Description: Macrophages are major cells of inflammatory process and take part in a large number of physiological and pathological processes. According to tissue environment, they can polarize into pro-inflammatory (M1) or alternative (M2) cells. Although many evidences have hinted to a potential role of cell-surface glycosaminoglycans (GAGs) in the functions of macrophages, the effect of M1 or M2 polarization on the biosynthesis of these polysaccharides has not been investigated so far. GAGs are composed of repeat sulfated disaccharide units. Heparan (HS) and chondroitin/dermatan sulfates (CS/DS) are the major GAGs expressed at the cell membrane. They are involved in numerous biological processes, which rely on their ability to selectively interact with a large panel of proteins. More than 20 genes encoding sulfotransferases have been implicated in HS and CS/DS biosynthesis, and the functional repertoire of HS and CS/DS has been related to the expression of these isoenzymes. In this study, we analyzed the expression of sulfotransferases as a response to macrophage polarization. We found that M1 and M2 activation drastically modified the profiles of expression of numerous HS and CS/DS sulfotransferases. This was accompanied by the expression of GAGs with distinct structural features. We then demonstrated that GAGs of M2 macrophages were efficient to present fibroblast growth factor-2 in an assay of tumor cell proliferation, thus indicating that changes in GAG structure may contribute to the functions of polarized macrophages. Altogether, our findings suggest a regulatory mechanism in which fine modifications in GAG biosynthesis may participate to the plasticity of macrophage functions.

Description: A wide body of literature has highlighted how high achievement in mathematics in secondary school does not necessarily motivate students to both choose and succeed on mathematically demanding programmes at post-compulsory level. The recent Enterprising Science project (Archer et al. (2015, J. Res. Sci. Teach., 52, 922–948)) and before that, the ASPIRES project (Archer et al. (2013, London: Kings College)), have both highlighted that access to science capital is perhaps more important than prior achievement in shaping students’ aspirations and their future trajectories in Science, Technology, Engineering and Mathematics. In this article, we critically analyse the notion of science capital and its role in mediating students’ choice of and experience of studying mathematically demanding degree programmes at university. Drawing on data from the TransMaths project, we present two cases—Stacey and Elton—who are both enrolled on the same ‘Mathematics for Physics’ course at university. We show that although both discuss access to science capital in narrating their choice of degree, they do so in different ways and this invariably interplays with different forms of identification with ‘Mathematics for Physics’. We conclude that there is a need to re-conceptualize science capital so that the dialectic relationship between its exchange and use value is theorized more fully. Whilst some students may access science capital as a means to accumulate capital (e.g. qualifications) for its own sake (exchange value), others appear to recognize the ‘use value’ of science learning and knowledge and this produces different forms of engagement with science (and mathematics). We therefore argue that authoring oneself in the name of a STEM identity is crucial in mediating how one perceives science capital. Finally, we argue that mathematics should be a central part of this framework since it significantly contributes to the exchange value of science as a form of capital (especially Physics), but it also offers use value in scientific labour (e.g. in modelling scientific problems).

Description: Background Assessment of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) might be an important tool in identifying human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients unlikely to derive benefit from anti-HER2 therapies. However, studies to date have failed to demonstrate its predictive role in any treatment setting. Patients and methods Prospectively collected baseline core biopsies from 429 early-stage HER2-positive breast cancer patients treated with trastuzumab, lapatinib, or their combination in the Neo-ALTTO study were stained using two anti-PTEN monoclonal antibodies (CST and DAKO). The association of PTEN status and PI3K pathway activation (defined as either PTEN loss and/or PIK3CA mutation) with total pathological complete response (tpCR) at surgery, event-free survival (EFS), and overall survival (OS) was evaluated. Results PTEN loss was observed in 27% and 29% of patients (all arms, n = 361 and n = 363) for CST and DAKO, respectively. PTEN loss was more frequently observed in hormone receptor (HR)-negative (33% and 36% with CST and DAKO, respectively) compared with HR-positive tumours (20% and 22% with CST and DAKO, respectively). No significant differences in tpCR rates were observed according to PTEN status. PI3K pathway activation was found in 47% and 48% of patients (all arms, n = 302 and n = 301) for CST and DAKO, respectively. Similarly, tpCR rates were not significantly different for those with or without PI3K pathway activation. Neither PTEN status nor PI3K pathway activation were predictive of tpCR, EFS, or OS, independently of treatment arm or HR status. High inter-antibody and inter-observer agreements were found (〉90%). Modification of scoring variables significantly affected the correlation between PTEN and HR status but not with tpCR. Conclusion These data show that PTEN status determination is not a useful biomarker to predict resistance to trastuzumab and lapatinib-based therapies. The lack of standardization of PTEN status determination may influence correlations between expression and relevant clinical end points. Clinical Trials This trial is registered with ClinicalTrials.gov: NCT00553358.

