Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5 (FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone–tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal (IP) administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.

The RAD54 and RAD51 genes are involved in genetic recombination and double-strand break repair in the yeast Saccharomyces cerevisiae. The Rad51 protein is thought to be a yeast analogue of the Eschericia coli recA gene product and catalyzes strand exchange between homologous single-and double-stranded DNAs in vitro. RAD54 exhibits homologies to several known ATPases and is a member of the SWI2/MOT1 family. We show here that the Rad54 protein interacts with the Rad51 protein in vivo and in vitro and that the NH 2 -terminal 115 residues of the Rad54 protein are necessary for this interaction. Combined with previously reported results, these data imply that the Rad54 protein is part of a multiprotein yeast recombination complex.The RAD52 epistasis group includes genes involved in homologous recombination in the yeast Saccharomyces cerevisiae. Mutations in these genes result in phenotypes that include an inability to repair double-stranded breaks, as well as defects in mitotic and meiotic recombination (1-4). The Rad51, Rad55, and Rad57 proteins show considerable homology to the Eschericia coli RecA protein, the paradigmatic prokaryotic strand transferase. Indeed, Rad51 protein has been shown to mediate strand exchange in vitro between homologous single-and double-stranded DNAs in the presence of replication protein A (RPA), 1 the yeast single-stranded DNA-binding protein (5). A number of results suggest that the Rad51 protein functions as part of a multiprotein complex in vivo. For example, the Rad51 and Rad52 proteins have been shown to bind one another both in vivo (6) and in vitro (7), and there is genetic evidence that Rfa1 is associated with the putative recombination complex (8, 9). Furthermore, experiments from the Berg (Stanford University School of Medicine) and Symington (Columbia College of Physicians and Surgeons) laboratories demonstrated that Rad51 protein binds to the Rad55 protein in vivo, which in turn interacts with Rad57 protein (10,11).In this report, we present both in vivo and in vitro evidence for a direct association between the Rad51 protein and the RAD54 gene product, another member of the RAD52 epistasis group (12, 13). The discovery of a Rad54-Rad51 protein interaction provides further support for the existence of a "protein machine" for mitotic recombination in yeast and raises the possibility that the Rad54 protein could play a direct role in strand exchange. EXPERIMENTAL PROCEDURESYeast Strains-The strain used for the two-hybrid experiments was CB14.1-9a (MAT␣ ade2 ura3 URA3::GAL1-lacZ his3 leu2 gal4Dgal80D trp1 lys2 LYS2::GAL1-HIS3). The wild-type strain employed for expression of the epitope-tagged proteins was W303-1A (MAT␣ ade2-1 can1-100 his3-11,15 leu2-3, 112 trp1-1 ura3-1). His6Rad51 protein was expressed in U687, a rad51⌬ mutant (MAT␣ ade2-1 can 1-100 his3- 11,15 leu2-3, 112 trp1-1 ura3-1 rad51::LEU2). U671 is a rad54⌬ mutant (MAT␣ ade2-1 can1-100, his3-11,15 leu2-3, 112 trp1-1 ura3-1 rad54::LEU2).Plasmids-The parent vectors for making GAL4 activation domain (AD) and DNA-bindi...

Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C) expressions but decreased hypothalamic cannabinoid receptor-1 expression. Treatment of immortalized mouse neurons with APN demonstrated that APN-mediated effects on TPH2, CART, and Htr2C expression levels were abolished by downregulating adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL)-1 expression. Pharmacological increase in sympathetic activity stimulated adipogenic differentiation of bone marrow stromal cells (BMSC) and reversed APN-induced expression of the lysine-specific demethylases involved in regulating their commitment to the osteoblastic lineage. In conclusion, we found that APN regulates bone metabolism via central and peripheral mechanisms to decrease sympathetic tone, inhibit osteoclastic differentiation, and promote osteoblastic commitment of BMSC.

Naturalization (the establishment of a self-sustaining population for at least a decade) is a fundamental precondition for plant invasion and so compiling a complete inventory of naturalized alien species is necessary for predicting and hence preventing such invasion. However, nationwide information on naturalized plants in China is still lacking. We compiled a nationwide list of the naturalized plant species of China, based on various literature reports. The list comprised a total of 861 naturalized plant species belonging to 110 families and 465 genera. The three most dominant families were Compositae, Poaceae, and Leguminosae, accounting for 16, 13 and 12% of naturalized plants, respectively. Among genera, Euphorbia and Solanum had the most naturalized species, followed by Ipomoea, Amaranthus, Oenothera, and Trifolium. Over half of all aliens were of American origin (52%), followed by those with European (14%) and Asian (13%) origins. Annuals and perennial herbs were prevalent among naturalized species; comparison to other studies suggests however that the invasive potential is higher among plants with longer life cycles than those of annuals. The taxonomic pattern of plant naturalization in China is similar to patterns worldwide. However, the low proportion of naturalized plants within the Chinese flora overall suggests that the potential for plant invasions in China may be high. Therefore, greater attention should be focused on naturalization of alien plants in China, especially concerning species of dominant families or genera, and those with a perennial life cycle.

Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occurring more than 2 years after HCT for malignant disease. Graft versus tumor (GVT) is a major component of the overall beneficial effects of allogeneic HCT in the treatment of hematological malignancies. Better understanding of GVHD pathogenesis is important to identify new therapeutic targets for GVHD prevention and therapy. Emerging data suggest opposing roles for different T cell subsets, e.g., IFN-γ producing CD4+ and CD8+ T cells (Th1 and Tc1), IL-4 producing T cells (Th2 and Tc2), IL-17 producing T cells (Th17 and Tc17), IL-9 producing T cells (Th9 and Tc9), IL-22 producing T cells (Th22), T follicular helper cells (Tfh), regulatory T-cells (Treg) and tissue resident memory T cells (Trm) in GVHD and GVT etiology. In this review, we first summarize the general description of the cytokine signals that promote the differentiation of T cell subsets and the roles of these T cell subsets in the pathogenesis of GVHD. Next, we extensively explore preclinical findings of T cell subsets in both GVHD/GVT animal models and humans. Finally, we address recent findings about the roles of T-cell subsets in clinical GVHD and current strategies to modulate T-cell differentiation for treating and preventing GVHD in patients. Further exploring and outlining the immune biology of T-cell differentiation in GVHD that will provide more therapeutic options for maintaining success of allo-HCT.

MWA, by the simultaneous application of double antennae, can generate a larger ablation zone, in vivo, compared with multipolar RFA.

Chewing-side preference (CSP) may be associated with temporomandibular disorders. However, little information exists regarding whether CSP will lead to osseous changes of temporomandibular joint (TMJ) in asymptomatic participants. The aim of this study was to investigate the relationship between osseous morphology of TMJ in asymptomatic participants with CSP and without CSP. Of the 121 healthy dentate participants, 35 participants with left CSP, 38 with right CSP and other 48 without CSP were scanned by cone-beam computed tomography. The dimensions of the reconstructed images of opposing TMJs were compared. Statistical analyses were performed using spss 16.0 software. The results showed that there were no significant differences between the dimensions of bilateral structures of the TMJ (P1 > 0·05) in participants without CSP. However, the posterior-superior, posterior and lateral joint space of the preferred side were smaller than that of the unpreferred side in participants with CSP (P2 < 0·01) and bilateral TMJ in participants without CSP (P3 < 0·01). In addition, width of condylar neck of the unpreferred side both in sagittal and perpendicular to the long axis of condyle views was greater than that of the preferred side in participants with CSP (P2 < 0·01) and bilateral TMJ of participants without CSP (P4 < 0·01). Also, the inclination of articular eminence of the preferred side in view perpendicular to the long axis of condyle was less than that of the unpreferred side (P2 < 0·05). These findings suggest CSP affects osseous morphology of TMJ in asymptomatic participants.

Gap arthroplasty (GA) and interpositional arthroplasty (IA) are widely used for the treatment of temporomandibular joint ankylosis (TMJA). However, controversy remains as to whether IA is superior to GA. PubMed, EMBASE, the Cochrane Library, the Web of science and the China National Knowledge Infrastructure were searched for literature regarding these procedures (published from 1946 to July 28, 2014). A study was included in this analysis if it was: (1) a randomized controlled trial or non-randomized observational cohort study; (2) comparing the clinical outcomes between GA and IA with respect to the maximal incisal opening (MIO) and reankylosis; (3) with a follow-up period of at least 12 months. The methodological quality of the included studies was evaluated according to the Newcastle-Ottawa Scale Eight non-randomized observational cohort studies with 272 patients were included. All the statistical analyses were performed using the RevMan 5.3 and Stat 12. The pooled analysis showed no significant difference in the incidence of reankylosis between the IA group (13/120) and the GA group (29/163) (RR= 0.67, 95% CI=0.38 to 1.16; Z=1.43, p=0.15). The IA group showed a significantly larger MIO than the GA group (MD=1.96, 95% CI=0.21 to 3.72, Z=2.19, p=0.03, I2=0%). In conclusion, patients with TMJA could benefit more from IA than GA, with a larger MIO and a similar incidence of reankylosis. IA shows to be an adequate option in the treatment of TMJA based on the results of maximal incisal opening.