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Street, J.

Publications and source records attributed to Street, J..

3 recordsLinked to original sources

Head direction cells use a head-referenced dual-axis updating rule in 3D space

Head direction (HD) cells, comprising a compass signal for the brains spatial map, may update their firing during 3D movement by using a dual axis (DA) rule that summates head rotation around a local axis and local-axis rotation around the gravity axis. To test for operation of this rule we recorded HD cell activity from rats exploring a hemispherical surface. We assessed HD cell tuning curves in either the standard horizontal reference frame or in two reference frames governed by a DA rule, with the local axis referenced to the head (DAH) or local surface (DAS). Tuning curves were best when plotted in the DAH reference frame. This confirms that the cells use a head-referenced DA rule and indicates that the relationship of the head pose to gravity in two planes, one egocentric (head-plane) and one allocentric (earth-horizontal plane), forms a component of the inputs to the HD system.

neuroscience↗

Proteomic portraits reveal evolutionarily conserved and divergent responses to spinal cord injury

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of CSF and serum samples from 111 acute SCI patients and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at six months with an AUC of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response, and establish the CSF abundance of glial fibrillary acidic protein (GFAP) as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

neuroscience↗

Modulation of T helper 1 and T helper 2 immune balance in a stress mouse model during Chlamydia muridarum genital infection

A mouse model to study the effect of cold-induced stress on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Our previous results show that cold-induced stress increases the intensity of chlamydia genital infection, but little is known about the effect of cold-induced stress on differentiations and activities of T cell subpopulations and bone marrow derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines is not clear. The objective of this study was to examine whether cold-induced stress modulates the expression of transcription factors and hallmark cytokines of Th1 and Th2 or differentiation of BMDCs during C. muridarum genital infection in mice. Our results show that mRNA level of beta2-adrenergic receptor ({beta}2-AR) compared to {beta}1-AR and {beta}3-AR was high in mixed population of CD4+ T cells and BMDCs. Further, decreased expression of T-bet and low level of interferon-gamma (IFN-{gamma}) production and increased expression of GATA-3 and interleukin-4 (IL-4) production in CD4+ T of stressed mice was observed. Exposure of BMDCs to feroterol ({beta}2-AR agonist) or ICI,118551 ({beta}2-AR antagonist), respectively, revealed significant stimulation or inhibition of {beta}2-AR in stressed mice. Moreover, co-culturing of mature BMDC and naive CD4+ T cells resulted in increased production of IL-4, IL-10, and IL-17 in culture supernatants, suggesting that stimulation of {beta}2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that cold-induced stress is able to modulate the pattern of Th1 and Th2 cytokine environment, suggesting that it promotes the differentiation to Th2 rather than Th1 by the overexpression of GATA-3 correlated with elevated production of IL-4, IL-10, IL-23, and IL-17 in contrast to a low expression of T-bet correlated with less IFN-{gamma} secretion in the mouse model.

microbiology↗