Search

The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of 771 patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological cancers at risk of being subtracted by standard variant calling pipelines. Our work highlights the importance of contamination assessment for accurate somatic variants detection in research and clinical settings, especially with large-scale sequencing projects being utilised to deliver accurate data from which to make clinical decisions for patient care.Assessing tumour contamination in normal samples is critical for accurate variant calling in cancer samples. Here, the authors develop TINC, a computational method to determine the level of tumour in normal contamination, and demonstrate its application in the Genomics England 100,000 Genomes Project dataset. [ABSTRACT FROM AUTHOR]

Integrating human genomics and proteomics can help elucidate disease mechanisms, identify clinical biomarkers and discover drug targets1–4. Because previous proteogenomic studies have focused on common variation via genome-wide association studies, the contribution of rare variants to the plasma proteome remains largely unknown. Here we identify associations between rare protein-coding variants and 2,923 plasma protein abundances measured in 49,736 UK Biobank individuals. Our variant-level exome-wide association study identified 5,433 rare genotype–protein associations, of which 81% were undetected in a previous genome-wide association study of the same cohort5. We then looked at aggregate signals using gene-level collapsing analysis, which revealed 1,962 gene–protein associations. Of the 691 gene-level signals from protein-truncating variants, 99.4% were associated with decreased protein levels. STAB1 and STAB2, encoding scavenger receptors involved in plasma protein clearance, emerged as pleiotropic loci, with 77 and 41 protein associations, respectively. We demonstrate the utility of our publicly accessible resource through several applications. These include detailing an allelic series in NLRC4, identifying potential biomarkers for a fatty liver disease-associated variant in HSD17B13 and bolstering phenome-wide association studies by integrating protein quantitative trait loci with protein-truncating variants in collapsing analyses. Finally, we uncover distinct proteomic consequences of clonal haematopoiesis (CH), including an association between TET2-CH and increased FLT3 levels. Our results highlight a considerable role for rare variation in plasma protein abundance and the value of proteogenomics in therapeutic discovery.A set of three papers in Nature reports a new proteomics resource from the UK Biobank and initial analysis of common and rare genetic variant associations with plasma protein levels. [ABSTRACT FROM AUTHOR]

This paper first demonstrates that recognition of the diversity of ways that emotional responses modulate ongoing attention generates what I call the puzzle of emotional attention, which turns on the fact that distinct emotions (e.g., fear, happiness, disgust, admiration etc.) have different attentional profiles. The puzzle concerns why this is the case, such that a solution consists in explaining why distinct emotions have the distinct attentional profiles they do. It then provides an account of the functional roles of different emotions, as tied to their evaluative themes, which explains and further elucidates the distinctive attentional profiles of different emotions, so solving the puzzle of emotional attention. Following that, it outlines how such attentional profiles are reflected in the character of emotional experience and its attentional phenomenology. The resulting picture is a more detailed account of the connections between emotion and attention than is currently on offer in the philosophical literature. [ABSTRACT FROM AUTHOR]

Inference of species networks from genomic data under the Network Multispecies Coalescent Model is currently severely limited by heavy computational demands. It also remains unclear how complicated networks can be for consistent inference to be possible. As a step toward inferring a general species network, this work considers its tree of blobs, in which non-cut edges are contracted to nodes, so only tree-like relationships between the taxa are shown. An identifiability theorem, that most features of the unrooted tree of blobs can be determined from the distribution of gene quartet topologies, is established. This depends upon an analysis of gene quartet concordance factors under the model, together with a new combinatorial inference rule. The arguments for this theoretical result suggest a practical algorithm for tree of blobs inference, to be fully developed in a subsequent work. [ABSTRACT FROM AUTHOR]

A central claim in contemporary philosophy of mind is that the phenomenal character of experience is entirely determined by its content. This paper considers an alternative called Mode Intentionalism. According to this view, phenomenal character outruns content because the intentional mode contributes to the phenomenal character of the experience. I assess a phenomenal contrast argument in support of this view, arguing that the cases appealed to allow for interpretations which do not require positing intentional modes as phenomenologically manifest aspects of experience. [ABSTRACT FROM AUTHOR]

