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Find video protocols related to scientific articles indexed in Pubmed.
Deep sequencing of small chromatin-associated RNA: isolation and library preparation.
Methods Mol. Biol.
PUBLISHED: 05-23-2014
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Chromatin-associated RNA (caRNA) is a newly identified class of RNA molecules stably associated with chromatin, maintaining the higher order structure of euchromatic regions in an accessible form (Schubert et al., Mol Cell, doi:10.1016/j.molcel.2012.08.021, 2012). This section provides a detailed protocol describing the isolation of small caRNA from Drosophila cells and preparation of libraries suited for stranded small (20-200 bp) RNA deep sequencing on the Illumina platform.
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The NHL domain of BRAT is an RNA-binding domain that directly contacts the hunchback mRNA for regulation.
Genes Dev.
PUBLISHED: 04-04-2014
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The Drosophila protein brain tumor (Brat) forms a complex with Pumilio (Pum) and Nanos (Nos) to repress hunchback (hb) mRNA translation at the posterior pole during early embryonic development. It is currently thought that complex formation is initiated by Pum, which directly binds the hb mRNA and subsequently recruits Nos and Brat. Here we report that, in addition to Pum, Brat also directly interacts with the hb mRNA. We identify Brat-binding sites distinct from the Pum consensus motif and show that RNA binding and translational repression by Brat do not require Pum, suggesting so far unrecognized Pum-independent Brat functions. Using various biochemical and biophysical methods, we also demonstrate that the NHL (NCL-1, HT2A, and LIN-41) domain of Brat, a domain previously believed to mediate protein-protein interactions, is a novel, sequence-specific ssRNA-binding domain. The Brat-NHL domain folds into a six-bladed ? propeller, and we identify its positively charged top surface as the RNA-binding site. Brat belongs to the functional diverse TRIM (tripartite motif)-NHL protein family. Using structural homology modeling, we predict that the NHL domains of all TRIM-NHL proteins have the potential to bind RNA, indicating that Brat is part of a conserved family of RNA-binding proteins.
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Diagnosis failure led to the recurrence of an intra-articular osteoid osteoma at the talus neck after arthroscopic excision.
Foot Ankle Surg
PUBLISHED: 03-12-2014
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Juxta-articular localization is not exceptional for an osteoid osteoma of the ankle. Arthroscopic treatment has been recently proposed. A case of recurrence of an osteoid osteoma at the talar neck is reported after arthroscopic resection performed following a diagnosis failure. The need for accurate imaging technique to precisely define and localize the nidus and the requirement to include osteoid osteoma in the differential diagnosis of monoarticular pain are discussed.
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Judgments of dominance from the face track physical strength.
Evol Psychol
PUBLISHED: 02-22-2014
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It is commonly assumed that judgments of dominance from faces partly rely on implicit judgments of bodily strength. In two studies, we demonstrate such a relation for both computer-generated and natural photos of male faces. We find support when aggregating data across participants, when analyzing with hierarchical models, and also when strength and dominance are judged by different raters. Moreover, we identify common predictors that underlie perceptions of both strength and dominance: brow height, eye length, chin length, and the widths of the nose and mouth.
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Adult type granulosa cell tumor of the testis with a heterologous sarcomatous component: case report and review of the literature.
Diagn Pathol
PUBLISHED: 02-06-2014
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Adult testicular granulosa cell tumors are rare sex cord- stromal tumors of which only 45 have been previously reported. As compared with their ovarian counterparts, these tumors may follow a more aggressive course because the proportion of malignant cases is higher. We report here a unique case of a 78-year Caucasian with a left sided adult type granulosa cell tumor with a heterologous sarcomatous tumor component. A heterologous sarcomatous component has occasionally been observed in ovarian tumors but never in testicular granulosa cell tumors. The sarcomatous component showed a higher number of mitotic figures (1/Hpf) and a marked proliferation rate (up to 50% Ki 67 positive cells) compared with the granulosa type tumor component. CD 99 and the progesterone receptor were positive in both tumor components, inhibin and calretinin only in the granulosa cells, and pancytokeratin only in the sarcomatouse one. Key words: testis - ovary - granulosa cells - sarcoma - inhibin Runing title: testicular sarcomatous granulosa tumor.
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MRI-Based Assessment of Safe Margins in Tumor Surgery.
Sarcoma
PUBLISHED: 01-19-2014
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Introduction. In surgical oncology, histological analysis of excised tumor specimen is the conventional method to assess the safety of the resection margins. We tested the feasibility of using MRI to assess the resection margins of freshly explanted tumor specimens in rats. Materials and Methods. Fourteen specimen of sarcoma were resected in rats and analysed both with MRI and histologically. Slicing of the specimen was identical for the two methods and corresponding slices were paired. 498 margins were measured in length and classified using the UICC classification (R0, R1, and R2). Results. The mean difference between the 498 margins measured both with histology and MRI was 0.3?mm (SD 1.0?mm). The agreement interval of the two measurement methods was [-1.7?mm; 2.2?mm]. In terms of the UICC classification, a strict correlation was observed between MRI- and histology-based classifications (? = 0.84, P < 0.05). Discussion. This experimental study showed the feasibility to use MRI images of excised tumor specimen to assess the resection margins with the same degree of accuracy as the conventional histopathological analysis. When completed, MRI acquisition of resected tumors may alert the surgeon in case of inadequate margin and help advantageously the histopathological analysis.
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Sensitive and specific detection of EML4-ALK rearrangements in non-small cell lung cancer (NSCLC) specimens by multiplex amplicon RNA massive parallel sequencing.
Lung Cancer
PUBLISHED: 01-03-2014
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Recurrent gene fusions of anaplastic lymphoma receptor tyrosine kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) have been recently identified in ?5% of non-small cell lung cancers (NSCLCs) and are targets for selective tyrosine kinase inhibitors. While fluorescent in situ hybridization (FISH) is the current gold standard for detection of EML4-ALK rearrangements, several limitations exist including high costs, time-consuming evaluation and somewhat equivocal interpretation of results. In contrast, targeted massive parallel sequencing has been introduced as a powerful method for simultaneous and sensitive detection of multiple somatic mutations even in limited biopsies, and is currently evolving as the method of choice for molecular diagnostic work-up of NSCLCs.
