Psychosocial aspects of androgenetic alopecia

The main objective of the studies described in this thesis is to study the psychosocial problems of men and women with androgenetic alopecia who applied for treatment. In chapter 2, the psychological characteristics of 59 men with androgenetic alopecia from a sample of the general population were compared with those of men without androgenetic alopecia and a group of men with androgenetic alopecia from a clinical population. Chapter 3 is devoted to a study at the psychological characteristics of a group of men with androgenetic alopecia who participated in a clinical triaL The questions are: I. Do men with androgenetic alopecia who apply for treatment have unfavourable personality traits and specific hair problems?, 2. Does subjectively perceived regrowth of hair lead to an improvement in social and psychological well being and a reduction in hair problems? and 3. ls the effect of perceived hair regrowth larger in younger than in older men? The study described in chapter 4 is devoted to research at the psychological and social problems of women with androgenetic alopecia. The outcome is compared with two control groups; women with nonvisible dermatological disorders and men with androgenetic alopecia from a clinical population. Chapter 5 describes additional investigations into the characteristics and the level of psychological problems in women with androgenetic alopecia and their adaptation to their hair loss. The study questions are: I. What problems exist in various life areas in the women with androgenetic alopecia who applied for treatment? and 2. How many women with androgenetic alopecia show general psychosocial maladjustment which is attributable to androgenetic alopecia

Substrate control in stereoselective lanthionine biosynthesis.

Enzymes are typically highly stereoselective catalysts that enforce a reactive conformation on their native substrates. We report here a rare example in which the substrate controls the stereoselectivity of an enzyme-catalysed Michael-type addition during the biosynthesis of lanthipeptides. These natural products contain thioether crosslinks formed by a cysteine attack on dehydrated Ser and Thr residues. We demonstrate that several lanthionine synthetases catalyse highly selective anti-additions in which the substrate (and not the enzyme) determines whether the addition occurs from the re or si face. A single point mutation in the peptide substrate completely inverted the stereochemical outcome of the enzymatic modification. Quantum mechanical calculations reproduced the experimentally observed selectivity and suggest that conformational restraints imposed by the amino-acid sequence on the transition states determine the face selectivity of the Michael-type cyclization

Ribosomally Synthesized and Post-Translationally Modified Peptide Natural Products: New Insights into the Role of Leader and Core Peptides during Biosynthesis

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with a high degree of structural diversity and a wide variety of bioactivities. Understanding the biosynthetic machinery of these RiPPs will benefit the discovery and development of new molecules with potential pharmaceutical applications. In this review, we discuss the features of the biosynthetic pathways to different RiPP classes, and propose mechanisms regarding recognition of the precursor peptide by the posttranslational modification enzymes. We propose that the leader peptides function as allosteric regulators that bind the active form of the biosynthetic enzymes in a conformational selection process. We also speculate how enzymes that generate polycyclic products of defined topologies may have been selected for during evolution

Heeding Supply Chain Disruption Warnings:When And How Do Cross‐Functional Teams Ensure Firm Robustness?

Firms can adopt several strategies to increase their robustness to potential supply chain (SC) disruptions. One promising strategy is the use of a cross-functional team with representatives from functional departments. Such a team may facilitate sharing relevant information, enabling the firm to respond effectively to SC disruption warnings. However, despite their potential, cross-functional teams also differ in their ability to respond to SC disruption warnings and to ensure firm robustness. Extending insights from information-processing theory and team research to the field of SC management, we propose that a cross-functional team’s ability to handle high numbers of SC disruption warnings depends on the extent to which the team adopts centralized decision-making, with one or two members orchestrating the decision-making process. We also introduce internal integration problems as a mediating mechanism explaining why a cross-functional team lacking centralized decision-making may be unable to handle high numbers of SC disruption warnings. In two independent studies, we use multi-source data on cross-functional teams’ performance in dealing with SC disruption warnings during a realistic SC management simulation; the results support our predictions

Biosynthesis of Rhizocticins, Antifungal Phosphonate Oligopeptides Produced by Bacillus subtilis ATCC6633

SummaryRhizocticins are phosphonate oligopeptide antibiotics containing the C-terminal nonproteinogenic amino acid (Z)-l-2-amino-5-phosphono-3-pentenoic acid (APPA). Here we report the identification and characterization of the rhizocticin biosynthetic gene cluster (rhi) in Bacillus subtilis ATCC6633. Rhizocticin B was heterologously produced in the nonproducer strain Bacillus subtilis 168. A biosynthetic pathway is proposed on the basis of bioinformatics analysis of the rhi genes. One of the steps during the biosynthesis of APPA is an unusual aldol reaction between phosphonoacetaldehyde and oxaloacetate catalyzed by an aldolase homolog RhiG. Recombinant RhiG was prepared, and the product of an in vitro enzymatic conversion was characterized. Access to this intermediate allows for biochemical characterization of subsequent steps in the pathway

Discovery of Unique Lanthionine Synthetases Reveals New Mechanistic and Evolutionary Insights

Identification of a new class of lanthionine synthetases provides insight into the mechanism and evolution of cyclic peptide biosynthesis

Molecular Cloning and Heterologous Expression of the Dehydrophos Biosynthetic Gene Cluster

SummaryDehydrophos is a vinyl phosphonate tripeptide produced by Streptomyces luridus with demonstrated broad-spectrum antibiotic activity. To identify genes necessary for biosynthesis of this unusual compound we screened a fosmid library of S. luridus for the presence of the phosphoenolpyruvate mutase gene, which is required for biosynthesis of most phosphonates. Integration of one such fosmid clone into the chromosome of S. lividans led to heterologous production of dehydrophos. Deletion analysis of this clone allowed identification of the minimal contiguous dehydrophos cluster, which contained 17 open reading frames (ORFs). Bioinformatic analyses of these ORFs are consistent with a proposed biosynthetic pathway that generates dehydrophos from phosphoenolpyruvate. The early steps of this pathway are supported by analysis of intermediates accumulated by blocked mutants and in vitro biochemical experiments