Effect of Litter Treatment on the Occurrence of Foot Pad Lesions

Pododermatitis (foot pad lesions) is one of the main welfare problems in modern broiler production in countries with developed poultry farming. Factors contributing to the occurrence of these lesions are nutrition, stocking density and material used for litter. There are a number of different procedures that can be applied in order to prevent and reduce the number of lesions with the most pronounced defects. The experiment was conducted on broiler chickens grown in 10 buildings of 240 m2 each. The stocking density was 35 kg/m2. The experiment was set up in five treatments with two replicates. Treatment one (T1) - control with a straw litter, treatment two (T2) - litter treated with microbial preparation Micropan®, treatment three (T3) – litter with addition of lignin, treatment four (T4) – litter with addition of lignin and Micropan® and treatment five (T5) - chopped straw without supplements. At the end of the experiment, on day 42 the intensity of the lesions was scored on the slaughter line. The presence of lesions was scored using scale from 0 (no lesions) to 3 (plantar pads with more than 50% damage). Based on the results of the trial it can be concluded that litter has a significant impact on the presence and the degree of foot pad lesions. The lowest score of foot pad lesions was observed in the treatment T5 (chopped straw). Different treatments of litters may also contribute to the solution of the problem of pododermatitis since the results in all treated groups (T2, T3, T4 and T5) were better when compared to the control

Hantavirus infections in forestry workers

Bjedov, L., Margaletić, J., Vucelja, M., Medved, M.M., Matijević, I., Krajinović, L.C., Markotic, A

Autophagy in healthy aging and disease

Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health

Host-microbe-drug-nutrient screen identifies bacterial effectors of metformin therapy

Metformin is the first-line therapy for treating type-2 diabetes and a promising anti-aging drug. We set out to address the fundamental question of how gut microbes and nutrition, key regulators of host physiology, impact the effects of metformin. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we developed a high-throughput four-way screen to define the underlying host-microbe-drug-nutrient interactions. We show that microbes integrate cues from metformin and the diet through the phosphotransferase signalling pathway that converges on the transcriptional regulator Crp. A detailed experimental characterization of metformin effects downstream of Crp in combination with metabolic modelling of the microbiota in metformin-treated type-2 diabetic patients predicts the production of microbial agmatine, a regulator of metformin effects on host lipid metabolism and lifespan. Our high-throughput screening platform paves the way for identifying exploitable drug-nutrient-microbiome interactions to improve host health and longevity through targeted microbiome therapie

A Drosophila

Glucocerebrosidase (GBA1) mutations are associated with Gaucher disease (GD), an autosomal recessive disorder caused by functional deficiency of glucocerebrosidase (GBA), a lysosomal enzyme that hydrolyzes glucosylceramide to ceramide and glucose. Neuronopathic forms of GD can be associated with rapid neurological decline (Type II) or manifest as a chronic form (Type III) with a wide spectrum of neurological signs. Furthermore, there is now a well-established link between GBA1 mutations and Parkinson's disease (PD), with heterozygote mutations in GBA1 considered the commonest genetic defect in PD. Here we describe a novel Drosophila model of GD that lacks the two fly GBA1 orthologs. This knock-out model recapitulates the main features of GD at the cellular level with severe lysosomal defects and accumulation of glucosylceramide in the fly brain. We also demonstrate a block in autophagy flux in association with reduced lifespan, age-dependent locomotor deficits and accumulation of autophagy substrates in dGBA-deficient fly brains. Furthermore, mechanistic target of rapamycin (mTOR) signaling is downregulated in dGBA knock-out flies, with a concomitant upregulation of Mitf gene expression, the fly ortholog of mammalian TFEB, likely as a compensatory response to the autophagy block. Moreover, the mTOR inhibitor rapamycin is able to partially ameliorate the lifespan, locomotor, and oxidative stress phenotypes. Together, our results demonstrate that this dGBA1-deficient fly model is a useful platform for the further study of the role of lysosomal-autophagic impairment and the potential therapeutic benefits of rapamycin in neuronopathic GD. These results also have important implications for the role of autophagy and mTOR signaling in GBA1-associated PD

Monotonicity of Fitness Landscapes and Mutation Rate Control

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms

Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response

Dramatic rise of mutators has been found to accompany adaptation of bacteria in response to many kinds of stress. Two views on the evolutionary origin of this phenomenon emerged: the pleiotropic hypothesis positing that it is a byproduct of environmental stress or other specific stress response mechanisms and the second order selection which states that mutators hitchhike to fixation with unrelated beneficial alleles. Conventional population genetics models could not fully resolve this controversy because they are based on certain assumptions about fitness landscape. Here we address this problem using a microscopic multiscale model, which couples physically realistic molecular descriptions of proteins and their interactions with population genetics of carrier organisms without assuming any a priori fitness landscape. We found that both pleiotropy and second order selection play a crucial role at different stages of adaptation: the supply of mutators is provided through destabilization of error correction complexes or fluctuations of production levels of prototypic mismatch repair proteins (pleiotropic effects), while rise and fixation of mutators occur when there is a sufficient supply of beneficial mutations in replication-controlling genes. This general mechanism assures a robust and reliable adaptation of organisms to unforeseen challenges. This study highlights physical principles underlying physical biological mechanisms of stress response and adaptation

Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster

Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan. Ideally, such manipulations should be specific and minimise off-target effects, and it is important to discover additional methods for ‘clean’ lifespan manipulation. Here we report an initial study into the effect of up-regulating autophagy on lifespan and fertility in Drosophila melanogaster by dietary addition of Torin1. Activation of autophagy using this selective TOR inhibitor was associated with significantly increased lifespan in both sexes. Torin1 induced a dose-dependent increase in lifespan in once-mated females. There was no evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed females exhibited significantly elevated fecundity, but also elevated egg infertility, resulting in no net change in overall fertility. This supports the idea that lifespan can be extended without trade-offs in fertility and suggest that Torin1 may be a useful tool with which to pursue anti-ageing research