It is a familiar feature of our affective psychology that our moods 'crystalize' into emotions, and that our emotions 'diffuse' into moods. Providing a detailed philosophical account of these affective shifts, as I will call them, is the central aim of this paper. Drawing on contemporary philosophy of emotion and mood, alongside distinctive ideas from the phenomenologically-inspired writer Robert Musil, a broadly 'intentional' and 'evaluativist' account will be defended. I argue that we do best to understand important features of these affective shifts–which I document across this paper–in terms of intentional and evaluative aspects of the respective states of moods and emotion. At same the time, the account is pitched at the phenomenological level, as dealing with affective shifts primarily in terms of moods and emotions as experiential states, with respect to which it feels-like-something to be undergoing the relevant affective experience. The paper also applies the intentional-evaluative model of affective shifts to anxiety in more detail, developing the idea that certain patterns of affective shift, particularly those that allow for a kind of 'emotional release', can contribute to a subject's well-being. [ABSTRACT FROM AUTHOR]

We performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; β = 0.14; P = 6.2 × 10−12). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10−40), exon 4 inclusion (P = 4.29 × 10−34), and decreased exon 3 and 5 splicing (P = 7.85 × 10−43), replicated using RT-PCR in 15 adrenal samples. As CYP11B1 encodes 11-β-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism. Olja Grgic, Matthew Gazzara, and Alessandra Chesi et al. perform a genome-wide association study meta-analysis for skeletal age in two pediatric cohorts. They observe that variation in the adrenal gene, CYP11B1, impacts its alternative splicing, suggesting that adrenal steroidogenesis may contribute toward variation in skeletal age in otherwise healthy children. [ABSTRACT FROM AUTHOR]

This paper provides an assessment of the bodily-attitudinal theory of emotions, according to which emotions are felt bodily attitudes of action readiness. After providing a reconstruction of the view and clarifying its central commitments two objections are considered (absence of bodily phenomenology and what kind of bodily awareness). An alternative object side interpretation of felt action readiness is then provided, which undermines the motivation for the bodily-attitudinal theory and creates problems for its claims concerning the content of emotional experience. The conclusion is that while the bodily-attitudinal theory marks out a distinctive proposal concerning the question of what emotions are, there remain significant issues which need addressing if it is to be a plausible competitor to existing theories of emotion. [ABSTRACT FROM AUTHOR]

The homotopy analysis method (HAM) has been shown to approximate solutions to nonlinear problems of various types. The method is useful because of the flexibility in defining the auxiliary parameter ħ and that no assumption concerning relative size of parameters is required. We use the HAM to approximate frequency and solution of a conservative nonlinear oscillator which has many applications including lasers, epidemics, and microparasites. The oscillator is modeled by the simplified Liénard Equation x ¨ + ϵ x ˙ x + x = 0 . We compare our results for the weakly-nonlinear case to those gained from a more traditional perturbation technique, the Poincaré–Lindstedt method. We then show results from the HAM in the strongly-nonlinear regime and discuss some benefits and limitations of the method including conditions for convergence. [ABSTRACT FROM AUTHOR]

Many philosophers have understood the representational dimension of affective states along the model of perceptual experiences. This paper argues affective experiences involve a kind of personal level affective representation disanalogous from the representational character of perceptual experiences. The positive thesis is that affective representation is a non-transparent, non-sensory form of evaluative representation, whereby a felt valenced attitude represents the object of the experience as minimally good or bad, and one experiences that evaluative standing as having the power to causally motivate the relevant attitude. I show how this view can make sense of distinctive features of affective experiences, such as their valence and connection to value in a way which moves beyond current evaluativist views of affect. [ABSTRACT FROM AUTHOR]

