Activity

As human thermoregulatory responses to maintain core body temperature (T

) under multiple stressors such as cold, hypoxia, and dehydration (e.g., exposure to high-altitude) are varied, the combined effects of cold, hypoxia, and dehydration status on T

in rats were investigated. The following environmental conditions were constructed (1) thermoneutral (24°C) or cold (10°C), (2) normoxia (21% O

) or hypoxia (12% O

), and (3) euhydration or dehydration (48h water deprivation), resulted in eight environmental conditions [2 ambient temperatures (T

) × 2 oxygen levels × 2 hydration statuses)]. Each condition lasted for 24h.

Normoxic conditions irrespective of hypoxia or dehydration did not strongly decrease the area under the curve (AUC) in T

during the 24 period, whereas, hypoxic conditions caused greater decreases in the AUC in T

, which was accentuated with cold and dehydration (T

 × O

 × hydration, P = 0.040 by three-way ANOVA). In contrast, multiple stressors (T

 × O

 × hydration or T

 × O

or O

 × hydration or T

 × hydration) did not affect locomotor activity counts (all P > 0.05), but a significant simple main effect for O

and T

was observed (P < 0.001). Heat loss index was not affected by all environmental conditions (all P > 0.05). In conclusion, decreases in T

were most affected by multiple environmental stressors such as cold, hypoxia, and dehydration.

 0.05). In conclusion, decreases in Tcore were most affected by multiple environmental stressors such as cold, hypoxia, and dehydration.

Our previous studies demonstrated that adipose-derived mesenchymal stromal cells (ASCs) have immunomodulatory effects that prolong allograft survival in a rodent hind-limb allotransplant model. In this study, we investigated whether the effects of immunomodulation by ASCs on allograft survival are correlated with B cell regulation.

B cells isolated from splenocytes were cocultured with ASCs harvested from adipose tissue from rodent groin areas for in vitro experiments. In an in vivo study, hind-limb allotransplantation from Brown-Norway to Lewis rats was performed, and rats were treated with ASCs combined with short-term treatment with anti-lymphocyte serum (ALS)/cyclosporine (CsA) as immunosuppressants. Peripheral blood and transplanted tissue were collected for further analysis.

An in vitro study revealed that ASCs significantly suppressed lipopolysaccharide-activated B cell proliferation and increased the percentage of Bregs. The levels of immunoregulatory cytokines, such as TGF-β1 and IL-10, were significantly increased in supernatants of stimulated B cells cocultured with ASCs. The in vivo study showed that treatment with ASCs combined with short-term ALS/CsA significantly reduced the B cell population in alloskin tissue, increased the proportion of circulating CD45Ra

/Foxp3

B cells, and decreased C4d expression in alloskin.

ASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines.

ASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines.Mutations in the RYR1 gene, encoding the skeletal muscle calcium channel RyR1, lead to congenital myopathies, through expression of a channel with abnormal permeability and/or in reduced amount, but the direct functional whole organism consequences of exclusive reduction in RyR1 amount have never been studied. We have developed and characterized a mouse model with inducible muscle specific RYR1 deletion. Tamoxifen-induced recombination in the RYR1 gene at adult age resulted in a progressive reduction in the protein amount reaching a stable level of 50% of the initial amount, and was associated with a progressive muscle weakness and atrophy. Measurement of calcium fluxes in isolated muscle fibers demonstrated a reduction in the amplitude of RyR1-related calcium release mirroring the reduction in the protein amount. Alterations in the muscle structure were observed, with fibers atrophy, abnormal mitochondria distribution and membrane remodeling. An increase in the expression level of many proteins was observed, as well as an inhibition of the autophagy process. This model demonstrates that RyR1 reduction is sufficient to recapitulate most features of Central Core Disease, and accordingly similar alterations were observed in muscle biopsies from Dusty Core Disease patients (a subtype of Central Core Disease), pointing to common pathophysiological mechanisms related to RyR1 reduction.

The winter tick (Dermacentor albipictus) has garnered significant attention throughout North America for its impact on wildlife health, and especially for moose (Alces alces), where high tick burdens may result in host hair loss, anemia, and can prove fatal. The environmental transmission of D. albipictus larvae to a host is a critical event that has direct impact on infestation success, yet in-field observations of this life stage are lacking. In Yukon, Canada, D. albipictus had previously been found on hosts, but its larval life stage had not been detected in the field, despite previous sampling attempts.

We sampled for D. albipictus larvae using traditional flagging methods in Ibex Valley and Braeburn, Yukon. Sites were sampled repeatedly for D. albipictus larvae by flagging from late August to end of October in 2018 and late August to end of November 2019.

Larvae of D. albipictus were collected throughout Ibex Valley, at approximate densities ranging from 0.04 to 4236 larvae/100m

. Larvae were presorth of 60° latitude in Yukon, Canada. These new observations provide critical information on the spatial distribution of the host-seeking life stage of D. albipictus and confirm that this species is completing its whole life cycle in southern Yukon. selleck kinase inhibitor Understanding the environmental conditions where larvae spend their vulnerable period off-host in this northern location can inform both management strategies and projections of future range expansion which may occur with a changing climate.