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SUMMARYCyclophilin D (CypD) promotes opening of the mitochondrial permeability transition pore (MPTP) which plays a key role in both cell physiology and pathology. It is, therefore beneficial for cells to tightly regulate CypD and MPTP but little is known about such regulation. We have reported before that CypD is downregulated and MPTP deactivated during differentiation in various tissues. Herein, we identify BMP/Smad signaling, a major driver of differentiation, as a transcriptional repressor of the CypD gene, Ppif. Using osteogenic induction of mesenchymal lineage cells as a model of BMP/Smad-dependent differentiation, we show that CypD is in fact transcriptionally repressed during this process. The importance of such CypD downregulation is evidenced by the negative effect of CypD ‘rescue’ via gain-of-function on osteogenesis both in vitro and in vivo. In sum, we characterized BMP/Smad signaling as a regulator of CypD expression and elucidated the role of CypD downregulation during cell differentiation.

Current methods to model species habitat use through space and diel time are limited. Development of such models is critical when considering rapidly changing habitats where species are forced to adapt to anthropogenic change, often by shifting their diel activity across space. We use an occupancy modeling framework to develop a new model, the multi-state diel occupancy model (MSDOM), which can evaluate species diel activity against continuous response variables which may impact diel activity within and across seasons or years. We used two case studies, fosa in Madagascar and coyote in Chicago, USA, to conceptualize the application of this model and to quantify the impacts of human activity on species spatial use in diel time. We found support that both species varied their habitat use by diel states—in and across years, and by human disturbance. Our results exemplify the importance of understanding animal diel activity patterns and how human disturbance can lead to temporal habitat loss. The MSDOM will allow more focused attention in ecology and evolution studies on the importance of the short temporal scale of diel time in animal-habitat relationships and lead to improved habitat conservation and management.

Working memory (WM) performance can be improved by an informative cue presented during storage. This effect, termed a retro-cue benefit, can be used to explore mechanisms of attentional prioritization in WM. Directing attention to a single item stored in memory is known to increase memory precision while decreasing the likelihood of incorrect item reports and random guesses, but it is unclear whether similar benefits manifest when participants direct attention to multiple items stored in memory. We tested this possibility by quantifying memory performance when participants were cued to prioritize one or two items stored in working memory. Consistent with prior work, cueing participants to prioritize a single memory item yielded higher recall precision, fewer swap errors, and fewer guesses relative to a neutral cue condition. Conversely, cueing participants to prioritize two memory items yielded fewer swap errors relative to a neutral condition, but no differences in recall precision or guess rates. Although swap rates were less likely during the cue-two vs. neutral conditions, planned comparisons revealed that when participants made swap errors during cue-two trials they were far more likely to confuse two prioritized stimuli than they were to confuse a prioritized stimulus vs. a non-prioritized stimulus. Our results suggest that it is possible to prioritize multiple items stored in memory, with the caveat that doing so may increase the probability of confusing prioritized items.

OBJECTIVE The soluble triggering receptor expressed on myeloid cells (TREM-1)-like transcript 1 (sTLT-1) has a modulatory effect on the activation of TREM-1. We compared plasma sTLT-1 levels between patients with systemic lupus erythematosus (SLE) and healthy individuals and determined the association between sTLT-1 levels and clinical features and patient-reported outcomes (PROs) among patients with lupus. METHODS An unmatched case-control study was conducted in 46 patients with SLE and 28 healthy subjects. sTLT-1 plasma levels were determined using enzyme-linked immunosorbent assay. Demographic factors, SLE manifestations, comorbidities, pharmacologic profile, disease activity (per SLAM-R), damage accrual, and PROs (as per Lupus Patient-Reported Outcome [LupusPRO]) were studied. RESULTS Patients with SLE were found to have lower sTLT-1 levels compared with healthy individuals (9.0±7.2 vs. 18.6±22.3 pg/mL, p=0.008). Among patients with SLE, higher sTLT-1 levels were found in those taking corticosteroids (11.1±8.8 vs. 6.9±4.6 pg/mL, p=0.014). Significant correlations were found for the cognition (r=-0.442, p=0.027) and desires/goals (r=0.435, p=0.030) domains of LupusPRO. A tendency was observed between sTLT-1 levels and the SLAM-R (r=-0.278, p=0.064) and the lupus symptoms (r=-0.388, p=0.055) and physical health (r=-0.382, p=0.060) domains of LupusPRO. CONCLUSION Compared with healthy individuals, sTLT-1 levels were significantly lower in patients with SLE. Among patients with SLE, correlations were observed for some domains of LupusPRO. Given that sTLT-1 has anti-inflammatory properties, the deficiency of this protein could play an important role in the pathogenesis of SLE.