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Obesity has become an epidemic concern in modern society. The chronic obesity is associated with metabolic disorders, such as hyperglycemia, hyperlipidemia, fatty liver, and cadiovascular disease, which cause high risk for mortality. The novel potential strategy to overcome obesity is to "burn out" the extra fat via "browning" of the white adipose tissues. The phytochemical resveratrol (Res) has attracted substantial attention due to its powerful amelioratory effects in metabolic diseases. However, how Res regulates the browning of adipose tissues remains largely elusive. Our data show that the NAD+ -dependent deacetylase silent information regulator 1 (Sirt1) mediates Res-induced browning and fat reduction of adipocytes, as well as other Res-improved metabolic phenotypes including hyperglycemina and hyperlipidemia in mice. Interestingly, we found that the major metabolites of Res in vivo (Res-3-O-glucuronide, Res-4'-O-glucuronide, and Res-3-O-sulfate) were much less potent in promoting browning gene expressions and reducing fat content in comparison to Res itself in mouse and human adipocytes in vitro, suggesting the importance and necessarity to enhance the bioavailability of Res in vivo in consideration of therapeutic application. Taken together, our findings clarify the beneficial effects of Res on excess fat utilization via promotion of browning in a Sirt1-dependent manner, suggesting the potential therapeutic application of Res in the treatment of obesity and related metabolic disorders. © 2020 Federation of American Societies for Experimental Biology.BACKGROUND Quantitative bacterial culture and susceptibility testing is the gold standard diagnostic for determining bacterial urinary tract infection. Transport of samples to external reference laboratories is common practice in veterinary medicine. OBJECTIVE To compare bacterial culture and susceptibility results from clinical urine samples when streak plate inoculation is performed immediately after sample collection versus after transport to a reference laboratory. To determine the clinical implications of discrepant culture results. ANIMALS One hundred and ninety-four canine and 45 feline urine samples that were submitted for urinalysis and urine culture and susceptibility testing. METHODS This was a prospective, cross-sectional study. Streak plate inoculations were performed on urine samples immediately after collection and also after transport to a reference laboratory. Samples were stored in plain sterile tubes and refrigerated up to 24 hours before transport. Culture results were compared, and discordant results were evaluated for clinical relevance. Signalment, comorbidities, lower urinary tract signs, and antimicrobial history were recorded. RESULTS Kappa coefficient for agreement between plating methods was 0.884. Twenty-two (71%) of 31 discrepant results were determined to have no clinical impact. Though 35% of clean midstream samples had discrepant culture results, only 8% of these had clinical impact. Conversely, 8.6% from cystocentesis were discrepant, but 41% of these had clinical impact. CONCLUSIONS AND CLINICAL IMPORTANCE Provided urine samples are stored and transported appropriately, the immediate preplating of urine for culture and susceptibility testing is unnecessary in the majority of cases. Despite more discrepancies in plating methods for midstream samples, the minority were of clinical importance. SBE-β-CD © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.Vitiligo, a common skin disorder, is characterized by the loss of functional melanocytes resulting in the depigmentation of skin. Previous studies have demonstrated molecular and architectural alterations in the epidermal keratinocytes upon loss of melanocytes. The physiological implications of these "altered" keratinocytes are yet not known. We investigated the wound healing efficiency of lesional vs nonlesional skin in 12 subjects with stable nonsegmental vitiligo using histological and ultrastructural evaluation of partial-thickness wounds. The wounds were examined 12 days postinjury, coinciding with the reepithelialization phase of healing marked primarily by keratinocyte migration and proliferation. This study demonstrated a significant difference in the reepithelialization potential between the lesional and nonlesional skin. While all 12 nonlesional wounds demonstrated considerable neoepidermis formation on the 12th day post wound, only four of the corresponding lesional samples showed comparable reepithelialization; the rest remaining in the inflammatory phase. Ultrastructural studies using transmission electron microscopy as well as immunohistochemical staining revealed a reduced number of desmosomes, shorter keratin tonofilaments and an increase in myofibroblast population in the dermis of lesional reepithelialized tissue compared to the nonlesional reepithelialized samples. This study implicates gross functional perturbations in the lesional skin during physiological wound healing in vitiligo, suggesting that the breakdown of keratinocyte-melanocyte network results in delayed wound repair kinetics in the lesional skin when compared to patient-matched nonlesional skin. © 2020 by the Wound Healing Society.P2X7 is an ATP-gated membrane ion channel that is expressed by multiple cell types. Brief exposure to ATP induces the opening of a nonselective cation channel; while repeated or prolonged exposure induces formation of a transmembrane pore. This process may be partially regulated by alternative splicing of full-length P2RX7A pre-mRNA, producing isoforms that delete or retain functional domains. Here, we report cloning and expression of a novel P2RX7 splice variant, P2RX7L, that is, characterized by skipping of exons 7 and 8. In HEK 293 cells, expression of P2RX7L produces a protein isoform, P2X7L, that forms a heteromer with P2X7A. A haplotype defined by six single nucleotide polymorphisms (SNPs) (rs208307, rs208306, rs36144485, rs208308, rs208309, and rs373655596) promotes allele-specific alternative splicing, increasing mRNA levels of P2RX7L and another isoform, P2RX7E, which in addition has a truncated C-terminus. Skipping of exons 7 and 8 is predicted to delete critical amino acids in the ATP-binding site.

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