Methanethiol, dimethyl sulfide and acetone over biologically productive waters in the southwest Pacific Ocean

Atmospheric methanethiol (MeSHa), dimethyl sulfide (DMSa) and acetone (acetonea) were measured over biologically productive frontal waters in the remote southwest Pacific Ocean in summertime 2012 during the Surface Ocean Aerosol Production (SOAP) voyage. MeSHa mixing ratios varied from below the detection limit (<10ppt) up to 65ppt and were 3%–36% of parallel DMSa mixing ratios. MeSHa and DMSa were correlated over the voyage(R2=0.3,slope=0.07)with a stronger correlation over a coccolithophore-dominated phytoplankton bloom (R2= 0.5, slope 0.13). The diurnal cycle for MeSHa shows similar behaviour to DMSa with mixing ratios varying by a factor of ∼2 according to time of day with the minimum levels of both MeSHa and DMSa occurring at around 16:00LT (local time, all times in this paper are in local time). A positive flux of MeSH out of the ocean was calculated for three different nights and ranged from 3.5 to 5.8µmolm−2 d−1, corresponding to 14%–24% of the DMS flux (MeSH/(MeSH+DMS)). Spearman rank correlations with ocean biogeochemical parameters showed a moderate to-strong positive, highly significant relationship between both MeSHa and DMSa with seawater DMS (DMSsw) and a moderate correlation with total dimethylsulfoniopropionate (total DMSP). A positive correlation of acetonea with water temperature and negative correlation with nutrient concentrations are consistent with reports of acetone production in warmer subtropical waters. Positive correlations of acetonea with cryptophyte and eukaryotic phytoplankton numbers, and high-molecular-weight sugars and chromophoric dissolved organic matter (CDOM), suggest an organic source. This work points to a significant ocean source of MeSH, highlighting the need for further studies into the distribution and fate of MeSH, and it suggests links between atmospheric acetone levels and biogeochemistry over the midlatitude ocean. In addition, an intercalibration of DMSa at ambient levels using three independently calibrated instruments showed ∼15%–25% higher mixing ratios from an atmospheric pressure ionisation chemical ionisation mass spectrometer (mesoCIMS) compared to a gas chromatograph with a sulfurchemiluminescencedetector(GC-SCD)and proton transfer reaction mass spectrometer (PTR-MS). Some differences were attributed to the DMSa gradient above the sea surface and differing approaches of integrated versus discrete measurements. Remaining discrepancies were likely due to different calibrationscales,suggesting that further investigation of the stability and/or absolute calibration of DMSstandards used at sea is warranted

The Hierarchical Age-Period-Cohort model: Why does it find the results that it finds?

It is claimed the hierarchical-age–period–cohort (HAPC) model solves the age–period–cohort (APC) identification problem. However, this is debateable; simulations show situations where the model produces incorrect results, countered by proponents of the model arguing those simulations are not relevant to real-life scenarios. This paper moves beyond questioning whether the HAPC model works, to why it produces the results it does. We argue HAPC estimates are the result not of the distinctive substantive APC processes occurring in the dataset, but are primarily an artefact of the data structure—that is, the way the data has been collected. Were the data collected differently, the results produced would be different. This is illustrated both with simulations and real data, the latter by taking a variety of samples from the National Health Interview Survey (NHIS) data used by Reither et al. (Soc Sci Med 69(10):1439–1448, 2009) in their HAPC study of obesity. When a sample based on a small range of cohorts is taken, such that the period range is much greater than the cohort range, the results produced are very different to those produced when cohort groups span a much wider range than periods, as is structurally the case with repeated cross-sectional data. The paper also addresses the latest defence of the HAPC model by its proponents (Reither et al. in Soc Sci Med 145:125–128, 2015a). The results lend further support to the view that the HAPC model is not able to accurately discern APC effects, and should be used with caution when there appear to be period or cohort near-linear trends

Fine mapping of candidate effector genes for heart rate

An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality

Explicit Model Checking of Very Large MDP using Partitioning and Secondary Storage

The applicability of model checking is hindered by the state space explosion problem in combination with limited amounts of main memory. To extend its reach, the large available capacities of secondary storage such as hard disks can be exploited. Due to the specific performance characteristics of secondary storage technologies, specialised algorithms are required. In this paper, we present a technique to use secondary storage for probabilistic model checking of Markov decision processes. It combines state space exploration based on partitioning with a block-iterative variant of value iteration over the same partitions for the analysis of probabilistic reachability and expected-reward properties. A sparse matrix-like representation is used to store partitions on secondary storage in a compact format. All file accesses are sequential, and compression can be used without affecting runtime. The technique has been implemented within the Modest Toolset. We evaluate its performance on several benchmark models of up to 3.5 billion states. In the analysis of time-bounded properties on real-time models, our method neutralises the state space explosion induced by the time bound in its entirety.Comment: The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-24953-7_1

