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1.
Nat Immunol ; 20(10): 1372-1380, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31451789

RESUMO

In multicellular organisms, duplicated genes can diverge through tissue-specific gene expression patterns, as exemplified by highly regulated expression of RUNX transcription factor paralogs with apparent functional redundancy. Here we asked what cell-type-specific biologies might be supported by the selective expression of RUNX paralogs during Langerhans cell and inducible regulatory T cell differentiation. We uncovered functional nonequivalence between RUNX paralogs. Selective expression of native paralogs allowed integration of transcription factor activity with extrinsic signals, while non-native paralogs enforced differentiation even in the absence of exogenous inducers. DNA binding affinity was controlled by divergent amino acids within the otherwise highly conserved RUNT domain and evolutionary reconstruction suggested convergence of RUNT domain residues toward submaximal strength. Hence, the selective expression of gene duplicates in specialized cell types can synergize with the acquisition of functional differences to enable appropriate gene expression, lineage choice and differentiation in the mammalian immune system.


Assuntos
Subunidades alfa de Fatores de Ligação ao Core/genética , Sistema Imunitário/fisiologia , Células de Langerhans/fisiologia , Especificidade de Órgãos/genética , Linfócitos T Reguladores/fisiologia , Animais , Diferenciação Celular , Linhagem da Célula , Sequência Conservada , Evolução Molecular , Duplicação Gênica , Humanos , Mamíferos , Transdução de Sinais , Transcriptoma
2.
Trends Biochem Sci ; 46(7): 564-578, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33551235

RESUMO

The core histone tails are critical in chromatin structure and signaling. Studies over the past several decades have provided a wealth of information on the histone tails and their interaction with chromatin factors. However, the conformation of the histone tails in a chromatin relevant context has remained elusive. Only recently has enough evidence emerged to start to build a structural model of the tails in the context of nucleosomes and nucleosome arrays. Here, we review these studies and propose that the histone tails adopt a high-affinity fuzzy complex with DNA, characterized by robust but dynamic association. Furthermore, we discuss how these DNA-bound conformational ensembles promote distinct chromatin structure and signaling, and that their fuzzy nature is important in transitioning between functional states.


Assuntos
Histonas , Nucleossomos , Cromatina , DNA , Histonas/metabolismo , Conformação de Ácido Nucleico
3.
J Fluoresc ; 33(2): 413-421, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36435903

RESUMO

Single molecule FRET (Forster resonance energy transfer) is very powerful method for studying biomolecular binding dynamics and conformational transitions. Only a few donor - acceptor dye pairs have been characterized for use in single-molecule FRET (smFRET) studies. Hence, introducing and characterizing additional FRET dye pairs is important in order to widen the scope of applications of single-molecule FRET in biomolecular studies. Here we characterize the properties of the Cy3.5 and Cy5.5 dye pair under FRET at the single-molecule level using naked double-stranded DNA (dsDNA) and the nucleosome. We show that this pair of dyes is photostable for ~ 5 min under continuous illumination. We also report Cy3.5-Cy5.5 FRET proximity dependence and stability in the presence of several biochemical buffers and photoprotective reagents in the context of double-stranded DNA. Finally, we demonstrate compatibility of the Cy3.5-Cy5.5 pair for smFRET in vitro studies of nucleosomes.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Ácidos Nucleicos , Transferência Ressonante de Energia de Fluorescência/métodos , Nucleossomos , Carbocianinas/química , DNA/química , Corantes , Corantes Fluorescentes/química
4.
Artif Organs ; 47(1): 214-216, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36254560

RESUMO

Re-transplantation is the preferred treatment for patients with chronic heart transplant failure. If re-transplantation is not a viable option due to the patient's comorbidities, left ventricle assist device can be used as the destination treatment. An interdisciplinary approach with thorough follow-up can help in the early detection and treatment of complications associated with LVAD.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Humanos , Transplante de Coração/efeitos adversos , Coração Auxiliar/efeitos adversos , Insuficiência Cardíaca/cirurgia , Comorbidade , Ventrículos do Coração , Resultado do Tratamento
5.
Nucleic Acids Res ; 49(9): e53, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33660771

