Prediction of knot size in uneven-sized Norway spruce stands in Sweden

The size of knots is negatively correlated with bending strength in sawn timber and it is therefore used as a quality grading criterion in national roundwood grading standards. Some standards even use the size of the largest knot as the sole estimate for individual log knottiness. The size of knots is determined by crown horizontal extension, which in turn is dependent on the impact of competing trees. Thus, with knot size models that are competition-dependent, roundwood quality due to knottiness can be simulated for different management alternatives. However, these types of models, calibrated on uneven-sized Norway spruce in Fennoscandia, are currently not available. Therefore, the objective of this study is to develop a competition-dependent model framework for prediction of the largest knot size per stem height section, for application within uneven-sized Norway spruce stands. Data from terrestrial laser scanning of an uneven-sized stand in southern Sweden are used to calibrate a modular prediction framework, consisting of interlinked allometric statistical models. Alternative framework sub-models are presented and the preferred model combination can be selected according to context and available input data. The flexible modular format enables further development of separate sub-components for adaptation to growing conditions not covered by the current calibration range

The effects of human milk oligosaccharides on gut microbiota, metabolite profiles and host mucosal response in patients with irritable bowel syndrome

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-N-neotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health

Characterization of Degenerative Changes in the Temporomandibular Joint of the Bengal Tiger (Panthera tigris tigris) and Siberian Tiger (Panthera tigris altaica)

The articulation of the temporomandibular joint (TMJ) is composed of the temporal bone dorsally, the mandibular condyle ventrally and a fibrous articular disc. The TMJ disc plays an essential role in distributing load between the two articular surfaces. Degeneration of the disc in the presence of joint pathology has been shown in man; however, TMJ pathology has not been documented previously in tigers (Panthera tigris). The mandibular condyle and TMJ disc of a Bengal tiger (P. tigris tigris) and a Siberian tiger (P. tigris altaica) were evaluated grossly and the TMJ disc was characterized biochemically and mechanically. Characterization of the TMJ disc verified region- and direction-dependent biochemical and mechanical properties, reflective of the functional demands on the joint. Degenerative joint disease was observed in both cases and this was more severe in the Siberian tiger. Simultaneous evaluation of joint pathology, biochemical composition and mechanical properties of the TMJ disc revealed a loss in functional properties (tensile anisotropy) of the disc as joint pathology advanced from moderate to severe. TMJ degeneration may compromise the ability of the animal to eat and thrive and may be a factor contributing to the endangered status of these species

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Model uncertainty in the ecosystem approach to fisheries

Fisheries scientists habitually consider uncertainty in parameter values, but often neglect uncertainty about model structure. The importance of this latter source of uncertainty is likely to increase with the greater emphasis on ecosystem models in the move to an ecosystem approach to fisheries (EAF). It is therefore necessary to increase awareness about pragmatic approaches with which fisheries modellers and managers can account for model uncertainty and so we review current ways of dealing with model uncertainty in fisheries and other disciplines. These all involve considering a set of alternative models representing different structural assumptions, but differ in how those models are used. The models can be used to identify bounds on possible outcomes, find management actions that will perform adequately irrespective of the true model, find management actions that best achieve one or more objectives given weights assigned to each model, or formalise hypotheses for evaluation through experimentation. Data availability is likely to limit the use of approaches that involve weighting alternative models in an ecosystem setting, and the cost of experimentation is likely to limit its use. Practical implementation of the EAF should therefore be based on management approaches that acknowledge the uncertainty inherent in model predictions and are robust to it. Model results must be presented in a way that represents the risks and trade-offs associated with alternative actions and the degree of uncertainty in predictions. This presentation should not disguise the fact that, in many cases, estimates of model uncertainty may be based on subjective criteria. The problem of model uncertainty is far from unique to fisheries, and coordination among fisheries modellers and modellers from other communities will therefore be useful

A Transductionally Retargeted Adenoviral Vector for Virotherapy of Her2/neu-Expressing Prostate Cancer

Gene regulation and cell differentiatio