Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Evaluation of the proliferation markers Ki-67/MIB-1, mitosin, survivin, pHH3, and DNA topoisomerase IIα in human anaplastic astrocytomas - an immunohistochemical study

<p>Abstract</p> <p>Background</p> <p>Histological malignancy grading of astrocytomas can be challenging despite criteria given by the World Health Organisation (WHO). Grading is fundamental for optimal prognostication and treatment, and additional biomarkers are needed to support the histopathological diagnosis. Estimation of proliferative activity has gained much enthusiasm, and the present study was designed to evaluate and compare novel immunohistochemical proliferative markers in human anaplastic astrocytomas.</p> <p>Methods</p> <p>Proliferative activity was determined in twenty-seven cases with antibodies reactive against the Ki-67 antigen, mitosin, survivin, pHH3, and DNA topoisomerase IIα, and they were mutually compared as well as related to mitotic activity.</p> <p>Results</p> <p>The markers correlated well with each other, but poorly with mitoses, probably because of small and squeezed tumour samples, in which identification of mitoses can be difficult. Positive association to overall survival was observed as well.</p> <p>Conclusions</p> <p>Our data show that these markers may assist significantly in the evaluation of proliferative activity in anaplastic astrocytomas and even have prognostic value.</p

Mosaicism for combined tetrasomy of chromosomes 8 and 18 in a dysmorphic child: A result of failed tetraploidy correction?

<p>Abstract</p> <p>Background</p> <p>Mosaic whole-chromosome tetrasomy has not previously been described as a cause of fetal malformations.</p> <p>Case presentation</p> <p>In a markedly dysmorphic child with heart malformations and developmental delay, CGH analysis of newborn blood DNA suggested a 50% dose increase of chromosomes 8 and 18, despite a normal standard karyotype investigation. Subsequent FISH analysis revealed leukocytes with four chromosomes 8 and four chromosomes 18. The child's phenotype had resemblance to both mosaic trisomy 8 and mosaic trisomy 18. The double tetrasomy was caused by mitotic malsegregation of all four chromatids of both chromosome pairs. A possible origin of such an error is incomplete correction of a tetraploid state resulting from failed cytokinesis or mitotic slippage during early embryonic development.</p> <p>Conclusion</p> <p>This unique case suggests that embryonic cells may have a mechanism for tetraploidy correction that involves mitotic pairing of homologous chromosomes.</p

Gold nanoparticles: New routes across old boundaries

In recent years, gold nanoparticles have emerged as unique non-invasive drug carriers for targeting drugs to their site of action. Their site specificity has helped in increasing drugs’ efficacy at lower dose as well as reduction in their side effects. Moreover, their excellent optical properties and small size offer their utilization as diagnostic tools to diagnose tumors as well as other diseases. This review focuses on various approaches that have been used in last several years for preparation of gold nanoparticles, their characterization techniques and theranostic applications. Their toxicity related aspects are also highlighted. Gold nanoparticles are useful as theranostic agents, owing to their small size, biocompatible nature, size dependent physical, chemical and optical properties etc. However, the challenges associated with these nanoparticles such as scale up, cost, low drug payload, toxicity and stability have been the major impediments in their commercialization. The review looks into all these critical issues and identifies the possibilities to overcome these challenges for successful positioning of metallic nanoparticles in market

Allotransplanted Neurons Used to Repair Peripheral Nerve Injury Do Not Elicit Overt Immunogenicity

A major problem hindering the development of autograft alternatives for repairing peripheral nerve injuries is immunogenicity. We have previously shown successful regeneration in transected rat sciatic nerves using conduits filled with allogeneic dorsal root ganglion (DRG) cells without any immunosuppression. In this study, we re-examined the immunogenicity of our DRG neuron implanted conduits as a potential strategy to overcome transplant rejection. A biodegradable NeuraGen® tube was infused with pure DRG neurons or Schwann cells cultured from a rat strain differing from the host rats and used to repair 8 mm gaps in the sciatic nerve. We observed enhanced regeneration with allogeneic cells compared to empty conduits 16 weeks post-surgery, but morphological analyses suggest recovery comparable to the healthy nerves was not achieved. The degree of regeneration was indistinguishable between DRG and Schwann cell allografts although immunogenicity assessments revealed substantially increased presence of Interferon gamma (IFN-γ) in Schwann cell allografts compared to the DRG allografts by two weeks post-surgery. Macrophage infiltration of the regenerated nerve graft in the DRG group 16 weeks post-surgery was below the level of the empty conduit (0.56 fold change from NG; p<0.05) while the Schwann cell group revealed significantly higher counts (1.29 fold change from NG; p<0.001). Major histocompatibility complex I (MHC I) molecules were present in significantly increased levels in the DRG and Schwann cell allograft groups compared to the hollow NG conduit and the Sham healthy nerve. Our results confirmed previous studies that have reported Schwann cells as being immunogenic, likely due to MHC I expression. Nerve gap injuries are difficult to repair; our data suggest that DRG neurons are superior medium to implant inside conduit tubes due to reduced immunogenicity and represent a potential treatment strategy that could be preferable to the current gold standard of autologous nerve transplant

The role of venture capitalists in the regional innovation ecosystem : a comparison of networking patterns between private and publicly backed venture capital funds

This paper empirically examines the development of social networks among venture capitalists and other professionals of the regional innovation ecosystem. Using an online survey of venture capitalists, the article considers their networking behaviour, focusing particularly on the distinction between those employed by private and those employed by publicly backed venture capital funds, and on the composition and spatial search of their networks. It investigates whether the frequency of interaction between venture capitalists and other members of the innovation ecosystem is associated with the nature of the venture capital funds. The paper provides the first detailed investigation of the relationship between different types of venture capitalists and other players of the innovation ecosystem such as universities incubators, research institutes, and business support organisations. The results show that there are distinctive differences within the two seemingly similar professional groups (private and public venture capitalists), and public dependence of the venture capital fund is strongly and significantly associated with higher volumes of interactions. The more publicly dependent a fund is, the more it interacts with other players of the innovation system. This finding has important implications for both academics and practitioners and suggests that publicly backed funds have a wider role to play in mobilising the different players of the regional innovation ecosystem