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Chow, M.

Publications and source records attributed to Chow, M..

5 recordsLinked to original sources

Lower limb pointing to assess intersegmental dynamics after incomplete spinal cord injury and the associated role of proprioceptive impairments.

BackgroundDisorders in the recovery of gait strategies in individuals with incomplete spinal cord injury (SCI) suggest difficulties in controlling lower limb intersegmental dynamics, which could relate to proprioceptive impairments. To probe discrete aspects of lower limb interjoint coordination, we present here a novel protocol to assess lower limb motor strategies and evaluate the influence of proprioceptive impairments following SCI. MethodsTwelve able-bodied controls and 16 participants with SCI performed lower limb pointing to three targets that involved combined hip and knee flexion, or hip or knee flexion only while standing, with either full or obstructed visual feedback. We quantified lower limb proprioceptive sense in individuals with SCI using a robotic gait device. We used motion analysis to determine lower limb joint angles and foot trajectory, computed inverse dynamics to quantify joint and intersegmental dynamics, and derived muscle torque as an indicator of the motor strategies produced to control the motion to each target. We used linear mixed-effects models to assess differences between the control and SCI groups on end-point performance and muscle torque, and to assess the relationship of muscle torque with end-point performance and proprioceptive sense. ResultsGroups differed in motor strategies, but not end-point performance, when pointing to all three targets. Compared to controls, the SCI group had difficulty controlling knee muscle torque when performing the hip-flexion-only target (p = 0.008) or when flexing the hip and knee simultaneously (p = 0.0004). To complete the knee-flexion-only target, the SCI group had difficulties generating the required hip extensor muscle torque to maintain the thigh in neutral (p = 0.0001). These altered motor strategies in individuals with SCI were associated with proprioceptive impairments and end-point performance. ConclusionThis novel lower limb pointing task can identify disordered motor strategies in individuals with SCI, especially at the knee, and are associated with proprioceptive impairment. Variations of this paradigm can be employed to further understand differences in motor strategies between controls and individuals with SCI, and the impact of proprioceptive deficits.

neuroscience↗

Prefrontal Cortex Astroglia Modulate Anhedonia-like Behavior

Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.

neuroscience↗

Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment

The ability to monitor anti-tumor CD8+ T cell responses in the blood has tremendous therapeutic potential. Here, we used paired single-cell RNA sequencing and T cell receptor (TCR) sequencing to detect and characterize "tumor matching" (TM) CD8+ T cells in the blood of mice with MC38 tumors and melanoma patients using the TCR as a molecular barcode. TM cells showed increased activation compared to non-matching T cells in blood, and appeared less exhausted than matching counterparts in tumor. Importantly, PD-1, which has been used to identify putative circulating anti-tumor CD8+ T cells, showed poor sensitivity for identifying TM cells. By leveraging the transcriptome we identified candidate cell surface marker panels for TM cells in mice and melanoma patients, and validated NKG2D, CD39, and CX3CR1 in mice. These data demonstrate that the TCR can be used to identify tumor-relevant populations for comprehensive characterization, reveal unique transcriptional properties of TM cells, and develop marker panels for tracking and analysis of these cells. SummaryUsing single-cell RNA-sequencing coupled with TCR sequencing, we detected CD8+ T cell clones shared between blood and tumor in mice and melanoma patients, characterized these matching clones in blood and tumor, and identified potential biomarkers for their isolation in blood.

immunology↗

Alanine Metabolism in Bacillus subtilis

Despite a long history of genetic manipulation of Bacillus subtilis using auxotrophic markers in genetic manipulation, the genes involved in alanine metabolism have not been characterised fully. Here we show that B. subtilis expresses an alanine uptake permease, YtnA (DatA), that has a major role in the assimilation of D-alanine from the environment. Since this isomer of the amino acid is not normally abundant it likely source is form the cells own cell wall probably through the action of carboxypeptidases and/or the spontaneous release of D-alanine from the teichoic acids. Also in this work we clarify the synthetic pathways acting in the biosynthesis of alanine. Genetically we show that, unlike E. coli where multiple enzymes have a biochemical activity that can generate alanine, in B. subtilis the primary synthetic enzyme for alanine is encoded by alaT, although a second gene, dat, is present that can support slow growth of an alanine auxotroph however our data suggests that this enzyme probably synthesises D-alanine. In summary this work has provided an explanation of the observation that growth of B. subtilis is linked with an efficient recycling system for D-alanine that is released from the cell as the cell envelope is processed to permit cell enlargement. The results also suggest that the relative abundance of D- and L-alanine that might be linked with cytosolic pool of D and L-glutamate, and so enabling tight coupling protein and cell envelope synthesis with the metabolic status of the cell.

microbiology↗

Which author is which? Gender Authorship Position in Aquaculture Literature

Examining authorship position in aquaculture facilitates an improved understanding of status of women in the discipline, as authorship is a critical factor in professional success. In a review of more than eight million papers in the JSTOR Corpus across disciplines, West et al. 2013 found that men predominate in the first and last author positions and women are underrepresented in single-authored papers. Other studies have assessed women authorship, and found that a gender gap in published literature persists. This study applies the large sample size and methodology of West et al. 2013 to the broad discipline of aquaculture, and compares these results to gender authorship in the International Aquaculture Curated Database (IACD) - a compilation of 543 peer-reviewed publications supported by four international aquaculture programs headquartered at Oregon State University -- and two curated databases in the JSTOR in the Web of Science.\n\nResults reveal that the percentage of women authors (13.8%) was similar for the JSTOR aquaculture subsample and the IACD (15.7%), yet significantly lower for that of the Web of Science database (3.7%). Women are not well represented any of the databases, and remain underrepresented as authors in any position in aquaculture journals. To contextualize our findings, we examined the number of women graduates in agricultural, biological, natural, and social sciences who earned degrees in the U.S. from 1991-2015. Results from the U.S. Department of Educations National Center for Education Statistics and the percent of female graduates in the IACD show that the percent of women graduates each year has increased with women representing more than 50% of graduates, providing contextualization for the proportion of women in the discipline. Learning how authorship has changed in the aquaculture discipline over the recent decades is critical for promoting gender equity for future aquaculture scholarship and the sustainability of the professional discipline.

scientific communication and education↗