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1.
J Cogn Neurosci ; 36(7): 1265-1281, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38652104

RESUMO

Human faces and bodies represent various socially important signals. Although adults encounter numerous new people in daily life, they can recognize hundreds to thousands of different individuals. However, the neural mechanisms that differentiate one person from another person are unclear. This study aimed to clarify the temporal dynamics of the cognitive processes of face and body personal identification using face-sensitive ERP components (P1, N170, and N250). The present study performed three blocks (face-face, face-body, and body-body) of different ERP adaptation paradigms. Furthermore, in the above three blocks, ERP components were used to compare brain biomarkers under three conditions (same person, different person of the same sex, and different person of the opposite sex). The results showed that the P1 amplitude for the face-face block was significantly greater than that for the body-body block, that the N170 amplitude for a different person of the same sex condition was greater than that for the same person condition in the right hemisphere only, and that the N250 amplitude gradually increased as the degree of face and body sex-social categorization grew closer (i.e., same person condition > different person of the same sex condition > different person of the opposite sex condition). These results suggest that early processing of the face and body processes the face and body separately and that structural encoding and personal identification of the face and body process the face and body collaboratively.


Assuntos
Eletroencefalografia , Potenciais Evocados , Reconhecimento Facial , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Reconhecimento Facial/fisiologia , Potenciais Evocados/fisiologia , Percepção do Tempo/fisiologia , Percepção Social , Encéfalo/fisiologia
2.
J Pept Sci ; 29(5): e3464, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36459408

RESUMO

Human seleno-epidermal growth factor (seleno-EGF), a 53-residue peptide where all six cysteine residues of the parent human EGF sequence were replaced by selenocysteines, was synthesized and the oxidative folding of a polypeptide containing three diselenide bonds was compared to that of the parent cysteine peptide. The crude high performance liquid chromatography (HPLC) profiles clearly showed that both the native EGF and its selenocysteine-analogue fold smoothly, yielding a single sharp peak, proving that even in the case of three disulfide-bonded polypeptides the disulfide-to-diselenide bond substitution is highly isomorphous, as confirmed by conformational circular dichroism measurements and particularly by the biological assays.


Assuntos
Cisteína , Selenocisteína , Humanos , Selenocisteína/química , Cisteína/química , Fator de Crescimento Epidérmico/química , Peptídeos/química , Dissulfetos/química , Dobramento de Proteína
3.
Pediatr Surg Int ; 39(1): 253, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37624479

RESUMO

Pediatric liver transplantation is a lifesaving state-of-the-art operation for children with various liver diseases, including cholestatic diseases, metabolic disorders, acute liver failure, and primary malignant liver tumors. Among these indications, transplantation for biliary atresia and hepatoblastoma is discussed in this review because pediatric surgeons are usually involved in their initial treatments. For biliary atresia, pediatric surgeons are advised to keep dissection of the hilar structures to a minimum during Kasai portoenterostomy in order to make total hepatectomy easier at transplantation. Early referral to a transplant team is recommended when worrisome signs of liver dysfunction, cirrhosis, portal hypertension and growth retardation are noted. Hepatoblastoma with multiplicity or located close to major vessels may indicate unresectability, and the transplant team needs to be consulted early after neoadjuvant chemotherapy is started. The graft size, including its thickness, needs to be evaluated before transplantation for small children, as tailoring the shape of the partial graft may be necessary during the transplant procedure.


Assuntos
Atresia Biliar , Hepatoblastoma , Neoplasias Hepáticas , Transplante de Fígado , Cirurgiões , Criança , Humanos , Atresia Biliar/cirurgia , Hepatoblastoma/cirurgia
4.
J Orthop Sci ; 28(4): 795-801, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35690542

RESUMO

BACKGROUND: This study was performed to assess the clinical and radiographic results at a minimum of 2 years after ligament reconstruction suspension arthroplasty (LRSA) that comprised full trapeziectomy and suspensionplasty using the palmaris longus tendon and the Mini TightRope (Arthrex, Naples, FL) for advanced thumb carpometacarpal arthritis. METHODS: We clinically and radiographically evaluated 26 thumbs in 26 patients who had undergone LRSA at least 2 years previously. The mean follow-up period was 35.9 months. We evaluated the subjective clinical outcomes (visual analogue scale and Quick Disabilities of the Arm, Shoulder, and Hand scores) and objective clinical outcomes (range of motion, pinch strength, grip strength, and trapezial space height ratio). RESULTS: At the final follow-up evaluation, the mean visual analogue scale score was 11.1 (standard deviation (SD) 13.4) and the mean Quick Disabilities of the Arm, Shoulder, and Hand questionnaire score was 9.39 (SD 10.1). The mean palmar and radial abduction were 62.3° (SD 11.8°) and 63.8° (SD 9.09°), respectively. The mean key pinch and grip strength were 3.92 (SD 1.07) kg and 19.7 (SD 7.77) kg, respectively. The mean trapezial space ratio was 0.21 (SD 0.10). The subjective clinical outcomes, range of motion, and pinch strength were significantly improved compared with preoperatively. CONCLUSIONS: LRSA for advanced-stage thumb carpometacarpal osteoarthritis relieves pain, improves range of motion and strength, and obtains favourable subjective patient-reported clinical outcomes.


Assuntos
Articulações Carpometacarpais , Osteoartrite , Humanos , Polegar/cirurgia , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Tendões/cirurgia , Artroplastia/métodos , Articulações Carpometacarpais/diagnóstico por imagem , Articulações Carpometacarpais/cirurgia , Suturas
5.
J Orthop Sci ; 28(4): 789-794, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35430128

RESUMO

BACKGROUND: Management of metacarpophalangeal (MCP) hyperextension deformity in thumb carpometacarpal (CMC) joint arthritis is challenging. It remains unclear how the preoperative MCP joint angle affects the outcomes. The present study aimed to clarify the associations between postoperative MCP hyperextension deformity and outcomes, and to determine the preoperative MCP joint angle that can predict poor outcomes. METHODS: We investigated the functional outcomes of patients who underwent surgery for CMC arthritis at two institutions from 2016 to 2020. All patients received a modified Thompson technique, ligament reconstruction suspension arthroplasty, and had no additional treatment for MCP hyperextension. The patients were divided into three groups according to their postoperative MCP joint angles: Group A, <10°; Group B, 10°-20°; Group C, >20°. Evaluations included preoperative and postoperative VAS, Quick DASH, range of motion (ROM), grip power, pinch strength, first web space angle, and postoperative trapezial space ratio (TSR). RESULTS: Overall, 66 eligible patients (72 thumbs) were identified and received follow-up for a mean of 25.2 months. The 72 thumbs were assigned to Group A (n = 38), Group B (n = 16), and Group C (n = 18). Group C had significantly lower preoperative MCP joint angle and postoperative grip power, pinch strength, and TSR compared with the Group A (P < 0.05). However, there were no significant differences in VAS, Quick DASH, ROM, and first web space angle (P > 0.05). The preoperative risk factor for highly residual MCP hyperextension was preoperative MCP joint angle (OR = 1.078; P = 0.001), with a cut-off value of 21.5° (AUC = 0.79; sensitivity = 0.813; specificity = 0.821). CONCLUSIONS: Postoperative MCP hyperextension of >20° after ligament reconstruction with trapeziectomy has adverse effects on functional outcomes. In cases with preoperative MCP joint angle of >21.5°, additional treatment for MCP hyperextension should be considered.


Assuntos
Articulações Carpometacarpais , Artropatias , Osteoartrite , Humanos , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Estudos Retrospectivos , Prognóstico , Articulação Metacarpofalângica/diagnóstico por imagem , Articulação Metacarpofalângica/cirurgia , Articulações Carpometacarpais/diagnóstico por imagem , Articulações Carpometacarpais/cirurgia , Amplitude de Movimento Articular , Polegar/cirurgia , Ligamentos
6.
Undersea Hyperb Med ; 50(3): 265-272, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37708059

RESUMO

Background: Electronic devices remain highly restricted from use during hyperbaric oxygen (HBO2) treatment due to risk of fire in a pressurized, oxygen-rich environment. Over recent decades, point-of- care ultrasound (POCUS) has established utility in most clinical environments except hyperbaric chambers, where only heavily modified POCUS devices have been used. This study evaluated proof of concept, safety, and performance of a wireless off-the-shelf handheld POCUS device in the hyperbaric environment. Materials and Methods: The GE Vscan Air was initially tested in a Class C chamber with 100% nitrogen up to 4.0 ATA and monitored. Second, the Vscan Air was paired with an encased Apple iPad, tested previously for hyperbaric use, and both were pressurized to 2.4 ATA in a Class A chamber (21% oxygen) and evaluated. Similarly, it was then tested at 2.8 ATA and also paired wirelessly with an iPad outside the chamber. Device temperature, image quality, functionality, and wireless connection were tested continuously. Results: The GE Vscan Air automatically shut off due to power button depression during initial compression; thus the power button was punctured with an 18-gauge needle to equalize gas pressure. Thereafter, the system performed well throughout all tests without degradation in function or image quality. The device did not overheat nor reach temperatures concerning for fire hazard. Further, wireless connection to out-of-chamber devices was maintained. Conclusions: Our results suggest that the GE Vscan Air can be used with minor modification in a multi- place hyperbaric chamber. Wireless functionality allows for pairing with a screen and device outside the chamber.

