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Find video protocols related to scientific articles indexed in Pubmed.
Comparative study of the second and third generation of Gamma nail for trochanteric fractures. Review of 218 cases.
J Orthop Trauma
PUBLISHED: 07-02-2014
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The aim of this study is to compare the complications of the Trochanteric Gamma Nail (TGN) and the Gamma 3 Nail (G3), focusing on cutout failure.
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Modeling bacterial population growth from stochastic single-cell dynamics.
Appl. Environ. Microbiol.
PUBLISHED: 06-13-2014
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A few bacterial cells may be sufficient to produce a food-borne illness outbreak, provided that they are capable of adapting and proliferating on a food matrix. This is why any quantitative health risk assessment policy must incorporate methods to accurately predict the growth of bacterial populations from a small number of pathogens. In this aim, mathematical models have become a powerful tool. Unfortunately, at low cell concentrations, standard deterministic models fail to predict the fate of the population, essentially because the heterogeneity between individuals becomes relevant. In this work, a stochastic differential equation (SDE) model is proposed to describe variability within single-cell growth and division and to simulate population growth from a given initial number of individuals. We provide evidence of the model ability to explain the observed distributions of times to division, including the lag time produced by the adaptation to the environment, by comparing model predictions with experiments from the literature for Escherichia coli, Listeria innocua, and Salmonella enterica. The model is shown to accurately predict experimental growth population dynamics for both small and large microbial populations. The use of stochastic models for the estimation of parameters to successfully fit experimental data is a particularly challenging problem. For instance, if Monte Carlo methods are employed to model the required distributions of times to division, the parameter estimation problem can become numerically intractable. We overcame this limitation by converting the stochastic description to a partial differential equation (backward Kolmogorov) instead, which relates to the distribution of division times. Contrary to previous stochastic formulations based on random parameters, the present model is capable of explaining the variability observed in populations that result from the growth of a small number of initial cells as well as the lack of it compared to populations initiated by a larger number of individuals, where the random effects become negligible.
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Phonons and hybrid modes in the high and low temperature far infrared dynamics of hexagonal TmMnO3.
J Phys Condens Matter
PUBLISHED: 06-11-2014
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We report on temperature dependent TmMnO3 far infrared emissivity and reflectivity spectra from 1910?K to 4?K. At the highest temperature the number of infrared bands is lower than that predicted for centrosymmetric P63/mmc (D(4)(6h)) (Z = 2) space group due to high temperature anharmonicity and possible defect induced bitetrahedra misalignments. On cooling, at ~1600?±?40?K, TmMnO3 goes from non-polar to an antiferroelectric-ferroelectric polar phase reaching the ferroelectric onset at ~700?K. Room temperature reflectivity is fitted using 19 oscillators and this number of phonons is maintained down to 4?K. A weak phonon anomaly in the band profile at 217?cm(-1) (4?K) suggests subtle Rare Earth magneto-electric couplings at ~TN and below. A low energy collective excitation is identified as a THz instability associated with room temperature eg electrons in a d-orbital fluctuating environment. It condenses into two modes that emerge pinned to the E-type antiferromagnetic order hardening simultaneously down to 4?K. They obey power laws with TN as the critical temperature and match known zone center magnons. The one peaking at 26?cm(-1), with critical exponent ?=0.42 as for antiferromagnetic order in a hexagonal lattice, is dependent on the Rare Earth ion. The higher frequency companion at ~50?cm(-1), with ?=0.25, splits at ~TN into two peaks. The weaker band of the two is assimilated to the upper branch of the gap opening in the transverse acoustical (TA) phonon branch crossing the magnetic dispersion found in YMnO3. (Petit et al 2007 Phys. Rev. Lett. 99 266604). The stronger second band at ~36?cm(-1) corresponds to the lower branch of the TA gap. We assign both excitations as zone center magneto-electric hybrid quasiparticles, concluding that in NdMnO3 perovskite the equivalent picture corresponds to an instability which may be driven by an external field to transform NdMnO3 into a multiferroic compound by perturbation enhancing the TA phonon-magnetic correlation.
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Improving DNA data exchange: validation studies on a single 6 dye STR kit with 24 loci.
Forensic Sci Int Genet
PUBLISHED: 04-08-2014
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The idea of developing a new multiplex STR amplification system was conceived in 2011 as an effective way to implement the new European standard set (ESS) of 12 STR markers adopted by The Council of the European Union in 2009 while maintaining an effective compatibility and information exchange with the historical DNA profiles contained in the Spanish national DNA database (around 200,000 DNA profiles) mainly based on the 13 CODIS core STR loci plus D19S433 and D2S1338 markers. With this goal in mind we proposed to test and validate a single STR amplification system for simultaneous analysis of 21 STR markers covering both CODIS and ESS core STR loci plus three additional markers (D19S433, D2S1338, and SE33) also contained in commonly used STR kits and national DNA databases. In 2012, we started the first beta-testing with a 6-dye STR kit prototype containing 24 loci (now known as the GlobalFiler™ PCR Amplification Kit) developed by Life Technologies in response to the CODIS Core Loci Working Group's recommendation to expand the CODIS Core Loci. This prototype included our proposal of 21 autosomal STR markers and two Y-chromosome markers (DYS391 and Y-indel) and maximizes concordance with established databases and previously analyzed samples by maintaining primer sequences of previous Identifiler(®)/NGM SElect™ kits for the 21 STR markers except for TPOX. This paper describes the validation studies conducted with the first commercial available 6-dye STR kit for casework using a 3500 genetic analyzer for fragment detection that included the analysis of the following parameters and aspects: analytical threshold, sensitivity & stochastic threshold, heterozygous balance, stutter threshold, precision and accuracy, repeatability and reproducibility, genotype concordance, DNA mixtures, species specificity, and stability studies with case type samples. The studies demonstrated that the GlobalFiler™ system provided equivalent overall performance to previous forensic STR PCR kits, but with enhanced discrimination power for a better match efficiency that would reduce the chance of adventitious matches during DNA data exchange among national DNA databases.
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A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.
Josephine Purps, Sabine Siegert, Sascha Willuweit, Marion Nagy, Cíntia Alves, Renato Salazar, Sheila M T Angustia, Lorna H Santos, Katja Anslinger, Birgit Bayer, Qasim Ayub, Wei Wei, Yali Xue, Chris Tyler-Smith, Miriam Baeta Bafalluy, Begoña Martínez-Jarreta, Balazs Egyed, Beate Balitzki, Sibylle Tschumi, David Ballard, Denise Syndercombe Court, Xinia Barrantes, Gerhard Bäßler, Tina Wiest, Burkhard Berger, Harald Niederstätter, Walther Parson, Carey Davis, Bruce Budowle, Helen Burri, Urs Borer, Christoph Koller, Elizeu F Carvalho, Patricia M Domingues, Wafaa Takash Chamoun, Michael D Coble, Carolyn R Hill, Daniel Corach, Mariela Caputo, Maria E D'Amato, Sean Davison, Ronny Decorte, Maarten H D Larmuseau, Claudio Ottoni, Olga Rickards, Di Lu, Chengtao Jiang, Tadeusz Dobosz, Anna Jonkisz, William E Frank, Ivana Furac, Christian Gehrig, Vincent Castella, Branka Gršković, Cordula Haas, Jana Wobst, Gavrilo Hadzic, Katja Drobnic, Katsuya Honda, Yiping Hou, Di Zhou, Yan Li, Shengping Hu, Shenglan Chen, Uta-Dorothee Immel, Rüdiger Lessig, Zlatko Jakovski, Tanja Ilievska, Anja E Klann, Cristina Cano García, Peter de Knijff, Thirsa Kraaijenbrink, Aikaterini Kondili, Penelope Miniati, Maria Vouropoulou, Lejla Kovacevic, Damir Marjanović, Iris Lindner, Issam Mansour, Mouayyad Al-Azem, Ansar El Andari, Miguel Marino, Sandra Furfuro, Laura Locarno, Pablo Martín, Gracia M Luque, Antônio Alonso, Luís Souto Miranda, Helena Moreira, Natsuko Mizuno, Yasuki Iwashima, Rodrigo S Moura Neto, Tatiana L S Nogueira, Rosane Silva, Marina Nastainczyk-Wulf, Jeanett Edelmann, Michael Köhl, Shengjie Nie, Xianping Wang, Baowen Cheng, Carolina Núñez, Marian Martínez de Pancorbo, Jill K Olofsson, Niels Morling, Valerio Onofri, Adriano Tagliabracci, Horolma Pamjav, Antónia Völgyi, Gusztav Barany, Ryszard Pawlowski, Agnieszka Maciejewska, Susi Pelotti, Witold Pepiński, Monica Abreu-Glowacka, Christopher Phillips, Jorge Cárdenas, Danel Rey-Gonzalez, Antonio Salas, Francesca Brisighelli, Cristian Capelli, Ulises Toscanini, Andrea Piccinini, Marilidia Piglionica, Stefania L Baldassarra, Rafal Ploski, Magdalena Konarzewska, Emila Jastrzebska, Carlo Robino, Antti Sajantila, Jukka U Palo, Evelyn Guevara, Jazelyn Salvador, Maria Corazon De Ungria, Jae Joseph Russell Rodriguez, Ulrike Schmidt, Nicola Schlauderer, Pekka Saukko, Peter M Schneider, Miriam Sirker, Kyoung-Jin Shin, Yu Na Oh, Iulia Skitsa, Alexandra Ampati, Tobi-Gail Smith, Lina Solis de Calvit, Vlastimil Stenzl, Thomas Capal, Andreas Tillmar, Helena Nilsson, Stefania Turrina, Domenico De Leo, Andrea Verzeletti, Venusia Cortellini, Jon H Wetton, Gareth M Gwynne, Mark A Jobling, Martin R Whittle, Denilce R Sumita, Paulina Wolanska-Nowak, Rita Y Y Yong, Michael Krawczak, Michael Nothnagel, Lutz Roewer.
