Late Miocene marine ostracods from Santa Maria island,Azores (NE Atlantic): Systematics,palaeoecology and palaeobiogeography

The nine oceanic islands that comprise the Azores archipelago are located in the middle of the northern Atlantic Ocean. In this isolated archipelago, there is a rich fossil record in one of the islands, Santa Maria. In this island, samples were collected in the Upper Miocene composite section of Malbusca outcrop, located in the southern shore of the island, and the fossil marine Ostracoda were studied. This work represents the first report of fossil ostracods from the Azores archipelago. Thirteen species were found, representing seven families and 12 genera (Xestoleberis, Loxoconcha, Callistocythere, Leptocythere, Dameriacella, Aurila, Heliocythere, Pachycaudites, Neonesidea, Cyamocytheridea, ?Quadracythere and Paracypris). Among the identified species, one new species, Leptocythere azorica n. sp., is described. Loxoconcha (two species) was the most diversified genus. The collected species are mainly ornamented and typical of warm waters and epi-neritic habitats (～ 10–50 m of depth).     

Stem-cell approaches for kidney repair: choosing the right cells

With the increasing rate of end-stage renal failure and limited alternatives for its treatment, stem cell (SC) therapy for kidney injury is urgently needed. Choosing the right SC type is the critical step in realizing the potential of this therapeutic approach. Four possible sources of SCs are envisioned for the development of this type of treatment: (i) bone-marrow-derived SCs (BMSCs), (ii) renal adult SCs, (iii) embryonic SCs and (iv) fetal renal SCs. We suggest that resident SCs recently identified in the Bowman's capsule of adult human kidneys might prospectively be the ideal cell type for treatment of both acute and chronic renal injury because they display the potential to differentiate into multiple types of renal cells. However, BMSCs also represent an attractive alternative, especially for the treatment of patients affected by acute renal failure.     

ErbB4 expression in neural progenitor cells (ST14A) is necessary to mediate neuregulin-1beta1-induced migration

Activation of the receptor tyrosine kinase ErbB4 leads to various cellular responses such as proliferation, survival, differentiation, and chemotaxis. Two pairs of naturally occurring ErbB4 isoforms differing in their juxtamembrane (JMa/JMb) and C termini (cyt1/cyt2) have been described. To examine the role of ErbB4 in neuron migration, we cloned and stably transfected each of the four ErbB4 isoforms in ST14A cells (a neural progenitor cell line derived from the striatum of embryonic day 14 rats) endogenously expressing the other members of the ErbB family: ErbB1, ErbB2, and ErbB3. Using immunoprecipitation assays, we showed that the neuregulin-1beta1 (NRG1beta1) stimulus induced ErbB4 tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3K) recruitment and activation (as demonstrated by Akt phosphorylation) either directly (ErbB4 cyt1 isoform) or indirectly (ErbB4 cyt2 isoform). We examined the ability of the four ErbB4 isoforms to induce chemotaxis and cell proliferation in response to NRG1beta1 stimulation. Using migration assays, we observed that only ErbB4-expressing cells stimulated with NRG1beta1 showed a significant increase in migration, whereas the growth rate remained unchanged. Additional assays showed that inhibition of PI3K (but not of phospholipase Cgamma) dramatically reduced migratory activity. Our data show that ErbB4 signaling via PI3K activation plays a fundamental role in controlling NRG1beta1-induced migration.     

Expert Opinions on Improving Femicide Data Collection across Europe: A Concept Mapping Study

Femicide, defined as the killings of females by males because they are females, is becoming recognized worldwide as an important ongoing manifestation of gender inequality. Despite its high prevalence or widespread prevalence, only a few countries have specific registries about this issue. This study aims to assemble expert opinion regarding the strategies which might feasibly be employed to promote, develop and implement an integrated and differentiated femicide data collection system in Europe at both the national and international levels. Concept mapping methodology was followed, involving 28 experts from 16 countries in generating strategies, sorting and rating them with respect to relevance and feasibility. The experts involved were all members of the EU-Cost-Action on femicide, which is a scientific network of experts on femicide and violence against women across Europe. As a result, a conceptual map emerged, consisting of 69 strategies organized in 10 clusters, which fit into two domains: “Political action” and “Technical steps”. There was consensus among participants regarding the high relevance of strategies to institutionalize national databases and raise public awareness through different stakeholders, while strategies to promote media involvement were identified as the most feasible. Differences in perceived priorities according to the level of human development index of the experts’ countries were also observed.     

Light‐dependent reversible phosphorylation of the minor photosystem II antenna Lhcb6 (CP24) occurs in lycophytes

Evolution of vascular plants required compromise between photosynthesis and photodamage. We analyzed representative species from two divergent lineages of vascular plants, lycophytes and euphyllophytes, with respect to the response of their photosynthesis and light‐harvesting properties to increasing light intensity. In the two analyzed lycophytes, Selaginella martensii and Lycopodium squarrosum, the medium phase of non‐photochemical quenching relaxation increased under high light compared to euphyllophytes. This was thought to be associated with the occurrence of a further thylakoid phosphoprotein in both lycophytes, in addition to D2, CP43 and Lhcb1‐2. This protein, which showed light intensity‐dependent reversible phosphorylation, was identified in S. martensii as Lhcb6, a minor LHCII antenna subunit of PSII. Lhcb6 is known to have evolved in the context of land colonization. In S. martensii, Lhcb6 was detected as a component of the free LHCII assemblies, but also associated with PSI. Most of the light‐induced changes affected the amount and phosphorylation of the LHCII assemblies, which possibly mediate PSI–PSII connectivity. We propose that Lhcb6 is involved in light energy management in lycophytes, participating in energy balance between PSI and PSII through a unique reversible phosphorylation, not yet observed in other land plants.     

