Long-term potentiation at C-fibre synapses by low-level presynaptic activity in vivo

Inflammation, trauma or nerve injury trigger low-level activity in C-fibres and may cause long-lasting hyperalgesia. Long-term potentiation (LTP) at synapses of primary afferent C-fibres is considered to underlie some forms of hyperalgesia. In previous studies, high- but not low-frequency conditioning stimulation of C-fibres has, however, been used to induce LTP in pain pathways. Recently we could show that also conditioning low-frequency stimulation (LFS) at C-fibre intensity induces LTP in vitro as well as in the intact animal, i.e. with tonic descending inhibition fully active. In the slice preparation, this form of LTP requires a rise in postsynaptic Ca2+-concentration and activation of Ca2+-dependent signalling pathways. Here, we investigated the signalling mechanisms underlying this novel form of LTP in vivo. We found that the signal transduction pathways causing LFS-induced LTP in vivo include activation of neurokinin 1 and N-methyl-D-aspartate receptors, rise of [Ca2+]i from intracellular stores and via T-type voltage-dependent Ca2+ channels, activation of phospholipase C, protein kinase C and Ca2+-calmodulin dependent kinase II. These pathways match those leading to hyperalgesia in behaving animals and humans. We thus propose that LTP induced by low-level activity in C-fibres may underlie some forms of hyperalgesia

Are taxonomy details of relevance to ecologists? An example from microcopepods of the Red Sea

The marine microcopepod family Oncaeidae in the Red Sea has been the subject of comprehensive ecological studies over the past 15 years, providing for the first time insights into their community structure, vertical distribution and feeding ecology. Owing to taxonomic problems in species identification, however, many of the earlier ecological results were based on provisionally named species or morphotypes. A recent, ongoing taxonomic study of Red Sea Oncaeidae resulted in a considerable increase in the estimated numbers of species, since many of the species had not been described before. The present paper focuses on the potential significance of an improved taxonomic resolution of oncaeids with respect to various ecological aspects in this area, such as indicator species, community analysis and vertical distribution. The progress in our knowledge of the diversity of Red Sea Oncaeidae is summarized, including latest findings on the taxonomy and zoogeography of very small species (<0.5 mm), and the importance of sibling species in the family is pointed out. The south–north gradient in species diversity of Oncaeidae within the Red Sea appears to be greater than previously assumed, since several of the newly described species were restricted to the southern part. The number of endemic species among Red Sea oncaeids is very low, however, most of the new species being also recorded outside the Red Sea. New quantitative data on the abundance and vertical distribution of selected oncaeid siblings obtained during a recent cruise in the northern Red Sea are provided to exemplify the changes in the knowledge of oncaeid community structure attributable to the improved taxonomic resolution. The potential ecological importance of a more differentiated consideration of oncaeid species in marine microcopepod communities is discusse

Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents

... WITHOUT RIGHT ANGLE.

Currently sculptural design is one of the most discussed themes in architecture. Due to their light weight, easy transportation and assembly, as well as an almost unlimited structural variety, parameterised spatial structures are excellently suited for constructive realisation of free formed claddings. They subdivide the continuous surface into a structure of small sized nodes, straight members and plane glass panels. Thus they provide an opportunity to realise arbitrary double-curved claddings with a high degree of transparency, using industrial semi-finished products (steel sections, flat glass). Digital design strategies and a huge number of similar looking but in detail unique structural members demand a continuous digital project handling. Within a research project, named MYLOMESH, a free-formed spatial structure was designed, constructed, fabricated and assembled. All required steps were carried out based on digital data. Different digital connections (scripts) between varying software tools, which are usually not used in the planning process of buildings, were created. They allow a completely digital workflow. The project, its design, meshing, constructive detailing and the above-mentioned scripts are described in this paper