7.
J Biol Chem ; 296: 100217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33839679

RESUMO

Heme oxygenase (HO) converts heme to carbon monoxide, biliverdin, and free iron, products that are essential in cellular redox signaling and iron recycling. In higher plants, HO is also involved in the biosynthesis of photoreceptor pigment precursors. Despite many common enzymatic reactions, the amino acid sequence identity between plant-type and other HOs is exceptionally low (∼19.5%), and amino acids that are catalytically important in mammalian HO are not conserved in plant-type HOs. Structural characterization of plant-type HO is limited to spectroscopic characterization by electron spin resonance, and it remains unclear how the structure of plant-type HO differs from that of other HOs. Here, we have solved the crystal structure of Glycine max (soybean) HO-1 (GmHO-1) at a resolution of 1.06 Å and carried out the isothermal titration calorimetry measurements and NMR spectroscopic studies of its interaction with ferredoxin, the plant-specific electron donor. The high-resolution X-ray structure of GmHO-1 reveals several novel structural components: an additional irregularly structured region, a new water tunnel from the active site to the surface, and a hydrogen-bonding network unique to plant-type HOs. Structurally important features in other HOs, such as His ligation to the bound heme, are conserved in GmHO-1. Based on combined data from X-ray crystallography, isothermal titration calorimetry, and NMR measurements, we propose the evolutionary fine-tuning of plant-type HOs for ferredoxin dependency in order to allow adaptation to dynamic pH changes on the stroma side of the thylakoid membrane in chloroplast without losing enzymatic activity under conditions of fluctuating light.


Assuntos
Ferredoxinas/química , Glycine max/química , Heme Oxigenase-1/química , Heme/química , Ferro/química , Proteínas de Plantas/química , Sequência de Aminoácidos , Biliverdina/química , Biliverdina/metabolismo , Monóxido de Carbono/química , Monóxido de Carbono/metabolismo , Domínio Catalítico , Cloroplastos/química , Cloroplastos/enzimologia , Clonagem Molecular , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Ferredoxinas/genética , Ferredoxinas/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Heme/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Ligação de Hidrogênio , Ferro/metabolismo , Simulação de Acoplamento Molecular , Ressonância Magnética Nuclear Biomolecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Glycine max/enzimologia , Glycine max/genética , Tilacoides/química , Tilacoides/enzimologia
8.
Radiology ; 302(3): 557-565, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34904874

RESUMO

Background The histologic nature of coronary high-intensity plaques (HIPs) at T1-weighted MRI in patients with stable coronary artery disease remains to be fully understood. Coronary atherosclerosis T1-weighted characterization (CATCH) enables HIP detection by simultaneously acquiring dark-blood plaque and bright-blood anatomic reference images. Purpose To determine if intraplaque hemorrhage (IPH) or lipid is the predominant substrate of HIPs on T1-weighted images by comparing CATCH MRI scans with findings on near-infrared spectroscopy (NIRS) intravascular US (IVUS) images. Materials and Methods This study retrospectively included consecutive patients who underwent CATCH MRI before NIRS IVUS between December 2019 and February 2021 at two facilities. At MRI, HIP was defined as plaque-to-myocardium signal intensity ratio of at least 1.4. The presence of an echolucent zone at IVUS (reported to represent IPH) was recorded. NIRS was used to determine the lipid component of atherosclerotic plaque. Lipid core burden index (LCBI) was calculated as the fraction of pixels with a probability of lipid-core plaque greater than 0.6 within a region of interest. Plaque with maximum LCBI within any 4-mm-long segment (maxLCBI4 mm) greater than 400 was regarded as lipid rich. Multivariable analysis was performed to evaluate NIRS IVUS-derived parameters associated with HIPs. Results There were 205 plaques analyzed in 95 patients (median age, 74 years; interquartile range [IQR], 67-78 years; 75 men). HIPs (n = 42) at MRI were predominantly associated with an echolucent zone at IVUS (79% [33 of 42] vs 8.0% [13 of 163], respectively; P < .001) and a higher maxLCBI4 mm at NIRS (477 [IQR, 258-738] vs 232 [IQR, 59-422], respectively; P < .001) than non-HIPs. In the multivariable model, HIPs were independently associated with an echolucent zone (odds ratio, 24.5; 95% CI: 9.3, 64.7; P < .001), but not with lipid-rich plaque (odds ratio, 2.0; 95% CI: 0.7, 5.4; P = .20). Conclusion The predominant substrate of T1-weighed MRI-defined high-intensity plaques in stable coronary artery disease was intraplaque hemorrhage, not lipid. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Stuber in this issue.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Placa Aterosclerótica/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Ultrassonografia de Intervenção/métodos , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos
9.
Reprod Biol Endocrinol ; 20(1): 58, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351143