RESUMO

Molecular machines within cells dynamically assemble, disassemble and reorganize. Molecular interactions between their components can be observed at the single-molecule level and quantified using colocalization single-molecule spectroscopy, in which individual labeled molecules are seen transiently associating with a surface-tethered partner, or other total internal reflection fluorescence microscopy approaches in which the interactions elicit changes in fluorescence in the labeled surface-tethered partner. When multiple interacting partners can form ternary, quaternary and higher order complexes, the types of spatial and temporal organization of these complexes can be deduced from the order of appearance and reorganization of the components. Time evolution of complex architectures can be followed by changes in the fluorescence behavior in multiple channels. Here, we describe the kinetic event resolving algorithm (KERA), a software tool for organizing and sorting the discretized fluorescent trajectories from a range of single-molecule experiments. KERA organizes the data in groups by transition patterns, and displays exhaustive dwell time data for each interaction sequence. Enumerating and quantifying sequences of molecular interactions provides important information regarding the underlying mechanism of the assembly, dynamics and architecture of the macromolecular complexes. We demonstrate KERA's utility by analyzing conformational dynamics of two DNA binding proteins: replication protein A and xeroderma pigmentosum complementation group D helicase.


Assuntos
Software , Algoritmos , DNA/química , Fluorescência , Cinética , Conformação Proteica , Domínios Proteicos , Proteína de Replicação A/química , Proteína Grupo D do Xeroderma Pigmentoso/química
6.
Childs Nerv Syst ; 39(6): 1565-1571, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36700950

RESUMO

BACKGROUND: Hydrocephalus is commonly associated with Chiari malformation (CM) particularly CM type II. The traditional treatment of hydrocephalus in these patients has been cerebrospinal fluid diversion by shunts. Endoscopic third ventriculostomy (ETV) has emerged as an alternative procedure in these patients. PURPOSE: Assessment of the clinical and radiological outcomes of ETV in the management of hydrocephalus in children with CM II. METHODS: This is a prospective study conducted on 18 patients with CM II associated with hydrocephalus admitted to Cairo University hospitals between January 2020 and June 2021. These patients had been managed surgically by ETV. Clinical outcome was assessed based on improvement of manifestations of increased intracranial pressure while radiological outcome was based on the findings of postoperative computed tomography. In cases with early failure, serial lumbar puncture (LP) was performed for 2 days. RESULTS: ETV was performed as a secondary procedure in 4 cases. The overall success rate of the procedure was 72%, and its success rate as a secondary procedure was 100%. Serial LP was effective in decreasing early failure in 44.4% of cases. Radiological regression of hydrocephalic changes was detected in 50% of the cases. CONCLUSION: ETV is an efficient and safe procedure in the treatment of hydrocephalus in children with Chiari malformation II, particularly when performed as a secondary procedure. Serial LP following the procedure increases the success rate in patients with early failure.


Assuntos
Malformação de Arnold-Chiari , Hidrocefalia , Neuroendoscopia , Terceiro Ventrículo , Humanos , Criança , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/cirurgia , Ventriculostomia/métodos , Estudos Prospectivos , Terceiro Ventrículo/diagnóstico por imagem , Terceiro Ventrículo/cirurgia , Resultado do Tratamento , Neuroendoscopia/métodos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Estudos Retrospectivos
7.
Sensors (Basel) ; 22(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35957213

RESUMO

Impedance spectroscopy has became an essential non-invasive tool for quality assessment measurements of the biochemical and biophysical changes in plant tissues. The electrical behaviour of biological tissues can be captured by fitting its bio-impedance data to a suitable circuit model. This paper investigates the use of power-law filters in circuit modelling of bio-impedance. The proposed models are fitted to experimental data obtained from eight different fruit types using a meta-heuristic optimization method (the Water Cycle Algorithm (WCA)). Impedance measurements are obtained using a Biologic SP150 electrochemical station, and the percentage error between the actual impedance and the fitted models' impedance are reported. It is found that a circuit model consisting of a combination of two second-order power-law low-pass filters shows the least fitting error.


