and Elbow Surgeons score, 88.6; and subjective shoulder value, 88.5%. Four complications were observed: (1) intraoperative coracoid process fracture, (2) nonunion, (3) delayed union, and (4) shoulder stiffness. The case with a coracoid process fracture during coracoid tunnel generation was converted to the K-wire tension band technique. CONCLUSION: CC stabilization using a suture button device for Neer type IIB lateral clavicle fractures yielded satisfactory radiologic and clinical outcomes. The major advantage of this technique is that implant removal is not required.


Assuntos
Clavícula/lesões , Clavícula/cirurgia , Fixação Interna de Fraturas , Fraturas Ósseas/cirurgia , Dispositivos de Fixação Ortopédica , Adulto , Idoso , Clavícula/diagnóstico por imagem , Feminino , Fraturas Ósseas/classificação , Fraturas Ósseas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Avaliação de Resultados da Assistência ao Paciente , Complicações Pós-Operatórias , Estudos Retrospectivos , Adulto Jovem
20.
Plant J ; 84(1): 29-40, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26248809

RESUMO

Plants constantly monitor changes in photoperiod and temperature throughout the year to synchronize flowering with optimal environmental conditions. In the temperate zones, both photoperiod and temperature fluctuate in a somewhat predictable manner through the seasons, although a transient shift to low temperature is also encountered during changing seasons, such as early spring. Although low temperatures are known to delay flowering by inducing the floral repressor FLOWERING LOCUS C (FLC), it is not fully understood how temperature signals are coordinated with photoperiodic signals in the timing of seasonal flowering. Here, we show that the cold signaling activator INDUCER OF CBF EXPRESSION 1 (ICE1), FLC and the floral promoter SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) constitute an elaborate signaling network that integrates cold signals into flowering pathways. The cold-activated ICE1 directly induces the gene encoding FLC, which represses SOC1 expression, resulting in delayed flowering. In contrast, under floral promotive conditions, SOC1 inhibits the binding of ICE1 to the promoters of the FLC gene, inducing flowering with a reduction of freezing tolerance. These observations indicate that the ICE1-FLC-SOC1 signaling network contributes to the fine-tuning of flowering during changing seasons.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/genética , Transdução de Sinais , Fatores de Transcrição/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Domínio MADS/metabolismo , Fatores de Transcrição/metabolismo
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa