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Find video protocols related to scientific articles indexed in Pubmed.
Thymic hyperplasia following chemotherapy in adults with lymphoma: (18)F-FDG PET/CT findings and correlation with the T cell repopulation.
Leuk. Lymphoma
PUBLISHED: 11-20-2014
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Abstract Thymic hyperplasia (TH) after chemotherapy is an infrequent phenomenon in adults. This study analyzed the incidence and metabolic activity of TH on (18)F fluorodeoxyglucose ((18)F FDG) positron emission tomography / computed tomography (PET/CT) in this population. By reviewing 471 PET/CT recordings of 211 adults with lymphoma, increased FDG uptake within an enlarged thymus regarded as TH was observed in 27 patients aged 18-53 years. FDG uptake in hyperplasic thymus was mild and diffuse, with a maximum standard uptake value (SUVmax) of 2.6±0.9. Its intensity varied with different occurring times following chemotherapy. In addition, by comparing the recovery of T cell subsets in patients with TH (n=20) and without TH (n=28), no impact of the presence of TH was found on the repopulation of total CD4(+) and CD8(+) T cells within the first year after treatment. These data may be helpful to avoid misinterpretation of increased thymic uptake in adults.
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Edwardsiella tarda MliC: a lysozyme inhibitor that participates in pathogenesis in a manner that parallels Ivy.
Infect. Immun.
PUBLISHED: 11-19-2014
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Edwardsiella tarda, a bacterial pathogen to farmed fish as well as humans, possesses the genes of two lysozyme inhibitors, i.e. ivyEt and mliCEt. We have recently studied IvyEt and found it implicated in E. tarda virulence. In the present study, we characterized MliCEt in comparison with IvyEt in a turbot model. MliCEt contains the FWSKG motif and two cysteines (C33 and C98) that are highly conserved in subgroup I MliC but unknown in functional importance. To examine the essentialness of these conserved structural features, recombinant MliCEt (rMliC) and its mutants bearing C33S and W79A (of the FWSKG motif) substitutions were prepared. Subsequent analysis showed that rMliC (i) inhibited lysozyme-induced lysis of a Gram-positive bacterium, (ii) reduced serum-facilitated lysozyme killing of E. tarda, and (iii), when introduced into turbot, promoted bacterial dissemination in fish tissues. C33S mutation had no influence on the activity of rMliC, while W79A mutation slightly but significantly enhanced the activity of rMliC. Both the mliCEt (TX?mliC) and the ivyEt knockouts were severely attenuated in the ability of tissue invasion, host lethality, serum surviving, and intracellular replication. The lost virulence of TX?mliC was restored by complementation with an introduced mliCEtgene. Compared to ivyEt or mliCEt single knockout, mliCEt-ivyEt double knockout was significantly impaired in most of the virulence features. Together these results provide the first evidence that the conserved cysteine is functionally dispensable to a subgroup 1 MliC, and that as a virulence factor, MliCEt most likely works in a concerted and parallel manner with Ivy.
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Frequency of and risk factors associated with catastrophic musculoskeletal injuries in Quarter Horses at two Midwestern racetracks: 67 cases (2000-2011).
J. Am. Vet. Med. Assoc.
PUBLISHED: 10-31-2014
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Objective-To determine the incidence and anatomic location of and potential risk factors for catastrophic musculoskeletal injuries (CMIs) in racing Quarter Horses. Design-Retrospective matched case-control study. Animals-67 racing Quarter Horse racehorses euthanized because of CMIs and 134 matched controls. Procedures-Data for Quarter Horses that sustained CMIs and the total number of race starts for each year were obtained from 2 Midwestern racing jurisdictions from 2000 through 2011. Information for each horse with a CMI and for 2 randomly selected control horses that ran in the same race but did not incur a CMI were obtained from race records, past performance reports, and video analysis. Results-There were 61,797 race starts and 82 CMIs from 2000 through 2011 at the 2 racetracks studied, for an overall CMI incidence of 1.33 CMIs/1,000 starts. Sixty-seven horses with CMIs for which complete data were available and 134 matched control horses were included in the study. There was no difference in the incidence of CMIs between the 2 racetracks or over the years studied. The right forelimb was injured in 38 of the 67 (56.7%) horses. Injures to the carpus (24/67 [35.8%]) and metacarpophalangeal joint (fetlock joint; 23/67 [34.3%]) occurred most frequently. Case-control data indicated that the horses with a CMI had fewer starts, were more likely to have stumbled at the break, had a more erratic stride, were fatigued, and trailed in the race, compared with matched controls from the same races. Irrespective of race distance, most of the horses (47/67 [70.1%]) were injured after or within 10 yards before the finish line. Conclusions and Clinical Relevance-The results of the present study may aid in the identification of racing Quarter Horses at risk for CMIs. The cluster of injuries near the finish line provides a specific focus for future research into methods of injury prevention in this population of racehorses.
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Integrating GO and KEGG terms to characterize and predict acute myeloid leukemia-related genes.
Hematology
PUBLISHED: 10-25-2014
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Background/objective Acute myeloid leukemia (AML) is a progressive and malignant cancer of myelogenous blood cells, which disturbs the production of normal blood cells. Although several risk and genetic factors (AML-related genes) have been investigated, the concrete mechanism underlying the development of AML remains unclear. In view of this, it is crucial to develop an effective computational method for meaningfully characterizing AML genes and accurately predicting novel AML genes. Methods In this study, we integrated gene ontology (GO) and KEGG annotations as features to characterize AML genes. We also provided an optimal set of features for predicting AML-related genes by using the minimum redundancy maximum relevance (mRMR) algorithm and dagging metaclassifier. Results We obtained 26 optimal GO terms that characterized AML genes well. Finally, we predicted 464 novel genes to provide clinical researchers with additional candidates and useful insights for further analysis of AML. Discussion An in-depth feature analysis indicated that the results are quite consistent with previous knowledge. We developed a systematic method to identify the possible underlying mechanism of AML by analyzing the related genes. Our method has the ability to identify the types of features that are optimal to meaningfully interpret AML and accurately predict more AML genes for further clinical researches.
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Stratospheric temperature measurement with scanning Fabry-Perot interferometer for wind retrieval from mobile Rayleigh Doppler lidar.
Opt Express
PUBLISHED: 10-17-2014
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Temperature detection remains challenging in the low stratosphere, where the Rayleigh integration lidar is perturbed by aerosol contamination and ozone absorption while the rotational Raman lidar is suffered from its low scattering cross section. To correct the impacts of temperature on the Rayleigh Doppler lidar, a high spectral resolution lidar (HSRL) based on cavity scanning Fabry-Perot Interferometer (FPI) is developed. By considering the effect of the laser spectral width, Doppler broadening of the molecular backscatter, divergence of the light beam and mirror defects of the FPI, a well-behaved transmission function is proved to show the principle of HSRL in detail. Analysis of the statistical error of the HSRL is carried out in the data processing. A temperature lidar using both HSRL and Rayleigh integration techniques is incorporated into the Rayleigh Doppler wind lidar. Simultaneous wind and temperature detection is carried out based on the combined system at Delhi (37.371°N, 97.374°E; 2850 m above the sea level) in Qinghai province, China. Lower Stratosphere temperature has been measured using HSRL between 18 and 50 km with temporal resolution of 2000 seconds. The statistical error of the derived temperatures is between 0.2 and 9.2 K. The temperature profile retrieved from the HSRL and wind profile from the Rayleigh Doppler lidar show good agreement with the radiosonde data. Specifically, the max temperature deviation between the HSRL and radiosonde is 4.7 K from 18 km to 36 km, and it is 2.7 K between the HSRL and Rayleigh integration lidar from 27 km to 34 km.
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Influence of bony resection margins and surgicopathological factors on outcomes in limb-sparing surgery for extremity osteosarcoma.
Pediatr Blood Cancer
PUBLISHED: 09-19-2014
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Limb-sparing surgery for osteosarcoma requires taking wide bony resection margins while maximizing preservation of native bone and joint. However, the optimal bony margin and factors associated with recurrence and survival outcomes in these patients are not well established.
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Anti-Inflammatory Drugs and Risk of Alzheimer's Disease: An Updated Systematic Review and Meta-Analysis.
J. Alzheimers Dis.
PUBLISHED: 09-18-2014
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Background: In the past 20 years, substantial evidence from laboratory and epidemiologic studies have suggested that anti-inflammatory medications could defer or prevent the occurrence of Alzheimer's disease (AD). However, several studies do not corroborate these findings. Objective: To evaluate the association of anti-inflammatory drug use on the incidence of AD. Methods: Pubmed, Embase, and Cochrane Library databases were searched up to March 2014. Studies evaluating the association between use of anti-inflammatory drugs and AD risk were included. Relative risks (RRs) with 95% confidence intervals (CIs) were meta-analyzed using random effects models and were grouped by anti-inflammatory type and duration of drug use. Results: In observational studies, use of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with a reduced risk of AD (RR, 0.72; 95%CI, 0.62-0.84) compared to no use of NSAIDs, especially in long term users (RR, 0.36; 95%CI, 0.17-0.74); the risks of AD were also lower in both aspirin (RR, 0.77; 95%CI, 0.63-0.95) and non-aspirin NSAID users (RR, 0.65; 95%CI, 0.47-0.88) compared with nonusers; whereas the use of corticosteroids showed no significant association (RR, 0.62; 95%CI, 0.26-1.46). In the single randomized controlled trial (RCT), NSAID use showed no significant effect on AD risk among dementia-free individuals (p > 0.05). Conclusion: Observational studies support the use of NSAIDs for prevention of AD, but RCT do not. Well-designed studies and innovative approaches are required to illuminate the exact relationship between NSAID use and AD risk. The appropriate dosage and duration of use to benefit and the safety are also needed to determine.
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Redescription of Protoopalina pingi Nie, 1935 inhabiting the recta of Hylarana guentheri and Pelophylax nigromaculatus in China.
Parasite
PUBLISHED: 09-12-2014
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A redescription of Protoopalina pingi Nie, 1935 is presented in this paper to complete Nie's description at both light and scanning electron microscope levels. These organisms were collected from the recta of the frogs Hylarana guentheri Boulenger, 1882 and Pelophylax nigromaculatus Hallowell, 1861 from Jialing River, Sichuan Province and Honghu Lake, Hubei Province, respectively, in China. This is the first record of its occurrence in H. guentheri and P. nigromaculatus. The body of P. pingi is elongated and somewhat spindle-like in shape, slightly narrowed and bluntly rounded at the anterior extremity, while the posterior end is tapering or sharply pointed. The body surface is thickly flagellated, with the caudal tip being barren. The falx, located at the margin of the anterior end, is composed of a narrow band of kinetosomes. Four round or oval-shaped nuclei, usually arranged in a straight line, are situated in the middle region of the body. Comparisons are made between P. pingi and its congeners.
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Physiotherapy Intervention in Alzheimer's Disease: Systematic Review and Meta-Analysis.
J. Alzheimers Dis.
PUBLISHED: 09-10-2014
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Background: Many studies reported that physiotherapy interventions are available to treat Alzheimer's disease (AD), but the efficacy remains uncertain. Objective: To evaluate the effectiveness of physiotherapy intervention on AD. Methods: The data sources were searched from literature databases, journals, and reference lists from 1 January 1990 to the end of 1 April 2014. Randomized and non-randomized controlled trials with physiotherapy intervention were included in our meta-analysis. Jadad score and Newcastle-Ottawa scale were used to assess the quality of included trials. Outcome measures were cognition function, physical function, activity of daily life (ADL) and neuropsychiatric inventory (NPI). Results: 23 trials met the inclusion standard finally. Significant changes were seen in cognitive function: Mini-Mental State Examination score (weighted mean difference (WMD): 1.84, 95% confidence interval (CI): [0.76, to, 2.93], p < 0.0001), and verbal fluency (standard mean difference (SMD): 0.34, 95% CI: [0.01 to 0.66], p = 0.04). Other outcomes are also significant, they were timed up and go test (SMD: 0.56, 95% CI: [0.30 to 0.83], p < 0.0001), berg functional balance scale (SMD: 1.11, 95% CI: [0.37 to 1.84], p = 0.003), 6-min walk distance test (SMD: 141.45, 95% CI: [11.72 to 271.18], p = 0.03), ADL (SMD: 0.78, 95% CI: [0.33 to 1.23], p = 0.0007) and NPI (SMD: -0.69, 95% CI: [-1.31 to -0.07], p = 0.03). Conclusion: The available data indicate that physiotherapy intervention may have benefits in AD. However, current data are not definitive; more carefully designed and conducted observational studies are needed to definitively establish that whether physiotherapy intervention can effectively alleviate symptoms of AD.
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[The drug-drug interaction mediated by efflux transporters and CYP450 enzymes].
Yao Xue Xue Bao
PUBLISHED: 08-26-2014
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Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-glycoprotein (P-gp), multidrug resistance associated protein (MRP) and breast cancer resistance protein (BCRP) in conjunction with metabolizing enzymes (cytochrome P450, CYP450) are major factors in such interaction. In recent years, a large number of studies have shown that P-gp plays a role in the oxidative metabolism of its substrates that are also substrates of CYP3A4. Combined actions of P-gp and CYP3A could account in some part for the low oral bioavailability determined for many of these dual substrates. P-gp along with efflux transporters (MRP and BCRP) having overlapping substrate specificity plays critical role in drug disposition. The relationship between MRP or BCRP and CYP3A is similar to that between P-gp and CYP3A. In this paper, we summarize the classification of efflux transporters, the main metabolizing enzymes CYP3A, clinical significance interactions mediated by efflux transporters and CYP450 enzymes and in vitro studies.
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The role of telomeres and telomerase in hematologic malignancies and hematopoietic stem cell transplantation.
J Hematol Oncol
PUBLISHED: 08-20-2014
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Telomeres are specific nucleoprotein structures at the ends of eukaryotic chromosomes. Telomeres and telomere-associated proteins maintain genome stability by protecting the ends of chromosomes from fusion and degradation. In normal somatic cells, the length of the telomeres gradually becomes shortened with cell division. In tumor cells, the shortening of telomeres length is accelerated under the increased proliferation pressure. However, it will be maintained at an extremely short length as the result of activation of telomerase. Significantly shortened telomeres, activation of telomerase, and altered expression of telomere-associated proteins are common features of various hematologic malignancies and are related with progression or chemotherapy resistance in these diseases. In patients who have received hematopoietic stem cell transplantation (HSCT), the telomere length and the telomerase activity of the engrafted donor cells have a significant influence on HSCT outcomes. Transplantation-related factors should be taken into consideration because of their impacts on telomere homeostasis. As activation of telomerase is widespread in tumor cells, it has been employed as a target point in the treatment of neoplastic hematologic disorders. In this review, the characteristics and roles of telomeres and telomerase both in hematologic malignancies and in HSCT will be summarized. The current status of telomerase-targeted therapies utilized in the treatment of hematologic malignancies will also be reviewed.
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Ultrastructural study of Balantidium ctenopharyngodoni Chen, 1955 (Class: Litostomatea) from China with an emphasis on its vestibulum.
Acta Parasitol.
PUBLISHED: 08-15-2014
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A detailed description of the fine structure of Balantidium ctenopharyngodoni Chen, 1955 with an emphasis on its vestibulum is given in the present paper. As to the vestibular kinetids, special attention is paid to the characters of T1, T2 microtubules and nematodesmata. Serving as the major skeleton to the vestibular cortex, the T1, T2 and Pc microtubules are described herein and their support function is also discussed. Moreover, the well-developed nematodesmata of the vestibular kinetids that form a large basket-like complex are described in detail.
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FAK is required for tension-dependent organization of collective cell movements in Xenopus mesendoderm.
Dev. Biol.
PUBLISHED: 08-13-2014
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Collective cell movements are integral to biological processes such as embryonic development and wound healing and also have a prominent role in some metastatic cancers. In migrating Xenopus mesendoderm, traction forces are generated by cells through integrin-based adhesions and tension transmitted across cadherin adhesions. This is accompanied by assembly of a mechanoresponsive cadherin adhesion complex containing keratin intermediate filaments and the catenin-family member plakoglobin. We demonstrate that focal adhesion kinase (FAK), a major component of integrin adhesion complexes, is required for normal morphogenesis at gastrulation, closure of the anterior neural tube, axial elongation and somitogenesis. Depletion of zygotically expressed FAK results in disruption of mesendoderm tissue polarity similar to that observed when expression of keratin or plakoglobin is inhibited. Both individual and collective migrations of mesendoderm cells from FAK depleted embryos are slowed, cell protrusions are disordered, and cell spreading and traction forces are decreased. Additionally, keratin filaments fail to organize at the rear of cells in the tissue and association of plakoglobin with cadherin is diminished. These findings suggest that FAK is required for the tension-dependent assembly of the cadherin adhesion complex that guides collective mesendoderm migration, perhaps by modulating the dynamic balance of substrate traction forces and cell cohesion needed to establish cell polarity.
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Efficacy and Adverse Effects of Ginkgo Biloba for Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis.