Assuntos
Algoritmos , Espectroscopia Dielétrica , Impedância Elétrica
8.
Sensors (Basel) ; 22(21)2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36366230

RESUMO

BACKGROUND AND AIM: due to the rapid growth of data communication and multimedia system applications, security becomes a critical issue in the communication and storage of images. This study aims to improve encryption and decryption for various types of images by decreasing time consumption and strengthening security. METHODOLOGY: An algorithm is proposed for encrypting images based on the Carlisle Adams and Stafford Tavares CAST block cipher algorithm with 3D and 2D logistic maps. A chaotic function that increases the randomness in the encrypted data and images, thereby breaking the relation sequence through the encryption procedure, is introduced. The time is decreased by using three secure and private S-Boxes rather than using six S-Boxes, as in the traditional method. Moreover, the CAST encryption algorithm was modified to be used on the private keys and substitution stage (S-Boxes), with the keys and S-Boxes of the encryption algorithm being generated according to the 2D and 3D chaotic map functions. The proposed system passed all evaluation criteria, including (MSE, PSNR, EQ, MD, SC, NC, AD, SNR, SIM, MAE, Time, CC, Entropy, and histograms). RESULTS: Moreover, the results also illustrate that the created S-Boxes passed all evaluation criteria; compared with the results of the traditional method that was used in creating S-Box, the proposed method achieved better results than other methods used in the other works. The proposed solution improves the entropy which is between (7.991-7.999), reduces the processing time which is between (0.5-11 s/Images), and improves NCPR, which is between (0.991-1). CONCLUSIONS: The proposed solution focuses on reducing the total processing time for encryption and decryption and improving transmission security. Finally, this solution provides a fast security system for surgical telepresence with secure real-time communication. The complexity of this work needs to know the S-Box creation method used, the chaotic method, the values of the chaotic parameters, and which of these methods was used in the encryption process.


Assuntos
Algoritmos , Segurança Computacional , Entropia
9.
J Craniofac Surg ; 30(8): 2464-2468, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403509

RESUMO

Despite the improvement of primary repair of nasal deformities during the management of cleft lip in infancy, this does not exclude the need for revision rhinoplasty in adulthood for complete patients' rehabilitation. The purpose of this study was to evaluate the aesthetic outcome of secondary rhinoplasty using costal cartilage grafts in patients with unilateral cleft lip nasal deformity. Twenty patients who were operated at earlier ages for correction of cleft lip and had a residual unilateral cleft lip nasal deformity were included in this study. Costal cartilage rib grafts were harvested; carved and used for maxillary augmentation, columellar strut graft, and lateral crural strut graft. Five anthropometric measurements (nostril height, width and gap area, columellar axis deviation angle and nasal base inclination angle) were used for evaluation of aesthetic results. The ratio of nostril width, height and gap area between the cleft side and the non-cleft side showed significant improvement (P <0.05). The columellar axis deviation showed significant improvement towards the midline (P = 0.004), and the alar base inclination showed improvement towards the horizontal line (P = 0.0045). In conclusion, the aesthetic outcomes of secondary cleft lip rhinoplasty using the costal cartilage are satisfactory. The costal cartilage has the required strength, is easily carved and maintains shape for considerable time.


Assuntos
Fenda Labial/cirurgia , Cartilagem Costal/cirurgia , Adolescente , Antropometria , Feminino , Humanos , Masculino , Nariz/cirurgia , Procedimentos Ortopédicos , Rinoplastia/métodos , Costelas/cirurgia , Resultado do Tratamento , Adulto Jovem
10.
World J Urol ; 36(11): 1835-1843, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29761225