Forensic Sci Int Genet
PUBLISHED: 03-28-2014
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In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.
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Miltefosine increases lipid and protein dynamics in Leishmania amazonensis membranes at concentrations similar to those needed for cytotoxicity activity.
Antimicrob. Agents Chemother.
PUBLISHED: 03-10-2014
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Miltefosine (MT) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled lipid and a thiol-specific spin label in the plasma membrane of Leishmania promastigotes showed that MT causes dramatic increases in membrane dynamics. Although these alterations can be detected using a spin-labeled lipid, our experimental results indicated that MT interacts predominantly with the protein component of the membrane. Cell lysis was also detected by analyzing the supernatants of centrifuged samples for the presence of spin-labeled membrane fragments and cytoplasmic proteins. Using a method for the rapid incorporation of MT into the membrane, these effects were measured immediately after treatment under the same range of MT concentrations that cause cell growth inhibition. Cytotoxicity, estimated via microscopic counting of living and dead cells, indicated ?70% cell death at the concentration of MT at which EPR spectroscopy detected a significant change in membrane dynamics. After this initial impact on the number of viable parasites, the processes of cell death and growth continued during the first 4 h of incubation. The EPR spectra of spin-labeled membrane-bound proteins were consistent with more expanded and solvent-exposed protein conformations, suggesting a detergent-like action. Thus, MT may form micelle-like structures around polypeptide chains, and proteins with a higher hydrophobicity may induce the penetration of hydrophilic groups of MT into the membrane, causing its rupture.
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Cochlear implantation outcomes in advanced otosclerosis.
Am J Otolaryngol
PUBLISHED: 02-25-2014
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Several studies support the use of cochlear implants (CI) in far-advanced otosclerosis (FAO).
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Impact of lipid dynamic behavior on physical stability, in vitro release and skin permeation of genistein-loaded lipid nanoparticles.
Eur J Pharm Biopharm
PUBLISHED: 02-19-2014
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The aim of this study was to develop lipid nanoparticles to deliver genistein (GEN) to deeper skin layers. To do so, the impact of lipid dynamic behavior (nanoparticle flexibility) on stability, release and skin permeation studies was verified. GEN-loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were obtained and characterization was undertaken. Freshly prepared nanoparticles were produced with similar features (i.e., drug loading). However, a higher level of crystallization in GEN-SLN formulation was observed in differential scanning calorimetry experiments. Electron paramagnetic resonance measurements showed a lower mobility of the spin labels in the SLN, which would indicate that NLC could be more flexible than SLN. Despite the fact that NLC demonstrated more fluidity, GEN was released more slowly from NLC than from SLN. Skin permeation studies demonstrated that lipid nanoparticles increased GEN skin retention. More flexible particles (NLC) also favored drug penetration into deeper skin layers. GEN-NLC would seem to be a promising formulation for GEN topical delivery.
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The formation of wood and its control.
Curr. Opin. Plant Biol.
PUBLISHED: 02-11-2014
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Wood continues to increase in importance as a sustainable source of energy and shelter. Wood formation is a dynamic process derived from plant secondary (radial) growth. Several experimental systems have been employed to study wood formation and its regulation. The use of genetic manipulation approaches and genome-wide analyses in model plants have significantly advanced our understanding of wood formation. In this review, we provide an update of our knowledge of the genetic and hormonal regulation of wood formation based on research in different plants systems, as well as considering the subject from an evo-devo perspective.
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Cell death in amastigote forms of Leishmania amazonensis induced by parthenolide.
BMC Microbiol.
PUBLISHED: 01-24-2014
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Leishmania amazonensis infection results in diverse clinical manifestations: cutaneous, mucocutaneous or visceral leishmaniasis. The arsenal of drugs available for treating Leishmania infections is limited. Therefore, new, effective, and less toxic leishmaniasis treatments are still needed. We verified cell death in amastigote forms of Leishmania amazonensis induced by the sesquiterpene lactone parthenolide.
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Terpenes increase the lipid dynamics in the Leishmania plasma membrane at concentrations similar to their IC50 values.
PLoS ONE
PUBLISHED: 01-01-2014
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Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×10(6) parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, ?-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4-9%) at their respective IC50 values. For assays with high cell concentrations (2×10(9) parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis.
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Paramagnetic collective electronic mode and low temperature hybrid modes in the far infrared dynamics of orthorhombic NdMnO?.
J Phys Condens Matter
PUBLISHED: 09-03-2013
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We report on the far- and mid-infrared reflectivity of NdMnO3 from 4 to 300 K. Two main features are distinguished in the infrared spectra: active phonons in agreement with expectations for the orthorhombic [Formula: see text]-Pbnm (Z = 4) space group remaining constant down to 4 K and a well defined collective excitation in the THz region due to eg electrons in a d-orbital fluctuating environment. We trace its origin to the NdMnO3 high-temperature orbital disordered intermediate phase not being totally dynamically quenched at lower temperatures. This results in minute orbital misalignments that translate into randomized non-static eg electrons within orbitals yielding a room-temperature collective excitation. Below TN ? 78 K, electrons gradually localize, inducing long-range magnetic order as the THz band condenses into two modes that emerge pinned to the A-type antiferromagnetic order. They harden simultaneously down to 4 K, obeying power laws with TN as the critical temperature and exponents ? ? 0.25 and ? ? 0.53, as for a tri-critical point and Landau magnetic ordering, respectively. At 4 K they match known zone center spin wave modes. The power law dependence is concomitant with a second order transition in which spin modes modulate orbital instabilities in a magnetoelectric hybridized orbital-charge-spin-lattice scenario. We also found that phonon profiles also undergo strong changes at TN ? 78 K due to magnetoelasticity.
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Long-term results of the transattical approach: an alternative technique for cochlear implantation.
Eur Arch Otorhinolaryngol
PUBLISHED: 08-07-2013
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Cochlear implantation through the standard posterior tympanotomy approach may sometimes be challenging. In cases with complicated anatomy or malformations, an alternative surgical technique may be chosen. The transattical approach is a simple technique based on a mastoidectomy and a transmeatal cochleostomy. The electrode is driven to the middle ear through the attic. This way it overcomes some of the standard techniques drawbacks. Our aim is to assess the value of this alternative approach in cochlear implant surgery. We conducted a comparative retrospective study; we included 74 patients operated by transattical approach and 59 patients operated with the standard technique. Auditory performance and complications at long term follow-up were compared. The consequences of the different trajectory of the electrode in the transattical approach were also studied. No significant differences were found between both groups regarding complication rates and cochlear implant performance. The electrodes integrity was not significantly affected by its different position and angles, when compared to the standard approach. We conclude that transattical approach is a safe technique for cochlear implantation. It may be considered as an alternative to the posterior tympanotomy approach for those cases where this cannot be performed.
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High temperature far-infrared dynamics of orthorhombic NdMnO3: emissivity and reflectivity.
J Phys Condens Matter
PUBLISHED: 05-16-2013
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We report on near normal far- and mid-infrared emission and reflectivity of NdMnO3 perovskite from room temperature to sample decomposition above 1800 K. At 300 K the number of infrared active phonons is in close agreement with the 25 calculated for the orthorhombic D(2h)(16)-Pbnm (Z = 4) space group. Their number gradually decreases as we approach the temperature of orbital disorder at ~1023 K where the orthorhombic O lower temperature cooperative phase coexists with the cubic orthorhombic O. At above ~1200 K, the three infrared active phonons coincide with that expected for cubic Pm-3m (Z = 1) in the high temperature insulating regime. Heating samples in dry air triggers double exchange conductivity by Mn(3+) and Mn(4+) ions and a small polaron mid-infrared band. Fits to the optical conductivity single out the octahedral antisymmetric and symmetric vibrational modes as the main phonons in the electron-phonon interactions at 875 K. For 1745 K, it is enough to consider the symmetric stretching internal mode. An overdamped defect induced Drude component is clearly outlined at the highest temperatures. We conclude that rare earth manganite eg electrons are prone to spin, charge, orbital, and lattice couplings in an intrinsic orbital distorted perovskite lattice, favoring embryonic low energy collective excitations.
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[News items on human papillomavirus and its vaccine in the Valencian press (2006-2011)].
Gac Sanit
PUBLISHED: 02-15-2013
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The process of introducing the human papillomavirus (HPV) vaccine aimed at teenage girls has not been entirely without controversy in Spain. This vaccine was originally hyped as a preventive measure in the fight against cervical cancer but the resulting euphoria was tempered by a message calling for evidence. During administration of the second dose of the vaccine in February 2009, an unexpected turn of events attracted vast media coverage when two teenagers experienced adverse effects after immunization in Valencia (Spain). This study analyzes the scope and content of news items on HPV, immunization and cervical cancer published between 2006 and 2011 in two widely disseminated regional newspapers in Valencia. We also discuss the extent to which the messages transmitted may have influenced acceptability of the vaccine.
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Interaction of miltefosine with the lipid and protein components of the erythrocyte membrane.
J Pharm Sci
PUBLISHED: 02-11-2013
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Miltefosine (MT) is an alkylphospholipid that has been approved for the treatment of breast cancer metastasis and visceral leishmaniasis, although its mechanism of action remains poorly understood. Electron paramagnetic resonance spectroscopy of a spin-labeled lipid and a thiol-specific spin label showed that MT causes an increase in the molecular dynamics of erythrocyte ghost membranes and detergent-resistant membranes (DRMs) prepared from erythrocyte ghosts. In the vesicles of lipid raft constituents, it was shown that 20 mol % sphingomyelin could be replaced by 20 mol % MT with no change in the molecular dynamics. The effect of MT in DRMs was more pronounced than in erythrocyte ghosts, supporting the hypothesis that MT is a lipid raft modulator. At the reported MT-plasma concentrations found during the treatment of leishmaniasis (31-90 µg/mL), our measurements in the blood plasma indicated a hemolytic level of 2%-5%. The experiments indicated that MT acts predominantly on the protein component of the membrane. MT aggregates may wrap around the hydrophobic polypeptide chains, forming micelle-like structures that stabilize protein conformations more exposed to the solvent. Proteins with higher hydrophobicity may induce the penetration of the hydrophilic groups of MT into the membrane and cause it to rupture.
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Amplicon DNA melting analysis for the simultaneous detection of Brucella spp and Mycobacterium tuberculosis complex. Potential use in rapid differential diagnosis between extrapulmonary tuberculosis and focal complications of brucellosis.
PLoS ONE
PUBLISHED: 02-03-2013
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Some sites of extrapulmonary tuberculosis and focal complications of brucellosis are very difficult to differentiate clinically, radiologically, and even histopathologically. Conventional microbiological methods for the diagnosis of extrapulmonary tuberculosis and complicated brucellosis not only lack adequate sensitivity, they are also time consuming, which could lead to an unfavourable prognosis. The aim of this work was to develop a multiplex real-time PCR assay based on SYBR Green I to simultaneously detect Brucella spp and Mycobacterium tuberculosis complex and evaluate the efficacy of the technique with different candidate genes. The IS711, bcsp31 and omp2a genes were used for the identification of Brucella spp and the IS6110, senX3-regX3 and cfp31 genes were targeted for the detection of the M. tuberculosis complex. As a result of the different combinations of primers, nine different reactions were evaluated. A test was defined as positive only when the gene combinations were capable of co-amplifying both pathogens in a single reaction tube and showed distinguishable melting temperatures for each microorganism. According to the melting analysis, only three combinations of amplicons (senX3-regX3+bcsp31, senX3-regX3+IS711 and IS6110+IS711) were visible. Detection limits of senX3-regX3+bcsp31 and senX3-regX3+IS711 were of 2 and 3 genome equivalents for M. tuberculosis complex and Brucella while for IS6110+IS711 they were of 200 and 300 genome equivalents, respectively. The three assays correctly identified all the samples, showing negative results for the control patients. The presence of multicopy elements and GC content were the components most influencing the efficiency of the test; this should be taken into account when designing a multiplex-based SYBR Green I assay. In conclusion, multiplex real time PCR assays based on the targets senX3-regX3+bcsp31 and senX3-regX3+IS711 using SYBR Green I are highly sensitive and reproducible. This may therefore be a practical approach for the rapid differential diagnosis between extrapulmonary tuberculosis and complicated brucellosis.
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[Public health service prescriptions of vaccines not included in systematic vaccination programs in Valencian community, Spain, during the period 2004-2009].
Rev. Esp. Salud Publica
PUBLISHED: 09-06-2011
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In the context of the policies of rational use of medicine, and in order to achieve an efficient management of the vaccinations programs, we expect to know the number of packings and cost of prescribed vaccines not included in the vaccination programs of Valencian Community and its departments during 2009 and to analyze its evolution since 2004, focusing on an analysis of Heptavalent pneumococcal conjugate vaccine in children under two years old.
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Stapedectomy in sheep: an animal model for surgical training.
Otol. Neurotol.
PUBLISHED: 06-08-2011
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Stapedectomy is a surgical technique that requires progressive training. The external and middle ear of sheep have a close resemblance to the human and have been previously used as surgical training models. In our project we describe the anatomy of the middle and external ear in sheep focusing on surgical landmarks and technique in order to determine whether the sheeps ear is an adequate model for stapedectomy training.
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A public-professional web-bridge for vaccines and vaccination: user concerns about vaccine safety.
Vaccine
PUBLISHED: 06-02-2011
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Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required.
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Inference of complex biological networks: distinguishability issues and optimization-based solutions.
BMC Syst Biol
PUBLISHED: 05-31-2011
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The inference of biological networks from high-throughput data has received huge attention during the last decade and can be considered an important problem class in systems biology. However, it has been recognized that reliable network inference remains an unsolved problem. Most authors have identified lack of data and deficiencies in the inference algorithms as the main reasons for this situation.
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On the interaction of bovine serum albumin with ionic surfactants: temperature induced EPR changes of a maleimide nitroxide reflect local protein dynamics and probe solvent accessibility.
Colloids Surf B Biointerfaces
PUBLISHED: 03-28-2011
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The interaction of bovine serum albumin (BSA) with the ionic surfactants sodium dodecylsulfate (SDS, anionic), cetyltrimethylammonium chloride (CTAC, cationic) and N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS, zwitterionic) was studied by electron paramagnetic resonance (EPR) spectroscopy of spin label covalently bound to the single free thiol group of the protein. EPR spectra simulation allows to monitor the protein dynamics at the labeling site and to estimate the changes in standard Gibbs free energy, enthalpy and entropy for transferring the nitroxide side chain from the more motionally restricted to the less restricted component. Whereas SDS and CTAC showed similar increases in the dynamics of the protein backbone for all measured concentrations, HPS presented a smaller effect at concentrations above 1.5mM. At 10mM of surfactants and 0.15 mM BSA, the standard Gibbs free energy change was consistent with protein backbone conformations more expanded and exposed to the solvent as compared to the native protein, but with a less pronounced effect for HPS. In the presence of the surfactants, the enthalpy change, related to the energy required to dissociate the nitroxide side chain from the protein, was greater, suggesting a lower water activity. The nitroxide side chain also detected a higher viscosity environment in the vicinity of the paramagnetic probe induced by the addition of the surfactants. The results suggest that the surfactant-BSA interaction, at higher surfactant concentration, is affected by the affinities of the surfactant to its own micelles and micelle-like aggregates. Complementary DLS data suggests that the temperature induced changes monitored by the nitroxide probe reflects local changes in the vicinity of the single thiol group of Cys-34 BSA residue.
