A residue close to ?1 loop F disrupts modulation of GABAA receptors by benzodiazepines while their binding is maintained

Benzodiazepines act at the major isoforms of GABA type A receptors where they potentiate the current evoked by the agonist GABA. The underlying mechanism of this potentiation is poorly understood, but hypothesized to be related to the mechanism that links agonist binding to channel opening in these ligand activated ion channels. The loop F of the ?(1) and the ?(2) subunit have been implicated in channel gating, and loop F of the ?(2) subunit in the modulation by benzodiazepines. We have identified the conservative point mutation Y168F located N-terminally of loop F in the ?(1) subunit that fails to affect agonist properties. Interestingly, it disrupts modulation by benzodiazepines, but leaves high affinity binding to the benzodiazepine binding site intact. Modulation by barbiturates and neurosteroids is also unaffected. Residue ?(1) Y168 is not located either near the binding pockets for GABA, or for benzodiazepines, or close to the loop F of the ?(2) subunit. Our results support the fact, that broader regions of ligand gated receptors are conformationally affected by the binding of benzodiazepines. We infer that also broader regions could contribute to signaling from GABA agonist binding to channel opening.

Electromyographic activity of the cervical flexor muscles in patients with temporomandibular disorders while performing the craniocervical flexion test: a cross-sectional study

Most patients with temporomandibular disorders (TMD) have been shown to have cervical spine dysfunction. However, this cervical dysfunction has been evaluated only qualitatively through a general clinical examination of the cervical spine.

Artists' advance: decreased upper alpha power while drawing in artists compared with non-artists

Brain mechanisms associated with artistic talents or skills are still not well understood. This exploratory study investigated differences in brain activity of artists and non-artists while drawing previously presented perspective line-drawings from memory and completing other drawing-related tasks. Electroencephalography (EEG) data were analyzed for power in the frequency domain by means of a Fast Fourier Transform (FFT). Low Resolution Brain Electromagnetic Tomography (LORETA) was applied to localize emerging significances. During drawing and related tasks, decreased power was seen in artists compared to non-artists mainly in upper alpha frequency ranges. Decreased alpha power is often associated with an increase in cognitive functioning and may reflect enhanced semantic memory performance and object recognition processes in artists. These assumptions are supported by the behavioral data assessed in this study and complement previous findings showing increased parietal activations in non-artists compared to artists while drawing. However, due to the exploratory nature of the analysis, additional confirmatory studies will be needed.

Platelets increase while serum reduces the differentiation and activity of osteoclasts in vitro

Platelets modulate formation of osteoclasts and osteoblasts, but research with different preparations of platelets remains inconclusive. Here, we assessed whether serum components modulate the effect of platelet preparations. In murine bone marrow cultures, osteoclastogenesis was investigated in the presence of platelet-released supernatant (PRS), serum containing PRS (SC-PRS), and serum. Osteoclastogenesis was quantified by the numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, TRAP activity and resorption assays. Also human osteoclastogenesis assays were performed. Viability and proliferation were tested by MTT and (3) [H]thymidine incorporation assays, respectively. Osteoblastogenesis was assessed by histochemical staining for alkaline phosphatase-of murine bone marrow cultures and human MG63 cells. We found PRS to increase the number of TRAP(+) multinucleated cells in the early phase and TRAP activity in the later phase of osteoclastogenesis. SC-PRS and serum decreased the number and activity of TRAP(+) multinucleated cells. Both serum containing preparations reduced viability and proliferation of hematopoietic progenitors. PRS decreased the numbers of alkaline phosphatase-positive colonies while SC-PRS and serum increased osteoblastmarkers in MG63. Proliferation of MG63 was stimulated by all preparations. These results show that activated platelets support osteoclastogenesis, while platelet preparations that contain serum components decrease osteoclastogenesis and increase osteoblastogenesis in vitro, suggesting that serum components modulate the effects of platelets on osteoclastogenesis and osteoblastogenesis.

Everolimus is a potent inhibitor of activated hepatic stellate cell functions in vitro and in vivo , while demonstrating anti-angiogenic activities

Progression of liver fibrosis to HCC (hepatocellular carcinoma) is a very complex process which involves several pathological phenomena, including hepatic stellate cell activation, inflammation, fibrosis and angiogenesis. Therefore inhibiting multiple pathological processes using a single drug can be an effective choice to curb the progression of HCC. In the present study, we used the mTOR inhibitor everolimus to observe its effect on the in vitro activation of hepatic stellate cells and angiogenesis. The results of the present study demonstrated that everolimus treatment blocked the functions of the immortalized human activated hepatic stellate cell line LX-2 without affecting the viability and migration of primary human stellate cells. We also observed that treatment with everolimus (20 nM) inhibited collagen production by activated stellate cells, as well as cell contraction. Everolimus treatment was also able to attenuate the activation of primary stellate cells to their activated form. Angiogenesis studies showed that everolimus blocked angiogenesis in a rat aortic ring assay and inhibited the tube formation and migration of liver sinusoidal endothelial cells. Finally, everolimus treatment reduced the load of tumoral myofibroblasts in a rat model of HCC. These data suggest that everolimus targets multiple mechanisms, making it a potent blocker of the progression of HCC from liver fibrosis.