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DCC is expressed in a CD166-positive subpopulation of chondrocytes in human osteoarthritic cartilage and modulates CRE activity.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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In a recent study we determined a strong differential expression of DCC in OA compared to normal chondrocytes and a strong impact of the DCC receptor on cellular mobility triggered by its ligand Netrin-1. Migration of chondrocytes or their progenitor cells may play a role in remodeling of cartilage and pathological conditions. The purpose of this study is to identify subsets of chondrocytes expressing DCC and to understand signaling pathways used by DCC in chondrocytes.
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Enhanced CO2 capture in binary mixtures of 1-alkyl-3-methylimidazolium tricyanomethanide ionic liquids with water.
J Phys Chem B
PUBLISHED: 10-01-2013
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Absorption of carbon dioxide and water in 1-butyl-3-methylimidazoliun tricyanomethanide ([C4C1im][TCM]) and 1-octyl-3-methylimidazolium tricyanomethanide ([C8C1im][TCM]) ionic liquids (ILs) was systematically investigated for the first time as a function of the H2O content by means of a gravimetric system together with in-situ Raman spectroscopy, excess molar volume (V(E)), and viscosity deviation measurements. Although CO2 absorption was marginally affected by water at low H2O molar fractions for both ILs, an increase of the H2O content resulted in a marked enhancement of both the CO2 solubility (ca. 4-fold) and diffusivity (ca. 10-fold) in the binary [C(n)C1im][TCM]/H2O systems, in contrast to the weak and/or detrimental influence of water in most physically and chemically CO2-absorbing ILs. In-situ Raman spectroscopy on the IL/CO2 systems verified that CO2 is physically absorbed in the dry ILs with no significant effect on their structural organization. A pronounced variation of distinct tricyanomethanide Raman modes was disclosed in the [C(n)C1im][TCM]/H2O mixtures, attesting to the gradual disruption of the anion-cation coupling by the hydrogen-bonded water molecules to the [TCM](-) anions, in accordance with the positive excess molar volumes and negative viscosity deviations for the binary systems. Most importantly, CO2 absorption in the ILs/H2O mixtures at high water concentrations revealed that the [TCM](-) Raman modes tend to restore their original state for the heavily hydrated ILs, in qualitative agreement with the intriguing nonmonotonous transients of CO2 absorption kinetics unveiled by the gravimetric measurements for the hybrid solvents. A molecular exchange mechanism between CO2 in the gas phase and H2O in the liquid phase was thereby proposed to explain the enhanced CO2 absorption in the hybrid [C(n)C1im][TCM]//H2O solvents based on the subtle competition between the TCM-H2O and TCM-CO2 interactions, which renders these ILs very promising for CO2 separation applications.
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Using Arduino microcontroller boards to measure response latencies.
Behav Res Methods
PUBLISHED: 04-16-2013
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Latencies of buttonpresses are a staple of cognitive science paradigms. Often keyboards are employed to collect buttonpresses, but their imprecision and variability decreases test power and increases the risk of false positives. Response boxes and data acquisition cards are precise, but expensive and inflexible, alternatives. We propose using open-source Arduino microcontroller boards as an inexpensive and flexible alternative. These boards connect to standard experimental software using a USB connection and a virtual serial port, or by emulating a keyboard. In our solution, an Arduino measures response latencies after being signaled the start of a trial, and communicates the latency and response back to the PC over a USB connection. We demonstrated the reliability, robustness, and precision of this communication in six studies. Test measures confirmed that the error added to the measurement had an SD of less than 1 ms. Alternatively, emulation of a keyboard results in similarly precise measurement. The Arduino performs as well as a serial response box, and better than a keyboard. In addition, our setup allows for the flexible integration of other sensors, and even actuators, to extend the cognitive science toolbox.
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Methocarbamol CRI for symptomatic treatment of pyrethroid intoxication: a report of three cases.
J Am Anim Hosp Assoc
PUBLISHED: 03-27-2013
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Pyrethroids are popular for use in companion animals due to their relatively low mammalian toxicity and efficacy against arthropods. Nonetheless, pyrethroid intoxication has been reported in cats and dogs, and cats appear to be more susceptible due to difficulty in biotransformation and excretion of pyrethroids. Pyrethroid intoxications are generally due to either the improper use or accidental ingestion of approved products. Methocarbamol, given as intermittent injections, is a common first-line treatment choice for the tremors associated with pyrethroid intoxication. Two cats and one dog were treated with a methocarbamol continuous rate infusion (CRI) for pyrethroid intoxication. Clinical signs of toxicity resolved within a few hr in all three cases, with no adverse drug effects. A methocarbamol CRI can be considered in animals presenting with pyrethroid intoxication.
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Arabidopsis DEAD-box RNA helicase UAP56 interacts with both RNA and DNA as well as with mRNA export factors.
PLoS ONE
PUBLISHED: 03-01-2013
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The DEAD-box protein UAP56 (U2AF65-associcated protein) is an RNA helicase that in yeast and metazoa is critically involved in mRNA splicing and export. In Arabidopsis, two adjacent genes code for an identical UAP56 protein, and both genes are expressed. In case one of the genes is inactivated by a T-DNA insertion, wild type transcript level is maintained by the other intact gene. In contrast to other organisms that are severely affected by elevated UAP56 levels, Arabidopsis plants that overexpress UAP56 have wild type appearance. UAP56 localises predominantly to euchromatic regions of Arabidopsis nuclei, and associates with genes transcribed by RNA polymerase II independently from the presence of introns, while it is not detected at non-transcribed loci. Biochemical characterisation revealed that in addition to ssRNA and dsRNA, UAP56 interacts with dsDNA, but not with ssDNA. Moreover, the enzyme displays ATPase activity that is stimulated by RNA and dsDNA and it has ATP-dependent RNA helicase activity unwinding dsRNA, whereas it does not unwind dsDNA. Protein interaction studies showed that UAP56 directly interacts with the mRNA export factors ALY2 and MOS11, suggesting that it is involved in mRNA export from plant cell nuclei.