RESUMO

BACKGROUND: Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of women of reproductive age. Ovarian endometriosis (OE) is the most common lesion in endometriosis and may cause infertility, in addition to dysmenorrhea. Hormonal treatments, which are the conventional treatment methods for endometriosis, suppress ovulation and hence are not compatible with fertility. The inflammasome is a complex that includes Nod-like receptor (NLR) family proteins, which sense pathogen-associated molecular patterns and homeostasis-altering molecular processes. It has been reported that the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inflammasome, which contributes to the activation of interleukin-1 beta (IL-1ß), might be related to the progression of endometriosis. Therefore, the aim of the present study was to evaluate non-hormonal therapies for OE, such as inhibitors of the NLRP3 inflammasome. METHODS: The expression of NLRP3 was measured in the eutopic endometrium (EM) of patients with and without endometriosis and OE samples, as well as stromal cells derived from the endometrium of patients with and without endometriosis and OE samples (endometrial stromal cells with endometriosis [ESCs] and cyst-derived stromal cells [CSCs]). The effects of an NLRP3 inhibitor (MCC950) on ESCs and CSCs survival and IL-1ß production were evaluated. We then administered MCC950 to a murine model of OE to evaluate its effects on OE lesions and ovarian function. RESULTS: NLRP3 gene and protein expression levels were higher in OE and CSCs than in EM and ESCs, respectively. MCC950 treatment significantly reduced the survival of CSCs, but not that of ESCs. Moreover, MCC950 treatment reduced the co-localization of NLRP3 and IL-1ß in CSCs, as well as IL-1ß concentrations in CSCs supernatants. In the murine model, MCC950 treatment reduced OE lesion size compared to phosphate-buffered saline treatment (89 ± 15 vs. 49 ± 9.3 mm3 per ovary; P < 0.05). In the MCC950-treated group, IL-1ß and Ki67 levels in the OE-associated epithelia were reduced along with the oxidative stress markers of granulosa cells. CONCLUSIONS: These results indicated that NLRP3/IL-1ß is involved in the pathogenesis of endometriosis and that NLRP3 inhibitors may be useful for suppressing OE and improving the function of ovaries with endometriosis.


Assuntos
Endometriose , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Endometriose/tratamento farmacológico , Feminino , Furanos/farmacologia , Humanos , Indenos/farmacologia , Inflamassomos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Sulfonamidas/farmacologia
10.
Biodegradation ; 33(2): 117-133, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34989928

RESUMO

Application of genetically engineered bacterial strains for biodegradation of hydrocarbons is a sustainable solution for treating pollutants as well as in industrial applications. However, the process of bioengineering should be carefully carried out to optimize the output. Investigation of regulatory genes for bioengineering is essential for developing synthetic circuits for effective biocatalysts. Here we focus on LcaR, a putative transcriptional regulator affecting the expression of alkB2 and lcaR operon that has a high potential to become a tool in designing such pathways. Four LcaR dimers bind specifically to the upstream regulatory region where divergent promoters of alkB2 and lcaR genes are located with high affinity at a Kd of 0.94 ± 0.17 nM and a Hill coefficient is 1.7 ± 0.3 demonstrating cooperativity in the association. Ligand binding alters the conformation of LcaR, which releases the regulator from its cognate DNA. Tetradecanal and hexadecanal act as natural ligands of LcaR with an IC50 values of 3.96 ± 0.59 µg/ml and 0.68 ± 0.21 µg/ml, respectively. The structure and function of transcription factors homologous to LcaR have not been characterized to date. This study provides insight into regulatory mechanisms of alkane degradation with a direction towards potential applications in bioengineering for bioremediation and industrial applications.


Assuntos
Alcanos , Pseudomonas aeruginosa , Alcanos/metabolismo , Proteínas de Bactérias/metabolismo , Biodegradação Ambiental , Bioengenharia , Pseudomonas aeruginosa/metabolismo
11.
Int J Mol Sci ; 23(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36555561

RESUMO

"Plant-type" ferredoxins (Fds) in the thylakoid membranes of plants, algae, and cyanobacteria possess a single [2Fe-2S] cluster in active sites and mediate light-induced electron transfer from Photosystem I reaction centers to various Fd-dependent enzymes. Structural knowledge of plant-type Fds is relatively limited to static structures, and the detailed behavior of oxidized and reduced Fds has not been fully elucidated. It is important that the investigations of the effects of active-center reduction on the structures and dynamics for elucidating electron-transfer mechanisms. In this study, model systems of oxidized and reduced Fds were constructed from the high-resolution crystal structure of Chlamydomonas reinhardtii Fd1, and three 200 ns molecular dynamics simulations were performed for each system. The force field parameters of the oxidized and reduced active centers were independently obtained using quantum chemical calculations. There were no substantial differences in the global conformations of the oxidized and reduced forms. In contrast, active-center reduction affected the hydrogen-bond network and compactness of the surrounding residues, leading to the increased flexibility of the side chain of Phe61, which is essential for the interaction between Fd and the target protein. These computational results will provide insight into the electron-transfer mechanisms in the Fds.


Assuntos
Cianobactérias , Ferredoxinas , Ferredoxinas/metabolismo , Simulação de Dinâmica Molecular , Transporte de Elétrons , Cianobactérias/metabolismo , Plantas/metabolismo , Oxirredução
12.
BMC Oral Health ; 22(1): 332, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941575

RESUMO

BACKGROUND: A novel type of implant (Straumann® BLX implant) has been developed for certain stability from the mechanical and biological aspects and is expected for the implant placement in atrophic maxilla with sinus floor elevation (SFE). PURPOSE: The aim of this study was to evaluate the primary stability in the implants with different macrodesigns in an SFE simulated model. Primary stabilities defined as maximum insertion torque (MIT) and implant stability quotient (ISQ) were compared between this novel type of implant and other types. MATERIALS AND METHODS: Five types of Straumann® 10 mm length implants (Standard Plus; SP, Tapered Effect; TE, Bone Level; BL, Bone Level Tapered; BLT and BLX) and two types of Straumann® 6 mm length implants (SP short, BLX short) were used in this study. Each implant was inserted through 5 mm-thick porcine iliac crest blocks (an SFE simulated model). Primary stability was evaluated by using MIT and ISQ. RESULTS: The mean value of MIT for BLX group showed significantly higher values than SP, BL (p < 0.01), and TE (p < 0.05) groups. The mean value of ISQ for BLX group was significantly higher than the other groups (p < 0.01). The mean value of MIT and ISQ for BLX and BLX short group were significantly higher than those for SP and SP short group (p < 0.01). CONCLUSIONS: In an SFE simulated ex vivo model, BLX group showed the highest values. These results suggest that implant selection can play a crucial role in the achievement of primary stability during SFE and simultaneous implant placement.


Assuntos
Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Animais , Implantação Dentária Endóssea/métodos , Planejamento de Prótese Dentária , Maxila/cirurgia , Levantamento do Assoalho do Seio Maxilar/métodos , Suínos , Torque
13.
J Biol Chem ; 295(12): 3982-3989, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32014992

RESUMO

Axonemal dynein is a microtubule-based molecular motor that drives ciliary/flagellar beating in eukaryotes. In axonemal dynein, the outer-arm dynein (OAD) complex, which comprises three heavy chains (α, ß, and γ), produces the main driving force for ciliary/flagellar motility. It has recently been shown that axonemal dynein light chain-1 (LC1) binds to the microtubule-binding domain (MTBD) of OADγ, leading to a decrease in its microtubule-binding affinity. However, it remains unclear how LC1 interacts with the MTBD and controls the microtubule-binding affinity of OADγ. Here, we have used X-ray crystallography and pulldown assays to examine the interaction between LC1 and the MTBD, identifying two important sites of interaction in the MTBD. Solving the LC1-MTBD complex from Chlamydomonas reinhardtii at 1.7 Å resolution, we observed that one site is located in the H5 helix and that the other is located in the flap region that is unique to some axonemal dynein MTBDs. Mutational analysis of key residues in these sites indicated that the H5 helix is the main LC1-binding site. We modeled the ternary structure of the LC1-MTBD complex bound to microtubules based on the known dynein-microtubule complex. This enabled us to propose a structural basis for both formations of the ternary LC1-MTBD-microtubule complex and LC1-mediated tuning of MTBD binding to the microtubule, suggesting a molecular model for how axonemal dynein senses the curvature of the axoneme and tunes ciliary/flagellar beating.