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Biotechnology tools in agriculture: recent patents involving soybean, corn and sugarcane.
Recent Pat Food Nutr Agric
PUBLISHED: 01-14-2011
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The technological opportunities opened up by biotechnology in agriculture are diverse, including plant breeding, the partial or total relief of pesticides chemicals usage, the improvement of soil fertility, the improvement of the quality attributes of various foods. Specifically, various tricks of biotechnology can be used for higher seed yield, resistance to diseases and insects, better stems and roots, tolerance to drought and heat, and better agronomic quality. A number of recent works considerably widen the potential of plant biotechnology where transformation methods and studies of molecular genomics have been described. For example, transformation techniques and search for new selectable markers involving biolistic technique, gene transfer technique using the soil bacterium Agrobacterium tumefaciens, selection technique based on the use of mannose, utilization of genes promoting endogenous hormone production under the control of chemical stimulants, further more, engineering the nuclear genome without antibiotic resistance genes and engineering the plastid genome. We are presenting in this paper some of the recent patents on methods and techniques involving genes coding proteins and breeding techniques with possible agronomic applicability on crops economically important, such as soybean, corn and sugarcane.
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Lifespan of human amniotic fluid-derived multipotent mesenchymal stromal cells.
Cytotherapy
PUBLISHED: 01-05-2011
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Human multipotent mesenchymal stromal cells (hMSC) have become one of the main interests in regenerative medicine because of their ability to differentiate into different lineages. Human amniotic fluid is reported to contain MSC (hAMSC) and therefore may be a useful source of cells for clinical applications. However, our understanding of the behavior of these cells in indefinite in vitro culture conditions is very limited.
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The impact of conservation on the status of the worlds vertebrates.
Michael Hoffmann, Craig Hilton-Taylor, Ariadne Angulo, Monika Böhm, Thomas M Brooks, Stuart H M Butchart, Kent E Carpenter, Janice Chanson, Ben Collen, Neil A Cox, William R T Darwall, Nicholas K Dulvy, Lucy R Harrison, Vineet Katariya, Caroline M Pollock, Suhel Quader, Nadia I Richman, Ana S L Rodrigues, Marcelo F Tognelli, Jean-Christophe Vié, John M Aguiar, David J Allen, Gerald R Allen, Giovanni Amori, Natalia B Ananjeva, Franco Andreone, Paul Andrew, Aida Luz Aquino Ortiz, Jonathan E M Baillie, Ricardo Baldi, Ben D Bell, S D Biju, Jeremy P Bird, Patricia Black-Decima, J Julian Blanc, Federico Bolaños, Wilmar Bolivar-G, Ian J Burfield, James A Burton, David R Capper, Fernando Castro, Gianluca Catullo, Rachel D Cavanagh, Alan Channing, Ning Labbish Chao, Anna M Chenery, Federica Chiozza, Viola Clausnitzer, Nigel J Collar, Leah C Collett, Bruce B Collette, Claudia F Cortez Fernandez, Matthew T Craig, Michael J Crosby, Neil Cumberlidge, Annabelle Cuttelod, Andrew E Derocher, Arvin C Diesmos, John S Donaldson, J W Duckworth, Guy Dutson, S K Dutta, Richard H Emslie, Aljos Farjon, Sarah Fowler, Jörg Freyhof, David L Garshelis, Justin Gerlach, David J Gower, Tandora D Grant, Geoffrey A Hammerson, Richard B Harris, Lawrence R Heaney, S Blair Hedges, Jean-Marc Hero, Baz Hughes, Syed Ainul Hussain, Javier Icochea M, Robert F Inger, Nobuo Ishii, Djoko T Iskandar, Richard K B Jenkins, Yoshio Kaneko, Maurice Kottelat, Kit M Kovacs, Sergius L Kuzmin, Enrique La Marca, John F Lamoreux, Michael W N Lau, Esteban O Lavilla, Kristin Leus, Rebecca L Lewison, Gabriela Lichtenstein, Suzanne R Livingstone, Vimoksalehi Lukoschek, David P Mallon, Philip J K McGowan, Anna McIvor, Patricia D Moehlman, Sanjay Molur, Antonio Muñoz Alonso, John A Musick, Kristin Nowell, Ronald A Nussbaum, Wanda Olech, Nikolay L Orlov, Theodore J Papenfuss, Gabriela Parra-Olea, William F Perrin, Beth A Polidoro, Mohammad Pourkazemi, Paul A Racey, James S Ragle, Mala Ram, Galen Rathbun, Robert P Reynolds, Anders G J Rhodin, Stephen J Richards, Lily O Rodriguez, Santiago R Ron, Carlo Rondinini, Anthony B Rylands, Yvonne Sadovy de Mitcheson, Jonnell C Sanciangco, Kate L Sanders, Georgina Santos-Barrera, Jan Schipper, Caryn Self-Sullivan, Yichuan Shi, Alan Shoemaker, Frederick T Short, Claudio Sillero-Zubiri, Débora L Silvano, Kevin G Smith, Andrew T Smith, Jos Snoeks, Alison J Stattersfield, Andrew J Symes, Andrew B Taber, Bibhab K Talukdar, Helen J Temple, Rob Timmins, Joseph A Tobias, Katerina Tsytsulina, Denis Tweddle, Carmen Ubeda, Sarah V Valenti, Peter Paul van Dijk, Liza M Veiga, Alberto Veloso, David C Wege, Mark Wilkinson, Elizabeth A Williamson, Feng Xie, Bruce E Young, H Resit Akçakaya, Leon Bennun, Tim M Blackburn, Luigi Boitani, Holly T Dublin, Gustavo A B da Fonseca, Claude Gascon, Thomas E Lacher, Georgina M Mace, Susan A Mainka, Jeffery A McNeely, Russell A Mittermeier, Gordon McGregor Reid, Jon Paul Rodríguez, Andrew A Rosenberg, Michael J Samways, Jane Smart, Bruce A Stein, Simon N Stuart.
Science
PUBLISHED: 10-26-2010
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Using data for 25,780 species categorized on the International Union for Conservation of Nature Red List, we present an assessment of the status of the worlds vertebrates. One-fifth of species are classified as Threatened, and we show that this figure is increasing: On average, 52 species of mammals, birds, and amphibians move one category closer to extinction each year. However, this overall pattern conceals the impact of conservation successes, and we show that the rate of deterioration would have been at least one-fifth again as much in the absence of these. Nonetheless, current conservation efforts remain insufficient to offset the main drivers of biodiversity loss in these groups: agricultural expansion, logging, overexploitation, and invasive alien species.
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Serine residues in the LAT adaptor are essential for TCR-dependent signal transduction.
J. Leukoc. Biol.
PUBLISHED: 10-12-2010
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The adaptor protein LAT has a prominent role in the transduction of intracellular signals elicited by the TCR/CD3 complex. Upon TCR engagement, LAT becomes tyrosine-phosphorylated and thereby, recruits to the membrane several proteins implicated in the activation of downstream signaling pathways. However, little is known about the role of other conserved motifs present in the LAT sequence. Here, we report that the adaptor LAT contains several conserved serine-based motifs, which are essential for proper signal transduction through the TCR. Mutation of these serine motifs in the human T cell line Jurkat prevents proper calcium influx, MAPK activation, and IL-2 production in response to TCR/CD3 stimulation. Moreover, this mutant form of LAT has a reduced ability to bind to PLC-?1 and SLP-76, although phosphorylation of tyrosine residues 132, 171, and 191 is not decreased, raising a possible role for the serine-based motifs of LAT for the binding of important partners. The functional role of LAT serine-based motifs in signal transduction could be mediated by an effect on tyrosine phosphorylation, as their mutation significantly diminishes the phosphorylation of tyrosine residue 226. In addition, these serine motifs seem to have a regulatory role, given that upon their mutation, ZAP-70 shows enhanced phosphorylation. Therefore, the LAT serine-based motifs likely regulate signaling pathways that are essential for T cell physiology.
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[Test-retest and interobserver reliability of a Spanish version (MMSE-37) of the Folstein minimental test, adapted to populations with a low level of schooling].
Rev Neurol
PUBLISHED: 06-02-2010
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Several versions of Folsteins minimental test (MMSE, Minimental State Examination) exist in Spanish. One of them is the 37-point MMSE (MMSE-37), which is adapted to people with a low cultural level. AIM. To study the interobserver and test-retest reliability of the MMSE-37.
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Enhancement of the Curie temperature along the perovskite series RCu3Mn4O12 driven by chemical pressure of R3+ cations (R = rare earths).
