Improve Alignment of Research Policy and Societal Values

Historically, scientific and engineering expertise has been key in shaping research and innovation (R&I) policies, with benefits presumed to accrue to society more broadly over time (1). But there is persistent and growing concern about whether and how ethical and societal values are integrated into R&I policies and governance, as we confront public disbelief in science and political suspicion toward evidence-based policy-making (2). Erosion of such a social contract with science limits the ability of democratic societies to deal with challenges presented by new, disruptive technologies, such as synthetic biology, nanotechnology, genetic engineering, automation and robotics, and artificial intelligence. Many policy efforts have emerged in response to such concerns, one prominent example being Europe's Eighth Framework Programme, Horizon 2020 (H2020), whose focus on “Responsible Research and Innovation” (RRI) provides a case study for the translation of such normative perspectives into concrete policy action and implementation. Our analysis of this H2020 RRI approach suggests a lack of consistent integration of elements such as ethics, open access, open innovation, and public engagement. On the basis of our evaluation, we suggest possible pathways for strengthening efforts to deliver R&I policies that deepen mutually beneficial science and society relationships.Horizon 2020(H2020)741402Merit, Expertise and Measuremen

Over-expression of Grhl2 causes spina bifida in the Axial defects mutant mouse

Cranial neural tube defects (NTDs) occur in mice carrying mutant alleles of many different genes, whereas isolated spinal NTDs (spina bifida) occur in fewer models, despite being common human birth defects. Spina bifida occurs at high frequency in the Axial defects (Axd) mouse mutant but the causative gene is not known. In the current study, the Axd mutation was mapped by linkage analysis. Within the critical genomic region, sequencing did not reveal a coding mutation whereas expression analysis demonstrated significant up-regulation of grainyhead-like 2 (Grhl2) in Axd mutant embryos. Expression of other candidate genes did not differ between genotypes. In order to test the hypothesis that over-expression of Grhl2 causes Axd NTDs, we performed a genetic cross to reduce Grhl2 function in Axd heterozygotes. Grhl2 loss of function mutant mice were generated and displayed both cranial and spinal NTDs. Compound heterozygotes carrying both loss (Grhl2 null) and putative gain of function (Axd) alleles exhibited normalization of spinal neural tube closure compared with Axd/+ littermates, which exhibit delayed closure. Grhl2 is expressed in the surface ectoderm and hindgut endoderm in the spinal region, overlapping with grainyhead-like 3 (Grhl3). Axd mutants display delayed eyelid closure, as reported in Grhl3 null embryos. Moreover, Axd mutant embryos exhibited increased ventral curvature of the spinal region and reduced proliferation in the hindgut, reminiscent of curly tail embryos, which carry a hypomorphic allele of Grhl3. Overall, our data suggest that defects in Axd mutant embryos result from over-expression of Grhl2

Clinical significance of HIV-1 coreceptor usage

The identification of phenotypically distinct HIV-1 variants with different prevalence during the progression of the disease has been one of the earliest discoveries in HIV-1 biology, but its relevance to AIDS pathogenesis remains only partially understood. The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells. The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades. In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage

The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?

International audienceIn most viral infections, protection through existing vaccines is linked to the presence of vaccine-induced neutralizing antibodies (NAbs). However, more than 30 years after the identification of AIDS, the design of an immunogen able to induce antibodies that would neutralize the highly diverse HIV-1 variants remains one of the most puzzling challenges of the human microbiology. The role of antibodies in protection against HIV-1 can be studied in a natural situation that is the mother-to-child transmission (MTCT) context. Indeed, at least at the end of pregnancy, maternal antibodies of the IgG class are passively transferred to the fetus protecting the neonate from new infections during the first weeks or months of life. During the last few years, strong data, presented in this review, have suggested that some NAbs might confer protection toward neonatal HIV-1 infection. In cases of transmission, it has been shown that the viral population that is transmitted from the mother to the infant is usually homogeneous, genetically restricted and resistant to the maternal HIV-1-specific antibodies. Although the breath of neutralization was not associated with protection, it has not been excluded that NAbs toward specific HIV-1 strains might be associated with a lower rate of MTCT. A better identification of the antibody specificities that could mediate protection toward MTCT of HIV-1 would provide important insights into the antibody responses that would be useful for vaccine development. The most convincing data suggesting that NAbs migh confer protection against HIV-1 infection have been obtained by experiments of passive immunization of newborn macaques with the first generation of human monoclonal broadly neutralizing antibodies (HuMoNAbs). However, these studies, which included only a few selected subtype B challenge viruses, provide data limited to protection against a very restricted number of isolates and therefore have limitations in addressing the hypervariability of HIV-1. The recent identification of highly potent second-generation cross-clade HuMoNAbs provides a new opportunity to evaluate the efficacy of passive immunization to prevent MTCT of HIV-1

