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Experimental and Modeling Study of the Phase Behavior of (Methane + CO2 + Water) Mixtures.
J Phys Chem B
PUBLISHED: 11-20-2014
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In this paper we report phase-equilibrium measurements on the system (methane + carbon dioxide + water) carried out with a high-pressure quasi-static analytical apparatus. The measurements have been made under conditions of two-phase vapor-liquid equilibrium, three-phase vapor-liquid-liquid equilibrium, and four-phase vapor-liquid-liquid-hydrate equilibrium. The compositions of three coexisting fluid phases have been obtained along eight isotherms at temperatures from (285.15 to 303.5) K and at pressures up to either the upper critical end point (UCEP) or up to the hydrate formation locus. Compositions of coexisting vapor and liquid phases have been obtained along three isotherms at temperatures from (323.15 to 423.15) K and pressures up to 20 MPa. The quadruple curve, along which hydrates coexists with the three fluid phases, was also measured along its entire length. The VLLE data obtained for this mixture have been compared with the predictions of the statistical associating fluid theory for potentials of variable range (SAFT-VR), implemented with the square-well potential using parameters fitted to pure-component and binary-mixture data. Specifically, we used the SAFT-VR parameters reported by Míguez and co-workers [Míguez, J. M.; dos Ramos, M. C.; Piñeiro, M. M.; Blas, F. J. J. Phys. Chem. B 2011, 115, 9604.]. The pressure along the quadruple curve was compared with the predictions of two different thermodynamic models. Furthermore, a detailed study of the ternary mixtures was carried out based on comparison with available ternary data of the type CO2 + n-alkane + water and available data for the constituent binary subsystems. In this way, we analyzed the observed effects on the solubility when the n-alkane component was changed or a third component was added.
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[Severe lower gastrointestinal bleeding due to GIST tumor. Radiological embolization and surgery].
Cir Cir
PUBLISHED: 11-14-2014
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Gastrointestinal stromal tumors (GIST) were identified only recently. These tumors usually have no symptoms, although they are localized, operable and curable. Although rare, if they are not diagnosed and treated early, they become very aggressive. The most common manifestation is gastrointestinal bleeding from mucosal erosion. Their presentation as severe lower gastrointestinal bleeding is exceptional.
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Nucleosome-specific, time-dependent changes in histone modifications during activation of the early growth response 1 (Egr1) gene.
J. Biol. Chem.
PUBLISHED: 11-08-2014
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Histone posttranslational modifications and nucleosome remodeling are coordinate events involved in eukaryotic transcriptional regulation. There are relatively few data on the time-course with which these events occur in individual nucleosomes. As a contribution to fill this gap, we first describe the nature and time-course of structural changes in the nucleosomes -2, -1 and +1 of the murine Egr1 gene upon induction. To initiate the transient activation of the gene, we used the stimulation of MLP29 cells with phorbol esters and the in vivo activation after partial hepatectomy. In both models, nucleosomes -1 and +1 are partially evicted while nucleosomes +1 and -2 slide downstream during transcription. The sliding of the latter nucleosome allows EGR1 protein to bind its site, resulting in the repression of the gene. To decide whether EGR1 is involved in the sliding of nucleosome -2, Egr1 was knocked down. In the absence of detectable EGR1, the nucleosome still slides and remains downstream longer than in control cells, suggesting that the product of the gene may be rather involved in the returning of the nucleosome to the basal position. On the other hand, the presence of 8 epigenetic histone marks has been determined at a mononucleosomal level in that chromatin region. H3S10phK14ac, H3K4me3, H3K9me3 and H3K27me3 are characteristic of nucleosome +1, H3K9ac and H4K16ac are mainly found in nucleosome -1 and H3K27ac predominates in nucleosomes -2 and -1. The temporal changes in these marks suggest distinct functions for some of them, while changes in H3K4me3 may result from histone turnover.
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[Short bowel: from resection to transplantation].
Nutr Hosp
PUBLISHED: 11-04-2014
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Short bowel syndrome (SBS) is characterized by a significant reduction in the effective intestinal surface by an anatomical or functional loss of the small intestine. It mainly occurs after extensive bowel resection, intestinal intrinsic disease or surgical bypass. The main complications are malabsorption, maldigestion, malnutrition, dehydratation y, potentially, lethal metabolic lesions. The treatment is based on appropiate, individualized nutritional support; however, the most recent outcomes on bowel transplantation (BT) and a great rate of survivors achieving complete digestive autonomy and able to carry out activities according to theirage allow for considering BT as the first choice therapy in patients with irreversible intestinal failure in whom poor prognosis with parenteral nutrition is foreseen. In this paper the most outstanding aspects of SBS are revised.
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In vitro activity of 'Mexican Arnica' Heterotheca inuloides Cass natural products and some derivatives against Giardia intestinalis.
Parasitology
PUBLISHED: 11-04-2014
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SUMMARY Giardiasis is a gastrointestinal disease that affects humans and other animals caused by parasitic protists of the genus Giardia. Giardia intestinalis (Syn. Giardia lamblia; Giardia duodenalis) infections can cause acute or chronic diarrhoea, dehydration, abdominal discomfort and weight loss. Metronidazole is the most widely used drug for treating giardiasis. Although effective, metronidazol has undesirable secondary effects. Plants used in traditional medicine as antidiarrhoeals or antiparasitics may represent alternative sources for new compounds to treat giardiasis. Heterotheca inuloides Cass. (Asteraceae/Compositae) plant is widely used in Mexican traditional medicine. The following secondary metabolites were isolated from H. inuloides flowers: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), 1R,4R-hydroxy-1,2,3,4-tetrahydrocadalen-15-oic acid (4), quercetin (5), quercetin-3,7,3'-trimethyl ether (6), quercetin-3,7,3',4'-tetramethyl ether (7) and eriodictyol-7,4'-dimethyl ether (8). The activity of these compounds against Giardia intestinalis trophozoites was assessed in vitro as was the activity of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (9), 7-benzoxy-3,4-dihydrocadalene (10), 7-acetoxycadalene (11), 7-benzoxycadalene (12), quercetin pentaacetate (13) and 7-hydroxycalamenene (14). Among these, 7-hydroxy-3,4-dihydrocadalene (1) and 7-hydroxycalamenene (14) were the most active, whereas the remaining compounds showed moderate or no activity. The G. intestinalis trophozoites exposed to compound 1 showed marked changes in cellular architecture along with ultrastructural disorganization. The aim of this study was to evaluate the giardicidal activity of selected H. inuloides metabolites and some semisynthetic derivatives using an in vitro experimental model of giardiasis.
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Amifostine reduces radiation-induced complications in a murine model of expander-based breast reconstruction.
Plast. Reconstr. Surg.
PUBLISHED: 10-31-2014
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Immediate expander-based breast reconstruction after mastectomy is a prevalent option for many women with breast cancer. When coupled with adjuvant radiation therapy, however, radiation-induced skin and soft-tissue injury diminish the success of this reconstructive technique. The authors hypothesize that prophylactic administration of the cytoprotectant amifostine will reduce soft-tissue complications from irradiation, aiding expander-based reconstruction.
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Primary Cutaneous Small/Medium CD4+ T-Cell Lymphoma Occurring During Treatment With Vemurafenib for Advanced Melanoma.
Am J Dermatopathol
PUBLISHED: 10-31-2014
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: The discovery of BRAF mutations in 40%-60% of melanomas led to the development of BRAF inhibitors, which exhibit objective response in over 50% of patients. However, up to 98% of the patients develop at least 1 side effect. We report for the first time a patient with metastatic melanoma harboring BRAF V600E mutation that develops a primary, cutaneous small/medium CD4 T-cell lymphoma secondarily to the treatment with vemurafenib. A 54-year-old man with a history of metastatic melanoma treated with the oral BRAF inhibitor vemurafenib presents, 4 months after the initiation of the treatment, with multiple, nodular firm nonulcerated lesions on his back. Two skin biopsies from the lesions revealed a primary, cutaneous small/medium CD4 T-cell lymphoma.The extensive use of recently approved mutation-specific RAF inhibitors seems to be speeding up the emergence of unknown nonpreventable toxicities of these agents. Our patient developed a primary, cutaneous small/medium CD4 T-cell lymphoma, which presented 4 months after the commencement of vemurafenib. Although no treatment interruption is normally required, a close monitoring of the patients with advanced melanomas treated with vemurafenib seems imperative to optimize the management strategies.
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[Satisfactory cervical cytology. Circular exocervical cytologic smears against longitudinal exocervical smears].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 10-30-2014
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In the Mexican Institute of Social Security, since 1962 the exocervical sample is normally extended with a circular motion technique (the usual technique). In 2006, the Ministry of Health established that the exocervical sample shall be extended with longitudinal technique (standard technique). We proposed a new technique: the exocervical widespread. Our objective was to evaluate the efficacy and quality of three techniques.
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[Efficacy of motivational interventions in the treatment of overweight and obesity].
Nutr Hosp
PUBLISHED: 10-23-2014
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Changing unhealthy behaviors: Diet and physical activity are key to treating obesity. The objective of this study is to determine whether an intervention group motivational intervention group by nurses trained by expert psychologist, complementary to the usual intervention is more effective than the latter in the treatment of overweight and obesity in relation to weight reduction percentage and the persistence over time of the reduction achieved.
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The Rac Inhibitor EHop-016 Inhibits Mammary Tumor Growth and Metastasis in a Nude Mouse Model.
Transl Oncol
PUBLISHED: 10-01-2014
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Metastatic disease still lacks effective treatments, and remains the primary cause of cancer mortality. Therefore, there is a critical need to develop better strategies to inhibit metastatic cancer. The Rho family GTPase Rac is an ideal target for anti-metastatic cancer therapy, because Rac is a key molecular switch that is activated by a myriad of cell surface receptors to promote cancer cell migration/invasion and survival. Previously, we reported the design and development of EHop-016, a small molecule compound, which inhibits Rac activity of metastatic cancer cells with an IC50 of 1 ?M. EHop-016 also inhibits the activity of the Rac downstream effector p21-activated kinase (PAK), lamellipodia extension, and cell migration in metastatic cancer cells. Herein, we tested the efficacy of EHop-016 in a nude mouse model of experimental metastasis, where EHop-016 administration at 25 mg/kg body weight (BW) significantly reduced mammary fat pad tumor growth, metastasis, and angiogenesis. As quantified by UPLC MS/MS, EHop-016 was detectable in the plasma of nude mice at 17 to 23 ng/ml levels at 12 h following intraperitoneal (i.p.) administration of 10 to 25 mg/kg BW EHop-016. The EHop-016 mediated inhibition of angiogenesis In Vivo was confirmed by immunohistochemistry of excised tumors and by In Vitro tube formation assays of endothelial cells. Moreover, EHop-016 affected cell viability by down-regulating Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as increasing caspase 3/7 activities in metastatic cancer cells. In conclusion, EHop-016 has potential as an anticancer compound to block cancer progression via multiple Rac-directed mechanisms.
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SPX1 is a phosphate-dependent inhibitor of PHOSPHATE STARVATION RESPONSE 1 in Arabidopsis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-30-2014
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To cope with growth in low-phosphate (Pi) soils, plants have evolved adaptive responses that involve both developmental and metabolic changes. PHOSPHATE STARVATION RESPONSE 1 (PHR1) and related transcription factors play a central role in the control of Pi starvation responses (PSRs). How Pi levels control PHR1 activity, and thus PSRs, remains to be elucidated. Here, we identify a direct Pi-dependent inhibitor of PHR1 in Arabidopsis, SPX1, a nuclear protein that shares the SPX domain with yeast Pi sensors and with several Pi starvation signaling proteins from plants. Double mutation of SPX1 and of a related gene, SPX2, resulted in molecular and physiological changes indicative of increased PHR1 activity in plants grown in Pi-sufficient conditions or after Pi refeeding of Pi-starved plants but had only a limited effect on PHR1 activity in Pi-starved plants. These data indicate that SPX1 and SPX2 have a cellular Pi-dependent inhibitory effect on PHR1. Coimmunoprecipitation assays showed that the SPX1/PHR1 interaction in planta is highly Pi-dependent. DNA-binding and pull-down assays with bacterially expressed, affinity-purified tagged SPX1 and ?PHR1 proteins showed that SPX1 is a competitive inhibitor of PHR1 binding to its recognition sequence, and that its efficiency is highly dependent on the presence of Pi or phosphite, a nonmetabolizable Pi analog that can repress PSRs. The relative strength of the SPX1/PHR1 interaction is thus directly influenced by Pi, providing a link between Pi perception and signaling.
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In Vivo Disruption of an Rb-E2F-Ezh2 Signaling Loop Causes Bladder Cancer.
Cancer Res.
PUBLISHED: 09-24-2014
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Bladder cancer is a highly prevalent human disease in which retinoblastoma (Rb) pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here, we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate bladder cancer development. The characterization of the mouse tumors revealed multiple molecular features of human bladder cancer, including the activation of E2F transcription factor and subsequent Ezh2 expression and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. These mice represent a genetically defined model for human high-grade superficial bladder cancer. Whole transcriptional characterizations of mouse and human bladder tumors revealed a significant overlap and confirmed the predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, the increased tumor recurrence and progression in human patients with superficial bladder cancer is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial bladder cancer and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development. Cancer Res; 74(22); 6565-77. ©2014 AACR.
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Femoral Revision Arthroplasty for Su Type 3 Supracondylar Periprosthetic Knee Fractures.
J Knee Surg
PUBLISHED: 09-24-2014
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Periprosthetic distal femoral fractures can present significant reconstructive challenges when associated with poor bone stock, comminution, or component loosening. Revision arthroplasty with stemmed components or distal femoral replacement arthroplasty often becomes necessary. This retrospective study reviewed the results of femoral revision arthroplasty in 16 knees with acute, extreme distal (Su type 3), supracondylar periprosthetic fractures using cemented, midlevel constrained implants. The mean patient age was 71 years and mean follow-up was 5 years. All fractures united with mean Knee Society scores of 86 and 55, at the last follow-up. All patients returned to preinjury activity level. Complications included one valgus malunion with shortening and one reoperation for functional lateral instability. This treatment modality achieved reliable fracture union and return of function. Moreover, the final salvage option of distal femoral arthroplasty is preserved.
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Corticosteroid versus platelet-rich plasma injection in epicondylitis.
Orthop Nurs
PUBLISHED: 09-19-2014
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Lateral epicondylitis (LE) is often considered an inflammatory disease characterized by tendon microtears that are followed by an incomplete reparative response that leads to chronic pain and decreased function on the upper extremity. A modality that is commonly used for the treatment of LE is the injection of corticosteroids. Evidence supports corticosteroid injections to be an effective short-term intervention that lacks intermediate and long-term relief as well as having negative effects on tenocyte proliferation, which is essential in the tissue healing process. Platelet-rich plasma (PRP) has been shown to be more effective, providing longer positive results with a lower recurrence rate. PRP's powerful growth factor stimulates tissue repair and protects tenocytes from the cytotoxic effects caused by corticosteroids. Unfortunately, the efficacy of PRP has been questioned because of past study designs. Nevertheless, recent studies provide practice-changing evidence that supports the use of PRP for the treatment of LE.
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Primary Cutaneous Spindle Cell B-Cell Lymphoma of Follicle Origin Mimicking Acne Rosacea.
Am J Dermatopathol
PUBLISHED: 09-18-2014
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: Primary cutaneous spindle cell lymphoma is a unique morphologic variant of cutaneous B-cell follicle center lymphoma characterized by a prominent population of spindle-shaped, medium, and large B lymphocytes with a poorly formed storiform pattern.We report a case of a 35-year-old woman who presented with a well-defined erythematous plaque with 2 nodular, nontender nonscaling nonulcerated lesions on her right cheek mimicking acne rosacea. Microscopic examination revealed a tumor mainly centered in the reticular dermis and mostly composed of spindle-shaped large B lymphocytes exhibiting bizarre shapes with "boomerang-like" or "spermatozoa-like" appearance. The immunohistochemical staining demonstrated neoplastic lymphocytes positive for CD20, CD79?, and BCL-6, and negative for CD3, CD43, CD10, BCL-2, and MUM-1. These results supported the diagnosis of a follicle center B-cell lymphoma with spindle cells.Although this rare variant of primary cutaneous B-cell lymphoma is not included in the recent WHO-EORTC classification, the rarity of this tumor and its unique morphologic appearance frequently leads to misdiagnosis and delays its treatment.
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Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients.
Medicine (Baltimore)
PUBLISHED: 09-03-2014
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Giant cell arteritis (GCA) is a relapsing disease. However, the nature, chronology, therapeutic impact, and clinical consequences of relapses have been scarcely addressed. We conducted the present study to investigate the prevalence, timing, and characteristics of relapses in patients with GCA and to analyze whether a relapsing course is associated with disease-related complications, increased glucocorticoid (GC) doses, and GC-related adverse effects. The study cohort included 106 patients, longitudinally followed by the authors for 7.8?±?3.3 years. Relapses were defined as reappearance of disease-related symptoms requiring treatment adjustment. Relapses were classified into 4 categories: polymyalgia rheumatica (PMR), cranial symptoms (including ischemic complications), systemic disease, or symptomatic large vessel involvement. Cumulated GC dose during the first year of treatment, time required to achieve a maintenance prednisone dose <10?mg/d (T10), <5?mg/d (T5), or complete prednisone discontinuation (T0), and GC-related side effects were recorded. Sixty-eight patients (64%) experienced at least 1 relapse, and 38 (36%) experienced 2 or more. First relapse consisted of PMR in 51%, cranial symptoms in 31%, and systemic complaints in 18%. Relapses appeared predominantly, but not exclusively, within the first 2 years of treatment, and only 1 patient developed visual loss. T10, T5, and T0 were significantly longer in patients with relapses than in patients without relapse (median, 40 vs 27 wk, p ?
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Does Tourniquet Time in Primary Total Knee Arthroplasty Influence Clinical Recovery?
J Knee Surg
PUBLISHED: 09-02-2014
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There are limited data on the influence of a reduced tourniquet time strategy on the clinical outcome of primary total knee arthroplasty (TKA). The aim of our study was to prospectively compare clinical recovery in two groups of patients undergoing TKA based on differences in tourniquet strategy at the same institution. Group A (40 patients) consisted of TKAs performed by a surgeon using tourniquet from incision to arthrotomy closure, and group B (40 patients) consisted of TKAs performed by another surgeon using tourniquet only during cementation. The surgical technique, implants, perioperative management, and patient demographics were similar between groups. Average tourniquet time was significantly higher in group A (71.7 minutes) as compared with group B (36.8 minutes). The maximum hemoglobin (Hb)/hematocrit (Hct) drop was statistically higher in group B (Hb drop?=?3.5?±?0.9 g/dL; Hct drop?=?11?±?3) as compared with group A (Hb drop?=?2.9?±?0.9 g/dL; Hct drop?=?9?±?2; Hb drop p?=?0.01; Hct drop p?=?0.002). There were no significant differences in visual analogue scale pain scores, narcotic consumption, ability to straight leg raise during hospital stay, range of motion (ROM) at discharge, as well as isometric quadriceps strength, ROM, Short Form 36 scores, Knee Society scores at 6 weeks, 3 months, and 1?year follow-up with a similar multimodal pain management protocol. Radiographic analysis revealed no differences in cement penetration around the tibial component in any zone. Four patients developed pulmonary embolism (three in group A, one in group B) and five patients underwent manipulation under anesthesia for stiffness (four in group A, one in group B). Thus, the use of a tourniquet only during cementing in TKA increases the hemoglobin drop and does not significantly influence pain or clinical recovery with available numbers, but was associated with a lower incidence of early complications. It is a learned surgical skill which significantly reduces tourniquet time and achieves a similar quality of cementing.
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Vascular analysis as a proxy for mechanostransduction response in an isogenic, irradiated murine model of mandibular distraction osteogenesis.
Microvasc. Res.
PUBLISHED: 08-27-2014
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Head and neck cancer is a debilitating and disfiguring disease. Although numerous treatment options exist, an array of debilitating side effects accompany them, causing physiological and social problems. Distraction osteogenesis (DO) can avoid many of the pathologies of current reconstructive strategies; however, due to the deleterious effects of radiation on bone vascularity, DO is generally ineffective. This makes investigating the effects of radiation on neovasculature during DO and creating quantifiable metrics to gauge the success of future therapies vital. The purpose of this study was to develop a novel isogenic rat model of impaired vasculogenesis of the regenerate mandible in order to determine quantifiable metrics of vascular injury and associated damage.
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Melanoma: diagnosis, staging, and treatment. Consensus group recommendations.
Adv Ther
PUBLISHED: 08-22-2014
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The incidence of malignant melanoma is increasing worldwide. In Spain, its incidence is increasing faster than any other cancer type, with a 5-year survival rate of about 85%. The impact and characteristics of malignant melanoma in the Spanish population can be ascertained from the national melanoma registry of the Academia Española de Dermatología y Venereología. This review presents consensus group recommendations for the diagnosis, staging and treatment of malignant melanoma in Spain. Incidence and mortality are discussed, as well as evaluation of various prevention and treatment strategies. Prognostic factors, such as BRAF and C-KIT mutations, which are expected to become routine staging procedures over the next few years, are outlined, especially in relation to treatment options. The use of recently approved targeted agents such as ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitor, and vemurafenib, a BRAF inhibitor, in metastatic disease are also discussed.
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Protein crystal structure obtained at 2.9 Å resolution from injecting bacterial cells into an X-ray free-electron laser beam.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-18-2014
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It has long been known that toxins produced by Bacillus thuringiensis (Bt) are stored in the bacterial cells in crystalline form. Here we describe the structure determination of the Cry3A toxin found naturally crystallized within Bt cells. When whole Bt cells were streamed into an X-ray free-electron laser beam we found that scattering from other cell components did not obscure diffraction from the crystals. The resolution limits of the best diffraction images collected from cells were the same as from isolated crystals. The integrity of the cells at the moment of diffraction is unclear; however, given the short time (? 5 µs) between exiting the injector to intersecting with the X-ray beam, our result is a 2.9-Å-resolution structure of a crystalline protein as it exists in a living cell. The study suggests that authentic in vivo diffraction studies can produce atomic-level structural information.
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Catalysis. Highly active copper-ceria and copper-ceria-titania catalysts for methanol synthesis from CO?.
Science
PUBLISHED: 08-02-2014
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The transformation of CO2 into alcohols or other hydrocarbon compounds is challenging because of the difficulties associated with the chemical activation of CO2 by heterogeneous catalysts. Pure metals and bimetallic systems used for this task usually have low catalytic activity. Here we present experimental and theoretical evidence for a completely different type of site for CO2 activation: a copper-ceria interface that is highly efficient for the synthesis of methanol. The combination of metal and oxide sites in the copper-ceria interface affords complementary chemical properties that lead to special reaction pathways for the CO2?CH3OH conversion.
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Acral Mycosis Fungoides With Epidermal Microvesiculation Mucinosis.
Am J Dermatopathol
PUBLISHED: 07-23-2014
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: Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma. This entity may present with a wide spectrum of clinicopathological manifestations and mimic different dermatoses. Among its histopathological variants, spongiosis is an infrequent finding, and spongiotic microvesiculation is particularly rare. Mucinous deposition is a common event in folliculosebaceous units of folliculotropic MF but rarely described within the epidermis. Herein, we report a patient with eczematous palmoplantar lesions whereby the histological, immunohistochemical, and molecular studies confirmed to be a unique case of MF showing epidermal microvesiculation mucinosis.
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Charge Polarization at a Au-TiC Interface and the Generation of Highly Active and Selective Catalysts for the Low-Temperature Water-Gas Shift Reaction.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-14-2014
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Au atoms in contact with TiC(001) undergo significant charge polarization. Strong metal-support interactions make Au/TiC(001) an excellent catalyst for the low-temperature water-gas shift (WGS), with turnover frequencies orders of magnitude larger than those observed for conventional metal/oxide catalysts. DFT calculations indicate that the WGS reaction follows an associative mechanism with HOCO as a key intermediate.
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Regulatory and functional connection of microphthalmia-associated transcription factor and anti-metastatic pigment epithelium derived factor in melanoma.
Neoplasia
PUBLISHED: 07-13-2014
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Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor (MITF) in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.
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Tamoxifen, an anticancer drug, is an activator of human aldehyde dehydrogenase 1A1.
Proteins
PUBLISHED: 06-25-2014
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The modulation of aldehyde dehydrogenase (ALDH) activity has been suggested as a promising option for the prevention or treatment of many diseases. To date, only few activating compounds of ALDHs have been described. In this regard, N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide has been used to protect the heart against ischemia/reperfusion damage. In the search for new modulating ALDH molecules, the binding capability of different compounds to the active site of human aldehyde dehydrogenase class 1A1 (ALDH1A1) was analyzed by molecular docking, and their ability to modulate the activity of the enzyme was tested. Surprisingly, tamoxifen, an estrogen receptor antagonist used for breast cancer treatment, increased the activity and decreased the Km for NAD(+) by about twofold in ALDH1A1. No drug effect on human ALDH2 or ALDH3A1 was attained, showing that tamoxifen was specific for ALDH1A1. Protection against thermal denaturation and competition with daidzin suggested that tamoxifen binds to the aldehyde site of ALDH1A1, resembling the interaction of N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide with ALDH2. Further kinetic analysis indicated that tamoxifen activation may be related to an increase in the Kd for NADH, favoring a more rapid release of the coenzyme, which is the rate-limiting step of the reaction for this isozyme. Therefore, tamoxifen might improve the antioxidant response, which is compromised in some diseases. Proteins 2014. © 2014 Wiley Periodicals, Inc.
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Multiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes.
Hum. Mol. Genet.
PUBLISHED: 06-16-2014
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Determining the full complement of protein-coding genes is a key goal of genome annotation. The most powerful approach for confirming protein-coding potential is the detection of cellular protein expression through peptide mass spectrometry (MS) experiments. Here, we mapped peptides detected in seven large-scale proteomics studies to almost 60% of the protein-coding genes in the GENCODE annotation of the human genome. We found a strong relationship between detection in proteomics experiments and both gene family age and cross-species conservation. Most of the genes for which we detected peptides were highly conserved. We found peptides for >96% of genes that evolved before bilateria. At the opposite end of the scale, we identified almost no peptides for genes that have appeared since primates, for genes that did not have any protein-like features or for genes with poor cross-species conservation. These results motivated us to describe a set of 2001 potential non-coding genes based on features such as weak conservation, a lack of protein features, or ambiguous annotations from major databases, all of which correlated with low peptide detection across the seven experiments. We identified peptides for just 3% of these genes. We show that many of these genes behave more like non-coding genes than protein-coding genes and suggest that most are unlikely to code for proteins under normal circumstances. We believe that their inclusion in the human protein-coding gene catalogue should be revised as part of the ongoing human genome annotation effort.
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A randomized, controlled, prospective study evaluating the effect of patellar eversion on functional outcomes in primary total knee arthroplasty.
J Bone Joint Surg Am
PUBLISHED: 05-31-2014
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Patellar mobilization technique during total knee arthroplasty has been debated, with some suggesting that lateral retraction, rather than eversion, of the patella may be beneficial. We hypothesized that patients with knees surgically exposed using patellar lateral retraction would have comparable outcomes with patients with knees surgically exposed using patellar eversion.
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Feeding Habits and Trophic Level of the Panama Grunt Pomadasys panamensis, an Important Bycatch Species from the Shrimp Trawl Fishery in the Gulf of California.
ScientificWorldJournal
PUBLISHED: 05-26-2014
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The Panama grunt is an abundant and commercially important species in the southeastern Gulf of California, but the research undertaken on this species is scarce despite its ecological and economic importance. We studied the feeding habits of Panama grunt through stomach content analyses as a first step towards understanding the biology of this species in the study area. Our results indicate that the Panama grunt is a benthic predator throughout its life cycle and feeds mainly on infaunal crustaceans. Diet differences among grunt were not found according to size, diet, or season. Shannon diversity index results indicate that Panama grunt has a limited trophic niche breadth with a diet dominated by a limited number of taxa as crustaceans. The estimated trophic level of this species is 3.59. Overall, the Panama grunt is a carnivorous fish occupying the intermediate levels of the trophic pyramid.
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Familial nonmedullary thyroid cancer: Screening, clinical, molecular and genetic findings.
Biochim. Biophys. Acta
PUBLISHED: 05-26-2014
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Thyroid cancer, the commonest of endocrine malignancies, continues increasing in incidence being the 5th more prevalent cancer among women in the United States in 2012. Familial thyroid cancer has become a well-recognized, unique, clinical entity in patients with thyroid cancer originating from follicular cells, that is, nonmedullary thyroid carcinoma. Hereditary nonmedullary thyroid cancer may occur as a minor component of familial cancer syndromes (familial adenomatous polyposis, Gardner's syndrome, Cowden's disease, Carney's complex type 1, Werner's syndrome, and papillary renal neoplasia) or as a primary feature (familial nonmedullary thyroid cancer [FNMTC]). Although there is some controversy, some epidemiologic and clinical kindred studies have shown that FNMTC is associated with more aggressive disease than sporadic cases, with higher rates of multicentric tumours, lymph node metastasis, extrathyroidal invasion, and shorter disease-free survival. This way, preventing screening will allow earlier detection, more timely intervention, and hopefully improved outcomes for patients and their families. On the other hand, in the last years, an important number of genetic studies on FNMTC have been published, trying to determine its genetic contribution. However, the genetic inheritance of FNMTC remains unclear; but it is believed to be autosomal dominant with incomplete penetrance and variable expressivity. This paper provides an extensive overview of FNMTC from several points of view. Firstly, the impact of early detection on prognosis, secondly, the management and follow-up of FNMTC patients, and finally, the role of susceptibility loci, microRNAs (miRNAs) and telomerases in recently identified isolated cases of FNMTC.
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Role of micro-RNA in colorectal cancer screening.
Cir Esp
PUBLISHED: 05-15-2014
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MicroRNAs are involved in carcinogenesis through postranscriptional gene regulatory activity. These molecules are involved in various physiological and pathological functions, such as apoptosis, cell proliferation and differentiation, which indicates their functionality in carcinogenesis as tumour suppressor genes or oncogenes. Several studies have determined the presence of microRNAs in different neoplastic diseases such as colon, prostate, breast, stomach, pancreas, and lung cancer. There are promising data on the usefulness of quantifying microRNAs in different organic fluids and tissues. We have conducted a review of the determinations of microRNAs in the diagnosis of colorectal cancer.
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?-Synuclein inclusions in the skin of Parkinson's disease and parkinsonism.
Ann Clin Transl Neurol
PUBLISHED: 05-11-2014
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The presence in the brain of ?-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of ?-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. Our goals were, first, to demonstrate the presence of ?-synuclein inclusions in the skin and, second, to detect quantitative differences between patients with PD and atypical parkinsonism (AP).
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Gastric necrosis: A late complication of nissen fundoplication.
World J Gastrointest Surg
PUBLISHED: 04-08-2014
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Gastric necrosis is a rare condition because of the rich blood supply and the extensive submucosal vascular network of the stomach. "Gas-bloat" syndrome is a well known Nissen fundoplication postoperative complication. It may cause severe gastric dilatation, but very rarely an ischemic compromise of the organ. Other factors, such as gastric outlet obstruction, may concur to cause an intraluminal pressure enough to blockade venous return and ultimately arterial blood supply and oxygen deliver, leading to ischaemia. We report a case of a 63-year-old women, who presented a total gastric necrosis following laparoscopic Nissen fundoplication and a pyloric phytobezoar which was the trigger event. No preexisting gastric motility disorders were present by the time of surgery, as demonstrated in the preoperative barium swallow, thus a poor mastication (patient needed no dentures) of a high fiber meal (cabbage) may have been predisposing factors for the development of a bezoar in an otherwise healthy women at the onset of old age. A total gastrectomy with esophagojejunostomy was performed and patient was discharged home after a 7-d hospital stay with no immediate complications. We also discuss some technical aspects of the procedure that might be important to reduce the incidence of this complication.
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Analysis of two autoimmunity genes, IRAK1 and MECP2, in giant cell arteritis.
Clin. Exp. Rheumatol.
PUBLISHED: 04-07-2014
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The Xq28 region, containing IRAK and MECP2, represent a common susceptibility locus for a high number of autoimmune diseases. Our aim in the present study was to evaluate the influence of the IRAK1 and MECP2 autoimmunity-associated genetic variants in the giant cell arteritis (GCA) susceptibility and its clinical subphenotypes.
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Prognostic value of dual-specificity phosphatase 6 expression in non-small cell lung cancer.
Tumour Biol.
PUBLISHED: 03-27-2014
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Dual-specificity phosphatase 6 (DUSP6/MKP-3) is a mitogen-activated protein kinase phosphatase that regulates extracellular signal-regulated kinases (ERKs) activity via feedback mechanisms, with an increasingly recognized role in tumour biology. The aim of this study was to explore the role of DUSP6 expression in the prognosis of human non-small cell lung cancer (NSCLC). DUSP6 expression levels were evaluated by real-time quantitative reverse transcription polymerase chain reaction (PCR) in 60 NSCLC samples from patients who underwent pulmonary resection at 12 de Octubre University Hospital. We performed a statistical analysis to investigate the correlation of DUSP6 expression and the clinical outcomes. We found that 66.7 % of the tumour samples show the downregulation of DUSP6 at the messenger RNA (mRNA) levels compared to benign epithelial lung tissues and 55 % of them show at least twofold downregulation of DUSP6 gene expression. Patients were classified into three groups according to their DUSP6 expression levels and those with very low levels (at least twofold downregulation) had the worst outcomes. Using the value of twice below the mean value in benign epithelial lung tissue as a cutoff, the overall survival of patients with very low DUSP6 levels was significantly lower than that in the rest of patients (31.9?±?18.8 months vs. not reached, P?=?0.049). This was most pronounced in adenocarcinoma histology and high-stage tumour samples. Our results suggest that DUSP6 gene expression in tumour samples may be a prognostic marker in NSCLC.
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Positron emission tomography assessment of large vessel inflammation in patients with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case-control study.
Ann. Rheum. Dis.
PUBLISHED: 03-24-2014
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Positron emission tomography (PET) scan is emerging as a promising imaging technique to detect large-vessel inflammation in giant cell arteritis (GCA). However, the lack of a standardised definition of arteritis based on (18)fluorodeoxyglucose (FDG) uptake is an important limitation to the use of PET scan for diagnostic purposes.
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Extracellular signal-regulated kinase (ERK) expression and activation in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival.
Tumour Biol.
PUBLISHED: 03-14-2014
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Extracellular signal-regulated kinase (ERK) has been considered as a critical regulator of diverse cellular processes such as proliferation, survival and motility, being implicated in the malignant transformation in several tissue types. The present study aimed to evaluate the clinical significance of total ERK1 (t-ERK1) and phosphorylated ERK1/2 (p-ERK1/2) protein expression in mobile tongue squamous cell carcinoma (SCC). t-ERK1 and p-ERK1/2 protein expression in tumour cells and infiltrating the tumour microenvironment lymphoid cells was assessed immunohistochemically on 47 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. Enhanced nuclear t-ERK1 and p-ERK1/2 expression in tumour cells was associated with the absence of perineural invasion (p = 0.043) and shorter overall patients' survival (log-rank test, p = 0.028), respectively. Enhanced t-ERK1 expression in infiltrating lymphoid cells was significantly associated with female gender, absence of vascular and perineural invasion, lymph node metastases and early depth of invasion (p = 0.008, p = 0.019, p = 0.011, p = 0.036 and p = 0.001, respectively), as well as with longer disease-free survival times (log-rank test, p = 0.038). Enhanced p-ERK1/2 expression in infiltrating lymphoid cells was significantly associated with the presence of vascular invasion and lymph node metastases (p = 0.019 and p = 0.004, respectively) and shorter overall patients' survival (log-rank test, p = 0.013). In multivariate analysis, p-ERK1/2 expression in tumour cells and infiltrating lymphoid cells was identified as independent prognostic factors of overall survival (Cox regression analysis, p = 0.045 and p = 0.032, respectively). The present study supported evidence that ERK signalling pathway may exert a potential role in the pathophysiological aspects of the mobile tongue SCC, presenting also potential utility as a biomarker for patients' survival and reinforcing the development of novel anti-cancer therapies targeting ERK signalling cascade in this type of human malignancy.
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RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway.
Cancer Cell
PUBLISHED: 03-13-2014
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Although common cancer hallmarks are well established, lineage-restricted oncogenes remain less understood. Here, we report an inherent dependency of melanoma cells on the small GTPase RAB7, identified within a lysosomal gene cluster that distinguishes this malignancy from over 35 tumor types. Analyses in human cells, clinical specimens, and mouse models demonstrated that RAB7 is an early-induced melanoma driver whose levels can be tuned to favor tumor invasion, ultimately defining metastatic risk. Importantly, RAB7 levels and function were independent of MITF, the best-characterized melanocyte lineage-specific transcription factor. Instead, we describe the neuroectodermal master modulator SOX10 and the oncogene MYC as RAB7 regulators. These results reveal a unique wiring of the lysosomal pathway that melanomas exploit to foster tumor progression.
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Development of porous titanium for biomedical applications: A comparison between loose sintering and space-holder techniques.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 03-04-2014
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One of the most important concerns in long-term prostheses is bone resorption as a result of the stress shielding due to stiffness mismatch between bone and implant. The aim of this study was to obtain porous titanium with stiffness values similar to that exhibited by cortical bone. Porous samples of commercial pure titanium grade-4 were obtained by following both loose-sintering processing and space-holder technique with NaCl between 40 and 70% in volume fraction. Both mechanical properties and porosity morphology were assessed. Young's modulus was measured using uniaxial compression testing, as well as ultrasound methodology. Complete characterization and mechanical testing results allowed us to determine some important findings: (i) optimal parameters for both processing routes; (ii) better mechanical response was obtained by using space-holder technique; (iii) pore geometry of loose sintering samples becomes more regular with increasing sintering temperature; in the case of the space-holder technique that trend was observed for decreasing volume fraction; (iv) most reliable Young's modulus measurements were achieved by ultrasound technique.
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Modern Trunnions Are More Flexible: A Mechanical Analysis of THA Taper Designs.
Clin. Orthop. Relat. Res.
PUBLISHED: 02-24-2014
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There is renewed concern surrounding the potential for corrosion at the modular head-neck junction to cause early failure in contemporary THAs. Although taper corrosion involves a complex interplay of many factors, a previous study suggested that a decrease in flexural rigidity of the femoral trunnion may be associated with an increased likelihood of corrosion at retrieval.
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PLCG1 mutations in cutaneous T-cell lymphomas.
Blood
PUBLISHED: 02-04-2014
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Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of primary cutaneous T-cell lymphoproliferative processes, mainly composed of mycosis fungoides and Sézary syndrome, the aggressive forms of which lack an effective treatment. The molecular pathogenesis of CTCL is largely unknown, although neoplastic cells show increased signaling from T-cell receptors (TCRs). DNAs from 11 patients with CTCL, both normal and tumoral, were target-enriched and sequenced by massive parallel sequencing for a selection of 524 TCR-signaling-related genes. Identified variants were validated by capillary sequencing. Multiple mutations were found that affected several signaling pathways, such as TCRs, nuclear factor ?B, or Janus kinase/signal transducer and activator of transcription, but PLCG1 was found to be mutated in 3 samples, 2 of which featured a redundant mutation (c.1034T>C, S345F) in exon 11 that affects the PLCx protein catalytic domain. This mutation was further analyzed by quantitative polymerase chain reaction genotyping in a new cohort of 42 patients with CTCL, where it was found in 19% of samples. Immunohistochemical analysis for nuclear factor of activated T cells (NFAT) showed that PLCG1-mutated cases exhibited strong NFAT nuclear immunostaining. Functional studies demonstrated that PLCG1 mutants elicited increased downstream signaling toward NFAT activation, and inhibition of this pathway resulted in reduced CTCL cell proliferation and cell viability. Thus, increased proliferative and survival mechanisms in CTCL may partially depend on the acquisition of somatic mutations in PLCG1 and other genes that are essential for normal T-cell differentiation.
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[Life style and metabolic control in DiabetIMSS program].
Gac Med Mex
PUBLISHED: 02-01-2014
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To compare the lifestyle and metabolic control of diabetes patients included and not included in the DiabetIMSS program.
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Symptomatic flexion instability in posterior stabilized primary total knee arthroplasty.
Orthopedics
PUBLISHED: 01-30-2014
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Flexion instability in posterior-stabilized total knee arthroplasty is a relatively uncommon but distinct problem that is often underdiagnosed and may require surgical management. This retrospective study evaluated the authors' management strategy and assessed the results of revision surgery. The authors identified 19 knees that underwent revision for isolated flexion instability after primary posterior-stabilized total knee arthroplasty. All patients had typical symptoms and signs of flexion instability, which include diffuse pain, especially when negotiating stairs, a sense of instability without giving way, recurrent joint effusions, and diffuse periarticular tenderness. Knee Society scores were used to assess pain and function. Complete revision was performed in 11 knees, femoral revision with a thicker insert was performed in 1 knee, and isolated tibial polyethylene insert exchange was performed in 7 knees. Postoperatively, all patients reported improvement in instability symptoms and signs associated with improvement in mean Knee Society scores. Revision surgery with careful gap balancing is successful in the management of isolated flexion instability in posterior-stabilized total knee arthroplasty. Isolated tibial polyethylene insert exchange may have a role in selected patients where component malalignment and malrotation is ruled out and a thicker and/or semiconstrained insert can be used, while limiting the resultant flexion contracture to less than 5°.
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Diagnosis and classification of polyarteritis nodosa.
J. Autoimmun.
PUBLISHED: 01-28-2014
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Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis preferentially targeting medium-sized arteries and not associated with glomerulonephritis or small vessel involvement. Anti-neutrophil cytoplasmic antibodies are typically negative. PAN may be triggered by viral infections, particularly hepatitis B virus, but remains idiopathic in most cases. Clinical manifestations of PAN are multisystemic. Peripheral nerve and skin are the most frequently affected tissues. Involvement of the gastrointestinal tract, kidneys, heart, and central nervous system is associated with higher mortality. Laboratory abnormalities reveal a prominent acute phase response but are non-specific. Histologic confirmation of vasculitis in medium sized arteries is desirable and biopsies must be obtained from symptomatic organs if feasible. Skin or muscle and nerve are preferred because of higher diagnostic yield and safety. If biopsies are negative or cannot be obtained, visceral angiography, may reveal multiple micro-aneurysms supporting the diagnosis of PAN. Current treatment policy includes high-dose corticosteroids, which are combined with immunosuppressive agents when critical organ involvement or life-threatening complications occur. IV pulse cyclophosphamide in the remission induction phase, later switched to a safer immunosuppressant for remission maintenance is a frequently used therapeutic approach. A recent consensus algorithm for the classification of PAN has attempted to overcome some of the caveats of the 1990 American College of Rheumatology (ACR) classification criteria which have proven to be unsatisfactory, and has also confirmed the low prevalence of PAN compared to other systemic necrotizing vasculitides. European league against rheumatic diseases (EULAR)/ACR endorsed international cooperation to establish new diagnostic/classification criteria is currently under way.
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Zn-bis-glutathionate is the best co-substrate of the monomeric phytochelatin synthase from the photosynthetic heavy metal-hyperaccumulator Euglena gracilis.
Metallomics
PUBLISHED: 01-24-2014
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The phytochelatin synthase from photosynthetic Euglena gracilis (EgPCS) was analyzed at the transcriptional, kinetic, functional, and phylogenetic levels. Recombinant EgPCS was a monomeric enzyme able to synthesize, in the presence of Zn(2+) or Cd(2+), phytochelatin2-phytochelatin4 (PC2-PC4) using GSH or S-methyl-GS (S-methyl-glutathione), but not ?-glutamylcysteine or PC2 as a substrate. Kinetic analysis of EgPCS firmly established a two-substrate reaction mechanism for PC2 synthesis with Km values of 14-22 mM for GSH and 1.6-2.5 ?M for metal-bis-glutathionate (Me-GS2). EgPCS showed the highest Vmax and catalytic efficiency with Zn-(GS)2, and was inactivated by peroxides. The EgPCS N-terminal domain showed high similarity to that of other PCSases, in which the typical catalytic core (Cys-70, His-179 and Asp-197) was identified. In contrast, the C-terminal domain showed no similarity to other PCSases. An EgPCS mutant comprising only the N-terminal 235 amino acid residues was inactive, suggesting that the C-terminal domain is essential for activity/stability. EgPCS transcription in Euglena cells was not modified by Cd(2+), whereas its heterologous expression in ycf-1 yeast cells provided resistance to Cd(2+) stress. Phylogenetic analysis of the N-terminal domain showed that EgPCS is distant from plants and other photosynthetic organisms, suggesting that it evolved independently. Although EgPCS showed typical features of PCSases (constitutive expression; conserved N-terminal domain; kinetic mechanism), it also exhibited distinct characteristics such as preference for Zn-(GS)2 over Cd-(GS)2 as a co-substrate, a monomeric structure, and ability to solely synthesize short-chain PCs, which may be involved in conferring enhanced heavy-metal resistance.
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Vitamin D concentrations in familial combined hyperlipidemia: effects of lipid lowering treatment.
Diabetol Metab Syndr
PUBLISHED: 01-21-2014
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Vitamin D deficiency has been linked to several cardiovascular risk factors but information regarding vitamin D concentrations in familial combined hyperlipidemia (FCHL) is lacking. Our objective was to examine vitamin D concentrations in patients with FCHL and to study the effects of lipid-lowering therapy.
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Acute dilated cardiomyopathy in a patient with beriberi and cryoglobulinaemic vasculitis: an unusual potential complication of two rare disorders.
Clin. Exp. Rheumatol.
PUBLISHED: 01-14-2014
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We report the case of a 45-year-old patient who presented with acute dilated cardiomyopathy. During admission the patient was consecutively diagnosed with cryoglobulinaemic vasculitis and beriberi. In both diseases, cardiac involvement may occur as dilated cardiomyopathy. Thiamin deficiency was the final cause for the severe cardiac manifestations (cardiac acute beriberi or Shoshin syndrome), which returned to normal after thiamin supplementation.
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Similar improvement in gait parameters following direct anterior & posterior approach total hip arthroplasty.
J Arthroplasty
PUBLISHED: 01-11-2014
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We compared gait parameters prior to, at 6 months and 1 year following total hip arthroplasty (THA) performed via direct anterior approach (DAA) and posterior approach (PA) by a single surgeon in 22 patients. A gait analysis system involving reflective markers, infrared cameras and a multicomponent force plate was utilized. Postoperatively, the study cohort demonstrated improvement in flexion/extension range of motion (ROM) (P = 0.001), peak flexion (P = 0.005) and extension (P = 0.002) moments with no differences between groups. Internal/external ROM improved significantly in the DAA group (P = 0.04) with no change in the PA group. THA performed via DAA and PA offers similar improvement in gait parameters with the exception of internal/external ROM which might be related to the release and repair of external rotators during PA THA.
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Implementation of a novel in vitro model of infection of reconstituted human epithelium for expression of virulence genes in methicillin-resistant Staphylococcus aureus strains isolated from catheter-related infections in Mexico.
Ann. Clin. Microbiol. Antimicrob.
PUBLISHED: 01-09-2014
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Methicillin-resistant Staphylococcus aureus (MRSA) are clinically relevant pathogens that cause severe catheter-related nosocomial infections driven by several virulence factors.
