Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

<p>Abstract</p> <p>Background</p> <p>Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation.</p> <p>Methods</p> <p>The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [⁶⁰Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [⁶⁰Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [⁶⁰Co] γ-rays; Group C included cells treated with 8 Gy of [⁶⁰Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis.</p> <p>Results</p> <p>Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [⁶⁰Co] γ-rays (<it>P </it>< 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E treated with BPA-BNCT were significantly higher than those in Group B and Group C irradiated by [⁶⁰Co] γ-rays (<it>P </it>< 0.01). The clonogenicity of glioma cells was reduced by BPA-BNCT compared with cells treated in the reactor (Group F, G, H, I), and with the control cells (<it>P </it>< 0.01). Upon BPA-BNCT treatment, the Bax level increased in glioma cells, whereas Bcl-2 expression decreased.</p> <p>Conclusions</p> <p>Compared with ��-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by BNCT may be related to activation of Bax and downregulation of Bcl-2.</p

TissUExM enables quantitative ultrastructural analysis in whole vertebrate embryos by expansion microscopy

Super-resolution microscopy reveals the molecular organization of biological structures down to the nanoscale. While it allows the study of protein complexes in single cells, small organisms, or thin tissue sections, there is currently no versatile approach for ultrastructural analysis compatible with whole vertebrate embryos. Here, we present tissue ultrastructure expansion microscopy (TissUExM), a method to expand millimeter-scale and mechanically heterogeneous whole embryonic tissues, including Drosophila wing discs, whole zebrafish, and mouse embryos. TissUExM is designed for the observation of endogenous proteins. It permits quantitative characterization of protein complexes in various organelles at super-resolution in a range of ∼3 mm-sized tissues using conventional microscopes. We demonstrate its strength by investigating tissue-specific ciliary architecture heterogeneity and ultrastructural defects observed upon ciliary protein overexpression. Overall, TissUExM is ideal for performing ultrastructural studies and molecular mapping in situ in whole embryos

Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information availabl

On How Network Architecture Determines the Dominant Patterns of Spontaneous Neural Activity

In the absence of sensory stimulation, neocortical circuits display complex patterns of neural activity. These patterns are thought to reflect relevant properties of the network, including anatomical features like its modularity. It is also assumed that the synaptic connections of the network constrain the repertoire of emergent, spontaneous patterns. Although the link between network architecture and network activity has been extensively investigated in the last few years from different perspectives, our understanding of the relationship between the network connectivity and the structure of its spontaneous activity is still incomplete. Using a general mathematical model of neural dynamics we have studied the link between spontaneous activity and the underlying network architecture. In particular, here we show mathematically how the synaptic connections between neurons determine the repertoire of spatial patterns displayed in the spontaneous activity. To test our theoretical result, we have also used the model to simulate spontaneous activity of a neural network, whose architecture is inspired by the patchy organization of horizontal connections between cortical columns in the neocortex of primates and other mammals. The dominant spatial patterns of the spontaneous activity, calculated as its principal components, coincide remarkably well with those patterns predicted from the network connectivity using our theory. The equivalence between the concept of dominant pattern and the concept of attractor of the network dynamics is also demonstrated. This in turn suggests new ways of investigating encoding and storage capabilities of neural networks

Clusters of galaxies : observational properties of the diffuse radio emission

Clusters of galaxies, as the largest virialized systems in the Universe, are ideal laboratories to study the formation and evolution of cosmic structures...(abridged)... Most of the detailed knowledge of galaxy clusters has been obtained in recent years from the study of ICM through X-ray Astronomy. At the same time, radio observations have proved that the ICM is mixed with non-thermal components, i.e. highly relativistic particles and large-scale magnetic fields, detected through their synchrotron emission. The knowledge of the properties of these non-thermal ICM components has increased significantly, owing to sensitive radio images and to the development of theoretical models. Diffuse synchrotron radio emission in the central and peripheral cluster regions has been found in many clusters. Moreover large-scale magnetic fields appear to be present in all galaxy clusters, as derived from Rotation Measure (RM) studies. Non-thermal components are linked to the cluster X-ray properties, and to the cluster evolutionary stage, and are crucial for a comprehensive physical description of the intracluster medium. They play an important role in the cluster formation and evolution. We review here the observational properties of diffuse non-thermal sources detected in galaxy clusters: halos, relics and mini-halos. We discuss their classification and properties. We report published results up to date and obtain and discuss statistical properties. We present the properties of large-scale magnetic fields in clusters and in even larger structures: filaments connecting galaxy clusters. We summarize the current models of the origin of these cluster components, and outline the improvements that are expected in this area from future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics Review. 58 pages, 26 figure