RESUMO

OBJECTIVE: To evaluate differences in pathological features and prognostics across four bladder cancer histopathological types: urothelial carcinoma (UC), urothelial carcinoma with variant histology (UCV), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), utilizing a large cohort of radical cystectomy (RC) patients. METHODS: A retrospective analysis of patients who underwent RC at a single institution in Egypt between 1997 and 2004 was performed. Kaplan-Meier and multivariable analyses were performed to evaluate the prognostic significance of pathological features including tumor stage, grade, lymphovascular invasion (LVI), and lymph node (LN) involvement in the different subtypes on disease-free survival (DFS). RESULTS: 1238 patients (975 male, 263 female) were included, of whom 577 (47%) had UC, 174 (14%) UCV, 398 (32%) SCC, and 89 (7%) ADC. Median age was 54 (20-87) years and median follow-up was 40 months (0-110). There were significant differences in stage, grade, LVI, LN involvement, and presence of schistosomiasis across the subtypes (all p < 0.05). The prognostic significance of LVI was more evident in SCC (HR 2.14, p = 0.003) and ADC (HR 2.17, p = 0.044) than in UC (HR 1.66, p = 0.008). LN involvement was the strongest prognostic factor in UCV (HR 2.14, p = 0.012). CONCLUSIONS: There are significant differences in clinicopathological features and their prognostic impact across bladder cancer subtypes. The prognostic significance of LVI is more evident in SCC and ADC, while LN involvement is more prognostic in UCV. Determining independent predictors in individual subtypes can guide multimodal treatment selection and clinical trial design.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células de Transição/cirurgia , Cistectomia , Neoplasias da Bexiga Urinária/cirurgia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/patologia , Estudos de Coortes , Intervalo Livre de Doença , Egito/epidemiologia , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Esquistossomose Urinária/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Adulto Jovem
11.
J Craniofac Surg ; 29(4): 992-997, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29481504

RESUMO

Stem cell therapy is a revolutionary new way to stimulate mesenchymal tissue regeneration. The platelets concentrate products started with platelet-rich plasma (PRP), followed by platelet-rich fibrin (PRF), whereas concentrated growth factors (CGF) are the latest generation of the platelets concentrate products which were found in 2011. The aim of the present study was to evaluate the potential of combining autologous bone marrow concentrates and CGF for treatment of bone defects resulting from enucleation of mandibular pathologic lesions. Twenty patients (13 males and 7 females) with mandibular benign unilateral lesions were included, and divided into 2 groups. Group I consisted of 10 patients who underwent enucleation of the lesions followed by grafting of the bony defects with autologous bone marrow concentrates and CGF. Group II consisted of 10 patients who underwent enucleation of the lesions without grafting (control). Radiographic examinations were done immediately postoperative, then at 1, 3, 6, and 12 months, to evaluate the reduction in size and changes in bone density at the bony defects. Results indicated a significant increase in bone density with respect to the baseline levels in both groups (P < 0.05). The increase in bone density was significantly higher in group I compared with group II at the 6- and 12-month follow-up examinations (P < 0.05). The percent of reduction in the defects' size was significantly higher in group I compared with group II after 12 months (P = 0.00001). In conclusion, the clinical application of autologous bone marrow concentrates with CGF is a cost effective and safe biotechnology, which accelerates bone regeneration and improves the density of regenerated bone.


Assuntos
Transplante de Medula Óssea/métodos , Regeneração Óssea/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular , Mandíbula , Extratos de Tecidos , Transplante Autólogo/métodos , Adolescente , Adulto , Medula Óssea/química , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Masculino , Mandíbula/efeitos dos fármacos , Mandíbula/cirurgia , Doenças Mandibulares/tratamento farmacológico , Doenças Mandibulares/cirurgia , Pessoa de Meia-Idade , Extratos de Tecidos/farmacologia , Extratos de Tecidos/uso terapêutico , Adulto Jovem
12.
Small ; 13(16)2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28145623

RESUMO

A highly manufacturable deep reactive ion etching based process involving a hybrid soft/hard mask process technology shows high aspect ratio complex geometry Lego-like silicon electronics formation enabling free-form (physically flexible, stretchable, and reconfigurable) electronic systems.

