Estimating risk probabilities for sickness from behavioural patterns to identify health challenges in dairy cows with multivariate cumulative sum control charts

Dairy cattle housing is characterised by increasing herd sizes and the need for assisting technical tools to monitor the cows’ health. This study investigated the combination of logistic regression models with multivariate cumulative sum (MCUSUM) control charts in healthmonitoring of dairy cattle. Sensor information of 618 cows with 791 lactations (138 438 cow days), nine behavioural variables were included as parts of the behavioural patterns: physical activity (“neck activity”, “leg activity”, “walking duration”), resting (“lying duration”, “standing duration”, “transitions from lying to standing”) and feeding (“feeding duration”, “rumination duration”, “inactivity duration”) behaviour. For each of these behavioural patterns, a logistic regression model with the health status (sick vs not sick) as a dependent variable was designed after a variable selection (herd level) based on the herd dataset with 618 cows (618 lactations; 115 547 cow days), which included the variables of each behaviour pattern and the stage of lactation nested in the number of lactations as explanatory variables. The explanatory variables were added stepwise to the model, with the final model being selected with respect to the lowest values of Akaike’s and Bayes’ information criteria. Each model was then applied to a dataset with 173 cows (22 891 cow days) at cow level, resulting in individual daily risk probabilities for getting sick. Thus, risk probabilities of each behavioural pattern were estimated and included in the MCUSUM control charts to identify cows at risk of disease. The performance of the MCUSUM control charts was cross-validated to identify the best fitting reference value k and the threshold value h. Alerts given within 5 days prior to diagnosis were counted as detected sicknesses. The performance resulted in a block sensitivity of 70.9–81.4%, specificity of 87.9–94.2% and a false-positive rate of 5.8–12.1%. The performance was confirmed while testing the entire algorithm resulting in a mean area under the receiver operating characteristics curve of 0.89. Calculating precision and the F₁-score resulted in a precision of 49.0–60.9% (training: 48.8–63.5%) and an F₁-score of 61.1–65.7% in testing (training: 61.0–67.0%). The precision-recall curve (PRC) was derived from precision and recall with an area under the PRC of 0.70 in training and testing. In summary, the present study was able to develop an algorithm showing good classification potential for the online monitoring of sickness behaviour.     

Divergence across diet,time and populations rules out parallel evolution in the gut microbiomes of Trinidadian guppies

Diverse microbial consortia profoundly influence animal biology, necessitating an understanding of microbiome variation in studies of animal adaptation. Yet, little is known about such variability among fish, in spite of their importance in aquatic ecosystems. The Trinidadian guppy, Poecilia reticulata, is an intriguing candidate to test microbiome-related hypotheses on the drivers and consequences of animal adaptation, given the recent parallel origins of a similar ecotype across streams. To assess the relationships between the microbiome and host adaptation, we used 16S rRNA amplicon sequencing to characterize gut bacteria of two guppy ecotypes with known divergence in diet, life history, physiology and morphology collected from low-predation (LP) and high-predation (HP) habitats in four Trinidadian streams. Guts were populated by several recurring, core bacteria that are related to other fish associates and rarely detected in the environment. Although gut communities of lab-reared guppies differed from those in the wild, microbiome divergence between ecotypes from the same stream was evident under identical rearing conditions, suggesting host genetic divergence can affect associations with gut bacteria. In the field, gut communities varied over time, across streams and between ecotypes in a stream-specific manner. This latter finding, along with PICRUSt predictions of metagenome function, argues against strong parallelism of the gut microbiome in association with LP ecotype evolution. Thus, bacteria cannot be invoked in facilitating the heightened reliance of LP guppies on lower-quality diets. We argue that the macroevolutionary microbiome convergence seen across animals with similar diets may be a signature of secondary microbial shifts arising some time after host-driven adaptation.     

Use of high-density tiling microarrays to identify mutations globally and elucidate mechanisms of drug resistance in Plasmodium falciparum

Background

The identification of genetic changes that confer drug resistance or other phenotypic changes in pathogens can help optimize treatment strategies, support the development of new therapeutic agents, and provide information about the likely function of genes. Elucidating mechanisms of phenotypic drug resistance can also assist in identifying the mode of action of uncharacterized but potent antimalarial compounds identified in high-throughput chemical screening campaigns against Plasmodium falciparum.

