Modeling Patient-Derived Glioblastoma with Cerebral Organoids

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Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and therapeutic outcome – MONET – study

Background

In orthodontic treatment, anchorage control is a fundamental aspect. Usually conventional mechanism for orthodontic anchorage control can be either extraoral or intraoral that is headgear or intermaxillary elastics. Their use are combined with various side effects such as tipping of occlusal plane or undesirable movements of teeth. Especially in cases, where key-teeth are missing, conventional anchorage defined as tooth-borne anchorage will meet limitations. Therefore, the use of endosseous implants for anchorage purposes are increasingly used to achieve positional stability and maximum anchorage.

Methods/Design

The intended study is designed as a prospective, multicenter randomized controlled trial (RCT), comparing and contrasting the effect of early loading of palatal implant therapy versus implant loading after 12 weeks post implantation using the new ortho-implant type II anchor system device (Orthosystem Straumann, Basel, Switzerland). 124 participants, mainly adult males or females, whose diagnoses require temporary stationary implant-based anchorage treatment will be randomized 1:1 to one of two treatment groups: group 1 will receive a loading of implant standard therapy after a healing period of 12 week (gold standard), whereas group 2 will receive an early loading of orthodontic implants within 1 week after implant insertion. Participants will be at least followed for 12 months after implant placement. The primary endpoint is to investigate the behavior of early loaded palatal implants in order to find out if shorter healing periods might be justified to accelerate active orthodontic treatment. Secondary outcomes will focus e.g. on achievement of orthodontic treatment goals and quantity of direct implant-bone interface of removed bone specimens. As tertiary objective, a histologic and microtomography evaluation of all retrieved implants will be performed to obtain data on the performance of the SLA surface in human bone evaluation of all retrieved implants. Additionally, resonance frequency analysis (RFA, Osstell? mentor) will be used at different times for clinically monitoring the implant stability and for histological comparison in order to measure the reliability of the resonance frequency measuring device.

Trial registration

Current Controlled Trials ISRCTN97142521.     

Increased insulin-stimulated Akt pSer473 and cytosolic SHP2 protein abundance in human skeletal muscle following acute exercise and short-term training.

The purpose of the present study was to determine in human skeletal muscle whether a single exercise bout and 7 days of consecutive endurance (cycling) training 1) increased insulin-stimulated Akt pSer(473) and 2) altered the abundance of the protein tyrosine phosphatases (PTPases), PTP1B and SHP2. In healthy, untrained men (n = 8; 24 +/- 1 yr), glucose infusion rate during a hyperinsulinemic euglycemic clamp, when compared with untrained values, was not improved 24 h following a single 60-min bout of endurance cycling but was significantly increased ( approximately 30%; P < 0.05) 24 h following completion of 7 days of exercise training. Insulin-stimulated Akt pSer(473) was approximately 50% higher (P < 0.05) 24 h following the acute bout of exercise, with this effect remaining after 7 days of training (P < 0.05). Insulin-stimulated insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation were not altered 24 h after acute exercise and short-term training. Insulin did not acutely regulate the localization of the PTPases, PTP1B or SHP2, although cytosolic protein abundance of SHP2 was increased (P < 0.05; main effect) 24 h following acute exercise and short-term training. In conclusion, insulin-sensitive Akt pSer(473) and cytosolic SHP2 protein abundance are higher after acute exercise and short-term training, and this effect appears largely due to the residual effects of the last bout of prior exercise. The significance of exercise-induced alterations in cytosolic SHP2 and insulin-stimulated Akt pSer(473) on the improvement in insulin sensitivity requires further elucidation.     

Possible apoptotic mechanism in epidermal cell acantholysis induced by pemphigus vulgaris autoimmunoglobulins

Through a still unclear mechanism, pemphigus vulgaris autoantibodies (PV-IgG) induce intra-epidermal acantholytic lesions responsible for severe to fatal skin wounding. We present evidence that PV lesions contain apoptotic keratinocytes, and that cell death is induced in the lesional tissue apparently before cell separation. These data suggest that apoptosis could be the cause of the acantholytic phenomenon. We show that PV-IgG and an antibody against Fas receptor (anti-FasR) induce lesions in vitro in a similar way, causing: (1) secretion of soluble FasL; (2) elevated cellular amounts of FasR, FasL (soluble and membranal), Bax and p53 proteins; (3) reduction in levels of cellular Bcl-2; (4) enrichment in caspase 8, and activation of caspases 1 and 3; (5) co-aggregation of FasL and FasR with caspase 8 in membranal death-inducing signaling complex (DISC). Hence, the Fas-mediated death signaling pathway seems to be involved in lesion formation. Moreover, we have shown that in skin organ cultures and in keratinocyte cultures, PV-IgG can induce caspase activation and DNA fragmentation, and caspase inhibitors can prevent the formation of PV-IgG-induced epidermal lesions. Altogether, these results suggest that PV-IgG-induced acantholysis may proceed through the death-signaling pathway. They highlight new perspectives on mechanisms of tissue damage in autoimmune diseases.     

