64 research outputs found
Chemical Power for Microscopic Robots in Capillaries
The power available to microscopic robots (nanorobots) that oxidize
bloodstream glucose while aggregated in circumferential rings on capillary
walls is evaluated with a numerical model using axial symmetry and
time-averaged release of oxygen from passing red blood cells. Robots about one
micron in size can produce up to several tens of picowatts, in steady-state, if
they fully use oxygen reaching their surface from the blood plasma. Robots with
pumps and tanks for onboard oxygen storage could collect oxygen to support
burst power demands two to three orders of magnitude larger. We evaluate
effects of oxygen depletion and local heating on surrounding tissue. These
results give the power constraints when robots rely entirely on ambient
available oxygen and identify aspects of the robot design significantly
affecting available power. More generally, our numerical model provides an
approach to evaluating robot design choices for nanomedicine treatments in and
near capillaries.Comment: 28 pages, 7 figure
C-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle
Caprine-like Generalized Hypoplasia Syndrome (SHGC) is an autosomal-recessive disorder in Montbéliarde cattle. Affected animals present a wide range of clinical features that include the following: delayed development with low birth weight, hind limb muscular hypoplasia, caprine-like thin head and partial coat depigmentation. Here we show that SHGC is caused by a truncating mutation in the CEP250 gene that encodes the centrosomal protein C-Nap1. This mutation results in centrosome splitting, which neither affects centriole ultrastructure and duplication in dividing cells nor centriole function in cilium assembly and mitotic spindle organization. Loss of C-Nap1-mediated centriole cohesion leads to an altered cell migration phenotype. This discovery extends the range of loci that constitute the spectrum of autosomal primary recessive microcephaly (MCPH) and Seckel-like syndromes
Oxidized LDL Receptor 1 (OLR1) as a Possible Link between Obesity, Dyslipidemia and Cancer
Recent studies have linked expression of lectin-like ox-LDL receptor 1
(OLR1) to tumorigenesis. We analyzed microarray data from
Olr1 knockout (KO) and wild type (WT) mice for genes
involved in cellular transformation and evaluated effects of
OLR1 over-expression in normal mammary epithelial cells
(MCF10A) and breast cancer cells (HCC1143) in terms of gene expression,
migration, adhesion and transendothelial migration. Twenty-six out of 238 genes
were inhibited in tissues of OLR1 KO mice; the vast majority of OLR1 sensitive
genes contained NF-ÎșB binding sites in their promoters. Further studies
revealed broad inhibition of NF-kB target genes outside of the
transformation-associated gene pool, with enrichment themes of defense response,
immune response, apoptosis, proliferation, and wound healing. Transcriptome of
Olr1 KO mice also revealed inhibition of de
novo lipogenesis, rate-limiting enzymes fatty acid synthase
(Fasn), stearoyl-CoA desaturase (Scd1) and
ELOVL family member 6 (Elovl6), as well as lipolytic
phospholipase A2 group IVB (Pla2g4b). In studies comparing
MCF10A and HCC1143, the latter displayed 60% higher OLR1
expression. Forced over-expression of OLR1 resulted in
upregulation of NF-ÎșB (p65) and its target pro-oncogenes involved in
inhibition of apoptosis (BCL2, BCL2A1,
TNFAIP3) and regulation of cell cycle
(CCND2) in both cell lines. Basal expression of
FASN, SCD1 and PLA2G4B,
as well as lipogenesis transcription factors PPARA,
SREBF2 and CREM, was higher in HCC1143
cells. Over-expression of OLR1 in HCC1143 cells also enhanced
cell migration, without affecting their adherence to TNFα-activated
endothelium or transendothelial migration. On the other hand,
OLR1 neutralizing antibody inhibited both adhesion and
transmigration of untreated HCC1143 cells. We conclude that
OLR1 may act as an oncogene by activation of NF-kB target
genes responsible for proliferation, migration and inhibition of apoptosis and
de novo lipogenesis genes
CD40-Activated B Cells Can Efficiently Prime Antigen-Specific NaĂŻve CD8+ T Cells to Generate Effector but Not Memory T cells
Background: The identification of the signals that should be provided by antigen-presenting cells (APCs) to induce a CD8 + T cell response in vivo is essential to improve vaccination strategies using antigen-loaded APCs. Although dendritic cells have been extensively studied, the ability of other APC types, such as B cells, to induce a CD8 + T cell response have not been thoroughly evaluated. Methodology/Principal Findings: In this manuscript, we have characterized the ability of CD40-activated B cells, stimulated or not with Toll-like receptor (TLR) agonists (CpG or lipopolysaccharide) to induce the response of mouse naĂŻve CD8 + T cells in vivo. Our results show that CD40-activated B cells can directly present antigen to naĂŻve CD8 + T cells to induce the generation of potent effectors able to secrete cytokines, kill target cells and control a Listeria monocytogenes infection. However, CD40-activated B cell immunization did not lead to the proper formation of CD8 + memory T cells and further maturation of CD40-activated B cells with TLR agonists did not promote the development of CD8 + memory T cells. Our results also suggest that inefficient generation of CD8 + memory T cells with CD40-activated B cell immunization is a consequence of reduced Bcl-6 expression by effectors and enhanced contraction of the CD8 + T cell response. Conclusions: Understanding why CD40-activated B cell immunization is defective for the generation of memory T cells and gaining new insights about signals that should be provided by APCs are key steps before translating the use of CD40-B cel
Eukaryote DIRS1-like retrotransposons: an overview
<p>Abstract</p> <p>Background</p> <p>DIRS1-like elements compose one superfamily of tyrosine recombinase-encoding retrotransposons. They have been previously reported in only a few diverse eukaryote species, describing a patchy distribution, and little is known about their origin and dynamics. Recently, we have shown that these retrotransposons are common among decapods, which calls into question the distribution of DIRS1-like retrotransposons among eukaryotes.</p> <p>Results</p> <p>To determine the distribution of DIRS1-like retrotransposons, we developed a new computational tool, ReDoSt, which allows us to identify well-conserved DIRS1-like elements. By screening 274 completely sequenced genomes, we identified more than 4000 DIRS1-like copies distributed among 30 diverse species which can be clustered into roughly 300 families. While the diversity in most species appears restricted to a low copy number, a few bursts of transposition are strongly suggested in certain species, such as <it>Danio rerio </it>and <it>Saccoglossus kowalevskii</it>.</p> <p>Conclusion</p> <p>In this study, we report 14 new species and 8 new higher taxa that were not previously known to harbor DIRS1-like retrotransposons. Now reported in 61 species, these elements appear widely distributed among eukaryotes, even if they remain undetected in streptophytes and mammals. Especially in unikonts, a broad range of taxa from Cnidaria to Sauropsida harbors such elements. Both the distribution and the similarities between the DIRS1-like element phylogeny and conventional phylogenies of the host species suggest that DIRS1-like retrotransposons emerged early during the radiation of eukaryotes.</p
Collimation for the LHC high intensity beams
The unprecedented design intensities of the LHC require several important advances in beam collimation. With its more than 100 collimators, acting on various planes and beams, the LHC collimation system is the biggest and most performing such system ever designed and constructed. The solution for LHC collimation is explained, the technical components are introduced and the initial performance is presented. Residual beam leakage from the system is analysed. Measurements and simulations are presented which show that collimation efficiencies of better than 99.97 % have been measured with the 3.5 TeV proton beams of the LHC, in excellent agreement with expectations.peer-reviewe
Fertilité : déterminisme génétique et étude métabolique des problÚmes de fertilité des vaches laitiÚres hautes productrices
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