Results

Here we show that tiling microarrays can detect de novo a large proportion of the genetic changes that differentiate one genome from another. We show that we detect most single nucleotide polymorphisms or small insertion deletion events and all known copy number variations that distinguish three laboratory isolates using readily accessible methods. We used the approach to discover mutations that occur during the selection process after transfection. We also elucidated a mechanism by which parasites acquire resistance to the antimalarial fosmidomycin, which targets the parasite isoprenoid synthesis pathway. Our microarray-based approach allowed us to attribute in vitro derived fosmidomycin resistance to a copy number variation event in the pfdxr gene, which enables the parasite to overcome fosmidomycin-mediated inhibition of isoprenoid biosynthesis.

Conclusions

We show that newly emerged single nucleotide polymorphisms can readily be detected and that malaria parasites can rapidly acquire gene amplifications in response to in vitro drug pressure. The ability to define comprehensively genetic variability in P. falciparum with a single overnight hybridization creates new opportunities to study parasite evolution and improve the treatment and control of malaria.     

Epistasis in a quantitative trait captured by a molecular model of transcription factor interactions

With technological advances in genetic mapping studies more of the genes and polymorphisms that underlie Quantitative Trait Loci (QTL) are now being identified. As the identities of these genes become known there is a growing need for an analysis framework that incorporates the molecular interactions affected by natural polymorphisms. As a step towards such a framework we present a molecular model of genetic variation in sporulation efficiency between natural isolates of the yeast, Saccharomyces cerevisiae. The model is based on the structure of the regulatory pathway that controls sporulation. The model captures the phenotypic variation between strains carrying different combinations of alleles at known QTL. Compared to a standard linear model the molecular model requires fewer free parameters, and has the advantage of generating quantitative hypotheses about the affinity of specific molecular interactions in different genetic backgrounds. Our analyses provide a concrete example of how the thermodynamic properties of protein-protein and protein-DNA interactions naturally give rise to epistasis, the non-linear relationship between genotype and phenotype. As more causative genes and polymorphisms underlying QTL are identified, thermodynamic analyses of quantitative traits may provide a useful framework for unraveling the complex relationship between genotype and phenotype.     

Effects of light on cyanide‐resistant respiration and alternative oxidase function in Arabidopsis seedlings

Mitochondrial alternative oxidase (AOX), the unique respiratory terminal oxidase in plants, catalyzes the energy wasteful cyanide (CN)‐resistant respiration and plays a role in optimizing photosynthesis. Although it has been demonstrated that leaf AOX is upregulated after illumination, the in vivo mechanism of AOX upregulation by light and its physiological significance are still unknown. In this report, red light and blue light‐induced AOX (especially AOX1a) expressions were characterized. Phytochromes, phototropins and cryptochromes, all these photoreceptors mediate the light‐response of AOX1a gene. When aox1a mutant seedlings were grown under a high‐light (HL) condition, photobleaching was more evident in the mutant than the wild‐type plants. More reactive oxygen species (ROS) accumulation and inefficient dissipation of chloroplast reducing‐equivalents in aox1a mutant may account for its worse adaptation to HL stress. When etiolated seedlings were exposed to illumination for 4 h, chlorophyll accumulation was largely delayed in aox1a plants. We first suggest that more reduction of the photosynthetic electron transport chain and more accumulation of reducing‐equivalents in the mutant during de‐etiolation might be the main reasons.     

Function and regulation of the mitochondrial Sirtuin isoform Sirt5 in Mammalia

Sirtuins are a family of protein deacetylases that catalyze the nicotinamide adenine dinucleotide (NAD⁺)-dependent removal of acetyl groups from modified lysine side chains in various proteins. Sirtuins act as metabolic sensors and influence metabolic adaptation but also many other processes such as stress response mechanisms, gene expression, and organismal aging. Mammals have seven Sirtuin isoforms, three of them – Sirt3, Sirt4, and Sirt5 – located to mitochondria, our centers of energy metabolism and apoptosis initiation. In this review, we shortly introduce the mammalian Sirtuin family, with a focus on the mitochondrial isoforms. We then discuss in detail the current knowledge on the mitochondrial isoform Sirt5. Its physiological role in metabolic regulation has recently been confirmed, whereas an additional function in apoptosis regulation remains speculative. We will discuss the biochemical properties of Sirt5 and how they might contribute to its physiological function. Furthermore, we discuss the potential use of Sirt5 as a drug target, structural features of Sirt5 and of an Sirt5/inhibitor complex as well as their differences to other Sirtuins and the current status of modulating Sirt5 activity with pharmacological compounds.