Inorg Chem
PUBLISHED: 05-14-2010
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The compounds of the title series have been prepared from citrate precursors under moderate pressure conditions (P = 2 GPa) and 1000 degrees C in the presence of KClO(4) as oxidizing agent. The crystal structures are cubic, space group Im3 (No. 204); the unit cell parameters linearly vary from a = 7.3272(4) A (R = La) to a = 7.2409(1) A (R = Lu) at room temperature. A neutron or synchrotron X-ray diffraction study of all the members of the series reveals an interesting correlation between some structural parameters and the magnetic properties. The electron injection effect upon replacement of Ca(2+) with R(3+) cations in the parent CaCu(3)Mn(4)O(12) oxide leads to a substantial increment of the ferrimagnetic Curie temperature (T(C)). An essential ingredient is supplied by the internal pressure of the R(3+) cations upon a decrease in size along the rare-earth series, from La to Lu: the concomitant compression of the MnO(6) octahedral units for the small rare earths provides progressively shorter Mn-O distances and improves the overlapping between Mn and O orbitals, thereby promoting superexchange and enhancing T(C) by 50 K along the series. This interaction is also reinforced by a ferromagnetic component that depends on the local distortion of the MnO(6) octahedra, which also increases along the series, constituting an additional factor, via intersite virtual charge transfer t-e orbital hybridization, for the observed increment of T(C).
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Molecular dynamics and partitioning of di-tert-butyl nitroxide in stratum corneum membranes: effect of terpenes.
Lipids
PUBLISHED: 03-08-2010
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In this work, we have used electron paramagnetic resonance (EPR) spectroscopy of the small spin label di-tert-butyl nitroxide (DTBN), which partitions the aqueous and hydrocarbon phases, to study the interaction of the terpenes alpha-terpineol, 1,8-cineole, L(-)-carvone and (+)-limonene with the uppermost skin layer, the stratum corneum, and the membrane models of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). The EPR spectra indicated that the terpenes increase both the partition coefficient and the rotational correlation time of the spin labels in the stratum corneum membranes, whereas similar effects were observed in the DMPC and DPPC bilayers only at temperatures below the liquid-crystalline phase. The EPR parameter associated to probe polarity inside the membranes showed thermotropically induced changes, suggesting relocations of spin probe, which were dependent on the membrane phases. While the DMPC and DPPC bilayers showed abrupt changes in the partitioning and rotational correlation time parameters in the phase transitions, the SC membranes were characterized by slight changes in the total range of measured temperatures, presenting the greatest changes or membranes reorganizations in the temperature range of approximately 50 to approximately 74 degrees C. The results suggest that terpenes act as spacers, weakening the hydrogen-bonded network at the polar interface and thus fluidizing the stratum corneum lipids.
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An iterative identification procedure for dynamic modeling of biochemical networks.
BMC Syst Biol
PUBLISHED: 02-17-2010
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Mathematical models provide abstract representations of the information gained from experimental observations on the structure and function of a particular biological system. Conferring a predictive character on a given mathematical formulation often relies on determining a number of non-measurable parameters that largely condition the models response. These parameters can be identified by fitting the model to experimental data. However, this fit can only be accomplished when identifiability can be guaranteed.
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Discovery of potent and selective bicyclic A(2B) adenosine receptor antagonists via bioisosteric amide replacement.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-11-2010
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Several new potent and selective A(2B) adenosine receptor antagonists have been prepared in which the aryl-amide moiety of the lead series, exemplified by 1a, has been replaced by bioisosteric bicyclic moieties. Although the majority of compounds had generally improved microsomal stability as compared to 1a, this was not translated into overall improvements in the pharmacokinetic profiles of a representative set of compounds.
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Approximating the distribution of population size in stochastic multiregional matrix models with fast migration.
Philos Trans A Math Phys Eng Sci
PUBLISHED: 11-04-2009
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In this work we deal with a multiregional model in discrete time for an age-structured population which lives in an environment that changes randomly with time and is distributed in different spatial patches. In addition, and as is often the case in applications, we assume that migration is fast with respect to demography. Using approximate aggregation techniques we make use of the existence of different time scales in the model and reduce the dimension of the system obtaining a stochastic Leslie model in which the variables are the total population in each age class. Literature shows that, under reasonable conditions, the distribution of population size in matrix models with environmental stochasticity is asymptotically lognormal, and is characterized by two parameters, stochastic growth rate (s.g.r.) and scaled logarithmic variance (s.l.v.), that, in most practical cases, cannot be computed exactly. We show that the s.g.r. and the s.l.v. of the original multiregional model can be approximated by those corresponding to the reduced stochastic Leslie model, therefore simplifying its analysis. Moreover, we illustrate the usefulness of the reduction procedure by presenting some practical cases in which, although the explicit computation of the s.g.r. and the s.l.v. of the original multiregional model is not feasible, we can calculate its analogues for the reduced model.
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Ancestry analysis in the 11-M Madrid bomb attack investigation.
PLoS ONE
PUBLISHED: 07-08-2009
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The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR) profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a critical part of the investigation and was instigated to help refine the search for further suspects. Although mitochondrial DNA (mtDNA) and Y-chromosome markers routinely demonstrate informative geographic differentiation, the populations compared in this analysis were known to show a proportion of shared mtDNA and Y haplotypes as a result of recent gene-flow across the western Mediterranean, while any two loci can be unrepresentative of the ancestry of an individual as a whole. We based our principal analysis on a validated 34plex autosomal ancestry-informative-marker single nucleotide polymorphism (AIM-SNP) assay to make an assignment of ancestry for DNA from seven unmatched case samples including a handprint from a bag containing undetonated explosives together with personal items recovered from various locations in Madrid associated with the suspects. To assess marker informativeness before genotyping, we predicted the probable classification success for the 34plex assay with standard error estimators for a naïve Bayesian classifier using Moroccan and Spanish training sets (each n = 48). Once misclassification error was found to be sufficiently low, genotyping yielded seven near-complete profiles (33 of 34 AIM-SNPs) that in four cases gave probabilities providing a clear assignment of ancestry. One of the suspects predicted to be North African by AIM-SNP analysis of DNA from a toothbrush was identified late in the investigation as Algerian in origin. The results achieved illustrate the benefit of adding specialized marker sets to provide enhanced scope and power to an already highly effective system of DNA analysis for forensic identification.
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Reduction of supercritical multiregional stochastic models with fast migration.
Acta Biotheor.
PUBLISHED: 06-08-2009
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In this work we study the behavior of a time discrete multiregional stochastic model for a population structured in age classes and spread out in different spatial patches between which individuals can migrate. The dynamics of the population is controlled both by reproduction-survival and by migration. These processes take place at different time scales in the sense of the latter being much faster than the former. We incorporate the effect of demographic stochasticity into the population, which results in both dynamics being modelled by multitype Bienaymé-Galton-Watson branching processes. We present a multitype global model that incorporates the effect of both processes and, making use of the existence of different time scales for demography and migration, build a reduced model in which the variables correspond to the total population in each age class. We extend previous results that relate the behavior of the original and the reduced model showing that, given a large enough separation of time scales between demography and migration, we can obtain information about the behavior of the multitype global model through the study of the simpler reduced model. We concentrate on the case where the two systems are supercritical and therefore the expected number of individuals grows to infinity, and show that we can approximate the asymptotic structure of the population vector and the asymptotic population size of the original system through the study of the reduced model.
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Exploring multiplicity conditions in enzymatic reaction networks.
Biotechnol. Prog.
PUBLISHED: 06-05-2009
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In this work, a novel algorithmic approach to detect multiplicity of steady states in enzymatic reaction networks is presented. The method exploits the structural properties of networks derived from the Chemical Reaction Network Theory. In first instance, the space of parameters is divided in different regions according to the qualitative behavior induced by the parameters in the long term dynamics of the network. Once the regions are identified, a condition for the appearance of multiplicities is checked in the different regions by solving a given optimization problem. In this way, the method allows the characterization of the whole parameter space of biochemical networks in terms of the appearance or not of multistability. The approach is illustrated through a well-known case of enzymatic catalysis with substrate inhibition.
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The role of the Pb2+ 6s lone pair in the structure of the double perovskite Pb2ScSbO6.
