Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-γ co-activator-1 α (PGC1-α). Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.

/pdf/a-pgc1-a-dependent-myokine-that-drives-brown-fat-like-2kbx57f12b.pdf

A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis

How much does the microbiota influence the host's phenotype? Ridaura et al. ([1241214][1] ; see the Perspective by [ Walker and Parkhill ][2]) obtained uncultured fecal microbiota from twin pairs discordant for body mass and transplanted them into adult germ-free mice. It was discovered that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids. Moreover, obese-phenotype mice were invaded by members of the Bacteroidales from the lean mice, but, happily, the lean animals resisted invasion by the obese microbiota.

 [1]: http://www.sciencemag.org/content/341/6150/1241214.full
 [2]: /lookup/doi/10.1126/science.1243787

/pdf/gut-microbiota-from-twins-discordant-for-obesity-modulate-5aeltwsuvw.pdf

Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice

https://www.mergenmetz.nl/menn/wp-content/uploads/2012/07/Insirine-of-bewegen-artikel-in-Cell.pdf

Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human

Mitochondria: In Sickness and in Health

During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.

Muscles, exercise and obesity: skeletal muscle as a secretory organ

Replying to J. A. Timmons, K. Baar, P. K. Davidsen & P. J. Atherton , 10.1038/nature11364 (2012)

Boström et al. reply

The CLARITY method renders brains optically transparent to enable high-resolution imaging in the structurally intact brain. Anatomically annotating CLARITY brains is necessary for discovering which regions contain signals of interest. Manually annotating whole-brain, terabyte CLARITY images is difficult, time-consuming, subjective, and error-prone. Automatically registering CLARITY images to a pre-annotated brain atlas offers a solution, but is difficult for several reasons. Removal of the brain from the skull and subsequent storage and processing cause variable non-rigid deformations, thus compounding inter-subject anatomical variability. Additionally, the signal in CLARITY images arises from various biochemical contrast agents which only sparsely label brain structures. This sparse labeling challenges the most commonly used registration algorithms that need to match image histogram statistics to the more densely labeled histological brain atlases. The standard method is a multiscale Mutual Information B-spline algorithm that dynamically generates an average template as an intermediate registration target. We determined that this method performs poorly when registering CLARITY brains to the Allen Institute's Mouse Reference Atlas (ARA), because the image histogram statistics are poorly matched. Therefore, we developed a method (Mask-LDDMM) for registering CLARITY images, that automatically find the brain boundary and learns the optimal deformation between the brain and atlas masks. Using Mask-LDDMM without an average template provided better results than the standard approach when registering CLARITY brains to the ARA. The LDDMM pipelines developed here provide a fast automated way to anatomically annotate CLARITY images. Our code is available as open source software at this http URL.

Deformably Registering and Annotating Whole CLARITY Brains to an Atlas via Masked LDDMM

Nanog is a transcription factor identified by its ability to maintain the self-renewal of ES cells in the absence of leukemia inhibitory factor (LIF). Nanog protein contains an N-terminal domain (ND), a DNA-binding homeobox domain (HD) and a C-terminal domain (CD). We previously reported that the CD in Nanog is a transcriptional activation domain essential for the in vivo function of Nanog. Here we demonstrated that the ND in Nanog is also functionally important. Deletion of the ND reduces the transcriptional activity of Nanog on either artificial reporters or native Nanog promoters. This truncated Nanog is also less effective in regulating the endogenous Nanog target genes. Furthermore, the ND truncation disrupted the ability of Nanog to maintain ES cell self-renewal as well. We found that the ND is not required for the nuclear localization of Nanog. These results suggest that the regulation of endogenous pluripotent genes such as oct3/4 and rex-1 is required for the in vivo function of Nanog.

The N-terminal domain is a transcriptional activation domain required for Nanog to maintain ES cell self-renewal

Objective To evaluate the consistency between SUDOSCAN examinations and electromyography (EMG) results in patients with diabetes. Methods A total of 326 patients with diabetes (201 males and 125 females) who were hospitalized in the endocrinology ward of the Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine) from June 2020 to February 2021 were selected as participants. All the patients were tested using a SUDOSCAN conductance analyzer for electrical skin conductivities and EMG for nerve conduction. The differences and consistencies between the results of the two examinations were analyzed. McNemar’s test was used to analyze the differences between the results, and Cohen’s kappa test was utilized to test the consistencies. Results A total of 174 patients had abnormal SUDOSCAN results, and 152 patients had normal SUDOSCAN results. The EMG results of 299 patients were abnormal, and the EMG results of 27 patients were normal. The McNemar test result was P = 0.000, and the differences between the results of the SUDOSCAN and EMG examinations were statistically significant (P < 0.01). No significant consistency was found between the SUDOSCAN and EMG results, meaning that the consistency between the two examination results was not statistically significant (P = 0.868, P > 0.05). The difference between the results was statistically significant (P < 0.05), and the consistency was poor (kappa = 0.005). Conclusion Differences existed between the SUDOSCAN examination and EMG results, and the results of the two examination methods were inconsistent, indicating that SUDOSCAN examinations cannot replace EMG examinations for DSPN.

https://www.dovepress.com/getfile.php?fileID=85113

Consistency Analysis Between SUDOSCAN Examinations and Electromyography Results in Patients with Diabetes

The present disclosure provides methods of preparing a biological specimen for imaging analysis, comprising fixing and clearing the biological specimen and subsequently analyzing the cleared biological specimen using microscopy. Also included are methods of quantifying cells, for example, active populations of cells in response to a stimulant. The present disclosure also provides devices for practicing the described methods. A flow-assisted clearing device provides rapid clearing of hydrogel-embedded biological specimens without the need of specialized equipment such as electrophoresis or perfusion devices.

Li Ye

Papers

Boström et al. reply

Deformably Registering and Annotating Whole CLARITY Brains to an Atlas via Masked LDDMM

The N-terminal domain is a transcriptional activation domain required for Nanog to maintain ES cell self-renewal

Consistency Analysis Between SUDOSCAN Examinations and Electromyography Results in Patients with Diabetes

Method for imaging and analysis of a biological specimen