Emotion theory includes attempts to reduce or assimilate emotions to states such as bodily feelings, beliefs-desire combinations, and evaluative judgements. Resistance to such approaches is motivated by the claim that emotions possess a sui generis phenomenology. Uriah Kriegel defends a new form of emotion reductivism which avoids positing irreducible emotional phenomenology by specifying emotions' phenomenal character in terms of a combination of other phenomenologies. This article argues Kriegel's approach, and similar proposals, are unsuccessful, since typical emotional experiences are constituted by sui generis feelings towards value. [ABSTRACT FROM AUTHOR]

Superrotation is a dynamical regime where the atmosphere circulates around the planet in the direction of planetary rotation with excess angular momentum in the equatorial region. Superrotation is known to exist in the atmospheres of Venus, Titan, Jupiter, and Saturn in the solar system. Some of the exoplanets also exhibit superrotation. Our understanding of superrotation in a framework of circulation regimes of the atmospheres of terrestrial planets is in progress thanks to the development of numerical models; a global instability involving planetary-scale waves seems to play a key role, and the dynamical state depends on the Rossby number, a measure of the relative importance of the inertial and Coriolis forces, and the thermal inertia of the atmosphere. Recent general circulation models of Venus's and Titan's atmospheres demonstrated the importance of horizontal waves in the angular momentum transport in these atmospheres and also an additional contribution of thermal tides in Venus's atmosphere. The atmospheres of Jupiter and Saturn also exhibit strong superrotation. Recent gravity data suggests that these superrotational flows extend deep into the planet, yet currently no single mechanism has been identified as driving this superrotation. Moreover, atmospheric circulation models of tidally locked, strongly irradiated exoplanets have long predicted the existence of equatorial superrotation in their atmospheres, which has been attributed to the result of the strong day-night thermal forcing. As predicted, recent Doppler observations and infrared phase curves of hot Jupiters appear to confirm the presence of superrotation on these objects. [ABSTRACT FROM AUTHOR]

Arguments for attributing non-conceptual content to experience have predominantly been motivated by aspects of the visual perception of empirical properties. In this article, I pursue a different strategy, arguing that a specific class of affective-evaluative experiences have non-conceptual content. The examples drawn on are affective-evaluative experiences of first exposure, in which the subject has a felt valenced intentional attitude towards evaluative properties of the object of their experience, but lacks any powers of conceptual discrimination regarding those evaluative properties. I also show that by accepting this thesis we can explain relevant features of evaluative understanding. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) is a powerful technique for determining the petrophysical properties (porosity, permeability, and fluid mobility) of subsurface reservoirs through well logs, laboratory core analysis, or surface measurements of drill cuttings at the rig site. In well logging, NMR is considered a lithology-independent tool, but in surface measurements, it is possible to determine the apparent magnetic susceptibility contrast between the rock and a saturating liquid from a measure of the free induction decay. The magnetic susceptibility of the rock is influenced by paramagnetic minerals (iron and manganese oxides) and provides a simple method for detecting variations in lithology, particularly shale bands. Here, NMR measurements of apparent magnetic susceptibility contrast are obtained on a selection of core plugs, powdered rock, and drilled cuttings using a commercial bench top instrument, and shown to correlate to the iron content of the samples. This rapid and robust analysis complements the standard NMR petrophysical measurements and could be used to detect formation tops in near-real-time at the rig site. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) comprises a constellation of metabolic abnormalities that substantially increase risk for chronic illnesses. Autonomic dysregulation is closely linked to MetS, and while pathophysiological models often address chronic stress exposure, none have examined how such physiological contributions operate situationally, in a clinical setting. We used ambulatory impedance cardiography to examine indicators of cardiac autonomic control (CAC) in a sample of 50 adult primary care patients with and without MetS. Indices of independent sympathetic and parasympathetic cardiovascular control in primary care outpatients were measured during a brief stress reactivity assessment. We compared interdependent CAC features, including cardiac autonomic balance (i.e., sympathovagal reciprocity) and cardiac autonomic regulation (i.e., sympathovagal coactivation) and found significant differences among MetS participants as compared to healthy controls. In particular, cardiac autonomic regulation scores were higher among MetS patients when discussing medication concerns, and cardiac autonomic balance scores were lower among MetS patients when discussing daily stressors. These results suggest that patients meeting criteria for MetS demonstrate momentary variations in CAC depending on personally relevant health topics. The potential for future research is discussed with a focus on prospective data collection to enhance diagnostic procedures and treatment monitoring. [ABSTRACT FROM AUTHOR]

