1,162 research outputs found
Speciation of Arsenic in Exfoliated Urinary Bladder Epithelial Cells from Individuals Exposed to Arsenic in Drinking Water
BackgroundThe concentration of arsenic in urine has been used as a marker of exposure to inorganic As (iAs). Relative proportions of urinary metabolites of iAs have been identified as potential biomarkers of susceptibility to iAs toxicity. However, the adverse effects of iAs exposure are ultimately determined by the concentrations of iAs metabolites in target tissues.ObjectiveIn this study we examined the feasibility of analyzing As species in cells that originate in the urinary bladder, a target organ for As-induced cancer in humans.MethodsExfoliated bladder epithelial cells (BECs) were collected from urine of 21 residents of Zimapan, Mexico, who were exposed to iAs in drinking water. We determined concentrations of iAs, methyl-As (MAs), and dimethyl-As (DMAs) in urine using conventional hydride generation-cryotrapping-atomic absorption spectrometry (HG-CT-AAS). We used an optimized HG-CT-AAS technique with detection limits of 12–17 pg As for analysis of As species in BECs.ResultsAll urine samples and 20 of 21 BEC samples contained detectable concentrations of iAs, MAs, and DMAs. Sums of concentrations of these As species in BECs ranged from 0.18 to 11.4 ng As/mg protein and in urine from 4.8 to 1,947 ng As/mL. We found no correlations between the concentrations or ratios of As species in BECs and in urine.ConclusionThese results suggest that urinary levels of iAs metabolites do not necessarily reflect levels of these metabolites in the bladder epithelium. Thus, analysis of As species in BECs may provide a more effective tool for risk assessment of bladder cancer and other urothelial diseases associated with exposures to iAs
Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells
Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins
Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.
Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD
A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses
Many contemporary studies have shown that astrocytes play a significant role
in modulating both short and long form of synaptic plasticity. There are very
few experimental models which elucidate the role of astrocyte over Long-term
Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of
astrocytes in induction of LTP at single hippocampal synapses. They suggested a
purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA)
Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic
induction were not investigated. Here, in this article, we propose a
mathematical model for astrocyte modulated LTP which successfully emulates the
experimental findings of Perea & Araque (2007). Our study suggests the role of
retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically
modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to
appear
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Rarity of monodominance in hyperdiverse Amazonian forests.
Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors
Transmission of West Nile Virus by Culex quinquefasciatus Say Infected with Culex Flavivirus Izabal
Unlike most known flaviviruses (Family, Flaviviridae: Genus, Flavivirus), insect-only flaviviruses are a unique group of flaviviruses that only infect invertebrates. The study of insect-only flaviviruses has increased in recent years due to the discovery and characterization of numerous novel flaviviruses from a diversity of mosquito species around the world. The widespread discovery of these viruses has prompted questions regarding flavivirus evolution and the potential impact of these viruses on the transmission of flaviviruses of public health importance such as WNV. Therefore, we tested the effect of Culex flavivirus Izabal (CxFV Izabal), an insect-only flavivirus isolated from Culex quinquefasciatus mosquitoes in Guatemala, on the growth and transmission of a strain of WNV isolated concurrently from the same mosquito species and location. Prior infection of C6/36 (Aedes albopictus mosquito) cells or Cx. quinquefasciatus with CxFV Izabal did not alter the replication kinetics of WNV, nor did it significantly affect WNV infection, dissemination, or transmission rates in two different colonies of mosquitoes that were fed blood meals containing varying concentrations of WNV. These data demonstrate that CxFV probably does not have a significant effect on WNV transmission efficiency in nature
Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production
NAD+ is both a co-enzyme for hydride transfer enzymes and a
substrate of sirtuins and other NAD+ consuming enzymes.
NAD+ biosynthesis is required for two different regimens
that extend lifespan in yeast. NAD+ is synthesized from
tryptophan and the three vitamin precursors of NAD+: nicotinic
acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells
with NAD+ precursors increases intracellular
NAD+ levels and extends replicative lifespan. Here we show
that both nicotinamide riboside and nicotinic acid are not only vitamins but are
also exported metabolites. We found that the deletion of the nicotinamide
riboside transporter, Nrt1, leads to increased export of nicotinamide riboside.
This discovery was exploited to engineer a strain to produce high levels of
extracellular nicotinamide riboside, which was recovered in purified form. We
further demonstrate that extracellular nicotinamide is readily converted to
extracellular nicotinic acid in a manner that requires intracellular
nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is
elevated by the deletion of the nicotinic acid transporter, Tna1. The data
indicate that NAD+ metabolism has a critical extracellular
element in the yeast system and suggest that cells regulate intracellular
NAD+ metabolism by balancing import and export of
NAD+ precursor vitamins
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