Substantial evidence indicates that amino acid conjugates of indole-3-acetic acid (IAA) function in auxin homeostasis, yet the plant enzymes involved in their biosynthesis have not been identified. ...We tested whether several Arabidopsis thaliana enzymes that are related to the auxin-induced soybean (Glycine max) GH3 gene product synthesize IAA-amino acid conjugates. In vitro reactions with six recombinant GH3 enzymes produced IAA conjugates with several amino acids, based on thin layer chromatography. The identity of the Ala, Asp, Phe, and Trp conjugates was verified by gas chromatographymass spectrometry. Insertional mutations in GH3.1, GH3.2, GH3.5, and GH3.17 resulted in modestly increased sensitivity to IAA in seedling root. Overexpression of GH3.6 in the activation-tagged mutant dfl1-D did not significantly alter IAA level but resulted in 3.2- and 4.5-fold more IAA-Asp than in wild-type seedlings and mature leaves, respectively. In addition to IAA, dfl1-D was less sensitive to indole-3-butyric acid and naphthaleneacetic acid, consistent with the fact that GH3.6 was active on each of these auxins. By contrast, GH3.6 and the other five enzymes tested were inactive on halogenated auxins, and dfl1-D was not resistant to these. This evidence establishes that several GH3 genes encode IAA-amido synthetases, which help to maintain auxin homeostasis by conjugating excess IAA to amino acids.
Glycobiology is the comprehensive biological investigation of carbohydrates. The study of the role and function of complex carbohydrates often requires the attachment of carbohydrates to surfaces, ...their tagging with fluorophores, or their conversion into natural or non‐natural glycoconjugates, such as glycopeptides or glycolipids. Glycobiology and its “omics”, glycomics, require easy and robust chemical methods for the construction of these glycoconjugates. This review gives an overview of the rapidly expanding field of chemical reactions that selectively convert unprotected carbohydrates into glycoconjugates through the anomeric position. The discussion is divided in terms of the anomeric bond type of the newly formed glycoconjugates, including O‐, N‐, S‐, and C‐glycosides.
Let's make it easier: Glycoconjugates are fundamental in chemical biology and medicinal chemistry for investigation of glycan–protein interactions, as drugs, for glyco‐engineering of biopharmaceutical proteins, and for development of new diagnostic tools, among other roles. This review provides an overview of available methods for direct and protecting‐group‐free preparation of glycoconjugates from native carbohydrate ligands.
This study examined to what extent family policies differently affect poverty among single-parent households and two-parent households. We distinguished between reconciliation policies (tested with ...parental leave and the proportion of unpaid leave) and financial support policies (tested with family allowances). We used data from the Luxembourg Income Study Database, covering 519,825 households in 18 OECD countries from 1978 to 2008, combined with data from the Comparative Family Policy Database. Single parents face higher poverty risks than coupled parents, and single mothers more so than single fathers. We found that employment reduces poverty, particularly for parents in professional occupations and for coupled parents who are dual earners. Longer parental leave, a smaller proportion of unpaid leave, and higher amounts of family allowances were associated with lower poverty among all households with children. Parental leave more effectively facilitated the employment of single mothers, thereby reducing their poverty more than among couples and single fathers. We found some evidence that family allowances reduced poverty most strongly among single fathers. An income decomposition showed that family allowances reduce poverty among two-parent households with up to 3 percentage points, and among single-parent households (mothers and fathers) up to 13 percentage points.
Halogenated natural products (MHC-1, TriBHD, TetraBHD, MeO-PBDEs, Q1, and related PMBPs) and halogenated flame retardants (PBDEs, HBB, Dec 602, Dec 603, and DP) in blubber and brain are reported from ...five Alboran Sea delphinids (Spain). Both HNPs and HFRs were detected in brain, implying that they are able to surpass the blood-brain barrier and reach the brain, which represents a new finding for some compounds, such as Q1 and PMBPs, MHC-1, TriBHD, TetraBHD, or Dec 603. Moreover, some compounds (TetraBHD, BDE-153, or HBB) presented higher levels in brain than in blubber. This study evidence the high concentrations of HNPs in the marine environment, especially in top predators. It shows the importance of further monitoring these natural compounds and evaluating their potential toxicity, when most studies focus on anthropogenic compounds only. While no bioaccumulation was found for ∑HNPs, ∑HFRs increased significantly with body size for both common and striped dolphins. Studies evaluating BBB permeation mechanisms of these compounds together with their potential neurotoxic effects in dolphins are recommended.
Methylation patterns established and maintained at CpG sites may be altered by single nucleotide polymorphisms (SNPs) within these sites and may affect the regulation of nearby genes. Our aims were ...to: 1) identify and generate a database of SNPs potentially subject to epigenetic control by DNA methylation via their involvement in creating, removing or displacing CpG sites (meSNPs), and; 2) investigate the association of these meSNPs with CpG islands (CGIs), and with methylation profiles of DNA extracted from tissues from cattle with divergent feed efficiencies detected using MIRA-Seq. Using the variant annotation for 56,969,697 SNPs identified in Run5 of the 1000 Bull Genomes Project and the UMD3.1.1 bovine reference genome sequence assembly, we identified and classified 12,836,763 meSNPs according to the nature of variation created at CpGs. The majority of the meSNPs were located in intergenic regions (68%) or introns (26.3%). We found an enrichment (p<0.01) of meSNPs located in CGIs relative to the genome as a whole, and also in differentially methylated sequences in tissues from animals divergent for feed efficiency. Seven meSNPs, located in differentially methylated regions, were fixed for methylation site creating (MSC) or destroying (MSD) alleles in the differentially methylated genomic sequences of animals differing in feed efficiency. These meSNPs may be mechanistically responsible for creating or deleting methylation targets responsible for the differential expression of genes underlying differences in feed efficiency. Our methyl SNP database (dbmeSNP) is useful for identifying potentially functional "epigenetic polymorphisms" underlying variation in bovine phenotypes.