Assuntos
Proteínas de Algas/metabolismo , Chlamydomonas reinhardtii/metabolismo , Dineínas/metabolismo , Flagelos/fisiologia , Proteínas de Algas/química , Dineínas do Axonema/química , Dineínas do Axonema/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Dineínas/química , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica em alfa-Hélice , Domínios Proteicos , Estrutura Quaternária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo
14.
J Biol Chem ; 295(1): 170-180, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31776187

RESUMO

Calcium (Ca2+) and redox signaling enable cells to quickly adapt to changing environments. The signaling protein calredoxin (CRX) from the green alga Chlamydomonas reinhardtii is a chloroplast-resident thioredoxin having Ca2+-dependent activity and harboring a unique combination of an EF-hand domain connected to a typical thioredoxin-fold. Using small-angle X-ray scattering (SAXS), FRET, and NMR techniques, we found that Ca2+-binding not only induces a conformational change in the EF-hand domain, but also in the thioredoxin domain, translating into the onset of thioredoxin redox activity. Functional analyses of CRX with genetically altered EF-hands revealed that EF-hand 4 is important for mediating the communication between the two domains. Moreover, we crystallized a variant (C174S) of the CRX target protein peroxiredoxin 1 (PRX1) at 2.4 Å resolution, modeled the interaction complex of the two proteins, and analyzed it by cross-linking and MS analyses, revealing that the interaction interface is located close to the active sites of both proteins. Our findings shed light on the Ca2+ binding-induced changes in CRX structure in solution at the level of the overall protein and individual domains and residues.


Assuntos
Sinalização do Cálcio , Proteínas de Ligação ao Cálcio/metabolismo , Tiorredoxinas de Cloroplastos/metabolismo , Motivos EF Hand , Proteínas de Ligação ao Cálcio/química , Chlamydomonas reinhardtii , Tiorredoxinas de Cloroplastos/química , Simulação de Dinâmica Molecular , Ligação Proteica
15.
J Cell Sci ; 132(11)2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31076512

RESUMO

Peroxisomes cooperate with mitochondria in the performance of cellular metabolic functions, such as fatty acid oxidation and the maintenance of redox homeostasis. However, whether peroxisomes also regulate mitochondrial fission-fusion dynamics or mitochondrion-dependent apoptosis remained unclear. We now show that genetic ablation of the peroxins Pex3 or Pex5, which are essential for peroxisome biogenesis, results in mitochondrial fragmentation in mouse embryonic fibroblasts (MEFs) in a manner dependent on Drp1 (also known as DNM1L). Conversely, treatment with 4-PBA, which results in peroxisome proliferation, resulted in mitochondrial elongation in wild-type MEFs, but not in Pex3-knockout MEFs. We further found that peroxisome deficiency increased the levels of cytosolic cytochrome c and caspase activity under basal conditions without inducing apoptosis. It also greatly enhanced etoposide-induced caspase activation and apoptosis, which is indicative of an enhanced cellular sensitivity to death signals. Taken together, our data unveil a previously unrecognized role for peroxisomes in the regulation of mitochondrial dynamics and mitochondrion-dependent apoptosis. Effects of peroxin gene mutations on mitochondrion-dependent apoptosis may contribute to pathogenesis of peroxisome biogenesis disorders.This article has an associated First Person interview with the first author of the paper.


Assuntos
Apoptose/fisiologia , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/fisiologia , Peroxissomos/metabolismo , Animais , Butilaminas/farmacologia , Caspases/metabolismo , Linhagem Celular , Citocromos c/metabolismo , Dinaminas/metabolismo , Humanos , Lipoproteínas/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Peroxinas/genética , Transtornos Peroxissômicos/patologia , Receptor 1 de Sinal de Orientação para Peroxissomos/genética , Interferência de RNA , RNA Interferente Pequeno/genética
16.
Reprod Biol Endocrinol ; 19(1): 179, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872568