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Critical size bone defect reconstruction by an autologous 3D osteogenic-like tissue derived from differentiated adipose MSCs.
Biomaterials
PUBLISHED: 01-31-2013
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For critical size bone defects and bone non-unions, bone tissue engineering using osteoblastic differentiated adipose mesenchymal stem cells (AMSCs) is limited by the need for a biomaterial to support cell transplantation. An osteoblastic three-dimensional autologous graft made of AMSCs (3D AMSC) was developed to solve this issue. This autograft was obtained by supplementing the osteoblastic differentiation medium with demineralized bone matrix. Two surgical models were developed to assess the potential of this 3D osteogenic AMSC autograft. A four-level spinal fusion using polyetheretherketone cages was designed in six pigs to assess the early phase of ossification (8-12 weeks postimplantation). In each pig, four groups were compared: cancellous bone autograft, freeze-dried irradiated cancellous pig bone, 3D AMSC, and an empty cage. A critical size femoral defect (n = 4, bone non-union confirmed 6 months postoperatively) was used to assess the 3D AMSCs ability to achieve bone fusion. Pigs were followed by CT scan and explanted specimens were analyzed for bone tissue remodeling by micro-CT scan, micro-radiography, and histology/histomorphometry. In the spine fusion model, bone formation with the 3D AMSC was demonstrated by a significant increase in bone content. In the critical-size femoral defect model, the 3D AMSC achieved new bone formation and fusion in a poorly vascularized fibrotic environment. This custom-made 3D osteogenic AMSC autograft is a therapeutic solution for bone non-unions and for critical-size defects.
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Changes in higher order structures of chromatin by RNP complexes.
RNA Biol
PUBLISHED: 01-25-2013
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More than four decades ago, it was shown that RNA stably associates with chromatin. These studies indicated that chromatin-associated RNAs (caRNA) might be involved in the organization of chromatin structure. However, it is only recently that pools of chromatin-associated RNAs were characterized and functional studies were initiated. In Drosophila cells, an RNP complex consisting of snoRNAs and Decondensation factor 31 (Df31) is stably tethered to chromatin, mediated by the RNA- and histone-binding activities of Df31. Biochemical and functional characterizations suggest a structural role of this complex in chromatin organization. The binding of the Df31-snoRNA complex to chromatin results in the opening and the maintenance of accessible higher order structures of chromatin. We suggest that different classes of chromatin-associated RNPs are required for the targeted opening of higher order structures of chromatin, enabling the activation of DNA-dependent processes such as transcription.
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Can the normobaric oxygen paradox (NOP) increase reticulocyte count after traumatic hip surgery?
J Clin Anesth
PUBLISHED: 01-17-2013
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To determine if the normobaric oxygen paradox (NOP) was effective in increasing reticulocyte count and reducing postoperative requirements for allogeneic red blood cell transfusion after traumatic hip surgery.
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Galactosyl-knock-out engineered pig as a xenogenic donor source of adipose MSCs for bone regeneration.
Biomaterials
PUBLISHED: 01-10-2013
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Pig adipose mesenchymal stem cells (AMSCs) could be proposed for the improvement of bone substitute. However, these xenogenic cells retain a galactosyl (Gal) epitope that elicits xenorejection. Our work aims to use Gal-Knock-Out (Gal-KO) pig AMSCs to associate cellular immunomodulation, humoral down-elicitation of Gal-KO cells and osteogenic capacity of AMSCs. Human and pig AMSCs were compared for proliferation/differentiation kinetics and bone neoformation in vivo. Humoral reaction against pig Gal+ vs. Gal-KO AMSCs and immunomodulation properties of Gal+ vs. Gal-KO AMSCs were assessed in vitro. Humoral/cellular reactions against Gal+ vs. Gal-KO osteogenic differentiated pig AMSC xenografts were assessed in an immunocompetent rodent model. Expansion/differentiation/bone neoformation was significantly improved with differentiated pig AMSCs compared with human cells. Based on immunohistochemistry and cell-based ELISA, Gal+ AMSCs had higher sensitivity to preformed/induced anti-pig antibodies than Gal-KO AMSCs. In vitro cellular immunomodulation was similar between Gal+ and Gal-KO AMSCs. In vivo, a significant reduction of anti-pig IgG was found at 1 month in rats implanted with Gal-KO AMSCs compared with those implanted with Gal+ AMSCs. Lymphocyte/macrophage infiltration of osteogenic differentiated pig AMSC xenografts was significantly lower at post-operative day (POD) 7 in recipients of Gal-KO vs. Gal+ pig cells. No significant difference was found at POD 28. The combination of the cellular immunomodulation with the Gal-KO phenotype of AMSCs can significantly improve the cellular engraftment of pig osteogenic cells by delaying xenorejection.
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ScriptingRT: A Software Library for Collecting Response Latencies in Online Studies of Cognition.
PLoS ONE
PUBLISHED: 01-01-2013
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ScriptingRT is a new open source tool to collect response latencies in online studies of human cognition. ScriptingRT studies run as Flash applets in enabled browsers. ScriptingRT provides the building blocks of response latency studies, which are then combined with generic Apache Flex programming. Six studies evaluate the performance of ScriptingRT empirically. Studies 1-3 use specialized hardware to measure variance of response time measurement and stimulus presentation timing. Studies 4-6 implement a Stroop paradigm and run it both online and in the laboratory, comparing ScriptingRT to other response latency software. Altogether, the studies show that Flash programs developed in ScriptingRT show a small lag and an increased variance in response latencies. However, this did not significantly influence measured effects: The Stroop effect was reliably replicated in all studies, and the found effects did not depend on the software used. We conclude that ScriptingRT can be used to test response latency effects online.
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First order melting transitions of highly ordered dipalmitoyl phosphatidylcholine gel phase membranes in molecular dynamics simulations with atomistic detail.
