Exploitation of structural and regulatory diversity in glutamate racemases

Glutamate racemase is an enzyme essential to the bacterial cell wall biosynthesis pathway, and has therefore been considered as a target for antibacterial drug discovery. We characterized the glutamate racemases of several pathogenic bacteria using structural and biochemical approaches. Here we describe three distinct mechanisms of regulation for the family of glutamate racemases: allosteric activation by metabolic precursors, kinetic regulation through substrate inhibition, and D-glutamate recycling using a d-amino acid transaminase. In a search for selective inhibitors, we identified a series of uncompetitive inhibitors specifically targeting Helicobacter pylori glutamate racemase that bind to a cryptic allosteric site, and used these inhibitors to probe the mechanistic and dynamic features of the enzyme. These structural, kinetic and mutational studies provide insight into the physiological regulation of these essential enzymes and provide a basis for designing narrow-spectrum antimicrobial agents.     

Adrenergic reinnervation of the denervated rat urinary bladder.

In rats undergoing unilateral extirpation of the pelvic ganglion, the adrenergic innervation disappeared on the ipsilateral side of the urinary bladder. It had reappeared after 6--9 weeks.     

The effect of hexosamine inhibitors on the secretion ofγ-globulin

Zusammenfassung Hemmung von Hexosamin vermag die Sekretion von-Globulin durch antikörperproduzierende Zellen unter in vitro Bedingungen nicht zu verhindern. Dies könnte darauf hinweisen, dass unter den gewählten Bedingungen kohlehydratfreie-Globulinmoleküle sezerniert werden.     

Adrenergic reinnervation of the denervated rat urinary bladder

Summary In rats undergoing unilateral extirpation of the pelvic ganglion, the adrenergic innervation disappeared on the ipsilateral side of the urinary bladder. It had reappeared after 6–9 weeks.This work was supported by grants from the Faculty of Medicine in Lund to M.E.     

Systemic Research Practices Towards the Development of an Eco-Community in Vietnam: some Joint Post-Facto Reflections

In this article we discuss how an interdisciplinary research team partnered with a variety of stakeholders concerned with and/or affected by the impacts of climate change in the Red River Delta of Vietnam. The research, undertaken from 2016 to 2018, drew upon a wide range of methods to investigate systemically these impacts – with a view to the research inputting into the development of (more) sustainable ways of living. The research solicited various accounts of the experience of climate change in the community, set up learning processes in community meetings, and created an interface with government officials positioned at commune, district, provincial, and national levels. The intention was to offer support towards developing a learning process (broadly defined as including learnings/systemic inquiry across organizational levels of the society) to pursue options for sustainable living. The article offers our post-facto reflections which render more explicit (to ourselves and for the benefit of audiences) how the research team, with Hoang as lead researcher, facilitated the inquiry process towards developing a synthesis which underscored the assets for resilience to climate change and supported interventions to strengthen such (defined) assets.

     

Ecology drives a global network of gene exchange connecting the human microbiome

Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution. In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence, antibiotic resistance and xenobiotic metabolism to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events. Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates (P = 3.0 × 10(-270)). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.     

Co-design Research and Business Development: Case of Scandinavian Airlines (SAS)

This paper is presenting a case study of Scandinavian Airlines Systems (SAS) showing how improvements of service quality aspects with Avatars can be managed with a Co-design research approach. The Co-design practices are carried out in different fields of studies. Some of the key advocates of Co-design originate from business. In this study the four steps of Co-design approach is applied. From the first step of Co-design, through interviews, log analysis and a channel survey, findings show that the failed dialogues with Avatar Eva are mainly concerned with five factors: interactivity; dialogue capability; consistency; knowledge; and synonyms. In the second step, carrying out customer workshops, we suggested ten ideal scenarios for Avatar Eva to perform better. In the third step, SAS decision makers decided to implement the first three scenarios: Eva’s synonyms; knowledge and Eva’s consistency. In the fourth step, another channel survey was carried out as well as a new log analysis to know the impact of the redevelopment above three scenarios. An important result of the study was that the company adopted a continuous use of Co-design as an approach of continuous improvement of the service quality performed by the Avatar Eva. It also opens a new set of questions framing the relation and transformation between Co-design as a research approach for knowledge creation and Co-design as a method for innovation and service quality improvements. The study presents an Extended Co-design Model, which illustrates how the Co-design inspires staff to use it for other functions within and without the SAS.