Pevonedistat targeted therapy inhibits canine melanoma cell growth through induction of DNA re‐replication and senescence

MLN4924 (pevonedistat) is a potent and selective NEDD8‐activating enzyme (NAE) inhibitor. The NEDD8‐regulated neddylation system is responsible for the regulated degradation of intracellular proteins with important cellular functions in cancer cell growth, apoptosis, angiogenesis and metastasis. In human melanoma, inhibition of NAE results in induction of DNA re‐replication, S phase cell cycle arrest, DNA damage and apoptosis. The study aimed to assess the anti‐cancer effect of MLN4924 on canine malignant melanoma cell lines and patient samples and to elucidate the underlying mechanisms. Canine melanoma cell lines and primary patient samples were evaluated for cell viability after incubation with varying concentrations of MLN4924 or dimethyl sulfoxide. Apoptosis, cell proliferation and senescence assays were performed to address underlying mechanisms of MLN4924‐mediated anti‐tumour effects. Gene expression of seven previously identified deregulated genes in human melanoma was compared in sensitive vs resistant samples. MLN4924 treatment significantly reduced the viability of canine melanoma cell lines and primary samples in a dose‐ and time‐dependent manners. MLN4924 promoted cell apoptosis and inhibited cell growth through induction of DNA re‐replication and cell senescence. While the majority of canine melanoma samples demonstrated sensitivity at nanomolar ranges, some samples were resistant to the treatment. Modulation of P21 levels correlated with canine melanoma cell sensitivity. These results provided justification for further exploration of MLN4924 as a treatment of canine melanoma.     

Potential role of lava lizards as pollinators across the Galápagos Islands

Lizards have been reported as important pollinators on several oceanic islands. Here we evaluate the potential role of Galápagos lava lizards (Microlophus spp.) as pollinators across their radiation. Over 3 years, we sampled pollen transport by 9 lava lizard species on the 10 islands where they are present, including 7 single‐island endemics. Overall, only 25 of 296 individuals sampled (8.4%) transported pollen of 10 plant species, the most common being Prosopis juliflora, Exodeconus miersii, Sesuvium sp. and Cordia leucophlyctis. At least 8 of these plant species were native, and none were confirmed as introduced to the archipelago. Despite the low overall proportion of individuals carrying pollen, this was observed in 7 of the nine lizard species, and on 8 of the ten main islands (Española, Fernandina, Floreana, Isabela, Marchena, Pinta, Santa Cruz and Santiago), suggesting that this is a widespread interaction. The results reported here support the potential role of lava lizards as pollinators across their radiation, although they may represent a relatively modest contribution when compared with birds and insects. However, we cannot discard that lizards may be ecologically significant for particular plant species and ecosystems given the specific climatic condition and functional diversity of each island.     

Norovirus outbreak in a natural playground: A One Health approach

Norovirus constitutes the most frequently identified infectious cause of disease outbreaks associated with untreated recreational water. When investigating outbreaks related to surface water, a One Health approach is insightful. Historically, there has been a focus on potential contamination of recreational water by bird droppings and a recent publication demonstrating human noroviruses in bird faeces suggested this should be investigated in future water‐related norovirus outbreaks. Here, we describe a One Health approach investigating a norovirus outbreak in a natural playground. On social media, a large amount of waterfowl were reported to defecate near these playground premises leading to speculations about their potential involvement. Surface water, as well as human and bird faecal specimens, was tested for human noroviruses. Norovirus was found to be the most likely cause of the outbreak but there was no evidence for transmission via waterfowl. Cases had become known on social media prior to notification to the public health service underscoring the potential of online media as an early warning system. In view of known risk factors, advice was given for future outbreak investigations and natural playground design.     

A common variant on chromosome 9p21 affects the risk of myocardial infarction

The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here, we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.     

Rubidium measured by XRF as a predictor of soil particle size in limestone and siliceous parent materials

Purpose

Information about particle size distribution (PSD) and soil texture is essential for understanding soil drainage, porosity, nutrient availability, and trafficability. The sieve-pipette/gravimetric method traditionally used for particle size analysis is labour-intensive and resource-intensive. X-ray fluorescence (XRF) spectrometry may provide a rapid alternative. The study’s aim was to examine the use of XRF for rapid determination of PSD in Irish soils.