J. Alzheimers Dis.
PUBLISHED: 08-11-2014
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Background: Research into Ginkgo biloba has been ongoing for many years, while the benefit and adverse effects of Ginkgo biloba extract EGb761 for cognitive impairment and dementia has been discussed controversially. Objective: To discuss new evidence on the clinical and adverse effects of standardized Ginkgo biloba extract EGb761 for cognitive impairment and dementia. Methods: MEDLINE, EMBASE, Cochrane, and other relevant databases were searched in March 2014 for eligible randomized controlled trials of Ginkgo biloba EGb761 therapy in patients with cognitive impairment and dementia. Results: Nine trials met our inclusion criteria. Trials were of 22-26 weeks duration and included 2,561 patients in total. In the meta-analysis, the weighted mean differences in change scores for cognition were in favor of EGb761 compared to placebo (-2.86, 95%CI -3.18; -2.54); the standardized mean differences in change scores for activities in daily living (ADLs) were also in favor of EGb761 compared to placebo (-0.36, 95%CI -0.44; -0.28); Peto OR showed a statistically significant difference from placebo for Clinicians' Global Impression of Change (CGIC) scale (1.88, 95%CI 1.54; 2.29). All these benefits are mainly associated with EGb761 at a dose of 240 mg/day. For subgroup analysis in patients with neuropsychiatric symptoms, 240 mg/day EGb761 improved cognitive function, ADLs, CGIC, and also neuropsychiatric symptoms with statistical superiority than for the whole group. For the Alzheimer's disease subgroup, the main outcomes were almost the same as the whole group of patients with no statistical superiority. Finally, safety data revealed no important safety concerns with EGb761. Conclusions: EGb761 at 240 mg/day is able to stabilize or slow decline in cognition, function, behavior, and global change at 22-26 weeks in cognitive impairment and dementia, especially for patients with neuropsychiatric symptoms.
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Association between Stroke and Alzheimer's Disease: Systematic Review and Meta-Analysis.
J. Alzheimers Dis.
PUBLISHED: 08-07-2014
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Alzheimer's disease (AD) and stroke are common disorders of aging, but the relationship between these two disorders remains uncertain. Recent evidence recognized that they frequently co-occur and are influenced by each another, while other studies have produced inconsistent results. We conducted this systematic review and meta-analysis of stroke on risk for AD and AD on risk for stroke subtypes to clarify the relation between these two disorders on the basis of the studies published from 1975 to November 2013 in the PubMed, EMBASE, and Cochrane Library databases. In total, 7 cohort studies and 2 nested case-control studies met the inclusion criteria for meta-analysis. For stroke, the pooled effect size for AD risk was 1.59 (95% CI 1.25-2.02; z = 3.76; p = 0.000). For AD dementia, it was not associated with risk of all strokes or ischemic stroke (IS), but the risk of intracerebral hemorrhage (ICH was higher among persons with AD. The pooled RR for AD in relation to incident IS did not indicate a significant association (RR: 1.13; 95% CI 0.75-1.70; z = 0.58; p = 0.565). The pooled effect size for AD and ICH risk was 1.41 (95% CI 1.21-1.66; z = 4.27; p < 0.001). Stroke significantly and independently increased risk for AD and in turn AD increased risk for ICH. These results confirm that AD and ICH may have common pathogenesis and share preventive treatment measures.
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Society of Thoracic Surgeons 2008 cardiac risk models predict in-hospital mortality of heart valve surgery in a Chinese population: A multicenter study.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 08-06-2014
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The Society of Thoracic Surgeons 2008 cardiac surgery risk models have been developed for heart valve surgery with and without coronary artery bypass grafting. The aim of our study was to evaluate the performance of Society of Thoracic Surgeons 2008 cardiac risk models in Chinese patients undergoing single valve surgery and the predicted mortality rates of those undergoing multiple valve surgery derived from the Society of Thoracic Surgeons 2008 risk models.
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Association of ATM Gene Polymorphism with PTC Metastasis in Female Patients.
Int J Endocrinol
PUBLISHED: 08-05-2014
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Ataxia telangiectasia mutated (ATM) gene is critical in the process of recognizing and repairing DNA lesions and is related to invasion and metastasis of malignancy. The incidence rate of papillary thyroid cancer (PTC) has increased for several decades and is higher in females than males. In this study, we want to investigate whether ATM polymorphisms are associated with gender-specific metastasis of PTC. 358 PTC patients in Northern China, including 109 males and 249 females, were included in our study. Four ATM single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Association between genotypes and the gender-specific risk of metastasis was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis. Significant associations were observed between rs189037 and metastasis of PTC in females under different models of inheritance (codominant model: OR = 0.15, 95% CI 0.04-0.56, P = 0.01 for GA versus GG and OR = 0.08, 95% CI 0.01-0.74, P = 0.03 for AA versus GG, resp.; dominant model: OR = 0.49, 95% CI 0.25-0.98, P = 0.04; overdominant model: OR = 0.47, 95% CI 0.25-0.89, P = 0.02). However, no association remained significant after Bonferroni correction. Our findings suggest a possible association between ATM rs189037 polymorphisms and metastasis in female PTCs.
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Serum protein S9, SOD3 and MMP9 as new diagnostic biomarkers for pulmonary tuberculosis by iTRAQ-coupled two-dimensional LC-MS/MS.
Proteomics
PUBLISHED: 07-31-2014
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This study aimed to discover the novel non-invasive biomarkers for the diagnosis of pulmonary tuberculosis (TB). We applied iTRAQ 2D LC-MS/MS technique to investigate protein profiles in patients with pulmonary TB and other lung diseases. A total of 34 differentially expressed proteins (24 up-regulated proteins and 10 down-regulated proteins) were identified in the serum of pulmonary TB patients. Significant differences in protein S100-A9 (S100A9), extracellular superoxide dismutase [Cu-Zn] (SOD3), and matrix metalloproteinase 9 (MMP9) were found between pulmonary TB and other lung diseases by ELISA. Correlations analysis revealed that the serum concentration of MMP9 in the pulmonary TB was in moderate correlation with SOD3 (r = 0.581) and S100A9 (r = 0.471), while SOD3 was in weak correlation with S100A9 (r = 0.287). The combination of serum S100A9, SOD3, and MMP9 levels could achieve 92.5% sensitivity and 95% specificity to discriminate between pulmonary TB and healthy controls, 90% sensitivity and 87.5% specificity to discriminate between pulmonary TB and pneumonia, and 85% sensitivity and 92.5% specificity to discriminate between pulmonary TB and lung cancer, respectively. The results showed that S100A9, SOD3, and MMP9 may be potential diagnostic biomarkers for pulmonary TB, and provided experimental basis for the diagnosis of pulmonary TB. This article is protected by copyright. All rights reserved.
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CEBPE polymorphism confers an increased risk of childhood acute lymphoblastic leukemia: a meta-analysis of 11 case-control studies with 5,639 cases and 10,036 controls.
Ann. Hematol.
PUBLISHED: 07-28-2014
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The association between CCAAT/enhancer binding protein-? (CEBPE) rs2239633 polymorphism and acute lymphoblastic leukemia (ALL) risk has been reported, but results of previous studies remain controversial and ambiguous. To assess the association between CEBPE rs2239633 polymorphism and childhood ALL risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM), we identified outcome data from all articles estimating the association between CEBPE rs2239633 polymorphism and childhood ALL risk. The pooled odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. A significant association between CEBPE rs2239633 polymorphism with childhood ALL was found (OR?=?1.19, 95 % CI 1.11-1.28, P?
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Characterization of the porcine epidemic diarrhea virus codon usage bias.
Infect. Genet. Evol.
PUBLISHED: 07-26-2014
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Porcine epidemic diarrhea virus (PEDV) has been responsible for several recent outbreaks of porcine epidemic diarrhea (PED) and has caused great economic loss in the swine-raising industry. Considering the significance of PEDV, a systemic analysis was performed to study its codon usage patterns. The relative synonymous codon usage value of each codon revealed that codon usage bias exists and that PEDV tends to use codons that end in T. The mean ENC value of 47.91 indicates that the codon usage bias is low. However, we still wanted to identify the cause of this codon usage bias. A correlation analysis between the codon compositions (A3s, T3s, G3s, C3s, and GC3s), the ENC values, and the nucleotide contents (A%, T%, G%, C%, and GC%) indicated that mutational bias plays role in shaping the PEDV codon usage bias. This was further confirmed by a principal component analysis between the codon compositions and the axis values. Using the Gravy, Aroma, and CAI values, a role of natural selection in the PEDV codon usage pattern was also identified. Neutral analysis indicated that natural selection pressure plays a more important role than mutational bias in codon usage bias. Natural selection also plays an increasingly significant role during PEDV evolution. Additionally, gene function and geographic distribution also influence the codon usage bias to a degree.
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Detection of antibodies against porcine epidemic diarrhea virus in serum and colostrum by indirect ELISA.
Vet. J.
PUBLISHED: 07-24-2014
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An indirect porcine epidemic diarrhea virus (PEDV) anti-immunoglobulin (Ig) G ELISA based on the S1 portion of the spike protein was validated and compared with an indirect immunofluorescence assay. In serum samples from experimentally infected pigs (n?=?35), anti-IgG PEDV antibodies were detected as early as 7 days post-infection. In field serum samples (n?=?239), the diagnostic sensitivity of the S1 ELISA was 100% and the diagnostic specificity was 94%. The S1 ELISA showed no cross-reactivity with antibodies against other porcine coronaviruses. Colostrum samples (n?=?133) were also tested for anti-PEDV IgG and IgA. The diagnostic sensitivity was 92% for IgG and 100% for IgA, and the diagnostic specificity was 90% for IgG and 99.4% for IgA. These data suggest that the S1 ELISA is a sensitive and specific test that could also be used to evaluate PEDV colostral immunity.
