Biochemical evidence for an alternate pathway in N-linked glycoprotein biosynthesis

Asparagine-linked glycosylation is a complex protein modification conserved among all three domains of life. Herein we report the in vitro analysis of N-linked glycosylation from the methanogenic archaeon Methanococcus voltae. Using a suite of synthetic and semisynthetic substrates, we show that AglK initiates N-linked glycosylation in M. voltae through the formation of α-linked dolichyl monophosphate N-acetylglucosamine, which contrasts with the polyprenyl diphosphate intermediates that feature in both eukaryotes and bacteria. Notably, AglK has high sequence homology to dolichyl phosphate β-glucosyltransferases, including Alg5 in eukaryotes, suggesting a common evolutionary origin. The combined action of the first two enzymes, AglK and AglC, afforded an α-linked dolichyl monophosphate glycan that serves as a competent substrate for the archaeal oligosaccharyl transferase AglB. These studies provide what is to our knowledge the first biochemical evidence revealing that, despite the apparent similarity of the overall pathways, there are actually two general strategies to achieve N-linked glycoproteins across the domains of life.National Institutes of Health (U.S.) (Grant GM039334

Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced

Structure-activity relationship study on Tyr9 of urotensin-II(4-11): identification of a partial agonist of the UT receptor.

Urotensin-II (U-II) activates the U-II receptor (UT) to modulate a range of biological responses at both central and peripheral sites. Previous studies have demonstrated that the sequence Trp7-Lys8-Tyr9 of the cyclic portion of the peptide is crucial for biological activity. Here, we describe a focused structure–activity study of Tyr9 which has been replaced with a series of non-coded amino acids in the U-II(4–11) template. Thirteen analogs were synthesized and pharmacologically tested for intracellular calcium mobilization in HEK293 cells stably expressing the rat UT receptor. The results of this study demonstrated the following Tyr9 structure–activity features: (i) the position of the OH group of the side chain is not important for biological activity, (ii) the distance of the phenol moiety from the peptide backbone and its conformational freedom are crucial for UT receptor recognition, (iii) this position is important not only for receptor occupation but also for its activation since the 3,5-diiodoTyr9 chemical modification generated a potent partial agonist. This pharmacological activity of [3,5-diiodoTyr9]U-II(4–11) was confirmed in bioassay experiments performed using the rat thoracic aorta as a U-II sensitive preparation

Structure-activity relationship study on Tyr9 of urotensin-II(4-11): identification of a partial agonist of the UT receptor

Urotensin-II (U-II) activates the U-II receptor (UT) to modulate a range of biological responses at both central and peripheral sites. Previous studies have demonstrated that the sequence Trp7-Lys8-Tyr9 of the cyclic portion of the peptide is crucial for biological activity. Here, we describe a focused structure\u2013activity study of Tyr9 which has been replaced with a series of non-coded amino acids in the U-II(4\u201311) template. Thirteen analogs were synthesized and pharmacologically tested for intracellular calcium mobilization in HEK293 cells stably expressing the rat UT receptor. The results of this study demonstrated the following Tyr9 structure\u2013activity features: (i) the position of the OH group of the side chain is not important for biological activity, (ii) the distance of the phenol moiety from the peptide backbone and its conformational freedom are crucial for UT receptor recognition, (iii) this position is important not only for receptor occupation but also for its activation since the 3,5-diiodoTyr9 chemical modification generated a potent partial agonist. This pharmacological activity of [3,5-diiodoTyr9]U-II(4\u201311) was confirmed in bioassay experiments performed using the rat thoracic aorta as a U-II sensitive preparation

Old-Age Security and Silver Workers: An Empirical Survey Identifies Challenges for Companies, Insurers and Society

As a result of demographic development, pension reforms have been passed to make them more sustainable for the future. More recently, understanding of the importance of the employment of older workers has been increasing but there is still the need for a policy shift. Moreover, the future shortage of qualified staff will noticeably affect the growth of many developed economies in the next decades. This explorative paper focuses on the present empirical situation and expectations of the workforce capacity of older persons in good mental and physical health: paid and unpaid active retirees in Germany (Silver Workers). The lifestyles of Silver Workers as well as reasons for engagement in post-retirement activities and necessary framework conditions of work during retirement are described. The qualitative and quantitative survey allows us to derive practical recommendations for leadership, human resource management and policies, as well as for the insurance industry. The authors estimate that integrating Silver Workers can contribute to macroeconomic growth potential, relieve old-age pension systems (“Fourth Pillar”) and provide new business opportunities. The Geneva Papers (2009) 34, 137–157. doi:10.1057/gpp.2008.44

Molecular basis of lipid-linked oligosaccharide recognition and processing by bacterial oligosaccharyltransferase

ISSN:1545-9993ISSN:1545-998