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Age-related sarcopenia constitutes an important health problem associated with adverse outcomes. Sarcopenia is closely associated with fat infiltration in muscle, which is attributable to interstitial mesenchymal progenitors. Mesenchymal progenitors are nonmyogenic in nature but are required for homeostatic muscle maintenance. However, the underlying mechanism of mesenchymal progenitor-dependent muscle maintenance is not clear, nor is the precise role of mesenchymal progenitors in sarcopenia. Here, we show that mice genetically engineered to specifically deplete mesenchymal progenitors exhibited phenotypes markedly similar to sarcopenia, including muscle weakness, myofiber atrophy, alterations of fiber types, and denervation at neuromuscular junctions. Through searching for genes responsible for mesenchymal progenitor-dependent muscle maintenance, we found that Bmp3b is specifically expressed in mesenchymal progenitors, whereas its expression level is significantly decreased during aging or adipogenic differentiation. The functional importance of BMP3B in maintaining myofiber mass as well as muscle-nerve interaction was demonstrated using knockout mice and cultured cells treated with BMP3B. Furthermore, the administration of recombinant BMP3B in aged mice reversed their sarcopenic phenotypes. These results reveal previously unrecognized mechanisms by which the mesenchymal progenitors ensure muscle integrity and suggest that age-related changes in mesenchymal progenitors have a considerable impact on the development of sarcopenia., Introduction Sarcopenia, the loss of skeletal muscle mass and strength, constitutes an important health problem associated with adverse outcomes such as disability, poor quality of life, and even death. A [...]

Black spot needle blight is a serious conifer disease of Pinus sylvestris var. mongolica occurring in Northeast China, which is usually caused by the plant pathogenic fungus Pestalotiopsis neglecta. From the diseased pine needles collected in Honghuaerji, the P. neglecta strain YJ-3 was isolated and identified as the phytopathogen, and its culture characteristics were studied. Then, we generated a highly contiguous 48.36-Mbp genome assembly (N50 = 6.62 Mbp) of the P. neglecta strain YJ-3 by combining the PacBio RS II Single Molecule Real Time (SMRT) and Illumina HiSeq X Ten sequencing platforms. The results showed that a total of 13,667 protein-coding genes were predicted and annotated using multiple bioinformatics databases. The genome assembly and annotation resource reported here will be useful for the study of fungal infection mechanisms and pathogen–host interaction. [ABSTRACT FROM AUTHOR]

Sarcopenia is an important health problem associated with adverse outcomes. Although the etiology of sarcopenia remains poorly understood, factors apart from muscle fibers, including humoral factors, might be involved. Here, we used cytokine antibody arrays to identify humoral factors involved in sarcopenia and found a significant increase in levels of milk fat globule epidermal growth factor 8 (MFG‐E8) in skeletal muscle of aged mice, compared with young mice. We found that the increase in MFG‐E8 protein at arterial walls and neuromuscular junctions (NMJs) in muscles of aged mice. High levels of MFG‐E8 at NMJs and an age‐related increase in arterial MFG‐E8 have also been identified in human skeletal muscle. In NMJs, MFG‐E8 is localized on the surface of terminal Schwann cells, which are important accessory cells for the maintenance of NMJs. We found that increased MFG‐E8 at NMJs precedes age‐related denervation and is more prominent in sarcopenia‐susceptible fast‐twitch than in sarcopenia‐resistant slow‐twitch muscle. Comparison between fast and slow muscles further revealed that arterial MFG‐E8 can be uncoupled from sarcopenic phenotype. A genetic deficiency in MFG‐E8 attenuated age‐related denervation of NMJs and muscle weakness, providing evidence of a pathogenic role of increased MFG‐E8. Thus, our study revealed a mechanism by which increased MFG‐E8 at NMJs leads to age‐related NMJ degeneration and suggests that targeting MFG‐E8 could be a promising therapeutic approach to prevent sarcopenia. [ABSTRACT FROM AUTHOR]

WRKY proteins play important regulatory roles in plant developmental processes such as senescence, trichome initiation and embryo morphogenesis. In strawberry, only FaWRKY1 (Fragaria × ananassa) has been characterized, leaving numerous WRKY genes to be identified and their function characterized. The publication of the draft genome sequence of the strawberry genome allowed us to conduct a genome-wide search for WRKY proteins in Fragaria vesca, and to compare the identified proteins with their homologs in model plants. Fifty-nine FvWRKY genes were identified and annotated from the F. vesca genome. Detailed analysis, including gene classification, annotation, phylogenetic evaluation, conserved motif determination and expression profiling, based on RNA-seq data, were performed on all members of the family. Additionally, the expression patterns of the WRKY genes in different fruit developmental stages were further investigated using qRT-PCR, to provide a foundation for further comparative genomics and functional studies of this important class of transcriptional regulators in strawberry. [ABSTRACT FROM AUTHOR]