Dalton Trans
PUBLISHED: 06-01-2009
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The new double perovskite Pb2ScSbO6 was synthesized by standard ceramic procedures; the Rietveld refinement of room temperature neutron powder diffraction data shows that the crystal structure is well defined in the space group Fm3[combining macron]m. It contains a completely ordered array of alternating ScO6 and SbO6 octahedra sharing corners; the PbO12 polyhedra present an off-center displacement of the lead atoms along the [111] direction, due to the electrostatic repulsion between the Pb2+ 6s lone pair and the Pb-O bonds of the cuboctahedron. Dielectric permittivity measurements show a peak near 343 K, with a Curie-Weiss response above this temperature, which suggests an antiferroelectric behavior. Finally we present a DFT study of the electronic structure of Pb2ScSbO6, showing a great difference between the electronic density within SbO6 and ScO6 octahedra.
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A new perovskite polytype in the high-pressure sequence of BaIrO(3).
J. Am. Chem. Soc.
PUBLISHED: 05-28-2009
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The high-pressure sequence of the perovskite polytypes of BaIrO(3) has been investigated in the pressure range up to 10 GPa. At ambient pressure the so-called "9R" polytype has been prepared by solid-state reaction and slow cooling in air to yield an almost fully oxygen-stoichiometric BaIrO(2.96(1)) composition. The crystal structure has been refined from XRD data in the monoclinic C2/m space group with a = 10.0046(3) A, b = 5.75362(14) A, c = 15.1839(4) A, beta = 103.27(1) degrees ; it contains trimers of face-sharing octahedra (or Ir(3)O(12) trioctahedra) that are linked by their vertices to form columns parallel to the c-axis with a stacking of layers of corner sharing (c) and face sharing (h) IrO(6) octahedra along the sequence hhchhc. This structure is stable up to 3 GPa; at 4 GPa a new 5H polytype has been stabilized as a pure phase. The crystal structure has been solved by ab initio procedures from powder XRD data. It is monoclinic with a = 9.9511(2) A, b = 5.7503(1) A, c = 13.71003(3) A, beta = 118.404(2) degrees , and it was refined in the C2/m space group from NPD data collected at room temperature. This polytype can be described as a stacking of IrO(6) octahedra along the sequence hchcc. The structure contains chains of double dimer units of face-sharing octahedra; the twin dimers are connected to single layers of vertex-sharing octahedra, forming infinite chains along c. This is a unique stacking that, with this repetition length, has never been described before among the hexagonal polytypes of ABO(3) perovskites. The 5H polytype is stable in a narrow pressure range; at 5 GPa the 6H structure is formed, stable up to 10 GPa. The 6H-BaIrO(3) polytype is monoclinic, space group C2/c, with a = 5.7483(2) A, b = 9.9390(3) A, c = 14.3582(5) A, beta = 91.319(2) degrees . The structure consists of dimers of face-sharing octahedra separated by single corner-sharing octahedra, showing the sequence hcchcc along the c-axis. At 10 GPa the cubic 3C perovskite structure could be identified as a minority phase, with a = 4.0611(7) A, defined in the Pm3m space group. The precarious stability of the 5H polytype, as well as the novel pressure sequence displayed by BaIrO(3) that is distinct from the classical sequence 9R-4H-6H-3C exhibited by many transition metal oxides, for instance BaRuO(3), is a result of the particular stability of the "9R" ambient-pressure structure, which is reinforced by a strong Ir-Ir bond across the octahedral faces, and the Ir-Ir Coulombic repulsion across shared faces that destabilizes the 4H polytype relative to the 6H phase to allow stabilization of the hybrid 5H polytype in a narrow presure range.
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Energy-dispersive X-ray absorption spectroscopy at LNLS: investigation on strongly correlated metal oxides.
J Synchrotron Radiat
PUBLISHED: 05-16-2009
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An energy-dispersive X-ray absorption spectroscopy beamline mainly dedicated to X-ray magnetic circular dichroism (XMCD) and material science under extreme conditions has been implemented in a bending-magnet port at the Brazilian Synchrotron Light Laboratory. Here the beamline technical characteristics are described, including the most important aspects of the mechanics, optical elements and detection set-up. The beamline performance is then illustrated through two case studies on strongly correlated transition metal oxides: an XMCD insight into the modifications of the magnetic properties of Cr-doped manganites and the structural deformation in nickel perovskites under high applied pressure.
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[Meningioma of the internal auditory canal: A rare entity].
Acta Otorrinolaringol Esp
PUBLISHED: 05-08-2009
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We present the case of a 61-year-old man in whom the magnetic resonance imaging performed prior to left cochlear implant surgery revealed a lesion in the right internal auditory canal resembling a vestibular Schwannoma. Left cochlear implant surgery was performed and three months later, the right internal auditory canal lesion was removed. The final histopathological analysis revealed it to be a meningioma.
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PTPN22 C1858T polymorphism and human brucellosis.
Scand. J. Infect. Dis.
PUBLISHED: 04-07-2009
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The PTPN22 gene encodes for an intracellular lymphoid-specific phosphatase (Lyp) that has a negative regulatory effect on T-cell activation. The minor allele of the single nucleotide polymorphism (SNP) in the PTPN22 gene encoding the Lyp-tyrosine phosphatase has been associated with multiple autoimmune disorders and with susceptibility to M. tuberculosis. It is possible, therefore, that variants of this gene may also be involved in susceptibility to another intracellular pathogen, B. melitensis, which gives rise to human brucellosis. Accordingly, we studied 111 patients with brucellosis and 150 healthy controls who had had no prior contact with the pathogen. Genotyping of the PTPN22 1858CT was performed by an allele discrimination assay with TaqMan 5. We found no statistically significant differences between the patients and the controls in genotype or allele frequencies of PTPN22 1858CT. These data suggest that this variant is not associated with human brucellosis.
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[Fulvestrant in heavily pretreated postmenopausal women with advanced breast cancer].
Med Clin (Barc)
PUBLISHED: 04-01-2009
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Fulvestrant (Flv) is a pure antiestrogen without agonist activity. Flv is effective as second line treatment in postmenopausal women with advanced breast cancer after tamoxifen.
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Forensic analysis of dog (Canis lupus familiaris) mitochondrial DNA sequences: an inter-laboratory study of the GEP-ISFG working group.
Forensic Sci Int Genet
PUBLISHED: 02-16-2009
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A voluntary collaborative exercise aiming at the mitochondrial analysis of canine biological samples was carried out in 2006-2008 by the Non-Human Forensic Genetics Commission of the Spanish and Portuguese Working Group (GEP) of the International Society for Forensic Genetics (ISFG). The participating laboratories were asked to sequence two dog samples (one bloodstain and one hair sample) for the mitochondrial D-loop region comprised between positions 15,372 and 16,083 using suggested primers and PCR conditions, and to compare their results against a reference sequence. Twenty-one participating laboratories reported a total of 67.5% concordant results, 15% non-concordant results, and 17.5% no results. The hair sample analysis presented more difficulty to the participants than the bloodstain analysis, with a high percentage (29%) failing to obtain a result. The high level of participation showed the interest of the community in the analysis of dog forensic samples but the results reveal that crucial methodological issues need to be addressed and further training is required in order to respond proficiently to the demands of forensic casework.
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Interaction of bovine serum albumin (BSA) with ionic surfactants evaluated by electron paramagnetic resonance (EPR) spectroscopy.
Colloids Surf B Biointerfaces
PUBLISHED: 01-27-2009
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EPR spectra of 5- and 16-doxyl stearic acid nitroxide probes (5-DSA and 16-DSA, respectively) bound to bovine serum albumin (BSA) revealed that in the presence of ionic surfactants, at least, two label populations coexist in equilibrium. The rotational correlation times (tau) indicated that component 1 displays a more restricted mobility state, associated to the spin labels bound to the protein; the less immobilized component 2 is due to label localization in the surfactant aggregates. For both probes, the increase of surfactant concentration leads to higher motional levels of component 1 followed by a simultaneous decrease of this fraction of nitroxides and its conversion into component 2. For 10mM cethyltrimethylammonium chloride (CTAC), the nitroxides are 100% bound to the protein, whereas at 10mM N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS) and sodium dodecyl sulfate (SDS) the fractions of bound nitroxides are reduced to 18% and 86%, respectively. No significant polarity changes were observed in the whole surfactant concentration range for component 1. Moreover, at higher surfactant concentration, component 2 exhibited a similar polarity as in the pure surfactant micelles. For 16-DSA the surfactant effect is different: at 10mM of HPS and CTAC the fractions of bound nitroxides are 76% and 49%, respectively, while at 10mM SDS they are present exclusively in a micellar environment, consistent with 100% of component 2. Overall, both SDS and HPS are able to effectively displace the nitroxide probes from the protein binding sites, while CTAC seems to affect the nitroxide binding to a significantly smaller extent.