Description: K2-19 is the second multiplanetary system discovered with K2 observations. The system is composed of two Neptune size planets close to the 3:2 mean-motion resonance. To better characterize the system we obtained two additional transit observations of K2-19b and five additional radial velocity observations. These were combined with K2 data and fitted simultaneously with the system dynamics (photodynamical model) which increases the precision of the transit time measurements. The higher transit time precision allows us to detect the chopping signal of the dynamic interaction of the planets that in turn permits to uniquely characterize the system. Although the reflex motion of the star was not detected, dynamic modelling of the system allowed us to derive planetary masses of M b = 44 ± 12 M and M c = 15.9 ± 7.0 M for the inner and the outer planets, respectively, leading to densities close to Uranus. We also show that our method allows the derivation of mass ratios using only the 80 d of observations during the first campaign of K2.

Description: The spread of farming out of the Balkans and into the rest of Europe followed two distinct routes: An initial expansion represented by the Impressa and Cardial traditions, which followed the Northern Mediterranean coastline; and another expansion represented by the LBK (Linearbandkeramik) tradition, which followed the Danube River into Central Europe. Although genomic data now exist from samples representing the second migration, such data have yet to be successfully generated from the initial Mediterranean migration. To address this, we generated the complete genome of a 7,400-year-old Cardial individual (CB13) from Cova Bonica in Vallirana (Barcelona), as well as partial nuclear data from five others excavated from different sites in Spain and Portugal. CB13 clusters with all previously sequenced early European farmers and modern-day Sardinians. Furthermore, our analyses suggest that both Cardial and LBK peoples derived from a common ancient population located in or around the Balkan Peninsula. The Iberian Cardial genome also carries a discernible hunter–gatherer genetic signature that likely was not acquired by admixture with local Iberian foragers. Our results indicate that retrieving ancient genomes from similarly warm Mediterranean environments such as the Near East is technically feasible.

Description: This paper presents the gravimetric analysis together with seismic data as an integral application in order to identify the continental–oceanic crust boundary (COB) of the Argentine continental margin from 36°S to 50°S in a continuous way. The gravimetric and seismic data are made up of large grids of data obtained from satellite altimetry and marine research. The methodology consists of three distinct methods: (i) the application of enhancement techniques to gravimetric anomalies, (ii) the calculation of crustal thinning from 3-D gravity inversion modelling of the crust–mantle discontinuity and (iii) 2-D gravimetric modelling supported by multichannel reflection and refraction seismic profiles. In the first method, the analytic signal, Theta map, and tilt angle and its horizontal derivative were applied. In the second method, crustal thickness was obtained as the difference in the depths of the crystalline basement and the crust–mantle discontinuity; the latter was obtained via gravimetric inversion. Finally, 2-D modelling was performed from free-air anomalies in two representative sections by considering as restriction surfaces those coming from the interpretation of seismic data. The results of the joint application of enhancement techniques and 2-D and 3-D modelling have enabled continuous interpretation of the COB. In this study, the COB was determined continuously from the integration of 2-D profiles of the enhancement techniques, taking account of crustal thickness and performing 2-D gravimetric modelling. The modelling technique was complemented by regional studies integrated with multichannel seismic reflection and seismic refraction lines, resulting in consistent enhancement techniques.