Alzheimer's pathology targets distinct memory networks in the ageing brain

Alzheimer’s disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer’s disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-β deposition in the progression from ageing to Alzheimer’s disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20–93 years; 47 amyloid-β-positive) and 20 amyloid-β-positive patients with mild cognitive impairment or Alzheimer’s disease dementia (65–95 years). Tau burden was relatively higher in anterior-temporal regions in normal ageing and this difference was further pronounced in the presence of amyloid-β and cognitive impairment, indicating exacerbation of ageing-related processes in Alzheimer’s disease. In contrast, amyloid-β deposition dominated in posterior-medial regions. A subsample of 50 cognitively normal older (26 amyloid-β-positive) and 25 young adults performed an object and scene memory task while functional MRI data were acquired. Group comparisons showed that tau-positive (n = 18) compared to tau-negative (n = 32) older adults showed lower mnemonic discrimination of object relative to scene images [t(48) = −3.2, P = 0.002]. In a multiple regression model including regional measures of both pathologies, higher anterior-temporal flortaucipir (tau) was related to relatively worse object performance (P = 0.010, r = −0.376), whereas higher posterior-medial PiB (amyloid-β) was related to worse scene performance (P = 0.037, r = 0.309). The functional MRI data revealed that tau burden (but not amyloid-β) was associated with increased task activation in both systems and a loss of functional specificity, or dedifferentiation, in posterior-medial regions. The loss of functional specificity was related to worse memory. Our study shows a regional dissociation of Alzheimer’s disease pathologies to distinct memory networks. While our data are cross-sectional, they indicate that with ageing, tau deposits mainly in the anterior-temporal system, which results in deficits in mnemonic object discrimination. As Alzheimer’s disease develops, amyloid-β deposits preferentially in posterior-medial regions additionally compromising scene discrimination and anterior-temporal tau deposition worsens further. Finally, our findings propose that the progression of tau pathology is linked to aberrant activation and dedifferentiation of specialized memory networks that is detrimental to memory function

DNA methylation patterns respond to thermal stress in the viviparous cockroach Diploptera punctata

It is increasingly recognized that epigenetic mechanisms play a key role in acclimatisation and adaptation to thermal stress in invertebrates. DNA methylation and its response to temperature variation has been poorly studied in insects. Here, we investigated DNA methylation and hydroxymethylation patterns in the viviparous cockroach Diploptera punctata at a global and gene specific level in response to variation in temperature. We specifically studied methylation percentage in the heat shock protein 70 (Hsp70), whose function is linked to thermal plasticity and resistance. We found high levels of DNA methylation in several tissues but only low levels of DNA hydroxymethylation in the brain. Hsp70 methylation patterns showed significant differences in response to temperature. We further found that global DNA methylation variation was considerably lower at 28°C compared to higher or lower temperatures, which may be indicative of the optimal temperature for this species. Our results demonstrate that DNA methylation could provide a mechanism for insects to dynamically respond to changing temperature conditions in their environment

Visual Ability and Searching Behavior of Adult Laricobius nigrinus, a Hemlock Woolly Adelgid Predator

Very little is known about the searching behavior and sensory cues that Laricobius spp. (Coleoptera: Derodontidae) predators use to locate suitable habitats and prey, which limits our ability to collect and monitor them for classical biological control of adelgids (Hemiptera: Adelgidae). The aim of this study was to examine the visual ability and the searching behavior of newly emerged L. nigrinus Fender, a host-specific predator of the hemlock woolly adelgid, Adelges tsugae Annand (Hemiptera: Phylloxeroidea: Adelgidae). In a laboratory bioassay, individual adults attempting to locate an uninfested eastern hemlock seedling under either light or dark conditions were observed in an arena. In another bioassay, individual adults searching for prey on hemlock seedlings (infested or uninfested) were continuously video-recorded. Beetles located and began climbing the seedling stem in light significantly more than in dark, indicating that vision is an important sensory modality. Our primary finding was that searching behavior of L. nigrinus, as in most species, was related to food abundance. Beetles did not fly in the presence of high A. tsugae densities and flew when A. tsugae was absent, which agrees with observed aggregations of beetles on heavily infested trees in the field. At close range of prey, slow crawling and frequent turning suggest the use of non-visual cues such as olfaction and contact chemoreception. Based on the beetles' visual ability to locate tree stems and their climbing behavior, a bole trap may be an effective collection and monitoring tool

An Appraisal of the Maternal Mortality Decline in Nepal

Peer reviewedPublisher PD