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4-Nerolidylcatechol and its synthetic analogues: antioxidant activity and toxicity evaluation.
Eur J Med Chem
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4-Nerolidylcatechol (1) is a secondary metabolite of plants and is described as a promising anti-inflammatory, antimalarial, antiulcerogenic, analgesic and cytotoxic compound possibly due to its antioxidant profile. In this study, we evaluated the pharmacologic activity and the antioxidant and toxicological profiles of compound (1) and its synthetic analogues (2-6). The synthetic analogues were designed from the lead compound, (1), using a molecular-simplification strategy. Compound 5 showed, by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ?-carotene systems, similar antioxidant activity when compared to compound (1). The oxidative stress in erythrocyte membrane demonstrated the highly protective effect of compounds (4), (5) and (6) and high antioxidant/pro-oxidant activity in relation to the concentrations of compounds (1) and (3). Compounds (2), (4), (5) and (6) were haemobiocompatible. All compounds (1-6) showed cytotoxic effects in 3T3 cells, but compounds (2) and (6) were highly cytotoxic in this lineage when compared to compound (1). Compound (5) had a lower myelosuppressive effect in haematopoietic progenitor cells compared to (1). Both compounds, (1) and (5), showed low genotoxic effects in vitro, on human lymphocyte cells. In addition, these compounds also showed low-toxicity in vivo as defined a LD50 > 2000 mg/kg. In this assay, we did not observe death in the animals exposed to treatment with (1) and (5) compound. In conclusion, the structural design of the analogues as validated once compound (5) was found to have an antioxidant profile that was as potent as the lead compound (1). In addition, considering the safety profile, these compounds are promising as preventive and/or therapeutic agents against oxidative damage.
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Intratympanic steroids as primary initial treatment of idiopathic sudden sensorineural hearing loss. The Hospital Universitario Ramón y Cajal experience and review of the literature.
Eur Arch Otorhinolaryngol
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The objective of this study was to determine the effectiveness, dosage, safety and comfort of intratympanic steroids as primary initial treatment of idiopathic sudden sensorineural hearing loss (ISSHL). Prospective nonrandomized clinical practice study was performed in Tertiary referral center university hospital. A total of 35 consecutive patients suffering from newly diagnosed sudden sensorineural hearing loss with mean pure-tone average thresholds of 81 ± 21 dB were treated. No previous therapy had been undertaken. Intratympanic steroid injection as primary initial treatment was administered during 2 weeks on a twice a week schedule, between 2010 and 2011. Treatment was started on average within 2 days of symptoms onset. Pre and post-treatment audiometric evaluations were analyzed on follow-up as well as tolerance of the procedure and possible adverse effects. 66-85 % of patients achieved successful treatment according to the different outcome criteria used to evaluate hearing improvement (Furuhashi criteria/improvement of ?10 dB in pure-tone average). Mean post-treatment improvement regarding pure-tone average was 34 ± 21 dB. A 48 ± 43 % improvement in speech discrimination score was observed. Patients received an average of 18 mg of methylprednisolone per injection and a total dose of 72 mg per treatment cycle. No serious adverse effects were noted. Intratympanic steroid injection is an effective, safe and well-tolerated office based-procedure for the treatment of ISSHL as primary initial treatment that can avoid the potential adverse effects of systemic steroids. A higher dose, schedule of administration as well as standardization of hearing recovery criteria still need to be established.
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Population genetic data of 30 autosomal indels in Central Spain and the Basque Country populations.
Forensic Sci Int Genet
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Samples from 71 unrelated Central Spain individuals and 60 Basque Country autochthonous individuals were typed with the Investigator DIPplex kit (30 biallelic autosomal mini-indels and amelogenin) and their allele frequencies were determined. Results demonstrated the assumption of independence within and between the loci analyzed. Different partially silent alleles were observed for the locus HLD97 (rs17238892) produced by a neighboring SNP (A/G), located 61 bp downstream from the main indel site as shown by sequencing analysis.
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Trypanocidal action of (-)-elatol involves an oxidative stress triggered by mitochondria dysfunction.
Mar Drugs
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Natural compounds have shown good potential for the discovery of new chemotherapeutics for the treatment of Chagas disease. Recently, our group reported the effective trypanocidal activity of (-)-elatol, extracted from the red macroalgae Laurencia dendroidea present in the Brazilian coast against Trypanosoma cruzi. However, the mechanism of action of this compound has remained unclear. There are only hypotheses concerning its action on mitochondrial function. Here, we further investigated the mechanisms of action of (-)-elatol on trypomastigotes of T. cruzi. For this, we evaluated some biochemical alterations in trypomastigotes treated with (-)-elatol. Our results show that (-)-elatol induced depolarization of the mitochondrial membrane, an increase in the formation of mitochondrial superoxide anion and loss of cell membrane and DNA integrity. Additionally, (-)-elatol induced formation of autophagic vacuoles and a decrease in cell volume. All together, these results suggest that the trypanocidal action of (-)-elatol involves multiple events and mitochondria might be the initial target organelle. Our hypothesis is that the mitochondrial dysfunction leads to an increase of ROS production through the electron transport chain, which affects cell membrane and DNA integrity leading to different types of parasite death.
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[Variability in the reporting of adverse reactions to the pandemic and seasonal influenza vaccine: seasons 2009-2010 and 2010-2011. Valencian community, Spain].
Rev. Esp. Salud Publica
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The loss of confidence in the safety of vaccines derived from alarm conditions, as in the case of the flu pandemic may affect both vaccination coverage and the sensitivity to the reporting of suspected adverse reactions associated vaccines (SRAAV). The aim of the study is to describe the adverse effects reported to the vaccine against pandemic influenza in the 2009-2010 season and against seasonal influenza in 2009-2010 and 2010-2011 seasons, by type of vaccine, risk groups and by age group in the Valencian Community (CV).
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Toxicity of terpenes on fibroblast cells compared to their hemolytic potential and increase in erythrocyte membrane fluidity.
Toxicol In Vitro
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Terpenes are considered potent skin permeation enhancers with low toxicity. Electron paramagnetic resonance (EPR) spectroscopy of the spin label 5-doxyl stearic acid (5-DSA) was used to monitor the effect of sesquiterpene nerolidol and various monoterpenes on membrane fluidity in erythrocyte and fibroblast cells. In addition, the hemolytic levels and cytotoxic effects on cultured fibroblast cells were also measured to investigate possible relationships between the cellular irritation potentials of terpenes and the ability to modify membrane fluidity. All terpenes increased cell membrane fluidity with no significant differences between the monoterpenes, but the effect of sesquiterpene was significantly greater than that of the monoterpenes. The IC(50) values for the terpenes in the cytotoxicity assay indicated that 1,8-cineole showed lower cytotoxicity and ?-terpineol and nerolidol showed higher cytotoxicity. The correlation between the hemolytic effect and the IC(50) values for fibroblast viability was low (R=0.61); however, in both tests, nerolidol was among the most aggressive of terpenes and 1,8-cineole was among the least aggressive. Obtaining information concerning the toxicity and potency of terpenes could aid in the design of topical formulations optimized to facilitate drug absorption for the treatment of many skin diseases.
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Correlation between the crystal structure and the Curie temperature in RCu3(Mn3Fe)O12 (R = rare-earth) complex perovskites.
Dalton Trans
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New members of the family of complex-perovskite oxides with the formula RCu(3)(Mn(3)Fe)O(12) (R = Ce, Pr, Tb, Dy, Ho, Er, Tm, Yb, Lu and Y) have been synthesized and characterized. Polycrystalline samples have been prepared from citrate precursors treated under moderate pressure conditions (2-3.5 GPa) and 1000 °C in the presence of KClO(4) as an oxidizing agent. All the samples have been studied by neutron powder diffraction (NPD) at 300 K and 2 K. These oxides crystallize in the cubic space group Im3 (no. 204). Mn(4+)/Mn(3+) and Fe(3+) occupy at random the octahedral B positions of the perovskite structure. These materials have also been characterized by magnetic and magnetotransport measurements. The observed enhancement of T(C) along the RCu(3)(Mn(3)Fe)O(12) series is understood as an effect of the chemical pressure on the (Mn,Fe)-O bonds as R(3+) size decreases. The semiconducting behaviour observed in all of the samples is related with the introduction of Fe at B position. Despite the drastic change of the transport properties, significant negative magnetoresistance values are observed in the Fe-containing compounds both at 10 K and 300 K.
