Cyclization of the Urokinase Receptor-Derived Ser-Arg-Ser-Arg-Tyr Peptide Generates a Potent Inhibitor of Trans-Endothelial Migration of Monocytes

The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR_88-92 is the minimal sequence required to induce cell motility. We and others have previously documented that the uPAR_88-92 sequence, even in the form of synthetic linear peptide (SRSRY), interacts with the formyl peptide receptor type 1 (FPR1), henceforth inducing cell migration of several cell lines, including monocytes. FPR1 is mainly expressed by mammalian phagocytic leukocytes and plays a crucial role in chemotaxis. In this study, we present evidence that the cyclization of the SRSRY sequence generates a new potent and stable inhibitor of monocyte trafficking. In rat basophilic leukaemia RBL-2H3/ETFR cells expressing high levels of constitutively activated FPR1, the cyclic SRSRY peptide ([SRSRY]) blocks FPR1 mediated cell migration by interfering with both internalization and ligand-uptake of FPR1. Similarly to RBL-2H3/ETFR cells, [SRSRY] competes with fMLF for binding to FPR1 and prevents agonist-induced FPR1 internalization in human monocyte THP-1 cells. Unlike scramble [RSSYR], [SRSRY] inhibits fMLF-directed migration of monocytes in a dose-dependent manner, with IC₅₀ value of 0.01 nM. PMA-differentiated THP-1 cell exposure to fMLF gradient causes a marked cytoskeletal re-organization with the formation of F-actin rich pseudopodia that are prevented by the addition of [SRSRY]. Furthermore, [SRSRY] prevents migration of human primary monocytes and trans-endothelial migration of monocytes. Our findings indicate that [SRSRY] is a new FPR1 inhibitor which may suggest the development of new drugs for treating pathological conditions sustained by increased motility of monocytes, such as chronic inflammatory diseases.     

A multi-trait systems approach reveals a response cascade to bleaching in corals

Background

Climate change causes the breakdown of the symbiotic relationships between reef-building corals and their photosynthetic symbionts (genus Symbiodinium), with thermal anomalies in 2015–2016 triggering the most widespread mass coral bleaching on record and unprecedented mortality on the Great Barrier Reef. Targeted studies using specific coral stress indicators have highlighted the complexity of the physiological processes occurring during thermal stress, but have been unable to provide a clear mechanistic understanding of coral bleaching.

Results

Here, we present an extensive multi-trait-based study in which we compare the thermal stress responses of two phylogenetically distinct and widely distributed coral species, Acropora millepora and Stylophora pistillata, integrating 14 individual stress indicators over time across a simulated thermal anomaly. We found that key stress responses were conserved across both taxa, with the loss of symbionts and the activation of antioxidant mechanisms occurring well before collapse of the physiological parameters, including gross oxygen production and chlorophyll a. Our study also revealed species-specific traits, including differences in the timing of antioxidant regulation, as well as drastic differences in the production of the sulfur compound dimethylsulfoniopropionate during bleaching. Indeed, the concentration of this antioxidant increased two-fold in A. millepora after the corals started to bleach, while it decreased 70% in S. pistillata.

Conclusions

We identify a well-defined cascading response to thermal stress, demarking clear pathophysiological reactions conserved across the two species, which might be central to fully understanding the mechanisms triggering thermally induced coral bleaching. These results highlight that bleaching is a conserved mechanism, but specific adaptations linked to the coral’s antioxidant capacity drive differences in the sensitivity and thus tolerance of each coral species to thermal stress.

     

Folk Phytotherapy in Paediatric Health Care in Central and Southern Italy: a Review

Complementary and alternative medicine (CAM) consists of systems and practices used to prevent or treat illness, and/or promote health and wellbeing, generally with herbal remedies. In recent decades, ethnobotanical and ethnopharmacological surveys have received increased attention among populations in central and southern Italy traditionally highly conservative regarding knowledge of folk medicine. This review highlights the use of wild and cultivated plants in paediatric health care. From a search of articles published between 1978 and 2017 we found a total of 34 containing reports of medicinal plants specifically used for treating children’s diseases, listing 83 taxa belonging to 37 families in 116 recorded cases of medicinal plant use. Tuscany has the highest number of plant use reports and the highest number of species used in a single region, followed by Campania and Sicily. Allium sativum is the most widely reported species, cited in eight regions. We identified eight ailment categories. Plants used as anthelmintics and for gastro-intestinal and skin diseases are widely used.     

Production of Manoalide and Its Analogues by the Sponge <Emphasis Type="Italic">Luffariella variabilis</Emphasis> Is Hardwired

The Great Barrier Reef sponge Luffariella variabilis (Poléjaeff 1884) produces a range of potent anti-inflammatory compounds as its major metabolites. These major metabolites—manoalide monoacetate, manoalide, luffariellin A and seco-manoalide—were monitored temporally and spatially to quantify the potential yield from wild harvest or aquaculture. Production of the major metabolites was hardwired at the population level with little variation in space and time over meters to tens of kilometers in the Palm Islands, Queensland, Australia. Manoalide monoacetate (35 to 70 mg g⁻¹ dry weight of sponge) was consistently the most abundant compound followed by manoalide (15 to 20 mg g⁻¹ dry weight). Luffariellin A and seco-manoalide were 10 to 70 times less abundant and varied between 0 and 3 mg g⁻¹ dry weight. On a larger spatial scale, L. variabilis from Davies Reef and Magnetic Island contained the same rank order and yields of compounds as the Palm Islands, indicating a generality of pattern over at least 100 km. The “hardwiring” of metabolite production at the population level by L. variabilis was also reflected in the lack of any inductive effect on metabolite production. In addition, individually monitored sponges produced fixed ratios of the major metabolites over time (years). However, these ratios varied between individuals, with some individuals consistently producing high levels of manoalide and manoalide monoacetate, providing the potential for selection of high-yielding stocks.     

An alternative model for the early peopling of southern South america revealed by analyses of three mitochondrial DNA haplogroups

After several years of research, there is now a consensus that America was populated from Asia through Beringia, probably at the end of the Pleistocene. But many details such as the timing, route(s), and origin of the first settlers remain uncertain. In the last decade genetic evidence has taken on a major role in elucidating the peopling of the Americas. To study the early peopling of South America, we sequenced the control region of mitochondrial DNA from 300 individuals belonging to indigenous populations of Chile and Argentina, and also obtained seven complete mitochondrial DNA sequences. We identified two novel mtDNA monophyletic clades, preliminarily designated B2l and C1b13, which together with the recently described D1g sub-haplogroup have locally high frequencies and are basically restricted to populations from the extreme south of South America. The estimated ages of D1g and B2l, about ～15,000 years BP, together with their similar population dynamics and the high haplotype diversity shown by the networks, suggests that they probably appeared soon after the arrival of the first settlers and agrees with the dating of the earliest archaeological sites in South America (Monte Verde, Chile, 14,500 BP). One further sub-haplogroup, D4h3a5, appears to be restricted to Fuegian-Patagonian populations and reinforces our hypothesis of the continuity of the current Patagonian populations with the initial founders. Our results indicate that the extant native populations inhabiting South Chile and Argentina are a group which had a common origin, and suggest a population break between the extreme south of South America and the more northern part of the continent. Thus the early colonization process was not just an expansion from north to south, but also included movements across the Andes.