Retention of native-like structure in an acyclic counterpart of a β-sheet antibiotic

AbstractAn acyclic derivative of the cyclic peptide antibiotic, ramoplanin, has been prepared. In aqueous solution, two-dimensional NMR spectroscopy indicates that the acyclic form adopts a threshold population of conformers in which at least part of the β-sheet characteristic of the intact ramoplanin persists. Thus, despite losing the entropic benefit which the macrocycle must lend to β-sheet formation, the polypeptide chain of the acyclic ramoplanin appears to display an innate tendency to adopt a native-like conformation

Spectral Energy Distributions of Be and Other Massive Stars

We present spectrophotometric data from 0.4 to 4.2 microns for bright, northern sky, Be stars and several other types of massive stars. Our goal is to use these data with ongoing, high angular resolution, interferometric observations to model the density structure and sky orientation of the gas surrounding these stars. We also present a montage of the H-alpha and near-infrared emission lines that form in Be star disks. We find that a simplified measurement of the IR excess flux appears to be correlated with the strength of emission lines from high level transitions of hydrogen. This suggests that the near-IR continuum and upper level line fluxes both form in the inner part of the disk, close to the star.Comment: 2010, PASP, 122, 37

Mid-infrared spectral evidence for a luminous dust enshrouded source in Arp220

We have re-analyzed the 6-12 micron ISO spectrum of the ultra-luminous infrared galaxy Arp220 with the conclusion that it is not consistent with that of a scaled up version of a typical starburst. Instead, both template fitting with spectra of the galaxies NGC4418 and M83 and with dust models suggest that it is best represented by combinations of a typical starburst component, exhibiting PAH emission features, and a heavily absorbed dust continuum which contributes ~40% of the 6-12 micron flux and likely dominates the luminosity. Of particular significance relative to previous studies of Arp220 is the fact that the emission feature at 7.7 micron comprises both PAH emission and a broader component resulting from ice and silicate absorption against a heavily absorbed continuum. Extinction to the PAH emitting source, however, appears to be relatively low. We tentatively associate the PAH emitting and heavily dust/ice absorbed components with the diffuse emission region and the two compact nuclei respectively identified by Soifer et al. (2002) in their higher spatial resolution 10 micron study. Both the similarity of the absorbed continuum with that of the embedded Galactic protostars and results of the dust models imply that the embedded source(s) in Arp220 could be powered by, albeit extremely dense, starburst activity. Due to the high extinction, it is not possible with the available data to exclude that AGN(s) also contribute some or all of the observed luminosity. In this case, however, the upper limit measured for its hard X-ray emission would require Arp220 to be the most highly obscured AGN known.Comment: 11 pages, 9 figures. Accepted for publication in A&A. Also available at http://www.astro.rug.nl/~spoon/publications.htm

Drilling their own graves:How the European oil and gas supermajors avoid sustainability tensions through mythmaking

This study explores how paradoxical tensions between economic growth and environmental protection are avoided through organizational mythmaking. By examining the European oil and gas supermajors’ ‘‘CEOspeak’’ about climate change, we show how mythmaking facilitates the disregarding, diverting, and/or displacing of sustainability tensions. In doing so, our findings further illustrate how certain defensive responses are employed: (1) regression, or retreating to the comforts of past familiarities, (2) fantasy, or escaping the harsh reality that fossil fuels and climate change are indeed irreconcilable, and (3) projecting, or shifting blame to external actors for failing to address climate change. By highlighting the discursive effects of enacting these responses, we illustrate how the European oil and gas supermajors self-determine their inability to substantively address the complexities of climate change. We thus argue that defensive responses are not merely a form of mismanagement as the paradox and corporate sustainability literature commonly suggests, but a strategic resource that poses serious ethical concerns given the imminent danger of issues such as climate change

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Using citizen science data to assess the vulnerability of bottlenose dolphins to human impacts along England's South Coast

