Lethal and Sublethal Effects of the Anti-sea Lice Formulation Salmosan® on the Pacific Spot Prawn (Pandalus Platyceros)

The effects of the aquaculture chemotherapeutant Salmosan® (active ingredient [a.i.]: azamethiphos) were examined in Pacific spot prawns (Pandalus platyceros) at three temperatures (5, 11, and 17°C). Post-molt prawns were more sensitive to Salmosan® than intermolt prawns; repeated (3x) 1-hr LC50 values for post-molt prawns ranged from 17 (9.3–31 95% confident intervals) to 40 (25–63) μg/L a.i. while intermolt prawns survived 3 × 1-hr exposures up to 100 μg/L a.i. Using LC50 values, Salmosan® was approximately 2.4 times more toxic at 17 versus 5°C. Temperature significantly altered chemosensory and locomotory behaviors in intermolt prawns with the highest activity at the intermediate temperature. Significant decreases in antennule flicking (84 and 104% over controls) were seen at 17°C after 3 × 1-hr pulse exposures to 50 and 100 μg/L a.i., respectively. Temperature, but not Salmosan®, affected molting success: at 17°C significantly lower survival was seen during ecdysis (60% of those at 5°C) and at 5°C, molt time was longer (41 ± 3 days) compared to 11°C (34 ± 4 days) or 17°C (21 ± 4 days). Life stage (molt status) and environmental parameters (temperature) alter the effects of Salmosan® to non-target spot prawns

Comparison of echocardiographic methods for calculating left ventricular mass in elite rugby football league athletes and the impact on chamber geometry

Background: Recommendations for the echocardiographic assessment of left ventricular (LV) mass in the athlete suggest the use of the linear method using a two-tiered classification system (2TC). The aims of this study were to compare the linear method and the area-length (A-L) method for LV mass in elite rugby football league (RFL) athletes and to establish how any differences impact the classification of LV geometry using 2TC and four-tier (4TC) classification systems. Methods: Two hundred and twenty (220) male RFL athletes aged 25 ± 5 (14–34 years) were recruited. All athletes underwent echocardiography and LV mass was calculated by the American Society of Echocardiography (ASE) corrected Linear equation (2D) and the A-L method. Left ventricular mass Index (LVMi) was used with relative wall thickness to determine geometry in the 2TC and with concentricity and LV end diastolic volume index for the 4TC. Method specific recommended cut-offs were utilised. Results: Higher values of absolute (197 ± 34 vs. 181 ± 34 g; p < 0.0001) and indexed (92 ± 13 vs. 85 ± 13 g/m2; p < 0.0001) measures of LV mass were obtained from A-L compared to the linear method. Normal LV geometry was demonstrated in 98.2% and 80% of athletes whilst eccentric hypertrophy in 1.4% and 19.5% for linear and A-L respectively. Both methods provided 0.5% as having concentric remodelling and 0% as having concentric hypertrophy. Allocation to the 4TC resulted in 97% and 80% with normal geometry, 0% and 8.6% with eccentric dilated hypertrophy, 0% and 7.7% with eccentric non-dilated hypertrophy, 1.4% and 0.5% with concentric remodelling and 1.4% and 3% with concentric non-dilated hypertrophy for linear and A-L methods respectively. No participants had concentric dilated hypertrophy from either methods. Conclusion: The linear and A-L method for calculation of LV mass in RFL athletes are not interchangeable with significantly higher values obtained using A-L method impacting on geometry classification. More athletes present with eccentric hypertrophy using 2TC and eccentric dilated/non-dilated using 4TC. Further studies should be aimed at establishing the association of A-L methods of LV mass and application of the 4TC to the multi-factorial demographics of the athlete

Draft Genome Sequence of Acetobacter aceti Strain 1023, a Vinegar Factory Isolate

The genome sequence of Acetobacter aceti 1023, an acetic acid bacterium adapted to traditional vinegar fermentation, comprises 3.0 Mb (chromosome plus plasmids). A. aceti 1023 is closely related to the cocoa fermenter Acetobacter pasteurianus 386B but possesses many additional insertion sequence elements

Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c)

Treatment with Menin inhibitor (MI) disrupts the interaction between Menin and MLL1 or MLL1-fusion protein (FP), inhibits HOXA9/MEIS1, induces differentiation and loss of survival of AML harboring MLL1 re-arrangement (r) and FP, or expressing mutant (mt)-NPM1. Following MI treatment, although clinical responses are common, the majority of patients with AML with MLL1-r or mt-NPM1 succumb to their disease. Pre-clinical studies presented here demonstrate that genetic knockout or degradation of Menin or treatment with the MI SNDX-50469 reduces MLL1/MLL1-FP targets, associated with MI-induced differentiation and loss of viability. MI treatment also attenuates BCL2 and CDK6 levels. Co-treatment with SNDX-50469 and BCL2 inhibitor (venetoclax), or CDK6 inhibitor (abemaciclib) induces synergistic lethality in cell lines and patient-derived AML cells harboring MLL1-r or mtNPM1. Combined therapy with SNDX-5613 and venetoclax exerts superior in vivo efficacy in a cell line or PD AML cell xenografts harboring MLL1-r or mt-NPM1. Synergy with the MI-based combinations is preserved against MLL1-r AML cells expressing FLT3 mutation, also CRISPR-edited to introduce mtTP53. These findings highlight the promise of clinically testing these MI-based combinations against AML harboring MLL1-r or mtNPM1

Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus

Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D), focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip) and absolute methylation values were estimated using a Bayesian algorithm (BATMAN). Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10−4, permutation p = 1.0×10−3). Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10−7). Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM), encapsulates a Highly Conserved Non-Coding Element (HCNE) that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA) SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases

How big is big enough? Toward a sustainable future by examining alternatives to the conventional economic growth paradigm

This study addresses how the sustainability crisis may be overcome by using alternatives to the conventional economic growth paradigm. Based on a literature review, the paper identifies and discusses three alternatives, namely negative, zero and positive economic growth. These alternatives are compared from a feasibility and policy perspective in relation to the transition toward sustainable development. The three alternatives are associated with very far‐reaching sets of policies that have different focal points with regard to how the paradigm shift from the conventional growth paradigm can be realized. All these alternatives, however, challenge the effectiveness of market forces. The shortcomings of the alternatives (resistance to voluntary transition with negative or zero growth, no proper consideration of the rebound effect for positive growth) hinder the transition and must be further addressed by policy‐makers in public and private sectors, as well as by civil society

Risk of Suicide Is Insufficient Warrant for Coercive Treatment for Mental Illness

Mental health laws in many jurisdictions currently permit coercive treatment for persons with mental illness who are thought to be at risk of harm to themselves or others. These laws are often used to provide involuntary treatment to persons who are thought to be at risk of suicide. In this article we argue that legislated coercive psychiatric treatment should not be triggered by an assessment of the likelihood of harm, including a likelihood of suicide, but should be available only where a person is found to lack capacity to make their own decisions about their own health risks, after appropriate support has been given. We suggest that current opposition this approach may find its origin in factors including uncertainties about the idea of vulnerability and its relationship to capacity as well as tendency to minimise the real costs of psychiatric treatment and coercion against the aim of suicide prevention. Given the limits of suicide risk assessment, we argue that a public policy that allows involuntary preventative detention of competent persons thought to be at risk of suicide, places too great a burden on all persons living with mental illness to be justified. We suggest that we are better placed to serve the interests and respect the human rights of people with mental illness if we respect and support the right of persons to make decisions, rather than focussing on perceived vulnerabilities and calculations of suicide risk