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Find video protocols related to scientific articles indexed in Pubmed.
Relevance of Calcitonin Cut-off in the Follow-up of Medullary Thyroid Carcinoma for Conventional Imaging and 18-Fluorine-Fluorodihydroxyphenylalanine PET.
Anticancer Res.
PUBLISHED: 11-05-2014
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The American thyroid association (ATA) recommends that additional imaging procedures supplement cervical ultrasonography (US) in any patient with a basal calcitonin value above 150 pg/ml in the follow-up of medullary thyroid carcinoma (MTC). The aim of the present study was to reaffirm or challenge this cut-off for 18-Fluorine-Fluorodihydroxyphenylalanine positron emission tomography (18F-DOPA PET) and conventional imaging ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI)).
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Quantitative Apparent Diffusion Coefficient as a Noninvasive Imaging Biomarker for the Differentiation of Invasive Breast Cancer and Ductal Carcinoma In Situ.
Invest Radiol
PUBLISHED: 10-22-2014
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The objective of this study was to evaluate whether apparent diffusion coefficient (ADC) obtained through diffusion-weighted imaging magnetic resonance imaging at 3 T can be used as an imaging biomarker to differentiate invasive breast cancer from noninvasive ductal carcinoma in situ (DCIS).
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Introduction of an Automated User-Independent Quantitative Volumetric Magnetic Resonance Imaging Breast Density Measurement System Using the Dixon Sequence: Comparison With Mammographic Breast Density Assessment.
Invest Radiol
PUBLISHED: 10-22-2014
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The purposes of this study were to introduce and assess an automated user-independent quantitative volumetric (AUQV) breast density (BD) measurement system on the basis of magnetic resonance imaging (MRI) using the Dixon technique as well as to compare it with qualitative and quantitative mammographic (MG) BD measurements.
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High-Resolution Peripheral Quantitative CT Imaging: Cortical Porosity, Poor Trabecular Bone Microarchitecture, and Low Bone Strength in Lung Transplant Recipients.
Radiology
PUBLISHED: 10-10-2014
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Purpose To characterize bone microarchitecture and quantify bone strength in lung transplant ( LT lung transplant ) recipients by using high-resolution ( HR high resolution ) peripheral quantitative computed tomographic (CT) imaging of the ultradistal radius. Materials and Methods After study approval by the local ethics committee, all participants provided written informed consent. Included were 118 participants (58 LT lung transplant recipients [mean age, 46.8 years ± 1.9; 30 women, 28 men] and 60 control participants [mean age, 39.9 years ± 1.9; 41 women, 19 men]) between April 2010 and May 2012. HR high resolution peripheral quantitative CT of the ultradistal radius was performed and evaluated for bone mineral density and trabecular and cortical bone microarchitecture. Mechanical competence was quantified by microfinite element analysis. Differences between LT lung transplant recipients and control participants were determined by using two-way factorial analysis of covariance with age adjustment. Results Total and trabecular bone mineral density were significantly lower (-13.4% and -16.4%, respectively; P = .001) in LT lung transplant recipients than in healthy control participants. LT lung transplant recipients had lower trabecular number (-9.7%; P = .004) and lower trabecular thickness (-8.1%; P = .025). Trabecular separation and trabecular network heterogeneity were higher (+24.3% and +63.9%, respectively; P = .007 and P = .012, respectively) in LT lung transplant recipients. Moreover, there was pronounced cortical porosity (+31.3%; P = .035) and lower cortical thickness (-10.2%, P = .005) after LT lung transplant . In addition, mechanical competence was impaired, which was reflected by low stiffness (-15.0%; P < .001), low failure force (-14.8%; P < .001), and low bone strength (-14.6%; P < .001). Conclusion Men and women with recent LT lung transplant showed severe deficits in cortical and trabecular bone microarchitecture. Poor bone microarchitecture and low bone strength are likely to contribute to high fracture susceptibility observed in LT lung transplant recipients. © RSNA, 2014.
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Biochemical Characterization of Pathogenic Mutations in Human Mitochondrial Methionyl-tRNA Formyltransferase.
J. Biol. Chem.
PUBLISHED: 10-06-2014
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N-formylation of initiator methionyl-tRNA (Met-tRNA(Met)) by methionyl-tRNA formyltransferase (MTF) is important for translation initiation in bacteria, mitochondria and chloroplasts. Unlike all other translation systems, the metazoan mitochondrial system is unique in using a single methionine tRNA (tRNA(Met)) for both initiation and elongation. A portion of Met-tRNA(Met) is formylated for initiation while the remainder is used for elongation. Recently, we showed that compound heterozygous mutations within the nuclear gene encoding human mitochondrial MTF (mt-MTF) significantly reduced mitochondrial translation efficiency leading to combined OXPHOS deficiency and Leigh syndrome in two unrelated patients. Patient P1 has a stop codon mutation in one of the MTF genes and a S209L mutation in the other MTF gene. P2 has a S125L mutation in one of the MTF genes and the same S209L mutation as P1 in the other MTF gene. Here, we have investigated the effect of mutations at S125 and S209 on activities of human mt-MTF and of the corresponding mutations, A89 or A172, respectively, on activities of E. coli MTF. The S125L mutant has 653 fold lower activity, whereas the S209L mutant has 36 fold lower activity. Thus, both patients depend upon residual activity of the S209L mutant to support low levels of mitochondrial protein synthesis. We discuss the implications of these and other results on whether the effect of the S209L mutation on mitochondrial translational efficiency is due to reduced activity of the mutant mt-MTF and/or reduced levels of the mutant mt-MTF.
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?-Blockers and Cardiovascular Events in Patients With and Without Myocardial Infarction: Post Hoc Analysis From the CHARISMA Trial.
Circ Cardiovasc Qual Outcomes
PUBLISHED: 09-30-2014
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The long-term efficacy of ?-blockers in patients with and without myocardial infarction (MI) is controversial.
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Physician (investigator) inertia in apparent treatment-resistant hypertension - Insights from large randomized clinical trials.
Blood Press.
PUBLISHED: 08-27-2014
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Background. Treatment of resistant hypertension has attained much attention during the past few years and naturally so has the prevalence of resistant hypertension. In the search for sources of such documentation, the lack of blood pressure (BP) control in randomized clinical outcome trials in hypertension has been used as indication of treatment-resistant hypertension. In the present study, we aimed at using previously unpublished information from monitoring of clinical trials in investigating the mechanism explaining why large fractions of patients in the trials remained uncontrolled for their high BP. Methods. We report insight information from LIFE (n = 9193), VALUE (n = 15,245), ASCOT (n = 19,257) and ACCOMPLISH (n = 11,506). Data stored during the course of the trials for monitoring purposes were scrutinized for fractions of patients with BP control, which was BP < 140/90 mmHg in all trials, and we identified monitoring data showing fractions of patients who had been uptitrated to the various dosing levels or combinations of study drugs in the trials. Fractions of patients who had not been uptitrated on drugs and who remained without BP control identified the level of physician (investigator) inertia in these trials. Results. In the LIFE Study the majority of patients remained with systolic BP > 140 mmHg throughout. Approximately 1500 patients remained on the first dose titration step despite not having reached target BP. In the VALUE Trial 59.5% had reached systolic BP target 2 years into the study; 23.9% of patients remained on the lowest study dose and only 15.1% had been uptitrated to the highest study dose. In the ASCOT Trial, as many as 28% of participants had not reached target diastolic BP at year 4 in the study, and of these patients 37% still remained on the first drug dose titration step. In the ACCOMPLISH Trial approximately 80% had achieved the systolic BP target at study end; however, during the course of the trial approximately 25% of participants remained uncontrolled and at 6 months almost 60% of these patients had not been titrated to the highest drug dose level. Conclusion. These data, taken from the monitoring phases of large outcome trials in hypertension, show that inertia, the lack of titration of study drugs to higher dosing levels or drug combinations according to the study protocols, is a major cause of not reaching BP targets in the trials. Thus, fractions of patients not reaching BP targets in outcome trials cannot be taken as evidence of treatment-resistant hypertension.