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Characterizing multistationarity regimes in biochemical reaction networks.
PLoS ONE
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Switch like responses appear as common strategies in the regulation of cellular systems. Here we present a method to characterize bistable regimes in biochemical reaction networks that can be of use to both direct and reverse engineering of biological switches. In the design of a synthetic biological switch, it is important to study the capability for bistability of the underlying biochemical network structure. Chemical Reaction Network Theory (CRNT) may help at this level to decide whether a given network has the capacity for multiple positive equilibria, based on their structural properties. However, in order to build a working switch, we also need to ensure that the bistability property is robust, by studying the conditions leading to the existence of two different steady states. In the reverse engineering of biological switches, knowledge collected about the bistable regimes of the underlying potential model structures can contribute at the model identification stage to a drastic reduction of the feasible region in the parameter space of search. In this work, we make use and extend previous results of the CRNT, aiming not only to discriminate whether a biochemical reaction network can exhibit multiple steady states, but also to determine the regions within the whole space of parameters capable of producing multistationarity. To that purpose we present and justify a condition on the parameters of biochemical networks for the appearance of multistationarity, and propose an efficient and reliable computational method to check its satisfaction through the parameter space.
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Dynamic optimization of distributed biological systems using robust and efficient numerical techniques.
BMC Syst Biol
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Systems biology allows the analysis of biological systems behavior under different conditions through in silico experimentation. The possibility of perturbing biological systems in different manners calls for the design of perturbations to achieve particular goals. Examples would include, the design of a chemical stimulation to maximize the amplitude of a given cellular signal or to achieve a desired pattern in pattern formation systems, etc. Such design problems can be mathematically formulated as dynamic optimization problems which are particularly challenging when the system is described by partial differential equations.This work addresses the numerical solution of such dynamic optimization problems for spatially distributed biological systems. The usual nonlinear and large scale nature of the mathematical models related to this class of systems and the presence of constraints on the optimization problems, impose a number of difficulties, such as the presence of suboptimal solutions, which call for robust and efficient numerical techniques.
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Changes in CDKN2D , TP53, and miR125a expression: potential role in the evaluation of human amniotic fluid-derived mesenchymal stromal cell fitness.
Genes Cells
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Human amniotic fluid-derived mesenchymal stromal cells (hAMSC) have become one of the main cell populations used in regenerative medicine and for the study of various clinical disorders. These cells have a great capacity for proliferation and differentiation and do not form teratomas when transplanted into animal models, and their stemness seems to be between embryonic cells and adult mesenchymal cells. Before their use in cell therapy, they must be cultured and expanded in vitro, but the effect this process has on their fitness, a determining factor for the success or failure of cell therapy, is unknown. We undertook a follow-up of gene and microRNAs (miRNAs) expression using microarray of hAMSC for the first 15 passages. Significant changes were noted in the expression of various mRNAs and miRNAs, particularly down-regulation of TP53, increased expression of hsa-miR-125a and up-regulation of CDKN2D . The variations in TP53 and hsa-miR-125a may act as an indicator of the stemness of the hAMSC, whereas CDKN2D may indicate the begging of early senescence process in a p53-independent mechanism. The genes described in this study will help evaluate the fitness of hAMSC, thus guaranteeing their biological quality for use in regenerative medicine.
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Interaction of miltefosine with intercellular membranes of stratum corneum and biomimetic lipid vesicles.
Int J Pharm
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Miltefosine (MT) is an alkylphospholipid approved for breast cancer metastasis and visceral leishmaniasis treatments, although the respective action mechanisms at the molecular level remain poorly understood. In this work, the interaction of miltefosine with the lipid component of stratum corneum (SC), the uppermost skin layer, was studied by electron paramagnetic resonance (EPR) spectroscopy of several fatty acid spin-labels. In addition, the effect of miltefosine on (i) spherical lipid vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and (ii) lipids extracted from SC was also investigated, by EPR and time-resolved polarized fluorescence methods. In SC of neonatal Wistar rats, 4% (w/w) miltefosine give rise to a large increase of the fluidity of the intercellular membranes, in the temperature range from 6 to about 50°C. This effect becomes negligible at temperatures higher that ca. 60°C. In large unilamelar vesicles of DPPC no significant changes could be observed with a miltefosine concentration 25% molar, in close analogy with the behavior of biomimetic vesicles prepared with bovine brain ceramide, behenic acid and cholesterol. In these last samples, a 25 mol% molar concentration of miltefosine produced only a modest decrease in the bilayer fluidity. Although miltefosine is not a feasible skin permeation enhancer due to its toxicity, the information provided in this work could be of utility in the development of a MT topical treatment of cutaneous leishmaniasis.
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Ancient DNA from hunter-gatherer and farmer groups from Northern Spain supports a random dispersion model for the Neolithic expansion into Europe.
PLoS ONE
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The phenomenon of Neolithisation refers to the transition of prehistoric populations from a hunter-gatherer to an agro-pastoralist lifestyle. Traditionally, the spread of an agro-pastoralist economy into Europe has been framed within a dichotomy based either on an acculturation phenomenon or on a demic diffusion. However, the nature and speed of this transition is a matter of continuing scientific debate in archaeology, anthropology, and human population genetics. In the present study, we have analyzed the mitochondrial DNA diversity in hunter-gatherers and first farmers from Northern Spain, in relation to the debate surrounding the phenomenon of Neolithisation in Europe.
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Fish discards management: pollution levels and best available removal techniques.
Mar. Pollut. Bull.
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Fish discards and by-catch issues are highly topical subjects that are permanently under a social focus. Two main approaches are being considered to address this discard problem: reducing the by-catch and increasing by-catch utilization. Interest in increased by-catch valorization may arise from a greater demand for fish products, such as the development of new markets for previously discarded species, the use of low-value specimens for aquaculture or the creation of value-added fish products for the food, pharmaceutical or cosmetic industries. However, contaminants present in fish discards may be transferred to their valorized products, leading to possible long-term bioaccumulation and subsequent adverse health effects. In this valorization framework, the aim is to promote responsible and sustainable management of marine resources. The pollutant levels in catches from European fisheries and the best available decontamination techniques for marine valorized discards/by-products are compiled and analyzed in this work.
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Collective phase-like mode and the role of lattice distortions at TN ~TC in RMn2O5 (R= Pr, Sm, Gd, Tb, Bi).
J Phys Condens Matter
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We report on electronic collective excitations in RMn(2)O(5) (R =Pr, Sm, Gd, Tb) showing condensation starting at and below ~T(N) ~T(C)~ 40-50 K. Their origin is understood as partial delocalized e(g) electron orbitals in the Jahn-Teller distortion of the pyramid dimer with strong hybridized Mn(3+)-O bonds. Our local probes, Raman, infrared, and x-ray absorption, back the conclusion that there is no structural phase transition at T(N)~T(C). Ferroelectricity is magnetically assisted by electron localization triggering lattice polarizability by unscreening. We have also found phonon hardening as the rare earth is sequentially replaced. This is understood as a consequence of lanthanide contraction. It is suggested that partially f-electron screened rare earth nuclei might be introducing a perturbation to e(g) electrons prone to delocalize as the superexchange interaction takes place.
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CRNreals: a toolbox for distinguishability and identifiability analysis of biochemical reaction networks.
Bioinformatics
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Chemical reaction network theory is widely used in modeling and analyzing complex biochemical systems such as metabolic networks and cell signalling pathways. Being able to produce all the biologically and chemically important qualitative dynamical features, chemical reaction networks (CRNs) have attracted significant attention in the systems biology community. It is well-known that the reliable inference of CRN models generally requires thorough identifiability and distinguishability analysis together with carefully selected prior modeling assumptions. Here, we present a software toolbox CRNreals that supports the distinguishability and identifiability analysis of CRN models using recently published optimization-based procedures. Availability and implementation: The CRNreals toolbox and the associated documentation are available at http://www.iim.csic.es/~gingproc/CRNreals/. The toolbox runs under the popular MATLAB computational environment and supports several free and commercial linear programming and mixed integer linear programming solvers.
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Pyrazine-based Syk kinase inhibitors.
Bioorg. Med. Chem. Lett.
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A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay.
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Evaluation of a low cost cryopreservation system on the biology of human amniotic fluid-derived mesenchymal stromal cells.
Cryobiology
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Human amniotic-derived mesenchymal stromal cells (hAMSC) are a novel population of multipotent stem cells that have been shown to have great potential for use in regenerative medicine. However, procedures to store and preserve hAMSC for future clinical applications have not been explored extensively.
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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.