Editorial: Coralline algae: Past, present, and future perspectives

Following the success of the Frontiers in Marine Science Research Topic on “Coralline Algae: Globally Distributed Ecosystem Engineers,” the Research Topic on “Coralline Algae: Past, Present and Future Perspectives” was launched to extend the opportunity for publishing further knowledge about these diverse ecosystem engineers across a broader time scale. In this Research Topic, an additional nine original research articles have been published, strengthening our understanding of coralline algae past, present, and future, including their biology, physiology and ecology. From reconstructing coralline algal assemblages during the Paleocene/Eocene thermal maximum, to understanding current trophodynamics and benthic-pelagic coupling in rhodolith beds, to assessing the adaptability of coralline algae to future warming, the original research articles in this Research Topic cover a time frame of 55.6 million years and span across an Atlantic biogeographical range from Brazil to the high Arctic.1521610info:eu-repo/semantics/publishedVersio

Editorial: Coralline algae: Past, present, and future perspectives

Following the success of the Frontiers in Marine Science Research Topic on “Coralline Algae: Globally Distributed Ecosystem Engineers,” the Research Topic on “Coralline Algae: Past, Present and Future Perspectives” was launched to extend the opportunity for publishing further knowledge about these diverse ecosystem engineers across a broader time scale. In this Research Topic, an additional nine original research articles have been published, strengthening our understanding of coralline algae past, present, and future, including their biology, physiology and ecology. From reconstructing coralline algal assemblages during the Paleocene/Eocene thermal maximum, to understanding current trophodynamics and benthic-pelagic coupling in rhodolith beds, to assessing the adaptability of coralline algae to future warming, the original research articles in this Research Topic cover a time frame of 55.6 million years and span across an Atlantic biogeographical range from Brazil to the high Arctic.info:eu-repo/semantics/publishedVersio

Editorial: coralline algae: globally distributed ecosystem engineers

From the early days of phycology, coralline algae (CA) have been considered the most formidable and widely distributed algae (Woelkerling, 1988). They compose an abundant and highly diverse group, divided into geniculate (articulated) and non-geniculate species (crusts and rhodolith/maërl forms). CA are present in almost every coastal ecosystem around the world, from the intertidal to mesophotic zones (Johansen et al., 1981; Steneck, 1986; Foster, 2001). They are important ecosystem engineers that provide hard, three-dimensional substrates for a highly diverse fauna and flora (Nelson, 2009), building habitats like the globally distributed rhodolith (or maërl) beds (Foster, 2001), and the large algal bioconstructions that abound in the Mediterranean (coralligenous assemblages, intertidal rims; Ingrosso et al., 2018). In addition, the CaCO3 precipitation within cell walls leads to a high fossilization potential of CA, which are considered the best fossil record among macrobenthic autotrophs since they first appeared in the Lower Cretaceous (Aguirre et al., 2000). It also makes CA major carbonate producers (van der Heijden and Kamenos, 2015), which, considering their abundance and wide distribution, gives them an important role in oceanic carbon cycling and reef building (Adey, 1998; Chisholm, 2003; Martin et al., 2006; Perry et al., 2008) and makes them a group of significant economic interest (Coletti and Frixa, 2017). Like many other marine ecosystems, CA habitats will be negatively affected by future climate change, e.g., due to reduced CA calcification/growth (Martin andHall-Spencer, 2017; Cornwall et al., 2019) that may eventually lead to ecosystem degradation and reduction of habitat complexity and biodiversity.FCT: UID/Multi/04326/2019; European Union (EU): 844703 and 2018-W-MS-35; FINEP/Rede CLIMA 01.13.0353-00; National Council for Scientific and Technological Development (CNPq) 426215/2016; National Science Foundation Ocean Sciences International Postdoctoral Research Fellow program 1521610 nvironmental Protection Agency in Ireland .info:eu-repo/semantics/publishedVersio

Thymus transplantation for complete DiGeorge syndrome: European experience

Background: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods: Twelve patients with cDGS were transplanted with allogeneic cultured thymus. Objective: To confirm and extend the results previously obtained in a single centre. Results: Two patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x10663 /L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per106 65 T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1). Conclusions: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Biochemical characterization of signaling pathways regulating cell survival

The granulocyte/macrophage colony stimulating factor (GM-CSF) exerts its antiapoptotic effects on hemopoietic cells by activating multiple cellular signaling pathways including the phosphatidylinositol 3'-OH kinase (PI3K) cell survival pathway and the Ras-Raf-MEK-ERK kinase cascade. I hypothesized that cytokines activate each of these pathways to regulate components of the apoptotic machinery, including members of the Bcl-2 family. The mechanism by which cytokines such as GM-CSF regulate expression of Bcl-2 family members was examined in several models, including primary human eosinophils and basophils, and the hemopoietic cell lines TF-1 and MC/9. Protein expression of one pro-survival Bcl-2 family member, Mcl-1, was found to be dependent upon phosphatidylinositol (PI) 3-kinase. The cytokine-induced increase in Mcl-1 mRNA transcription was not dependent upon PI3K, thus dissociating the immediate-early transcription factors responsible for Mcl-1 transcription from the PI3K signaling pathway. In contrast, Mcl-1 mRNA levels were dependent upon MEK activation, suggesting a role for the Ras-MEK-ERK pathway in Mcl-1 transcription. However, activation of PI3K was shown to be necessary for GM-CSF to stimulate Mcl-1 protein translation. This was not due to any effect on prolonging the half-life of the protein. I was also interested in other pathways that may regulate PI3K and Mcl-1 to affect cell survival. The second messenger ceramide has been implicated in a host of cellular processes including growth arrest and apoptosis. The relationship between ceramide signaling and the activation of PI3K and its downstream target, protein kinase B (PKB) was examined in detail. PKB activation was observed following stimulation of cells with GM-CSF. Addition of cell-permeable analogs, C₂- or C₆-ceramide, caused a partial loss (50-60%) of PKB activation and resulted in reduced Mcl-1 translation. These reductions were not a result of a decrease in PI(3,4,5)P₃ or PI(3,4)P₂ generation by PI3K. Two residues of PKB (threonine 308 and serine 473) require phosphorylation for maximal PKB activation. Ser⁴⁷³ phosphorylation was consistently reduced by treatment with ceramide, whereas Thr³⁰⁸ phosphorylation remained unaffected. In further experiments, ceramide appeared to accelerate Ser⁴⁷³ dephosphorylation, suggesting the activation of a phosphatase. Consistent with this, the reduction in Ser⁴⁷³ phosphorylation was inhibited by the phosphatase inhibitors okadaic acid and calyculin A. Surprisingly, Thr³⁰⁸ phosphorylation was abolished in cells treated with these inhibitors, revealing a novel mechanism of regulation of Thr³⁰⁸ phosphorylation. These results demonstrate that PDK2-catalyzed phosphorylation of Ser⁴⁷³ is the principal target of a ceramide-activated phosphatase, which may regulate cell survival by reducing the level of pro-survival proteins such as Mcl-1.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat

Joane Cardinal-Schubert : Two Decades

Accompanying a retrospective exhibition of Cardinal-Schubert's paintings and installations from 1977 through 1997, this catalogue contains an interpretive essay by Burns and an interview with the artist by G. McMaster. Issues concerning the environment, human rights and racism are discussed in relation to the lost history and cultural genocide of First Nations people. Includes a brief history of the Muttart Public Art Gallery, an artist's statement and photos from personnal archives. Biographical notes on the artist and the interviewer. 3 bibl. ref