13.
Neurourol Urodyn ; 35(4): 497-502, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25663249

RESUMO

AIMS: Post-exstrophy incontinence is a challenge because continence is difficult to achieve and more difficult to maintain. Feasibility and outcomes of a bulbourethral sling to treat post-exstrophy incontinence is shown in this report. METHODS: A retropubic bulbourethral sling was applied to male patients with incontinence post-exstrophy-epispadius repair. The study included children with total (continuous) incontinence who underwent multiple previous anti-incontinence procedures, ranging from bladder neck injection to bladder neck reconstruction. Preoperative assessment includes urinalysis, renal US, VCUG, 1-hr pad test and urodynamics. The bulbourethral sling applied is made of polypropylene and is suspended by 4 pairs of nylon sutures, to support the bulbar urethra within its covering muscles with the sutures tied on the rectus muscles. Continence was evaluated as well as adverse events. RESULTS: Seventeen children, (median age 8.7 years) completed 24-month of follow up. All had CPRE. Five children (29.27%) were dry. Four micturated through the urethra and one by catheterizing his cutaneous stoma every 3-4 hr. In none, PVR exceeded 10% of expected capacity. Four children underwent re-tightening 1-4 weeks after removal of urethral catheter. Perineal wound dehiscence occurred in one, perineal/suprapubic pain in seven and epididymo-orchitis in one child. CONCLUSION: The current technique is promising for difficult cases of incontinence after CPRE. It is safe, as no serious adverse events occurred during follow up period. It is economic and re-tightening is easy to perform. Neurourol. Urodynam. 35:497-502, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Slings Suburetrais , Uretra/cirurgia , Incontinência Urinária/cirurgia , Adolescente , Criança , Pré-Escolar , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Bexiga Urinária/cirurgia , Incontinência Urinária/etiologia , Urodinâmica
14.
BMC Surg ; 16: 5, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26830195

RESUMO

BACKGROUND: The interaction of depression and anesthesia and surgery may result in significant increases in morbidity and mortality of patients. Major depressive disorder is a frequent complication of surgery, which may lead to further morbidity and mortality. LITERATURE SEARCH: Several electronic data bases, including PubMed, were searched pairing "depression" with surgery, postoperative complications, postoperative cognitive impairment, cognition disorder, intensive care unit, mild cognitive impairment and Alzheimer's disease. REVIEW OF THE LITERATURE: The suppression of the immune system in depressive disorders may expose the patients to increased rates of postoperative infections and increased mortality from cancer. Depression is commonly associated with cognitive impairment, which may be exacerbated postoperatively. There is evidence that acute postoperative pain causes depression and depression lowers the threshold for pain. Depression is also a strong predictor and correlate of chronic post-surgical pain. Many studies have identified depression as an independent risk factor for development of postoperative delirium, which may be a cause for a long and incomplete recovery after surgery. Depression is also frequent in intensive care unit patients and is associated with a lower health-related quality of life and increased mortality. Depression and anxiety have been widely reported soon after coronary artery bypass surgery and remain evident one year after surgery. They may increase the likelihood for new coronary artery events, further hospitalizations and increased mortality. Morbidly obese patients who undergo bariatric surgery have an increased risk of depression. Postoperative depression may also be associated with less weight loss at one year and longer. The extent of preoperative depression in patients scheduled for lumbar discectomy is a predictor of functional outcome and patient's dissatisfaction, especially after revision surgery. General postoperative mortality is increased. CONCLUSIONS: Depression is a frequent cause of morbidity in surgery patients suffering from a wide range of conditions. Depression may be identified through the use of Patient Health Questionnaire-9 or similar instruments. Counseling interventions may be useful in ameliorating depression, but should be subject to clinical trials.


Assuntos
Transtorno Depressivo/etiologia , Dor Pós-Operatória/psicologia , Cuidados Críticos , Delírio , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/terapia , Humanos , Dor Pós-Operatória/etiologia , Fatores de Risco
15.
J Urol ; 193(2): 451-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25200806

RESUMO

PURPOSE: We evaluated the association of multiple biomarkers with clinical outcomes in patients treated with radical cystectomy for squamous cell carcinoma of the bladder to identify the best prognostic panel of markers. MATERIALS AND METHODS: Immunohistochemistry for 14 biomarkers was performed on tissue microarray sections of 151 radical cystectomy specimens showing squamous cell carcinoma. Biomarker alterations, pathological features and oncologic outcomes were evaluated. The panel of biomarkers that best predicted the oncologic outcome was determined. Outcomes were stratified based on a prognostic score according to the number of altered biomarkers. The accuracy of oncologic outcome prediction was evaluated by ROC curves. RESULTS: The study included 151 patients. Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Median followup was 63.2 months. The best prognostic panel of markers included COX-2, FGF-2, p53, Bax and EGFR. On multivariate Cox regression analysis a prognostic score based on marker alterations was an independent predictor of intermediate and high risk of disease recurrence (HR 3.2, p = 0.008 and HR 15.5, p ≤ 0.001) and bladder cancer specific mortality (HR 5.2, p = 0.009 and HR 19.4, p ≤ 0.001, respectively). A multivariate prognostic model incorporating the prognostic score demonstrated significantly better performance to predict the outcome compared to clinicopathological parameters only (0.78 vs 0.64). CONCLUSIONS: Biomarkers have significant potential to predict the outcome of radical cystectomy for squamous cell carcinoma. An increased number of altered markers may identify patients at high risk who might benefit from multimodal treatment approaches.


