Large-scale testing of phytoplankton diversity indices for environmental assessment in Mediterranean sub-regions (Adriatic, Ionian and Aegean Seas)

Abstract According to the methodological standards established by Marine Strategy Framework Directive, the assessment for the pelagic habitat under the Biodiversity Descriptor should be carried out at the regional or sub-regional level. In the case of Mediterranean Sea, the sub-regional assessment seems optimal to take into account biogeographic differences in species composition and functional characteristics. Previous research has shown that phytoplankton diversity indicators are efficient for reliable environmental assessments, although more effort has been recommended to test these indicators on a wide spatial scale to cover wider gradients of natural and anthropogenic pressures. In this work, a set of eight diversity indices was tested against the pressure levels within a common data set of the structure and abundance of phytoplankton communities from the Adriatic, Ionian and Aegean Seas. Expert knowledge was used to define four categories of impacts that take into account partial pressures, such as point and non-point pollution, industry, ports and fisheries. At the level of the common data set, most of the diversity, evenness and dominance indices could only distinguish between the highest level of impact and the rest of impact categories. These indices maintained the distinction between two levels of subsequently dichotomised impacts (no to low impact vs. high impact) across latitudinal and longitudinal gradients. On average, the indices were less sensitive to impacts in the northernmost and westernmost areas than in the southernmost and easternmost areas, although they still showed a significant response. The results also suggest that phytoplankton communities become more uniform and less dominated by a single taxon as sampling depth increases at sites with low impact, while evenness and dominance at impacted sites remain similar at all depths. In order to establish meaningful definitions of good environmental status and targets for pelagic habitats in the Mediterranean Sea, it is necessary to establish spatially specific thresholds by additional examination of indices of good performance

CUX1-related neurodevelopmental disorder: deep insights into phenotype-genotype spectrum and underlying pathology

Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1+/− mouse model. Through international collaboration, we assembled the phenotypic and molecular information for 34 individuals (23 unpublished individuals). We analyze brain CUX1 expression and susceptibility to epilepsy in Cux1+/− mice. We describe 34 individuals, from which 30 were unrelated, with 26 different null and four missense variants. The leading symptoms were mild to moderate delayed speech and motor development and borderline to moderate intellectual disability. Additional symptoms were muscular hypotonia, seizures, joint laxity, and abnormalities of the forehead. In Cux1+/− mice, we found delayed growth, histologically normal brains, and increased susceptibility to seizures. In Cux1+/− brains, the expression of Cux1 transcripts was half of WT animals. Expression of CUX1 proteins was reduced, although in early postnatal animals significantly more than in adults. In summary, disease-causing CUX1 variants result in a non-syndromic phenotype of developmental delay and intellectual disability. In some individuals, this phenotype ameliorates with age, resulting in a clinical catch-up and normal IQ in adulthood. The post-transcriptional balance of CUX1 expression in the heterozygous brain at late developmental stages appears important for this favorable clinical course.CAG was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number P50 HD103525. This work was funded by PID2020-112831GB-I00 AEI /10.13039/501100011033 (MN). SS was supported by a grant from the NIH/NINDS (K23NS119666). SWS is supported by the Hospital for Sick Children Foundation, Autism Speaks, and the University of Toronto McLaughlin Center. EM-G was supported by a grant from MICIU FPU18/06240. EVS. was supported by a grant from the NIH (EY025718). CRF was supported by the fund to support clinical research careers in the Region of Southern Denmark (Region Syddanmarks pulje for kliniske forskerkarriereforløb).Peer reviewe

Time to Rethink Refugee and Migrant Health in Europe: Moving from Emergency Response to Integrated and Individualized Health Care Provision for Migrants and Refugees

In the last three years, the European Union (EU) is being confronted with the most significant influx of migrants and refugees since World War II. Although the dimensions of this influx—taking the global scale into account—might be regarded as modest, the institutional response to that phenomenon so far has been suboptimal, including the health sector. While inherent challenges of refugee and migrant (R&M) health are well established, it seems that the EU health response oversees, to a large extend, these aspects. A whole range of emergency-driven health measures have been implemented throughout Europe, yet they are failing to address adequately the changing health needs and specific vulnerabilities of the target population. With the gradual containment of the migratory and refugee waves, three years after the outbreak of the so-called ‘refugee crisis’, we are, more than ever, in need of a sustainable and comprehensive health approach that is aimed at the integration of all of migrants and refugees—that is, both the new and old population groups that are already residing in Europe—in the respective national health systems

Association of Pregnant Women’s Perinatal Depression with Sociodemographic, Anthropometric and Lifestyle Factors and Perinatal and Postnatal Outcomes: A Cross-Sectional Study

Background: In recent decades, the incidence of depression has gradually increased in the general population globally. Depression is also common during gestation and could result in detrimental gestational complications for both the mother and the fetus. The survey presented aimed to evaluate whether pregnant women’s perinatal depression could be associated with socio-demographic, anthropometry and lifestyle factors, and perinatal and postnatal outcomes. Methods: This is a cross-sectional survey conducted on 5314 pregnant women. Socio-demographic and lifestyle factors were recorded by relevant questionnaires via face-to-face interviews. Anthropometric parameters were measured by qualified personnel. Perinatal depressive symptomatology status was evaluated by Beck’s Depression Inventory (BDI-II) questionnaire. Results: Depressive symptoms throughout gestation were found in 35.1% of the enrolled women. Perinatal depression was significantly associated with lower educational and economic level, pre-pregnancy regular smoking and reduced levels of Mediterranean diet adherence levels, a higher prevalence of gestational diabetes and preterm birth, as well as a higher incidence of delivering by caesarean section and abnormal childbirth weight. Perinatal depression was also significantly associated with a higher prevalence of maternal postpartum depression and lower prevalence of exclusive breastfeeding practices, as well as with a higher incidence of childhood asthma. Conclusions: Pregnant women’s perinatal depression appears to be associated with various socio-demographic, anthropometry, and lifestyle characteristics and with a higher frequency of several adverse pregnancy complications. The present findings emphasize the importance of pregnant women’s perinatal mental health, highlighting the need to develop and apply public strategies and policies for psychological counseling and support of future mothers to minimize probable risk factors that may trigger perinatal depression. Novel well-organized, follow-up surveys of enhanced validity are highly recommended to establish more definitive conclusions

Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro

HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC), and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA mutated and PIK3CA-wild type HER2/neu amplified USC cell lines. Cell viability and cell cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC-xenografts. We found both single agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long lasting growth inhibition in both USC xenografts when compared to single agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA or pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild type PIK3CA resistant to chemotherapy

Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo

OBJECTIVE: To evaluate the efficacy of Taselisib, a selective inhibitor of PIK3CA, against primary uterine serous carcinomas (USC) harboring PIK3CA mutations and HER2/neu gene amplification. METHODS: Sensitivity to taselisib was evaluated by flow-cytometry viability assays in vitro against nine primary USC cell lines. Cell cycle distribution and downstream signaling were assessed by measuring the DNA content of cells and by phosphorylation of the S6 protein by flow-cytometry. Preclinical efficacy of taselisib was also evaluated in vivo in a mouse model. RESULTS: Four USC cell lines harbored HER2/neu gene amplification by FISH and two of them harbored oncogenic PIK3CA mutations. Taselisib caused a strong differential growth inhibition in both HER2/neu FISH positive and HER2/neu FISH positive/PIK3CA mutated USC cell lines when compared to lines that were FISH negative and PIK3CA wild type (taselisib IC(50) mean±SEM= 0.042 ± 0.006 µM in FISH+ versus 0.38 ± 0.06 µM in FISH- tumors, P <0.0001). Taselisib growth-inhibition was associated with a significant and dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and dose-dependent decline in the phosphorylation of S6. Taselisib was highly active at reducing tumor growth in vivo in USC mouse xenografts harboring PIK3CA mutation and overexpressing HER2/neu (P=0.007). Mice treated with taselisib had significantly longer survival when compared to control mice (P<0.0001). CONCLUSIONS: Taselisib represents a novel therapeutic option in patients harboring PIK3CA mutations and/or HER2/neu gene amplification

CoCoNet: Towards coast to coast networks of marine protected areas (From the shore to the high and deep sea), coupled with sea-based wind energy potential

This volume contains the main results of the EC FP7 "The Ocean of Tomorrow" Project CoCoNet, divided in two sections: 1) a set of guidelines to design networks of Marine Protected Areas in the Mediterranean and the Black Seas; 2) a smart wind chart that will allow evaluating the possibility of installing Offshore Wind Farms in both seas. The concept of Cells of Ecosystem Functioning, based on connectivity, is introduced to define natural units of management and conservation. The definition of Good Environmental Status, as defined in the Marine Strategy Framework Directive, is fully embraced to set the objectives of the project, by adopting a holistic approach that integrates a full set of disciplines, ranging from physics to bio-ecology, economics, engineering and many sub-disciplines. The CoCoNet Consortium involved scientist sfrom 22 states, based in Africa, Asia, and Europe, contributing to build a coherent scientific community

Editorial. A supplement of Scires-it on the COCONET european project

The Supplement to vol. 6, 2016 of SCIRES-IT contains the result of CoCoNet (Towards COast to COast NETworks of marine protected areas, coupled with sea-based wind energy potential), a project of the EU Oceans of Tomorrow programme (http://www.coconet-fp7.eu). The European Union requires Open Access to the results of the projects resulting from its support to scientific advancement. This is in full accordance with the policy of SCIRES-IT, an eco-sustainable open–access journal, which joins the main principles of the Berlin Declaration on Open Access with the aims of the International Convention on Biological Diversity. CoCoNet tackled two problems that are closely linked with each other: the protection of the marine environment and clean energy production. Hence, the Supplement is divided into two parts that, together, form a unicum

CoCoNet: towards coast to coast networks of marine protected areas (from the shore to the high and deep sea), coupled with sea-based wind energy potential

This volume contains the main results of the EC FP7 “The Ocean of Tomorrow” Project CoCoNet, divided in two sections: 1) a set of guidelines to design networks of Marine Protected Areas in the Mediterranean and the Black Seas; 2) a smart wind chart that will allow evaluating the possibility of installing Offshore Wind Farms in both seas. The concept of Cells of Ecosystem Functioning, based on connectivity, is introduced to define natural units of management and conservation. The definition of Good Environmental Status, as defined in the Marine Strategy Framework Directive, is fully embraced to set the objectives of the project, by adopting a holistic approach that integrates a full set of disciplines, ranging from physics to bio-ecology, economics, engineering and many sub-disciplines. The CoCoNet Consortium involved scientist sfrom 22 states, based in Africa, Asia, and Europe, contributing to build a coherent scientific community