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Delayed gadolinium-enhanced MRI of the fibrocartilage disc of the temporomandibular joint - a feasibility study.
Magn Reson Imaging
PUBLISHED: 08-15-2014
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To 1) test the feasibility of delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) at 3 T in the temporomandibular joint (TMJ) and 2) to determine the optimal delay for measurements of the TMJ disc after i.v. contrast agent (CA) administration.
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Host-Derived CD8(+) Dendritic Cells Protect Against Acute Graft-versus-Host Disease after Experimental Allogeneic Bone Marrow Transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-13-2014
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Graft-versus-host disease (GVHD) is a frequent life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT) and induced by donor-derived T cells that become activated by host antigen-presenting cells. To address the relevance of host dendritic cell (DC) populations in this disease, we used mouse strains deficient in CD11c(+) or CD8?(+) DC populations in a model of acute GVHD where bone marrow and T cells from BALB/c donors were transplanted into C57BL/6 hosts. Surprisingly, a strong increase in GVHD-related mortality was observed in the absence of CD11c(+) cells. Likewise, Batf3-deficient (Batf3(-/-)) mice that lack CD8?(+) DCs also displayed a strongly increased GVHD-related mortality. In the absence of CD8?(+) DCs, we detected an increased activation of the remaining DC populations after HSCT, leading to an enhanced priming of allogeneic T cells. Importantly, this was associated with reduced numbers of regulatory T cells and transforming growth factor-? levels, indicating an aggravated failure of peripheral tolerance mechanisms after HSCT in the absence of CD8?(+) DCs. In summary, our results indicate a critical role of CD8?(+) DCs as important inducers of regulatory T cell-mediated tolerance to control DC activation and T cell priming in the initiation phase of GVHD.
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Mapping the binding pocket of a novel, high-affinity, slow dissociating tachykinin NK3 receptor antagonist: biochemical and electrophysiological characterization.
Neuropharmacology
PUBLISHED: 08-05-2014
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The NK3 receptor is a GPCR that is prominently expressed in limbic areas of the brain, many of which have been implicated in schizophrenia. Phase II clinical trials in schizophrenia with two selective NK3 antagonists (osanetant and talnetant) have demonstrated significant improvement in positive symptoms. The objective of this study was to characterize the properties of a novel dual NK2/NK3 antagonist, RO5328673. [(3)H]RO5328673 bound to a single saturable site on hNK2, hNK3 and gpNK3 with high-affinity. RO5328673 acted as an insurmountable antagonist at both human and guinea-pig NK3 receptors in the [(3)H]IP accumulation assay. In binding kinetic analyses, [(3)H]RO5328673 had fast association and dissociation rates at hNK2 while it had a fast association rate and a remarkably slow dissociation rate at gp and hNK3. In electrophysiological recordings of gp SNpc, RO5328673 inhibited the senktide-induced potentiation of spontaneous activity of dopaminergic neurons with an insurmountable mechanism of action. RO5328673 exhibited in-vivo activity in gerbils, robustly reversing the senktide-induced locomotor activity. The TM2 residue gpNK3-A114(2.58) (threonine in all other species) was identified as the critical residue for the RO5328673's slower dissociation kinetics and stronger insurmountable mode of antagonism in the guinea-pig as compared to hNK3-T139(2.58). Using site-directed mutagenesis, [(3)H]RO5328673 binding and rhodopsin-based modeling, the important molecular determinants of the RO5328673-binding pocket of hNK3 were determined. A comparison of the RO5328673-binding pocket with that of osanetant showed that two antagonists have similar contact sides on hNK3 binding crevice except for three mutations V95L(1.42), Y247W(5.38), V255I(5.46), which behaved differently between interacting modes of two antagonists in hNK3.
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Placental pathologies on fetal MRI are associated with high impairment rates: a prospective long-term outcome study.
J. Matern. Fetal. Neonatal. Med.
PUBLISHED: 07-24-2014
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Abstract Objective: Placental anomalies visualized at midgestation by MRI are shown to be related to pregnancy outcome. We performed a prospective cohort study to investigate the influence of placental pathologies diagnosed with fetal MRI on long-term neurodevelopmental outcome. Methods: In our hospital-based, cross-sectional study, all fetal MRI examinations of pregnancies with vascular placental pathology (i.e. infarction with/without hemorrhage, subchorionic thrombi/hemorrhages, intervillous thrombi/hemorrhages or retroplacental hematoma) between 2003 and 2007 were included. The extent of the pathology was expressed as the percentage of abnormality related to the whole placental volume. Pathohistological reports were correlated to MRI findings. Infants were prospectively investigated using Bayley developmental scales at the age of 2-3.5 years. Impairment was categorized as a Bayley scale two SDs below normal (<85 points). Results: There were 31 singletons and 25 offspring of multiple pregnancies included in the analyses. Impairment rates were 32.2% in singletons and 32.0% in multiple births. No correlation between neuro/motordevelopmental outcome at 2-3.5 years and the type, extent or gestational week at the time of diagnoses of placental vascular pathologies was found. Conclusion: The long-term outcome of children with vascular placental pathologies on fetal MRI was associated with a high impairment rate after 2-3.5 years, both on motor- and neurodevelopmental Bayley scales. Neurological impairment did not correlate with the extent of placental involvement, intrauterine growth restriction, gestational age at birth or multiple state.
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Light sheet microscopy.
Methods Cell Biol.
PUBLISHED: 06-30-2014
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This chapter introduces the concept of light sheet microscopy along with practical advice on how to design and build such an instrument. Selective plane illumination microscopy is presented as an alternative to confocal microscopy due to several superior features such as high-speed full-frame acquisition, minimal phototoxicity, and multiview sample rotation. Based on our experience over the last 10 years, we summarize the key concepts in light sheet microscopy, typical implementations, and successful applications. In particular, sample mounting for long time-lapse imaging and the resulting challenges in data processing are discussed in detail.
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Improved differentiation of benign and malignant breast tumors with multiparametric 18fluorodeoxyglucose positron emission tomography magnetic resonance imaging: a feasibility study.
Clin. Cancer Res.
PUBLISHED: 06-26-2014
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To assess whether multiparametric (18)fluorodeoxyglucose positron emission tomography magnetic resonance imaging (MRI) (MP (18)FDG PET-MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), three-dimensional proton MR spectroscopic imaging (3D (1)H-MRSI), and (18)FDG-PET enables an improved differentiation of benign and malignant breast tumors.
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Novel application of multi-stimuli network inference to synovial fibroblasts of rheumatoid arthritis patients.
BMC Med Genomics
PUBLISHED: 06-25-2014
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Network inference of gene expression data is an important challenge in systems biology. Novel algorithms may provide more detailed gene regulatory networks (GRN) for complex, chronic inflammatory diseases such as rheumatoid arthritis (RA), in which activated synovial fibroblasts (SFBs) play a major role. Since the detailed mechanisms underlying this activation are still unclear, simultaneous investigation of multi-stimuli activation of SFBs offers the possibility to elucidate the regulatory effects of multiple mediators and to gain new insights into disease pathogenesis.
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Autonomous spatial orientation in patients with mild to moderate Alzheimer's disease by using mobile assistive devices: a pilot study.
J. Alzheimers Dis.
PUBLISHED: 06-25-2014
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Spatial orientation declines early in patients with Alzheimer's disease (AD) and is a major cause for institutionalization of patients.
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High-resolution reconstruction of the beating zebrafish heart.
Nat. Methods
PUBLISHED: 06-16-2014
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The heart's continuous motion makes it difficult to capture high-resolution images of this organ in vivo. We developed tools based on high-speed selective plane illumination microscopy (SPIM), offering pristine views into the beating zebrafish heart. We captured three-dimensional cardiac dynamics with postacquisition synchronization of multiview movie stacks, obtained static high-resolution reconstructions by briefly stopping the heart with optogenetics and resolved nonperiodic phenomena by high-speed volume scanning with a liquid lens.
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Normal mandibular growth and diagnosis of micrognathia at prenatal MRI.
