E-skills

This policy paper draws on data from the Household and Individual Access and Usage Survey conducted across 17 African countries regarding connectivity and access to ICTs. The paper proposes that the stock of citizens with completed secondary and tertiary education is the best indicator for computer and internet skills. This research identifies an indicator that captures e-skills better than existing indicators in use. E-skills permit those who have them to participate more effectively in the global information economy and society, access opportunities to conduct business, and engage and transact more efficiently

Final countdown for biodiversity hotspots

Most of Earth's biodiversity is found in 36 biodiversity hotspots, yet less than 10% natural intact vegetation remains. We calculated models projecting the future state of most of these hotspots for the year 2050, based on future climatic and agroeconomic pressure. Our models project an increasing demand for agricultural land resulting in the conversion of >50% of remaining natural intact vegetation in about one third of all hotspots, and in 2-6 hotspots resulting from climatic pressure. This confirms that, in the short term, habitat loss is of greater concern than climate change for hotspots and their biodiversity. Hotspots are most severely threatened in tropical Africa and parts of Asia, where demographic pressure and the demand for agricultural land is highest. The speed and magnitude of pristine habitat loss is, according to our models, much greater than previously shown when combining both scenarios on future climatic and agroeconomic pressure

The mycotoxin phomoxanthone A disturbs the form and function of the inner mitochondrial membrane.

Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, the buffering of cytosolic Ca2+ and the initiation of apoptosis. Compounds that interfere with these functions are termed mitochondrial toxins, many of which are derived from microbes, such as antimycin A, oligomycin A, and ionomycin. Here, we identify the mycotoxin phomoxanthone A (PXA), derived from the endophytic fungus Phomopsis longicolla, as a mitochondrial toxin. We show that PXA elicits a strong release of Ca2+ from the mitochondria but not from the ER. In addition, PXA depolarises the mitochondria similarly to protonophoric uncouplers such as CCCP, yet unlike these, it does not increase but rather inhibits cellular respiration and electron transport chain activity. The respiration-dependent mitochondrial network structure rapidly collapses into fragments upon PXA treatment. Surprisingly, this fragmentation is independent from the canonical mitochondrial fission and fusion mediators DRP1 and OPA1, and exclusively affects the inner mitochondrial membrane, leading to cristae disruption, release of pro-apoptotic proteins, and apoptosis. Taken together, our results suggest that PXA is a mitochondrial toxin with a novel mode of action that might prove a useful tool for the study of mitochondrial ion homoeostasis and membrane dynamics

The type II secretion system (Xcp) of Pseudomonas putida is active and involved in the secretion of phosphatases.

The genome of the Gram-negative bacterium Pseudomonas putida harbours a complete set of xcp genes for a type II protein secretion system (T2SS). This study shows that expression of these genes is induced under inorganic phosphate (Pi ) limitation and that the system enables the utilization of various organic phosphate sources. A phosphatase of the PhoX family, previously designated UxpB, was identified, which was produced under low Pi conditions and transported across the cell envelope in an Xcp-dependent manner demonstrating that the xcp genes encode an active T2SS. The signal sequence of UxpB contains a twin-arginine translocation (Tat) motif as well as a lipobox, and both processing by leader peptidase II and Tat dependency were experimentally confirmed. Two different tat gene clusters were detected in the P.?putida genome, of which one, named tat-1, is located adjacent to the uxpB and xcp genes. Both Tat systems appeared to be capable of transporting the UxpB protein. However, expression of the tat-1 genes was strongly induced by low Pi levels, indicating a function of this system in survival during Pi starvation

Discordant assessment of tumor biomarkers by histopathological and molecular assays in the EORTC randomized controlled 10041/BIG 03-04 MINDACT trial breast cancer

Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Scientists' warning to humanity on insect extinctions

Here we build on the manifesto ‘World Scientists’ Warning to Humanity, issued by the Alliance of World Scientists. As a group of conservation biologists deeply concerned about the decline of insect populations, we here review what we know about the drivers of insect extinctions, their consequences, and how extinctions can negatively impact humanity. We are causing insect extinctions by driving habitat loss, degradation, and fragmentation, use of polluting and harmful substances, the spread of invasive species, global climate change, direct overexploitation, and co-extinction of species dependent on other species. With insect extinctions, we lose much more than species. We lose abundance and biomass of insects, diversity across space and time with consequent homogenization, large parts of the tree of life, unique ecological functions and traits, and fundamental parts of extensive networks of biotic interactions. Such losses lead to the decline of key ecosystem services on which humanity depends. From pollination and decomposition, to being resources for new medicines, habitat quality indication and many others, insects provide essential and irreplaceable services. We appeal for urgent action to close key knowledge gaps and curb insect extinctions. An investment in research programs that generate local, regional and global strategies that counter this trend is essential. Solutions are available and implementable, but urgent action is needed now to match our intentions.Peer reviewe