Coastal bottlenose dolphin populations are highly vulnerable due to their small population sizes and proximity to human activities. Long‐term studies in the UK have monitored populations protected within Special Areas of Conservation (SACs) since the 1990s, but a small community of bottlenose dolphins inhabiting the coastal waters of southern England has received much less attention. The English Channel is one of the most heavily impacted marine ecosystems worldwide and increasing anthropogenic pressures pose a severe threat to the long‐term viability of this population. Conservation measures to protect these animals have been hindered by a lack of knowledge of population size, distribution and ranging behaviour. This study aimed to fill these knowledge gaps. A citizen science sighting network yielded 7458 sighting reports of bottlenose dolphins between 2000 and 2020. Resightings of identified individuals were used to estimate abundance, distribution, and ranging behaviour. Social structure analysis revealed a discrete interconnected group of animals in shallow coastal waters, which did not appear to mix with conspecifics identified further offshore. A Bayesian multi‐site mark–recapture analysis estimated that this population comprises around 48 animals (CV = 0.18, 95% HPDI = 38–66). These dolphins ranged between North Cornwall and Sussex, with an average individual range of 530 km (68–760 km). Areas of high‐modelled habitat suitability were found to overlap with high levels of anthropogenic pressure, with pollution and boat traffic identified as the most pervasive threats. Although adult survival rates indicated that the population was relatively stable from 2008 to 2019 (0.945 (0.017 ± SE)), the small population size implies a significant risk to their long‐term viability and resilience to environmental change. By highlighting the most deleterious anthropogenic activities and regions of conservation significance, our results will be useful for developing management policies for threat mitigation and population conservation, to protect this vulnerable group of dolphins

Progress and challenges in the vaccine-based treatment of head and neck cancers

Head and neck (HN) cancer represents one of the most challenging diseases because the mortality remains high despite advances in early diagnosis and treatment. Although vaccine-based approaches for the treatment of advanced squamous cell carcinoma of the head and neck have achieved limited clinical success, advances in cancer immunology provide a strong foundation and powerful new tools to guide current attempts to develop effective cancer vaccines. This article reviews what has to be rather what has been done in the field for the development of future vaccines in HN tumours

Skeletal Muscle NADPH Oxidase Is Increased and Triggers Stretch-Induced Damage in the mdx Mouse

Recent studies have shown that oxidative stress contributes to the pathogenesis of muscle damage in dystrophic (mdx) mice. In this study we have investigated the role of NADPH oxidase as a source of the oxidative stress in these mice. The NADPH oxidase subunits gp91phox, p67phox and rac 1 were increased 2–3 fold in tibilais anterior muscles from mdx mice compared to wild type. Importantly, this increase occurred in 19 day old mice, before the onset of muscle necrosis and inflammation, suggesting that NADPH oxidase is an important source of oxidative stress in mdx muscle. In muscles from 9 week old mdx mice, gp91phox and p67phox were increased 3–4 fold and NADPH oxidase superoxide production was 2 times greater than wild type. In single fibers from mdx muscle NADPH oxidase subunits were all located on or near the sarcolemma, except for p67phox,which was expressed in the cytosol. Pharmacological inhibition of NADPH oxidase significantly reduced the intracellular Ca2+ rise following stretched contractions in mdx single fibers, and also attenuated the loss of muscle force. These results suggest that NADPH oxidase is a major source of reactive oxygen species in dystrophic muscle and its enhanced activity has a stimulatory effect on stretch-induced Ca2+ entry, a key mechanism for muscle damage and functional impairment

Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help

Background: Using in vivo mouse models, the mechanisms of CD4+ T cell help have been intensively investigated. However, a mechanistic analysis of human CD4+ T cell help is largely lacking. Our goal was to elucidate the mechanisms of human CD4+ T cell help of CD8+ T cell proliferation using a novel in vitro model. Methods/Principal Findings: We developed a genetically engineered novel human cell-based artificial APC, aAPC/mOKT3, which expresses a membranous form of the anti-CD3 monoclonal antibody OKT3 as well as other immune accessory molecules. Without requiring the addition of allogeneic feeder cells, aAPC/mOKT3 enabled the expansion of both peripheral and tumor-infiltrating T cells, regardless of HLA-restriction. Stimulation with aAPC/mOKT3 did not expand Foxp3+ regulatory T cells, and expanded tumor infiltrating lymphocytes predominantly secreted Th1-type cytokines, interferon-γ and IL-2. In this aAPC-based system, the presence of autologous CD4+ T cells was associated with significantly improved CD8+ T cell expansion in vitro. The CD4+ T cell derived cytokines IL-2 and IL-21 were necessary but not sufficient for this effect. However, CD4+ T cell help of CD8+ T cell proliferation was partially recapitulated by both adding IL-2/IL-21 and by upregulation of IL-21 receptor on CD8+ T cells. Conclusions: We have developed an in vitro model that advances our understanding of the immunobiology of human CD4+ T cell help of CD8+ T cells. Our data suggests that human CD4+ T cell help can be leveraged to expand CD8+ T cells in vitro