Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild‐type (WT) mice, leptin receptor‐deficient db/db mice, leptin‐deficient ob/ob mice, and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast‐lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast‐lined bone perimeter in ob/ob mice. In spite of normal osteoclast‐lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic‐like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. © 2013 American Society for Bone and Mineral Research

The incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with the incidence of obes

Brain MRI scans synthesized using generative adversarial networks can be used as inputs in an existing deep learning model, thus allowing for their application in case MRI data are missing. Background Missing MRI sequences represent an obstacle in the development and use of deep learning (DL) models that require multiple inputs. Purpose To determine if synthesizing brain MRI scans usi...

MicroRNAs (miRNAs) have emerged as regulators of a broad spectrum of neurodevelopmental processes, including brain morphogenesis, neuronal differentiation, and survival. While the role of miRNAs in establishing and maintaining the developing nervous system is widely appreciated, the developmental neurobehavioral role of miRNAs has yet to be defined. Here we show that transient disruption of brain morphogenesis by ethanol exposure results in behavioral hyperactivity in larval zebrafish challenged with changes in lighting conditions. Aberrations in swimming activity persist in juveniles that were developmentally exposed to ethanol. During early neurogenesis, multiple gene expression profiling studies revealed widespread changes in mRNA and miRNA abundance in ethanol‐exposed embryos. Consistent with a role for miRNAs in neurobehavioral development, target prediction analyses identified multiple miRNAs misexpressed in the ethanol‐exposed cohorts that were also predicted to target inversely expressed transcripts known to influence brain morphogenesis. In vivo knockdown of miR‐9/9∗ or miR‐153c persistently phenocopied the effect of ethanol on larval and juvenile swimming behavior. Structural analyses performed on adults showed that repression of miR‐153c during development impacts craniofacial skeletal development. Together, these data support an integral role for miRNAs in the establishment of vertebrate neurobehavioral and skeletal systems.—Tal, T. L., Franzosa, J. A., Tilton, S. C., Philbrick, K. A., Iwaniec, U. T., Turner, R. T., Waters, K. M., Tanguay, R. L. MicroRNAs control neurobehavioral development and function in zebrafish. FASEB J. 26, 1452‐1461 (2012). www.fasebj.org

Objective Epidemiological studies indicate that higher bone mass is associated with moderate alcohol consumption in postmenopausal women. However, the underlying cellular mechanisms responsible for the putative beneficial effects of alcohol on bone are unknown. Excessive bone turnover, combined with an imbalance whereby bone resorption exceeds bone formation, is the principal cause of postmenopausal bone loss. This study investigated the hypothesis that moderate alcohol intake attenuates bone turnover after menopause. Methods Bone mineral density was determined by dual-energy x-ray absorptiometry in 40 healthy postmenopausal women (mean ± SE age, 56.3 ± 0.5 y) who consumed alcohol at 19 ± 1 g/day. Serum levels of the bone formation marker osteocalcin and the resorption marker C-terminal telopeptide (CTx) were measured by immunoassay at baseline (day 0) and after alcohol withdrawal for 14 days. Participants then consumed alcohol and were assayed on the following morning. Results Bone mineral density at the trochanter and total hip were positively correlated to the level of alcohol consumption. Serum osteocalcin and CTx increased after abstinence (4.1 ± 1.6%, P = 0.01 and 5.8 ± 2.6%, P = 0.02 compared with baseline, respectively). Osteocalcin and CTx decreased after alcohol readministration, compared with the previous day (−3.4 ± 1.4%, P = 0.01 and −3.5 ± 2.1%, P = 0.05, respectively), to values that did not differ from baseline (P > 0.05). Conclusions Abstinence from alcohol results in increased markers of bone turnover, whereas resumption of alcohol reduces bone turnover markers. These results suggest a cellular mechanism for the increased bone density observed in postmenopausal moderate alcohol consumers. Specifically, the inhibitory effect of alcohol on bone turnover attenuates the detrimental skeletal consequences of excessive bone turnover associated with menopause.

Removing non-brain tissues such as the skull, scalp and face from head computed tomography (CT) images is an important field of study in brain image processing applications. It is a prerequisite step in numerous quantitative imaging analyses of neurological diseases as it improves the computational speed and accuracy of quantitative analyses and image coregistration. In this study, we present an accurate method based on fully convolutional neural networks (fCNN) to remove non-brain tissues from head CT images in a time-efficient manner. The method includes an encoding part which has sequential convolutional filters that produce activation maps of the input image in low dimensional space; and it has a decoding part consisting of convolutional filters that reconstruct the input image from the reduced representation. We trained the fCNN on 122 volumetric head CT images and tested on 22 unseen volumetric CT head images based on an expert’s manual brain segmentation masks. The performance of our method on the test set is: Dice Coefficient= 0.998±0.001 (mean ± standard deviation), recall=0.998±0.001, precision=0.998±0.001, and accuracy=0.9995±0.0001. Our method extracts complete volumetric brain from head CT images in 2s which is much faster than previous methods. To the best of our knowledge, this is the first study using fCNN to perform skull stripping from CT images. Our approach based on fCNN provides accurate extraction of brain tissue from head CT images in a time-efficient manner.