Prenat. Diagn.
PUBLISHED: 06-11-2014
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The aim of this article is to present reference data for fetal mandibular growth on magnetic resonance imaging, enabling the diagnosis of micrognathia.
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High-sensitivity cardiac troponin T and copeptin assays to improve diagnostic accuracy of exercise stress test in patients with suspected coronary artery disease.
Eur J Prev Cardiol
PUBLISHED: 04-05-2014
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The average diagnostic sensitivity of exercise stress tests (ESTs) is lower than that of other non-invasive cardiac stress tests. The aim of the study was to examine whether high-sensitivity cardiac troponin T (hs-cTnT) or copeptin concentrations rise in response to inducible myocardial ischaemia and may improve the diagnostic accuracy of ESTs.
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Total sacrectomy for recurrent rectal cancer - A case report featuring technical details and potential pitfalls.
Int J Surg Case Rep
PUBLISHED: 03-23-2014
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Total sacrectomy for recurrent rectal cancer is controversial. However, recent publications suggest encouraging outcomes with high sacral resections. We present the first case report describing technical aspects, potential pitfalls and treatment of complications associated with total sacrectomy performed as a treatment of recurrent rectal cancer.
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CT colonography: effect of computer-aided detection of colonic polyps as a second and concurrent reader for general radiologists with moderate experience in CT colonography.
Eur Radiol
PUBLISHED: 03-20-2014
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To assess the effectiveness of computer-aided detection (CAD) as a second reader or concurrent reader in helping radiologists who are moderately experienced in computed tomographic colonography (CTC) to detect colorectal polyps.
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Multilayer mounting for long-term light sheet microscopy of zebrafish.
J Vis Exp
PUBLISHED: 03-19-2014
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Light sheet microscopy is the ideal imaging technique to study zebrafish embryonic development. Due to minimal photo-toxicity and bleaching, it is particularly suited for long-term time-lapse imaging over many hours up to several days. However, an appropriate sample mounting strategy is needed that offers both confinement and normal development of the sample. Multilayer mounting, a new embedding technique using low-concentration agarose in optically clear tubes, now overcomes this limitation and unleashes the full potential of light sheet microscopy for real-time developmental biology.
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Inverse association between bone microarchitecture assessed by HR-pQCT and coronary artery calcification in patients with end-stage renal disease.
Bone
PUBLISHED: 03-11-2014
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It is a matter of debate whether vascular calcification and bone loss are simultaneously occurring but largely independent processes or whether poor bone health predisposes to vascular calcification, especially in patients with kidney disease. Here we investigated the association between the changes of microarchitecture in weight bearing bone and the extent of coronary artery calcification in patients with chronic renal failure. The bone microarchitecture of the tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT), bone mineral density using dual X-ray absorptiometry (DXA) of the lumbar spine, femoral neck and distal radius as well as coronary artery calcification using multi-slice CT and reported as Agatston score were measured in 66 patients with end-stage renal disease on chronic hemodialysis. Markers of bone turnover, vitamin D status and intact parathyroid hormone (iPTH) were assessed. CAC score was found to be <100 in 39% and ?100 in 61% of patients. The median [95% CI] total CAC score was 282 [315-2587]. By univariate analysis, significant correlations between CAC and age (R=0.52, p<0.001), weight (R=0.3, p<0.01) and serum cross laps (CTX, R=-0.39, p<0.01) were found, and parameters of bone microarchitecture were numerically but not significantly lower in patients with CAC scores ?100. In multivariate analysis stratifying for gender and correcting for age, tibial density (Dtot) and bone volume/total volume (BV/TV) were significantly lower in patients with CAC scores ?100 (p<0.05 for both). Low trabecular bone volume and decreased cortical bone density are associated with coronary artery calcification in dialysis patients.
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Hydrophobic actuation of a DNA origami bilayer structure.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-11-2014
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Amphiphilic compounds have a strong tendency to form aggregates in aqueous solutions. It is shown that such aggregation can be utilized to fold cholesterol-modified, single-layered DNA origami structures into sandwich-like bilayer structures, which hide the cholesterol modifications in their interior. The DNA bilayer structures unfold after addition of the surfactant Tween?80, and also in the presence of lipid bilayer membranes, with opening kinetics well described by stretched exponentials. It is also demonstrated that by combination with an appropriate lock and key mechanism, hydrophobic actuation of DNA sandwiches can be made conditional on the presence of an additional molecular input such as a specific DNA sequence.
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Improved diagnostic accuracy with multiparametric magnetic resonance imaging of the breast using dynamic contrast-enhanced magnetic resonance imaging, diffusion-weighted imaging, and 3-dimensional proton magnetic resonance spectroscopic imaging.
Invest Radiol
PUBLISHED: 02-26-2014
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The purpose of this study was to compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as a single parameter to multiparametric (MP) MRI with 2 (DCE MRI and diffusion-weighted imaging [DWI]) and 3 (DCE MRI, DWI, and 3-dimensional proton magnetic resonance spectroscopic imaging [3D H-MRSI]) parameters in breast cancer diagnosis.
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Rapid detection of bone metastasis at thoracoabdominal CT: accuracy and efficiency of a new visualization algorithm.
Radiology
PUBLISHED: 01-31-2014
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To retrospectively assess the use of a combination of cancellous bone reconstructions (CBR) and multiplanar reconstructions (MPRs) for the detection of bone metastases at thoracoabdominal computed tomography (CT) compared with the use of MPRs alone.
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Intravenous laser blood irradiation and tocilizumab in a patient with juvenile arthritis.
Case Rep Med
PUBLISHED: 01-27-2014
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This study presents effects of intravenous laser blood irradiation (ILBI) in a transient immunodeficiency patient with juvenile idiopathic arthritis (JIA) treated with an interleukin-6 receptor inhibitor (Tocilizumab). Biological agents induce JIA remission, but some patients do not respond favorably to this final therapeutic line of defense. ILBI was performed in a 16-year-old male patient, with JIA and transient immunodeficiency. When ILBI was introduced, the patient was receiving disease-modifying drugs, steroids, tocilizumab, and physical therapy. Because the disease was not well controlled, ILBI was applied in addition to other ongoing therapies. The patient underwent 1 session daily, and 10 successive sessions per month, repeated every 3 months, for 7 months. Patient evaluation was performed before ILBI was started and at 3, 6, 9, and 12 months after ILBI initiation, using the ACR Pediatric response. The outcome was evaluated using Pediatric 50, 70, and 90 responses and compared to initial status, after 3, 6, 9, and 12 months. At the end of study, the titre of IgA and IgG levels returned to normal. Synergistic anti-inflammatory effect of ILBI was evident, if applied additionally in combination with tocilizumab, in a patient with a therapy-resistant severe form of JIA and related subacute transient immunodeficiency.
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Donor and host B cell-derived IL-10 contributes to suppression of graft-versus-host disease.
Eur. J. Immunol.
PUBLISHED: 01-20-2014
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Graft-versus-host disease (GvHD) is a frequent life-threatening complication following allogeneic HSC transplantation (HSCT). IL-10 is a regulatory cytokine with important roles during GvHD, yet its relevant sources, and mode of action, remain incompletely defined in this disease. Using IL-10-deficient donor or host mice (BALB/c or C57BL/6, respectively) in a MHC-mismatched model for acute GvHD, we found a strongly aggravated course of the disease with increased mortality when either donor or host cells could not produce this cytokine. A lack of IL-10 resulted in increased allogeneic T-cell responses and enhanced activation of host DCs in spleen and MLNs. Remarkably, IL-10 was prominently produced by host- and donor-derived CD5(int) CD1d(int) TIM-1(int) B cells in this disease, and consistent with this, allogeneic HSCT resulted in exacerbated GvHD when mice lacking IL-10 expression in B cells were used as donor or host, compared with controls. Taken together, this study demonstrates that host and donor B cell-derived IL-10 provides a unique mechanism of suppression of acute GvHD, and suggests that DCs are the targets of this B cell-mediated suppressive effect. These findings open novel therapeutic possibilities based on the use of B cells to increase the feasibility of allogeneic HSCT.