Background: Observational studies have associated adiposity with an increased risk of colorectal cancer (CRC). However, such studies do not establish a causal relationship. To minimise bias from confounding we performed a Mendelian randomisation (MR) analysis to examine the relationship between adiposity and CRC.Methods: We used SNPs associated with adult body mass index (BMI), waist-hip ratio (WHR), childhood obesity and birth weight as instrumental variables in a MR analysis of 9254 CRC cases and 18 386 controls.Results: In the MR analysis, the odds ratios (ORs) of CRC risk per unit increase in BMI, WHR and childhood obesity were 1.23 (95% CI: 1.02-1.49, P=0.033), 1.59 (95% CI: 1.08-2.34, P=0.019) and 1.07 (95% CI: 1.03-1.13, P=0.018), respectively. There was no evidence for association between birth weight and CRC (OR=1.22, 95% CI: 0.89-1.67, P=0.22). Combining these data with a concurrent MR-based analysis for BMI and WHR with CRC risk (totalling to 18 190 cases, 27 617 controls) provided increased support, ORs for BMI and WHR were 1.26 (95% CI: 1.10-1.44, P=7.7 × 10(-4)) and 1.40 (95% CI: 1.14-1.72, P=1.2 × 10(-3)), respectively.Conclusions: These data provide further evidence for a strong causal relationship between adiposity and the risk of developing CRC highlighting the urgent need for prevention and treatment of adiposity. [ABSTRACT FROM AUTHOR]

Background: The increasing incidence of testicular germ cell tumour (TGCT) combined with its strong heritable basis suggests that stratified screening for the early detection of TGCT may be clinically useful. We modelled the efficiency of such a personalised screening approach, based on genetic risk profiling in combination with other diagnostic tools.Methods: We compared the number of cases potentially detectable in the population under a number of screening models. The polygenic risk scoring (PRS) model was assumed to have a log-normal relative risk distribution across the 19 currently known TGCT susceptibility variants. The diagnostic performance of testicular biopsy and non-invasive semen analysis was also assessed, within a simulated combined screening programme.Results: The area under the curve for the TGCT PRS model was 0.72 with individuals in the top 1% of the PRS having a nine-fold increased TGCT risk compared with the population median. Results from population-screening simulations only achieved a maximal positive predictive value (PPV) of 60%, highlighting broader clinical factors that challenge such strategies, not least the rare nature of TGCT. In terms of future improvements, heritability estimates suggest that a significant number of additional genetic risk factors for TGCT remain to be discovered, identification of which would potentially yield improvement of the PPV to 80-90%.Conclusions: While personalised screening models may offer enhanced TGCT risk discrimination, presently the case for population-level testing is not compelling. However, future advances, such as more routine generation of whole genome data is likely to alter the landscape. More targeted screening programs may plausibly then offer clinical benefit, particularly given the significant survivorship issues associated with the successful treatment of TGCT. [ABSTRACT FROM AUTHOR]

The present investigation uses facial electromyography (fEMG) to measure patterns of affective expression in individuals with psychometrically defined schizotypy during presentation of neutral and negative visual images. Twenty-eight individuals with elevated schizotypal features and 20 healthy controls observed a series of images from the International Affective Picture System (IAPS) and provided self-report ratings of affective valence and arousal while their physiological responses were recorded. The groups were evenly divided by sex. A three-way interaction in fEMG measurement revealed that while males with psychometrically defined schizotypy demonstrated the expected pattern of blunted/constricted facial affective expression relative to male controls in the context of negative images, females displayed the opposite pattern. That is, females with psychometrically defined schizotypy demonstrated significant elevations in negative facial affective expression relative to female controls while viewing negative images. We argue that these findings corroborate previously reported impressions of sex differences in affective expression in schizotypy. We discuss implications for assessment and diagnostic procedures among individuals with disorders along the schizophrenia spectrum. [ABSTRACT FROM AUTHOR]