J Chem Phys
PUBLISHED: 08-10-2011
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Molecular dynamics simulations with atomistic detail of the gel phase and melting transitions of dipalmitoyl phosphatidylcholine bilayers in water reveal the dependency of many thermodynamic and structural parameters on the initial system ordering. We quantitatively compare different methods to create a gel phase system and we observe that a very high ordering of the gel phase starting system is necessary to observe behavior which reproduces experimental data. We performed heating scans with speeds down to 0.5 K/ns and could observe sharp first order phase transitions. Also, we investigated the transition enthalpy as the natural intrinsic parameter of first order phase transitions, and obtained a quantitative match with experimental values. Furthermore, we performed systematic investigations of the statistical distribution and heating rate dependency of the microscopic phase transition temperature.
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The enhanced performance of bone allografts using osteogenic-differentiated adipose-derived mesenchymal stem cells.
Biomaterials
PUBLISHED: 06-17-2011
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Adipose tissue was only recently considered as a potential source of mesenchymal stem cells (MSCs) for bone tissue engineering. To improve the osteogenicity of acellular bone allografts, adipose MSCs (AMSCs) and bone marrow MSCs (BM-MSCs) at nondifferentiated and osteogenic-differentiated stages were investigated in vitro and in vivo. In vitro experiments demonstrated a superiority of AMSCs for proliferation (6.1±2.3 days vs. 9.0±1.9 days between each passage for BM-MSCs, respectively, P<0.001). A significantly higher T-cell depletion (revealed by mixed lymphocyte reaction, [MLR]) was found for AMSCs (vs. BM-MSCs) at both non- and differentiated stages. Although nondifferentiated AMSCs secreted a higher amount of vascular endothelial growth factor [VEGF] in vitro (between 24 and 72 h of incubation at 0.1-21% O(2)) than BM-MSCs (P<0.001), the osteogenic differentiation induced a significantly higher VEGF release by BM-MSCs at each condition (P<0.001). After implantation in the paraspinal muscles of nude rats, a significantly higher angiogenesis (histomorphometry for vessel development (P<0.005) and VEGF expression (P<0.001)) and osteogenesis (as revealed by osteocalcin expression (P<0.001) and micro-CT imagery for newly formed bone tissue (P<0.05)) were found for osteogenic-differentiated AMSCs in comparison to BM-MSCs after 30 days of implantation. Osteogenic-differentiated AMSCs are the best candidate to improve the angio-/osteogenicity of decellularized bone allografts.
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Telling things apart: the distance between response keys influences categorization times.
Psychol Sci
PUBLISHED: 06-09-2011
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People use spatial distance to talk and think about differences between concepts, and it has been argued that using space to think about different categories provides a scaffold for the categorization process. In the current study, we investigated the possibility that the distance between response keys can influence categorization times in binary classification tasks. In line with the hypothesis that distance between response keys can facilitate response selection in a key-press version of the Stroop task, our results showed that responses on incongruent Stroop trials were significantly facilitated when participants performed the Stroop task with response keys located far apart, compared with when they performed the task with response keys located close together. These results support the idea that the spatial structuring of response options facilitates categorizations that require cognitive effort, and that people can incorporate environmental structures such as spatial distance in their thought processes. Keeping your hands apart might actually help to keep things apart in your mind.
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Self-other bodily merging in the context of synchronous but arbitrary-related multisensory inputs.
Exp Brain Res
PUBLISHED: 05-18-2011
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A debated issue in the multisensory literature concerns the relative contribution of bottom-up sensory components versus top-down cognitive elaborations in contributing to the rise and persistency of bodily illusion. Previous studies, for instance, have shown that simultaneity of sensory inputs and plausibility of the stimulated object play an important role in the rubber hand phenomenon, whereas violation of tactile expectancy does not disrupt the illusory feeling to own a fake hand. The present research examined this issue in the context of the "enfacement" phenomenon (i.e., self-other face-perception modification), using entirely arbitrary and non-ecological pairs of visual and tactile events. Visual and tactile stimulation was matched in terms of spatial location, but not linked by any previously learned associations, making temporal synchrony a critical binding factor. Participants received electro-tactile stimulations on their cheek, while they watched the face of a stranger illuminated on the cheek with a dot of white light. Synchronous (vs. asynchronous) stimulations yielded the enfacement effect. In addition, the stranger stimulated in synchrony was judged as more similar, physically and in terms of personality, and as closer to the self. These findings suggest that synchronous multisensory stimulation on the face can produce both perceptual and social binding, even in the absence of any previously learned associations between the stimulations.
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Slit3 inhibits activator protein 1-mediated migration of malignant melanoma cells.
Int. J. Mol. Med.
PUBLISHED: 05-05-2011
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The repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. Alterations of the Slit/Robo system have been observed in various pathological conditions and in cancer. However, until today no detailed studies on Slit function on melanoma migration are available. Therefore, we analysed the mRNA expression in melanoma cells and found induction of Robo3 expression compared to normal melanocytes. Functional assays performed with melanoma cells revealed that treatment with Slit3 led to strong inhibition of migration. Interestingly, we observed down-regulation of AP-1 activity and target gene expression after Slit3 treatment contributing to the negative regulation of migration. Taken together, our data showed that Slit3 reduces the migratory activity of melanoma cells, potentially by repulsion of the cells in analogy to the neuronal system. Further studies will be necessary to prove Slit activity in vivo, but due to its function, Slit3 activity may be helpful in the treatment of melanoma.
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Temperature dependence of the viscosity and conductivity of mildly functionalized and non-functionalized [Tf2N](-) ionic liquids.
Chemphyschem
PUBLISHED: 03-21-2011
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A series of bis(trifluoromethylsulfonyl)imide ionic liquids (ILs) with classical as well as mildly functionalized cations was prepared and their viscosities and conductivities were determined as a function of the temperature. Both were analyzed with respect to Arrhenius, Litovitz and Vogel-Fulcher-Tammann (VFT) behaviors, as well as in the context of their molecular volume (V(m)). Their viscosity and conductivity are highly correlated with V(m)/T or related expressions (R(2) ?0.94). With the knowledge of V(m) of new cations, these correlations allow the temperature-dependent prediction of the viscosity and conductivity of hitherto unknown, non- or mildly functionalized ILs with low error bars (0.05 and 0.04 log units, respectively). The influence of the cation structure and mild functionalization on the physical properties was studied with systematically altered cations, in which V(m) remained similar. The T(o) parameter obtained from the VFT fits was compared to the experimental glass temperature (T(g)) and the T(g)/T(o) ratio for each IL was calculated using both experimental values and Angells relationship. With Walden plots we investigated the IL ionicity and interpreted it in relation to the cation effects on the physical IL properties. We checked the validity of these V(m)/T relations by also including the recently published variable temperature viscosity and conductivity data of the [Al(OR(F))(4)](-) ILs with R(F) =C(H)(CF(3))(2) (error bars for the prediction: 0.09 and 0.10 log units, respectively).