Assuntos
Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/cirurgia , Cistectomia , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Biomarcadores/análise , Cistectomia/métodos , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
16.
Nano Lett ; 14(10): 5920-31, 2014 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-25204359

RESUMO

We report a dual illumination, single-molecule imaging strategy to dissect directly and in real-time the correlation between nanometer-scale domain motion of a DNA repair protein and its interaction with individual DNA substrates. The strategy was applied to XPD, an FeS cluster-containing DNA repair helicase. Conformational dynamics was assessed via FeS-mediated quenching of a fluorophore site-specifically incorporated into XPD. Simultaneously, binding of DNA molecules labeled with a spectrally distinct fluorophore was detected by colocalization of the DNA- and protein-derived signals. We show that XPD undergoes thermally driven conformational transitions that manifest in spatial separation of its two auxiliary domains. DNA binding does not strictly enforce a specific conformation. Interaction with a cognate DNA damage, however, stabilizes the compact conformation of XPD by increasing the weighted average lifetime of this state by 140% relative to an undamaged DNA. Our imaging strategy will be a valuable tool to study other FeS-containing nucleic acid processing enzymes.


Assuntos
Archaea/metabolismo , Proteínas Arqueais/metabolismo , DNA Helicases/metabolismo , DNA Arqueal/metabolismo , Microscopia de Fluorescência/instrumentação , Archaea/química , Proteínas Arqueais/química , Sítios de Ligação , DNA Helicases/química , Reparo do DNA , Desenho de Equipamento , Ligação Proteica , Estrutura Terciária de Proteína
17.
Stem Cell Res Ther ; 15(1): 23, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38281991

RESUMO

Over the past decade, there had been progress in the development of cell therapy for insulin-dependent diabetes. Nevertheless, important hurdles that need to be overcome still remain. Protocols for the differentiation of pluripotent stem cells into pancreatic progenitors or fully differentiated ß-cells have been developed. The resulting insulin-producing cells can control chemically induced diabetes in rodents and were the subject of several clinical trials. However, these cells are immunogenic and possibly teratogenic for their transplantation, and an immunoisolation device and/or immunosuppression is needed. A growing number of studies have utilized genetic manipulations to produce immune evasive cells. Evidence must be provided that in addition to the expected benefit, gene manipulations should not lead to any unforeseen complications. Mesenchymal stem/stromal cells (MSCs) can provide a viable alternative. MSCs are widely available from many tissues. They can form insulin-producing cells by directed differentiation. Experimentally, evidence has shown that the transplantation of allogenic insulin-producing cells derived from MSCs is associated with a muted allogeneic response that does not interfere with their functionality. This can be explained by the immunomodulatory functions of the MSC subpopulation that did not differentiate into insulin-producing cells. Recently, exosomes derived from naive MSCs have been used in the experimental domain to treat diabetes in rodents with varying degrees of success. Several mechanisms for their beneficial functions were proposed including a reduction in insulin resistance, the promotion of autophagy, and an increase in the T regulatory population. However, euglycemia was not achieved in any of these experiments. We suggest that exosomes derived from ß-cells or insulin-producing cells (educated) can provide a better therapeutic effect than those derived from undifferentiated cells.