During the Last Glacial Maximum, tropical sea surface temperatures were 1 to 3 °C cooler than present, but the altitude of the snowlines of tropical glaciers was lower than would be expected in light of these sea surface temperatures. Indeed, both glacial and twentieth-century snowlines seem to require lapse rates that are steeper than a moist adiabat. Here we use estimates of Last Glacial Maximum sea surface temperature in the Indo-Pacific warm pool based on the clumped isotope palaeotemperature proxy in planktonic foraminifera and coccoliths, along with radiative-convective calculations of vertical atmospheric thermal structure, to assess the controls on tropical glacier snowlines. Using extensive new data sets for the region, we demonstrate that mean environmental lapse rates are steeper than moist adiabatic during the recent and glacial. We reconstruct glacial sea surface temperatures 4 to 5 °C cooler than modern. We include modern and glacial sea surface temperatures in calculations of atmospheric convection that account for mixing between rising air and ambient air, and derive tropical glacier snowlines with altitudes consistent with twentieth-century and Last Glacial Maximum reconstructions. Sea surface temperature changes ≤3 °C are excluded unless glacial relative humidity values were outside the range associated with deep convection in the modern. We conclude that the entrainment of ambient air into rising air masses significantly alters the vertical temperature structure of the troposphere in modern and ancient regions of deep convection. Furthermore, if all glacial tropical temperatures were cooler than previously estimated, it would imply a higher equilibrium climate sensitivity than included in present models. [ABSTRACT FROM AUTHOR]

Quantitative in situ monitoring of oil recovery from sedimentary rock is demonstrated for the first time using advanced two-dimensional (2D) nuclear magnetic resonance (NMR) correlation measurements on a low field spectrometer. The laboratory-scale NMR system was chosen to provide a common physics of measurement with NMR well-logging tools. The NMR protocols are used to monitor recovery of a heavy Middle East crude oil from high permeability sandstone plugs using a brine (water) flood followed by chemical enhanced oil recovery agents: polymer and alkaline-surfactant-polymer solutions. 2D correlations between relaxation time ( T, T) and apparent self-diffusion coefficient D are used to obtain simultaneously a volumetric determination of the oil and aqueous fluid-phase saturations present in the porous material. The T − T and D − T correlations are bulk measurements of the entire rock core-plug; excellent agreement is shown between the measures of remaining oil (from NMR) and recovered oil (from gravimetric assay of the effluent). Furthermore, we introduce the capability to measure spatially resolved T distributions on a low field spectrometer using a rapid frequency-encoded y − T map. A non-uniform distribution of remaining oil is observed due to viscous instabilities in the flowing liquids; the final oil saturation ranges from $${S_{\rm o}^{\rm{(final)}} \approx 0}$$ to 20 % along the direction of flow. These results highlight the quantitative nature of the NMR data obtainable in low field NMR core analysis and also the importance of spatially resolved measurements when studying short core-plugs. [ABSTRACT FROM AUTHOR]

We describe a mission concept for a stand-alone Titan airplane mission: Aerial Vehicle for In-situ and Airborne Titan Reconnaissance (AVIATR). With independent delivery and direct-to-Earth communications, AVIATR could contribute to Titan science either alone or as part of a sustained Titan Exploration Program. As a focused mission, AVIATR as we have envisioned it would concentrate on the science that an airplane can do best: exploration of Titan's global diversity. We focus on surface geology/hydrology and lower-atmospheric structure and dynamics. With a carefully chosen set of seven instruments-2 near-IR cameras, 1 near-IR spectrometer, a RADAR altimeter, an atmospheric structure suite, a haze sensor, and a raindrop detector-AVIATR could accomplish a significant subset of the scientific objectives of the aerial element of flagship studies. The AVIATR spacecraft stack is composed of a Space Vehicle (SV) for cruise, an Entry Vehicle (EV) for entry and descent, and the Air Vehicle (AV) to fly in Titan's atmosphere. Using an Earth-Jupiter gravity assist trajectory delivers the spacecraft to Titan in 7.5 years, after which the AVIATR AV would operate for a 1-Earth-year nominal mission. We propose a novel 'gravity battery' climb-then-glide strategy to store energy for optimal use during telecommunications sessions. We would optimize our science by using the flexibility of the airplane platform, generating context data and stereo pairs by flying and banking the AV instead of using gimbaled cameras. AVIATR would climb up to 14 km altitude and descend down to 3.5 km altitude once per Earth day, allowing for repeated atmospheric structure and wind measurements all over the globe. An initial Team-X run at JPL priced the AVIATR mission at FY10 $715M based on the rules stipulated in the recent Discovery announcement of opportunity. Hence we find that a standalone Titan airplane mission can achieve important science building on Cassini's discoveries and can likely do so within a New Frontiers budget. [ABSTRACT FROM AUTHOR]

