Detection of mRNA using the BIACORE

We present the detection of native mRNA using the BIACORE system. The influence of different probes and flow rates on the detection is shown and compared to the hybridisation of oligonucleotides. Probes for mRNA detection were chosen by calculations of secondary structures using energy minimizing criteria based on the algorithm of Zuker. Probe concentrations were optimised as well as the regeneration conditions for the sensor surface. The influence of the flow rate appeared to be more marked for mRNA than for oligonucleotide hybridisation

Predicting EQ-5D-5L crosswalk from the PROMIS-29 profile for the United Kingdom, France, and Germany

BACKGROUND: EQ-5D health state utilities (HSU) are commonly used in health economics to compute quality-adjusted life years (QALYs). The EQ-5D, which is country-specific, can be derived directly or by mapping from self-reported health-related quality of life (HRQoL) scales such as the PROMIS-29 profile. The PROMIS-29 from the Patient Reported Outcome Measures Information System is a comprehensive assessment of self-reported health with excellent psychometric properties. We sought to find optimal models predicting the EQ-5D-5L crosswalk from the PROMIS-29 in the United Kingdom, France, and Germany and compared the prediction performances with that of a US model. METHODS: We collected EQ-5D-5L and PROMIS-29 profiles and three samples representative of the general populations in the UK (n = 1509), France (n = 1501), and Germany (n = 1502). We used stepwise regression with backward selection to find the best models to predict the EQ-5D-5L crosswalk from all seven PROMIS-29 domains. We investigated the agreement between the observed and predicted EQ-5D-5L crosswalk in all three countries using various indices for the prediction performance, including Bland-Altman plots to examine the performance along the HSU continuum. RESULTS: The EQ-5D-5L crosswalk was best predicted in France (nRMSEFRA = 0.075, nMAEFRA = 0.052), followed by the UK (nRMSEUK = 0.076, nMAEUK = 0.053) and Germany (nRMSEGER = 0.079, nMAEGER = 0.051). The Bland-Altman plots show that the inclusion of higher-order effects reduced the overprediction of low HSU scores. CONCLUSIONS: Our models provide a valid method to predict the EQ-5D-5L crosswalk from the PROMIS-29 for the UK, France, and Germany

Predicting EQ-5D-5L crosswalk from the PROMIS-29 profile for the United Kingdom, France, and Germany

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: Data is available on reasonable request.Background: EQ-5D health state utilities (HSU) are commonly used in health economics to compute quality-adjusted life years (QALYs). The EQ-5D, which is country-specific, can be derived directly or by mapping from self-reported health-related quality of life (HRQoL) scales such as the PROMIS-29 profile. The PROMIS-29 from the Patient Reported Outcome Measures Information System is a comprehensive assessment of self-reported health with excellent psychometric properties. We sought to find optimal models predicting the EQ-5D-5L crosswalk from the PROMIS-29 in the United Kingdom, France, and Germany and compared the prediction performances with that of a US model. Methods: We collected EQ-5D-5L and PROMIS-29 profiles and three samples representative of the general populations in the UK (n = 1509), France (n = 1501), and Germany (n = 1502). We used stepwise regression with backward selection to find the best models to predict the EQ-5D-5L crosswalk from all seven PROMIS-29 domains. We investigated the agreement between the observed and predicted EQ-5D-5L crosswalk in all three countries using various indices for the prediction performance, including Bland–Altman plots to examine the performance along the HSU continuum. Results: The EQ-5D-5L crosswalk was best predicted in France (nRMSEFRA = 0.075, nMAEFRA = 0.052), followed by the UK (nRMSEUK = 0.076, nMAEUK = 0.053) and Germany (nRMSEGER = 0.079, nMAEGER = 0.051). The Bland–Altman plots show that the inclusion of higher-order effects reduced the overprediction of low HSU scores. Conclusions: Our models provide a valid method to predict the EQ-5D-5L crosswalk from the PROMIS-29 for the UK, France, and Germany.Centre Virchow-Villerm

The genetic parameters of feed efficiency and its component traits in the turkey (Meleagris gallopavo)

Residual feed intake (RFI) and feed conversion ratio (FCR) can be incorporated into a breeding program as traits to select for feed efficiency. Alternatively, the direct measures used to calculate RFI and FCR can be analyzed to determine the underlying variation in the traits that impact overall efficiency. These constituent traits can then be appropriately weighted in an index to achieve genetic gain. To investigate feed efficiency in the turkey, feed intake and weight gain were measured on male primary breeder line turkeys housed in individual feeding cages from 15 to 19 weeks of age. The FCR and RFI showed moderate heritability values of 0.16 and 0.21, respectively. Feed intake, body weight, and weight gain were also moderately heritable (0.25, 0.35, and 0.18, respectively). Weight gain was negatively correlated to feed conversion ratio and was not genetically correlated to RFI. Body weight had a small and positive genetic correlation to RFI (0.09) and FCR (0.12). Feed intake was positively genetically correlated to RFI (0.62); however, there was no genetic correlation between feed intake and FCR. These estimates of heritability and the genetic correlations can be used in the development of an index to improve feed efficiency and reduce the cost of production

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.http://deepblue.lib.umich.edu/bitstream/2027.42/78314/1/1750-1326-5-45.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/2/1750-1326-5-45.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/3/1750-1326-5-45-S1.PDFPeer Reviewe

Genetic properties of feed efficiency parameters in meat-type chickens

<p>Abstract</p> <p>Background</p> <p>Feed cost constitutes about 70% of the cost of raising broilers, but the efficiency of feed utilization has not kept up the growth potential of today's broilers. Improvement in feed efficiency would reduce the amount of feed required for growth, the production cost and the amount of nitrogenous waste. We studied residual feed intake (RFI) and feed conversion ratio (FCR) over two age periods to delineate their genetic inter-relationships.</p> <p>Methods</p> <p>We used an animal model combined with Gibb sampling to estimate genetic parameters in a pedigreed random mating broiler control population.</p> <p>Results</p> <p>Heritability of RFI and FCR was 0.42-0.45. Thus selection on RFI was expected to improve feed efficiency and subsequently reduce feed intake (FI). Whereas the genetic correlation between RFI and body weight gain (BWG) at days 28-35 was moderately positive, it was negligible at days 35-42. Therefore, the timing of selection for RFI will influence the expected response. Selection for improved RFI at days 28-35 will reduce FI, but also increase growth rate. However, selection for improved RFI at days 35-42 will reduce FI without any significant change in growth rate. The nature of the pleiotropic relationship between RFI and FCR may be dependent on age, and consequently the molecular factors that govern RFI and FCR may also depend on stage of development, or on the nature of resource allocation of FI above maintenance directed towards protein accretion and fat deposition. The insignificant genetic correlation between RFI and BWG at days 35-42 demonstrates the independence of RFI on the level of production, thereby making it possible to study the molecular, physiological and nutrient digestibility mechanisms underlying RFI without the confounding effects of growth. The heritability estimate of FCR was 0.49 and 0.41 for days 28-35 and days 35-42, respectively.</p> <p>Conclusion</p> <p>Selection for FCR will improve efficiency of feed utilization but because of the genetic dependence of FCR and its components, selection based on FCR will reduce FI and increase growth rate. However, the correlated responses in both FI and BWG cannot be predicted accurately because of the inherent problem of FCR being a ratio trait.</p

