Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets

Introduction

Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials and methods

GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.

Results

We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.

Discussion

The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.

     

The avian nature of the brain and inner ear of Archaeopteryx

Archaeopteryx, the earliest known flying bird (avialan) from the Late Jurassic period, exhibits many shared primitive characters with more basal coelurosaurian dinosaurs (the clade including all theropods more bird-like than Allosaurus), such as teeth, a long bony tail and pinnate feathers. However, Archaeopteryx possessed asymmetrical flight feathers on its wings and tail, together with a wing feather arrangement shared with modern birds. This suggests some degree of powered flight capability but, until now, little was understood about the extent to which its brain and special senses were adapted for flight. We investigated this problem by computed tomography scanning and three-dimensional reconstruction of the braincase of the London specimen of Archaeopteryx. Here we show the reconstruction of the braincase from which we derived endocasts of the brain and inner ear. These suggest that Archaeopteryx closely resembled modern birds in the dominance of the sense of vision and in the possession of expanded auditory and spatial sensory perception in the ear. We conclude that Archaeopteryx had acquired the derived neurological and structural adaptations necessary for flight. An enlarged forebrain suggests that it had also developed enhanced somatosensory integration with these special senses demanded by a lifestyle involving flying ability.     

Inattivazione del profago a mezzo del calore

Zusammenfassung Die Erwärmung von lysogenen Staphylokokken auf 45° C während 20 min verhindert die Wirkung des thermischen Schocks sowohl auf die Bakteriophagen-Lysis wie auf diejenige bei niedriger Temperatur. Wird hingegen die Behandlung bei 45° C nach dem Schock durchgeführt, so bleibt sie wirkungslos.Diese Ergebnisse lassen vermuten, dass in lysogenen Staphylokokken eine Komponente vorhanden ist, die den phagischen Präkursoren vonKrueger enstpricht mit gleicher Wärmeempfindlichkeit. Identität mit dem Probakteriophagen ist möglich.     

Interaction between ‘Liquoid’ (sodium polyanetholsulphonate) and lysozyme in the immune haemolytic reaction

Riassunto È stato osservato che il lisozima provoca lisi di emazie sensibilizzate in presenza di un reagente per la titolazione di C'₃, preparato con siero di cavia trattato con Liquoid. È stato studiato il meccanismo di tale azione ed è stato dimostrato che essa è dovuta alla formazione di complessi tra il lisozima ed il Liquoid fissato dalle globuline del siero fornite di attività di C'₃. Tale azione del lisozima è indipendente dall'attività enzimatica in quanto anche il metil-lisozima ed il solfato di protamina provocano lo stesso fenomeno.     

Continental-scale patterns of canopy tree composition and function across Amazonia

The world's greatest terrestrial stores of biodiversity and carbon are found in the forests of northern South America, where large-scale biogeographic patterns and processes have recently begun to be described. Seven of the nine countries with territory in the Amazon basin and the Guiana shield have carried out large-scale forest inventories, but such massive data sets have been little exploited by tropical plant ecologists. Although forest inventories often lack the species-level identifications favoured by tropical plant ecologists, their consistency of measurement and vast spatial coverage make them ideally suited for numerical analyses at large scales, and a valuable resource to describe the still poorly understood spatial variation of biomass, diversity, community composition and forest functioning across the South American tropics. Here we show, by using the seven forest inventories complemented with trait and inventory data collected elsewhere, two dominant gradients in tree composition and function across the Amazon, one paralleling a major gradient in soil fertility and the other paralleling a gradient in dry season length. The data set also indicates that the dominance of Fabaceae in the Guiana shield is not necessarily the result of root adaptations to poor soils (nodulation or ectomycorrhizal associations) but perhaps also the result of their remarkably high seed mass there as a potential adaptation to low rates of disturbance.     

C3aR and C5aR1 act as key regulators of human and mouse β-cell function

Aims

Complement components 3 and 5 (C3 and C5) play essential roles in the complement system, generating C3a and C5a peptides that are best known as chemotactic and inflammatory factors. In this study we characterised islet expression of C3 and C5 complement components, and the impact of C3aR and C5aR1 activation on islet function and viability.

Materials and methods

Human and mouse islet mRNAs encoding key elements of the complement system were quantified by qPCR and distribution of C3 and C5 proteins was determined by immunohistochemistry. Activation of C3aR and C5aR1 was determined using DiscoverX beta-arrestin assays. Insulin secretion from human and mouse islets was measured by radioimmunoassay, and intracellular calcium ([Ca²⁺]i), ATP generation and apoptosis were assessed by standard techniques.

Results

C3 and C5 proteins and C3aR and C5aR1 were expressed by human and mouse islets, and C3 and C5 were mainly localised to β- and α-cells. Conditioned media from islets exposed for 1 h to 5.5 and 20 mM glucose stimulated C3aR and C5aR1-driven beta-arrestin recruitment. Activation of C3aR and C5aR1 potentiated glucose-induced insulin secretion from human and mouse islets, increased [Ca²⁺]i and ATP generation, and protected islets against apoptosis induced by a pro-apoptotic cytokine cocktail or palmitate.

Conclusions

Our observations demonstrate a functional link between activation of components of the innate immune system and improved β-cell function, suggesting that low-level chronic inflammation may improve glucose homeostasis through direct effects on β-cells.

     

The first Hapalotremus Simon, 1903 (Araneae: Theraphosidae) from Argentina: description and natural history of Hapalotremus martinorum sp. nov.

A new species of Hapalotremus Simon, 1903 from northern Argentina is described and illustrated. Hapalotremus martinorum sp. nov. differs from all other congeners by the colour pattern of live specimens. Males differ in the male palpal bulb morphology, with thickened and less curved embolus having a blunt subapical keel and less-developed apical keel. Females differ in the shape of the spermathecae, with the lateral bases more pronounced than the superiors and the upper edge more rounded. Specimens were captured inhabiting short burrows or crevices under stones in high cloud forests. Hapalotremus cyclothorax (Mello-Leitão 1923) is a junior synonym of Homoeomma montanum (Mello-Leitão, 1923), Hapalotremus scintillans (Mello-Leitão 1929) is a junior synonym of Pachistopelma rufonigrum Pocock, 1901, Hapalotremus exilis (Mello-Leitão 1923) and Hapalotremus muticus (Mello-Leitão 1923) are considered species inquirenda.

http://zoobank.org/urn:lsid:zoobank.org:pub:1758F6FD-8883-445D-A757-0AC7E120DCF6     

Effect of synthetic polynucleotides on the growth of transplantable tumours in BALB/c mice

Summary The effect of BALB/c mice pretreatment with tumour cells (a mammary adenocarcinoma, ADK-1t and an IgA secreting plasmocytoma, MOPC-315) adsorbed with poly I:C, poly I and poly C is examined. Only mice pretreated with cells of both tumours adsorbed with poly I:C and poly C proved to be extensively protected against challenge by homologous untreated tumour cells, whereas this was not so in the case of poly I. A possible explanation of this phenomenon is discussed.This work was supported by a research contract with the Italian National Research Council (C.N.R.).     

Effect of synthetic polynucleotides on the growth of transplantable tumours in BALB/c mice.

The effect of BALB/c mice pretreatment with tumour cells (a mammary adenocarcinoma, ADK-1t and an IgA secreting plasmocytoma, MOPC-315) adsorbed with poly I:C, poly I and poly C is examined. Only mice pretreated with cells of both tumours adsorbed with poly I:C and poly C proved to be extensively protected against challenge by homologous untreated tumour cells, whereas this was not so in the case of poly I. A possible explanation of this phenomenon is discussed.