Skeletal muscles undergo robust regeneration upon injury, and infiltrating immune cells play a major role in not only clearing damaged tissues but also regulating the myogenic process through ...secreted cytokines. Chemokine C‐C motif ligand 8 (Ccl8), along with Ccl2 and Ccl7, has been reported to mediate inflammatory responses to suppress muscle regeneration. Ccl8 is also expressed by muscle cells, but a role of the muscle cell‐derived Ccl8 in myogenesis has not been reported. In this study, we found that knockdown of Ccl8, but not Ccl2 or Ccl7, led to increased differentiation of C2C12 myoblasts. Analysis of existing single‐cell transcriptomic datasets revealed that both immune cells and muscle stem cells (MuSCs) in regenerating muscles express Ccl8, with the expression by MuSCs at a much lower level, and that the temporal patterns of Ccl8 expression were different in MuSCs and macrophages. To probe a function of muscle cell‐derived Ccl8 in vivo, we utilized a mouse system in which Cas9 was expressed in Pax7+ myogenic progenitor cells (MPCs) and Ccl8 gene editing was induced by AAV9‐delivered sgRNA. Depletion of Ccl8 in Pax7+ MPCs resulted in accelerated muscle regeneration after barium chloride‐induced injury in both young and middle‐aged mice, and intramuscular administration of a recombinant Ccl8 reversed the phenotype. Accelerated regeneration was also observed when Ccl8 was depleted in Myf5+ or MyoD+ MPCs by similar approaches. Our results suggest that muscle cell‐derived Ccl8 plays a unique role in regulating the initiation of myogenic differentiation during injury‐induced muscle regeneration.
Immune cells infiltrating injured skeletal muscles produce the chemokine Ccl8, which suppresses muscle regeneration. Muscle stem cells (or myogenic progenitor cells) also express Ccl8. The results of our in vitro and in vivo studies suggest that muscle cell‐derived Ccl8 has a negative role in muscle regeneration. Muscle stem cells and immune cells express vastly different levels of Ccl8 with distinct temporal patterns of expression during regeneration, suggesting that muscle cell‐derived Ccl8 may have a unique role in the regulation of regeneration.
Summary
Several observational studies have assessed the association between psoriasis, psoriatic arthritis (PsA) and type 2 diabetes mellitus, with inconclusive results. We set out to investigate the ...association between psoriasis, PsA and type 2 diabetes mellitus. Observational studies assessing the relationship between psoriasis or PsA and type 2 diabetes mellitus up to December 2012 were identified by electronic and hand searches in Medline, Embase, PubMed, the Cochrane Database of Systematic Reviews and Google Scholar. For each study we collected the first author's last name, publication year, country of origin, study design, characteristics of participants (sample size, age and sex), the variables incorporated into the multivariable analyses, and the odds ratios (ORs) of psoriasis associated with diabetes along with the corresponding 95% confidence intervals (CIs). From the data provided in each article, the crude OR was also calculated. Forty‐four observational studies (in 37 articles) were identified for the final analysis. The pooled OR from random‐effects analysis was determined to be 1·76 (95% CI 1·59–1·96). The highest risk was for patients suffering from PsA (OR 2·18, 95% CI 1·36–3·50). We also observed a dose effect in the risk of suffering from type 2 diabetes mellitus, as patients considered as having severe psoriasis had higher risk (OR 2·10, 95% CI 1·73–2·55) than the pooled OR. We perform meta‐regression and sensitivity analyses to explore sources of heterogeneity among the studies and to determine how they would influence the estimates, and found no significant influence in the results of the meta‐analyses. The findings support the association between psoriasis, PsA and type 2 diabetes mellitus. Some caution must be taken in the interpretation of these results because there may be heterogeneity between studies.
What's already known about this topic?
Several observational studies have assessed the association between psoriasis, psoriatic arthritis and type 2 diabetes mellitus, with inconclusive results.
What does this study add?
A systematic review and meta‐analysis including all observational studies up to December 2012.
Investigation of the influence of psoriatic arthritis and the severity of the disease on the risk of diabetes.
The effect of oral administration of probiotic bacteria cell walls (PBCWs) in the stimulation of the immune system in healthy BALB/c mice was evaluated. We focused our investigation mainly on ...intestinal epithelial cells (IECs) which are essential for coordinating an adequate mucosal immune response and on the functionality of macrophages. The probiotic bacteria and their cell walls were able to stimulate the IECs exhibiting an important activation and cytokine releases. Supplementation with PBCWs promoted macrophage activation from peritoneum and spleen, indicating that the PBCWs oral administration was able to improve the functionality of the macrophages. In addition, the PBCWs increased immunoglobulin A (IgA)-producing cells in the gut lamina propria in a similar way to probiotic bacteria, but this supplementation did not have an effect on the population of goblet cells in the small intestine epithelium. These results indicate that the probiotic bacteria and their cell walls have an important immunoregulatory effect on the IECs without altering the homeostatic environment but with an increase in IgA+ producing cells and in the innate immune cells, mainly those distant from the gut such as spleen and peritoneum. These findings about the capacity of the cell walls from probiotic bacteria to stimulate key cells, such as IECs and macrophages, and to improve the functioning of the immune system, suggest that those structures could be applied as a new oral adjuvant.
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