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A Candidate Gene Approach Identifies an IL33 Genetic Variant as a Novel Genetic Risk Factor for GCA.
PLoS ONE
PUBLISHED: 01-01-2014
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Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition.
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Nocebo effect in randomized clinical trials of antidepressants in children and adolescents: systematic review and meta-analysis.
Front Behav Neurosci
PUBLISHED: 01-01-2014
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To compare the incidence of adverse events between active and placebo arms of randomized clinical trials in depressive children and adolescents (C&A) with antidepressant treatments, in order to look for similarities in both groups that allow to establish a possible nocebo effect.
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PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases.
PLoS ONE
PUBLISHED: 01-01-2014
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Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL). The Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are important mediators of cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs) and pharmacologically (mainly with the pan-PIM inhibitor (PIMi) ETP-39010) in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL) cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.
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Malfunctioning of the Iron-Sulfur Cluster Assembly Machinery in Saccharomyces cerevisiae Produces Oxidative Stress via an Iron-Dependent Mechanism, Causing Dysfunction in Respiratory Complexes.
PLoS ONE
PUBLISHED: 01-01-2014
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Biogenesis and recycling of iron-sulfur (Fe-S) clusters play important roles in the iron homeostasis mechanisms involved in mitochondrial function. In Saccharomyces cerevisiae, the Fe-S clusters are assembled into apoproteins by the iron-sulfur cluster machinery (ISC). The aim of the present study was to determine the effects of ISC gene deletion and consequent iron release under oxidative stress conditions on mitochondrial functionality in S. cerevisiae. Reactive oxygen species (ROS) generation, caused by H2O2, menadione, or ethanol, was associated with a loss of iron homeostasis and exacerbated by ISC system dysfunction. ISC mutants showed increased free Fe2+ content, exacerbated by ROS-inducers, causing an increase in ROS, which was decreased by the addition of an iron chelator. Our study suggests that the increment in free Fe2+ associated with ROS generation may have originated from mitochondria, probably Fe-S cluster proteins, under both normal and oxidative stress conditions, suggesting that Fe-S cluster anabolism is affected. Raman spectroscopy analysis and immunoblotting indicated that in mitochondria from SSQ1 and ISA1 mutants, the content of [Fe-S] centers was decreased, as was formation of Rieske protein-dependent supercomplex III2IV2, but this was not observed in the iron-deficient ATX1 and MRS4 mutants. In addition, the activity of complexes II and IV from the electron transport chain (ETC) was impaired or totally abolished in SSQ1 and ISA1 mutants. These results confirm that the ISC system plays important roles in iron homeostasis, ROS stress, and in assembly of supercomplexes III2IV2 and III2IV1, thus affecting the functionality of the respiratory chain.
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Primary and secondary prevention of colorectal cancer.
Clin Med Insights Gastroenterol
PUBLISHED: 01-01-2014
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Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. Colorectal cancer (CRC) is the third most frequent cancer in men, after lung and prostate cancer, and is the second most frequent cancer in women after breast cancer. It is also the third cause of death in men and women separately, and is the second most frequent cause of death by cancer if both genders are considered together. CRC represents approximately 10% of deaths by cancer. Modifiable risk factors of CRC include smoking, physical inactivity, being overweight and obesity, eating processed meat, and drinking alcohol excessively. CRC screening programs are possible only in economically developed countries. However, attention should be paid in the future to geographical areas with ageing populations and a western lifestyle.19,20 Sigmoidoscopy screening done with people aged 55-64 years has been demonstrated to reduce the incidence of CRC by 33% and mortality by CRC by 43%.
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Phasing tiny crystals.
IUCrJ
PUBLISHED: 01-01-2014
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For tiny crystals, their diffraction intensities at and between the Bragg peaks become measurable due to the limited number of the unit cells, which can in principle be used to directly phase the crystal structures.
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Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes.
Ann. Rheum. Dis.
PUBLISHED: 12-12-2013
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Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ?35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes.
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Flow-induced wall mechanics of patient-specific aneurysmal cerebral arteries: Nonlinear isotropic versus anisotropic wall stress.
Proc Inst Mech Eng H
PUBLISHED: 11-26-2013
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Fluid-structure interaction simulations of three patient-specific models of cerebral aneurysms were carried out with the objective of quantifying the effects of non-Newtonian blood flow and the vessel mechanical behavior on the time-dependent fluid shear and normal stresses, and structural stress and stretch. The average wall shear stress at peak systole was found to be approximately one order of magnitude smaller than the shear stresses in the proximal communicating arteries, regardless of the shape or size of the aneurysms. Spatial distributions of oscillatory shear index were consistent with the reciprocal of wall shear stress distributions at peak systole for all aneurysm geometries, demonstrating that oscillatory shear index correlates inversely with wall shear at this time point in the cardiac cycle. An aneurysm wall modeled with an isotropic material resulted in an underestimation of both the maximum principal stress and stretch, compared to the anisotropic material model. For the three aneurysm geometries, anisotropic peak wall stresses were approximately 50% higher than for an isotropic material. Regardless of the constitutive material, the maximum stresses were consistently located at the aneurysm neck; stresses in the dome were 30% of those in the neck.
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PIK3CA gene alterations in bladder cancer are frequent and associate with reduced recurrence in non-muscle invasive tumors.
Mol. Carcinog.
PUBLISHED: 10-01-2013
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Bladder cancer (BC) is the fifth most common cancer in the world, being the non-muscle invasive tumors (NMIBC) the most frequent. NMIBC shows a very high frequency of recurrence and, in certain cases, tumor progression. The phosphatidylinositol 3-kinase (PI3K) pathway, which controls cell growth, tumorigenesis, cell invasion and drug response, is frequently activated in numerous human cancers, including BC, in part through alterations of PIK3CA gene. However, the significance of PIK3CA gene alterations with respect to clinicopathological characteristics, and in particular tumor recurrence and progression, remains elusive. Here, we analyzed the presence of mutations in FGFR3 and PIK3CA genes and copy number alterations of PIK3CA gene in bladder tumor and their correspondent paired normal samples from 87 patients. We observed an extremely high frequency of PIK3CA gene alterations (mutations, copy gains, or both) in tumor samples, affecting primarily T1 and T2 tumors. A significant number of normal tissues also showed mutations and copy gains, being coincident with those found in the corresponding tumor sample. In low-grade tumors PIK3CA mutations associated with FGFR3 mutations. Alterations in PIK3CA gene resulted in increased Akt activity in tumors. Interestingly, the presence of PIK3CA gene alterations, and in particular gene mutations, is significantly associated with reduced recurrence of NMIBC patients. Importantly, the presence of FGFR3 mutations may influence the clinical outcome of patients bearing alterations in PIK3CA gene, and increased recurrence was associated to FGFR3 mutated, PIK3CA wt tumors. These findings may have high relevance in terms of using PI3K-targeted therapies for BC treatment. © 2013 Wiley Periodicals, Inc.
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Circumscribed palmar hypokeratosis associated to a burn scar.
Am J Dermatopathol
PUBLISHED: 09-14-2013
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Circumscribed palmar or plantar hypokeratosis is a volar depression characterized by a circular area of well-circumscribed and erythematous skin on the palm or sole. It is a benign condition that occurs mainly as an asymptomatic lesion on the thenar or hypothenar areas of the palm of middle-aged or elderly patients. Since its first description 1 decade ago, the pathogenesis of this entity still remains unclear. Herein we report the first case of a circumscribed palmar hypokeratosis lesion associated to a burn scar, which corroborates the hypothesis of an acquired disorder caused by trauma.
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Nonsutured Hotz-Celsus technique performed by CO2 laser in two dogs and two cats.
Vet Ophthalmol
PUBLISHED: 09-03-2013
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It is described a new version of modified Hotz-Celsus technique performed in four patients, two cats and two dogs. The surgery was carried out using CO2 laser in order to avoid bleeding and decrease the anesthetic time. Besides, the wound created was not sutured and it healed by secondary intention without any complication. As a conclusion, this modification is a successful alternative to treat entropion in a safe and fast way.
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Successful embolization of a cytomegalovirus-related duodenal ulcer in a kidney-pancreas transplant recipient.
Prog Transplant
PUBLISHED: 09-03-2013
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One of the complications that can occur in pancreas transplant is a massive intestinal hemorrhage, although such a hemorrhage is very rarely caused by ulcers due to cytomegalovirus infection. Treatment is fundamentally based on relaparatomy, although in some cases interventional radiology can be an efficient alternative because it allows the exact bleeding point to be located and therapeutic embolization to be performed. In this case, a man with diabetes type 1 who was given a simultaneous kidney-pancreas transplant had an ulcer due to cytomegalovirus infection develop in the duodenal graft (in the early postoperative period), causing a severe hemorrhage in the lower part of the gastrointestinal tract that was controlled via selective embolization of a branch of the pancreaticoduodenal artery.
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Prospective long term follow-up of a cohort of patients with giant cell arteritis screened for aortic structural damage (aneurysm or dilatation).
Ann. Rheum. Dis.
PUBLISHED: 07-19-2013
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Aortic structural damage (ASD) may complicate the course of patients with giant cell arteritis (GCA). However the frequency and outcome of ASD has not been assessed in long term prospective studies.
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Treatment with angiotensin II receptor blockers is associated with prolonged relapse-free survival, lower relapse rate, and corticosteroid-sparing effect in patients with giant cell arteritis.
Semin. Arthritis Rheum.
PUBLISHED: 07-16-2013
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To determine whether concomitant treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is associated with changes in the outcome of patients with giant cell arteritis (GCA).
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Eosinophilic fasciitis as a manifestation of a cutaneous T-cell lymphoma not otherwise specified.
Am J Dermatopathol
PUBLISHED: 06-14-2013
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Eosinophilic fasciitis (EF) is a rare entity characterized by symmetrical and painful thickness and induration of the skin, especially localized on forearms and thorax and generally accompanied by eosinophilia. Although several reports indicate the relationship between EF and hematological disorders such as aplastic anemia, polycythemia vera, or myelomonocytic leukemia, the association with lymphomas is extremely rare. Only a few cases of EF have been previously described preceding or concomitant to the Hodgkin disease, peripheral T-cell lymphoma, B-cell lymphoma, and mycosis fungoides. We report for the first time a 76-year-old man with an EF associated with a peripheral T-cell lymphoma not otherwise specified. We review the relationship between both conditions. In conclusion, we present a unique case of EF as a manifestation of a T-cell lymphoma not otherwise specified. The present case demonstrates the importance of clinical and radiological studies in those cases of EF to rule out a visceral, lymph node, or cutaneous lymphoma.
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Transoral robotic-assisted free flap reconstruction after radiation therapy in hypopharyngeal carcinoma: report of two cases.
Eur Arch Otorhinolaryngol
PUBLISHED: 05-14-2013
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The objective was to assess the feasibility and safety of transoral robotic surgery (TORS)-assisted free flap reconstruction for hypopharyngeal carcinoma after radiation therapy. The study evaluated the feasibility, surgical margins, the need for a tracheotomy, a nasogastric tube as well as surgery-related complications. Two patients underwent TORS-assisted free flap reconstruction after radiation therapy. The resection margins were free of tumor in both patients. A tracheotomy was performed in one patient who had been decannulated on the sixth postoperative day. One patient resumed satisfactory oral feeding in the fourth postoperative month and the second patient on postoperative day 7. No intraoperative complication and one postoperative complication (neck hematoma) were reported. After a follow-up period of 24 and 30 months, no local recurrence was observed. TORS is feasible for hypopharyngeal resection and assisted free flap reconstruction after radiation therapy. It represents a further step in the development of minimally invasive surgery for the treatment of head and neck cancers with laryngeal preservation.
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Intermediate structures for higher level arrangements: catching disk-like micelles in decane phosphonic acid aqueous solutions.
J Phys Chem B
PUBLISHED: 05-14-2013
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It has been proposed that disk-like micelles may be precursors to the formation of lamellar liquid crystals. The possibility of obtaining n-decane phosphonic acid (DPA) disk-like micelles in aqueous solution without the addition of a second ionic surfactant led us to study in detail the low-concentration range of this system by both a battery of experimental techniques and molecular dynamics (MD) simulations. The experimental results indicate that premicelles with some capacity to solubilize dyes are formed at 0.05 mM. The critical micelle concentration (cmc) was found to be 0.260 ± 0.023 mM, much lower than that previously reported in the literature. Spherical micelles, which immediately grow, leading to disk-like micelles, are probably formed at this concentration. At 0.454 ± 0.066 mM, disk-like micelles become unstable, giving rise to the formation of an emulsion of lamellar mesophase that dominates the system beyond 0.670 ± 0.045 mM. These experimental results were corroborated by MD simulations which, additionally, allow describing the structure of the obtained micelles at atomic level. The analysis of the MD trajectories revealed the presence of strong intermolecular hydrogen bonds between the surfactant headgroups, producing a compact polar layer with low water content. The formation of such H-bond network could explain the ability of this surfactant to form disk-like micelles at concentrations close to the cmc.
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Changes in biomarkers after therapeutic intervention in temporal arteries cultured in Matrigel: a new model for preclinical studies in giant-cell arteritis.
Ann. Rheum. Dis.
PUBLISHED: 04-27-2013
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BACKGROUND: Search for therapeutic targets in giant-cell arteritis (GCA) is hampered by the scarcity of functional systems. We developed a new model consisting of temporal artery culture in tri-dimensional matrix and assessed changes in biomarkers induced by glucocorticoid treatment. METHODS: Temporal artery sections from 28 patients with GCA and 22 controls were cultured in Matrigel for 5 days in the presence or the absence of dexamethasone. Tissue mRNA concentrations of pro-inflammatory mediators and vascular remodelling molecules was assessed by real-time RT-PCR. Soluble molecules were measured in the supernatant fluid by immunoassay. RESULTS: Histopathological features were exquisitely preserved in cultured arteries. mRNA concentrations of pro-inflammatory cytokines (particularly IL-1? and IFN?), chemokines (CCL3/MIP-1?, CCL4/MIP-1?, CCL5/RANTES) and MMP-9 as well as IL-1? and MMP-9 protein concentrations in the supernatants were significantly higher in cultured arteries from patients compared with control arteries. The culture system itself upregulated expression of cytokines and vascular remodelling factors in control arteries. This minimised differences between patients and controls but underlines the relevance of changes observed. Dexamethasone downregulated pro-inflammatory mediator (IL-1?, IL-6, TNF?, IFN?, MMP-9, TIMP-1, CCL3 and CXCL8) mRNAs but did not modify expression of vascular remodelling factors (platelet derived growth factor, MMP-2 and collagens I and III). CONCLUSIONS: Differences in gene expression in temporal arteries from patients and controls are preserved during temporal artery culture in tri-dimensional matrix. Changes in biomarkers elicited by glucocorticoid treatment satisfactorily parallel results obtained in vivo. This may be a suitable model to explore pathogenetic pathways and to perform preclinical studies with new therapeutic agents.
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Benign atypical intravascular CD30(+) T-cell proliferation: a reactive condition mimicking intravascular lymphoma.
Am J Dermatopathol
PUBLISHED: 04-02-2013
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CD30 is a transmembrane glycoprotein molecule usually expressed in activated B and T cells. Although it has been considered a reliable marker for CD30 lymphomas, reactive inflammatory disorders may contain a significant number of CD30 cells mimicking lymphoproliferative disorders clinically or histologically. Intravascular lymphoma is a rare variant of non-Hodgkin lymphoma that can involve the skin in 40% of the patients. The majority of cases show a B-cell phenotype, and only a minority of cases are of T-cell or NK-cell origin. Moreover, 2 aggressive cases of intravascular large T-cell lymphoma have been described with a CD30 phenotype. Herein, we report 2 patients with skin lesions showing an atypical intravascular CD30 T-cell proliferation. Both the patients did not present systemic disease and therefore exhibit a favorable outcome. To the best of our knowledge, this is the second report in the literature of a benign intravascular CD30 T-cell proliferation that represents an intriguing differential diagnosis for intravascular lymphoma.
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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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