Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

Cosmic evolution and metal aversion in superluminous supernova host galaxies

The SUperluminous Supernova Host galaxIES (SUSHIES) survey aims to provide strong new constraints on the progenitors of superluminous supernovae (SLSNe) by understanding the relationship to their host galaxies. We present the photometric properties of 53 H-poor and 16 H-rich SLSN host galaxies out to $z\sim4$. We model their spectral energy distributions to derive physical properties, which we compare with other galaxy populations. At low redshift, H-poor SLSNe are preferentially found in very blue, low-mass galaxies with high average specific star-formation rates. As redshift increases, the host population follows the general evolution of star-forming galaxies towards more luminous galaxies. After accounting for secular evolution, we find evidence for differential evolution in galaxy mass, but not in the $B$-band and the far UV luminosity ($3\sigma$ confidence). Most remarkable is the scarcity of hosts with stellar masses above $10^{10}~M_\odot$ for both classes of SLSNe. In the case of H-poor SLSNe, we attribute this to a stifled production efficiency above $\sim0.4$ solar metallicity. However, we argue that, in addition to low metallicity, a short-lived stellar population is also required to regulate the SLSN production. H-rich SLSNe are found in a very diverse population of star-forming galaxies. Still, the scarcity of massive hosts suggests a stifled production efficiency above $\sim0.8$ solar metallicity. The large dispersion of the H-rich SLSNe host properties is in stark contrast to those of gamma-ray burst, regular core-collapse SN, and H-poor SLSNe host galaxies. We propose that multiple progenitor channels give rise to this sub-class

Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Perù

The MUSE view of the host galaxy of GRB 100316D

The low distance, $z=0.0591$, of GRB 100316D and its association with SN 2010bh represent two important motivations for studying this host galaxy and the GRB's immediate environment with the Integral-Field Spectrographs like VLT/MUSE. Its large field-of-view allows us to create 2D maps of gas metallicity, ionization level, and the star-formation rate distribution maps, as well as to investigate the presence of possible host companions. The host is a late-type dwarf irregular galaxy with multiple star-forming regions and an extended central region with signatures of on-going shock interactions. The GRB site is characterized by the lowest metallicity, the highest star-formation rate and the youngest ($\sim$ 20-30 Myr) stellar population in the galaxy, which suggest a GRB progenitor stellar population with masses up to 20 -- 40 $M_{\odot}$. We note that the GRB site has an offset of $\sim$660pc from the most luminous SF region in the host. The observed SF activity in this galaxy may have been triggered by a relatively recent gravitational encounter between the host and a small undetected ($L_{H\alpha} \leq 10^{36}$ erg/s) companion

Part-time hospitalisation and stigma experiences: a study in contemporary psychiatric hospitals

Background: Because numerous studies have revealed the negative consequences of stigmatisation, this study explores the determinants of stigma experiences. In particular, it examines whether or not part-time hospitalisation in contemporary psychiatric hospitals is associated with less stigma experiences than full-time hospitalisation. Methods: Survey data on 378 clients of 42 wards from 8 psychiatric hospitals are used to compare full-time clients, part-time clients and clients receiving part-time care as aftercare on three dimensions of stigma experiences, while controlling for symptoms, diagnosis and clients' background characteristics. Results: The results reveal that part-time clients without previous full-time hospitalisation report less social rejection than clients who receive full-time hospitalisation. In contrast, clients receiving part-time treatment as aftercare do not differ significantly from full-time clients concerning social rejection. No significant results for the other stigma dimensions were found. Conclusion: Concerning social rejection, immediate part-time hospitalisation could be recommended as a means of destigmatisation for clients of contemporary psychiatric hospitals

Predicting glycated hemoglobin levels in the non-diabetic general population:Development and validation of the DIRECT-DETECT prediction model - a DIRECT study