RESUMO

BACKGROUND: Ovarian endometrioma is a common gynecological disease that is often treated with surgery or hormonal treatment. Ovarian cystectomy, a surgical procedure for ovarian endometrioma, can result in impaired ovarian reserve. METHODS: We conducted a randomized controlled trial to evaluate the efficacy of hormonal treatment [gonadotropin-releasing hormone agonist (GnRHa) or dienogest (DNG)] for preserving ovarian reserve after cystectomy for ovarian endometrioma. The primary endpoint was the level of serum Anti-Müllerian hormone (AMH) as a marker of ovarian reserve. RESULTS: Before and after laparoscopic surgery, 22 patients in the GnRHa group and 27 patients in the DNG group were administered hormonal treatment for a total of 4 months. After 1-year follow-up, >60% of the patients in the DNG group retained over 70% of their pretreatment AMH levels, whereas no patient in the GnRHa group retained their AMH levels after cystectomy (P < 0.01). Interleukin-6 (IL-6) is a key cytokine involved in inflammation. Compared with the GnRHa group, patients in the DNG group had lower IL-6 levels at the end of treatment. CONCLUSIONS: Our data revealed that DNG is more effective than GnRHa in preserving ovarian reserve after cystectomy of ovarian endometrioma. This is achieved through the reduction of the inflammatory response during the perioperative period and other endometriosis-related inflammatory reactions. TRIAL REGISTRATION: The registration number of this trial is UMIN-CTR, UMIN000018569, registered 6 August 2015, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021492 , and Japan Registry of Clinical Trials, jRCTs041180140, registered 29 March 2019, https://jrct.niph.go.jp/en-latest-detail/jRCTs041180140 . This randomized controlled trial was conducted in accordance with the CONSORT guidelines.


Assuntos
Endometriose/cirurgia , Hormônio Liberador de Gonadotropina/agonistas , Antagonistas de Hormônios/uso terapêutico , Nandrolona/análogos & derivados , Reserva Ovariana/efeitos dos fármacos , Doenças da Bexiga Urinária/cirurgia , Adulto , Cistectomia , Endometriose/tratamento farmacológico , Feminino , Humanos , Laparoscopia , Nandrolona/uso terapêutico , Resultado do Tratamento , Doenças da Bexiga Urinária/tratamento farmacológico
17.
Thromb J ; 19(1): 78, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736457

RESUMO

BACKGROUND: The severity of pulmonary arterial hypertension (PAH) is classified based on mean pulmonary artery pressure (mPAP) levels. However, other markers have not been elucidated. Fibrinolytic markers, such as total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM), are known to reflect arterial endothelial function. However, the relationship between serum tPAI-1, TM and pulmonary circulation has not been completely determined. METHODS: This study included 100 consecutive patients (38 men), with a mean age of 68.9 ± 12.0 years, with cardiac diseases who underwent right heart catheterization. Serum coagulation and fibrinolytic marker levels were measured. RESULTS: The average mPAP value was 25.1 ± 13.1 mmHg for all patients. The mPAP levels revealed a significant positive correlation with serum tPAI-1 (ρ = 0.24, p = 0.042) and uric acid (ρ = 0.29, p = 0.0031) levels. In the group with mPAP levels less than 25 mmHg (n = 58, ave. 17.3 ± 4.3 mmHg), mPAP levels showed a significant positive correlation with serum tPA-1 (ρ = 0.34, p = 0.034) and TM (ρ = 0.34, p = 0.043) values. The mean tPAI-1 (29.8 ± 23.3 ng/ml, p = 0.047) and uric acid (5.7 ± 1.8 mg/dl, p = 0.026) levels were significantly less in those with lower mPAP levels. A multivariate analysis revealed that tPAI-1 alone was a significant independent characteristic marker of PAH (odds ratio 1.02, 95%CI 1.000-1.036, p = 0.034). CONCLUSIONS: These results indicate that serum tPAI-1 and TM may be useful predictors of severity, similar to mPAP in patients with PAH. They could be beneficial in predicting PAH among patients in the early stage of the disease.