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Annexin A2 knockdown inhibits hepatoma cell growth and sensitizes hepatoma cells to 5?fluorouracil by regulating ??catenin and cyclin D1 expression.
Mol Med Rep
PUBLISHED: 07-22-2014
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Hepatocellular carcinoma (HCC) is one of the most common cancer types, and chemotherapy plays an important role in treatment of HCC. However, long?term treatment with chemotherapeutic drugs such as 5?fluorouracil (5?FU) often results in chemoresistance, and the underlying mechanisms remain unclear. In this study, we showed that the annexin A2 (ANXA2) protein is highly expressed in hepatoma cells compared to healthy cells. Knockdown of the ANXA2 gene inhibited hepatoma cell growth, and the underlying mechanism may involve cell cycle inhibition through downregulation of ??catenin and cyclin D1. We also investigated the role of ANXA2 in chemotherapeutic treatment with 5?FU. 5?FU inhibited hepatoma cell growth, while ANXA2 overexpression reduced, and knockdown enhanced, the effects of 5?FU on hepatoma cell growth. Furthermore, ??catenin and cyclin D1 were asscociated with the ANXA2?induced resistance. Taken together, our data suggest that the ANXA2 protein is a critical factor in HCC and that its downregulation can enhance chemotherapeutic treatment with 5?FU. ANXA2 may thus constitute a new therapeutic target for HCC.
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Midlife vascular risk factors and the risk of Alzheimer's disease: a systematic review and meta-analysis.
J. Alzheimers Dis.
PUBLISHED: 07-16-2014
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We examine whether midlife vascular risk factors (VRFs) are associated with increased risk of incident Alzheimer's disease (AD) in a systematic review and meta-analysis of published cohort studies.
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High-voltage and high-rate symmetric supercapacitor based on MnO2-polypyrrole hybrid nanofilm.
Nanotechnology
PUBLISHED: 07-10-2014
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A manganese oxide (MnO(2)) nanosheet film, hybridized with a conducting polymer polypyrrole (PPy), was prepared through the direct reaction of a carbon cloth with potassium permanganate (KMnO(4)) and through the subsequent chemical polymerization; this type of prepared nanosheet has been used as an electrode for symmetric supercapacitors. The influence of the reaction time in the KMnO(4) solution on the capacitive property of the MnO(2) film was systematically investigated. Further experimentation revealed that the PPy with the high electrical conductivity had promoted the charge transfer in the MnO(2) nanofilm and had played an important role in enhancing the electrode performance (?45.6 mF cm(-2)). An areal capacitance of 25.9 mF cm(-2) and an excellent rate performance (?50.08% of the initial capacitance when the scan rate increases 100 times from 2.5 to 250 mV s(-1)) can be achieved for an aqueous symmetric supercapacitor that is assembled from the MnO(2)-PPy nanofilm. In particular, an operating voltage of 1.2 V can be delivered by choosing an appropriate electrolyte; this voltage level is much larger than that of traditional aqueous symmetric supercapacitors (?1.0 V) and contributes to a high energy density (?3.5 ?Wh cm(-2)). Under such a high output voltage, the device can still maintain ?86.21% of the initial capacitance, even after 2000 cycles.
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Occurrence and distribution of sulfonamides, tetracyclines, quinolones, macrolides, and nitrofurans in livestock manure and amended soils of Northern China.
Environ Sci Pollut Res Int
PUBLISHED: 06-29-2014
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A feasible and rapid analysis for the simultaneous determination of sulfonamides (SAs), tetracyclines (TCs), fluoroquinolones (FQs), macrolides (MACs) and nitrofurans (NFs) in livestock manure and soils was established by solid-phase extraction (SPE)-ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS). A total of 32 manure and 17 amended soil samples from the Liaoning and Tianjin areas in Northern China were collected for analysis. The largest detected frequencies and concentrations in manure samples were those of TCs (3326.6?±?12,302.6 ?g/kg), followed by FQs (411.3?±?1453.4 ?g/kg), SAs (170.6?±?1060.2 ?g/kg), NFs (85.1?±?158.1 ?g/kg), and MACs (1.4?±?4.8 ?g/kg). In general, veterinary antibiotics (VAs) were detected with higher concentrations in swine and chicken manure than in cattle manure, reflecting the heavy usage of VAs in swine and chicken husbandry in the studied area. Furthermore, higher residues of antibiotics were found in piglet and fattening swine manure than in sow manure. In addition, TCs were the most frequently (100 %) detected antibiotics in amended soil with higher concentrations (up to 10,967.1 ?g/kg) than any other VAs. The attenuation of SAs was more obvious than TCs in amended soil after fertilization, which can most likely be attributed to the stronger sorption of TCs than SAs to soil organic matter through cation exchange. This study illustrated the prevalence of TCs detected in both animal manure and fertilized agricultural soils in Northern China, which may increase the risk to human health through the food chain. Thus, TCs should be given more attention in the management of veterinary usage in livestock husbandry.
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Aprepitant reduces chemotherapy-induced vomiting in children and young adults with brain tumors.
J Pediatr Oncol Nurs
PUBLISHED: 06-27-2014
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Chemotherapy-induced nausea and vomiting are common and distressing side effects in patients with brain tumors and may be associated with radiation and the administration of highly emetogenic chemotherapy (HEC). Pediatric antiemetic guidelines recommend administration of a 5-hydroxytryptamine-3 (5HT3) receptor antagonists and the addition of aprepitant, a neurokinin 1 (NK1) antagonist with corticosteroids for the treatment of HEC. However, challenges persist in treating chemotherapy-induced nausea and vomiting in patients with brain tumors as corticosteroids are contraindicated due to potential impairment of the blood-brain barrier permeability. The objective was to determine whether a 5HT3 receptor antagonist and the addition of aprepitant, an NK1 antagonist without a corticosteroid, were effective in reducing HEC vomiting in pediatric brain tumor patients.
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Phase I Clinical Trial of Ifosfamide, Oxaliplatin, and Etoposide (IOE) in Pediatric Patients With Refractory Solid Tumors.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 06-20-2014
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Oxaliplatin, although related to cisplatin and carboplatin, has a more favorable toxicity profile and may offer advantages in combination regimens. We combined oxaliplatin, ifosfamide, and etoposide (IOE) and estimated the regimen's maximum tolerated dose (MTD) in children with refractory solid tumors. Dose-limiting toxicity (DLT) and MTD were assessed at 3 dose levels in a 21-day regimen: day 1, oxaliplatin 130 mg/m (consistent dose); days 1 to 3, ifosfamide 1200 mg/m/d (level 0) or 1500 mg/m/d (levels 1 and 2) and etoposide 75 mg/m/d (levels 0 and 1) or 100 mg/m/d (level 2). Course 1 filgrastim/pegfilgrastim was permitted after initial DLT determination, if neutropenia was dose limiting. Seventeen patients received 59 courses. Without filgrastim (n=9), DLT was neutropenia in 2 patients at dose level 1. No DLT was observed after adding filgrastim (n=8). There was no ototoxicity, nephrotoxicity >grade 1, or neurotoxicity >grade 2. One patient experienced a partial response and 9 had stable disease after 2 courses. In conclusion, the IOE regimen was well tolerated. Without filgrastim, neutropenia was dose limiting with MTD at ifosfamide 1200 mg/m/d and etoposide 75 mg/m/d. The MTD with filgrastim was not defined due to early study closure. Filgrastim allowed ifosfamide and etoposide dose escalation and should be included in future studies.
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Non-pharmacological interventions for patients with mild cognitive impairment: a meta-analysis of randomized controlled trials of cognition-based and exercise interventions.
J. Alzheimers Dis.
PUBLISHED: 06-15-2014
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Non-pharmacological interventions, including cognition-based intervention and physical exercise, are available for mild cognitive impairment (MCI), but their efficacy remains uncertain.
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Femtosecond crystallography of membrane proteins in the lipidic cubic phase.
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
PUBLISHED: 06-11-2014
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Despite recent technological advances in heterologous expression, stabilization and crystallization of membrane proteins (MPs), their structural studies remain difficult and require new transformative approaches. During the past two years, crystallization in lipidic cubic phase (LCP) has started gaining a widespread acceptance, owing to the spectacular success in high-resolution structure determination of G protein-coupled receptors (GPCRs) and to the introduction of commercial instrumentation, tools and protocols. The recent appearance of X-ray free-electron lasers (XFELs) has enabled structure determination from substantially smaller crystals than previously possible with minimal effects of radiation damage, offering new exciting opportunities in structural biology. The unique properties of LCP material have been exploited to develop special protocols and devices that have established a new method of serial femtosecond crystallography of MPs in LCP (LCP-SFX). In this method, microcrystals are generated in LCP and streamed continuously inside the same media across the intersection with a pulsed XFEL beam at a flow rate that can be adjusted to minimize sample consumption. Pioneering studies that yielded the first room temperature GPCR structures, using a few hundred micrograms of purified protein, validate the LCP-SFX approach and make it attractive for structure determination of difficult-to-crystallize MPs and their complexes with interacting partners. Together with the potential of femtosecond data acquisition to interrogate unstable intermediate functional states of MPs, LCP-SFX holds promise to advance our understanding of this biomedically important class of proteins.
