46 research outputs found
Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
Peer reviewe
Synaptic processes and immune-related pathways implicated in Tourette syndrome.
Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS
Operation and performance of the ATLAS semiconductor tracker
The semiconductor tracker is a silicon microstrip detector forming part of the inner tracking system of the ATLAS experiment at the LHC. The operation and performance of the semiconductor tracker during the first years of LHC running are described. More than 99% of the detector modules were operational during this period, with an average intrinsic hit efficiency of (99.74±0.04)%. The evolution of the noise occupancy is discussed, and measurements of the Lorentz angle, δ-ray production and energy loss presented. The alignment of the detector is found to be stable at the few-micron level over long periods of time. Radiation damage measurements, which include the evolution of detector leakage currents, are found to be consistent with predictions and are used in the verification of radiation background simulations
P162 Tumor resection using near-infrared indocyanine green fluorescence in nonpalpable breast mass
A comparison of bioreactors for culture of fetal mesenchymal stem cells for bone tissue engineering
10.1016/j.biomaterials.2010.07.097Biomaterials31338684-8695BIMA
Antitumor effect of intratumoral administration of dendritic cell combination with vincristine chemotherapy in a murine fibrosarcoma model
A new antitumor therapeutic strategy
utilizing the combined effect of chemotherapy and DC
(dendritic cell)-based immunotherapy was designed, and
the effect of intratumoral injections of unpulsed,
immature DCs was evaluated after in vivo pretreatment
of vincristine on tumor growth in a murine fibrosarcoma
tumor model.
Vincristine exerted a much more potent
apoptosis/necrosis-inducing effect on MCA-102 tumor
cells than on DCs both in vitro and in vivo. Moreover,
CD11c, CD40, CD80 and CD86 molecules on DCs were
not downregulated after treatment with vincristine either
in vitro or in vivo. The growth of tumor significantly
regressed in the group which received the combined
vincristine chemotherapy with intratumoral
administration of DCs in contrast to the untreated group,
the group treated with DCs alone, and the group treated
with vincristine alone. In particular, an upregulated
expression of CD40, CD80 and CD86 molecules on DCs
was found in the combination treatment group.
Furthermore, the number of CD4+ and CD8+ T cells and
the staining intensity of their CD4 and CD8 surface
molecules also increased after the combination
treatment.
Therefore, our results indicate the feasibility of this
combination therapy with vincristine chemotherapy and
DC-based immunotherapy as an efficient antitumor
strategy for the treatment of fibrosarcoma
Investigation of gene-environment interactions in relation to tic severity.
Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies