inbreedR: An R package for the analysis of inbreeding based on genetic markers

1. Heterozygosity fitness correlations (HFCs) have been used extensively to explore the impact of inbreeding on individual fitness. Initially, most studies used small panels of microsatellites, but more recently with the advent of next generation sequencing, large SNP datasets are becoming increasingly available and these provide greater power and precision to quantify the impact of inbreeding on fitness. 2. Despite the popularity of HFC studies, effect sizes tend to be rather small. One reason for this may be a low variation in inbreeding level across individuals. Using genetic markers, it is possible to measure variance in inbreeding through the strength of correlation in heterozygosity across marker loci, termed identity disequilibrium (ID). 3. ID can be quantified using the measure g2 which is also a central parameter in HFC theory that can be used within a wider framework to estimate the direct impact of inbreeding on both marker heterozygosity and fitness. However, no software exists to calculate g2 for large SNP datasets nor to implement this framework. 4. inbreedR is an R package that provides functions to calculate g2 based on microsatellite and SNP markers with associated p-values and confidence intervals. Within the framework of HFC theory, inbreedR also estimates the impact of inbreeding on marker heterozygosity and fitness. Moreover, we implemented easy-to-use simulations to explore the precision and magnitude of estimates based on different numbers of genetic markers. We hope this package will facilitate good practice in the analysis of HFCs and help to deepen our understanding of inbreeding effects in natural populations

Climate Change Effects on Slope Stability

Global warming is taking place and there is no doubt that the stability of natural and artificial slopes is influenced by climate change. In this context, the present study intends to show, as more quantitatively as possible, the effects of climate change on slopes stability. The analysis was developed considering a non-static approach suitable for meteorological phenomena which are expected to change in the next years. In the analysis a statistical method was combined with a mechanical one: the forecasts of the intensity growth of heavy precipitation were used, as well as the physical laws for describing the response of groundwater table to these rainfall events and the resulting slopes stability. A case study located in Monchiero (Cn), Italy, was used as a test for the analysis and the forecasts described above

Effects of housing, perches, genetics, and 25-hydroxycholecalciferol on keel bone deformities in laying hens

Several studies have shown a high prevalence of keel bone deformities in commercial laying hens. The aim of this project was to assess the effects of perch material, a vitamin D feed additive (25-hydroxyvitamin D3; HyD, DSM Nutritional Products, Basel, Switzerland), and genetics on keel bone pathology. The study consisted of 2 experiments. In the first experiment, 4,000 Lohmann Selected Leghorn hens were raised in aviary systems until 18 wk of age. Two factors were investigated: perch material (plastic or rubber-coated metal) and feed (with and without HyD). Afterward, the hens were moved to a layer house with 8 pens with 2 aviary systems. Daily feed consumption, egg production, mortality, and feather condition were evaluated. Every 6 wk, the keel bones of 10 randomly selected birds per pen were palpated and scored. In the second experiment, 2,000 Lohmann Brown (LB) hens and 2,000 Lohmann Brown parent stock (LBPS) hens were raised in a manner identical to the first experiment. During the laying period, the hens were kept in 24 identical floor pens but equipped with different perch material (plastic or rubber-coated metal). The same variables were investigated as in the first experiment. No keel bone deformities were found during the rearing period in either experiment. During the laying period, deformities gradually appeared and reached a prevalence of 35% in the first experiment and 43.8% in the second experiment at the age of 65 and 62 wk, respectively. In the first experiment, neither HyD nor the aviary system had any significant effect on the prevalence of keel bone deformities. In the second experiment, LBPS had significantly fewer moderate and severe deformities than LB, and rubber-coated metal perches were associated with a higher prevalence of keel bone deformities compared with plastic perches. The LBPS laid more but smaller eggs than the LB. Again, HyD did not affect the prevalence of keel bone deformities. However, the significant effect of breed affiliation strongly indicates a sizeable genetic component that may provide a basis for targeted selectio

Miravirsen (SPC3649) can inhibit the biogenesis of miR-122

MicroRNAs (miRNAs) are short noncoding RNAs, which bind to messenger RNAs and regulate protein expression. The biosynthesis of miRNAs includes two precursors, a primary miRNA transcript (pri-miRNA) and a shorter pre-miRNA, both of which carry a common stem-loop bearing the mature miRNA. MiR-122 is a liver-specific miRNA with an important role in the life cycle of hepatitis C virus (HCV). It is the target of miravirsen (SPC3649), an antimiR drug candidate currently in clinical testing for treatment of HCV infections. Miravirsen is composed of locked nucleic acid (LNAs) ribonucleotides interspaced throughout a DNA phosphorothioate sequence complementary to mature miR-122. The LNA modifications endow the drug with high affinity for its target and provide resistance to nuclease degradation. While miravirsen is thought to work mainly by hybridizing to mature miR-122 and blocking its interaction with HCV RNA, its target sequence is also present in pri- and pre-miR-122. Using new in vitro and cellular assays specifically developed to discover ligands that suppress biogenesis of miR-122, we show that miravirsen binds to the stem-loop structure of pri- and pre-miR-122 with nanomolar affinity, and inhibits both Dicer- and Drosha-mediated processing of miR-122 precursors. This inhibition may contribute to the pharmacological activity of the drug in ma

The 1600 CE Huaynaputina eruption as a possible trigger for persistent cooling in the North Atlantic region

Paleoclimate reconstructions have identified a period of exceptional summer and winter cooling in the North Atlantic region following the eruption of the tropical volcano Huaynaputina (Peru) in 1600 CE. A previous study based on numerical climate simulations has indicated a potential mechanism for the persistent cooling in a slowdown of the North Atlantic subpolar gyre (SPG) and consequent ocean-atmosphere feedbacks. To examine whether this mechanism could have been triggered by the Huaynaputina eruption, this study compares the simulations used in the previous study both with and without volcanic forcing and this SPG shift to reconstructions from annual proxies in natural archives and historical written records as well as contemporary historical observations of relevant climate and environmental conditions. These reconstructions and observations demonstrate patterns of cooling and sea-ice expansion consistent with, but not indicative of, an eruption trigger for the proposed SPG slowdown mechanism. The results point to possible improvements in future model-data comparison studies utilizing historical written records. Moreover, we consider historical societal impacts and adaptations associated with the reconstructed climatic and environmental anomalies

Germline genetic variants in men with prostate cancer and one or more additional cancers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138930/1/cncr30817.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138930/2/cncr30817_am.pd