RESUMO
The 5d^{1} ordered double perovskites present an exotic playground for studying novel multipolar physics due to large spin-orbit coupling. We present Re L_{3} edge resonant inelastic x-ray scattering (RIXS) results that reveal the presence of the dynamic Jahn-Teller effect in the A_{2}MgReO_{6} (A=Ca, Sr, Ba) family of 5d^{1} double perovskites. The spin-orbit excitations in these materials show a strongly asymmetric line shape and exhibit substantial temperature dependence, indicating that they are dressed with lattice vibrations. Our experimental results are explained quantitatively through a RIXS calculation based on a spin-orbit-lattice entangled electronic ground state with the dynamic Jahn-Teller effect taken into consideration. We find that the spin-orbit-lattice entangled state is robust against magnetic and structural phase transitions as well as against significant static Jahn-Teller distortions. Our results illustrate the importance of including vibronic coupling for a complete description of the ground state physics of 5d^{1} double perovskites.
RESUMO
OBJECTIVE: To compare the coronal plane with axial and sagittal planes in opportunistic screening of osteoporosis using computed tomography (CT). MATERIALS AND METHODS: A total of 100 patients aged ≥ 50 years who underwent both lumbar spine CT and dual-energy X-ray absorptiometry within 3 months were included. Osteoporosis was diagnosed based on dual-energy X-ray absorptiometry results. The CT number was measured at the center of the vertebral body in coronal, axial, and sagittal planes. To compare the coronal plane with axial and sagittal planes in diagnosing osteoporosis, the areas under the receiver operating characteristic curve (AUC) were compared and intraclass correlation coefficient (ICC) was calculated. The optimal cutoff values were calculated using Youden's index. RESULTS: The AUC of the coronal plane (0.80; 95% confidence interval [CI], 0.71-0.89) was not significantly different from that of the axial plane (0.78; 95% CI, 0.68-0.87; P = 0.39) and that of the sagittal plane (0.78; 95% CI, 0.69-0.87; P = 0.68). Excellent concordance rates were observed between coronal and axial planes with ICC of 0.95 (95% CI, 0.92-0.96) and between coronal and sagittal planes with ICC of 0.93 (95% CI, 0.85-0.96). The optimal cutoff values for the coronal, axial, and sagittal planes were 110, 112, and 112 HU, respectively. CONCLUSION: The coronal plane does not significantly differ from axial and sagittal planes in opportunistic screening of osteoporosis. Thus, the coronal plane as well as axial and sagittal planes can be used interchangeably in measuring bone mineral density using CT.
Assuntos
Osteoporose , Humanos , Osteoporose/diagnóstico por imagem , Densidade Óssea , Tomografia Computadorizada por Raios X/métodos , Absorciometria de Fóton/métodos , Programas de Rastreamento/métodos , Vértebras Lombares/diagnóstico por imagem , Estudos RetrospectivosRESUMO
OBJECTIVES: (1) To compare low-contrast detectability of a deep learning-based denoising algorithm (DLA) with ADMIRE and FBP, and (2) to compare image quality parameters of DLA with those of reconstruction methods from two different CT vendors (ADMIRE, IMR, and FBP). MATERIALS AND METHODS: Using abdominal CT images of 100 patients reconstructed via ADMIRE and FBP, we trained DLA by feeding FBP images as input and ADMIRE images as the ground truth. To measure the low-contrast detectability, the randomized repeat scans of Catphan® phantom were performed under various conditions of radiation exposures. Twelve radiologists evaluated the presence/absence of a target on a five-point confidence scale. The multi-reader multi-case area under the receiver operating characteristic curve (AUC) was calculated, and non-inferiority tests were performed. Using American College of Radiology CT accreditation phantom, contrast-to-noise ratio, target transfer function, noise magnitude, and detectability index (d') of DLA, ADMIRE, IMR, and FBPs were computed. RESULTS: The AUC of DLA in low-contrast detectability was non-inferior to that of ADMIRE (p < .001) and superior to that of FBP (p < .001). DLA improved the image quality in terms of all physical measurements compared to FBPs from both CT vendors and showed profiles of physical measurements similar to those of ADMIRE. CONCLUSIONS: The low-contrast detectability of the proposed deep learning-based denoising algorithm was non-inferior to that of ADMIRE and superior to that of FBP. The DLA could successfully improve image quality compared with FBP while showing the similar physical profiles of ADMIRE. KEY POINTS: ⢠Low-contrast detectability in the images denoised using the deep learning algorithm was non-inferior to that in the images reconstructed using standard algorithms. ⢠The proposed deep learning algorithm showed similar profiles of physical measurements to advanced iterative reconstruction algorithm (ADMIRE).
Assuntos
Aprendizado Profundo , Algoritmos , Humanos , Imagens de Fantasmas , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Plain radiography serves a pivotal role in diagnosing axial spondyloarthritis. However, a broad range of diagnostic performance of plain radiography has been reported. PURPOSE: To perform a systematic review and meta-analysis to measure the diagnostic performance of plain radiography for sacroiliitis in patients suspected of having axial spondyloarthritis using magnetic resonance imaging (MRI) findings as the reference standard. MATERIAL AND METHODS: Studies comparing radiography and MRI in the diagnosis of sacroiliitis in patients suspected of having axial spondyloarthritis were searched in PubMed and EMBASE. Additionally, studies analyzed SPondyloaArthritis Caught Early (SPACE), DEvenir des Spondylarthropathies Indifferenciées Récentes (DESIR), GErman Spondyloarthritis Inception Cohort (GESPIC), and South Swedish Arthritis Treatment Group (SSATG) cohorts were manually searched. Pooled sensitivity and specificity of radiography were calculated by using a bivariate random-effects model. Meta-regression analyses were performed to identify the sources of heterogeneity. RESULTS: Eight eligible studies with 1579 patients were included. The pooled sensitivity and specificity of radiography were 0.55 (95% confidence interval [CI] = 0.40-0.69) and 0.87 (95% CI = 0.72-0.95). The meta-regression analyses showed prospective study design and criteria for MRI positivity considering only active bone marrow edema were associated with lower sensitivity. CONCLUSION: The plain radiography showed low sensitivity and reasonable specificity in diagnosis of sacroiliitis in patients suspected of having axial spondyloarthritis.
Assuntos
Sacroileíte/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Radiografia , Sacroileíte/complicações , Espondilartrite/complicaçõesRESUMO
A correlated material in the vicinity of an insulator-metal transition (IMT) exhibits rich phenomenology and a variety of interesting phases. A common avenue to induce IMTs in Mott insulators is doping, which inevitably leads to disorder. While disorder is well known to create electronic inhomogeneity, recent theoretical studies have indicated that it may play an unexpected and much more profound role in controlling the properties of Mott systems. Theory predicts that disorder might play a role in driving a Mott insulator across an IMT, with the emergent metallic state hosting a power-law suppression of the density of states (with exponent close to 1; V-shaped gap) centered at the Fermi energy. Such V-shaped gaps have been observed in Mott systems, but their origins are as-yet unknown. To investigate this, we use scanning tunneling microscopy and spectroscopy to study isovalent Ru substitutions in Sr3(Ir1-xRux)2O7 (0 ≤ x ≤ 0.5) which drive the system into an antiferromagnetic, metallic state. Our experiments reveal that many core features of the IMT, such as power-law density of states, pinning of the Fermi energy with increasing disorder, and persistence of antiferromagnetism, can be understood as universal features of a disordered Mott system near an IMT and suggest that V-shaped gaps may be an inevitable consequence of disorder in doped Mott insulators.
RESUMO
OBJECTIVE: To develop a deep learning algorithm that can rule out significant rotator cuff tear based on conventional shoulder radiographs in patients suspected of rotator cuff tear. METHODS: The algorithm was developed using 6793 shoulder radiograph series performed between January 2015 and June 2018, which were labeled based on ultrasound or MRI conducted within 90 days, and clinical information (age, sex, dominant side, history of trauma, degree of pain). The output was the probability of significant rotator cuff tear (supraspinatus/infraspinatus complex tear with > 50% of tendon thickness). An operating point corresponding to sensitivity of 98% was set to achieve high negative predictive value (NPV) and low negative likelihood ratio (LR-). The performance of the algorithm was tested with 1095 radiograph series performed between July and December 2018. Subgroup analysis using Fisher's exact test was performed to identify factors (clinical information, radiography vendor, advanced imaging modality) associated with negative test results and NPV. RESULTS: Sensitivity, NPV, and LR- were 97.3%, 96.6%, and 0.06, respectively. The deep learning algorithm could rule out significant rotator cuff tear in about 30% of patients suspected of rotator cuff tear. The subgroup analysis showed that age < 60 years (p < 0.001), non-dominant side (p < 0.001), absence of trauma history (p = 0.001), and ultrasound examination (p < 0.001) were associated with negative test results. NPVs were higher in patients with age < 60 years (p = 0.024) and examined with ultrasound (p < 0.001). CONCLUSION: The deep learning algorithm could accurately rule out significant rotator cuff tear based on shoulder radiographs. KEY POINTS: ⢠The deep learning algorithm can rule out significant rotator cuff tear with a negative likelihood ratio of 0.06 and a negative predictive value of 96.6%. ⢠The deep learning algorithm can guide patients with significant rotator cuff tear to additional shoulder ultrasound or MRI with a sensitivity of 97.3%. ⢠The deep learning algorithm could rule out significant rotator cuff tear in about 30% of patients with clinically suspected rotator cuff tear.