The influence of elastic orthotic belt on sagittal profile in adolescent idiopathic thoracic scoliosis: a comparative radiographic study with Milwaukee brace

<p>Abstract</p> <p>Background</p> <p>The effectiveness of bracing on preventing curve progression in coronal plane for mild and moderate adolescent idiopathic scoliosis (AIS) patients has been confirmed by previous radiographic researches. However, a hypokyphotic effect on the sagittal plane has been reported by a few studies. A relatively increasing number of AIS patients were noticed to wear a new kind of elastic orthotic belt for the treatments of scoliosis without doctors' instructions. We postulate the correcting mechanism of this new appliance may cause flattening of the spine. To our knowledge, no study has investigated the effects of this new orthosis on the sagittal profile of AIS patients. The aim of this study was to evaluate and compare the effects of elastic orthotic belt and Milwaukee brace on the sagittal alignment in AIS patients.</p> <p>Methods</p> <p>Twenty-eight female AIS patients with mild or moderate thoracic curves were included in this study. Standing full-length lateral radiographs were obtained in three conditions: natural standing posture without any treatment, with elastic orthotic belt and with Milwaukee brace. Thoracic kyphosis (TK), lumber lordosis (LL) and pelvic incidence (PI) were measured and compared between the above three conditions.</p> <p>Results</p> <p>Both elastic orthotic belt and Milwaukee brace can lead to significant decrease of TK, however, the decrease of TK after wearing elastic orthotic belt is significantly larger than that after wearing Milwaukee brace. Compared with no treatment, LL was found to be significantly smaller after wearing Milwaukee brace, however, such significant decrease was not noted after wearing elastic orthotic belt. No significant changes were observed for the PI between 3 conditions.</p> <p>Conclusions</p> <p>The elastic orthotic belt could lead to more severe thoracic hypokyphosis when compared with Milwaukee brace. This belt may not be a suitable conservative method for the treatment of mild and moderate AIS patients.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Positional cloning of rp2 QTL associates the P450 genes CYP6Z1, CYP6Z3 and CYP6M7 with pyrethroid resistance in the malaria vector Anopheles funestus

Pyrethroid resistance in Anopheles funestus is threatening malaria control in Africa. Elucidation of underlying resistance mechanisms is crucial to improve the success of future control programs. A positional cloning approach was used to identify genes conferring resistance in the uncharacterised rp2 quantitative trait locus (QTL) previously detected in this vector using F6 advanced intercross lines (AIL). A 113 kb BAC clone spanning rp2 was identified and sequenced revealing a cluster of 15 P450 genes and one salivary protein gene (SG7-2). Contrary to A. gambiae, AfCYP6M1 is triplicated in A. funestus, while AgCYP6Z2 orthologue is absent. Five hundred and sixty-five new single nucleotide polymorphisms (SNPs)were identified for genetic mapping from rp2 P450s and other genes revealing high genetic polymorphisms with one SNP every 36 bp. A significant genotype/phenotype association was detected for rp2 P450s but not for a cluster of cuticular protein genes previously associated with resistance in A. gambiae. QTL mapping using F6 AIL confirms the rp2 QTL with an increase logarithm of odds score of 5. Multiplex gene expression profiling of 15 P450s and other genes around rp2 followed by individual validation using qRT–PCR indicated a significant overexpression in the resistant FUMOZ-R strain of the P450s AfCYP6Z1, AfCYP6Z3, AfCYP6M7 and the glutathione-s-transferase GSTe2 with respective fold change of 11.2,6.3, 5.5 and 2.8. Polymorphisms analysis of AfCYP6Z1 and AfCYP6Z3 identified amino acid changes potentially associated with resistance further indicating that these genes are controlling the pyrethroid resistance explained by the rp2 QTL. The characterisation of this rp2 QTL significantly improves our understanding of resistance mechanisms in A. funestus