Replication and discovery of musculoskeletal QTLs in LG/J and SM/J advanced intercross lines

AR056280 awarded to DAB and AL. AIHC supported by IMS and Elphinstone Scholarship from the University of Aberdeen. GRV supported by Medical Research Scotland (Vac-929-2016).Peer reviewedPublisher PD

Transcriptional and post-transcriptional effects of nerve growth factor on expression of the three neurofilament subunits in PC-12 cells.

Nerve growth factor (NGF) is known to increase the levels of neurofilament proteins in PC-12 pheochromocytoma cells. In this report, we show that the three neurofilament subunits, NF-L, NF-M, and NF-H, are not induced coordinately. NF-H accumulated only after longer term NGF treatment than required for NF-L and NF-M. While NGF treatment resulted in 12- and 14-fold increases in NF-L and NF-M mRNA levels, respectively, over a 14-day period, no increase in the level of NF-H mRNA was observed. This indicated that in PC-12 cells, control of NF-H expression by NGF may occur at the post-transcriptional level. NGF appeared to have no effect on the stability of NF-L mRNA, although it increased the stability of NF-M mRNA relative to that in control PC-12 cells. Analysis of the effect of NGF on the transcription of neurofilament genes showed 4- and 5-fold increases in the rates of NF-L and NF-M gene transcription, respectively, and no increase in the rate of NF-H gene transcription. Taken together these results demonstrate that NGF stimulates the expression of individual neurofilament subunits at the transcriptional and/or post-transcriptional levels

Learning Behavioural Context

The original publication is available at www.springerlink.co

SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras

SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. Consistently, SHANK3 silencing triggers increased plasma membrane Rap1 activity, cell spreading, migration and invasion. Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. Altogether, we establish SHANKs as critical regulators of G-protein signalling and integrin-dependent processes

Photochemically modified diamond-like carbon surfaces for neural interfaces

Diamond-like carbon (DLC) was modified using a UV functionalization method to introduce surface-bound amine and aldehyde groups. The functionalization process rendered the DLC more hydrophilic and significantly increased the viability of neurons seeded to the surface. The amine functionalized DLC promoted adhesion of neurons and fostered neurite outgrowth to a degree indistinguishable from positive control substrates (glass coated with poly-L-lysine). The aldehyde-functionalized surfaces performed comparably to the amine functionalized surfaces and both additionally supported the adhesion and growth of primary rat Schwann cells. DLC has many properties that are desirable in biomaterials. With the UV functionalization method demonstrated here it may be possible to harness these properties for the development of implantable devices to interface with the nervous system

ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.</p> <p>Methods</p> <p>A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.</p> <p>Results</p> <p>Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.</p> <p>Conclusions</p> <p>Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.</p