Aryl Hydrocarbon Receptor–Independent Toxicity of Weathered Crude Oil during Fish Development

Polycyclic aromatic hydrocarbons (PAHs), derived largely from fossil fuels and their combustion, are pervasive contaminants in rivers, lakes, and nearshore marine habitats. Studies after the Exxon Valdez oil spill demonstrated that fish embryos exposed to low levels of PAHs in weathered crude oil develop a syndrome of edema and craniofacial and body axis defects. Although mechanisms leading to these defects are poorly understood, it is widely held that PAH toxicity is linked to aryl hydrocarbon receptor (AhR) binding and cytochrome P450 1A (CYP1A) induction. Using zebrafish embryos, we show that the weathered crude oil syndrome is distinct from the well-characterized AhR-dependent effects of dioxin toxicity. Blockade of AhR pathway components with antisense morpholino oligonucleotides demonstrated that the key developmental defects induced by weathered crude oil exposure are mediated by low-molecular-weight tricyclic PAHs through AhR-independent disruption of cardiovascular function and morphogenesis. These findings have multiple implications for the assessment of PAH impacts on coastal habitats

A Correlation Between Circumstellar Disks and Rotation in the Upper Scorpius OB Association

We present projected rotational velocities for 20 early-type (B8-A9) and 74 late-type (F2-M8) members of the ~5 Myr old Upper Scorpius OB Association derived from high dispersion optical spectra obtained with the High Resolution Echelle Spectrometer (HIRES) on Keck I and the Magellan Inamori Kyocera Echelle (MIKE) on the Magellan Clay telescope. The spectroscopic sample is composed of stars and brown dwarfs with infrared signatures of circumstellar disks, both primordial and debris, and non-excess sources of comparable spectral type. We merge projected rotational velocities, accretion diagnostics, and Spitzer Space Telescope Infrared Array Camera (IRAC) and Multiband Imaging Photometer for Spitzer (MIPS) 24 micron photometry to examine the relationship between rotation and circumstellar disks. The rotational velocities are strongly correlated with spectral type, a proxy for mass, such that the median vsini for B8-A9 type stars is: 195(+/-)70 km/s, F2-K4: 37.8(+/-)7.4 km/s, K5-K9: 13.8(+21.3/-8.2) km/s, M0-M5: 16.52(+/-)5.3 km/s, and M5.5-M8: 17.72(+/-)8.1 km/s. We find with a probability of >0.99 that M-type stars and brown dwarfs having infrared excess suggestive of circumstellar disks rotate more slowly than their non-excess counterparts. A similar correlation is present among F2-K9 type stars, but only at the ~97% confidence level. Among the early-type (B8-A9) members, rotational velocities of the debris-disk and non-disk populations are indistinguishable. Considering the late-type (F2-M8) stars and brown dwarfs, we find a low fraction of slowly rotating, non-excess sources relative to younger star forming regions, suggesting that most have spun up following disk dissipation. The few late-type (F2-M5) debris disk sources, which may be representative of stars that have recently dispersed their inner disks, are evenly divided between slow and moderate rotators.Comment: 41 pages, 11 figures, accepted for publication in the Astrophysical Journa

Social, ethical and cultural responsibility as core values for doctoral researchers in the 21st century

With the dramatic events of a global pandemic, the beginning of the twenty-first century’s third decade has underlined that the world is facing universal challenges. The worldwide crisis scenario that COVID-19 has produced makes us realise that science and research do not function and operate in an independent sphere hidden within the proverbial ivory tower, but, on the contrary, are closely linked to the social, cultural and political systems they reside in. This creates opportunities and great tensions and, while exploring those, Chapter 9 connects to and builds on most of the dimensions described in the previous sections of the book. We refer primarily to Hannover Recommendations 1 and 7: 1. Establish a global joint value system for doctoral education based on an ecology of knowledges which recognises and seeks to overcome existing inequalities in the access to doctoral education and the provision of knowledge. 7. The pivotal goal of doctoral education must be and remain the development of original, responsible, and ethical thinkers, and the generation of new and original ideas and knowledge

Characterization of tryptophan oxidation affecting D1 degradation by FtsH in the photosystem II quality control of chloroplasts

Photosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH

Puget Sound Federal Task Force: Coordinating, leveraging and prioritizing diverse federal programs toward a healthy and sustainable Puget Sound