Solutions for humanity on how to conserve insects

The fate of humans and insects intertwine, especially through the medium of plants. Global environmental change, including land transformation and contamination, is causing concerning insect diversity loss, articulated in the companion review Scientists' warning to humanity on insect extinctions. Yet, despite a sound philosophical foundation, recognized ethical values, and scientific evidence, globally we are performing poorly at instigating effective insect conservation. As insects are a major component of the tapestry of life, insect conservation would do well to integrate better with overall biodiversity conservation and climate change mitigation. This also involves popularizing insects, especially through use of iconic species, through more media coverage, and more inclusive education. Insect conservationists need to liaise better with decision makers, stakeholders, and land managers, especially at the conceptually familiar scale of the landscape. Enough evidence is now available, and synthesized here, which illustrates that multiple strategies work at local levels towards saving insects. We now need to expand these locally-crafted strategies globally. Tangible actions include ensuring maintenance of biotic complexity, especially through improving temporal and spatial heterogeneity, functional connectivity, and metapopulation dynamics, while maintaining unique habitats, across landscape mosaics, as well as instigating better communication. Key is to have more expansive sustainable agriculture and forestry, improved regulation and prevention of environmental risks, and greater recognition of protected areas alongside agro-ecology in novel landscapes. Future-proofing insect diversity is now critical, with the benefits far reaching, including continued provision of valuable ecosystem services and the conservation of a rich and impressive component of Earth's biodiversity.Peer reviewe

70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.

The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.)

An Outer Membrane Receptor of Neisseria meningitidis Involved in Zinc Acquisition with Vaccine Potential

Since the concentration of free iron in the human host is low, efficient iron-acquisition mechanisms constitute important virulence factors for pathogenic bacteria. In Gram-negative bacteria, TonB-dependent outer membrane receptors are implicated in iron acquisition. It is far less clear how other metals that are also scarce in the human host are transported across the bacterial outer membrane. With the aim of identifying novel vaccine candidates, we characterized in this study a hitherto unknown receptor in Neisseria meningitidis. We demonstrate that this receptor, designated ZnuD, is produced under zinc limitation and that it is involved in the uptake of zinc. Upon immunization of mice, it was capable of inducing bactericidal antibodies and we could detect ZnuD-specific antibodies in human convalescent patient sera. ZnuD is highly conserved among N. meningitidis isolates and homologues of the protein are found in many other Gram-negative pathogens, particularly in those residing in the respiratory tract. We conclude that ZnuD constitutes a promising candidate for the development of a vaccine against meningococcal disease for which no effective universal vaccine is available. Furthermore, the results suggest that receptor-mediated zinc uptake represents a novel virulence mechanism that is particularly important for bacterial survival in the respiratory tract

Patients with coronary artery disease and diabetes need improved management: a report from the EUROASPIRE IV survey: a registry from the EuroObservational Research Programme of the European Society of Cardiology

BACKGROUND: In order to influence every day clinical practice professional organisations issue management guidelines. Cross-sectional surveys are used to evaluate the implementation of such guidelines. The present survey investigated screening for glucose perturbations in people with coronary artery disease and compared patients with known and newly detected type 2 diabetes with those without diabetes in terms of their life-style and pharmacological risk factor management in relation to contemporary European guidelines. ----- METHODS: A total of 6187 patients (18-80 years) with coronary artery disease and known glycaemic status based on a self reported history of diabetes (previously known diabetes) or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24 European countries 2012-2013. The patients were interviewed and investigated in order to enable a comparison between their actual risk factor control with that recommended in current European management guidelines and the outcome in previously conducted surveys. ----- RESULTS: A total of 2846 (46%) patients had no diabetes, 1158 (19%) newly diagnosed diabetes and 2183 (35%) previously known diabetes. The combined use of all four cardioprotective drugs in these groups was 53, 55 and 60%, respectively. A blood pressure target of 9.0% (>75 mmol/mol). Of the patients with diabetes 69% reported on low physical activity. The proportion of patients participating in cardiac rehabilitation programmes was low (≈40 %) and only 27% of those with diabetes had attended diabetes schools. Compared with data from previous surveys the use of cardioprotective drugs had increased and more patients were achieving the risk factor treatment targets. ----- CONCLUSIONS: Despite advances in patient management there is further potential to improve both the detection and management of patients with diabetes and coronary artery disease