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Puddles, parties, and professors: linking word categorization to neural patterns of visuospatial coding.
J Cogn Neurosci
PUBLISHED: 01-26-2011
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Behavioral evidence suggests that during word processing people spontaneously map object, valence, and power information to locations in vertical space. Specifically, whereas "overhead" (e.g., attic), positive (e.g., party), and powerful nouns (e.g., professor) are associated with "up," "underfoot" (e.g., carpet), negative (e.g., accident), and powerless nouns (e.g., assistant) are associated with "down." What has yet to be elucidated, however, is the precise nature of these effects. To explore this issue, an fMRI experiment was undertaken, during which participants were required to categorize the position in which geometrical shapes appeared on a computer screen (i.e., upper or lower part of the display). In addition, they also judged a series of words with regard to location (i.e., up vs. down), valence (i.e., good vs. bad), and power (i.e., powerful vs. powerless). Using multivoxel pattern analysis, it was found that classifiers that successfully distinguished between the positions of shapes in subregions of the inferior parietal lobe also provided discriminatory information to separate location and valence, but not power word judgments. Correlational analyses further revealed that, for location words, pattern transfer was more successful the stronger was participants propensity to use visual imagery. These findings indicate that visual coding and conceptual processing can elicit common representations of verticality but that divergent mechanisms may support the reported effects.
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Mighty metaphors: behavioral and ERP evidence that power shifts attention on a vertical dimension.
Brain Cogn
PUBLISHED: 01-21-2011
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Thinking about the abstract concept power may automatically activate the spatial up-down image schema (powerful up; powerless down) and consequently direct spatial attention to the image schema-congruent location. Participants indicated whether a word represented a powerful or powerless person (e.g. king or servant). Following each decision, they identified a target at the top or bottom of the visual field. In Experiment 1 participants identified the target faster when their spatial position was congruent with the perceived power of the preceding word than when it was incongruent. In Experiment 2 ERPs showed a higher N1 amplitude for congruent spatial positions. These results support the view that attention is driven to the image schema congruent location of a power word. Thus, power is partially understood in terms of vertical space, which demonstrates that abstract concepts are grounded in sensory-motor processing.
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In silico predictions of the temperature-dependent viscosities and electrical conductivities of functionalized and nonfunctionalized ionic liquids.
J Phys Chem B
PUBLISHED: 12-07-2010
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The viscosity (?) and electrical conductivity (?) of ionic liquids are, next to the melting point, the two key properties of general interest. The knowledge of temperature-dependent ? and ? data before their first synthesis would permit a much more target-oriented development of ionic liquids. We present in this work a novel approach to predict the viscosity and electrical conductivity of an ionic liquid without further input of experimental data. For the viscosity, only some basic physical observables like the Gibbs solvation energy (?G(solv)(*,?)), which was calculated at the affordable DFT-level (RI-)BP86/TZVP/COSMO, the molecular radius, calculated from the molecular volume V(m) of the ion volumes, and the symmetry number (?), according to group theory, are necessary as input. The temperature dependency (253-373 K) of the viscosity (4-19000 mPa s) was modeled by an Arrhenius approach. An alternative way, which avoids the deficits of the Arrhenius relation by a series expansion in the exponential term, is also presented. On the basis of their close connection, the same set of parameters is suitable to describe the electrical conductivity as well (238-468 K, 0.003-193 mS/cm). Nevertheless, more elegant alternatives like the usage of the Stokes-Einstein/Nernst-Einstein relation or the Walden rule are highlighted in this work. During this investigation, we additionally found an approach to predict the dielectric constant ?* of an ionic liquid at 298 K by using V(m) and ?G(solv)(*,?) between ?* = 9 and 43.
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Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-25-2010
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Chromatin remodeling complexes can translocate nucleosomes along the DNA in an ATP-dependent manner. Here, we studied autofluorescent protein constructs of the human ISWI family members Snf2H, Snf2L, the catalytically inactive Snf2L+13 splice variant, and the accessory Acf1 subunit in living human and mouse cells by fluorescence microscopy/spectroscopy. Except for Snf2L, which was not detected in the U2OS cell line, the endogenous ISWI proteins were abundant at nuclear concentrations between 0.14 and 0.83 ?M. A protein interaction analysis showed the association of multimeric Snf2H and Acf1 into a heterotetramer or higher-order ACF complex. During the G1/2 cell cycle phase, Snf2H and Snf2L displayed average residence times <150 ms in the chromatin-bound state. The comparison of active and inactive Snf2H/Snf2L indicated that an immobilized fraction potentially involved in active chromatin remodeling comprised only 1-3%. This fraction was largely increased at replication foci in S phase or at DNA repair sites. To rationalize these findings we propose that ISWI remodelers operate via a "continuous sampling" mechanism: The propensity of nucleosomes to be translocated is continuously tested in transient binding reactions. Most of these encounters are unproductive and efficient remodeling requires an increased binding affinity to chromatin. Due to the relatively high intranuclear remodeler concentrations cellular response times for repositioning a given nucleosome were calculated to be in the range of tens of seconds to minutes.
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PPARgamma-dependent regulation of adenylate cyclase 6 amplifies the stimulatory effect of cAMP on renin gene expression.
Mol. Endocrinol.