18.
Epilepsy Behav ; 125: 108402, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34775249

RESUMO

OBJECTIVE: To determine the characteristics of olfactory dysfunction in patients with temporal lobe epilepsy (TLE). METHODS: Odor identification was assessed using the odor stick identification test for Japanese (OSIT-J, full score 12 points) in 65 patients with TLE and in 74 controls. RESULTS: The mean OSIT-J score was significantly lower in patients with TLE (mean ±â€¯SD = 8.1 ±â€¯2.8; median = 9) than in the control subjects (mean ±â€¯SD = 10.6 ±â€¯1.1; median = 11) (P < 0.005). Olfactory dysfunction (hyposmia/anosmia) was associated with bilateral seizure foci and older age of onset in TLE. Patients who underwent temporal lobectomy for hippocampal sclerosis did not show significant decline after long-term recovery. The Indian ink part of OSIT-J was useful for the detection of olfactory deficits in patients with TLE (sensitivity = 47%, specificity = 93%). Patients with TLE tended to have preserved olfactory ability for stimulating odors and for familiar odors of daily life. SIGNIFICANCE: We observed characteristic odor identification deficits for individual odors used in OSIT-J. Our study findings provide deeper insight into the underlying mechanism of olfactory function in patients with TLE and may be beneficial in the clinical management of these patients.


Assuntos
Epilepsia do Lobo Temporal , Transtornos do Olfato , Idoso , Epilepsia do Lobo Temporal/complicações , Humanos , Odorantes , Transtornos do Olfato/etiologia , Convulsões , Olfato
19.
J Integr Neurosci ; 20(4): 1029-1038, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34997726

RESUMO

This brief report investigates the relationship between the lip color of women's faces and the latency and amplitude of the P1, N170, and early posterior negativity of event-related potential components. To show different color lipsticks affect face perception processing, we used EEG to observe these event-related potential components in 19 participants exposed to visual stimuli under four conditions: red lips, yellow lips, blue lips, and no-makeup. The results indicate a significantly higher attractiveness score for red lips than the other three conditions and a significantly shorter P1 peak latency for red lips than blue lips or no-makeup. This may reflect that red lips attract attention more than blue or natural lips in the early stages of face processing. The results indicate that the peak of early posterior negativity for red lips occurred significantly longer than for yellow lips, blue lips, or no-makeup. Early posterior negativity amplitudes were significantly larger to red lips than blue lips or no-makeup. These results may indicate that, at later stages of face processing, the high attractiveness of red lips is associated with slower and careful processing. In contrast, blue lips, which have a low attractiveness score, are processed speedily and carelessly. These present results suggest a novel possibility that P1 and early posterior negativity can be used as a biomarker for temporal face perception processing of facial attractiveness in the human brain.


Assuntos
Beleza , Córtex Cerebral/fisiologia , Percepção de Cores/fisiologia , Reconhecimento Facial/fisiologia , Percepção Social , Adolescente , Adulto , Eletroencefalografia , Potenciais Evocados , Feminino , Humanos , Masculino , Fatores de Tempo , Adulto Jovem
20.
Int Heart J ; 62(3): 510-519, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-33994509

RESUMO

A recent thinner strut drug-eluting stent might facilitate early strut coverage after its placement. We aimed to investigate early vascular healing responses after the placement of an ultrathin-strut bioresorbable-polymer sirolimus-eluting stent (BP-SES) compared to those with a durable-polymer everolimus-eluting stent (DP-EES) using optical coherence tomography (OCT) imaging.This study included 40 patients with chronic coronary syndrome (CCS) who underwent OCT-guided percutaneous coronary intervention (PCI). Twenty patients each received either BP-SES or DP-EES implantation. OCT was performed immediately after stent placement (baseline) and at 1-month follow-up.At one month, the percentage of uncovered struts reduced significantly in both the BP-SES (80.9 ± 10.3% to 2.9 ± 1.7%; P < 0.001) and DP-EES (81.9 ± 13.0% to 5.7 ± 1.8%; P < 0.001) groups, and the percentage was lower in the BP-SES group than in the DP-EES group (P < 0.001). In the BP-SES group, the percentage of malapposed struts also decreased significantly at 1 month (4.9 ± 3.7% to 2.6 ± 3.0%; P = 0.025), which was comparable to that of the DP-EES group (2.5 ± 2.2%; P = 0.860). The optimal cut-off value of the distance between the strut and vessel surface immediately after the placement to predict resolved malapposed struts was ≤ 160 µm for BP-SES and ≤ 190 µm for DP-EES.Compared to DP-EES, ultrathin-strut BP-SES demonstrated favorable vascular responses at one month, with a lower rate of uncovered struts and a comparable rate of malapposed struts.


Assuntos
Implantes Absorvíveis/estatística & dados numéricos , Doença das Coronárias/cirurgia , Stents Farmacológicos/estatística & dados numéricos , Intervenção Coronária Percutânea/instrumentação , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Doença das Coronárias/diagnóstico por imagem , Everolimo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sirolimo/administração & dosagem , Tomografia de Coerência Óptica
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