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Find video protocols related to scientific articles indexed in Pubmed.
Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas.
Gut
PUBLISHED: 11-12-2014
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Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome.
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Dynamic CT myocardial perfusion measurements of resting and hyperaemic blood flow in low-risk subjects with 128-slice dual-source CT.
Eur Heart J Cardiovasc Imaging
PUBLISHED: 11-08-2014
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The aim of the study was to measure rest and stress myocardial blood flow (MBF) values prospectively in a low-risk population with 128-slice dual-source computed tomography (CT) and to compare MBF/coronary flow reserve (CFR) values to that of a second population with a documented coronary artery disease (CAD).
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Factors Associated With Early Mortality After Living-Donor Liver Transplant.
Exp Clin Transplant
PUBLISHED: 10-25-2014
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We sought to identify the risk factors associated with the early mortality after a living-donor liver transplant.
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[MRI evaluation of the olfactory pathway].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-22-2014
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MRI scanning is an important technique to evaluate the olfactory system, special scanning parameters could reveal the fine structures of the olfactory pathway. Olfactory cleft, olfactory bulb/tract, olfactory sulcus and olfactory center are the main targets of the scanning. Chronic rhino-sinusitis, head trauma, congenital dysplasia and neural degenerative diseases are the primary causes of the olfactory dysfunction and have particular imaging presentations respectively. Besides indicating the olfactory pathway lesions, MRI could also present the etiology and the prognosis of the olfactory disorder.
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Anisotropic growth-induced synthesis of dual-compartment janus mesoporous silica nanoparticles for bimodal triggered drugs delivery.
J. Am. Chem. Soc.
PUBLISHED: 10-07-2014
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Multifunctional dual-compartment Janus mesoporous silica nanocomposites of UCNP@SiO2@mSiO2&PMO (UCNP = upconversion nanoparticle, PMO = periodic mesoporous organosilica) containing core@shell@shell structured UCNP@SiO2@mSiO2 nanospheres and PMO single-crystal nanocubes have been successfully synthesized via a novel anisotropic island nucleation and growth approach with the ordered mesostructure. The asymmetric Janus nanocomposites show a very uniform size of ?300 nm and high surface area of ?1290 m(2)/g. Most importantly, the Janus nanocomposites possess the unique dual independent mesopores with different pore sizes (2.1 nm and 3.5-5.5 nm) and hydrophobicity/hydrophilicity for loading of multiple guests. The distinct chemical properties of the silica sources and the different mesostructures of the dual-compartments are the necessary prerequisites for the formation of the Janus nanostructure. With the assistance of the near-infrared (NIR) to ultraviolet/visible (UV-vis) optical properties of UCNPs and heat-sensitive phase change materials, the dual-compartment Janus mesoporous silica nanocomposites can be further applied into nanobiomedicine for heat and NIR light bimodal-triggered dual-drugs controllable release. It realizes significantly higher efficiency for cancer cell killing (more than 50%) compared to that of the single-triggered drugs delivery system (?25%).
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Mechanisms of failure in nanoscale metallic glass.
Nano Lett.
PUBLISHED: 09-11-2014
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The emergence of size-dependent mechanical strength in nanosized materials is now well-established, but no fundamental understanding of fracture toughness or flaw sensitivity in nanostructures exists. We report the fabrication and in situ fracture testing of ?70 nm diameter Ni-P metallic glass samples with a structural flaw. Failure occurs at the structural flaw in all cases, and the failure strength of flawed samples was reduced by 40% compared to unflawed samples. We explore deformation and failure mechanisms in a similar nanometallic glass via molecular dynamics simulations, which corroborate sensitivity to flaws and reveal that the structural flaw shifts the failure mechanism from shear banding to cavitation. We find that failure strength and deformation in amorphous nanosolids depend critically on the presence of flaws.
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Extraordinary photoluminescence and strong temperature/angle-dependent Raman responses in few-layer phosphorene.
ACS Nano
PUBLISHED: 09-08-2014
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Phosphorene is a new family member of two-dimensional materials. We observed strong and highly layer-dependent photoluminescence in few-layer phosphorene (two to five layers). The results confirmed the theoretical prediction that few-layer phosphorene has a direct and layer-sensitive band gap. We also demonstrated that few-layer phosphorene is more sensitive to temperature modulation than graphene and MoS2 in Raman scattering. The anisotropic Raman response in few-layer phosphorene has enabled us to use an optical method to quickly determine the crystalline orientation without tunneling electron microscopy or scanning tunneling microscopy. Our results provide much needed experimental information about the band structures and exciton nature in few-layer phosphorene.
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SPHK1 regulates proliferation and survival responses in triple-negative breast cancer.
Oncotarget
PUBLISHED: 08-26-2014
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Triple-negative breast cancer (TNBC) is characterized by unique aggressive behavior and lack of targeted therapies. Among the various molecular subtypes of breast cancer, it was observed that TNBCs express elevated levels of sphingosine kinase 1 (SPHK1) compared to other breast tumor subtypes. High levels of SPHK1 gene expression correlated with poor overall and progression- free survival, as well as poor response to Doxorubicin-based treatment. Inhibition of SPHK1 was found to attenuate ERK1/2 and AKT signaling and reduce growth of TNBC cells in vitro and in a xenograft SCID mouse model. Moreover, SPHK1 inhibition by siRNA knockdown or treatment with SKI-5C sensitizes TNBCs to chemotherapeutic drugs. Our findings suggest that SPHK1 inhibition, which effectively counteracts oncogenic signaling through ERK1/2 and AKT pathways, is a potentially important anti-tumor strategy in TNBC. A combination of SPHK1 inhibitors with chemotherapeutic agents may be effective against this aggressive subtype of breast cancer.
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Prostacyclin decreases splanchnic vascular contractility in cirrhotic rats.
HBPD INT
PUBLISHED: 08-08-2014
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Prostacyclin has been shown to increase portal hypertension, but the mechanism is unclear. This study aimed to investigate whether the overproduction of prostacyclin (PGI2) in cirrhosis participates in the splanchnic vascular hyporesponsiveness to vasoconstrictors in cirrhotic rats.
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Ultrasonic integrated backscatter in assessing liver steatosis before and after liver transplantation.
HBPD INT
PUBLISHED: 08-08-2014
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Liver steatosis affects 20%-30% of adults. Because of the increasing gap between graft supplies and demands, livers with steatosis are frequently used in liver transplantation. But severely steatotic liver grafts are associated with a high risk of intraoperative and postoperative complications. Accurate assessment of fat content of donor livers and monitoring of the extent of steatosis in recipients are required for liver transplantation. The present study aimed to determine the correlation between liver echogenicity and fat content, and to evaluate the use of an ultrasonic integrated backscatter system (IBS) in the assessment of changes in fat content after liver transplantation.
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Genetic ablation of metadherin inhibits autochthonous prostate cancer progression and metastasis.
Cancer Res.
