α-MSH Stimulates Glucose Uptake in Mouse Muscle and Phosphorylates Rab-GTPase-Activating Protein TBC1D1 Independently of AMPK

The melanocortin system includes five G-protein coupled receptors (family A) defined as MC1R-MC5R, which are stimulated by endogenous agonists derived from proopiomelanocortin (POMC). The melanocortin system has been intensely studied for its central actions in body weight and energy expenditure regulation, which are mainly mediated by MC4R. The pituitary gland is the source of various POMC-derived hormones released to the circulation, which raises the possibility that there may be actions of the melanocortins on peripheral energy homeostasis. In this study, we examined the molecular signaling pathway involved in α-MSH-stimulated glucose uptake in differentiated L6 myotubes and mouse muscle explants. In order to examine the involvement of AMPK, we investigate α-MSH stimulation in both wild type and AMPK deficient mice. We found that α-MSH significantly induces phosphorylation of TBC1 domain (TBC1D) family member 1 (S237 and T596), which is independent of upstream PKA and AMPK. We find no evidence to support that α-MSH-stimulated glucose uptake involves TBC1D4 phosphorylation (T642 and S704) or GLUT4 translocation.     

Incorporation of 14CO2, into cardenolide and sapogenin steroids of Digitalis purpurea

The relative rates of biosynthesis of cardenolide and sapogenin steroids of Digitalis purpurea were estimated by their uptake of ¹⁴CO₂. The incorporation of label into both groups, although initially slow, indicated that biosynthesis occurs even at the end of the growing season. The sapogenins were produced more rapidly than the cardenolides at this stage of plant development. Within the group of sapogenins, digitogenin, the trihydroxy compound, was produced at a greater rate than the dihydroxy steroid gitogenin. In the case of the cardenolides, the trihydroxy gitoxigenin was produced at a slower rate than the dihydroxy digitoxigenin.     

Flosequinan in heart failure: acute haemodynamic and longer term symptomatic effects.

There is no single, simple test with which to evaluate new treatments for heart failure. Various methods need to be used, and a study of both the acute haemodynamic and longer term symptomatic effects of flosequinan, a new direct acting arteriolar and venous vasodilator, was therefore carried out in patients with heart failure. In one group of patients flosequinan increased cardiac output and caused a fall in pulmonary capillary wedge pressure, both effects lasting for 24 hours. In a double blind, placebo controlled study in another group flosequinan improved mean exercise tolerance from 9.9 to 12.7 minutes after four weeks of treatment. The drug also reduced perceived exertion during submaximal exercise and increased calf and therefore skeletal muscle blood flow. It reduced plasma renin activity and noradrenaline concentrations. Flosequinan possesses all the important properties of a drug likely to be of value in the treatment of heart failure.     

Meaning in Nature: Organic Manufacture?

The paper examines Marcello Barbieri’s (2007) Introduction to Biosemiotics. Highlighting debate within the biosemiotic community, it focuses on what the volume offers to those who explain human intellect in relation to what Turing called our ‘physical powers.’ In scrutinising the basis of world-modelling, parallels and contrasts are drawn with other work on embodied-embedded cognition. Models dominate biology. Is this a qualitative fact or does it point to biomechanisms? In evaluating the 18 contributions, it is suggested that the answers will shape the field. First, they will decide if biochemistry and explanatory reduction can be synergised by biosemantics. Second, they will show if our intellectual powers arise from biology. Does thinking use—not a language faculty—but what Marko? and colleagues call semiosis by the living? Resolution of such issues, it is suggested, can change how we view cognition. Above all, if the biomechanists win the day, cultural models can be regarded as extending natural meaning. On such a view, biomechanisms prompt us to act and perceive as we model our own natural models. This fits Craik’s vision: intellect gives us the alphanumerical ‘symbols’ that allow thoughts to have objective validity. For the biomechanist, this is explained—not by brains alone—but, rather, by acting under the constraints of historically extended sensoria.     

Nine decades of fish movement research in southern Africa: a synthesis of research and findings from 1928 to 2014

Unprecedented concern over the biological effects of over-exploitation, together with rapid technological advances in biotelemetry, have provided the impetus for much research, on a global scale, into the movement of marine animals. We reviewed 101 marine and estuarine fish movement studies from southern Africa, published from 1928 to 2014, with the aim of synthesising research trends and findings. Trends showed an increasing emphasis on fish movement research in publications in the sub-tropical and warm-temperate biogeographic regions along the south and east coasts of southern Africa. Although 63 % of publications featured only marine studies, research into fine-scale habitat use in estuaries has been on the increase, concomitant with increasing accessibility of biotelemetry. Overall, 26 families were identified in the surveyed literature with regionally endemic sparids featuring in 32 % of the publications. Ten movement themes were identified in the surveyed literature, including broad-scale movement patterns, which featured in 68 % of studies, followed by fine-scale habitat usage (33 %) and protected areas (26 %). The most prominent phenomenon, emerging from this research, is that of partial migration, which describes the occurrence of resident and migratory behaviour within a coexisting animal population. Substantial progress has also been made in unravelling the complexities of fine-scale habitat usage in marine reserves and in estuaries. While this knowledge has enabled more effective management of South Africa’s multi-user, multi-species fisheries, focus should now be directed at improving our understanding of the commonalities in movement behaviour, the associated driving forces behind this behaviour and the nature of movement across reserve boundaries.     

Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes

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