Sensitivity of fluvial sediment source apportionment to mixing model assumptions: A Bayesian model comparison

Mixing models have become increasingly common tools for apportioning fluvial sediment load to various sediment sources across catchments using a wide variety of Bayesian and frequentist modeling approaches. In this study, we demonstrate how different model setups can impact upon resulting source apportionment estimates in a Bayesian framework via a one-factor-at-a-time (OFAT) sensitivity analysis. We formulate 13 versions of a mixing model, each with different error assumptions and model structural choices, and apply them to sediment geochemistry data from the River Blackwater, Norfolk, UK, to apportion suspended particulate matter (SPM) contributions from three sources (arable topsoils, road verges, and subsurface material) under base flow conditions between August 2012 and August 2013. Whilst all 13 models estimate subsurface sources to be the largest contributor of SPM (median ∼76%), comparison of apportionment estimates reveal varying degrees of sensitivity to changing priors, inclusion of covariance terms, incorporation of time-variant distributions, and methods of proportion characterization. We also demonstrate differences in apportionment results between a full and an empirical Bayesian setup, and between a Bayesian and a frequentist optimization approach. This OFAT sensitivity analysis reveals that mixing model structural choices and error assumptions can significantly impact upon sediment source apportionment results, with estimated median contributions in this study varying by up to 21% between model versions. Users of mixing models are therefore strongly advised to carefully consider and justify their choice of model structure prior to conducting sediment source apportionment investigations

Quantitative mass spectrometry reveals a role for the GTPase Rho1p in actin organization on the peroxisome membrane

We have combined classical subcellular fractionation with large-scale quantitative mass spectrometry to identify proteins that enrich specifically with peroxisomes of Saccharomyces cerevisiae. In two complementary experiments, isotope-coded affinity tags and tandem mass spectrometry were used to quantify the relative enrichment of proteins during the purification of peroxisomes. Mathematical modeling of the data from 306 quantified proteins led to a prioritized list of 70 candidates whose enrichment scores indicated a high likelihood of them being peroxisomal. Among these proteins, eight novel peroxisome-associated proteins were identified. The top novel peroxisomal candidate was the small GTPase Rho1p. Although Rho1p has been shown to be tethered to membranes of the secretory pathway, we show that it is specifically recruited to peroxisomes upon their induction in a process dependent on its interaction with the peroxisome membrane protein Pex25p. Rho1p regulates the assembly state of actin on the peroxisome membrane, thereby controlling peroxisome membrane dynamics and biogenesis

Decline of Leach’s Storm Petrels Hydrobates leucorhous at the largest colonies in the northeast Atlantic

Leach’s Storm Petrel Hydrobates leucorhous has undergone substantial population declines at North Atlantic colonies over recent decades, but censusing the species is challenging because it nests in burrows and is only active at colonies at night. Acoustic playback surveys allow birds present in nest sites to be detected when they respond to recordings of vocalisations. However, not all birds respond to playback on every occasion, response rate is likely to decline with increasing distance between the bird and the playback location, and the observer may not detect all responses. As a result, various analysis methods have been developed to measure and correct for these imperfect response and detection probabilities. We applied two classes of methods (calibration plot and hierarchical distance sampling) to acoustic survey data from the two largest colonies of breeding Leach’s Storm Petrels in the northeast Atlantic: the St Kilda archipelago off the coast of northwest Scotland, and the island of Elliðaey in the Vestmannaeyjar archipelago off the southwest of Iceland. Our results indicate an overall decline of 68% for the St Kilda archipelago between 2000 and 2019, with a current best estimate of ~8,900 (95% CI: 7,800–10,100) pairs. The population on Elliðaey appears to have declined by 40 –49% between 1991 and 2018, with a current best estimate of ~5,400 (95% CI: 4,300–6,700) pairs. We also discuss the relative efficiency and precision of the two survey methods

Decline of Leach’s Storm Petrels Hydrobates leucorhous at the largest colonies in the northeast Atlantic

Leach’s Storm Petrel Hydrobates leucorhous has undergone substantial population declines at North Atlantic colonies over recent decades, but censusing the species is challenging because it nests in burrows and is only active at colonies at night. Acoustic playback surveys allow birds present in nest sites to be detected when they respond to recordings of vocalisations. However, not all birds respond to playback on every occasion, response rate is likely to decline with increasing distance between the bird and the playback location, and the observer may not detect all responses. As a result, various analysis methods have been developed to measure and correct for these imperfect response and detection probabilities. We applied two classes of methods (calibration plot and hierarchical distance sampling) to acoustic survey data from the two largest colonies of breeding Leach’s Storm Petrels in the northeast Atlantic: the St Kilda archipelago off the coast of northwest Scotland, and the island of Elliðaey in the Vestmannaeyjar archipelago off the southwest of Iceland. Our results indicate an overall decline of 68% for the St Kilda archipelago between 2000 and 2019, with a current best estimate of ~8,900 (95% CI: 7,800–10,100) pairs. The population on Elliðaey appears to have declined by 40 –49% between 1991 and 2018, with a current best estimate of ~5,400 (95% CI: 4,300–6,700) pairs. We also discuss the relative efficiency and precision of the two survey methods

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Global analysis of gene and protein expression in rat models of depression with analysis of gene-environment interaction and antidepressant effects.

Background and aims: The simultaneous and wide-scale analysis of gene and protein expression provides a powerful strategy for the exploration at molecular level of complex pathophysiological mechanisms, such as the response to treatment with psychotropic agents. GENDEP is an Integrated Project that combines large-scale clinical pharmacogenomic studies on depressed patients with preclinical investigations on animal models, focusing on treatment with proserotonergic and pronoradrenergic antidepressants. Methods: Two different, complementary rat models of depression were used: the flinders sensitive line (FSL) and the learned helplessness. FSL rats were additionally subjected to a maternal separation protocol to investigate the impact of gene-environment interaction. Animals were chronically treated with escitalopram or nortriptyline, with behavioural studies and transcriptomic and proteomic profiling, in order to identify novel genes and gene products differentially expressed in the different paradigms. Transcriptome analyses were performed from prefrontal cortex and hippocampus using Affymetrix GeneChips, whilst for proteomics two-dimensional electrophoresis with mass spectrometry was used. Further proteomic studies, including functional investigations focusing on the detection of protein phosphorylation changes, were performed on both total extracts and purified synaptic terminals. Finally, modifications of synaptic plasticity (LTP) in hippocampus were investigated by electrophysiology with parallel measurements of molecular correlates. Results and conclusions: Preliminary results on proteome and transcriptome analysis of escitalopram treated rats allowed the identification of molecular and functional correlates of vulnerability to the disease, the effect of early-life stress and the response to pharmacological treatment