Caring for ageing migrants in nursing homes: 'doing diversity' while 'doing death'

The proposed paper will present first results of a research project investigating how nursing homes in Switzerland deal with migrant elders who are in intensive need of care. Focusing on the end-of-life in institutional care settings, the intention is to explore the dimensions of ‘doing death’ in Swiss nursing homes when the elderly involved are of migrant background. The focus is laid on the co-construction of end of life in interactions between residents of migrant background and professional carers involved (often of migrant background themselves), and will thereby focus on processes of ‘doing diversity’ while ‘doing death’. To do so, we chose an ethnographic approach focusing on the participant observation of everyday practices of ‘doing death’ and ‘death work’ and on interviewing staff, residents and their relatives. Caring for ageing migrants at the end of their lives is studied in different types of assisted living at the end of life: The field of research was entered by studying a group specific department for residents of so-called ‘Mediterranean’ background. It was contrasted by a department stressing the individuality of each resident but including a considerable number of residents with migrant background. We are interested in how (and if at all) specific forms of ‘doing community’ within different types of departments may also lead to specific ways of ‘doing death’, which aim at a stronger embeddedness of dying trajectories in social relations of reciprocity and exchange. Furthermore, migrant ‘doing death’ is expected to be particularly negotiable since the potential diversities of symbolic reference systems and daily practices are widened. If the respective resident is limited in his/her capacities to play an active part in negotiating about ‘good care’ and ‘good dying’ – either due to language competences, which would be migrant specific, or due to degenerative diseases, which is not migrant specific – the field of negotiations will be left up to the professionals within the organization (and to the relatives, which are, however, not constantly present). Strategies of stereotyping the ‘other’ as well as driving nurses, caring aides and other professionals of migrant background into roles of ‘cultural experts’ or ‘transcultural translators’ are expected to be common in such situations. However, the task of negotiating what would be a ‘good dying’ and what measures are appropriate is always at stake in contemporary heterogeneous societies. Therefore we would argue that studying dying processes involving migrant residents is looking at paradigmatic manifestations of doing death in recent contexts of reflexive modernity.

Higher plant diversity promotes higher diversity of fungal pathogens, while it decreases pathogen infection per plant

Fungal plant pathogens are common in natural communities where they affect plant physiology, plant survival, and biomass production. Conversely, pathogen transmission and infection may be regulated by plant community characteristics such as plant species diversity and functional composition that favor pathogen diversity through increases in host diversity while simultaneously reducing pathogen infection via increased variability in host density and spatial heterogeneity. Therefore, a comprehensive understanding of multi-host multi-pathogen interactions is of high significance in the context of biodiversity-ecosystem functioning. We investigated the relationship between plant diversity and aboveground obligate parasitic fungal pathogen (''pathogens'' hereafter) diversity and infection in grasslands of a long-term, large-scale, biodiversity experiment with varying plant species (1-60 species) and plant functional group diversity (1-4 groups). To estimate pathogen infection of the plant communities, we visually assessed pathogen-group presence (i.e., rusts, powdery mildews, downy mildews, smuts, and leaf-spot diseases) and overall infection levels (combining incidence and severity of each pathogen group) in 82 experimental plots on all aboveground organs of all plant species per plot during four surveys in 2006. Pathogen diversity, assessed as the cumulative number of pathogen groups on all plant species per plot, increased log-linearly with plant species diversity. However, pathogen incidence and severity, and hence overall infection, decreased with increasing plant species diversity. In addition, co-infection of plant individuals by two or more pathogen groups was less likely with increasing plant community diversity. We conclude that plant community diversity promotes pathogen-community diversity while at the same time reducing pathogen infection levels of plant individuals.

Oxygen consumption while standing iwth and unstable shoe design

This study explored the effects of unstable shoe design on oxygen consumption. Methods. Oxygen consumption (VO2) and heart rate (HR) were measured in 16 individuals while barefoot, wearing unstable shoes (Masai Barefoot Technology) and wearing conventional sport shoes while standing and walking on a treadmill and for 5 individuals while walking around a 400 m track. Results. When wearing the MBT shoes, a significant (p < 0.01) increase of 9.3 ± 5.2% in VO2 was measured while standing quietly for 6 min. No differences in VO2 and HR were observed between the MBT shoes or weight-adjusted conventional shoes (to match the weight of the MBT shoes) while walking on a treadmill. However, significant increases (p < 0.01) in VO2 (4.4 ± 8.2%) and HR (3.6 ± 7.3%) were observed for the MBT shoes compared with being barefoot. No significant differences in VO2 and HR were recorded while walking around a 400 m track either with MBT shoes, weight-adjusted conventional shoes or barefoot. Nonetheless, a comparison of the MBT shoes with barefoot revealed a tendency for VO2 to be higher when wearing the MBT shoes (7.1 ± 6.5%, p < 0.1) although HR was not significantly affected. Conclusions. The unstable shoe design predominantly effects oxygen consumption while standing, most likely due to increased muscle activity of the lower extremities.