Assuntos
Aprendizado Profundo , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia/métodos , Lesões do Manguito Rotador/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Manguito Rotador/diagnóstico por imagem , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To determine the association of meniscal flounce with the pattern and location of the meniscal tear, concomitant ligamentous injury, amount of knee joint effusion, and flexion and rotation angles. MATERIALS AND METHODS: A total of 283 knees of 280 patients were retrospectively reviewed over a 9-month period. Thirty-one magnetic resonance images of patients with meniscal flounce were compared with those of age- and sex-matched control group (n = 62) without meniscal flounce. The presence of meniscal tear was evaluated and, if present, its location and pattern were recorded. The amount of joint effusion was graded, and the joint angle was measured. The Fisher's exact, Cochran-Armitage trend, and t tests were performed to compare the findings between the two groups. The decision tree analysis was employed to determine the most significant factor of meniscal flounce. RESULTS: Meniscal flounce was present in 11.0% (31/283) of the adult population. Approximately 80.6% of meniscal flounce occurred in the torn medial menisci. The presence of meniscal flounce was significantly associated with tears at the body (p = 0.007), posterior horn (p = 0.001), and meniscocapsular junction (p = 0.002) of the medial meniscus. The decision tree analysis revealed that the posterior horn tear of the medial meniscus was the most significant predictor of meniscal flounce. CONCLUSION: The most significant factor associated with meniscal flounce is tear at the posterior horn of the medial meniscus, followed by tear at the meniscocapsular junction.
Assuntos
Traumatismos do Joelho/diagnóstico por imagem , Ligamentos Articulares/lesões , Imageamento por Ressonância Magnética/métodos , Lesões do Menisco Tibial/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , RotaçãoRESUMO
OBJECTIVE. The objective of our study was to compare the sensitivity of a deep learning (DL) algorithm with the assessments by radiologists in diagnosing osteonecrosis of the femoral head (ONFH) using digital radiography. MATERIALS AND METHODS. We performed a two-center, retrospective, noninferiority study of consecutive patients (≥ 16 years old) with a diagnosis of ONFH based on MR images. We investigated the following four datasets of unilaterally cropped hip anteroposterior radiographs: training (n = 1346), internal validation (n = 148), temporal external test (n = 148), and geographic external test (n = 250). Diagnostic performance was measured for a DL algorithm, a less experienced radiologist, and an experienced radiologist. Noninferiority analyses for sensitivity were performed for the DL algorithm and both radiologists. Subgroup analysis for precollapse and postcollapse ONFH was done. RESULTS. Overall, 1892 hips (1037 diseased and 855 normal) were included. Sensitivity and specificity for the temporal external test set were 84.8% and 91.3% for the DL algorithm, 77.6% and 100.0% for the less experienced radiologist, and 82.4% and 100.0% for the experienced radiologist. Sensitivity and specificity for the geographic external test set were 75.2% and 97.2% for the DL algorithm, 77.6% and 75.0% for the less experienced radiologist, and 78.0% and 86.1% for the experienced radiologist. The sensitivity of the DL algorithm was noninferior to that of the assessments by both radiologists. The DL algorithm was more sensitive for precollapse ONFH than the assessment by the less experienced radiologist in the temporal external test set (75.9% vs 57.4%; 95% CI of the difference, 4.5-32.8%). CONCLUSION. The sensitivity of the DL algorithm for diagnosing ONFH using digital radiography was noninferior to that of both less experienced and experienced radiologist assessments.