Assuntos
Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Transplante de Células-Tronco Mesenquimais , Humanos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Estudos Prospectivos , Transplante de Células-Tronco Mesenquimais/métodos , Diferenciação Celular , Insulina/metabolismo
18.
Front Neurol ; 15: 1380654, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699050

RESUMO

Background: Recent years have seen the emergence of disease-modifying therapies in multiple sclerosis (MS), such as anti-cluster of differentiation 20 (anti-CD20) monoclonal antibodies, aiming to modulate the immune response and effectively manage MS. However, the relationship between anti-CD20 treatments and immunoglobulin G (IgG) levels, particularly the development of hypogammaglobulinemia and subsequent infection risks, remains a subject of scientific interest and variability. We aimed to investigate the intricate connection between anti-CD20 MS treatments, changes in IgG levels, and the associated risk of hypogammaglobulinemia and subsequent infections. Method: PubMed, Scopus, Embase, Cochrane, and Web of Science databases have been searched for relevant studies. The "R" software utilized to analyze the occurrence of hypogammaglobulinemia, infections and mean differences in IgG levels pre- and post-treatment. The subgrouping analyses were done based on drug type and treatment duration. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. Results: Thirty-nine articles fulfilled our inclusion criteria and were included in our review which included a total of 20,501 MS patients. The overall prevalence rate of hypogammaglobulinemia was found to be 11% (95% CI: 0.08 to 0.15). Subgroup analysis based on drug type revealed varying prevalence rates, with rituximab showing the highest at 18%. Subgroup analysis based on drug usage duration revealed that the highest proportion of hypogammaglobulinemia occurred in individuals taking the drugs for 1 year or less (19%). The prevalence of infections in MS patients with a focus on different infection types stratified by the MS drug used revealed that pulmonary infections were the most prevalent (9%) followed by urinary tract infections (6%), gastrointestinal infections (2%), and skin and mucous membrane infections (2%). Additionally, a significant decrease in mean IgG levels after treatment compared to before treatment, with a mean difference of 0.57 (95% CI: 0.22 to 0.93). Conclusion: This study provides a comprehensive analysis of the impact of anti-CD20 drugs on serum IgG levels in MS patients, exploring the prevalence of hypogammaglobulinemia, based on different drug types, treatment durations, and infection patterns. The identified rates and patterns offer a foundation for clinicians to consider in their risk-benefit. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=518239, CRD42024518239.

19.
Cureus ; 16(5): e59534, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38826953

RESUMO

A total of 22 patients with cleft palate aged 8 to 12 years were selected and categorized into two groups: the first group was treated with alternate rapid maxillary expansion and constriction (Alt-RAMEC) using an expander with differential opening (EDO) and facemask, while the second group was treated using slow maxillary expansion (SME) using an EDO. Finally, the pharyngeal airway volume in the two groups was compared using cone beam computed tomography (CBCT). CBCT scans were performed before expansion and six months following the expansion. Alveolar crest level, maxillary breadth, nasal cavity width, arch width, inclination of the molar teeth, buccal and palatal alveolar bone thickness, and maxillary alveolar width were all assessed. Paired t-tests (p=0.05) were applied to compare interphase data. The two groups showed a non-significant difference in terms of nasopharyngeal volume (cm3), oropharyngeal volume (cm3), and overall pre- and post-treatment results (p>0.005). Results of comparison of pre- and post-treatment periods in the Alt-RAMEC group revealed a significantly higher cleft volume (cm3) (p=0.001). Results of comparison of pre- and post-treatment periods in the SME group revealed a substantial rise in cleft volume (cm3) (p=0.003). Results from a comparison of the cleft volume (cm3) between the two study groups pre- and post-intervention revealed a non-significant difference (p=0.200 and 0.054, respectively).

20.
Adv Exp Med Biol ; 767: 47-73, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23161006

RESUMO

Effective transcription, replication, and maintenance of the genome require a diverse set of molecular machines to perform the many chemical transactions that constitute these processes. Many of these machines use single-stranded nucleic acids as templates, and their actions are often regulated by the participation of nucleic acids in multimeric structures and macromolecular assemblies that restrict access to chemical information. Superfamily II (SF2) DNA helicases and translocases are a group of molecular machines that remodel nucleic acid lattices and enable essential cellular processes to use the information stored in the duplex DNA of the packaged genome. Characteristic accessory domains associated with the subgroups of the superfamily direct the activity of the common motor core and expand the repertoire of activities and substrates available to SF2 DNA helicases, translocases, and large multiprotein complexes containing SF2 motors. In recent years, single-molecule studies have contributed extensively to the characterization of this ubiquitous and essential class of enzymes.


Assuntos
DNA Helicases , Replicação do DNA , DNA/química , DNA Helicases/química
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