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MR-Based Morphometry of the Posterior Fossa in Fetuses with Neural Tube Defects of the Spine.
PLoS ONE
PUBLISHED: 01-01-2014
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In cases of "spina bifida," a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD) is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA) and the maximum transverse diameter of the posterior fossa (TDPF) as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs.
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Metabolome analysis of Arabidopsis thaliana roots identifies a key metabolic pathway for iron acquisition.
PLoS ONE
PUBLISHED: 01-01-2014
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Fe deficiency compromises both human health and plant productivity. Thus, it is important to understand plant Fe acquisition strategies for the development of crop plants which are more Fe-efficient under Fe-limited conditions, such as alkaline soils, and have higher Fe density in their edible tissues. Root secretion of phenolic compounds has long been hypothesized to be a component of the reduction strategy of Fe acquisition in non-graminaceous plants. We therefore subjected roots of Arabidopsis thaliana plants grown under Fe-replete and Fe-deplete conditions to comprehensive metabolome analysis by gas chromatography-mass spectrometry and ultra-pressure liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry. Scopoletin and other coumarins were found among the metabolites showing the strongest response to two different Fe-limited conditions, the cultivation in Fe-free medium and in medium with an alkaline pH. A coumarin biosynthesis mutant defective in ortho-hydroxylation of cinnamic acids was unable to grow on alkaline soil in the absence of Fe fertilization. Co-cultivation with wild-type plants partially rescued the Fe deficiency phenotype indicating a contribution of extracellular coumarins to Fe solubilization. Indeed, coumarins were detected in root exudates of wild-type plants. Direct infusion mass spectrometry as well as UV/vis spectroscopy indicated that coumarins are acting both as reductants of Fe(III) and as ligands of Fe(II).
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Low-dose high-pitch CT angiography of the supraaortic arteries using sinogram-affirmed iterative reconstruction.
PLoS ONE
PUBLISHED: 01-01-2014
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To prospectively evaluate image quality and radiation dose using a low-dose computed tomography angiography protocol and iterative image reconstruction for high-pitch dual-source CT-angiography (DSCTA) of the supraaortic arteries.
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Neutrophil gelatinase-associated lipocalin (NGAL) for the early detection of contrast-induced nephropathy after percutaneous coronary intervention.
Scand. J. Clin. Lab. Invest.
PUBLISHED: 12-05-2013
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Background. Contrast-induced acute kidney injury (CI-AKI) occurs in up to 13% of patients undergoing percutaneous coronary intervention (PCI). Neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal impairment. We investigated whether increased urinary NGAL concentrations were predictive of CI-AKI within 2 days after PCI or of a higher re-hospitalization rate within 9 months. Methods. Consecutive patients (n = 128), with stable coronary heart disease and eGFR ? 30 mL/min/1.73 m(2), undergoing PCI were included. Venous serum samples for measurement of creatinine, blood urea nitrogen, and cystatin C and urine samples for NGAL measurement were collected 4 hours and 1 and 2 days after contrast medium application. Patients were followed over 9 months to determine clinical endpoints. Results. CI-AKI was observed in 14 patients (10.9%) after PCI. NGAL concentrations before PCI were significantly higher in patients with subsequent CI-AKI (19.8 ng/mL [14.4-35.8] vs. 11.6 ng/mL [5.6-28.2]; p = 0.04). There was no significant difference in NGAL concentrations 4 h after PCI between patients with and without CI-AKI. One day after PCI, NGAL concentrations were significant higher in patients developing CI-AKI (100.1 ng/mL [41.5-129.2] vs. 16.6 ng/mL [9.1-28.1]; p < 0.001). Compared to common biomarkers, NGAL best predicted CI-AKI (AUC 0.939 [95% CI 0.89-0.99; p < 0.001]). The re-hospitalization rate due to progressive renal insufficiency within 9 months was higher in the group with CI-AKI than the group without (4 [28.6%] vs. 4 [3.5%], p < 0.01). Conclusion. Urinary NGAL is a biomarker for predicting CI-AKI when measured 1 day after PCI.
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Dual-energy computed tomography compared with ultrasound in the diagnosis of gout.
Rheumatology (Oxford)
PUBLISHED: 10-17-2013
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Objectives. The aim of our study was to compare dual-energy CT (DECT) with US for the diagnosis of gouty arthritis and to correlate the imaging findings with results from synovial fluid aspiration whenever possible. Methods. We recruited 21 patients (17 male and 4 female) who presented with a clinical suspicion of acute or chronic gout in 37 joints. DECT scans of the hands, wrists, feet, ankles, knees and elbows were performed. For post-processing, a colour-coding gout software protocol was used. US examinations of the same joints were performed. In addition, joint fluid aspiration was performed in a total of 14 joints. Results. DECT images were positive for urate crystal deposits in 25 of 37 joints. US findings were positive in 24 of 37 examined joints. In 12 of 14 joints the synovial fluid aspiration was positive. CT and US findings correlated in 32 of 37 joints (86.5%; ? = 0.698, P < 0.001). CT and synovial fluid results correlated in 12 of 14 joints (85.7%; ? = 0.417, P = 0.119). US and cytology findings correlated in 14 of 14 joints (100%; ? = 1, P < 0.001). Conclusion. DECT and US have comparable sensitivity for the detection of gouty arthritis in a clinical setting. However, DECT results should be interpreted carefully, as there could be some false-negative findings.
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Dual Energy Computerized Tomography with a Split Bolus: A 1-Stop Shop for Patients with Suspected Urinary Stones?
J. Urol.
PUBLISHED: 10-15-2013
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We evaluated a dual energy, split bolus computerized tomography protocol that provides virtual noncontrast, parenchymal and urographic phases in a single scan. We assessed the sensitivity of the virtual noncontrast phase using this protocol to detect urinary stones compared to the gold standard of the true noncontrast phase.
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Biofabrication under fluorocarbon: a novel freeform fabrication technique to generate high aspect ratio tissue-engineered constructs.
Biores Open Access
PUBLISHED: 10-02-2013
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Bioprinting is a recent development in tissue engineering, which applies rapid prototyping techniques to generate complex living tissues. Typically, cell-containing hydrogels are dispensed layer-by-layer according to a computer-generated three-dimensional model. The lack of mechanical stability of printed hydrogels hinders the fabrication of high aspect ratio constructs. Here we present submerged bioprinting, a novel technique for freeform fabrication of hydrogels in liquid fluorocarbon. The high buoyant density of fluorocarbons supports soft hydrogels by floating. Hydrogel constructs of up to 30-mm height were generated. Using 3% (w/v) agarose as the hydrogel and disposable syringe needles as nozzles, the printer produced features down to 570-?m diameter with a lateral dispensing accuracy of 89??m. We printed thin-walled hydrogel cylinders measuring 4.8?mm in height, with an inner diameter of ?2.9?mm and a minimal wall thickness of ?650??m. The technique was successfully applied in printing a model of an arterial bifurcation. We extruded under fluorocarbon, cellularized alginate tubes with 5-mm outer diameter and 3-cm length. Cells grew vigorously and formed clonal colonies within the 7-day culture period. Submerged bioprinting thus seems particularly suited to fabricate hollow structures with a high aspect ratio like vascular grafts for cardiovascular tissue engineering as well as branching or cantilever-like structures, obviating the need for a solid support beneath the overhanging protrusions.
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The cellular ratio of immune tolerance (immunoCRIT) is a definite marker for aggressiveness of solid tumors and may explain tumor dissemination patterns.
