Tipping back the balance: recolonization of the Macquarie Island isthmus by king penguins (Aptenodytes patagonicus) following extermination for human gain

During the late 19th and early 20th centuries, when blubber oil fuelled house lamps, the king penguin population at Macquarie Island was reduced from two very large (perhaps hundreds of thousands of birds) colonies to about 3000 birds. One colony, located on the isthmus when the island was discovered in 1810, was extinct by 1894 and it took about 100 years for king penguins to re-establish a viable breeding population there. Here we document this recovery. The first eggs laid at Gadget Gully on the isthmus were recorded in late February 1995 but in subsequent years egg laying took place earlier between November and February (this temporal discontinuity is a consequence of king penguin breeding behaviour). The first chick was hatched in April 1995 but the first fledging was not raised until the following breeding season in October 1996. The colony increased on average 66% per annum in the five years between 1995 and 2000. King penguins appear resilient to catastrophic population reductions, and as the island\u27s population increases, it is likely that other previously abandoned breeding sites will be reoccupied

Purine Nucleoside Phosphorylase Targeted by Annexin V to Breast Cancer Vasculature for Enzyme Prodrug Therapy

Conceived and designed the experiments: JJK OD RGH. Performed the experiments: JJK OD. Analyzed the data: JJK OD RGH. Wrote the paper: JJK OD RGH.Background and PurposeThe targeting of therapeutics is a promising approach for the development of new cancer treatments that seek to reduce the devastating side effects caused by the systemic administration of current drugs. This study evaluates a fusion protein developed as an enzyme prodrug therapy targeted to the tumor vasculature. Cytotoxicity would be localized to the site of the tumor using a protein fusion of purine nucleoside phosphorylase (PNP) and annexin V. Annexin V acts as the tumor-targeting component of the fusion protein as it has been shown to bind to phosphatidylserine expressed externally on cancer cells and the endothelial cells of the tumor vasculature, but not normal vascular endothelial cells. The enzymatic component of the fusion, PNP, converts the FDA-approved cancer therapeutic, fludarabine, into a more cytotoxic form. The purpose of this study is to determine if this system has a good potential as a targeted therapy for breast cancer.MethodsA fusion of E. coli purine nucleoside phosphorylase and human annexin V was produced in E. coli and purified. Using human breast cancer cell lines MCF-7 and MDA-MB-231 and non-confluent human endothelial cells grown in vitro, the binding strength of the fusion protein and the cytotoxicity of the enzyme prodrug system were determined. Endothelial cells that are not confluent expose phosphatidylserine and therefore mimic the tumor vasculature.ResultsThe purified recombinant fusion protein had good enzymatic activity and strong binding to the three cell lines. There was significant cell killing (p<0.001) by the enzyme prodrug treatment for all three cell lines, with greater than 80% cytotoxicity obtained after 6 days of treatment.ConclusionThese results suggest that this treatment could be useful as a targeted therapy for breast cancer.Yeshttp://www.plosone.org/static/editorial#pee

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A comparative study of the cephalopod prey of Patagonian toothfish (Dissostichus eleginoides) and southern elephant seals (Mirounga leonina) near Macquarie Island

Within the Southern Ocean, Patagonian toothfish (Dissostichus eleginoides Smitt) and southern elephant seals (Mirounga leonina Linnaeus) forage mainly on fish and cephalopods. From what is known of their diets, the proportion of fish is greatest in toothfish diet. When foraging at-sea for squid, elephant seals and toothfish most often co-occur over continental shelves and submarine plateaux surrounding sub-Antarctic land masses within the Southern Ocean. I used traditional (non-molecular) techniques to compare the squid diet of these two predators. Of the 21 squid species identified, 10 were common to the diets of both predators. One species, Gonatus antarcticus, dominated (61%) the biomass of squid consumed by toothfish, but was of little importance to the elephant seals (2.3%). By contrast, Martialia hyadesi was the most important single species to the elephant seals’ diet (29%), but it contributed 1% to the toothfish diet. Onychoteuthids (Kondakovia longimana, Moroteuthis ingens and Morotenthis knipovitchi) were important to both predators’ diets. The median sizes of five cephalopod species (Slosarczykovia circumantarctica, Galiteuthis glacialis, Gonatus antarcticus, Moroteuthis ingens and Moroteuthis knipovitchi) which were common to both the seal and toothfish diets, were significantly larger in the toothfish stomachs than in the elephant-seal stomachs. Percent similarity indices for the squids that overlapped both diets were in some cases as high as 100%. However, after between-species differences in prey size consumption were accounted for, the similarities fell to between 20 and 50%. These results indicate that the strength of the trophic interaction between the seals and the fish might be weaker than previously thought. The consumption of significantly different-sized squid can also be used to suggest spatial (vertical) foraging separation of these two predators because there is evidence for ontogenetic change in the size of squid species with depth; older, and thus larger, squids live deeper than smaller individuals of the same species

LORICATE CHOANOFLAGELLATES FROM ELLIS FJORD, ANTARCTICA INCLUDING THE DESCRIPTION OF ACANTHOCORBIS TINTINNABULUM SP. NOV. (Ninth Symposium on Polar Biology)

The ice-free Vestfold Hills is deeply dissected by fjords and has a number of lakes and lagoons with seasonal connection to the sea. These diverse aquatic habitats vary greatly in salinity, ice cover, temperature, water depth and water column mixing. As part of ongoing studies on these water bodies, we have sampled the plankton from a basin at the head of Ellis Fjord, some 10 km from the open sea, where the temperature was 2.6℃ and the salinity was between 37.6 and 38.4‰. In enriched cultures from a 25 l sample taken from this basin we have found the loricate choanoflagellates, Acanthoeca brevipoda, Acanthocorbis unguiculata, Diaphanoeca grandis, Stephanoeca complexa, S. norrisii and S. diplocostata. From this site we describe the new species Acanthocorbis tintinnabulum. The 25 l sample was integrated over 0.8 m which encompassed the boundary layer between oxic and anoxic waters. The sample was stored at ca. 4℃ for 3 weeks and was anaerobic for that period. The species enriched from the sample were therefore able to withstand prolonged anoxia