The Puget Sound Federal Task Force (PSFTF) panel at the 2022 Salish Sea Ecosystem Conference will include presentations and an opportunity for discussion on current priority U.S. federal actions to protect and restore Puget Sound. PSFTF Co-chairs will provide an overview, including the role and relationship to treaty protected rights and resources. PSFTF Subteam Leads will highlight federal work on cross-cutting actions; fish passage; nearshore and shorelines; floodplains, riparian habitat, and estuaries; shellfish; stormwater; and science and monitoring. As background, with the Puget Sound Congressional delegation, Puget Sound Partnership, tribes and others recognizing that formal program and budget coordination at the federal level was needed to effectively protect and restore Puget Sound and Treaty protected resources, the White House Council on the Environmental Quality led nine federal Cabinet Secretaries and agency directors to sign a Memorandum of Understanding (MOU) forming the PSFTF. The MOU, signed in November 2016, outlines the structure of the PSFTF and the charge to PSFTF agencies to develop Action Plans on a rolling 5-year basis. The PSFTF is comprised of 13 federal agencies and co-chaired by EPA and NOAA. The PSFTF MOU, Action Plans and Progress Reports are available online at: https://www.epa.gov/puget-sound/puget-sound-federal-task-forc

Attrition between lines of therapy and real-world outcomes of patients with HER2-positive metastatic breast cancer in Europe: a cohort study leveraging electronic medical records

PurposeTo characterize real-world attrition rates across first-line (1L) to third-line (3L) therapies in patients with HER2-positive (HER2 +) metastatic breast cancer (mBC) receiving routine care in seven hospital systems across Europe (France, Germany, Italy, Spain, and the UK).MethodsThis retrospective, observational, multi-country, cohort study collected electronic medical record data from women aged ≥ 18 years diagnosed with HER2 + mBC from 2017–2021. The primary endpoint was attrition rate (the proportion of patients receiving a line of therapy [LOT] with no further evidence of subsequent LOTs). Key additional endpoints included treatment patterns, real-world time to treatment discontinuation (TTD), and time to next treatment (TTNT).Results29.6% (95% confidence interval [CI] 25.0–34.6) and 34.2% (95% CI 27.5–41.5) of treated patients with HER2 + mBC had no further evidence of treatment beyond 1L and second-line (2L) therapy, respectively. Attrition was primarily owing to death, move to end-of-life palliative care, loss to follow up, and “other” reasons. Treatment patterns were generally aligned with clinical guidelines. Decreases in TTD (12.1 months [95% CI 10.4–14.5] for 1L, 8.9 months [95% CI 7.3–11.9] for 2L, 6.4 months [95% CI 5.2–8.9] for 3L) and TTNT (15.4 months [95% CI 13.6–20.6] for 1L, 13.5 months [95% CI 10.8–19.4] for 2L) were observed with each subsequent LOT.ConclusionResults unveil a large proportion of patients who do not benefit from state-of-the-art subsequent LOT, and suggest diminishing effectiveness with each subsequent LOT

Impact of ageing and a synbiotic on the immune response to seasonal influenza vaccination; a randomised controlled trial

Background & Aims Ageing increases risk of respiratory infections and impairs the response to influenza vaccination. Pre- and probiotics offer an opportunity to modulate anti-viral defenses and the response to vaccination via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco-oligosaccharide, on the B and T cell response to seasonal influenza vaccination in young and older subjects. Methods In a double-blind, randomized controlled trial, 58 young (18-35y) and 54 older (60-85y) subjects were supplemented with the synbiotic for 8 weeks. At 4 weeks they were administered with a seasonal influenza vaccine. B and T cell phenotype and responsiveness to in vitro re-stimulation with the vaccine were assessed at baseline, 4, 6 and 8 weeks. Results B and T cell profiles differed markedly between young and older subjects. Vaccination increased numbers of memory, IgA+ memory, IgG+ memory and total IgG+ B cells in young subjects, but failed to do so in older subjects and did not significantly alter T cell subsets. Seroconversion to the H1N1 subunit in the older subjects was associated with higher post-vaccination numbers of plasma B cells, but seroconversion was less consistently associated with T cell phenotype. B and T cell subsets from both young and older subjects demonstrated a strong antigen-specific recall challenge, and although not influenced by age, responsiveness to the recall challenge was associated with seroconversion. In older subjects, CMV seropositivity was associated with a significantly lower recall response to the vaccine, but the synbiotic did not affect the responsiveness of B or T cells to re-stimulation with influenza vaccine. Conclusions Antigen-specific B and T cell activation following an in vitro recall challenge with the influenza vaccine was influenced by CMV seropositivity, but not by a synbiotic