Epigenetics
PUBLISHED: 09-26-2013
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The adaptive immune system is involved in tumor establishment and aggressiveness. Tumors of the ovaries, an immune-privileged organ, spread via transceolomic routes and rarely to distant organs. This is contrary to tumors of non-immune privileged organs, which often disseminate hematogenously to distant organs. Epigenetics-based immune cell quantification allows direct comparison of the immune status in benign and malignant tissues and in blood. Here, we introduce the "cellular ratio of immune tolerance" (immunoCRIT) as defined by the ratio of regulatory T cells to total T lymphocytes. The immunoCRIT was analyzed on 273 benign tissue samples of colorectal, bronchial, renal and ovarian origin as well as in 808 samples from primary colorectal, bronchial, mammary and ovarian cancers. ImmunoCRIT is strongly increased in all cancerous tissues and gradually augmented strictly dependent on tumor aggressiveness. In peripheral blood of ovarian cancer patients, immunoCRIT incrementally increases from primary diagnosis to disease recurrence, at which distant metastases frequently occur. We postulate that non-pathological immunoCRIT values observed in peripheral blood of immune privileged ovarian tumor patients are sufficient to prevent hematogenous spread at primary diagnosis. Contrarily, non-immune privileged tumors establish high immunoCRIT in an immunological environment equivalent to the bloodstream and thus spread hematogenously to distant organs. In summary, our data suggest that the immunoCRIT is a powerful marker for tumor aggressiveness and disease dissemination.
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Two-photon laser scanning microscopy as a useful tool for imaging and evaluating macrophage-, IL-4 activated macrophage- and osteoclast-based In Vitro degradation of beta-tricalcium phosphate bone substitute material.
Microsc. Res. Tech.
PUBLISHED: 09-03-2013
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Two-photon microscopy is an innovative technology that has high potential to combine the examination of soft and hard tissues in vitro and in vivo. Calcium phosphates are widely used substitutes for bone tissue engineering, since they are degradable and consequently replaced by newly formed tissue. It is well known that osteoclasts are responsible for the resorption processes during bone remodelling. We hypothesize that also macrophages are actively involved in the resorption process of calcium phosphate scaffolds and addressed this question in in vitro culture systems by two-photon laser scanning microscopy. Beta-tricalcium phosphate specimens were incubated with (1) macrophages, (2) interleukin-4 activated macrophages, and (3) osteoclasts for up to 21 days. Interestingly, macrophages degraded beta-tricalcium phosphate specimens in an equivalent fashion compared to osteoclasts and significantly more than IL-4 activated macrophages. An average of ?32% of the macrophages was partially filled with ceramic material while this was 18% for osteoclasts and 9% for IL-4 activated macrophages. For the first time by applying two-photon microscopy, our studies show the previously unrecognized potential of macrophages to phagocytose ceramic material, which is expected to have implication on osteoconductive scaffold design. Microsc. Res. Tech., 2013. © 2013 Wiley Periodicals, Inc.
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DNA methylation: an identity card for brain cells.
Genome Biol.
PUBLISHED: 08-27-2013
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A recently published study has revealed the genome-wide dynamics of DNA methylation and hydroxymethylation patterns at single-base resolution in the human and mouse developing brain.
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Release kinetics of N-terminal pro-B-type natriuretic peptide in a clinical model of acute myocardial infarction.
Clin. Chim. Acta
PUBLISHED: 08-23-2013
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N-terminal segment of B-type natriuretic peptide prohormone (NT-proBNP) is elevated in patients with acute myocardial infarction (AMI) thus providing both diagnostic information and prognostic information. The aim of the present study was to determine the time course of NT-proBNP release in patients undergoing transcoronary ablation of septal hypertrophy (TASH) a procedure mimicking AMI.
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Can dual-energy CT improve the assessment of tumor margins in oral cancer?
Oral Oncol.
PUBLISHED: 08-03-2013
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The aim was to investigate the image quality of dual-energy computed-tomography (DECT) compared to single-energy images at 80kV and 140kV in oral tumors.
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Stenosis quantification of coronary arteries in coronary vessel phantoms with second-generation dual-source CT: influence of measurement parameters and limitations.
AJR Am J Roentgenol
PUBLISHED: 07-26-2013
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The purpose of this study was to use second-generation dual-source CT to assess the influence of size, degree of stenosis, luminal contrast attenuation, and plaque geometry on stenosis quantification in a coronary artery phantom.
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Intravenous laser blood irradiation increases efficacy of etanercept in selected subtypes of juvenile idiopathic arthritis: an innovative clinical research approach.
Evid Based Complement Alternat Med
PUBLISHED: 07-03-2013
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This single-blind, placebo-controlled study assesses the efficacy of synergic administration of intravenous laser blood irradiation (ILBI) and etanercept in selected subtypes of juvenile idiopathic arthritis (JIA). Etanercept is a tumor necrosis factor alpha blocking agent with recognized importance in JIA. Laser radiation has immunomodulatory effects in animal and human studies. Fourteen patients (Group I) received ILBI and 9 patients (Group II) received placebo laser. ILBI was performed in addition to ongoing JIA medication, including etanercept. ILBI was administrated in 3 sets of 5 consecutive daily sessions, with a 7-week interval between every set of sessions. Evaluation was performed using ACR (American College of Rheumatology) Pediatric Criteria (ACR Pedi) at study enrollment and at 10 and 20 weeks, respectively. After 10 weeks, 85.7% of the patients in Group I fulfilled Pedi 30 criteria, compared to only 55.6% of the patients in Group II. After 20 weeks, all patients in both groups had a Pedi 30 response. In Group I, 92.8% of the subjects met the Pedi 50 response, compared to only 55.6% in the placebo group. One patient in Group I responded best, fulfilling Pedi 70 criteria. If applied synergistically, ILBI and etanercept would have an increased efficacy in promoting JIA remission.
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GRN2SBML: automated encoding and annotation of inferred gene regulatory networks complying with SBML.
Bioinformatics
PUBLISHED: 06-26-2013
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GRN2SBML automatically encodes gene regulatory networks derived from several inference tools in systems biology markup language. Providing a graphical user interface, the networks can be annotated via the simple object access protocol (SOAP)-based application programming interface of BioMart Central Portal and minimum information required in the annotation of models registry. Additionally, we provide an R-package, which processes the output of supported inference algorithms and automatically passes all required parameters to GRN2SBML. Therefore, GRN2SBML closes a gap in the processing pipeline between the inference of gene regulatory networks and their subsequent analysis, visualization and storage.
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Oxidative burst and neutrophil elastase contribute to clearance of Aspergillus fumigatus pneumonia in mice.
Immunobiology
PUBLISHED: 06-17-2013
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Polymorphonuclear neutrophils (PMN) are important for the control of invasive aspergillosis (IA), a major threat to immunocompromised individuals. For clearance of Aspergillus fumigatus infections, PMN employ their potent oxidative and non-oxidative mechanisms. To clarify the relative contribution of these mechanisms, we analyzed p47(phox-/-), gp91(phox-/-) and elastase (ELA) deficient mice (ELANE) after intratracheal infection with A. fumigatus. Infected p47(phox-/-) and gp91(phox-/-) mice died within 4 days and had a significant higher fungal burden in the lungs compared to wild-type controls. Interestingly, the survival of ELANE mice after infection was unimpaired suggesting that ELA is not essential here. Nevertheless, A. fumigatus clearance was delayed in ELANE mice indicating a partial contribution of ELA to fungal immunity. Comparing p47(phox-/-), gp91(phox-/-) or ELANE mice for PMN activation and recruitment to the lungs, we were unable to detect significant differences in vitro or in vivo among mutant or wild-type strains suggesting intact PMN functionality of basic effector mechanisms. Fungal killing in vitro by ELA deficient PMN was comparably reduced as in p47(phox-/-) and gp91(phox-/-) deficient PMN corroborating the importance of oxidative and non-oxidative PMN mechanisms for the control of fungal outgrowth. Taken together, this suggests that intact oxidative as well as non-oxidative PMN effector functions are highly relevant for the control of A. fumigatus infections in vitro and in vivo. While ELA contributes to clearance of A. fumigatus, the oxidative functions are essential for survival.
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Using high-performance (1)H NMR (HP-qNMR(®)) for the certification of organic reference materials under accreditation guidelines-Describing the overall process with focus on homogeneity and stability assessment.