Methods

Soils (n?=?355) from existing archives in Ireland were analysed with a benchtop energy-dispersive XRF (EDXRF). Correlation and regression analyses were determined to compare Rb, Fe, Al, and Si concentrations to % clay, % silt, and % sand. Also, linear regression models were developed to compare % clay, % sand, and % silt measured by the gravimetric method to values predicted by EDXRF.

Results

The relationship between element concentration and PSD was dependent on parent material. Rb, Al, and Fe showed a significant (p?<?0.05) correlation (r?>?0.50) with % clay and % sand in soils derived from limestone and siliceous stone parent materials. Rb was the best predictor for % clay (R²?=?0.49, RMSE?=?10.20) in soils derived from limestone and siliceous stone-derived soils.

Conclusion

Geochemistry and clay mineralogy of the soils’ parent material strongly influenced the EDXRF’s ability to predict particle size. The EDXRF could predict % clay in soils from parent materials which weather easily, but the opposite was true for soils with parent material recalcitrant to weathering. In conclusion, this study has shown that the EDXRF can screen % clay in soils derived from limestone and siliceous stone parent materials.

     

Realigning the land-sharing/land-sparing debate to match conservation needs: considering diversity scales and land-use history

The “land sharing versus land sparing” concept provides a framework for comparing potential land use patterns in terms of trade-offs between biodiversity conservation and agricultural yields at a landscape scale. Here, we raise two additional aspects to be considered in the sparing/sharing debate, supported by a review of available literature. First, beta and gamma (instead of alpha) diversity measures capture landscape scale variance in biodiversity in response to land use changes and should be considered for the long-term management of agricultural landscapes. Moreover, beta and gamma diversity may better account for comparisons of biodiversity between spared and shared land use options. Second, land use history has a pronounced influence on the complexity and variance in agricultural habitat niches at a landscape scale, which in turn may determine the relevance of sparing or sharing land use options. Appropriate and comparable biodiversity metrics and the recognition of landscape history are two vital preconditions in aligning biological conservation goals with maximized yields within the sparing/sharing framework.     

Genetic Variation and Association Mapping of Protein Concentration in Brown Rice Using a Diverse Rice Germplasm Collection

Protein is the second most abundant constituent in the rice grain next to starch. Association analysis for protein concentration in brown rice was performed using a “mini‐core” collection, which represents the germplasm diversity found in the USDA rice world collection. Protein concentration was determined in replicated trials conducted in two southern U.S. locations, and association mapping was performed by using 157 genomewide DNA markers. Protein concentration ranged from 5.4 to 11.9% among the 202 accessions. Protein variation owing to accession and accession × location interaction were highly significant. Ample variation was seen within each subpopulation by ancestry, as well as within the 14 geographic regions where the accessions originated. Accessions from Eastern Europe had the highest level of protein. Ten markers on eight chromosomes were significantly associated with protein concentration. Five of these markers occurred near known protein precursor genes or quantitative trait loci, and the other five markers were novel for the association with protein concentration in rice. The germplasm and genetic markers identified in this study will assist breeders in developing cultivars tailored for applications requiring specific protein concentration in the rice grain. The research results contribute to the potential discovery of novel rice storage protein pathways in the endosperm.     

Pregnancy detection in putatively unmated mink (Mustela vison) by serum progesterone level

The aim of this study was to determine whether blood plasma progesterone is a reliable indicator of pregnancy in mink at an early stage of gestation. We also attempted to establish the threshold value of progesterone as a pregnancy indicator. The analysis was carried out at a production farm on 42 standard female mink aged 1 year, which were grouped both according to the observed success of mating ("mated" and "unmated") and the level of blood serum progesterone measured afterwards ("pregnant" and "nonpregnant"). It was next verified whether a particular female had been assigned to the proper group in the first place. An analysis of accuracy of mating success assessment within the group of unmated females revealed that more than one-third of decisions were wrong, since some females that had been considered unmated ultimately whelped. This suggests that mating supervision by farm workers lacks reliability. A progesterone test for verification of such management decisions should limit the risk of err,or. We suggest that progesterone tests could be carried out using the threshold values 1.9 ng/ml and 20 ng/ml in blood sampled on 25 March and 8 April, respectively, although some level of uncertainty should be taken into account.