Two new phthalate derivatives, N1-(2-aminoethyl)-N2-isopentylphthalamide (1) and N1-isobuty-N2-tridecylphthalamide (2), were isolated from the marine sponge Haliclona sp. The structures of the new isolates were elucidated on the basis of extensive spectroscopic analysis and by comparison of the data with those of related secondary metabolites. [ABSTRACT FROM AUTHOR]

We previously reported 2 osteoporosis-susceptibility genes-formiminotransferase N-terminal sub-domain containing gene (FONG) and thrombospondin, type 1, domain-containing 7A (THSD7A)-in which we identified two common single-nucleotide polymorphisms, rs7605378 (FONG) and rs12673692 (THSD7A). The former was associated with a predisposition to osteoporosis and the latter with bone mineral density. To further elucidate the importance of these polymorphisms in the pathogenesis of osteoporosis, we examined their association with the incidence of vertebral fracture. DNA extracted from the renal cortex of 2427 consecutive Japanese autopsies (1331 men, mean age: 79 years; 1096 women, mean age: 82 years) were examined in this study. The presence or absence of vertebral fracture during each subject's lifetime was determined by a thorough examination of the clinical records, as well as autopsy reports. After adjustments for sex and age at autopsy, logistic regression analysis revealed that homozygotes for the risk alleles of rs7605378 (A-allele) or rs12673629 (A-allele) possess an increased risk of vertebral fracture. The subjects simultaneously homozygous for both the risk alleles of rs7605378 (AA genotype) and rs12673629 (AA genotype) showed significantly higher risk of vertebral fracture (odds ratio 2.401, 95% confidence interval 1.305-4.416, P=0.0048) than those who had at least one non-risk allele of either rs7605378 (AC/CC genotypes) or rs12673629 (AG/GG genotypes). The results suggest that Japanese subjects homozygous for the risk alleles of rs7605378 and rs12673629 have a higher risk of vertebral fracture. [ABSTRACT FROM AUTHOR]

Abstract: Gut hormone gastric inhibitory polypeptide (GIP) stimulates insulin secretion from pancreatic β-cells upon ingestion of nutrients. Inhibition of GIP signaling prevents the onset of obesity and consequent insulin resistance induced by high-fat diet. In this study, we investigated the role of GIP in accumulation of triglycerides into adipocytes and in fat oxidation peripherally using insulin receptor substrate (IRS)-1-deficient mice and revealed that IRS-1 −/− GIPR −/− mice exhibited both reduced adiposity and ameliorated insulin resistance. Furthermore, increased gene expression of CD36 and UCP2 in liver, and increased expression and enzyme activity of 3-hydroxyacyl-CoA dehydrogenase in skeletal muscle of IRS-1 −/− GIPR −/− mice might contribute to the lower respiratory quotient and the higher fat oxidation in light phase. These results suggest that GIP plays a crucial role in switching from fat oxidation to fat accumulation under the diminished insulin action as a potential target for secondary prevention of insulin resistance. [Copyright &y& Elsevier]

Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. In contrast, mice lacking the GIP receptor (Gipr-/-) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. Moreover, double-homozygous mice (Gipr-/-, Lepob/Lepob) generated by crossbreeding Gipr-/- and obese ob/ob (Lepob/Lepob) mice gained less weight and had lower adiposity than Lepob/Lepob mice. The Gipr-/- mice had a lower respiratory quotient and used fat as the preferred energy substrate, and were thus resistant to obesity. Therefore, GIP directly links overnutrition to obesity and it is a potential target for anti-obesity drugs. [ABSTRACT FROM AUTHOR]

The article presents a case study of the clinical characteristics of osteoporosis in patients with Werner syndrome (WS), a rare autosomal recessive genetic disorder. It discusses the diagnosis based on the presence of signs and symptoms. It suggests that defective osteoblast differentiation resulting from telomere dysfunction is a significant cellular mechanism in the early onset of osteoporosis in WS patients.

Many studies have shown that multidrug and toxic compound extrusion (MATE) is a new secondary transporter family that plays a key role in secondary metabolite transport, the transport of plant hormones and disease resistance in plants. However, detailed information on this family in Gleditsia sinensis has not yet been reported. In the present study, a total of 45 GsMATE protein members were identified and analysed in detail, including with gene classification, phylogenetic evaluation and conserved motif determination. Phylogenetic analysis showed that GsMATE proteins were divided into six subfamilies. Additionally, in order to understand these members' regulatory roles in growth and development in G. sinensis , the GsMATEs expression profiles in different tissues and different developmental stages of thorn were examined in transcriptome data. The results of this study demonstrated that the expression of all MATE genes varies in roots, stems and leaves. Notably, the expression levels of GsMATE26 , GsMATE32 and GsMATE43 differ most in the early stages of thorn development, peaking at higher levels than in later stages. Our results provide a foundation for further functional characterisation of this important class of transporter family in G. sinensis .