J Pharm Biomed Anal
PUBLISHED: 06-05-2013
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Quantitative NMR spectroscopy (qNMR) is gaining interest across both analytical and industrial research applications and has become an essential tool for the content assignment and quantitative determination of impurities. The key benefits of using qNMR as measurement method for the purity determination of organic molecules are discussed, with emphasis on the ability to establish traceability to "The International System of Units" (SI). The work describes a routine certification procedure from the point of view of a commercial producer of certified reference materials (CRM) under ISO/IEC 17025 and ISO Guide 34 accreditation, that resulted in a set of essential references for (1)H qNMR measurements, and the relevant application data for these substances are given. The overall process includes specific selection criteria, pre-tests, experimental conditions, homogeneity and stability studies. The advantages of an accelerated stability study over the classical stability-test design are shown with respect to shelf-life determination and shipping conditions.
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Role of the ribosomal P-site elements of m²G966, m?C967, and the S9 C-terminal tail in maintenance of the reading frame during translational elongation in Escherichia coli.
J. Bacteriol.
PUBLISHED: 05-31-2013
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The ribosomal P-site hosts the peptidyl-tRNAs during translation elongation. Which P-site elements support these tRNA species to maintain codon-anticodon interactions has remained unclear. We investigated the effects of P-site features of methylations of G966, C967, and the conserved C-terminal tail sequence of Ser, Lys, and Arg (SKR) of the S9 ribosomal protein in maintenance of the translational reading frame of an mRNA. We generated Escherichia coli strains deleted for the SKR sequence in S9 ribosomal protein, RsmB (which methylates C967), and RsmD (which methylates G966) and used them to translate LacZ from its +1 and -1 out-of-frame constructs. We show that the S9 SKR tail prevents both the +1 and -1 frameshifts and plays a general role in holding the P-site tRNA/peptidyl-tRNA in place. In contrast, the G966 and C967 methylations did not make a direct contribution to the maintenance of the translational frame of an mRNA. However, deletion of rsmB in the S9?3 background caused significantly increased -1 frameshifting at 37°C. Interestingly, the effects of the deficiency of C967 methylation were annulled when the E. coli strain was grown at 30°C, supporting its context-dependent role.
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Quantification of lower leg arterial calcifications by high-resolution peripheral quantitative computed tomography.
Bone
PUBLISHED: 05-14-2013
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Vascular calcifications and bone health seem to be etiologically linked via common risk factors such as aging and subclinical chronic inflammation. Epidemiologic studies have shown significant associations between low bone mineral density (BMD), fragility fractures and calcifications of the coronary arteries and the abdominal aorta. In the last decade, high-resolution peripheral quantitative computed tomography (HR-pQCT) has emerged as in-vivo research tool for the assessment of peripheral bone geometry, density, and microarchitecture. Although vascular calcifications are frequently observed as incidental findings in HR-pQCT scans, they have not yet been incorporated into quantitative HR-pQCT analyses. We developed a semi-automated algorithm to quantify lower leg arterial calcifications (LLACs), captured by HR-pQCT. The objective of our study was to determine validity and reliability of the LLAC measure. HR-pQCT scans were downscaled to a voxel size of 250?m. After subtraction of bone volumes from the scans, LLACs were detected and contoured by a semi-automated, dual-threshold seed-point segmentation. LLAC mass (in mg hydroxyapatite; HA) was calculated as the product of voxel-based calcification volume (mm(3)) and mean calcification density (mgHA/cm(3))/1000. To determine validity, we compared LLACs to coronary artery calcifications (CACs), as quantified by multi-detector computed tomography (MDCT) and Agatston scoring in forty-six patients on chronic hemodialysis. Moreover, we investigated associations of LLACs with age, time on dialysis, type-2 diabetes mellitus, history of stroke, and myocardial infarction. In a second step, we determined intra- and inter-reader reliability of the LLAC measure. In the validity study, LLACs were present (>0mgHA) in 76% of patients, 78% of patients had CACs (>0mgHA). Median LLAC was 6.65 (0.08-24.40)mgHA and median CAC as expressed by Agatston score was 266.3 (15.88-1877.28). We found a significant positive correlation between LLAC and CAC (rho=0.6; p<0.01). Dialysis patients with type-2 diabetes mellitus (DM; 35%) and history of stroke (13%) had higher median LLAC than patients without those conditions (DM 20.0 fold greater, p=0.006; Stroke 5.1 fold greater, p=0.047). LLAC was positively correlated with time on dialysis (rho=0.337, p=0.029), there was a trend towards a positive association of LLAC and age (rho=0.289, p=0.053). The reliability study yielded excellent intra- and inter-reader agreement of the LLAC measure (intra-reader ICC=0.999, 95% CI=0.998-1.000; inter-reader ICC=0.998, 95% CI=0.994-0.999). Our study indicates that the LLAC measure has good validity and excellent reliability. The use of HR-pQCT for the simultaneous evaluation of arterial calcifications, peripheral bone geometry, bone density, and bone microarchitecture should facilitate future research on osteo-vascular interactions and potential associations with cardiovascular events.
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Neutrophil gelatinase-associated lipocalin (NGAL) for the early detection of cardiac surgery associated acute kidney injury.
Scand. J. Clin. Lab. Invest.
PUBLISHED: 05-13-2013
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Acute kidney injury (AKI) is a common complication after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) may be an early biomarker for cardiac surgery-associated (CSA) AKI. We investigated whether increased urinary NGAL concentrations were predictive of AKI within 4 days after surgery and of mortality within 9 months.
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The early prediction of neonatal morbidity and mortality in singleton small for gestational age infants with a birthweight
Wien. Klin. Wochenschr.
PUBLISHED: 05-12-2013
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Identify factors for discrimination of "high" and "low risk" small for gestational age infants.
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The effect of crystallization of bioactive bioglass 45S5 on apatite formation and degradation.
Dent Mater
PUBLISHED: 05-02-2013
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Amorphous bioglass 45S5 has been used for many years as bone substitute material. Bioactive glasses are also suitable as coating materials for implants in order to improve the bone ongrowth behavior. We hypothesize that both the apatite formation on the surface and the chemical stability can be improved by crystallization of the bioglass.
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Functions of DNA methylation and hydroxymethylation in mammalian development.
Curr. Top. Dev. Biol.
PUBLISHED: 04-17-2013
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DNA methylation occurs at cytosines, predominantly in the CpG dinucleotide context and is a key epigenetic regulator of embryogenesis and stem-cell differentiation in mammals. The genomic patterns of 5-methylcytosine are extensively reprogrammed during early embryonic development as well as in the germ-cell lineage. Thanks to improvements in high-throughput mapping technologies, it is now possible to characterize the dynamics of this epigenetic mark at the genome scale. DNA methylation plays multiple roles during development and serves to establish long-term gene silencing. In 2009, it was revealed that 5-hydroxymethylcytosine (5hmC) is another prominent cytosine modification catalyzed by the enzymes of the TET family and abundant in certain cell types. 5hmC has been thought to serve as an intermediate in the reaction of DNA demethylation or act as a signal for chromatin factors. Here, we review the current knowledge on the roles of these DNA epigenetic marks in development, epigenetic reprogramming, and pluripotency.
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Distinctive contributions of the ribosomal P-site elements m2G966, m5C967 and the C-terminal tail of the S9 protein in the fidelity of initiation of translation in Escherichia coli.
Nucleic Acids Res.
PUBLISHED: 03-25-2013
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The accuracy of pairing of the anticodon of the initiator tRNA (tRNA(fMet)) and the initiation codon of an mRNA, in the ribosomal P-site, is crucial for determining the translational reading frame. However, a direct role of any ribosomal element(s) in scrutinizing this pairing is unknown. The P-site elements, m(2)G966 (methylated by RsmD), m(5)C967 (methylated by RsmB) and the C-terminal tail of the protein S9 lie in the vicinity of tRNA(fMet). We investigated the role of these elements in initiation from various codons, namely, AUG, GUG, UUG, CUG, AUA, AUU, AUC and ACG with tRNA(fMet(CAU) (tRNA(fMet) with CAU anticodon); CAC and CAU with tRNA(fMet(GUG); UAG with tRNA(fMet(CAU) ; UAC with tRNA(fMet(GUG) ; and AUC with tRNA(fMet(GUG) using in vivo and computational methods. Although RsmB deficiency did not impact initiation from most codons, RsmD deficiency increased initiation from AUA, CAC and CAU (2- to 3.6-fold). Deletion of the S9 C-terminal tail resulted in poorer initiation from UUG, GUG and CUG, but in increased initiation from CAC, CAU and UAC codons (up to 4-fold). Also, the S9 tail suppressed initiation with tRNA(fMet(CAU) lacking the 3GC base pairs in the anticodon stem. These observations suggest distinctive roles of 966/967 methylations and the S9 tail in initiation.
