Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production

Energy and glucose homeostasis are regulated by food intake and liver glucose production, respectively. The upper intestine has a critical role in nutrient digestion and absorption. However, studies indicate that upper intestinal lipids inhibit food intake as well in rodents and humans by the activation of an intestine-brain axis. In parallel, a brain-liver axis has recently been proposed to detect blood lipids to inhibit glucose production in rodents. Thus, we tested the hypothesis that upper intestinal lipids activate an intestine-brain-liver neural axis to regulate glucose homeostasis. Here we demonstrate that direct administration of lipids into the upper intestine increased upper intestinal long-chain fatty acyl-coenzyme A (LCFA-CoA) levels and suppressed glucose production. Co-infusion of the acyl-CoA synthase inhibitor triacsin C or the anaesthetic tetracaine with duodenal lipids abolished the inhibition of glucose production, indicating that upper intestinal LCFA-CoAs regulate glucose production in the preabsorptive state. Subdiaphragmatic vagotomy or gut vagal deafferentation interrupts the neural connection between the gut and the brain, and blocks the ability of upper intestinal lipids to inhibit glucose production. Direct administration of the N-methyl-d-aspartate ion channel blocker MK-801 into the fourth ventricle or the nucleus of the solitary tract where gut sensory fibres terminate abolished the upper-intestinal-lipid-induced inhibition of glucose production. Finally, hepatic vagotomy negated the inhibitory effects of upper intestinal lipids on glucose production. These findings indicate that upper intestinal lipids activate an intestine-brain-liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis.     

Calendars with Olympiad display and eclipse prediction on the Antikythera Mechanism

Previous research on the Antikythera Mechanism established a highly complex ancient Greek geared mechanism with front and back output dials. The upper back dial is a 19-year calendar, based on the Metonic cycle, arranged as a five-turn spiral. The lower back dial is a Saros eclipse-prediction dial, arranged as a four-turn spiral of 223 lunar months, with glyphs indicating eclipse predictions. Here we add surprising findings concerning these back dials. Though no month names on the Metonic calendar were previously known, we have now identified all 12 months, which are unexpectedly of Corinthian origin. The Corinthian colonies of northwestern Greece or Syracuse in Sicily are leading contenders-the latter suggesting a heritage going back to Archimedes. Calendars with excluded days to regulate month lengths, described in a first century bc source, have hitherto been dismissed as implausible. We demonstrate their existence in the Antikythera calendar, and in the process establish why the Metonic dial has five turns. The upper subsidiary dial is not a 76-year Callippic dial as previously thought, but follows the four-year cycle of the Olympiad and its associated Panhellenic Games. Newly identified index letters in each glyph on the Saros dial show that a previous reconstruction needs modification. We explore models for generating the unusual glyph distribution, and show how the eclipse times appear to be contradictory. We explain the four turns of the Saros dial in terms of the full moon cycle and the Exeligmos dial as indicating a necessary correction to the predicted eclipse times. The new results on the Metonic calendar, Olympiad dial and eclipse prediction link the cycles of human institutions with the celestial cycles embedded in the Mechanism's gearwork.     

A Systems Approach for Engaging Groups in Global Complexity: Capacity Building Through an Online Course

Sustainability is not simply about changing practices but more centrally about agreeing to change practices together. To achieve such an end, groups need to improve processes for making complex decisions together. An online course was designed and tested linking students in the United States and in Australia. Students engaged in a re-enactment of deliberations based on Hasan Ozbekhan’s “Predicament of Mankind,” which was constructed originally under assignment from the founders of the Club of Rome in 1970. This re-enactment included contemporary research for examples of a set of 49 continuous critical problems of mankind, asynchronous clarification of these problems using a wiki, pair-wise construction of a systems view of problems assessed to be of highest priority by the class, narrative analysis of the structure, and creative suggestions for resolving the systems problem based on resources available today. This report comments on the strengths and challenges identified in an initial application of an approach for building collaborative and systems thinking skills through an online course in a general education curriculum. Findings are particularly meaningful for contemporary policy makers as well as online educators.     

Systems Thinking and Systems Practice: Working in the Fifth Dimension

This paper describes how a messy organizational problem was tackled using a systems approach which led to a resolution of the problem and to an improvement in the working relationships of the people involved. The example also shows how people who are not familiar with systems thinking, as such, can quickly be helped to develop a shared systemic view of a complex situation using activity modeling. At a deeper level, the paper also shows how the underlying dynamics of the problem situation was altered as a result of using a cooperative, dialogical working method, leading to an improvement in the quality of service provided by that part of the organization. The paper uses Peter Senge's five disciplines of a learning organization, together with various systems concepts, as a framework for describing how the process of change was brought about through the simultaneous management of task and social processes, leading to both individual and organizational learning.     

Patterns of somatic mutation in human cancer genomes

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.