PUBLISHED: 09-22-2010
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The second messenger cAMP plays an important role in the regulation of renin gene expression. Nuclear receptor peroxisome proliferator-activated receptor-? (PPAR?) is known to stimulate renin gene transcription acting through PPAR?-binding sequences in renin promoter. We show now that activation of PPAR? by unsaturated fatty acids or thiazolidinediones drastically augments the cAMP-dependent increase of renin mRNA in the human renin-producing cell line Calu-6. The underlying mechanism involves potentiation of agonist-induced cAMP increase and up-regulation of adenylate cyclase 6 (AC6) gene expression. We identified a palindromic element with a 3-bp spacer (Pal3) in AC6 intron 1 (AC6Pal3). AC6Pal3 bound PPAR? and mediated trans-activation by PPAR? agonist. AC6 knockdown decreased basal renin mRNA level and attenuated the maximal PPAR?-dependent stimulation of the cAMP-induced renin gene expression. AC6Pal3 decoy oligonucleotide abrogated the PPAR?-dependent potentiation of cAMP-induced renin gene expression. Treatment of mice with PPAR? agonist increased AC6 mRNA kidney levels. Our data suggest that in addition to its direct effect on renin gene transcription, PPAR? "sensitizes" renin gene to cAMP via trans-activation of AC6 gene. AC6 has been identified as PPAR? target gene with a functional Pal3 sequence.
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How do we assign punishment? The impact of minimal and maximal standards on the evaluation of deviants.
Pers Soc Psychol Bull
PUBLISHED: 08-13-2010
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To explain the determinants of negative behavior toward deviants (e.g., punishment), this article examines how people evaluate others on the basis of two types of standards: minimal and maximal. Minimal standards focus on an absolute cutoff point for appropriate behavior; accordingly, the evaluation of others varies dichotomously between acceptable or unacceptable. Maximal standards focus on the degree of deviation from that standard; accordingly, the evaluation of others varies gradually from positive to less positive. This framework leads to the prediction that violation of minimal standards should elicit punishment regardless of the degree of deviation, whereas punishment in response to violations of maximal standards should depend on the degree of deviation. Four studies assessed or manipulated the type of standard and degree of deviation displayed by a target. Results consistently showed the expected interaction between type of standard (minimal and maximal) and degree of deviation on punishment behavior.
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Synchronous multisensory stimulation blurs self-other boundaries.
Psychol Sci
PUBLISHED: 08-02-2010
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In a study that builds on recent cognitive neuroscience research on body perception and social psychology research on social relations, we tested the hypothesis that synchronous multisensory stimulation leads to self-other merging. We brushed the cheek of each study participant as he or she watched a strangers cheek being brushed in the same way, either in synchrony or in asynchrony. We found that this multisensory procedure had an effect on participants body perception as well as social perception. Study participants exposed to synchronous stimulation showed more merging of self and the other than participants exposed to asynchronous stimulation. The degree of self-other merging was determined by measuring participants body sensations and their perception of face resemblance, as well as participants judgment of the inner state of the other, closeness felt toward the other, and conformity behavior. The results of this study show how multisensory integration can affect social perception and create a sense of self-other similarity.
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Biodegradability of organic nanoparticles in the aqueous environment.
Chemosphere
PUBLISHED: 07-14-2010
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Synthetic nanoparticles have already been detected in the aquatic environment. Therefore, knowledge on their biodegradability is of utmost importance for risk assessment but such information is currently not available. Therefore, the biodegradability of fullerenes, single, double, multi-walled as well as COOH functionalized carbon nanotubes and cellulose and starch nanocrystals in aqueous environment has been investigated according to OECD standards. The biodegradability of starch and cellulose nanoparticles was also compared with the biodegradability of their macroscopic counterparts. Fullerenes and all carbon nanotubes did not biodegrade at all, while starch and cellulose nanoparticles biodegrade to similar levels as their macroscopic counterparts. However, neither comfortably met the criterion for ready biodegradability (60% after 28 days). The cellulose and starch nanoparticles were also found to degrade faster than their macroscopic counterparts due to their higher surface area. These findings are the first report of biodegradability of organic nanoparticles in the aquatic environment, an important accumulation environment for manmade compounds.
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Quantitative determination of ion distributions in bacterial lipopolysaccharide membranes by grazing-incidence X-ray fluorescence.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-04-2010
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A model of the outer membrane of Gram-negative bacteria was created by the deposition of a monolayer of purified rough mutant lipopolysaccharides at an air/water interface. The density profiles of monovalent (K(+)) and divalent (Ca(2+)) cations normal to the lipopolysaccharides (LPS) monolayers were investigated using grazing-incidence X-ray fluorescence. In the absence of Ca(2+), a K(+) concentration peak was found in the negatively charged LPS headgroup region. With the addition of CaCl(2), Ca(2+) ions almost completely displaced K(+) ions from the headgroup region. By integrating the experimentally reconstructed excess ion density profiles, we obtained an accurate measurement of the effective charge density of LPS monolayers. The experimental findings were compared to the results of Monte Carlo simulations based on a coarse-grained minimal model of LPS molecules and showed excellent agreement.
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Steroid treatment alters adhesion molecule and chemokine expression in experimental acute graft-vs.-host disease of the intestinal tract.
Exp. Hematol.
PUBLISHED: 04-28-2010
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Acute graft-vs.-host disease (aGVHD) is a major complication after allogeneic bone marrow transplantation (allo-BMT) that is characterized by high morbidity and mortality. Systemic treatment with steroids has been the mainstay of first-line therapy of aGVHD, although controlled experimental data in this context are limited.
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Slit3 inhibits Robo3-induced invasion of synovial fibroblasts in rheumatoid arthritis.
Arthritis Res. Ther.
PUBLISHED: 03-18-2010
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The repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. However, until today no data are available on whether these repellent factors are involved in the regulation of synovial fibroblast (SF) activity in rheumatoid arthritis (RA).
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Modulation of cartilage differentiation by melanoma inhibiting activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP).
Exp. Mol. Med.
PUBLISHED: 02-19-2010
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Melanoma inhibiting activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin alpha5 and abolishing its activity. Active ERK signaling is known to block chondrogenic differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified cartilage layer of the articular cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes cartilage differentiation and inhibits differentiation into bone potentially by regulating signaling processes during differentiation.
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Functional implication of Netrin expression in malignant melanoma.
Cell. Oncol.
PUBLISHED: 11-27-2009
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Malignant melanoma cells are known to have altered expression of genes supporting proliferation and invasion, however, the expression of molecules of the Netrin family of repellent factors has not been analyzed in melanomas until now.