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Association between cancer and Alzheimer's disease: systematic review and meta-analysis.
J. Alzheimers Dis.
PUBLISHED: 06-08-2014
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This study examined the association between cancer and Alzheimer's disease (AD) by a quantitative meta-analysis of cohort studies. Studies were identified by searching PubMed database through 1966 to December 2013 using the terms "Alzheimer's disease", "neoplasm", and "cancer". Six studies met the inclusion criteria in the overall meta-analysis. We pooled effect sizes using fixed-effects and random-effects models. Furthermore, we also tested for heterogeneity and publication bias. The results suggested that individuals diagnosed with AD had a decreased risk for incident cancer by 42% (95% CI, 0.40-0.86; p < 0.05), and patients with a history of cancer had a 37% decreased risk of AD (RR = 0.63; 95% CI, 0.56-0.72; p = 0.495). The Egger's test for publication bias (p = 0.280) showed no significant evidence for bias in the data from studies on AD and cancer risk. In summary, our meta-analysis demonstrated an inverse association between cancer and AD.
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BRG1 overexpression in smooth muscle cells promotes the development of thoracic aortic dissection.
BMC Cardiovasc Disord
PUBLISHED: 06-06-2014
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Here we investigated Brahma-related gene 1 (BRG1) expression in aortic smooth muscle cells (SMCs) and its role in the regulation of the pathological changes in aortic SMCs of thoracic arotic dissection (TAD).
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Pharmacological treatment of neuropsychiatric symptoms in Alzheimer's disease: a systematic review and meta-analysis.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 05-31-2014
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A wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms, which are common in Alzheimer's disease (AD), but results from randomised controlled trials (RCTs) on the efficacy and safety of these agents are conflicting.
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APOE genotype and neuroimaging markers of Alzheimer's disease: systematic review and meta-analysis.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 05-20-2014
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We aimed to examine the association of apolipoprotein E (APOE) ?4 genotype with neuroimaging markers of Alzheimer's disease: hippocampal volume, brain amyloid deposition and cerebral metabolism.
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Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 05-16-2014
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Recently, several large randomised controlled trials about the treatments of cognitive impairment or dementia due to Parkinson's disease (CIND-PD or PDD) and dementia with Lewy bodies (DLB) were completed. Here, we systematically reviewed the studies (including the recent reports) to provide updated evidence for the treatments of CIND-PD, PDD and DLB.
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Maternal bisphenol a diet induces anxiety-like behavior in female juvenile with neuroimmune activation.
Toxicol. Sci.
PUBLISHED: 05-13-2014
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Maternal Bisphenol A (BPA) diet triggers anxiety in rodents, but the underlying mechanism is still unclear. Accumulating epidemiological and experimental data have demonstrated that the anxiety is associated with aberrant neuroimmune response. In this study, we found that maternal BPA diet (MBD) exacerbated anxiety-like behavior in female juvenile mice, and the molecular evidence further showed that this behavioral phenotype was connected to the neuroimmune activation, such as elevated tumor necrosis factor alpha (TNF-?) and interleukin (IL)-6 levels in prefrontal cortex (PFC) rather than in peripheral blood, which indicated that neuroimmune response might be ascribed to neuroglial activation because activated neuroglia cells could secrete proinflammatory cytokines. Subsequently, we found that ionized calcium-binding adapter molecule (Iba)-1 as a selective marker for microglia and glial fibrillary acidic protein as a specific marker for astrocyte were significantly increased at transcriptional and translational levels, which confirmed the neuroglial activation in this model. Therefore, we conclude that MBD induces excessive anxiety-like behavior in female juvenile with elevated TNF-? and IL-6 levels, as well as activated microglia and astrocyte in PFC. Herein caution must be taken to prevent potential risks from MBD becuase exacerbated anxiety-like behavior in female juvenile by MBD may be a critical contribution for subsequent growth or mental disorders.
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Eliciting neutralizing antibodies with gp120 outer domain constructs based on M-group consensus sequence.
Virology
PUBLISHED: 05-09-2014
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One strategy being evaluated for HIV-1 vaccine development is focusing immune responses towards neutralizing epitopes on the gp120 outer domain (OD) by removing the immunodominant, but non-neutralizing, inner domain. Previous OD constructs have not elicited strong neutralizing antibodies (nAbs). We constructed two immunogens, a monomeric gp120-OD and a trimeric gp120-OD×3, based on an M group consensus sequence (MCON6). Their biochemical and immunological properties were compared with intact gp120. Results indicated better preservation of critical neutralizing epitopes on gp120-OD×3. In contrast to previous studies, our immunogens induced potent, cross-reactive nAbs in rabbits. Although nAbs primarily targeted Tier 1 viruses, they exhibited significant breadth. Epitope mapping analyses indicated that nAbs primarily targeted conserved V3 loop elements. Although the potency and breadth of nAbs were similar for all three immunogens, nAb induction kinetics indicated that gp120-OD×3 was superior to gp120-OD, suggesting that gp120-OD×3 is a promising prototype for further gp120 OD-based immunogen development.
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SPRY4-mediated ERK1/2 signaling inhibition abolishes 17?-estradiol-induced cell growth in endometrial adenocarcinoma cell.
Gynecol. Endocrinol.
PUBLISHED: 05-08-2014
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Basic fibroblast growth factor (FGF2)-mediated Extracellular signal-regulated kinases1/2 (ERK1/2) signaling is a critical modulator in angiogenesis. SPRY4 has been reported to be a feedback negative regulator of FGFs-induced ERK1/2 signaling. The aim of this study was to explore the role of SPRY4 in endometrial adenocarcinoma cell.
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Screening and identification of potential biomarkers and establishment of the diagnostic serum proteomic model for the Traditional Chinese Medicine Syndromes of tuberculosis.
J Ethnopharmacol
PUBLISHED: 05-07-2014
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Chemotherapy is the mainstay of modern tuberculosis (TB) control. Traditional Chinese Medicine (TCM) can enhance the effect of anti-TB drug, promote the absorption of the foci in the lung and reduce drug toxicity. In TCM, the determination of treatment is based on ZHENG (also called TCM syndrome). To establish a diagnostic model by using proteomics technology in order to identify potential biomarkers for TCM syndromes of TB.
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Analysis of sequence variability in the pig CART gene and association of polymorphism with fatness traits in a F2 population.
Mol. Biol. Rep.
PUBLISHED: 05-02-2014
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CART (cocaine- and amphetamine-regulated transcript) peptides are neuromodulators that are involved in appetite control and energy homeostasis. It can inhibit food intake and reduce body weight that have received much attention, but a direct and comprehensive relationship with pigs differing in fatness which could be applied to breeding well has not been established. This study aims to search for polymorphism within the porcine CART gene and evaluate the effect of specific genotypes with regards to an association with fatness traits in a F2 population consisting of 230 individuals. Screening of 2264 bp DNA fragment covering the entire CART gene revealed 29 mutations and four indels (insertion or a deletion), in which four unlinked SNPs (single-nucleotide polymorphisms) could be digested by enzymes and subsequently genotyped in two purebreds and a F2 population. Landrace (lean-type), one of purebreds, presented significantly higher CART expression level than Lantang (obese-type) in most tissues studied. Association analysis revealed that three SNPs (T415C, C640T and C847T) displayed significantly association (p < 0.05) with fatness traits. Additionally, they are in almost complete linkage disequilibrium. Western blotting experiments on these three SNPs loci revealed difference in CART expression among individuals with different genotypes, and the individuals with lower average live backfat thickness (BFAW) expressed CART protein at a bit higher level than others. Our study screened and mapped the genetic variations in the porcine CART gene, and confirmed three functional SNPs which are promising molecular markers for pig production traits.