Venom delivery systems occur in a wide range of extant and fossil vertebrates and are primarily based on oral adaptations. Teeth range from unmodified (Komodo dragons) to highly specialized fangs similar to hypodermic needles (protero- and solenoglyphous snakes). Developmental biologists have documented evidence for an infolding pathway of fang evolution, where the groove folds over to create the more derived condition. However, the oldest known members of venomous clades retain the same condition as their extant relatives, resulting in no fossil evidence for the transition. Based on a comparison of previously known specimens with newly discovered teeth from North Carolina, we describe a new species of the Late Triassic archosauriform Uatchitodon and provide detailed analyses that provide evidence for both venom conduction and document a complete structural series from shallow grooves to fully enclosed tubular canals. While known only from teeth, Uatchitodon is highly diagnostic in possessing compound serrations and for having two venom canals on each tooth in the dentition. Further, although not a snake, Uatchitodon sheds light on the evolutionary trajectory of venom delivery systems in amniotes and provide solid evidence for venom conduction in archosaur-line diapsids. [ABSTRACT FROM AUTHOR]

The application of a nuclear magnetic resonance (NMR) diffusion measurement suitable for monitoring, in situ, the evolution of microstructure in commercial surfactant-based detergent drops as a response to drying is demonstrated for the first time. We utilise pulsed field gradient (PFG) NMR diffusion techniques to observe variations in self-diffusion coefficient, surface-to-volume ratio and characteristic pore size by probing the water content of the drops. Previously, we quantified the evolution of microstructure in vials of detergent paste using conventional PFG techniques. Now we apply a rapid PFG technique to enable this measurement during the relatively fast in situ drying of a drop with spherical geometry, relevant to spray drying processes. A finer structure is seen to form in the drops compared to the paste in the vials. [ABSTRACT FROM AUTHOR]

The effect of different extraction methods on the quality of crude palm oil processed using traditional (local) and mechanical methods in selected areas of Rivers and Bayelsa States and their storage stability were investigated. Certain quality determining parameters such as free fatty acids (FFA), peroxide value (PV), saponification value (SV), moisture, impurities and volatile matter (MIV) content were determined prior to and after storage for three months. The free fatty acids (FFA) ranged from 7 to 19 percent, peroxide value (PV) ranged from 3 mEq/kg to 6 mEq/kg and moisture, impurity and volatile matter (MIV) ranged from 0.21 to 0.64 percent for locally extracted crude palm oil samples and mechanically extracted crude palm oil samples. There was no significant difference (p > 0.05) in the FFA of samples A and E before and after storage for 3 months. Also two of the locally extracted crude samples (A and E) stored better while one of the samples (D) showed a high level of deterioration as shown in its high levels of FFA, PV and IV values. Samples A and E resulted in a better quality of oil in terms of FFA (av. 7.25%) and PV (av. 4.5 meg/kg) when compared to the mechanically extracted one (sample C) with FFA (10.0%) and PV (5.78 mEq/kg). However, all the locally and mechanically extracted crude palm oil samples could not meet the industrial and international standard quality for crude palm with FFA (2-5%) and PV (2-3.5 mEq/kg). Among the three different storage containers used under different storage conditions, plastic containers (PC) resulted in a better storage stability of the crude palm oils in terms of FFA, SV, and IV than transparent bottles stored on shelves (TBS) and amber-colored bottles stored on the bare floor (BPF). [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM. [ABSTRACT FROM AUTHOR]