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A mutation in the Arabidopsis thaliana cell wall biosynthesis gene pectin methylesterase 3 as well as its aberrant expression cause hypersensitivity specifically to Zn.
Plant J.
PUBLISHED: 03-22-2013
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Defects in metal homeostasis factors are often accompanied by the loss of metal tolerance. Therefore, we screened for mutants with compromised growth in the presence of excess Zn(2+) in order to identify factors involved in Zn biology in plants. Here we report the isolation of six ozs (overly Zn sensitive) ethyl methanesulfonate Arabidopsis thaliana mutants with contrasting patterns of metal sensitivity, and the molecular characterization of two mutants hypersensitive specifically to Zn(2+) . Mutant ozs1 represents a non-functional allele of the vacuolar Zn transporter AtMTP1, providing additional genetic evidence for its major role in Zn(2+) tolerance in seedlings. Mutant ozs2 carries a semi-dominant mutation in the gene encoding pectin methylesterase 3 (AtPME3), an enzyme catalyzing demethylesterification of pectin. The mutation results in impaired proteolytic processing of AtPME3. Ectopic expression of AtPME3 causes strong Zn(2+) hypersensitivity that is tightly correlated with transcript abundance. Together these observations suggest detrimental effects on Golgi-localized processes. The ozs2 but not the ozs1 phenotype can be suppressed by extra Ca(2+) , indicating changes in apoplastic cation-binding capacity. However, we did not detect any changes in bulk metal-binding capacity, overall pectin methylesterification status or cell wall ultrastructure in ozs2, leading us to hypothesize that the ozs2 mutation causes hypersensitivity towards the specific interference of Zn ions with cell wall-controlled growth processes.
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Texture-based and diffusion-weighted discrimination of parotid gland lesions on MR images at 3.0 Tesla.
NMR Biomed
PUBLISHED: 03-22-2013
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The purpose of this study was to evaluate whether texture-based analysis of standard MRI sequences and diffusion-weighted imaging can help in the discrimination of parotid gland masses. The MR images of 38 patients with a biopsy- or surgery-proven parotid gland mass were retrospectively analyzed. All patients were examined on the same 3.0 Tesla MR unit, with one standard protocol. The ADC (apparent diffusion coefficient) values of the tumors were measured with three regions of interest (ROIs) covering the entire tumor. Texture-based analysis was performed with the texture analysis software MaZda (version 4.7), with ROI measurements covering the entire tumor in three slices. COC (co-occurrence matrix), RUN (run-length matrix), GRA (gradient), ARM (auto-regressive model), and WAV (wavelet transform) features were calculated for all ROIs. Three subsets of 10 texture features each were used for a linear discriminant analysis (LDA) in combination with k nearest neighbor classification (k-NN). Using histology as a standard of reference, benign tumors, including subtypes, and malignant tumors were compared with regard to ADC and texture-based values, with a one-way analysis of variance with post-hoc t-tests. Significant differences were found in the mean ADC values between Warthin tumors and pleomorphic adenomas, as well as between Warthin tumors and benign lesions. Contrast-enhanced T1-weighted images contained the most relevant textural information for the discrimination between benign and malignant parotid masses, and also for the discrimination between pleomorphic adenomas and Warthin tumors. STIR images contained the least relevant texture features, particularly for the discrimination between pleomorphic adenomas and Warthin tumors. Texture analysis proved to differentiate benign from malignant lesions, as well as pleomorphic adenomas from Warthin tumors, based on standard T(1w) sequences (without and with contrast). Of all benign parotid masses, Warthin tumors had significantly lower ADC values than the other entities.
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Computed tomography pulmonary angiography in acute pulmonary embolism: the effect of a computer-assisted detection prototype used as a concurrent reader.
J Thorac Imaging
PUBLISHED: 03-15-2013
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To assess the effect of computer-assisted detection (CAD) on diagnostic accuracy, reader confidence, and reading time when used as a concurrent reader for the detection of acute pulmonary embolism in computed tomography pulmonary angiography.
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Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation.
BMC Syst Biol
PUBLISHED: 03-04-2013
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Network inference from gene expression data is a typical approach to reconstruct gene regulatory networks. During chondrogenic differentiation of human mesenchymal stem cells (hMSCs), a complex transcriptional network is active and regulates the temporal differentiation progress. As modulators of transcriptional regulation, microRNAs (miRNAs) play a critical role in stem cell differentiation. Integrated network inference aimes at determining interrelations between miRNAs and mRNAs on the basis of expression data as well as miRNA target predictions. We applied the NetGenerator tool in order to infer an integrated gene regulatory network.
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Contrast-enhanced MR imaging of hand and finger joints in patients with early rheumatoid arthritis: do we really need a full dose of gadobenate dimeglumine for assessing synovial enhancement at 3 T?
Radiology
PUBLISHED: 02-28-2013
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To investigate the diagnostic value of a half dose compared with a full dose of gadobenate dimeglumine in the assessment of synovitis or tenosynovitis in the wrist and finger joints in patients with early rheumatoid arthritis (RA) and a disease activity score greater than 3.2.
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Primacy of the 3B approach to control risk factors for cardiovascular disease in type 2 diabetes patients.
Am. J. Med.
PUBLISHED: 02-20-2013
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Individually, diabetes mellitus, hypertension, and dyslipidemia have been shown to increase the risk of cardiovascular disease. While traditional management of Type 2 diabetes has focused mainly on glycemic control, robust evidence supports the integration of hypertension and dyslipidemia management to reduce the risk of cardiovascular disease. The primary objective of this study was to assess the level of control of blood glucose, blood pressure, and blood lipids (3Bs) among patients with type 2 diabetes. An additional objective was to investigate the impact of hospital type, physician specialty, treatment pattern, and patient profile on clinical outcomes.
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Magnetic field interactions of copper-containing intrauterine devices in 3.0-Tesla magnetic resonance imaging: in vivo study.
Korean J Radiol
PUBLISHED: 02-18-2013
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An ex vivo study found a copper-containing intrauterine device (IUD) to be safe for women undergoing an MRI examination at a 3.0-T field. No significant artifacts caused by the metallic implant were detected. However, there are still no in vivo data about these concerns. The aim of this study was to evaluate 3.0-T magnetic field interactions of copper-containing IUDs in vivo.
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Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells.
J Innate Immun
PUBLISHED: 02-12-2013
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Triggering receptor expressed on myeloid cells 1 (TREM-1) is an important mediator of innate inflammatory responses in microbial infections and sepsis. TREM-1 ligation on neutrophils (PMN) or monocytes results in the production of proinflammatory cytokines. Engagement of TREM-1 induces the activation of MAP kinases as well as rapid Ca(2+) mobilization. However, a detailed understanding of TREM-1 signaling pathways is currently lacking. We evaluated the TREM-1 signaling hierarchy in monocytic cells and found that the acute myeloid leukemia cell line MUTZ-3 expresses TREM-1 in a natural and functional manner. We compared essential signaling molecules of the TREM-1, TLR and NLR cascade in MUTZ-3 cells as well as primary monocytes or PMN by Western blot analysis. These studies confirmed the essential role of phosphatidyl inositide 3-kinase (PI3K) and p38MAPK in the TREM-1 as well as the TLR or NLR cascade of monocytic cells. Importantly, PI3K and p38MAPK signals in monocytic cells both control Ca(2+) mobilization and are directly connected in the TREM-1 signaling hierarchy, which contrasts previous results obtained in PMN. Taken together, our results indicate cell type-specific differences in the TREM-1 signaling cascade and contribute to an enhanced understanding of the regulation of innate inflammatory responses. © 2013 S. Karger AG, Basel.