Research integrity at stake: conflicts of interest and industry ties in scientific publications

Trabajo presentado en la 26th International Conference on Science and Technology Indicators, celebrada en Granada (España) del 07 al 09 de septiembre de 2022.Large-scale and systematic analysis of CoI remained largely untapped due to major scientific databases' lack of indexing (Giles & Council, 2004). The situation changed in 2008 when the Web of Science (WoS) started to collect information on the funding acknowledgements of scientific publications. This has led to a renewed interest in analysing acknowledgements as paratextual traces of research practices (Desrochers et al., 2016). Nevertheless, most studies on the topic have been confined to the analysis of trends and patterns related to funding sources (for a review, see Álvarez-Bornstein and Montesi, 2021) or have dealt with acknowledgements as sources that provide new insights on influential contributions to scientific work (Cronin, Shaw & La Barre, 2003; Giles & Council, 2004; Díaz-Faes & Bordons, 2014). However, few studies have provided fine-grained analyses of CoI statements. A worth mentioning exception is Lewison & Sullivan (2015), who studied the presence of CoI financial statements on a sample of nearly 200,000 papers but focused only on the top 10 pharmaceutical companies in terms of R&D expenditures at that time. In this study, however, we conduct a large-scale analysis of CoI statements related to public-private partnerships, based on scientific outputs published between 2010 and 2020, to address the questions as follows: 1) What percentage of publications include CoI linked to the industry? 2) What is the distribution of publications disclosing CoI across research domains? 3) What industry ties are more frequently mentioned as representing potential CoI

Scientific knowledge production in European regions: patterns of growth, diversity and complexity

ABSTRACTWe study regional patterns of scientific knowledge production in Europe using all scientific publications in the period 2000?2014 attributed to 813 scientific subfields. We show that the existing scientific portfolio of regions offers opportunities for related diversification and discourages the creation of knowledge on topics unrelated to the local knowledge base. Many lagging regions show clear growth, but complex knowledge production remains highly concentrated in regions in the North and West of Europe. For lagging regions there are advantages in not specializing too soon and to first diversify before moving into developing more complex knowledge

Scientific knowledge production in European regions: patterns of growth, diversity and complexity

ABSTRACTWe study regional patterns of scientific knowledge production in Europe using all scientific publications in the period 2000?2014 attributed to 813 scientific subfields. We show that the existing scientific portfolio of regions offers opportunities for related diversification and discourages the creation of knowledge on topics unrelated to the local knowledge base. Many lagging regions show clear growth, but complex knowledge production remains highly concentrated in regions in the North and West of Europe. For lagging regions there are advantages in not specializing too soon and to first diversify before moving into developing more complex knowledge

High expression of the HMG box factor Sox-13 in arterial walls during embryonic development

Members of the Sox gene family of transcription factors are defined by the presence of an 80 amino acid homology domain, the High Mobility Group (HMG) box.Here we report the cloning and initial analysis of murine Sox-13. The 984 amino acids Sox-13 protein contains a single HMG box, a leucine zipper motif and a glutamine-rich stretch. These characteristics are shared with another member of the Sox gene family, Sox-6. High level embryonic expression of Sox-13 occurs uniquely in the arterial walls of 13.5 days post coitum (dpc) mice and later. Low level expression was observed in the inner ear of 13.5 dpc mice and in a limited number of cells in the thymus of 16.5 dpc mice, from which Sox-13 was originally cloned. At 18.5 dpc, Sox-13 is expressed in the tracheal epithelium below the vocal cord and in the hair follicles. The Sox-13 protein binds to the consensus HMG box motif, AACAAAG, but does not transactivate transcription through a concatamer of this motif. Sox-13, like other members of the Sox family likely plays an important role in developmen

Two Members of the Tcf Family Implicated in Wnt/β-Catenin Signaling during Embryogenesis in the Mouse

Tcf transcription factors interact with β-catenin and Armadillo to mediate Wnt/Wingless signaling. We now report the characterization of genes encoding two murine members of the Tcf family, mTcf-3 and mTcf-4. mTcf-3 mRNA is ubiquitously present in embryonic day 6.5 (E6.5) mouse embryos but gradually disappears over the next 3 to 4 days. mTcf-4 expression occurs first at E10.5 and is restricted to di- and mesencephalon and the intestinal epithelium during embryogenesis. The mTcf-3 and mTcf-4 proteins bind a canonical Tcf DNA motif and can complex with the transcriptional coactivator β-catenin. Overexpression of Wnt-1 in a mammary epithelial cell line leads to the formation of a nuclear complex between β-catenin and Tcf proteins and to Tcf reporter gene transcription. These data demonstrate a direct link between Wnt stimulation and β-catenin/Tcf transcriptional activation and imply a role for mTcf-3 and -4 in early Wnt-driven developmental decisions in the mouse embryo