RESUMO
PURPOSE: To analyze the causes of pain, imaging characteristics, and therapeutic effect of spinal injection in patients with extreme low back pain or sciatica. METHODS: We analyzed 381 consecutive patients with extreme low back pain or sciatica visiting our spinal intervention center between January and December 2017. Clinical and imaging characteristics were analyzed. The treatment response, defined as a numerical pain rating scale decrease of ≥ 30%, was measured. Fisher's exact test was performed to identify the association between the injection response and subsequent lumbar surgery rate. RESULTS: The most frequent cause of pain was spinal stenosis, followed by herniated intervertebral disc, facet osteoarthritis, and osteoporotic compression fracture. A herniated intervertebral disc was the most common disorder in patients < 50 years of age, while spinal stenosis was the most common in patients ≥ 50 years of age. Women comprised 66.4% of the study population. The majority of lumbar pathologies occurred below L3/4. Spinal injection was found to be effective in 44.2% of cases. Those who responded to the injection showed a significantly lower rate of lumbar surgery within 6 months (P = 0.004). CONCLUSIONS: Those with extreme low back pain or sciatica had clinical and imaging characteristics similar to those with typical low back pain referred for spinal injection. Spinal injection could be an effective method of pain control for patients with extreme low back pain or sciatica.
Assuntos
Injeções Espinhais , Dor Lombar/diagnóstico por imagem , Vértebras Lombares , Imageamento por Ressonância Magnética , Ciática/diagnóstico por imagem , Doenças da Coluna Vertebral/diagnóstico por imagem , Adulto , Idoso , Anestésicos Locais/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Humanos , Dor Lombar/tratamento farmacológico , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Ropivacaina/administração & dosagem , Ciática/tratamento farmacológico , Ciática/etiologia , Doenças da Coluna Vertebral/complicaçõesRESUMO
We report a resonant inelastic x-ray scattering study of the magnetic excitation spectrum in a highly insulating Eu_{2}Ir_{2}O_{7} single crystal that exhibits a metal-insulator transition at T_{MI}=111(7) K. A propagating magnon mode with a 20 meV bandwidth and a 28 meV magnon gap is found in the excitation spectrum at 7 K, which is expected in the all-in-all-out magnetically ordered state. This magnetic excitation exhibits substantial softening as the temperature is raised towards T_{MI} and turns into a highly damped excitation in the paramagnetic phase. Remarkably, the softening occurs throughout the whole Brillouin zone including the zone boundary. This observation is inconsistent with the magnon renormalization expected in a local moment system and indicates that the strength of the electron correlation in Eu_{2}Ir_{2}O_{7} is only moderate, so that electron itinerancy should be taken into account in describing its magnetism.
RESUMO
The honeycomb Kitaev-Heisenberg model is a source of a quantum spin liquid with Majorana fermions and gauge flux excitations as fractional quasiparticles. Here we unveil the highly unusual low-temperature heat conductivity κ of α-RuCl_{3}, a prime candidate for realizing such physics: beyond a magnetic field of B_{c}≈7.5 T, κ increases by about one order of magnitude, both for in-plane as well as out-of-plane transport. This clarifies the unusual magnetic field dependence unambiguously to be the result of severe scattering of phonons off putative Kitaev-Heisenberg excitations in combination with a drastic field-induced change of the magnetic excitation spectrum. In particular, an unexpected, large energy gap arises, which increases linearly with the magnetic field, reaching remarkable âω_{0}/k_{B}≈50 K at 18 T.
RESUMO
OBJECTIVE: The objective of our study was to evaluate the association between anterior tibial translation and injuries on the posterior horn medial meniscus (PHMM) and the integrity of the brake stop mechanism of the PHMM in the anterior cruciate ligament (ACL)-deficient knee. MATERIALS AND METHODS: This retrospective study included 85 consecutive patients with an arthroscopically confirmed complete ACL tear. Anterior tibial translation was quantitatively measured using sagittal MRI at the midpoint of the lateral femoral condyle. The "uncovered medial meniscus" sign was considered positive if a vertical line tangent to the posteriormost margin of the medial tibial plateau intersected the PHMM at the midpoint of the medial femoral condyle on sagittal MRI. Concomitant injuries on the structures of the posteromedial and posterolateral corners of the knee, including PHMM tear and meniscal ramp lesion, were recorded. Stratified subgroup analysis and multivariable regression analysis were performed to identify factors associated with anterior tibial translation. RESULTS: The uncovered medial meniscus sign was positive in 21.2% (18/85) of patients and was significantly associated with anterior tibial translation. In the stratified subgroup analysis and multivariable regression analysis, positive uncovered medial meniscus sign consistently showed a significant association with anterior tibial translation and generated an additional 2.8 mm of anterior tibial translation. Other injuries, including PHMM tear and meniscal ramp lesion, were not associated with anterior tibial translation. CONCLUSION: The uncovered medial meniscus sign showed a statistically significant correlation with anterior tibial translation and could be a useful marker for the lost brake stop mechanism of PHMM in the ACL-deficient knee.