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Role of deleted in colon carcinoma in osteoarthritis and in chondrocyte migration.
Rheumatology (Oxford)
PUBLISHED: 09-10-2009
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The concept of the chondrocyte as a stationary cell surrounded by an apparently impenetrable matrix has been challenged by in vitro observations in recent years. Chondrocyte migration may have a role in remodelling of the cartilage and pathological conditions. Candidate molecules are repellent factors for the regulation of chondrocyte migration, which are expressed in fetal and adult cartilage. We analysed the potential role of the receptor deleted in colon carcinoma (DCC) in chondrocytes, as this may exert attractive activities.
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Weight as an embodiment of importance.
Psychol Sci
PUBLISHED: 08-14-2009
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Four studies show that the abstract concept of importance is grounded in bodily experiences of weight. Participants provided judgments of importance while they held either a heavy or a light clipboard. Holding a heavy clipboard increased judgments of monetary value (Study 1) and made participants consider fair decision-making procedures to be more important (Study 2). It also caused more elaborate thinking, as indicated by higher consistency between related judgments (Study 3) and by greater polarization of agreement ratings for strong versus weak arguments (Study 4). In line with an embodied perspective on cognition, these findings suggest that, much as weight makes people invest more physical effort in dealing with concrete objects, it also makes people invest more cognitive effort in dealing with abstract issues.
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The effects of fenoterol inhalation after acid aspiration-induced lung injury.
Anesth. Analg.
PUBLISHED: 06-19-2009
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Acid aspiration is a serious complication that can occur during general anesthesia. Studies show that beta-agonists have beneficial effects on lung injury. Therefore, we tested the effect of the nebulized beta-agonist fenoterol on lung variables in a rodent model of acid-induced lung injury.
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Particle size influence in an impaction bone grafting model. Comparison of fresh-frozen and freeze-dried allografts.
J Biomech
PUBLISHED: 05-25-2009
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Impaction bone grafting with large particles is considered as mechanically superior to smaller morsels. Interest of freeze-dried irradiated bone for impaction bone grafting has been observed with small particles. Influence of bone process on other particle sizes still needed to be assessed.
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Bone morphogenetic protein 4 is induced in hepatocellular carcinoma by hypoxia and promotes tumour progression.
J. Pathol.
PUBLISHED: 05-12-2009
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Striking similarities exist between molecular mechanisms driving embryonic liver development and progression of hepatocellular carcinoma (HCC). Bone morphogenetic proteins (BMPs), particularly BMP4, have been proposed to regulate embryonic hepatic development. BMP expression has been observed in neoplasia but the expression and biological role of BMP4 in human HCC are unknown. We found increased BMP4 mRNA and protein in HCC cell lines and tissue samples compared to primary human hepatocytes and corresponding non-tumourous tissue. Hypoxia further induced BMP4 expression in HCC cells, which was abolished by transfection of a dominant negative form of HIF-1 alpha (dnHIF-1 alpha). However, gel shift assays revealed only minor binding activity in nuclear extracts from (hypoxic) HCC cells to a putative hypoxia-response element in the BMP4 promoter. Sequence analysis of the BMP4 promoter revealed two Ets-1 binding sites, and Ets-1 activity was increased in HCC cells under hypoxic conditions. Transfection of dnHIF-1 alpha completely abrogated hypoxia-induced Ets-1 activity as well as BMP4 expression. Overexpression of Ets-1 markedly enhanced BMP4 promoter activity, while antisense Ets-1 almost completely abolished basal as well as hypoxia-induced BMP4 expression. These data demonstrate that Ets-1 activity contributes to baseline expression of the BMP4 gene and is the predominant mediator of the HIF-dependent BMP4 induction under hypoxic conditions. To determine the functional relevance of BMP4 expression, HCC cell lines were treated with antisense BMP4 constructs or siRNA against BMP4. BMP4 suppression resulted in a strong reduction of the migratory and invasive potential and anchorage-independent growth. Furthermore, tube formation assays indicated that BMP4 expressed by HCC cells promotes vasculogenesis. Our findings demonstrate that BMP4 is increased in HCC and promotes HCC progression. Therefore, BMP4 expression may have clinical relevance, and interfering with BMP4 signalling appears as an attractive therapeutic target for this highly aggressive tumour.
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Preventive usage of broad spectrum chemokine inhibitor NR58-3.14.3 reduces the severity of pulmonary and hepatic graft-versus-host disease.
Int. J. Hematol.
PUBLISHED: 02-09-2009
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Pulmonary graft-versus-host disease (pGVHD) is a major complication after allogeneic bone marrow transplantation (BMT), which involves donor leukocyte migration into the lung along chemokine gradients, leading to pulmonary dysfunction and respiratory insufficiency. As broad spectrum chemokine inhibitor (BSCI) NR58-3.14.3 suppresses leukocyte migration in response to various chemokines, including CCL2, CCL3, CCL5, we investigated the effects of NR58-3.14.3 on the evolution of pGVHD. Lethally irradiated B6D2F1 mice received BMT from syngeneic (B6D2F1) or allogeneic (C57BL/6) donors, and animals were treated with either NR58-3.14.3 or vehicle control from day -1 to day +14. At week 6, in allogeneic recipients that received BSCI, inflammatory cell infiltrates in the lung were decreased, and reduced histopathologic changes translated into improved pulmonary function when compared to allo-controls. Acute GVHD of the liver was also diminished, whereas no differences were seen in the gut. Alloantigen-dependent splenic T cell expansion and systemic TNF-alpha and IFN-gamma levels were comparable in NR58-3.14.3-treated animals and allo-controls. No suppressive effect of NR58-3.14.3 on CTL cytotoxicity was found, and diminished cellular infiltrates in lung and liver were most likely due to decreased migration of mononuclear cells. Therefore, novel approaches involving BSCIs may provide a promising tool in the management of pGVHD.
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Are attitudes the problem, and do psychologists have the answer? Relational cognition underlies intergroup relations.
Behav Brain Sci
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The focus on negative attitudes toward other groups has led to a dichotomy between the prejudice reduction and the collective action approach. To solve the resulting problems identified by Dixon et al., we suggest analyzing the psychological processes underlying the construction of relationships (and their alternatives) between own and other groups.
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Df31 protein and snoRNAs maintain accessible higher-order structures of chromatin.
Mol. Cell
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Packaging of DNA into nucleosomes and the formation of higher-order chromatin structures determine DNA accessibility and activity of genome domains. We identified an RNA-dependent mechanism maintaining the open chromatin structure within euchromatic regions in Drosophila cells. The mechanism of reversible chromatin opening, reconstituted in vitro, depends on the Drosophila decondensation factor 31 (Df31) that specifically binds to RNA and localizes to euchromatic regions. Df31 is capable to tether a heterogeneous pool of short, single-stranded RNAs to chromatin. This class of chromatin-associated RNA (caRNA) is stably linked to chromatin and is largely composed of snoRNAs, which are preferentially bound by Df31. We suggest that the Df31-mediated linkage of snoRNAs and chromatin, forms a RNA-chromatin network resulting in the establishment of open chromatin domains. Analysis of caRNAs in human cells also reveals a strong enrichment of snoRNAs, implying a conserved role for these molecules in higher-order structures of chromatin.
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Fragments of SLIT3 inhibit cellular migration.
Int. J. Mol. Med.
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The repellent factor family of Slit molecules has been described as having a repulsive function in the developing nervous system on growing axons expressing the Roundabout (Robo) receptors. Recent studies determined the effects of Slit molecules on the migratory and invasive potential of several types of tumor cells but also on synovial fibroblasts (SFs) derived from rheumatoid arthritis (RA) patients. To optimize a potential therapeutic application we aimed at generatingfragments of Slit3 showing the same functional ability as the full-length molecule but having the advantage of a smaller size. Recombinant Slit3 proteins were expressed and analyzed by western blotting. Their activity was defined by functional assays such as migration assays with RASF and melanoma cells. Recombinant Slit3 containing only leucine rich repeat domain 2 (D2), the domain important for Robo binding and the minimal functional unit D2 dNC were both able to inhibit migration of RASFs as effectively as Slit3 with all 4 repeats. Collectively, our data showed that the ability of Slit3 to reduce the migratory activity of synovial cells from patients with RA and melanoma cells can be mimicked by small protein fragments derived from Slit3. Slit3 fragments may be helpful in therapeutic attempts; however, further studies are necessary in order to elucidate their activity in vivo.
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Treatment of deep articular talus lesions by matrix associated autologous chondrocyte implantation--results at five years.
Int Orthop
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Treatment of focal full-thickness chondral or osteochondral defects of the talus remains a challenge. The aim of this study was to evaluate the postoperative success and the long-term efficacy of matrix associated autologous chondrocyte implantation in these defects.
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Hypoferraemia during the early inflammatory response is dependent on tumour necrosis factor activity in a murine model of protracted peritonitis.
Mol Med Rep
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On the grounds of clinical, in vitro and in vivo studies, tumour necrosis factor (TNF) is considered to be one of the inflammatory cytokines that contributes to to the generation of hypoferraemia and anaemia of inflammation (AI). We used a recently described murine model for AI and hypoferraemia, based on sublethal caecal ligation and puncture (CLP) with ensuing protracted peritonitis, to investigate the contribution of TNF to the generation of hypoferraemia. During the early inflammatory response to CLP, a marked decrease in serum iron concentration occurs within 8 h. To determine whether TNF contributes to the generation of hypoferraemia at this time point, we studied TNF-deficient mice and wild-type mice that underwent CLP. The serum iron concentration was decreased in wild-type mice whereas TNF-deficient mice maintained normal serum iron levels following CLP. Hypoferraemia in wild-type mice was accompanied by the downregulation of ferroportin 1 (Fp1) in macrophages. In the macrophages of TNF-deficient mice, Fp1 was not downregulated following CLP. The initial expression of hepcidin was detectable at the mRNA level but not at the protein level by immunohisto-chemistry in wild-type and TNF-deficient mice. Therefore, hepcidin does not appear to be involved in the regulation of early hypoferraemia. TNF appears to regulate the expression of Fp1 by transcriptional control. Our results demonstrate that TNF mediates hypoferraemia during the early inflammatory response by regulating the expression of Fp1 in macrophages.
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Importance of dispersion forces for prediction of thermodynamic and transport properties of some common ionic liquids.
Phys Chem Chem Phys
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An extensive study of interaction energies in ion pairs of pyrrolidinium and imidazolium ionic liquids is presented. The Cnmpyr and Cnmim cations with varying alkyl chains from Methyl, Ethyl, n-Propyl to n-Butyl were combined with a wide range of routinely used IL anions such as chloride, bromide, mesylate (CH3SO3 or Mes), tosylate (CH3PhSO3 or Tos), bis(trifluoromethanesulfonyl)amide (NTf2), dicyanamide (N(CN)2 or dca), tetrafluoroborate (BF4) and hexafluorophosphate (PF6). A number of energetically favourable conformations were studied for each cation-anion combination. The interaction energy and its dispersion component of the single ion pairs were calculated using a sophisticated state-of-the-art approach: a second-order of Symmetry Adapted Perturbation Theory (SAPT). A comparison of energetics depending on the cation-anion type, as well as the mode of interaction was performed. Dispersion forces were confirmed to be of importance for the overall stabilisation of ionic liquids contributing from 28 kJ mol(-1) in pyrrolidinium ion pairs to 59 kJ mol(-1) in imidazolium ion pairs. The previously proposed ratio of total interaction energy to dispersion components and melting points was assessed for this set of ionic liquids and was found to correlate with their melting points for the anionic series, producing separate trends for the Cnmim and Cmpyr series of cations. Chlorides, bromides and tetrafluoroborates formed close-to-ideal correlations when both types of cations, Cnmim and Cnmpyr, were combined in the same trend. Correlation of the dispersion component of the interaction energy with transport properties such as conductivity and viscosity was also considered. For imidazolium-based ionic liquids strong linear correlations were obtained, whereas pyrrolidinium ionic liquids appeared to be insensitive to this correlation.
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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.