PUBLISHED: 07-29-2014
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Metadherin (MTDH) overexpression in diverse cancer types has been linked to poor clinical outcomes, but definitive genetic proof of its contributions to cancer remains incomplete. In particular, the degree to which MTDH may contribute to malignant progression in vivo is lacking. Here, we report that MTDH is amplified frequently in human prostate cancers where its expression levels are tightly correlated with prostate cancer progression and poor disease-free survival. Furthermore, we show that genetic ablation of MTDH in the transgenic adenomcarcinoma of mouse prostate (TRAMP) transgenic mouse model of prostate cancer blocks malignant progression without causing defects in the normal development of the prostate. Germline deletion of Mtdh in TRAMP mice prolonged tumor latency, reduced tumor burden, arrested progression of prostate cancer at well-differentiated stages, and inhibited systemic metastasis to distant organs, thereby decreasing cancer-related mortality ?10-fold. Consistent with these findings, direct silencing of Mtdh in prostate cancer cells decreased proliferation in vitro and tumor growth in vivo, supporting an epithelial cell-intrinsic role of MTDH in prostate cancer. Together, our findings establish a pivotal role for MTDH in prostate cancer progression and metastasis and define MTDH as a therapeutic target in this setting. Cancer Res; 74(18); 5336-47. ©2014 AACR.
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SPHK1 regulates proliferation and survival responses in triple-negative breast cancer.
Oncotarget
PUBLISHED: 07-11-2014
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Triple-negative breast cancer (TNBC) is characterized by unique aggressive behavior and lack of targeted therapies. Among the various molecular subtypes of breast cancer, it was observed that TNBCs express elevated levels of sphingosine kinase 1 (SPHK1) compared to other breast tumor subtypes. High levels of SPHK1 gene expression correlated with poor overall and progression- free survival, as well as poor response to Doxorubicin-based treatment. Inhibition of SPHK1 was found to attenuate ERK1/2 and AKT signaling and reduce growth of TNBC cells in vitro and in a xenograft SCID mouse model. Moreover, SPHK1 inhibition by siRNA knockdown or treatment with SKI-5C sensitizes TNBCs to chemotherapeutic drugs. Our findings suggest that SPHK1 inhibition, which effectively counteracts oncogenic signaling through ERK1/2 and AKT pathways, is a potentially important anti-tumor strategy in TNBC. A combination of SPHK1 inhibitors with chemotherapeutic agents may be effective against this aggressive subtype of breast cancer.
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Layer-dependent Band Alignment and Work Function of Few-Layer Phosphorene.
Sci Rep
PUBLISHED: 07-02-2014
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Using first-principles calculations, we study the electronic properties of few-layer phosphorene focusing on layer-dependent behavior of band gap, work function band alignment and carrier effective mass. It is found that few-layer phosphorene shows a robust direct band gap character, and its band gap decreases with the number of layers following a power law. The work function decreases rapidly from monolayer (5.16?eV) to trilayer (4.56?eV), and then slowly upon further increasing the layer number. Compared to monolayer phosphorene, there is a drastic decrease of hole effective mass along the ridge (zigzag) direction for bilayer phosphorene, indicating a strong interlayer coupling and screening effect. Our study suggests that 1). Few-layer phosphorene with a layer-dependent band gap and a robust direct band gap character is promising for efficient solar energy harvest. 2). Few-layer phosphorene outperforms monolayer counterpart in terms of a lighter carrier effective mass, a higher carrier density and a weaker scattering due to enhanced screening. 3). The layer-dependent band edges and work functions of few-layer phosphorene allow for modification of Schottky barrier with enhanced carrier injection efficiency. It is expected that few-layer phosphorene will present abundant opportunities for a plethora of new electronic applications.
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The microRNA-23b/27b/24 cluster promotes breast cancer lung metastasis by targeting metastasis-suppressive gene prosaposin.
J. Biol. Chem.
PUBLISHED: 06-25-2014
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MicroRNAs (miRNAs) have been shown to function as key regulators of tumor progression and metastasis. Recent studies have indicated that the miRNAs comprising the miR-23b/27b/24 cluster might influence tumor metastasis, although the precise nature of this regulation remains unclear. Here, expression of the miR-23b/27b/24 cluster is found to correlate with metastatic potential in mouse and human breast cancer cell lines and is elevated in metastatic lung lesions in human breast cancer patients. Ectopic expression of the miRNAs in the weakly metastatic mouse 4TO7 mammary tumor cell line had no effect on proliferation or morphology of tumor cells in vitro but was found to increase lung metastasis in a mouse model of breast cancer metastasis. Furthermore, gene expression profiling analysis of miRNA overexpressing 4TO7 cells revealed the direct targeting of prosaposin (PSAP), which encodes a secreted protein found to be inversely correlated with metastatic progression in human breast cancer patients. Importantly, ectopic expression of PSAP was able to suppress the metastatic phenotype in highly metastatic 4T1 and MDA-MB-231 SCP28 cells, as well as in cells ectopically expressing miR-23b/27b/24. These findings support a metastasis-promoting function of the miR-23b/27b/24 cluster of miRNAs, which functions in part through the direct inhibition of PSAP.
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Mesohepatectomy versus extended hemihepatectomy for centrally located hepatocellular carcinoma.
HBPD INT
PUBLISHED: 06-13-2014
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Extended hemihepatectomy is usually recommended to treat large centrally located hepatocellular carcinoma (HCC). However, the morbidity and mortality are high because of the postoperative liver failure. Mesohepatectomy is seldom used because of its technical complexity. This study aimed to evaluate the short-term and long-term curative effect of mesohepatectomy.
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Towards intrinsic charge transport in monolayer molybdenum disulfide by defect and interface engineering.
Nat Commun
PUBLISHED: 06-02-2014
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Molybdenum disulfide is considered as one of the most promising two-dimensional semiconductors for electronic and optoelectronic device applications. So far, the charge transport in monolayer molybdenum disulfide is dominated by extrinsic factors such as charged impurities, structural defects and traps, leading to much lower mobility than the intrinsic limit. Here we develop a facile low-temperature thiol chemistry route to repair the sulfur vacancies and improve the interface, resulting in significant reduction of the charged impurities and traps. High mobility >80?cm(2)?V(-1)?s(-1) is achieved in backgated monolayer molybdenum disulfide field-effect transistors at room temperature. Furthermore, we develop a theoretical model to quantitatively extract the key microscopic quantities that control the transistor performances, including the density of charged impurities, short-range defects and traps. Our combined experimental and theoretical study provides a clear path towards intrinsic charge transport in two-dimensional dichalcogenides for future high-performance device applications.
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?Np63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling.
Nat. Cell Biol.
PUBLISHED: 05-25-2014
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Emerging evidence suggests that cancer is populated and maintained by tumour-initiating cells (TICs) with stem-like properties similar to those of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ?Np63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signalling. Importantly, Fzd7-dependent enhancement of Wnt signalling by ?Np63 also governs tumour-initiating activity of the basal subtype of breast cancer. These findings establish ?Np63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms.
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Structural insights into the tumor-promoting function of the MTDH-SND1 complex.
Cell Rep
PUBLISHED: 05-22-2014
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Metadherin (MTDH) and Staphylococcal nuclease domain containing 1 (SND1) are overexpressed and interact in diverse cancer types. The structural mechanism of their interaction remains unclear. Here, we determined the high-resolution crystal structure of MTDH-SND1 complex, which reveals an 11-residue MTDH peptide motif occupying an extended protein groove between two SN domains (SN1/2), with two MTDH tryptophan residues nestled into two well-defined pockets in SND1. At the opposite side of the MTDH-SND1 binding interface, SND1 possesses long protruding arms and deep surface valleys that are prone to binding with other partners. Despite the simple binding mode, interactions at both tryptophan-binding pockets are important for MTDH and SND1's roles in breast cancer and for SND1 stability under stress. Our study reveals a unique mode of interaction with SN domains that dictates cancer-promoting activity and provides a structural basis for mechanistic understanding of MTDH-SND1-mediated signaling and for exploring therapeutic targeting of this complex.
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Meperidine relieves pain during transrectal ultrasound-guided prostate biopsy.
Saudi Med J
PUBLISHED: 05-15-2014
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To compare the efficacy and safety of intramuscular meperidine injection with periprostatic nerve block (PNB) during transrectal ultrasound-guided prostate biopsy.
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Signet-ring cell carcinoma coexisting with adenocarcinoma arising in a choledochal cyst: report of a case.
Surg. Today
PUBLISHED: 05-12-2014
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Signet-ring cell carcinoma (SRCC) is rare in the biliary system. We report a case of SRCC coexisting with adenocarcinoma, arising in a choledochal cyst of the extrahepatic bile duct. The patient was a 52-year-old man, hospitalized for the investigation of jaundice and pruritus. Abdominal computed tomography and magnetic resonance cholangiopancreatography showed a huge choledochal cyst and distal common bile duct cancer. The patient underwent a pancreaticoduodenectomy with extended lymph node dissection. Histologic examination confirmed an SRCC coexisting with adenocarcinoma arising in a choledochal cyst. Postoperative chemotherapy had to be discontinued after only two cycles because the patient suffered serious side effects. Recurrence was detected in the bilioenteric anastomosis 4 months after surgery, and he died 6 months after surgery. To our knowledge, this represents the first case of SRCC arising in a choledochal cyst of the extrahepatic bile duct ever to be reported.
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Increased negative supercoiling of mtDNA in TOP1mt knockout mice and presence of topoisomerases II? and II? in vertebrate mitochondria.
Nucleic Acids Res.
PUBLISHED: 05-06-2014
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Topoisomerases are critical for replication, DNA packing and repair, as well as for transcription by allowing changes in DNA topology. Cellular DNA is present both in nuclei and mitochondria, and mitochondrial topoisomerase I (Top1mt) is the only DNA topoisomerase specific for mitochondria in vertebrates. Here, we report in detail the generation of TOP1mt knockout mice, and demonstrate that mitochondrial DNA (mtDNA) displays increased negative supercoiling in TOP1mt knockout cells and murine tissues. This finding suggested imbalanced topoisomerase activity in the absence of Top1mt and the activity of other topoisomerases in mitochondria. Accordingly, we found that both Top2? and Top2? are present and active in mouse and human mitochondria. The presence of Top2?-DNA complexes in the mtDNA D-loop region, at the sites where both ends of 7S DNA are positioned, suggests a structural role for Top2 in addition to its classical topoisomerase activities.
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Research on testing the nonlinear optical performance of nonlinear optical materials based on the effect of second-harmonic generation.
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 05-03-2014
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In the present paper the authors report a research on testing the nonlinear optical performance of optical materials in visible and infrared band. Based on the second order nonlinear optic principle and the photoelectric signal detection technology, the authors have proposed a new testing scheme in which a infrared OPO laser and a method for separating the beams arising from frequency matching and the light produced by other optical effects were used. The OPO laser is adopted as light source to avoid the error of measurement caused by absorption because the double frequency signal of the material is in the transmittance band Our research work includes testing system composition, operational principle and experimental method. The experimental results of KTP, KDP, AGS tested by this method were presented. In the experiment several new infrared non-linear materials were found. This method possesses the merits of good stability and reliability, high sensitivity, simple operation and good reproducibility, which can effectively make qualitative and semi-quantitative test for optical material's nonlinear optical properties from visible to infrared. This work provides an important test -method for the research on second order nonlinear optical materials in visible, infrared and ultraviolet bands.
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Conserved residues that modulate protein trans-splicing of Npu DnaE split intein.
Biochem. J.
PUBLISHED: 04-25-2014
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The first crystal trans-structure of a naturally occurring split intein has been determined for the Npu (Nostoc punctiforme PCC73102) DnaE split intein. Guided by this structure, the residues NArg50 and CSer35, well conserved in DnaE split inteins, are identified to be critical in the trans-splicing of Npu DnaE split intein. An in vitro splicing assay demonstrates that NArg50 and CSer35 play synergistic roles in modulating its intein activity. The C-terminal CAsn36 exhibits two orientations of its side chain and interacts with both NArg50 and CSer35 through hydrogen bonding. These interactions likely facilitate the cyclization of asparagine in the course of protein splicing. The mutation of either residue reduces intein activity, and correlates with the low activity of the Ssp (Cyanobacterium synechocystis sp. strain PCC6803) DnaE split intein. On the other hand, NArg50 also forms a hydrogen bond with the highly conserved F-block CAsp17, thus influencing the N-S acyl shift during N-terminal cleavage. Sequence alignments show that residues NArg50 and CSer35 are rather conserved in those split inteins that lack a penultimate histidine residue. The conserved non-catalytic residues of split inteins modulate the efficiency of protein trans-splicing by hydrogen-bond interactions with the catalytic residues at the splice junction.
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Polarity-reversed robust carrier mobility in monolayer MoS? nanoribbons.
J. Am. Chem. Soc.
PUBLISHED: 04-21-2014
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Using first-principles calculations and deformation potential theory, we investigate the intrinsic carrier mobility (?) of monolayer MoS2 sheet and nanoribbons. In contrast to the dramatic deterioration of ? in graphene upon forming nanoribbons, the magnitude of ? in armchair MoS2 nanoribbons is comparable to its sheet counterpart, albeit oscillating with ribbon width. Surprisingly, a room-temperature transport polarity reversal is observed with ? of hole (h) and electron (e) being 200.52 (h) and 72.16 (e) cm(2) V(-1) s(-1) in sheet, and 49.72 (h) and 190.89 (e) cm(2) V(-1) s(-1) in 4 nm nanoribbon. The high and robust ? and its polarity reversal are attributable to the different characteristics of edge states inherent in MoS2 nanoribbons. Our study suggests that width reduction together with edge engineering provide a promising route for improving the transport properties of MoS2 nanostructures.
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Vitrectomy combined with periocular/intravitreal injection of steroids for rhegmatogenous retinal detachment associated with choroidal detachment.
Retina (Philadelphia, Pa.)
PUBLISHED: 04-17-2014
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To study the anatomical outcome of rhegmatogenous retinal detachment combined with choroidal detachment after pars plana vitrectomy with periocular/intravitreal injection of steroids.
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Convenient purification of gold clusters by co-precipitation for improved sensing of hydrogen peroxide, mercury ions and pesticides.
Chem. Commun. (Camb.)
PUBLISHED: 04-10-2014
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An effective separation process is developed to remove free protein from the protein-protected gold clusters via co-precipitation with zinc hydroxide on their surface. After dialysis, the purified clusters exhibit an enhanced fluorescence for improved sensitive detection and selective visualization.
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PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis.
Cancer Cell
PUBLISHED: 04-03-2014
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Metastatic dissemination is often initiated by the reactivation of an embryonic development program referred to as epithelial-mesenchymal transition (EMT). The transcription factor SNAIL promotes EMT and elicits associated pathological characteristics such as invasion, metastasis, and stemness. To better understand the posttranslational regulation of SNAIL, we performed a luciferase-based, genome-wide E3 ligase siRNA library screen and identified SCF-FBXO11 as an important E3 that targets SNAIL for ubiquitylation and degradation. Furthermore, we discovered that SNAIL degradation by FBXO11 is dependent on Ser-11 phosphorylation of SNAIL by protein kinase D1 (PKD1). FBXO11 blocks SNAIL-induced EMT, tumor initiation, and metastasis in multiple breast cancer models. These findings establish the PKD1-FBXO11-SNAIL axis as a mechanism of posttranslational regulation of EMT and cancer metastasis.
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Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients.
HBPD INT
PUBLISHED: 04-02-2014
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Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection.
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Effect of Calcium Carbonate Combined With Calcitonin on Hypercalcemia in Hemodialysis Patients.
Ther Apher Dial
PUBLISHED: 03-29-2014
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This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n?=?64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5?mg/dL. All patients were randomized (1?:?1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72?±?0.39 to 10.09?±?0.28?mg/dL (P < 0.05), serum phosphorus decreased from 6.79?±?1.05 to 5.46?±?1.18?mg/dL (P < 0.05), and serum iPTH levels in the Group I and Group II were not significantly different from the baseline. There were no significant differences in CACS in either group. There were no significant differences in the BMD values between Group I and baseline. In Group II, the BMD values at the lumbar spine and femoral neck were significantly lower than those before the trial and significantly lower than the corresponding values of Group I (P?
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DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach.
BMC Gastroenterol
PUBLISHED: 03-25-2014
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Methylation-induced silencing of promoter CpG islands in tumor suppressor genes plays an important role in human carcinogenesis. In colorectal cancer, the CpG island methylator phenotype (CIMP) is defined as widespread and elevated levels of DNA methylation and CIMP+ tumors have distinctive clinicopathological and molecular features. In contrast, the existence of a comparable CIMP subtype in gastric cancer (GC) has not been clearly established. To further investigate this issue, in the present study we performed comprehensive DNA methylation profiling of a well-characterised series of primary GC.
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Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/?-catenin pathway.
Nat Commun
PUBLISHED: 03-21-2014
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Upon stimulation by Wnt ligands, the canonical Wnt/?-catenin signalling pathway results in the stabilization of ?-catenin and its translocation into the nucleus to form transcriptionally active complexes with sequence-specific DNA-binding T-cell factor/lymphoid enhancer factor (TCF/LEF) family proteins. In the absence of nuclear ?-catenin, TCF proteins act as transcriptional repressors by binding to Groucho/Transducin-Like Enhancer of split (TLE) proteins that function as co-repressors by interacting with histone deacetylases whose activity leads to the generation of transcriptionally silent chromatin. Here we show that the transcription factor Ladybird homeobox 2 (Lbx2) positively controls the Wnt/?-catenin signalling pathway in the posterior lateral and ventral mesoderm of the zebrafish embryo at the gastrula stage, by directly interfering with the binding of Groucho/TLE to TCF, thereby preventing formation of transcription repressor complexes. These findings reveal a novel level of regulation of the canonical Wnt/?-catenin signalling pathway occurring in the nucleus and involving tissue-specific derepression of TCF by Lbx2.
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MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors.
Cancer Cell
PUBLISHED: 03-05-2014
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The Metadherin gene (MTDH) is prevalently amplified in breast cancer and associated with poor prognosis; however, its functional contribution to tumorigenesis is poorly understood. Using mouse models representing different subtypes of breast cancer, we demonstrated that MTDH plays a critical role in mammary tumorigenesis by regulating oncogene-induced expansion and activities of tumor-initiating cells (TICs), whereas it is largely dispensable for normal development. Mechanistically, MTDH supports the survival of mammary epithelial cells under oncogenic/stress conditions by interacting with and stabilizing Staphylococcal nuclease domain-containing 1 (SND1). Silencing MTDH or SND1 individually or disrupting their interaction compromises tumorigenenic potential of TICs in vivo. This functional significance of MTDH-SND1 interaction is further supported by clinical analysis of human breast cancer samples.
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Thyroid-like follicular carcinoma of the kidney: A report of two cases and literature review.
Oncol Lett
PUBLISHED: 02-20-2014
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There have only been a few reports of thyroid-like follicular carcinoma of the kidney (TLFCK) to date. In the present study, two patients with TLFCK are reported. Patient 1 was a 65-year-old male exhibiting repeated hematuria and right back pain. No tumors were located in the patient's thyroid or lungs. The physical examination revealed percussion tenderness over the right kidney region was noticed. Enhanced computed tomography (CT) indicated a right renal pelvic carcinoma, for which the patient underwent a radical right nephrectomy. Patient 2 was a 59-year-old male with a mass in the right kidney, located during a health examination and who exhibited no obvious clinical symptoms. The patient was clinically diagnosed with right renal carcinoma, confirmed by an enhanced CT. The patient underwent a radical right nephrectomy. The clinical features, imaging results, pathology, immune phenotypes, treatment and prognosis were analyzed. The associated literature was also reviewed. The cut surface of each tumor showed gray-white material with a central solid area, including scattered gray-brown necrotic and gray hemorrhagic areas and small cystic cavities. Microscopically, the arrangement of the tumor cells mimicked thyroid follicles with red-stained colloid-like material in the lumen. No renal hilar lymph node involvement was noted. The tumor tissue of patient 1 was immunohistochemically positive for vimentin, epithelial membrane antigen (EMA), cytokeratin (CK), CK7, and neuron specific enolase; and negative for CK34BE12, synapsin (Syn), CK20, cluster of differentiation 56 (CD56), CD10, Wilm's tumor-1 (WT-1), CD34, CD57, P53, CD99, thyroid transcription factor-1 (TTF-1), CD15 and thyroglobulin (TG); with a Ki-67 labeling index (LI) of 30%. The tumor tissue of patient 2 was immunohistochemically positive for vimentin, EMA, CK7 and CK20; and negative for CD56, CD10, WT-1, CD34, CD57, P53, CD117, TTF-1, CD15, CD99, TG, chromogranin A and Syn; with a Ki-67 LI of 20%. TLFCK is a rare renal tumor with low malignancy but medium invasiveness. It morphologically resembles thyroid follicular carcinoma but does not express TTF-1 or TG. Radical nephrectomy can achieve good patient outcomes.
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[Penile appearance, sexual function and sexual satisfaction of hypospadias patients after surgery: a long-term follow-up study].
Zhonghua Nan Ke Xue
PUBLISHED: 02-18-2014
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To evaluate the long-term outcomes of hypospadias surgery relating to penile appearance, sexual function and sexual satisfaction, and analyze the influencing factors by comparing them with those of healthy male adults.
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Vitrectomy treatment of retinal detachments related to choroidal coloboma involving the disk.
Retina (Philadelphia, Pa.)
PUBLISHED: 02-11-2014
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To evaluate the anatomical and functional outcomes of retinal detachment with choroidal coloboma involving the disk, by incising the entire intercalary membrane along the margin of the coloboma and displacing part of the macular retina to healthy retinal pigment epithelium (RPE), and then treating the entire margin of the RPE surrounding the coloboma with diode laser.
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Transcriptional factors smad1 and smad9 act redundantly to mediate zebrafish ventral specification downstream of smad5.
