Seasonal Moulting in Deer Mice (Peromyscus maniculatus) in the Rocky Mountains, Alberta

We recorded seasonal moulting in North American Deer Mice (Peromyscus maniculatus) in the Kananaskis River valley, Alberta, Canada, to test the hypothesis that moulting is restricted to the times of year that do not overlap with other high-energy demands, such as reproduction (spring and summer), or with low nutrient availability (winter). Although a seasonal trend showing a peak in moulting in the post-breeding period provided support for our prediction, a low level of continuous moulting did occur throughout the year

Impaired Notch Signaling Promotes \u3cem\u3eDe novo\u3c/em\u3e Squamous Cell Carcinoma Formation

Signaling through Notch receptors in the skin has been implicated in the differentiation, proliferation, and survival of keratinocytes, as well as in the pathogenesis of basal cell carcinoma (BCC). To determine the composite function of Notch receptor–mediated signaling in the skin and overcome potential redundancies between receptors, conditional transgenic mice were generated that express the pan-Notch inhibitor, dominant-negative Mastermind Like 1 (DNMAML1), to repress all canonical [CBF-1/Suppressor of hairless/LAG-1 (CSL)–dependent] Notch signaling exclusively in the epidermis. Here, we report that DNMAML1 mice display hyperplastic epidermis and spontaneously develop cutaneous squamous cell carcinoma (SCC) as well as dysplastic precursor lesions, actinic keratoses. Mice expressing epidermal DNMAML1 display enhanced accumulation of nuclear ß-catenin and cyclin D1 in suprabasilar keratinocytes and in lesional cells from SCCs, which was also observed in human cutaneous SCC. These results suggest a model wherein CSL-dependent Notch signaling confers protection against cutaneous SCC. The demonstration that inhibition of canonical Notch signaling in mice leads to spontaneous formation of SCC and recapitulates the disease in humans yields fundamental insights into the pathogenesis of SCC and provides a unique in vivo animal model to examine the pathobiology of cutaneous SCC and for evaluating novel therapies

Hepatic Proprotein Convertases Modulate HDL Metabolism

SummaryThe risk of atherosclerosis is inversely associated with plasma levels of high-density lipoprotein cholesterol (HDL-C). However, HDL metabolism is incompletely understood, and there are few effective approaches to modulate HDL-C levels. Here we show that inhibition in the liver of the classical proprotein convertases (PCs), but not the atypical PCs S1P and PCSK9, decreases plasma HDL-C levels. This metabolic effect of hepatic PCs is critically dependent on expression of endothelial lipase (EL), an enzyme that directly hydrolyzes HDL phospholipids and promotes its catabolism. Hepatic PCs reduce EL function through direct inactivating cleavage of EL as well as through activating cleavage of angiopoietin-like protein 3 (ANGPTL3), an endogenous inhibitor of EL. Thus, inhibition of hepatic PCs results in increased EL activity, leading to reduced HDL-C as well as impaired reverse cholesterol transport. The hepatic PC–ANGPTL3–EL–HDL pathway is therefore a novel mechanism controlling HDL metabolism and cholesterol homeostasis

Meeting report: a hard look at the state of enamel research.

The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field

Evaluating cognitive relationships with resting-state and task-driven blood oxygen level-dependent variability

Recent functional magnetic resonance imaging studies have reported that moment-to-moment variability in the blood oxygen level-dependent (BOLD) signal is positively associated with task performance and, thus, may reflect a behaviorally sensitive signal. However, it is not clear whether estimates of resting-state and task-driven BOLD variability are differentially related to cognition, as they may be driven by distinct sources of variance in the BOLD signal. Moreover, other studies have suggested that age differences in resting-state BOLD variability may be particularly sensitive to individual differences in cardiovascular, rather than neural, factors. In this study, we tested relationships between measures of behavioral task performance and BOLD variability during both resting-state and task-driven runs of a Stroop and an animacy judgment task in a large, well-characterized sample of cognitively normal middle-aged to older adults. Resting-state BOLD variability was related to composite measures of global cognition and attentional control, but these relationships were eliminated after correction for age or cardiovascular estimates. In contrast, task-driven BOLD variability was related to attentional control measured both inside and outside the scanner, and importantly, these relationships persisted after correction for age and cardiovascular measures. Overall, these results suggest that BOLD variability is a behaviorally sensitive signal. However, resting-state and task-driven estimates of BOLD variability may differ in the degree to which they are sensitive to age-related, cardiovascular, and neural mechanisms

Influence of Sex and Age on Muscle Sympathetic Nerve Activity of Healthy Normotensive Adults

As with blood pressure, age-related changes in muscle sympathetic nerve activity (MSNA) may differ nonlinearly between sexes. Data acquired from 398 male (age: 39±17; range: 18-78 years [mean±SD]) and 260 female (age: 37±18; range: 18-81 years) normotensive healthy nonmedicated volunteers were analyzed using linear regression models with resting MSNA burst frequency as the outcome and the predictors sex, age, MSNA, blood pressure, and body mass index modelled with natural cubic splines. Age and body mass index contributed 41% and 11%, respectively, of MSNA variance in females and 23% and 1% in males. Overall, changes in MSNA with age were sigmoidal. At age 20, mean MSNA of males and females were similar, then diverged significantly, reaching in women a nadir at age 30. After 30, MSNA increased nonlinearly in both sexes. Both MSNA discharge and blood pressure were lower in females until age 50 (17±9 versus 25±10 bursts·min-1; P\u3c1×10-19; 106±11/66±8 versus 116±7/68±9 mm Hg; P\u3c0.01) but converged thereafter (38±11 versus 35±12 bursts·min-1; P=0.17; 119±15/71±13 versus 120±13/72±9 mm Hg; P\u3e0.56). Compared with age 30, MSNA burst frequency at age 70 was 57% higher in males but 3-fold greater in females; corresponding increases in systolic blood pressure were 1 (95% CI, -4 to 5) and 12 (95% CI, 6-16) mm Hg. Except for concordance in females beyond age 40, there was no systematic change with age in any resting MSNA-blood pressure relationship. In normotensive adults, MSNA increases after age 30, with ascendance steeper in women