AKI with incomplete epithelial repair is a major contributor to CKD characterized by tubulointerstitial fibrosis. Injury-induced epithelial secretion of profibrotic factors is hypothesized to underlie this link, but the identity of these factors and whether epithelial injury is required remain undefined. We previously showed that activation of the canonical Wnt signaling pathway in interstitial pericytes cell autonomously drives myofibroblast activation in vivo. Here, we show that inhibition of canonical Wnt signaling also substantially prevented TGFbdependent myofibroblast activation in vitro. To investigate whether Wnt ligand derived from proximal tubule is sufficient for renal fibrogenesis, we generated a novel mouse strain with inducible proximal tubule Wnt1 secretion. Adult mice were treated with vehicle or tamoxifen and euthanized at 12 or 24 weeks postinjection. Compared with vehicle-treated controls, kidneys with tamoxifen-induced Wnt1 expression from proximal tubules displayed interstitial myofibroblast activation and proliferation and increased matrix protein production. PDGF receptor b-positive myofibroblasts isolated from these kidneys exhibited increased canonical Wnt target gene expression compared with controls. Notably, fibrotic kidneys had no evidence of inflammatory cytokine expression, leukocyte infiltration, or epithelial injury, despite the close histologic correlation of each with CKD. These results provide the first example of noninflammatory renal fibrosis. The fact that epithelialderived Wnt ligand is sufficient to drive interstitial fibrosis provides strong support for the maladaptive repair hypothesis in the AKI to CKD transition.

AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GAA and cerebral creatine levels (via brain MRS), and by GATM gene sequencing.

No abstract

Deploying deep learning (DL) models across multiple compute devices to train large and complex models continues to grow in importance because of the demand for faster and more frequent training. Data parallelism (DP) is the most widely used parallelization strategy, but as the number of devices in data parallel training grows, so does the communication overhead between devices. Additionally, a larger aggregate batch size per step leads to statistical efficiency loss, i.e., a larger number of epochs are required to converge to a desired accuracy. These factors affect overall training time and beyond a certain number of devices, the speedup from leveraging DP begins to scale poorly. In addition to DP, each training step can be accelerated by exploiting model parallelism (MP). This work explores hybrid parallelization, where each data parallel worker is comprised of more than one device, across which the model dataflow graph (DFG) is split using MP. We show that atscale, hybrid training will be more effective at minimizing end-to-end training time than exploiting DP alone. We project that for Inception-V3, GNMT, and BigLSTM, the hybrid strategy provides an end-to-end training speedup of at least 26.5%, 8%, and 22% respectively compared to what DP alone can achieve at scale.

The sexes differ in how and when they allocate energy towards reproduction, but how this influences phenotypic plasticity in daily activity patterns is unclear. Here, we use collar-mounted light loggers and triaxial accelerometers to examine factors that affect time spent above ground and overall dynamic body acceleration (ODBA), an index of activity-specific energy expenditure, across the active season of free-living, semi-fossorial arctic ground squirrels (Urocitellus parryii). We found high day-to-day variability in time spent above ground and ODBA with most of the variance explained by environmental conditions known to affect thermal exchange. In both years, females spent more time below ground compared with males during parturition and early lactation; however, this difference was fourfold larger in the second year, possibly, because females were in better body condition. Daily ODBA positively correlated with time spent above ground in both sexes, but females were more active per unit time above ground. Consequently, daily ODBA did not differ between the sexes when females were early in lactation, even though females were above ground three to six fewer hours each day. Further, on top of having the additional burden of milk production, ODBA data indicate females also had fragmented rest patterns and were more active during late lactation. Our results indicate that sex differences in reproductive requirements can have a substantial influence on activity patterns, but the size of this effect may be dependent on capital resources accrued during gestation.