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The management of patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation: In-hospital-data from the atrial fibrillation undergoing coronary artery stenting study.
Catheter Cardiovasc Interv
PUBLISHED: 02-09-2013
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Current recommendations on the management of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention with stent (PCI-S) essentially derive from small, single-center, retrospective datasets. To obtain larger and better quality data, we carried out the prospective, multicenter Atrial Fibrillation undergoing Coronary Artery Stenting (AFCAS) study. Therefore, consecutive patients with history of or ongoing AF undergoing PCI-S were enrolled, and occurrence of adverse ischemic and bleeding events recorded during 12 months follow-up. In this article, we report the in-hospital observations. Out of the 963 patients, in the majority of cases (49.1%) AF was permanent. The associated risk of stroke, as defined by a CHADS2 -score ?2, was in 70% of patients moderate to high. Upon enrolment in the registry, 69.3% of patients were on VKA therapy. Overall occurrence of in-hospital major adverse cardiac events was 4.5% (cardiovascular death 1.9%, urgent revascularization in 1.5%, and stroke/arterial thromboembolism in 0.6%). Bleeding complications occurred in 7.1% of patients, being severe in 2.5%. In a logistic regression analysis, no risk factor was independently associated with bleeding events, whereas Clopidogrel treatment decreased and female gender/treatment with gpIIb/IIIa-antagonists, respectively increased the risk for the combined ischemic endpoint. The majority of AF patients undergoing PCI-S are at high stroke risk, and therefore VKA treatment should not be withdrawn and combined anticoagulant and antiplatelet treatment is warranted. Current management appears largely in accordance with current recommendations, whereby accounting for the limited occurrence of in-hospital adverse ischemic and bleeding events. © 2013 Wiley Periodicals, Inc.
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Human long bone development in vivo: analysis of the distal femoral epimetaphysis on MR images of fetuses.
Radiology
PUBLISHED: 02-07-2013
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To investigate human long bone development in vivo by analyzing distal femoral epimetaphyseal structures and bone morphometrics on magnetic resonance (MR) images of fetuses.
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Assessing prenatal white matter connectivity in commissural agenesis.
Brain
PUBLISHED: 02-01-2013
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Complete or partial agenesis of the corpus callosum are rather common developmental abnormalities, resulting in a wide spectrum of clinical neurodevelopmental deficits. Currently, a significant number of these cases are detected by prenatal sonography during second trimester screening examinations. However, major uncertainties about a detailed morphological diagnosis and the clinical significance do not allow accurate prenatal counselling. Here, we were able to demonstrate the 3D connectivity of aberrant commissural tracts in 16 cases with complete and four cases with partial callosal agenesis using the foetal magnetic resonance imaging techniques of diffusion tensor imaging and tractography in utero and in vivo between gestational weeks 20 and 37. The misguided pre-myelinated callosal axons that represent the bundle of Probst were non-invasively visualized, and they showed a degree of structural integrity similar to that of the callosal pathways of age-matched foetuses without cerebral pathologies. In two foetuses, we were able to prove, by post-mortem histology, that diffusion tensor imaging allows the depiction of the bundle of Probst, even during early stages of pre-myelination at 20 and 22 gestational weeks. In cases with partial callosal agenesis, an aberrant sigmoid-shaped bundle was prenatally depicted, confirming the findings of heterotopic interhemispheric connectivity in adults with partial callosal agenesis. In addition to the corpus callosum, other white matter pathways were also involved, including somatosensory and motor pathways that showed significantly higher fractional anisotropy values in cases with callosal agenesis compared with control subjects. A detailed prenatal assessment of abnormal white matter connectivity in cases of midline anomalies will help to explain and understand the clinical heterogeneity in these cases, taking future foetal neurological counselling strategies to a new level.
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Mechanisms of cyclic nucleotide phosphodiesterases in modulating T cell responses in murine graft-versus-host disease.
PLoS ONE
PUBLISHED: 01-30-2013
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Graft-versus-host disease (GvHD) is a key contributor to the morbidity and mortality after allogeneic hematopoetic stem cell transplantation (HSCT). Regulatory Foxp3(+) CD4(+) T cells (Treg) suppress conventional T cell activation and can control GvHD. In our previous work, we demonstrate that a basic mechanism of Treg mediated suppression occurs by the transfer of cyclic adenosine monophosphate (cAMP) to responder cells. Whether this mechanism is relevant for Treg mediated suppression of GvHD is currently unknown. To address this question, bone marrow and T cells from C57BL/6 mice were transferred into lethally irradiated BALB/c recipients, and the course of GvHD and survival were monitored. Transplanted recipients developed severe GvHD that was strongly ameliorated by the transfer of donor Treg cells. Towards the underlying mechanisms, in vitro studies revealed that Treg communicated with DCs via gap junctions, resulting in functional inactivation of DC by a metabolic pathway involving cAMP that is modulated by the phosphodiesterase (PDE) 4 inhibitor rolipram. PDE2 or PDE3 inhibitors as well as rolipram suppressed allogeneic T cell activation, indirectly by enhancing Treg mediated suppression of DC activation and directly by inhibiting responder T cell proliferation. In line with this, we observed a cooperative suppression of GvHD upon Treg transfer and additional rolipram treatment. In conclusion, we propose that an important pathway of Treg mediated control of GvHD is based on a cAMP dependent mechanism. These data provide the basis for future concepts to manipulate allogeneic T cell responses to prevent GvHD.
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Gadoxetate-enhanced versus diffusion-weighted MRI for fused Ga-68-DOTANOC PET/MRI in patients with neuroendocrine tumours of the upper abdomen.
Eur Radiol
PUBLISHED: 01-24-2013
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To compare fused gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI (diffusion-weighted imaging) for the assessment of abdominal neuroendocrine tumours (NETs).
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Biochemical analysis of the articular disc of the temporomandibular joint with magnetic resonance T2 mapping: a feasibility study.
Clin Oral Investig
PUBLISHED: 01-16-2013
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Symptoms of temporomandibular joint (TMJ) dysfunction can seriously compromise patients quality of life. The aim of our study was to use magnetic resonance imaging (MRI) T2 mapping of the articular disc to determine whether T2 mapping of the TMJ disc is feasible in routine clinical imaging and to assess the normal T2 relaxation time distribution within the TMJ.
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High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics.
Nat Commun
PUBLISHED: 01-08-2013
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The ever-increasing speed and resolution of modern microscopes make the storage and post-processing of images challenging and prevent thorough statistical analyses in developmental biology. Here, instead of deploying massive storage and computing power, we exploit the spherical geometry of zebrafish embryos by computing a radial maximum intensity projection in real time with a 240-fold reduction in data rate. In our four-lens selective plane illumination microscope (SPIM) setup the development of multiple embryos is recorded in parallel and a map of all labelled cells is obtained for each embryo in <10 s. In these panoramic projections, cell segmentation and flow analysis reveal characteristic migration patterns and global tissue remodelling in the early endoderm. Merging data from many samples uncover stereotypic patterns that are fundamental to endoderm development in every embryo. We demonstrate that processing and compressing raw image data in real time is not only efficient but indispensable for image-based systems biology.
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Inference of dynamical gene-regulatory networks based on time-resolved multi-stimuli multi-experiment data applying NetGenerator V2.0.
BMC Syst Biol
PUBLISHED: 01-02-2013
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Inference of gene-regulatory networks (GRNs) is important for understanding behaviour and potential treatment of biological systems. Knowledge about GRNs gained from transcriptome analysis can be increased by multiple experiments and/or multiple stimuli. Since GRNs are complex and dynamical, appropriate methods and algorithms are needed for constructing models describing these dynamics. Algorithms based on heuristic approaches reduce the effort in parameter identification and computation time.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.