Assuntos
Lesões do Ligamento Cruzado Anterior/complicações , Imageamento por Ressonância Magnética , Lesões do Menisco Tibial/diagnóstico por imagem , Adulto , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Lesões do Menisco Tibial/complicações , Lesões do Menisco Tibial/cirurgia , Adulto JovemRESUMO
The combination of electronic correlation and spin-orbit coupling is thought to precipitate a variety of highly unusual electronic phases in solids, including topological and quantum spin liquid states. We report a Raman scattering study that provides evidence for unconventional excitations in α-RuCl_{3}, a spin-orbit coupled Mott insulator on the honeycomb lattice. In particular, our measurements reveal unusual magnetic scattering, typified by a broad continuum. The temperature dependence of this continuum is evident over a large scale compared to the magnetic ordering temperature, suggestive of frustrated magnetic interactions. This is confirmed through an analysis of the phonon linewidths, which show a related anomaly due to spin-phonon coupling. These observations are in line with theoretical expectations for the Heisenberg-Kitaev model and suggest that α-RuCl_{3} may be close to a quantum spin liquid ground state.
RESUMO
We report a combination of Fe Kß x-ray emission spectroscopy and density functional reduced Stoner theory calculations to investigate the correlation between structural and magnetic degrees of freedom in CaFe2(As1-xPx)2. The puzzling temperature behavior of the local moment found in rare earth-doped CaFe2As2 [H. Gretarsson et al., Phys. Rev. Lett. 110, 047003 (2013)] is also observed in CaFe2(As1-xPx)2. We explain this phenomenon based on first-principles calculations with scaled magnetic interaction. One scaling parameter is sufficient to describe quantitatively the magnetic moments in both CaFe2(As1-xPx)2 (x=0.055) and Ca0.78La0.22Fe2As2 at all temperatures. The anomalous growth of the local moments with increasing temperature can be understood from the observed large thermal expansion of the c-axis lattice parameter combined with strong magnetoelastic coupling. These effects originate from the strong tendency to form As-As dimers across the Ca layer in the CaFe2As2 family of materials. Our results emphasize the dual local-itinerant character of magnetism in Fe pnictides.
RESUMO
While most somatic cells undergoing induced pluripotent stem (iPS) cell reprogramming with Yamanaka factors accumulate at stable partially reprogrammed stages, the molecular mechanisms required to achieve full reprogramming are unknown. MicroRNAs (miRNAs) fine-tune mRNA translation and are implicated in reprogramming, but miRNA functional targets critical for complete iPS cell reprogramming remain elusive. We identified methyl-DNA binding domain protein 2 (MBD2) as an epigenetic suppressor, blocking full reprogramming of somatic to iPS cells through direct binding to NANOG promoter elements preventing transcriptional activation. When we overexpressed miR-302 cluster we observed a significant increase in conversion of partial to fully reprogrammed iPS cells by suppressing MBD2 expression, thereby increasing NANOG expression. Thus, expression of exogenous miR-302 cluster (without miR-367) is efficient in attaining a fully reprogrammed iPS state in partially reprogrammed cells by relieving MBD2-mediated inhibition of NANOG expression. Our studies provide a direct molecular mechanism involved in generating complete human iPS cell reprogramming to study disease pathogenesis, drug screening, and for potential cell-based therapies.
Assuntos
Reprogramação Celular/fisiologia , Epigênese Genética/genética , Proteínas de Homeodomínio/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , MicroRNAs/genética , Células Cultivadas , Reprogramação Celular/genética , Humanos , Imunoprecipitação , Células-Tronco Pluripotentes Induzidas/citologia , Proteína Homeobox NanogRESUMO
We report x-ray resonant magnetic scattering and resonant inelastic x-ray scattering studies of epitaxially strained Sr2IrO4 thin films. The films were grown on SrTiO3 and (LaAlO3)0.3(Sr2AlTaO6)0.7 substrates, under slight tensile and compressive strains, respectively. Although the films develop a magnetic structure reminiscent of bulk Sr2IrO4, the magnetic correlations are extremely anisotropic, with in-plane correlation lengths significantly longer than the out-of-plane correlation lengths. In addition, the compressive (tensile) strain serves to suppress (enhance) the magnetic ordering temperature TN, while raising (lowering) the energy of the zone-boundary magnon. Quantum chemical calculations show that the tuning of magnetic energy scales can be understood in terms of strain-induced changes in bond lengths.
Assuntos
Necrose da Cabeça do Fêmur/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Radiografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto JovemRESUMO
Purpose: To identify clinical and MR predictors of retro-odontoid pseudotumor (ROP) regression after posterior fixation in patients with atlantoaxial instability. Materials and Methods: We included patients who had undergone posterior fixation for atlantoaxial instability and preoperative and postoperative MR imaging. Patients were classified into two groups according to the degree of ROP regression after posterior fixation: regression (≥ 10% reduction) and no regression (< 10% reduction). Mann-Whitney and Fisher's exact tests were performed to identify the clinical (age and sex) and MR predictors (preoperative ROP thickness, ROP type, MR signal homogeneity of the ROP, spinal cord signal change, spinal cord atrophy, ossified posterior longitudinal ligament, os odontoideum, and atlantodental interval) associated with ROP regression. Results: We retrospectively assessed 11 consecutive patients (7 female; median age, 66 years [range, 31-84 years]). Posterior fixation induced ROP regression in eight (72.7%) patients. Older age and greater preoperative ROP thickness significantly correlated with ROP regression (p = 0.024 and 0.012, respectively). All patients with preoperative ROP thickness > 5 mm exhibited ROP regression. The other variables were not significantly associated with ROP regression. Conclusion: Older age and thicker preoperative ROP are associated with ROP regression after posterior fixation in patients with atlantoaxial instability.
RESUMO
SIRT1 is a founding member of a sirtuin family of 7 proteins and histone deacetylases. It is involved in cellular resistance to stress, metabolism, differentiation, aging, and tumor suppression. SIRT1(-/-) mice demonstrate embryonic and postnatal development defects. We examined hematopoietic and endothelial cell differentiation of SIRT1(-/-) mouse embryonic stem cells (ESCs) in vitro, and hematopoietic progenitors in SIRT1(+/+)(+/-), and (-/-) mice. SIRT1(-/-) ESCs formed fewer mature blast cell colonies. Replated SIRT1(-/-) blast colony-forming cells demonstrated defective hematopoietic potential. Endothelial cell production was unaltered, but there were defects in formation of a primitive vascular network from SIRT1(-/-)-derived embryoid bodies. Development of primitive and definitive progenitors derived from SIRT1(-/-) ESCs were also delayed and/or defective. Differentiation delay/defects were associated with delayed capacity to switch off Oct4, Nanog and Fgf5 expression, decreased ß-H1 globin, ß-major globin, and Scl gene expression, and reduced activation of Erk1/2. Ectopic expression of SIRT1 rescued SIRT1(-/-) ESC differentiation deficiencies. SIRT1(-/-) yolk sacs manifested fewer primitive erythroid precursors. SIRT1(-/-) and SIRT1(+/-) adult marrow had decreased numbers and cycling of hematopoietic progenitors, effects more apparent at 5%, than at 20%, oxygen tension, and these progenitors survived less well in vitro under conditions of delayed growth factor addition. This suggests a role for SIRT1 in ESC differentiation and mouse hematopoiesis.
Assuntos
Envelhecimento , Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/metabolismo , Sirtuína 1/metabolismo , Animais , Western Blotting , Separação Celular , Células-Tronco Embrionárias/citologia , Citometria de Fluxo , Expressão Gênica , Células-Tronco Hematopoéticas/citologia , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Sirtuína 1/deficiência , Sirtuína 1/genéticaRESUMO
Cryopreservation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) is crucial for cord blood (CB) banking and transplantation. We evaluated recovery of functional HPC cryopreserved as mononuclear or unseparated cells for up to 23.5 years compared with prefreeze values of the same CB units. Highly efficient recovery (80%-100%) was apparent for granulocyte-macrophage and multipotential hematopoietic progenitors, although some collections had reproducible low recovery. Proliferative potential, response to multiple cytokines, and replating of HPC colonies was extensive. CD34(+) cells isolated from CB cryopreserved for up to 21 years had long-term (≥ 6 month) engrafting capability in primary and secondary immunodeficient mice reflecting recovery of long-term repopulating, self-renewing HSCs. We recovered functionally responsive CD4(+) and CD8(+) T lymphocytes, generated induced pluripotent stem (iPS) cells with differentiation representing all 3 germ cell lineages in vitro and in vivo, and detected high proliferative endothelial colony forming cells, results of relevance to CB biology and banking.