Cowchock Syndrome Is Associated with a Mutation in Apoptosis-Inducing Factor

Cowchock syndrome (CMTX4) is a slowly progressive X-linked recessive disorder with axonal neuropathy, deafness, and cognitive impairment. The disease locus was previously mapped to an 11 cM region at chromosome X: q24-q26. Exome sequencing of an affected individual from the originally described family identified a missense change c.1478A>T (p.Glu493Val) in AIFM1, the gene encoding apoptosis-inducing factor (AIF) mitochondrion-associated 1. The change is at a highly conserved residue and cosegregated with the phenotype in the family. AIF is an FAD-dependent NADH oxidase that is imported into mitochondria. With apoptotic insults, a N-terminal transmembrane linker is cleaved off, producing a soluble fragment that is released into the cytosol and then transported into the nucleus, where it triggers caspase-independent apoptosis. Another AIFM1 mutation that predicts p.Arg201del has recently been associated with severe mitochondrial encephalomyopathy in two infants by impairing oxidative phosphorylation. The c.1478A>T (p.Glu493Val) mutation found in the family reported here alters the redox properties of the AIF protein and results in increased cell death via apoptosis, without affecting the activity of the respiratory chain complexes. Our findings expand the spectrum of AIF-related disease and provide insight into the effects of AIFM1 mutations.     

Late Miocene ostracod assemblages from eastern Mediterranean coral reef complexes (central Crete,Greece)

Ostracods from ten Late Miocene coral reef complexes built by Siderastrea, Tarbellastrea and Porites, cropping out in the Messara Plain (southern Iraklion basin, central Crete), have been investigated and five assemblages have been recognised, which point to different marine environments: (1) assemblage from the basal sandy silts, dominated by very shallow inner-infralittoral species, such as Cyamocytheridea meniscus, Cyamocytheridea obstipa, Cyamocytheridea dertonensis, Cytheretta semiornata and Nonurocythereis seminulum; (2) assemblage from the coral reef complexes within which Grinioneis haidingeri, Aurila cicatricosa, Cimbaurila diecii, Tenedocythere cruciata, Pokornyella italica and Callistocythere quadrangula are dominant and point to a stable inner-infralittoral environment characterised by warm, quiet and well-oxygenated waters; (3) assemblage from the silts intercalated among the coral reef complexes, mainly characterised by Neomonoceratina laskarevi, Cytheridea acuminata, Phlyctenophora farkasi and Aurila albicans together with Callistocythere spp., Xestoleberis communis and Xestoleberis dispar, which points to a very shallow marine environment rich in aquatic vegetation; (4) assemblage from the upper silts, which records the absolute dominance of Xestoleberis species, reflecting a very shallow and highly-vegetated environment and (5) assemblage from the uppermost silty clays, dominated by Hemicytherura defiorei, Xestoleberis spp. and Palmoconcha dertobrevis, accompanied by Acanthocythereis hystrix, Cytherella scutulum, Bairdoppilata conformis, Semicytherura spp., Krithe sp., Cytheropteron alatum, Bythocypris sp. and Pseudocythere caudata, which suggest deeper marine environments probably located in the outer infralittoral/inner-circalittoral zones. The studied section has been dated by means of calcareous nannoplankton to be not younger than Zone MNN9 (Early Tortonian), which is the biostratigraphical datum recorded in the fine-grained deposits that overlie the coral reef complexes. An age not older than Tortonian can be inferred by the stratigraphical distribution of the recognized ostracods. Thus, the coral reef complexes have been tentatively referred to the Early Tortonian.     

Co‐targeting the PI3K/mTOR and JAK2 signalling pathways produces synergistic activity against myeloproliferative neoplasms

Aberrant JAK2 signalling plays a central role in myeloproliferative neoplasms (MPN). JAK2 inhibitors have proven to be clinically efficacious, however, they are not mutation‐specific and competent enough to suppress neoplastic clonal haematopoiesis. We hypothesized that, by simultaneously targeting multiple activated signalling pathways, MPN could be more effectively treated. To this end we investigated the efficacy of BEZ235, a dual PI3K/mTOR inhibitor, alone and in combination with the JAK1/JAK2 inhibitor ruxolitinib, in different preclinical models of MPN. Single‐agent BEZ235 inhibited the proliferation and induced cell cycle arrest and apoptosis of mouse and human JAK2V617F mutated cell lines at concentrations significantly lower than those required to inhibit the wild‐type counterpart, and preferentially prevented colony formation from JAK2V617F knock‐in mice and patients' progenitor cells compared with normal ones. Co‐treatment of BEZ235 and ruxolitinib produced significant synergism in all these in‐vitro models. Co‐treatment was also more effective than single drugs in reducing the extent of disease and prolonging survival of immunodeficient mice injected with JAK2V617F‐mutated Ba/F3‐EPOR cells and in reducing spleen size, decreasing reticulocyte count and improving spleen histopathology in conditional JAK2V617F knock‐in mice. In conclusion, combined inhibition of PI3K/mTOR and JAK2 signalling may represent a novel therapeutic strategy in MPN.