Genomic heterogeneity of osteosarcoma - shift from single candidates to functional modules.

Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic level a highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers the identification of common drivers in OS biology. To identify the common molecular mechanisms involved in the maintenance of OS, we follow the hypothesis that all the copy number-associated differences between the patients are intercepted on the level of the functional modules. The implementation is based on a network approach utilizing copy number associated genes in OS, paired expression data and protein interaction data. The resulting functional modules of tightly connected genes were interpreted regarding their biological functions in OS and their potential prognostic significance. We identified an osteosarcoma network assembling well-known and lesser-known candidates. The derived network shows a significant connectivity and modularity suggesting that the genes affected by the heterogeneous genetic alterations share the same biological context. The network modules participate in several critical aspects of cancer biology like DNA damage response, cell growth, and cell motility which is in line with the hypothesis of specifically deregulated but functional modules in cancer. Further, we could deduce genes with possible prognostic significance in OS for further investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were located on chromosome 6q. The given systems biological approach provides evidence that heterogeneity on the genomic and expression level is ordered by the biological system on the level of the functional modules. Different genomic aberrations are pointing to the same cellular network vicinity to form vital, but already neoplastically altered, functional modules maintaining OS. This observation, exemplarily now shown for OS, has been under discussion already for a longer time, but often in a hypothetical manner, and can here be exemplified for OS

Correlates of individual voice and face preferential responses during resting state

Human nonverbal social signals are transmitted to a large extent by vocal and facial cues. The prominent importance of these cues is reflected in specialized cerebral regions which preferentially respond to these stimuli, e.g. the temporal voice area (TVA) for human voices and the fusiform face area (FFA) for human faces. But it remained up to date unknown whether there are respective specializations during resting state, i.e. in the absence of any cues, and if so, whether these representations share neural substrates across sensory modalities. In the present study, resting state functional connectivity (RSFC) as well as voice- and face-preferential activations were analysed from functional magnetic resonance imaging (fMRI) data sets of 60 healthy individuals. Data analysis comprised seed-based analyses using the TVA and FFA as regions of interest (ROIs) as well as multi voxel pattern analyses (MVPA). Using the face- and voice-preferential responses of the FFA and TVA as regressors, we identified several correlating clusters during resting state spread across frontal, temporal, parietal and occipital regions. Using these regions as seeds, characteristic and distinct network patterns were apparent with a predominantly convergent pattern for the bilateral TVAs whereas a largely divergent pattern was observed for the bilateral FFAs. One region in the anterior medial frontal cortex displayed a maximum of supramodal convergence of informative connectivity patterns reflecting voice- and face-preferential responses of both TVAs and the right FFA, pointing to shared neural resources in supramodal voice and face processing. The association of individual voice- and face-preferential neural activity with resting state connectivity patterns may support the perspective of a network function of the brain beyond an activation of specialized regions

Induced feelings of external influence during instructed imaginations in healthy subjects

The psychopathological phenomenon of delusions of influence comprises variable disturbances of the self-environment-border leading to the feeling of external influence on thoughts, feelings, impulses or behaviors. Delusions of influence are a hallmark in psychotic illness, but nevertheless, attenuated forms can also appear in healthy individuals. Here we present a newly developed paradigm to induce and assess feelings of external influence during instructed imaginations in healthy individuals. In the current study, we asked 60 healthy individuals to visually imagine different objects. To induce feelings of external influence, we applied one of three different physical setups (low-amplitude transcranial direct current stimulation, eye contact, or skin-to-skin hand touch), and informed the participants whether or not an external influence was attempted during the respective trial. The physical setup (setup vs. no setup, Z = −3.847, p < 0.001, r = 0.497) as well as the information given to the participants (confirmation vs. negation, Z = −5.218, p < 0.001, r = 0.674) alone were able to modulate the feeling of external influence in all three interventions. The impact of information (whether influence was attempted or not attempted) significantly exceeded the impact of the physical setup on the ratings of experienced external influence (Z = −2.394, p = 0.016, r = 0.310). Moreover, the response latency correlated with the estimated feeling of external influence (r(S) = 0.392, p = 0.002). Additional analyses addressed the influence of the emotional content of imagined objects and examined the intensity and emotional valence of the imaginations. Further supplemental analyses correlated external influence estimation of the participants with other psychopathological measures (trait markers for supernatural beliefs, proneness to hallucinations, and delusions and attributional style). In conclusion, this study endorses a quantitative model of psychopathological characteristics, in this case feelings of external influence that can be induced by external cues

Design of poly (ester imide)/polysulfone multiblock copolymers and their property profiles

New multiblock copolymers containing liquid crystalline poly(ester imide) blocks coupled with polysulfone segments have been synthesized by melt transesterification polycondensation. Connecting these segments with different molecular weights offers the opportunity to obtain both non-phase-separated and phase-separated polymers. Phase separation is detected by the occurrence of more than one glass transition as well as by transmission electron microscopy. The resulting properties depend strongly on the morphology. Non-phase-separated multiblock copolymers show synergistic effects with respect to the glass transition and the initial E modulus. The glass transition temperatures as well as the modulus of all multiblock copolymers are higher than those found of the parent homopolymers of the used blocks, which results additionally in a very high thermostability. The synthesized materials could be very interesting for both new membrane materials and barriers with controllable diffusion properties