AIMS/HYPOTHESIS: To develop a prediction model that can predict HbA1c levels after six years in the non-diabetic general population, including previously used readily available predictors. METHODS: Data from 5,762 initially non-diabetic subjects from three population-based cohorts (Hoorn Study, Inter99, KORA S4/F4) were combined to predict HbA1c levels at six year follow-up. Using backward selection, age, BMI, waist circumference, use of anti-hypertensive medication, current smoking and parental history of diabetes remained in sex-specific linear regression models. To minimize overfitting of coefficients, we performed internal validation using bootstrapping techniques. Explained variance, discrimination and calibration were assessed using R2, classification tables (comparing highest/lowest 50% HbA1c levels) and calibration graphs. The model was externally validated in 2,765 non-diabetic subjects of the population-based cohort METSIM. RESULTS: At baseline, mean HbA1c level was 5.6% (38 mmol/mol). After a mean follow-up of six years, mean HbA1c level was 5.7% (39 mmol/mol). Calibration graphs showed that predicted HbA1c levels were somewhat underestimated in the Inter99 cohort and overestimated in the Hoorn and KORA cohorts, indicating that the model's intercept should be adjusted for each cohort to improve predictions. Sensitivity and specificity (95% CI) were 55.7% (53.9, 57.5) and 56.9% (55.1, 58.7) respectively, for women, and 54.6% (52.7, 56.5) and 54.3% (52.4, 56.2) for men. External validation showed similar performance in the METSIM cohort. CONCLUSIONS/INTERPRETATION: In the non-diabetic population, our DIRECT-DETECT prediction model, including readily available predictors, has a relatively low explained variance and moderate discriminative performance, but can help to distinguish between future highest and lowest HbA1c levels. Absolute HbA1c values are cohort-dependent

On the diversity of superluminous supernovae: ejected mass as the dominant factor

We assemble a sample of 24 hydrogen-poor superluminous supernovae (SLSNe). Parameterizing the light-curve shape through rise and decline time-scales shows that the two are highly correlated. Magnetar-powered models can reproduce the correlation, with the diversity in rise and decline rates driven by the diffusion time-scale. Circumstellar interaction models can exhibit a similar rise–decline relation, but only for a narrow range of densities, which may be problematic for these models. We find that SLSNe are approximately 3.5 mag brighter and have light curves three times broader than SNe Ibc, but that the intrinsic shapes are similar. There are a number of SLSNe with particularly broad light curves, possibly indicating two progenitor channels, but statistical tests do not cleanly separate two populations. The general spectral evolution is also presented. Velocities measured from Fe II are similar for SLSNe and SNe Ibc, suggesting that diffusion time differences are dominated by mass or opacity. Flat velocity evolution in most SLSNe suggests a dense shell of ejecta. If opacities in SLSNe are similar to other SNe Ibc, the average ejected mass is higher by a factor 2–3. Assuming κ = 0.1 cm2 g−1, we estimate a mean (median) SLSN ejecta mass of 10 M⊙ (6 M⊙), with a range of 3–30 M⊙. Doubling the assumed opacity brings the masses closer to normal SNe Ibc, but with a high-mass tail. The most probable mechanism for generating SLSNe seems to be the core collapse of a very massive hydrogen-poor star, forming a millisecond magnetar

Highly luminous supernovae associated with gamma-ray bursts I. GRB 111209A/SN 2011kl in the context of stripped-envelope and superluminous supernovae

Context. GRB 111209A, one of the longest gamma-ray bursts (GRBs) ever observed, is linked to SN 2011kl, which is the most luminous GRB supernova (SN) detected so far. Several lines of evidence indicate that this GRB-SN is powered by a magnetar central engine. Aims. We place SN 2011kl into the context of large samples of SNe, addressing in more detail the question of whether this GRB-SN could be radioactively powered, and whether it represents an extreme version of a GRB-SN or an underluminous superluminous SN (SLSN). Methods. We modelled SN 2011kl using SN 1998bw as a template and derived a bolometric light curve including near-infrared data. We compared the properties of SN 2011kl to literature results on stripped-envelope and SLSNe. Results. A comparison in the k, s context, i.e. comparing SN 2011kl to SN 1998bw templates in terms of luminosity and light-curve stretch, clearly shows SN 2011kl is the most luminous GRB-SN to date and is spectrally very dissimilar to other events because it is significantly bluer/hotter. Although SN 2011kl does not reach the classical luminosity threshold of SLSNe and evolves faster than any of these objects, it resembles SLSNe more than the classical GRB-associated broad-lined Type Ic SNe in several aspects. Conclusions. GRB 111209A was a very energetic event, both at early (prompt emission) and at very late (SN) times. We show in a companion publication that with the exception of the extreme duration, the GRB and afterglow parameters are in agreement with the known distributions for these parameters. SN 2011kl, on the other hand, is exceptional both in luminosity and spectral characteristics, indicating that GRB 111209A was likely not powered by a standard-model collapsar central engine, further supporting our earlier conclusions. Instead, it reveals the possibility of a direct link between GRBs and SLSNe