Plant hormone homeostasis and the control of avocado fruit size

Control of plant hormone homeostasis is crucial for normal organdevelopment in plants. To elucidate the contribution of plant hormonehomeostasis to fruit growth, tissue distribution and activity of xanthinedehydrogenase (XDH), abscisic aldehyde (AB-ald)- and indole acetaldehyde(IA-ald) oxidase, and cytokinin oxidase (CKOX) were determined in seed, seedcoat and mesocarp of normal 'Hass avocado and its small-fruitphenotype during the linear phase of growth. Activity of these enzymes wasrelated to the tissue content of indole-3-acetic acid (IAA) and abscisic acid(ABA). IA-ald oxidase was present only in seed tissue whereas AB-ald oxidase andXDH activity was found in seed and mesocarp tissue. Seed of the small'Hass fruit had increased XDH and AB-ald oxidase activity and highendogenous ABA, but reduced IA-ald oxidase activity and adenine. There was nodifference in seed, seed coat and mesocarp CKOX activity between normal andsmall fruit. Inhibition of XDH activity in whole fruit by treatment withallopurinol decreased IAA and increased ABA of seed tissue. In mesocarp ofripening fruit allopurinol increased ABA and IAA but had no effect on levels ofiP. Results indicate that activity of IA-ald and AB-ald oxidases in avocadofruit contribute to maintenance of the IAA/ABA ratio in seed and mesocarp tissueand that increased AB-ald oxidase, or reduced IA-ald oxidase, may be part of thesyndrome associated with the appearance of a small-fruit phenotype.     

Sarcolemmal organization in skeletal muscle lacking desmin: evidence for cytokeratins associated with the membrane skeleton at costameres

The sarcolemma of fast-twitch muscle is organized into "costameres," structures that are oriented transversely, over the Z and M lines of nearby myofibrils, and longitudinally, to form a rectilinear lattice. Here we examine the role of desmin, the major intermediate filament protein of muscle in organizing costameres. In control mouse muscle, desmin is enriched at the sarcolemmal domains that lie over nearby Z lines and that also contain beta-spectrin. In tibialis anterior muscle from mice lacking desmin due to homologous recombination, most costameres are lost. In myofibers from desmin -/- quadriceps, by contrast, most costameric structures are stable. Alternatively, Z line domains may be lost, whereas domains oriented longitudinally or lying over M lines are retained. Experiments with pan-specific antibodies to intermediate filament proteins and to cytokeratins suggest that control and desmin -/- muscles express similar levels of cytokeratins. Cytokeratins concentrate at the sarcolemma at all three domains of costameres when the latter are retained in desmin -/- muscle and redistribute with beta-spectrin at the sarcolemma when costameres are lost. Our results suggest that desmin associates with and selectively stabilizes the Z line domains of costameres, but that cytokeratins associate with all three domains of costameres, even in the absence of desmin.     

On the influence of vessel planarity on local hemodynamics at the human carotid bifurcation

The human carotid artery bifurcation is a complex, three-dimensional structure exhibiting non-planarity and both in- and out-of-plane curvature. The aim of this study was to determine the relative importance of vessel planarity, a potential geometric risk factor for atherogenesis, in determining the local hemodynamics. A combination of computational fluid dynamics and magnetic resonance imaging was used to reconstruct the subject-specific hemodynamics for three subjects. Planar models were then constructed by translating the centroids of the lumen contours onto a plane defined by the centroids of the vessel branches near the bifurcation apex. A novel "patching" technique was used to convert the continuous arterial surfaces into contiguous but discrete patches according to an objective scheme, making it possible to compare the original and planar models without the need for registration and warping. Results suggest that the planarity of the vessel has a relatively minor effect on the spatial distribution of mean and oscillatory wall shear stress. Out-of-plane curvature was, however, found to have a marked influence on the extent and magnitude of these hemodynamic variables. We conclude that vessel curvature - whether in- or out-of-plane - rather than planarity may deserve further scrutiny as a potential geometric risk for atherogenesis.     

The legacy of Donald O. Hebb: more than the Hebb synapse

Neuroscientists associate the name of Donald O. Hebb with the Hebbian synapse and the Hebbian learning rule, which underlie connectionist theories and synaptic plasticity, but Hebb's work has also influenced developmental psychology, neuropsychology, perception and the study of emotions, as well as learning and memory. Here, we review the work of Hebb and its lasting influence on neuroscience in honour of the 2004 centenary of his birth.