J. Biol. Chem.
PUBLISHED: 01-31-2014
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Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play crucial roles during embryonic development and cell fate determination. Nuclear transduction of BMP signals requires the receptor type Smad proteins, Smad1, Smad5, and Smad9. However, how these Smad proteins cooperate in vivo to regulate various developmental processes is largely unknown. In zebrafish, it was widely believed that the maternally expressed smad5 is essential for dorso-ventral (DV) patterning, and the zygotically transcribed smad1 is not required for normal DV axis establishment. In the present study, we have identified zygotically expressed smad9, which cooperates with smad1 downstream of smad5, to mediate zebrafish early DV patterning in a functional redundant manner. Although knockdown of smad1 or smad9 alone does not lead to visible dorsalization, double knockdown strongly dorsalizes zebrafish embryos, which cannot be efficiently rescued by smad5 overexpression, whereas the dorsalization induced by smad5 knockdown can be fully rescued by overexpression of smad1 or smad9. We have further revealed that the transcription initiations of smad1 and smad9 are repressed by each other, that they are direct transcriptional targets of Smad5, and that smad9, like smad1, is required for myelopoiesis. In conclusion, our study uncovers that smad1 and smad9 act redundantly to each other downstream of smad5 to mediate ventral specification and to regulate embryonic myelopoiesis.
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Effect of CD74 on the prognosis of patients with resectable pancreatic cancer.
HBPD INT
PUBLISHED: 01-28-2014
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CD74 is known as a type II transmembrane glycoprotein that is associated with the major histocompatibility complex class II alpha and beta chains. Recent studies have demonstrated that the expression of CD74 is also linked to some forms of tumors. The present study was to assess the effect of CD74 expression on the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC).
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Copper toxicity to Phaeodactylum tricornutum: a survey of the sensitivity of various toxicity endpoints at the physiological, biochemical, molecular and structural levels.
Biometals
PUBLISHED: 01-20-2014
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Copper (Cu) is one of the most toxic metals in phytoplankton but the toxicity mechanisms of this metal are still not fully understood. This study examines the toxicity targets of Cu in the modeled marine diatom, Phaeodactylum tricornutum, at the physiological (cell division, DNA cell cycle), biochemical [pigments synthesis, reactive oxygen species (ROS) and malondialdehyde (MDA)], structural (subcellular observation by flow cytometry) and molecular (transcription of several metalloprotein genes) level. Cu toxicity was detectable at all these levels after 48 h of exposure to ?20 ?M total initial added Cu. The order of sensitivity of all the studied Cu toxicity endpoints was: G2/M phase > MDA > metalloproteins RNA of the photosynthetic electron transport chain (ETC) > metalloproteins RNA of the respiratory chains > G0/G1 phase > pigments ? S phase > propidium iodide > estimated cell yield > ROS. The relatively sensitive decrease of the transcription of metalloproteins RNA of the ETC in response to Cu exposure, if associated to an effective decrease in the expression of the proteins composing the ETC, may help to initially mitigate the ROS-mediated toxic effects of Cu in P. tricornutum. However, this cellular response to Cu was only transitory and the transcription of virtually all genes involved in redox electron transfer chains was up-regulated within an interval of 2 days. This study brings new insights into the cellular mechanisms of Cu toxicity by documenting the sensitivity and kinetics of multiple Cu-cellular targets in one marine alga.
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Destabilization of gold clusters for controlled nanosynthesis: from clusters to polyhedra.
Adv. Mater. Weinheim
PUBLISHED: 01-17-2014
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A precisely controlled destabilization of gold thiolate clusters is demonstrated to grow 12 {110}-faceted gold dodecahedra with greatly enhanced catalytic capability, and reveal the growth mechanism by DFT simulations. This greatly advances our understanding of nanocrystal growth and opens a new window for controlling the dissociation of clusters to produce nanocrystals with specific shapes.
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An accurate predictor of liver failure and death after hepatectomy: a single institution's experience with 478 consecutive cases.
World J. Gastroenterol.
PUBLISHED: 01-14-2014
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To establish a reliable definition of postoperative liver failure (PLF) and allow the prediction of outcomes after hepatectomy.
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CT volumetry for gastric carcinoma: association with TNM stage.
Eur Radiol
PUBLISHED: 01-13-2014
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We evaluated the feasibility of performing CT volumetry of gastric carcinoma (GC) and its correlation with TNM stage.
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Effect of low-dose tacrolimus with mycophenolate mofetil on renal function following liver transplantation.
World J. Gastroenterol.
PUBLISHED: 01-12-2014
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To determine whether low-dose tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is a safe approach to decrease the incidence of chronic kidney disease (CKD) in liver transplantation (LT) recipients.
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Nav1.8 channels in ganglionated plexi modulate atrial fibrillation inducibility.
Cardiovasc. Res.
PUBLISHED: 01-12-2014
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Emerging evidences indicate that SCN10A/NaV1.8 is associated with cardiac conduction and atrial fibrillation, but the exact role of NaV1.8 in cardiac electrophysiology remains poorly understood. The present study was designed to investigate the effects of blocking NaV1.8 channels in cardiac ganglionated plexi (GP) on modulating cardiac conduction and atrial fibrillation inducibility in the canine model.
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On the strength of ?-sheet crystallites of Bombyx mori silk fibroin.
J R Soc Interface
PUBLISHED: 01-01-2014
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Silk fibroin, a natural multi-domain protein, has attracted great attention due to its superior mechanical properties such as ultra-high strength and stretchability, biocompatibility, as well as its versatile biodegradability and processability. It is mainly composed of ?-sheet crystallites and amorphous domains. Although its strength is well known to be controlled by the dissociation of protein chains from ?-sheet crystallites, the way that water as the solvent affects its strength and the reason that its theoretically predicted strength is several times higher than experimental measurement remain unclear. We perform all-atom molecular dynamics simulations on a ?-sheet crystallite of Bombyx mori silk. We find that water solvent reduces the number and strength of hydrogen bonds between ?-chains, and thus greatly weakens the strength of silk fibroin. By dissociating protein chains at different locations from the crystallite, we also find that the pulling strength for the interior chains is several times higher than that for the surface/corner chains, with the former being consistent with the theoretically predicted value, while the latter on par with the experimental value. It is shown that the weakest rupture strength controls the failure strength of silk fibre. Hence, this work sheds light on the role of water in the strength of silk fibroin and also provides clues on the origin of the strength difference between theory and experiment.
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Reactive oxygen species are involved in regulating hypocontractility of mesenteric artery to norepinephrine in cirrhotic rats with portal hypertension.
Int. J. Biol. Sci.
PUBLISHED: 01-01-2014
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Oxidative stress is involved in the hypocontractility of visceral artery to vasoconstrictors and formation of hyperdynamic circulation in cirrhosis with portal hypertension. In the present study, we investigated the effect of reactive oxygen species (ROS) on the mesenteric artery contractility in CCl4-induced cirrhotic rats, and the roles of G protein-coupled receptors (GPCRs) desensitization and RhoA/Rho associated coiled-coil forming protein kinase (ROCK) pathways.
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Prognostic role of NLR in urinary cancers: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Recently, many studies explored the role of inflammation parameters such as neutrophil-to-lymphocyte ratio (NLR) in the prognosis of urinary cancers, but the results were not consistent.
