153 research outputs found
SiRNA Mediated Gene Silencing: A Mini Review
Abstract - RNA interference (RNAi) technology has become a novel tool for silencing gene expression in cells or organisms. RNA interference is the process that double-stranded RNA induces the homology-dependent degradation of cognate mRNA mediated by 21-23 nucleotide short interfering RNA (siRNA). RNA interference is a powerful mechanism of gene silencing that underlies many aspects of eukaryotic biology. On the molecular level, RNAi is mediated by a family of ribonucleoprotein (RNP) complexes called RNA-Induced Silencing Complexes (RISCs), which can be programmed to target virtually any nucleic acid sequence for silencing. The ability of RISC to locate target RNAs been co-opted by evolution many times to generate a broad spectrum of gene silencing pathways. The study about the Silencing of gene expression by siRNA is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. In this study, the applications of siRNA expressing recombinant adenovirus system in plants, animals and in cancer gene therapy are given importance with its modification
Quintessence, inflation and baryogenesis from a single pseudo-Nambu-Goldstone boson
We exhibit a model in which a single pseudo-Nambu-Goldstone boson explains
dark energy, inflation and baryogenesis. The model predicts correlated signals
in future collider experiments, WIMP searches, proton decay experiments, dark
energy probes, and the PLANCK satellite CMB measurements.Comment: 16 pages, 3 color figure
Asymptotes in SU(2) Recoupling Theory: Wigner Matrices, Symbols, and Character Localization
In this paper we employ a novel technique combining the Euler Maclaurin
formula with the saddle point approximation method to obtain the asymptotic
behavior (in the limit of large representation index ) of generic Wigner
matrix elements . We use this result to derive asymptotic
formulae for the character of an SU(2) group element and for
Wigner's symbol. Surprisingly, given that we perform five successive
layers of approximations, the asymptotic formula we obtain for is
in fact exact. This result provides a non trivial example of a
Duistermaat-Heckman like localization property for discrete sums.Comment: 36 pages, 3 figure
Tops and Writhing DNA
The torsional elasticity of semiflexible polymers like DNA is of biological
significance. A mathematical treatment of this problem was begun by Fuller
using the relation between link, twist and writhe, but progress has been
hindered by the non-local nature of the writhe. This stands in the way of an
analytic statistical mechanical treatment, which takes into account thermal
fluctuations, in computing the partition function. In this paper we use the
well known analogy with the dynamics of tops to show that when subjected to
stretch and twist, the polymer configurations which dominate the partition
function admit a local writhe formulation in the spirit of Fuller and thus
provide an underlying justification for the use of Fuller's "local writhe
expression" which leads to considerable mathematical simplification in solving
theoretical models of DNA and elucidating their predictions. Our result
facilitates comparison of the theoretical models with single molecule
micromanipulation experiments and computer simulations.Comment: 17 pages two figure
TWIST1 expression is associated with high-risk neuroblastoma and promotes primary and metastatic tumor growth.
The embryonic transcription factors TWIST1/2 are frequently overexpressed in cancer, acting as multifunctional oncogenes. Here we investigate their role in neuroblastoma (NB), a heterogeneous childhood malignancy ranging from spontaneous regression to dismal outcomes despite multimodal therapy. We first reveal the association of TWIST1 expression with poor survival and metastasis in primary NB, while TWIST2 correlates with good prognosis. Secondly, suppression of TWIST1 by CRISPR/Cas9 results in a reduction of tumor growth and metastasis colonization in immunocompromised mice. Moreover, TWIST1 knockout tumors display a less aggressive cellular morphology and a reduced disruption of the extracellular matrix (ECM) reticulin network. Additionally, we identify a TWIST1-mediated transcriptional program associated with dismal outcome in NB and involved in the control of pathways mainly linked to the signaling, migration, adhesion, the organization of the ECM, and the tumor cells versus tumor stroma crosstalk. Taken together, our findings confirm TWIST1 as promising therapeutic target in NB
On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes
The sensitivity of a search for sources of TeV neutrinos can be improved by
grouping potential sources together into generic classes in a procedure that is
known as source stacking. In this paper, we define catalogs of Active Galactic
Nuclei (AGN) and use them to perform a source stacking analysis. The grouping
of AGN into classes is done in two steps: first, AGN classes are defined, then,
sources to be stacked are selected assuming that a potential neutrino flux is
linearly correlated with the photon luminosity in a certain energy band (radio,
IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino
production in AGN, this correlation is motivated by hadronic AGN models, as
briefly reviewed in this paper.
The source stacking search for neutrinos from generic AGN classes is
illustrated using the data collected by the AMANDA-II high energy neutrino
detector during the year 2000. No significant excess for any of the suggested
groups was found.Comment: 43 pages, 12 figures, accepted by Astroparticle Physic
Toward an internally consistent astronomical distance scale
Accurate astronomical distance determination is crucial for all fields in
astrophysics, from Galactic to cosmological scales. Despite, or perhaps because
of, significant efforts to determine accurate distances, using a wide range of
methods, tracers, and techniques, an internally consistent astronomical
distance framework has not yet been established. We review current efforts to
homogenize the Local Group's distance framework, with particular emphasis on
the potential of RR Lyrae stars as distance indicators, and attempt to extend
this in an internally consistent manner to cosmological distances. Calibration
based on Type Ia supernovae and distance determinations based on gravitational
lensing represent particularly promising approaches. We provide a positive
outlook to improvements to the status quo expected from future surveys,
missions, and facilities. Astronomical distance determination has clearly
reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press
(chapter 8 of a special collection resulting from the May 2016 ISSI-BJ
workshop on Astronomical Distance Determination in the Space Age
Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis
This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis,
and it did not induce clinical, biochemical or histopathological alterations. The
nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications
Relations between Financing and Output in the Not-for-Profit Hospital
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68639/2/10.1177_107755878804500204.pd
Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy
Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy
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