TOOL TO CHECK TOPOLOGY AND GEOMETRY FOR SPATIAL STRUCTURES ON BASIS OF THE EXTENDED MAXWELL'S RULE

One of the simplest principle in the design of light-weight structures is to avoid bending. This can be achieved by dissolving girders into members acting purely in axial tension or compression. The employment of cables for the tensioned members leads to even lighter structures which are called cable-strut structures. They constitute a subclass of spatial structures. To give fast information about the general feasibility of an architectural concept employing cable-strut structures is a challenging task due to their sophisticated mechanical behavior. In this regard it is essential to control if the structure is stable and if pre-stress can be applied. This paper presents a tool using the spreadsheet software Microsoft (MS) Excel which can give such information. Therefore it is not necessary to purchase special software and the according time consuming training is much lower. The tool was developed on basis of the extended Maxwell's rule, which besides topology also considers the geometry of the structure. For this the rank of the node equilibrium matrix is crucial. Significance and determination of the rank and the implementation of the corresponding algorithms in MS Excel are described in the following. The presented tool is able to support the structural designer in an early stage of the project in finding a feasible architectural concept for cable-strut structures. As examples for the application of the software tool two special cable-strut structures, so called tensegrity structures, were examined for their mechanical behavior

Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer

<p>Abstract</p> <p>Background</p> <p>We have previously reported that expression of the Wnt antagonist genes <it>SFRP1 </it>and <it>SFRP5 </it>is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is also implicated in human breast cancer, and if so whether <it>SFRP2 </it>promoter methylation might serve as a potential tumor biomarker.</p> <p>Methods</p> <p>We analyzed <it>SFRP2 </it>mRNA expression and <it>SFRP2 </it>promoter methylation in 10 breast cell lines, 199 primary breast carcinomas, 20 matched normal breast tissues and 17 cancer-unrelated normal breast tissues using RT-PCR, realtime PCR, methylation-specific PCR and Pyrosequencing, respectively. SFRP2 protein expression was assessed by immunohistochemistry on a tissue microarray. Proliferation assays after transfection with an <it>SFRP2 </it>expression vector were performed with mammary MCF10A cells. Statistical evaluations were accomplished with SPSS 14.0 software.</p> <p>Results</p> <p>Of the cancerous breast cell lines, 7/8 (88%) lacked <it>SFRP2 </it>mRNA expression due to <it>SFRP2 </it>promoter methylation (<it>P </it>< 0.001). <it>SFRP2 </it>expression was substantially restored in most breast cell lines after treatment with 5-aza-2'-deoxycytidine and trichostatin A. In primary breast carcinomas SFRP2 protein expression was strongly reduced in 93 of 125 specimens (74%). <it>SFRP2 </it>promoter methylation was detected in 165/199 primary carcinomas (83%) whereas all cancer-related and unrelated normal breast tissues were not affected by <it>SFRP2 </it>methylation. <it>SFRP2 </it>methylation was not associated with clinicopathological factors or clinical patient outcome. However, loss of SFRP2 protein expression showed a weak association with unfavorable patient overall survival (<it>P </it>= 0.071). Forced expression of <it>SFRP2 </it>in mammary MCF10A cells substantially inhibited proliferation rates (<it>P </it>= 0.045).</p> <p>Conclusion</p> <p>The <it>SFRP2 </it>gene is a high-frequent target of epigenetic inactivation in human breast cancer. Its methylation leads to abrogation of <it>SFRP2 </it>expression, conferring a growth advantage to epithelial mammary cells. This altogether supports a tumor suppressive function of <it>SFRP2</it>. Although clinical patient outcome was not associated with <it>SFRP2 </it>methylation, the high frequency of this epimutation and its putative specificity to neoplastic cells may qualify <it>SFRP2 </it>promoter methylation as a potential candidate screening marker helping to improve early breast cancer detection.</p

A roadmap for the future design of human-robot collaboration

Human-robot collaboration systems are a new and interesting approach in the science of robotics. Collaborative robot systems can be used without protective fences in direct interaction with humans. For ongoing developments in human-robot collaboration, further improvements in a multitude of disciplines and research areas are necessary. The scope of interdisciplinary research work in this context is enormous and the scientific field is, due to the high level of interdisciplinarity, quite complex. In the debates within the Ladenburg Discourse⁎ on human-robot collaboration, it was agreed that guidelines for future research and development work would be very useful and would enable researchers to structure and position their work in this wide field. Duplications and redundancies could be avoided, and synergies and cooperations could be promoted. For those reasons, an extended set of thirteen theses is formulated. This paper describes these theses, as a summary of the Ladenburg Discourse, with the intention to provide a roadmap for human-robot collaboration