B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10−9) with opposing effects between CLL (P = 1.97 × 10−8) and HL (P = 3.31 × 10−3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10−12) was associated with increased CLL and HL risk (P = 4.68 × 10−12), and reduced MM risk (P = 1.12 × 10−2), and Gly70 in HLA-DQB1 (P = 3.15 × 10−10) showed opposing effects between CLL (P = 3.52 × 10−3) and HL (P = 3.41 × 10−9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs. [ABSTRACT FROM AUTHOR]

A sizable fraction of testicular germ cell tumour (TGCT) risk is expected to be explained by heritable factors. Recent genome-wide association studies (GWAS) have successfully identified a number of common SNPs associated with TGCT. It is however, unclear how much common variation there is left to be accounted for by other, yet to be identified, common SNPs and what contribution common genetic variation makes to the heritable risk of TGCT. We approached this question using two complimentary analytical techniques. We undertook a population-based analysis of the Swedish family-cancer database, through which we estimated that the heritability of TGCT at 48.9% (CI:47.2%-52.3%). We also applied Genome-Wide Complex Trait Analysis to 922 cases and 4,842 controls to estimate the heritability of TGCT. The heritability explained by known common risk SNPs identified by GWAS was 9.1%, whereas the heritability explained by all common SNPs was 37.4% (CI:27.6%-47.2%). These complementary findings indicate that the known TGCT SNPs only explain a small proportion of the heritability and many additional common SNPs remain to be identified. The data also suggests that a fraction of the heritability of TGCT is likely to be explained by other classes of genetic variation, such as rare disease-causing alleles. [ABSTRACT FROM AUTHOR]

A sizeable fraction of multiple myeloma (MM) is expected to be explained by heritable factors. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) influencing MM risk. While these SNPs only explain a small proportion of the genetic risk it is unclear how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to 2,282 cases and 5,197 controls individuals to estimate the heritability of MM. We estimated that the heritability explained by known common MM risk SNPs identified in GWAS was 2.9% (±2.4%), whereas the heritability explained by all common SNPs was 15.2% (±2.8%). Comparing the heritability explained by the common variants with that from family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In summary, our results suggest that known MM SNPs only explain a small proportion of the heritability and more common SNPs remain to be identified. [ABSTRACT FROM AUTHOR]

Tag-recapture programs to monitor the movements of fish populations are among some of the longest-running citizen-science datasets to date. Here, using half a century of yellowtail kingfish (Seriola lalandi, Carangidae) tag-recapture data collected through citizen-science projects, we report novel insights into population connectivity in Australia and New Zealand (NZ). Despite the importance of kingfish in commercial and recreational fisheries, substantial knowledge gaps about their stock structure and connectivity between jurisdictions hinder current management efforts. Between 1974 and 2022, 63,432 releases and 4636 recaptures (7.3%) of tagged kingfish were collected in Australia and NZ. Most tagged individuals (51.4%) were recaptured within 10 km of their original release location up to 14 years post-release (mean: 225 days), indicating some degree of site fidelity. However, 656 (14.2%) kingfish were recaptured over 100 km from their release location, with one fish travelling at least 2834 km in 702 days. Seasonal variability was evident for releases and recaptures, with more releases occurring in summer and autumn in most jurisdictions. Network analysis of recaptures revealed no connectivity between tagged kingfish from western and eastern Australia, supporting genetic delineation. By contrast, extensive connectivity exists across eastern Australia and NZ, with 87 kingfish moving between five Australian state jurisdictions, 316 individuals travelling across 15 bioregions and six kingfish moving between Australia and NZ. Our findings provide important new insights into the structure and connectivity of the eastern Australia kingfish stock and suggest increased collaboration between state and international fisheries jurisdictions may support improved stock assessment and management. [ABSTRACT FROM AUTHOR]