Oligosaccharides Isolated from MGO™ Manuka Honey Inhibit the Adhesion of Pseudomonas aeruginosa, Escherichia Coli O157:H7 and Staphylococcus Aureus to Human HT-29 cells

peer-reviewedHistorically, honey is known for its anti-bacterial and anti-fungal activities and its use for treatment of wound infections. Although this practice has been in place for millennia, little information exists regarding which manuka honey components contribute to the protective nature of this product. Given that sugar accounts for over 80% of honey and up to 25% of this sugar is composed of oligosaccharides, we have investigated the anti-infective activity of manuka honey oligosaccharides against a range of pathogens. Initially, oligosaccharides were extracted from a commercially-available New Zealand manuka honey—MGO™ Manuka Honey (Manuka Health New Zealand Ltd.)—and characterized by High pH anion exchange chromatography coupled with pulsed amperiometric detection. The adhesion of specific pathogens to the human colonic adenocarcinoma cell line, HT-29, was then assessed in the presence and absence of these oligosaccharides. Manuka honey oligosaccharides significantly reduced the adhesion of Escherichia coli O157:H7 (by 40%), Staphylococcus aureus (by 30%), and Pseudomonas aeruginosa (by 52%) to HT-29 cells. This activity was then proven to be concentration dependent and independent of bacterial killing. This study identifies MGO™ Manuka Honey as a source of anti-infective oligosaccharides for applications in functional foods aimed at lowering the incidence of infectious diseases

How Many Varieties of Capitalism? Comparing the Comparative Institutional Analyses of Capitalist Diversity

This essay reviews the development of approaches within the comparative capitalisms (CC) literature and points to three theoretical innovations which, taken together, define and distinguish these approaches as a group. First, national economies are characterized by distinct institutional configurations that generate a particular systemic 'logic' of economic action. Second, the CC literature suggests a theory of comparative institutional advantage in which different institutional arrangements have distinct strengths and weaknesses for different kinds of economic activity. Third, the literature has been interpreted to imply a theory of institutional path dependence. Behind these unifying characteristics of the literature, however, lie a variety of analytical frameworks and typologies of capitalism. This paper reviews and compares these different frameworks by highlighting the fundamental distinctions among them and drawing out their respective contributions and limitations in explaining economic performance and institutional dynamics. The paper concludes that the way forward for this literature lies in developing a more dynamic view of individual institutions, the linkages between domains, and the role of politics and power.In diesem Discussion Paper werden Ansätze der Comparative-Capitalism-Diskussion vorgestellt. Sie haben drei theoretische Innovationen gemein. Erstens: Nationale Ökonomien werden durch institutionelle Konfigurationen geprägt, die auf jeweils eigene "systemische Logiken" wirtschaftlichen Handelns hinwirken. Zweitens: Die Comparative-Capitalism-Literatur beinhaltet eine Theorie der komparativen institutionellen Vorteile, der zufolge institutionellen Konfigurationen spezifische Wettbewerbsvorteile zugeordnet werden können. Zudem, drittens, beinhaltet die Comparative-Capitalism-Literatur auch eine implizite Theorie der Pfadabhängigkeit. Trotz dieser Gemeinsamkeiten unterscheiden sich die Ansätze hinsichtlich analytischer Zugriffe und Vorschläge zur Typologisierung nationaler Kapitalismen. Beim Vergleich dieser Ansätze werden besonders deren Stärken und Schwächen bei der Analyse wirtschaftlicher Performanz und institutioneller Entwicklungsdynamiken hervorgehoben. Der Aufsatz kommt zu dem Schluss, dass die Comparative-Capitalism-Literatur in dreierlei Hinsicht der Weiterentwicklung bedarf: hinsichtlich einer dynamischeren Modellierung von Institutionen, einem besseren Verständnis der Interaktion institutioneller Domänen und der Berücksichtigung von Macht und Politik in der Analyse von Produktionsregimen

Under normoxia, 2-deoxy-D-glucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation

In tumor cells growing under hypoxia, inhibiting glycolysis with 2-deoxy-d-glucose (2-DG) leads to cell death, whereas under normoxic conditions cells similarly treated survive. Surprisingly, here we find that 2-DG is toxic in select tumor cell lines growing under normal oxygen tension. In contrast, a more potent glycolytic inhibitor, 2-fluorodeoxy-d-glucose, shows little or no toxicity in these cell types, indicating that a mechanism other than inhibition of glycolysis is responsible for their sensitivity to 2-DG under normoxia. A clue to this other mechanism comes from previous studies in which it was shown that 2-DG interferes with viral N-linked glycosylation and is reversible by exogenous addition of mannose. Similarly, we find that 2-DG interferes with N-linked glycosylation more potently in the tumor cell types that are sensitive to 2-DG under normoxia, which can be reversed by exogenous mannose. Additionally, 2-DG induces an unfolded protein response, including up-regulation of GADD153 (C/EBP-homologous protein), an unfolded protein response-specific mediator of apoptosis, more effectively in 2-DG-sensitive cells. We conclude that 2-DG seems to be toxic in select tumor cell types growing under normoxia by inhibition of N-linked glycosylation and not by glycolysis. Because in a phase I study 2-DG is used in combination with an anticancer agent to target hypoxic cells, our results raise the possibility that in certain cases, 2-DG could be used as a single agent to selectively kill both the aerobic (via interference with glycosylation) and hypoxic (via inhibition of glycolysis) cells of a solid tumor

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu

Genomic reconstruction of the SARS-CoV-2 epidemic in England

AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p