Climate change impacts on banana yields around the world

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this r4ecordData availability: All data used are publicly available and open access. All banana production data sources are listed in Supplementary Table 1. All climatic and topographic data sources are listed in the Methods.Nutritional diversity is a key element of food security1,2,3. However, research on the effects of climate change on food security has, thus far, focused on the main food grains4,5,6,7,8, while the responses of other crops, particularly those that play an important role in the developing world, are poorly understood. Bananas are a staple food and a major export commodity for many tropical nations9. Here, we show that for 27 countries—accounting for 86% of global dessert banana production—a changing climate since 1961 has increased annual yields by an average of 1.37 t ha−1. Past gains have been largely ubiquitous across the countries assessed and African producers will continue to see yield increases in the future. However, global yield gains could be dampened or disappear, reducing to 0.59 t ha−1 and 0.19 t ha−1 by 2050 under the climate scenarios for Representative Concentration Pathways 4.5 and 8.5, respectively, driven by declining yields in the largest producers and exporters. By quantifying climate-driven and technology-driven influences on yield, we also identify countries at risk from climate change and those capable of mitigating its effects or capitalizing on its benefits.Biotechnology and Biological Sciences Research Council (BBSRC)European Union Horizon 202

Relative contribution of effects included in contemporary groups for adjusted and actual 120-day and 210-day weights in Nelore cattle in Brazil

The objective of this research was to estimate the relative magnitude of effects included in contemporary groups (CG) and their interactions with adjusted and actual 120 d and 210 d weights in 72,731 male and female Nelore calves born from 1985 to 2005 in 40 herds from PMGRN (Genetic Improvement Program of Nelore). Ten models with different CG structures were compared. The analyses were done using the general linear models (GLM) procedure run in SAS software. All of the effects included in the CG for each model were significant (p < 0.001) for the four traits analyzed. Inclusion of semester or trimester of birth as part of a CG was more appropriate than its use as an independent effect in the model because it accounted for interactions with the other effects in the CG. Calf sex (CS) and dam age at calving (DAC) had similar effects across the models, which suggested independence from other effects in these models. The corresponding age deviation effect had a larger impact on actual weight at 120 d than any other effect in all of the models tested. The use of actual weights in models with no CS effect in CG provides an alternative that would allow better genetic connectedness among CGs and greater accuracy in genetic evaluations

Comparison of herbarium label data and published medicinal use: herbaria as an underutilized source of ethnobotanical information

The use of herbarium specimens as vouchers to support ethnobotanical surveys is well established. However, herbaria may be underutilized resources for ethnobotanical research that depends on the analysis of large datasets compiled across multiple sites. Here, we compare two medicinal use datasets, one sourced from published papers and the other from online herbaria to determine whether herbarium and published data are comparable and to what extent herbarium specimens add new data and fill gaps in our knowledge of geographical extent of plant use. Using Brazilian legumes as a case study, we compiled 1400 use reports from 105 publications and 15 Brazilian herbaria. Of the 319 species in 107 genera with cited medicinal uses, 165 (51%) were recorded only in the literature and 55 (17%) only on herbarium labels. Mode of application, plant part used, or therapeutic use was less often documented by herbarium specimen labels (17% with information) than publications (70%). However, medicinal use of 21 of the 128 species known from only one report in the literature was substantiated from independently collected herbarium specimens, and 58 new therapeutic applications, 25 new plant parts, and 16 new modes of application were added for species known from the literature. Thus, when literature reports are few or information-poor, herbarium data can both validate and augment these reports. Herbarium data can also provide insights into the history and geographical extent of use that are not captured in publications

A flexible mathematical model platform for studying branching networks : experimentally validated using the model actinomycete, Streptomyces coelicolor

Branching networks are ubiquitous in nature and their growth often responds to environmental cues dynamically. Using the antibiotic-producing soil bacterium Streptomyces as a model we have developed a flexible mathematical model platform for the study of branched biological networks. Streptomyces form large aggregates in liquid culture that can impair industrial antibiotic fermentations. Understanding the features of these could aid improvement of such processes. The model requires relatively few experimental values for parameterisation, yet delivers realistic simulations of Streptomyces pellet and is able to predict features, such as the density of hyphae, the number of growing tips and the location of antibiotic production within a pellet in response to pellet size and external nutrient supply. The model is scalable and will find utility in a range of branched biological networks such as angiogenesis, plant root growth and fungal hyphal networks