Transcription factors play vital roles in the developmental processes of plants. The SQUAMOSA promoter binding protein (SBP) genes encode a family of plant-specific transcription factors and plays many crucial roles in plant development. In this study, 16 SBP-box gene family members were identified in Ziziphus jujuba Mill. Dongzao (Dongzao), which were distributed over 8 chromosomes. They were classified into seven groups according to their phylogenetic relationships with other SBP-box gene families. Within each group, genes shared similar exon-intron structures and motif locations. The number of exons varied among the groups. We identified 12 homologous gene pairs between Dongzao and Arabidopsis . Expression profiling revealed that ZjSBP02 and ZjSBP14 expressed highly in mature fruits, ZjSBP01 expressed higher in mature leaves than other tissues and the expression level of ZjSBP12 was much higher in the flowers. The transcriptome analysis indicated that ZjSBPs had different expression patterns in various tissues. This study represents the first systematic analysis of the SBP-box gene family in Z. jujuba . The data presented here provides a foundation for understanding the crucial roles of ZjSBP genes in plant growth and development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Mitogen-activated protein kinase (MAPK) cascades are highly conserved signaling modules in eukaryotes, including yeasts, plants and animals. MAPK cascades are responsible for protein phosphorylation during signal transduction events, and typically consist of three protein kinases: MAPK, MAPK kinase, and MAPK kinase kinase. In this current study, we identified a total of 12 FvMAPK , 7 FvMAPKK , 73 FvMAPKKK , and one FvMAPKKKK genes in the recently published Fragaria vesca genome sequence. This work reported the classification, annotation and phylogenetic evaluation of these genes and an assessment of conserved motifs and the expression profiling of members of the gene family were also analyzed here. The expression profiles of the MAPK and MAPKK genes in different organs and fruit developmental stages were further investigated using quantitative real-time reverse transcription PCR (qRT-PCR). Finally, the MAPK and MAPKK expression patterns in response to hormone and abiotic stresses (salt, drought, and high and low temperature) were investigated in fruit and leaves of F. vesca . The results provide a platform for further characterization of the physiological and biochemical functions of MAPK cascades in strawberry., Competing Interests: The authors declare no conflict of interest.

A genetic risk score (GRS) was developed for predicting fracture risk based on the prevalence of vertebral fractures in 441 Japanese females with osteoporosis. A total of 979 (858 nonsynonymous and 121 silent) single-nucleotide polymorphisms (SNPs) located in 74 osteoporosis-susceptibility genes were genotyped and evaluated for their association with fracture prevalence. Four SNPs (protein kinase domain containing, cytoplasmic [ PKDCC ; rs4952590], CDK5-regulatory subunit-associated protein 1-like 1 [ CDKAL1 ; rs4712556], wingless-type MMTV-integration site family member 16 [ WNT16 ; rs2707466], and G-patch domain-containing gene 1 [ GPATCH1 ; rs10416265]) showed a significant association ( p  < 0.05) with the fracture, in which the minor allele of the former two SNPs was the protective allele and that of the latter two SNPs was the risk allele. Applying a dominant-genetic model, we allotted - 1 point each to the protective-allele carriers and 1 point each to the risk-allele carriers, and GRS values were calculated as the sum of the points. The receiver-operating characteristic curves showed that GRS adequately predicted vertebral fracture. For the model predicted by the GRS with and without the effect of age, areas under the curves were 0.788 (95% confidence interval [CI]: 0.736-0.840) and 0.667 (95% CI: 0.599-0.735), respectively. Multiple logistic regression analysis revealed that the odds ratio for the association between fracture prevalence and GRS was 3.27 (95% CI: 1.36-7.87, p  = 0.008) for scores of - 1 to 0 ( n  = 303) and 12.12 (95% CI: 4.19-35.07, p  < 0.001) for scores of 1 to 2 ( n  = 35) relative to a score of - 2 ( n  = 103). The GRS based on the four SNPs could help identify at-risk individuals and enable implementation of preventive measures for vertebral fracture.

Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role in the development of heart failure, no direct evidence has been documented so far. In order to investigate the pathological significance of oxidative stress in the heart, we generated heart/muscle-specific manganese superoxide dismutase-deficient mice. The mutant mice developed progressive congestive heart failure with specific molecular defects in mitochondrial respiration. In this paper, we showed for the first time that the oxidative stress caused specific morphological changes of mitochondria, excess formation of superoxide (O(2)(*)(-)), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility. Accordingly, administration of a superoxide dismutase mimetic significantly ameliorated the symptoms. These results implied that O(2)(*)(-) generated in mitochondria played a pivotal role in the development and progression of heart failure. We here present a bona fide model for human cardiac failure with oxidative stress valuable for therapeutic interventions.