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[Peripheral blood lymphocyte subsets and their relation with early response to treatment in patients with low or intermediate risk myelodysplastic syndrome (IPSS score ? 1.0) and chronic aplastic anemia].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 04-26-2014
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The purpose of this study was retrospectively to analyze the peripheral blood lymphocyte subset distribution in patients with low or intermediate risk myelodysplastic syndromes (IPSS ? 1.0) and chronic aplastic anemia (CAA), and their hematological changes of peripheral blood after treatment, so as to understand differences and their relation with early treatment response. The lymphocyte subsets in peripheral blood of 67 patient with low or intermediate risk MDS (IPSS ? 1.0), 54 patients with CAA and 73 healthy individuals were analyzed by flow cytometry. The results showed that Th cells, Th/Ts ratio in peripheral blood of low or intermediate risk MDS were 42.94% ± 10.80% and 1.80% ± 0.99% respectively, and were significantly higher than those in control group; the CD16(+) CD56(+) cell ratio was 11.22% ± 7.97%, and was significantly lower than that in control group, the difference was statistically significant (P < 0.05); Ts cells and CD19(+) cell ratio in peripheral blood of CAA patients were 30.87% ± 9.11% and 16.98% ± 7.40% respectively, and were significantly higher than those in control group; CD16(+) CD56(+) cell ratio was 9.81% ± 7.00%, and was significantly lower than that in normal control group, and the difference was statistically significant (P < 0.05); while the Th cells and Th/Ts ratio in low or intermediate risk MDS group were significantly higher than those in CAA group, and the difference was statistically significant (P < 0.05). After treatment for 6 mouths, the HI-E and HI-N rates in CD19(+) cell normal group of low or intermediate risk MDS patients were 18.2% (4/22) and 13.6% (3/22), and were significantly lower than that in the increased group and decreased group. In Ts cell increased group HI-N rate was 15.4% (2/13), and was significantly lower than that in normal group and decreased group. In Th/Ts ratio decreased group HI-N rate was 14.3% (2/14), and was significantly lower than that in the increase group and normal group, the difference was statistically significant (P < 0.05). After treatment of CAA for 6 months, the effective rate for CD3(+) cells, Th cells, Th/Ts ratio in decreased group was 71.4% (5/7), 56.3% (9/16), 50.0% (10/20), and were significantly higher than those in increased and normal group, and the difference was statistically significant (P < 0.05). It is concluded that the peripheral blood lymphocyte subsets of low or intermediate risk MDS(IPSS score ? 1.0) and CAA are abnormal, and these lymphocyte subsets are related with hematologic changes after early response to treatment.
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Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs.
Nat Commun
PUBLISHED: 04-22-2014
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The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumours; however, mutations at SMO have been found to abolish their antitumour effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6-2.8?Å resolution. The long and narrow cavity in the transmembrane domain of SMO harbours multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D473(6.54f) elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules.
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Association of eight EST-derived SNPs with carcass and meat quality traits in pigs.
J. Appl. Genet.
PUBLISHED: 04-15-2014
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The identification of genetic markers associated with important economic traits is fundamental to improving the productivity and quality of livestock. In this investigation, we searched for 177 expressed sequence tags (ESTs) putatively involved in meat quality from the available pig EST database, and detected eight single nucleotide polymorphisms (SNPs) in eight ESTs. We investigated the associations of these SNPs with 18 carcass and meat quality traits in a Landrace?×?Lantang F2 resource population (n?=?257). Association analysis revealed that seven SNPs (except E42) were associated with some of the carcass- and meat quality-related traits. Particularly, significant associations of three SNPs (E53, E82, and E36) with backfat thickness traits were observed. Further, the genetic effects of E53 on four live backfat thickness traits were validated in an independent population (n?=?221). More investigations about E53 sequence characteristics were performed, i.e., radiation hybrid (RH) mapping, 3'-RACE, and screening analysis of the positive BAC clones. Our research identified the genetic effects of eight EST-derived SNPs on carcass and meat quality traits, and suggested that E53 may be a useful marker for live backfat thickness traits in pig breeding programs.
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ATP promotes extracellular matrix biosynthesis of intervertebral disc cells.
Cell Tissue Res.
PUBLISHED: 04-11-2014
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We have recently found a high accumulation of extracellular adenosine triphosphate (ATP) in the center of healthy porcine intervertebral discs (IVD). Since ATP is a powerful extracellular signaling molecule, extracellular ATP accumulation might regulate biological activities in the IVD. The objective of this study was therefore to investigate the effects of extracellular ATP on the extracellular matrix (ECM) biosynthesis of porcine IVD cells isolated from two distinct anatomical regions: the annulus fibrosus (AF) and nucleus pulposus (NP). ATP treatment significantly promotes ECM deposition and corresponding gene expression (aggrecan and type II collagen) by both cell types in three-dimensional agarose culture. A significant increase in ECM accumulation has been found in AF cells at a lower ATP treatment level (20 ?M) compared with NP cells (100 ?M), indicating that AF cells are more sensitive to extracellular ATP than NP cells. NP cells also exhibit higher ECM accumulation and intracellular ATP than AF cells under control and treatment conditions, suggesting that NP cells are intrinsically more metabolically active. Moreover, ATP treatment also augments the intracellular ATP level in NP and AF cells. Our findings suggest that extracellular ATP not only promotes ECM biosynthesis via a molecular pathway, but also increases energy supply to fuel that process.
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Randomized clinical trial to evaluate the pathogenicity of Bibersteinia trehalosi in respiratory disease among calves.
BMC Vet. Res.
PUBLISHED: 04-11-2014
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Bibersteinia trehalosi causes respiratory disease in ruminants particularly in wild and domestic sheep. Recently, there has been an increased number of B. trehalosi isolates obtained from diagnostic samples from bovine respiratory disease cases. This study evaluated the role of B. trehalosi in bovine respiratory disease using an intra-tracheal inoculation model in calves. Thirty six cross bred 2-3 month old dairy calves were inoculated intra-tracheally with either leukotoxin negative B. trehalosi, leukotoxin positive B. trehalosi isolate, Mannheimia haemolytica, a combination of leukotoxin negative B. trehalosi and M. haemolytica or negative control. Calves were euthanized and necropsy performed on day 10 of study.
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Effect of recombinant bovine granulocyte colony-stimulating factor covalently bound to polyethylene glycol injection on neutrophil number and function in periparturient dairy cows.
J. Dairy Sci.
PUBLISHED: 04-07-2014
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Dairy cows often experience decreased immune function around the time of calving, typified by impaired polymorphonuclear neutrophil (PMN) function and a transient neutropenia. This is associated with increased disease incidence, including mastitis, retained placenta, and metritis. In an attempt to improve PMN functional capacity during the periparturient period, we injected cows with recombinant bovine granulocyte colony-stimulating factor covalently bound to polyethylene glycol (PEG rbG-CSF) twice subcutaneously, about 6d before calving and within 24h after calving. Twenty-one cows in their second pregnancy were enrolled in this study and divided into 2 groups: PEG rbG-CSF treated (n=11) and saline-treated controls (n=10). The PMN numbers quickly and dramatically increased after PEG rbG-CSF administration and remained elevated through the end of the experiment (13d after calving). Exocytosis of myeloperoxidase by stimulated PMN, which is generally decreased in periparturient cows, was markedly increased by PEG rbG-CSF after injection. Higher myeloperoxidase exocytosis persisted for at least 10d after calving. The PMN superoxide anion release and phagocytosis activity did not differ between groups. Injection of PEG rbG-CSF was safe for cows, with no significant negative effects observed. The greatest single effect of PEG rbG-CSF administration was a dramatic increase in circulating numbers of PMN. The increased numbers of PMN ready to move to a site of infection early in the course of an infection may improve the ability of the cow to ward off clinical disease in the periparturient period.
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Changes in memory and synaptic plasticity induced in male rats after maternal exposure to bisphenol A.
Toxicology
PUBLISHED: 04-06-2014
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Bisphenol A (BPA), a component of polycarbonate and epoxy resins, has been reported to adversely impact the central nervous system, especially with respect to learning and memory. However, the precise effect and specific mechanisms have not been fully elucidated. In the present study, pregnant Sprague-Dawley rats were orally administered with BPA at 0.05, 0.5, 5 or 50mg/kg·body weight (BW) per day from embryonic day 9 (E 9) to E 20. We examined the effects of maternal BPA exposure on memory and synaptic structure in the hippocampus of male offspring at postnatal day (PND) 21. Maternal BPA exposure significantly affected locomotor activity, exploratory habits, and emotional behavior in open field test, and increased reference and especially working memory errors in the radial arm maze during the postnatal developing stage. Maternal BPA exposure had an adverse effect on synaptic structure, including a widened synaptic cleft, a thinned postsynaptic density (PSD), unclear synaptic surface and disappeared synaptic vesicles. Furthermore, maternal BPA exposure decreased the mRNA and protein expressions of synaptophysin, PSD-95, spinophilin, GluR1 and NMDAR1 in the hippocampus of male offspring on PND 21. These results showed that fetal growth and development was more sensitive to BPA exposure. The decreased learning and memory induced by maternal exposure to BPA in this study may be involved in synaptic plasticity alteration.
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Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat.
Drug Metab. Dispos.
PUBLISHED: 04-01-2014
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This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp3a are both targets of the DDI between cilostazol and probenecid. Aspirin inhibits OAT3-mediated uptake of cilostazol and does not influence cilostazol metabolism.
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Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer's disease: a systematic review and meta-analysis.
J. Alzheimers Dis.
PUBLISHED: 03-26-2014
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The role of currently available drugs for Alzheimer's disease (AD) has been controversial, with some national formularies restricting their use, and health economists questioning whether the small clinical effects are economically worthwhile.
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New insights into the molecular phylogeny of Balantidium (Ciliophora, Vetibuliferida) based on the analysis of new sequences of species from fish hosts.
Parasitol. Res.