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Diagnostic and prognostic utility of a DNA hypermethylated gene signature in prostate cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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We aimed to identify a prostate cancer DNA hypermethylation microarray signature (denoted as PHYMA) that differentiates prostate cancer from benign prostate hyperplasia (BPH), high from low-grade and lethal from non-lethal cancers. This is a non-randomized retrospective study in 111 local Asian men (87 prostate cancers and 24 BPH) treated from 1995 to 2009 in our institution. Archival prostate epithelia were laser-capture microdissected and genomic DNA extracted and bisulfite-converted. Samples were profiled using Illumina GoldenGate Methylation microarray, with raw data processed by GenomeStudio. A classification model was generated using support vector machine, consisting of a 55-probe DNA methylation signature of 46 genes. The model was independently validated on an internal testing dataset which yielded cancer detection sensitivity and specificity of 95.3% and 100% respectively, with overall accuracy of 96.4%. Second validation on another independent western cohort yielded 89.8% sensitivity and 66.7% specificity, with overall accuracy of 88.7%. A PHYMA score was developed for each sample based on the state of methylation in the PHYMA signature. Increasing PHYMA score was significantly associated with higher Gleason score and Gleason primary grade. Men with higher PHYMA scores have poorer survival on univariate (p?=?0.0038, HR?=?3.89) and multivariate analyses when controlled for (i) clinical stage (p?=?0.055, HR?=?2.57), and (ii) clinical stage and Gleason score (p?=?0.043, HR?=?2.61). We further performed bisulfite genomic sequencing on 2 relatively unknown genes to demonstrate robustness of the assay results. PHYMA is thus a signature with high sensitivity and specificity for discriminating tumors from BPH, and has a potential role in early detection and in predicting survival.
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Influence of perineural invasion on survival and recurrence in patients with resected pancreatic cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-02-2013
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Perineural invasion (PNI) has been reported as one of the sources of locoregional recurrence in resected pancreatic cancer (PC). However the impact of PNI in resected pancreatic cancer remains controversial. The purpose of this study was to determine the association between PNI status and clinical outcomes.
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Microstructure versus flaw: mechanisms of failure and strength in nanostructures.
Nano Lett.
PUBLISHED: 11-01-2013
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Understanding failure in nanomaterials is critical for the design of reliable structural materials and small-scale devices with nanoscale components. No consensus exists on the effect of flaws on fracture at the nanoscale, but proposed theories include nanoscale flaw tolerance and maintaining macroscopic fracture relationships at the nanoscale with scarce experimental support. We explore fracture in nanomaterials using nanocrystalline Pt nanocylinders with prefabricated surface notches created using a "paused" electroplating method. In situ scanning electron microscopy (SEM) tension tests demonstrate that the majority of these samples failed at the notches, but that tensile failure strength is independent of whether failure occurred at or away from the flaw. Molecular dynamics simulations verify these findings and show that local plasticity is able to reduce stress concentration ahead of the notch to levels comparable with the strengths of microstructural features (e.g., grain boundaries). Thus, failure occurs at the stress concentration with the highest local stress whether this is at the notch or a microstructural feature.
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The role of surface oxygen in the growth of large single-crystal graphene on copper.
Science
PUBLISHED: 10-24-2013
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The growth of high-quality single crystals of graphene by chemical vapor deposition on copper (Cu) has not always achieved control over domain size and morphology, and the results vary from lab to lab under presumably similar growth conditions. We discovered that oxygen (O) on the Cu surface substantially decreased the graphene nucleation density by passivating Cu surface active sites. Control of surface O enabled repeatable growth of centimeter-scale single-crystal graphene domains. Oxygen also accelerated graphene domain growth and shifted the growth kinetics from edge-attachment-limited to diffusion-limited. Correspondingly, the compact graphene domain shapes became dendritic. The electrical quality of the graphene films was equivalent to that of mechanically exfoliated graphene, in spite of being grown in the presence of O.
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Structure-function studies of Escherichia coli?RnlA reveal a novel toxin structure involved in bacteriophage resistance.
Mol. Microbiol.
PUBLISHED: 09-20-2013
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Escherichia coli?RnlA-RnlB is a newly identified toxin-antitoxin (TA) system that plays a role in bacteriophage resistance. RnlA functions as a toxin with mRNA endoribonuclease activity and the cognate antitoxin RnlB inhibits RnlA toxicity in E.?coli cells. Interestingly, T4 phage encodes the antitoxin Dmd, which acts against RnlA to promote its own propagation, suggesting that RnlA-Dmd represents a novel TA system. Here, we have determined the crystal structure of RnlA refined to 2.10?Å. RnlA is composed of three independent domains: NTD (N-terminal domain), NRD (N repeated domain) and DBD (Dmd-binding domain), which is an organization not previously observed among known toxin structures. Small-angle X-ray scattering (SAXS) analysis revealed that RnlA forms a dimer in solution via interactions between the DBDs from both monomers. The in vitro and in vivo functional studies showed that among the three domains, only the DBD is responsible for recognition and inhibition by Dmd and subcellular location of RnlA. In particular, the helix located at the C-terminus of DBD plays a vital role in binding Dmd. Our comprehensive studies reveal the key region responsible for RnlA toxicity and provide novel insights into its structure-function relationship.
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Atrazine Affects the Circadian Rhythm of Microcystis Aeruginosa.
Chronobiol. Int.
PUBLISHED: 09-12-2013
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This study provides original data regarding the effects of atrazine (Atr) on the circadian rhythm of the cyanobacterium Microcystis aeruginosa. The results reveal that the circadian rhythms of the central circadian oscillator genes reached their peaks from 1 to 2.5?h after the light was switched on, and the circadian rhythms of physiologically related genes were highly synchronized with the central circadian oscillator genes. These circadian rhythms were consistent with cell growth at the physiological level. The circadian rhythms of the central circadian oscillator genes were altered, and their peaks disappeared or were delayed by the Atr treatment. Therefore, the rhythms of the physiologically related genes in this study also changed to synchronize the new circadian rhythms. And the physiological parameters were tightly correlated with the gene circadian rhythm in the Atr treatment, suggesting that Atr affects M. aeruginosa growth by possibly altering the circadian expression patterns of the clock. Furthermore, this influence is related to the exposure time point of Atr. Thus, chemicals treated in the suitable exposure time point can exert their fullest effects against cell growth.
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Comparative outcomes of the tubularized incised plate and transverse island flap onlay techniques for the repair of proximal hypospadias.
Int Urol Nephrol
PUBLISHED: 07-04-2013
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The optimal management of proximal hypospadias remains uncertain. In this study, the surgical outcomes of tubularized incised plate repair (TIP) and transverse island flap (TVIF) onlay urethroplasty in boys with hypospadias were compared.
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Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-19-2013
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Efforts to improve the clinical outcome of highly aggressive triple-negative breast cancer (TNBC) have been hindered by the lack of effective targeted therapies. Thus, it is important to identify the specific gene targets/pathways driving the invasive phenotype to develop more effective therapeutics. Here we show that ubiquitin-associated and SH3 domain-containing B (UBASH3B), a protein tyrosine phosphatase, is overexpressed in TNBC, where it supports malignant growth, invasion, and metastasis largely through modulating epidermal growth factor receptor (EGFR). We also show that UBASH3B is a functional target of anti-invasive microRNA200a (miR200a) that is down-regulated in TNBC. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity, which targets CBL ubiquitin ligase for dephosphorylation and inactivation, leading to EGFR up-regulation. Thus, UBASH3B may function as a crucial node in bridging multiple invasion-promoting pathways, thereby providing a potential therapeutic target for TNBC.
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Role of CT perfusion imaging in evaluating the effects of multiple burr hole surgery on adult ischemic Moyamoya disease.
Neuroradiology
PUBLISHED: 05-27-2013
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To evaluate the effects of the multiple burr hole (MBH) revascularization on ischemic type adult Moyamoya disease (MMD) by computed tomography perfusion (CTP).
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Phosphorus availability changes chromium toxicity in the freshwater alga Chlorella vulgaris.
Chemosphere
PUBLISHED: 05-10-2013
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Chromium (Cr) is one of the most serious pollutants in aquatic systems. This study examined the relationship between the toxic effects of Cr on the freshwater alga Chlorella vulgaris and phosphorus (P) availability on the algal physiology and ultrastructure. Cr inhibited C. vulgaris growth in a concentration- and time-dependent manner, and its inhibitory effect was related to the P concentration. In a low-P medium, Cr showed approximately 2.2-3.7-fold stronger toxicity than in a high-P medium. Cr was absorbed into the algal body where it disrupted the chloroplast structure and decreased the chlorophyll content. However, Cr had a weaker chlorophyll inhibitory ability and destructive power against the chloroplasts in the high-P medium than in the low-P medium due to the partial blockage of Cr absorption in high P-medium. Cr exposure also changed the metal ion and anion absorption profiles, which was also closely related to the concentration of P. Cr treatment increased the volume of the vacuole, and the larger vacuole reduced the space available for chloroplasts, as based on optical and electron microscopy results, but a higher P availability could alleviate this damage. These results suggest that high P alleviated the toxicity of Cr by decreasing Cr absorption and increasing the absorption of beneficial ions. It is, therefore, necessary to consider the phosphorus availability when the toxicity of metal compounds is evaluated.
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Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents.
Eur J Med Chem
PUBLISHED: 03-25-2013
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Two series of novel isosteviol-fused pyrazoline and pyrazole derivatives were facilely synthesized via intramolecular 1,3-dipolar cycloaddition and condensation reaction, respectively. All compounds were characterized by NMR, IR and HRMS spectra. The stereochemistry of compounds 9b, 10, 11a and 11v were further confirmed by X-ray crystallographic analysis. The antiproliferative activities of the structurally related pyrazoline and pyrazole derivatives were tested in vitro on four human malignant cell lines (SGC 7901, A549, Raji and HeLa): Our results revealed that isosteviol-fused pyrazole derivatives exhibited noteworthy cytotoxic activities. Among them, 2,4-di-Cl-phenylpyrazole derivative 11t displayed better cytotoxities with IC50 values: 2.71, 3.18, 1.09 and 13.52 ?M against SGC 7901, A549, Raji and HeLa, respectively, compared to cisplatin (IC50 values: 7.56, 17.78, 17.32 and 14.31 ?M, respectively).
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Efficacy of vitrectomy with triamcinolone assistance versus internal limiting membrane peeling for highly myopic macular hole retinal detachment.
Retina (Philadelphia, Pa.)
PUBLISHED: 03-20-2013
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To compare the outcomes of pars plana vitrectomy (PPV) with or without the adjuvant surgical procedures: triamcinolone acetonide (TA) assistance and/or internal limiting membrane (ILM) peeling for the treatment of highly myopic macular hole retinal detachment (MHRD).
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Outcome analysis of tubularized incised plate repair in hypospadias: is a catheter necessary?
Urol. Int.
PUBLISHED: 03-19-2013
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Tubularized incised plate (TIP) urethroplasty is performed by many pediatric urologists and has been widely accepted for repair of distal and mid-shaft hypospadias. However, the role of urethral catheter placement in TIP repair remains controversial. In this study, the surgical outcomes of indwelling urethral catheter and non-catheter TIP repairs in boys with hypospadias were compared.
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Purification, crystallization and preliminary crystallographic analysis of the 23S rRNA methyltransferase RlmM (Cm2498) from Escherichia coli.
Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun.
PUBLISHED: 03-07-2013
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RlmM is an AdoMet-dependent methyltransferase that is responsible for 2-O-methylation of C2498 in the peptidyl-transferase loop of bacterial 23S rRNA. This modification occurs before assembly of the 50S ribosomal subunit, and lack of C2498 methylation can cause a slight reduction in bacterial fitness. Here, the purification and crystallization of RlmM from Escherichia coli as well as its preliminary crystallographic analysis are presented. Cocrystallization of RlmM with AdoMet was carried out and X-ray diffraction data were collected to a resolution of 2.30 Å on beamline BL17U at the SSRF. However, electron density for AdoMet cannot be observed by comprehensive crystallographic analysis, indicating that it is not bound by RlmM during the cocrystallization process. The structure was solved by molecular replacement and refinement is in progress. The crystal contained one molecule in the asymmetric unit and belonged to space group P2(1), with unit-cell parameters a = 56.07, b = 59.38, c = 54.35 Å, ? = 94.84°, which differs from the P3(1) or P3(1)21 space groups of previously reported RlmM structures (PDB entries 4auk, 4atn and 4b17).
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Effects of intensive antihypertensive treatment on Chinese hypertensive patients older than 70 years.
J Clin Hypertens (Greenwich)
PUBLISHED: 02-17-2013
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This study was performed to investigate whether intensive antihypertensive treatment with achieved blood pressure (BP) ?140/90 mm Hg, as compared with standard treatment with achieved BP ?150/90 mm Hg, could further improve cardiovascular outcomes in Chinese hypertensive patients older than 70 years. A total of 724 participants were randomly assigned to intensive or standard antihypertensive treatment. After a mean follow-up of 4 years, the mean achieved BP was 135.7/76.2 mm Hg in the intensive treatment group and 149.7/82.1 mm Hg in the standard treatment group. The visit-to-visit variability in systolic BP and diastolic BP was lower in the intensive group than that in the standard group. Intensive antihypertensive treatment, compared with the standard treatment, decreased total and cardiovascular mortality by 41.7% and 50.3%, respectively, and reduced fatal/nonfatal stroke by 42.0% and heart failure death by 62.7%. Cox regression analysis indicated that the mean systolic BP (P=.020; 95% confidence interval, 1.006-1.069) and the standard deviation of systolic BP (P=.033; 95% confidence interval, 1.006-1.151) were risk factors for cardiovascular endpoint events. Intensive antihypertensive treatment with achieved 136/76 mm Hg was beneficial for Chinese hypertensive patients older than 70 years. Long-term visit-to-visit variability in systolic BP was positively associated with the incidence of cardiovascular events.
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Effects of hepatic impairment on the pharmacokinetics of everolimus: a single-dose, open-label, parallel-group study.
Clin Ther
PUBLISHED: 01-22-2013
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Although the pharmacokinetics of everolimus, an oral mammalian target of rapamycin inhibitor, have been characterized in patients with moderate hepatic impairment, they have not been assessed in those with mild or severe hepatic impairment.
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Subtractive phage display technology identifies zebrafish marcksb that is required for gastrulation.
Gene
PUBLISHED: 01-10-2013
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In the present study, we used a phage display technique to screen differentially expressed proteins from zebrafish post-gastrula embryos. With a subtractive screening approach, 6 types of single-chain Fv fragments (scFvs) were screened out from an scFv antibody phage display library by biopanning against zebrafish embryonic homogenate. Four scFv fragments (scFv1, scFv3, scFv4 and scFv6) showed significantly stronger binding to the tailbud embryos than to the 30%-epiboly embryos. A T7 phage display cDNA library was constructed from zebrafish tailbud embryos and used to identify the antigens potentially recognized by scFv1, which showed the highest frequency and strongest binding against the tailbud embryos. We acquired 4 candidate epitopes using scFv1 and the corresponding genes showed significantly higher expression levels at tailbud stage than at 30%-epiboly. The most potent epitope of scFv1 was the clone scFv1-2, which showed strong homology to zebrafish myristoylated alanine-rich C-kinase substrate b (Marcksb). Western blot analysis confirmed the high expression of marcksb in the post-gastrula embryos, and the endogenous expression of Marcksb was interfered by injection of scFv1. Zebrafish marcksb showed dynamic expression patterns during embryonic development. Knockdown of marcksb strongly affected gastrulation movements. Moreover, we revealed that zebrafish marcksb is required for cell membrane protrusion and F-actin alignment. Thus, our study uncovered 4 types of scFvs binding to zebrafish post-gastrula embryos, and the epitope of scFv1 was found to be required for normal gastrulation of zebrafish. To our knowledge, this was the first attempt to combine phage display technique with the embryonic and developmental study of vertebrates, and we were able to identify zebrafish marcksb that was required for gastrulation.
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Procedural Arrhythmia Termination and Long-Term Single-Procedure Clinical Outcome in Patients with Non-paroxysmal Atrial Fibrillation.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 01-04-2013
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The influence of procedural arrhythmia termination on long-term single-procedure clinical outcome in patients with non-paroxysmal atrial fibrillation (AF) remains controversial.
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Synthesis and in vitro cytotoxic activity evaluation of novel heterocycle bridged carbothioamide type isosteviol derivatives as antitumor agents.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-04-2013
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Two series of novel carbothioamide-substituted pyrazole and isoxazolidine derivatives were facilely prepared by functional interconversions in ring D of the tetracyclic diterpene isosteviol. The in vitro cytotoxic activities against four human tumor cell lines were evaluated. Our results indicated that carbothioamide-substituted pyrazole derivatives exhibited noteworthy cytotoxic activities. Specifically, compound 12p (IC(50)=6.51 ?M) had the most potent cytotoxicity against Raji cell, which may be exploitable as a lead compound for the development of potent antitumor agents.
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Structure analysis of the global metabolic regulator Crc from Pseudomonas aeruginosa.
IUBMB Life
PUBLISHED: 01-03-2013
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The global metabolic regulator catabolite repression control (Crc) has recently been found to modulate the susceptibility to antibiotics and virulence in the opportunistic pathogen Pseudomonas aeruginosa and been suggested as a nonlethal target for novel antimicrobials. In P. aeruginosa, Crc couples with the CA motifs from the small RNA CrcZ to form a post-transcriptional regulator system and is removed from the 5-end of the target mRNAs. In this study, we first reported the crystal structure of Crc from P. aeruginosa refined to 2.20 Å. The structure showed that it consists of two halves with similar overall topology and there are 11 ? strands surrounded by 13 helices, forming a four-layered ?/?-sandwich. The circular dichroism spectroscopy revealed that it is thermostable in solution and shares similar characteristics to that in crystal. Comprehensive structural analysis and comparison with the homologies of Crc showed high similarity with several known nucleases and consequently may be classified into a member exodeoxyribonuclease III. However, it shows distinct substrate specificity (RNA as the preferred substrate) compared to these DNA endonucleases. Structural comparisons also revealed potential RNA recognition and binding region mainly consisting of five flexible loops. Our structure study provided the basis for the future application of Crc as a target to develop new antibiotics.
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Insights into the cross-immunity mechanism within effector families of bacteria type VI secretion system from the structure of StTae4-EcTai4 complex.
PLoS ONE
PUBLISHED: 01-01-2013
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The Gram-negative bacteria type VI secretion system (T6SS) has been found to play an important role in interbacterial competition, biofilm formation and many other virulence-related processes. The bacteria harboring T6SS inject the effectors into their recipients cytoplasm or periplasm to kill them and meanwhile, to avoid inhibiting itself, the cognate immunity proteins were produced to acts as the effector inhibitor. Tae4 (type VI amidase effector 4) and Tai4 (type VI amidase immunity 4) are newly identified T6SS effector-immunity (EI) pairs. We have recently solved the structures of StTae4-Tai4 and EcTae4-Tai4 complexes from the human pathogens Salmonella typhimurium and Enterobacter cloacae, respectively. It is very interesting and important to discover whether there is cross-neutralization between St- and EcTai4 and whether their effector inhibition mechanism is conserved. Here, we determined the crystal structure of StTae4 in complex with EcTai4. The solution conformation study revealed it is a compact heterotetramer that consists of an EcTai4 homodimer binding two StTae4 molecules in solution, different from that in crystal. A remarkable shift can be observed in both the flexible winding loop of StTae4 and protruding loop of EcTai4 and disulfide bonds are formed to stabilize their overall conformations. The in vitro and in vivo interactions studies showed EcTai4 can efficiently rescue the cells from the toxicity of its cognate effectors StTae4, but can not neutralize the toxic activities of the effectors from other families. These findings provide clear structural evidence to support the previous observation of cross-immunity within T6SS families and provide a basis for understanding their important roles in polymicrobial environments.
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Scoring selection criteria including total tumour volume and pretransplant percentage of lymphocytes to predict recurrence of hepatocellular carcinoma after liver transplantation.
PLoS ONE
PUBLISHED: 01-01-2013
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The selection criteria for patients with hepatocellular carcinoma (HCC) to undergo liver transplantation should accurately predict posttransplant recurrence while not denying potential beneficiaries. In the present study, we attempted to identify risk factors associated with posttransplant recurrence and to expand the selection criteria.
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Mus81-mediated DNA cleavage resolves replication forks stalled by topoisomerase I-DNA complexes.
J. Cell Biol.
PUBLISHED: 11-30-2011
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Deoxyribonucleic acid (DNA) topoisomerases are essential for removing the supercoiling that normally builds up ahead of replication forks. The camptothecin (CPT) Top1 (topoisomerase I) inhibitors exert their anticancer activity by reversibly trapping Top1-DNA cleavage complexes (Top1ccs) and inducing replication-associated DNA double-strand breaks (DSBs). In this paper, we propose a new mechanism by which cells avoid Top1-induced replication-dependent DNA damage. We show that the structure-specific endonuclease Mus81-Eme1 is responsible for generating DSBs in response to Top1 inhibition and for allowing cell survival. We provide evidence that Mus81 cleaves replication forks rather than excises Top1ccs. DNA combing demonstrated that Mus81 also allows efficient replication fork progression after CPT treatment. We propose that Mus81 cleaves stalled replication forks, which allows dissipation of the excessive supercoiling resulting from Top1 inhibition, spontaneous reversal of Top1cc, and replication fork progression.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.