PUBLISHED: 03-14-2014
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We obtained sequences of the small subunit ribosomal RNA (rRNA) for two new isolates of Balantidium from fishes, Balantidium polyvacuolum and Balantidium ctenopharingodoni. This is the first introduction of molecular data of Balantidium species from fish hosts in the phylogenetic analyses of the ciliate subclass Trichostomatia. Despite the fact that these species share morphological characteristics common to other species of Balantidium, the phylogenetic analysis of their sequences has shown that they are to be placed in a different branch closely related to the so-called Australian clade. Thus, our results indicate that the genus Balantidium is polyphyletic and possibly should be represented by two different genera; however, the analysis of more species from other poikilothermic hosts (amphibians, reptiles) should be made before a revised taxonomical proposal could be made.
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Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator.
Science
PUBLISHED: 03-06-2014
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The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.
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Management of local recurrence of pediatric osteosarcoma following limb-sparing surgery.
Ann. Surg. Oncol.
PUBLISHED: 02-21-2014
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The optimal management of locally recurrent pediatric osteosarcoma is not established, especially after prior limb-sparing surgery. We describe our experience in the management of these patients and identify prognostic indicators of post-recurrence survival.
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TGF-beta signaling-dependent alleviation of dextran sulfate sodium-induced colitis by mesenchymal stem cell transplantation.
Mol. Biol. Rep.
PUBLISHED: 02-19-2014
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Alleviation of dextran sulfate sodium (DSS)-induced colitis was shown after by transplantation of bone marrow derived cells in mice. Nevertheless, the underlying mechanism remains elusive. In the present study, we transplanted primary mouse mesenchymal stem cells (MSC) into isogeneic mice with DSS-induced colitis. We found that MSC transplantation significantly alleviated the DSS-induced colitis. Inhibition of transforming growth factor beta (TGF-beta) signaling abrogated the therapeutic effect of MSC transplantation on DSS-colitis, suggesting a TGF-beta signaling-dependent manner. Moreover, MSC transplantation seemed to induce M2 macrophage polarization, which appeared to be the major source of TGF-beta in this model. Our data thus demonstrate that MSC transplantation may activate TGF-beta signaling pathways to promote the recovery of DSS-colitis.
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The application of laser microdissection in molecular detection and identification of aspergillus fumigatus from murine model of acute invasive pulmonary aspergillosis.
Mycopathologia
PUBLISHED: 02-11-2014
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Invasive aspergillosis (IA) is a major concern in patients with severe immune deficiency. As antifungal susceptibility varies in different fungal pathogens, accurate and timely identification of species is becoming imperative for guidance of therapy and reducing high mortality rates in patients with IA. But, in fact, the diagnosis is challenging and new validated techniques are required for the detection and identification of clinically relevant isolates. The laser capture microdissection (LCM) system enables analysis of cytologically and/or phenotypically defined cell types from heterogeneous tissue and has been used in diagnosis and fungal species identification in pulmonary aspergillosis of white storks. To establish the experimental foundation for clinical application of the system, we microdissected and collected Blankophor-stained single hyphal strands from tissue cryosections of murine model of invasive pulmonary aspergillosis (IPA) with A. fumigatus by LCM, subsequently processed for DNA extraction, PCR sequencing, and species molecular identification. The sensitivity of LCM-PCR sequencing was 89 % (89/100), and the specificity was 100 %. Moreover, the positive predictive value and negative predictive value were 100 and 78.43 %, respectively. The result approved that the LCM-based methods had the potential for accurately diagnosis and rapidly identification fungal pathogens of IPA.
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First analysis of synonymous codon usage in porcine circovirus.
Arch. Virol.
PUBLISHED: 02-01-2014
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Porcine circovirus (PCV) is grouped into two types: PCV1 and PCV2. PCV1 is isolated from cultured cells and usually causes no clinical diseases in pigs. PCV2 is a pathogen of severe pig disease and a great threat to swine health and production. In our study, to investigate the codon usage bias of PCV, the genomic sequences of PCV1 and PCV2 were analyzed. The results showed that the codon usage bias of PCV was very low. An effective number of codons (ENC) plot analysis indicated that mutational pressure influences the codon usage bias of PCV. Neutrality plot analysis showed that mutation bias dominated over natural selection in shaping the codon usage bias of PCV1, but mutation bias and natural selection contributed equally to the codon usage bias of PCV2. Principal component analysis showed that different ORFs and dinucleotide patterns were also factors influencing the codon usage bias of PCV. Our study is helpful in understanding the codon usage pattern of PCV and the evolution of PCV.
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Mechanical Pleurodesis Does Not Reduce Recurrence of Spontaneous Pneumothorax: A Randomized Trial.
Ann. Thorac. Surg.
PUBLISHED: 01-27-2014
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Mechanical pleurodesis is widely used to treat primary spontaneous pneumothorax to decrease postoperative recurrence after thoracoscopic bullectomy, but it is unclear whether it actually reduces primary spontaneous pneumothorax recurrence. We aimed to investigate the effectiveness of mechanical pleurodesis after thoracoscopic treatment of primary spontaneous pneumothorax.
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Effects of n-butylparaben on steroidogenesis and spermatogenesis through changed E? levels in male rat offspring.
Environ. Toxicol. Pharmacol.
PUBLISHED: 01-25-2014
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Parabens are widely used as antibacterial agents, which are concerned recently in the relationship between the use of parabens and reproductive toxicity. So that reassessment of the risk of parabens is needed. In this study, one of parabens, n-butylparaben (n-BP) was orally administered to pregnant Wistar rats (0, 64, 160, 400 and 1000 mg/kg/day) from gestation day (GD) 7 through postnatal day (PND) 21. Reduced anogenital distance (AGD) and delayed preputial separation (PPS) were observed in the male offspring. The weights of the testes were significantly reduced at PND 21-90. The weights of the epididymides were significantly reduced at all monitoring points, except PND 35. Seminal vesicle weights were significantly reduced on PND 21. Serum testosterone (T) was significantly decreased, especially on PND 49. The levels of 17?-estradiol (E2) showed an increase at each of the tested points except on PND 180. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels in the n-BP treated groups were lower on PND 21, 35 and 49 but elevated on PND 90 compared to control levels. n-BP reduced epididymal cauda sperm counts and daily sperm production in a dose-dependent manner; this difference was statistically significant at exposure groups of 400 and 1000 mg/kg/day. The present study strongly suggests that exposure to n-BP in utero and during lactation has adverse effects on the reproductive system in male offspring, with a no observed adverse effect level (NOAEL) of 160 mg/kg/day. To our knowledge, this is the first study that reports increased E2 levels of male rats following n-BP exposure; we suggest that E2 levels may be considered as biomarkers for some endocrine disrupting chemicals (EDCs).
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Interpreting the synergistic effect in combined ultrasonication-ozonation sewage sludge pre-treatment.
Chemosphere
PUBLISHED: 01-18-2014
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The sequential combination of ultrasonication and ozonation as sewage sludge treatment prior to anaerobic digestion was investigated. Synergistic volatile suspended solids (VSS) solubilization was observed when low energy ultrasonication (?12kJg(-1) TS) was followed by ozonation. 0.048gO3g(-1) TS ozonation induced the maximum VSS solubilization of 41.3% when the sludge was pre-ultrasonicated at 9kJg(-1) TS; while, the same ozone dosage applied without prior ultrasonication only induced 21.1% VSS solubilization. High molecular weight (MW) components (MW>500kDa) were found to be the main solubilization products when sludge was only ozonated. However, solubilization products by ozone were mainly in the form of low MW components (MW<27kDa) when sludge was pre-ultrasonicated. The high MW products generated by ultrasound were effectively degraded in the subsequent ozonation. Anaerobic biodegradability increased by 34.7% when ultrasonication (9kJg(-1) TS) and ozonation (0.036gO3g(-1) TS) were combined sequentially. The maximum methane production rate increased from 3.53 to 4.32, 4.21 and 4.54mL CH4d(-1) after ultrasonication, ozonation and ultrasonication-ozonation pre-treatments, respectively.
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Dairy consumption and risk of esophageal squamous cell carcinoma: A meta-analysis of observational studies.
Asia Pac J Clin Oncol
PUBLISHED: 01-17-2014
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Inconsistent results regarding the relations between consumption of dairy products and the risk of esophageal squamous cell carcinoma (ESCC) have been reported. In this report, we summarized the evidence by a meta-analysis of observational studies.
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High-level exogenous trans10, cis12 conjugated linoleic acid plays an anti-lipogenesis role in bovine mammary epithelial cells.
Anim. Sci. J.
PUBLISHED: 01-09-2014
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Primary bovine mammary epithelial cells (BMECs) were treated by 0, 37.5, 75, 112.5, 150??mol/L trans10, cis12 conjugated linoleic acid (CLA) to evaluate the effects of different level trans10, cis12 CLA on lipogenesis in BMEC. Addition of 75-150??mol/L trans10, cis12 CLA reduced significantly the triacylglycerol (TAG) content (P<0.05), but did not have inhibiting action on cell proliferation (P>0.05). Treatment with 150??mol/L trans10, cis12 CLA for 48?h resulted in a 17.1% reduction (P<0.0001) of medium chain fatty acids (MCFA, C14
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Porcine reproductive and respiratory syndrome virus (PRRSV) surveillance using pre-weaning oral fluid samples detects circulation of wild-type PRRSV.
Vet. Microbiol.
PUBLISHED: 01-08-2014
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Oral fluid samples collected from litters of piglets (n=600) one day prior to weaning were evaluated as a method to surveil for porcine reproductive and respiratory syndrome virus (PRRSV) infections in four sow herds of approximately 12,500 sow each. Serum samples from the litters' dam (n=600) were included for comparison. All four herds were endemically infected with PRRSV and all sows had been vaccinated ? 2 times with PRRSV modified-live virus vaccines. After all specimens had been collected, samples were randomized and assayed by PRRSV real-time reverse transcription polymerase chain reaction (RT-qPCR) and four PRRSV antibody ELISA assays (IgM, IgA, IgG, and Commercial Kit). All sow serum samples were negative by PRRSV RT-qPCR, but 9 of 600 oral fluid samples tested positive at two laboratories. Open reading frame 5 (ORF5) sequencing of 2 of the 9 positive oral fluid samples identified wild-type viruses as the source of the infection. A comparison of antibody responses in RT-qPCR positive vs. negative oral fluid samples showed significantly higher IgG S/P ratios in RT-qPCR-positive oral fluid samples (mean S/P 3.46 vs. 2.36; p=0.02). Likewise, sow serum samples from RT-qPCR-positive litter oral fluid samples showed significantly higher serum IgG (mean S/P 1.73 vs. 0.98; p<0.001) and Commercial Kit (mean S/P 1.97 vs. 0.98; p<0.001) S/P ratios. Overall, the study showed that pre-weaning litter oral fluid samples could provide an efficient and sensitive approach to surveil for PRRSV in infected, vaccinated, or presumed-negative pig breeding herds.
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Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma.
Onco Targets Ther
PUBLISHED: 01-01-2014
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Abnormal expression of micro-ribonucleic acid (miRNA [miR])-128 has been observed in various human cancer types, and its validated target genes are implicated in cancer-related cellular processes, such as cell proliferation, differentiation, and apoptosis. Especially, it has been demonstrated that miR-128 may play an important role in the proliferation of human osteosarcoma cells in vitro by directly inhibiting PTEN, which functions as a tumor suppressor in this malignancy. In the current study, we investigated the involvement of miR-128 and its target gene PTEN in tumor progression and prognosis in patients with primary osteosarcoma.
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Effect of dietary phosphorus content on milk production and phosphorus excretion in dairy cows.
J Anim Sci Biotechnol
PUBLISHED: 01-01-2014
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Phosphorus (P) supplementation is costly and can result in excess P excretion. This study investigated the effects of reducing dietary P on milk production and P excretion in dairy cows over a full lactation.
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The suppressive role of SOX7 in hepatocarcinogenesis.
PLoS ONE
PUBLISHED: 01-01-2014
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SOX7 is a transcription factor mediating various developmental processes. However, its role in hepatocellular carcinoma (HCC) remains unclear. Here, we assessed the role of SOX7 in hepatocarcinogenesis. We found HCC samples exhibited lower levels of SOX7 mRNA and protein expression than non-tumor samples, and the expression of SOX7 was negatively correlated with tumor size. SOX7 expression was also reduced in four HCC cell lines (SMMC-7721, Hep3B, HepG2 and Huh 7). Overexpression of SOX7 could inhibit HCC cell growth, with G1to S phase arrest. In SOX7-overexpression cells, cyclin D1 and c-myc, two cell cycle promoters, were down-regulated. Moreover, ectopic expression of cyclin D1 or c-myc could override G1 to S pahse arrest induced by SOX7. Furthermore, overexpression of SOX7 suppressed tumor formation with down-regulation of cyclin D1 and c-myc in vivo. The expression of Ki-67, a proliferation marker, was also reduced in SOX7-overexpression tumors. Taken together, our study suggests that SOX7 plays an important inhibitory role in hepatocarcinogenesis, and might be a novel target for HCC therapy.
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Generation of transgenic pigs by cytoplasmic injection of piggyBac transposase-based pmGENIE-3 plasmids.
Biol. Reprod.
PUBLISHED: 01-01-2014
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The process of transgenesis involves the introduction of a foreign gene, the transgene, into the genome of an animal. Gene transfer by pronuclear microinjection (PNI) is the predominant method used to produce transgenic animals. However, this technique does not always result in germline transgenic offspring and has a low success rate for livestock. Alternate approaches, such as somatic cell nuclear transfer using transgenic fibroblasts, do not show an increase in efficiency compared to PNI, while viral-based transgenesis is hampered by issues regarding transgene size and biosafety considerations. We have recently described highly successful transgenesis experiments with mice using a piggyBac transposase-based vector, pmhyGENIE-3. This construct, a single and self-inactivating plasmid, contains all the transpositional elements necessary for successful gene transfer. In this series of experiments, our laboratories have implemented cytoplasmic injection (CTI) of pmGENIE-3 for transgene delivery into in vivo-fertilized pig zygotes. More than 8.00% of the injected embryos developed into transgenic animals containing monogenic and often single transgenes in their genome. However, the CTI technique was unsuccessful during the injection of in vitro-fertilized pig zygotes. In summary, here we have described a method that is not only easy to implement, but also demonstrated the highest efficiency rate for nonviral livestock transgenesis.
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Towards decrypting cryptobiosis--analyzing anhydrobiosis in the tardigrade Milnesium tardigradum using transcriptome sequencing.
PLoS ONE
PUBLISHED: 01-01-2014
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Many tardigrade species are capable of anhydrobiosis; however, mechanisms underlying their extreme desiccation resistance remain elusive. This study attempts to quantify the anhydrobiotic transcriptome of the limno-terrestrial tardigrade Milnesium tardigradum.
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Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer's disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Peripheral blood Apolipoprotein E (ApoE) levels have been proposed as biomarkers of Alzheimer's disease (AD), but previous studies on levels of ApoE in blood remain inconsistent. This meta-analysis was designed to re-examine the potential role of peripheral ApoE in AD diagnosis and its potential value as a candidate biomarker.
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Serial femtosecond crystallography of G protein-coupled receptors.
Science
PUBLISHED: 12-21-2013
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X-ray crystallography of G protein-coupled receptors and other membrane proteins is hampered by difficulties associated with growing sufficiently large crystals that withstand radiation damage and yield high-resolution data at synchrotron sources. We used an x-ray free-electron laser (XFEL) with individual 50-femtosecond-duration x-ray pulses to minimize radiation damage and obtained a high-resolution room-temperature structure of a human serotonin receptor using sub-10-micrometer microcrystals grown in a membrane mimetic matrix known as lipidic cubic phase. Compared with the structure solved by using traditional microcrystallography from cryo-cooled crystals of about two orders of magnitude larger volume, the room-temperature XFEL structure displays a distinct distribution of thermal motions and conformations of residues that likely more accurately represent the receptor structure and dynamics in a cellular environment.
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In vitro analyses of mild heat stress in combination with antifungal agents against Aspergillus fumigatus biofilm.
Antimicrob. Agents Chemother.
PUBLISHED: 12-16-2013
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Aspergillus fumigatus biofilms still present a challenge for effective treatment in clinical settings. While mild heat stress has been introduced as a treatment for infectious diseases, the effectiveness of mild heat stress on A. fumigatus biofilm formation and antifungal susceptibility is still unknown. In the present study, confocal laser scanning microscopy (CLSM) was used to image and quantify Aspergillus fumigatus biofilm formation under three different regimens of continuous mild heat stress: at 37, 39, and 41°C respectively. Furthermore, fungal growth has been investigated under the above conditions in combination with antifungal drugs (Amphotericin B (AMB), Micafungin (MCF), Voriconazole (VOC)) at early and late stages. CLSM analysis showed that higher temperatures induce earlier germination and greater hyphal elongation, but poorer polar growth and reduced biofilm thickness. In the early stage of biofilm formation, the combination of 39 or 41°C treatment with MCF or VOC, produced no visible difference in biomass formation from similar treatments at 37°C with the same drug. Interestingly, AMB treatment at 37°C inhibited early stage biofilm formation to a much greater extent than at 39 and 41°C. At the late stage of biofilm formation, the mild heat treatments at 39 and 41°C with AMB, MCF, and VOC inhibited biomass formation compared to 37°C. The present data shows that mild heat stress has a negative regulation effect on biofilm formation in vitro, and antifungal drug improvement with mild heat treatment at late stage biofilm formation provides useful indications of possible effective strategies in clinical management of aspergillosis.
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The discovery and identification of a candidate proteomic biomarker of active tuberculosis.
BMC Infect. Dis.
PUBLISHED: 10-15-2013
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Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB.
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