Effects of Phytogenic Feed Additive and Enzyme on Growth Performance of Broilers Fed Diets with Reduced Energy Concentrations

The effects of dietary supplementation with phytogenic feed additives (PFA) and enzyme (E) on performance parameters were investigated using Ross 308 as hatched broilers fed standard diets or diets with reduced energy concentrations. Birds were assigned to 5 treatments with 5 replications each and fed either a standard basal diet or a re-formulated basal diet with reduced energy concentrations. Reduction was made according to enzyme matrix (Ronozyme WX, DSM). Treatments were: (1) Standard diet; (2) Negative control (NC) – 4% reduction in ME (3) NC + E; (4) NC + PFA (5) NC + E + PFA. Body weight and feed consumption were recorded weekly. Mortality was recorded on daily basis. Foot pad lesions were scored at day 35 using scale from 0 (no lesion) to 2 (lesion extending through skin). The results showed that birds fed Negative control diets had a significantly lower body weights (P0.05). Mortality and FCR did not differ significantly between treatments. Average foot pad lesion score was the highest in Negative control (1.05) and the lowest in NC+E (0.55). In conclusion, re-formulation of diets for 4% energy reduction decreased broiler growth rate. Supplementation of diets with PFA improved live weight especially in combination with enzyme, hence confirming a growth-promoting effect of both phytogenics and enzymes in broilers

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

Linseed Oil as a Source of Polyunsaturated Fatty Acids in Broiler Chicken Nutrition

The aim of the paper was to examine the effect of polyunsaturated fatty acids from linseed oil on productive performances and fatty acid composition of lipids of broiler chicken abdominal fat, as well as correlation and regression between consumed amount of oil and possibilities of their incorporation in the tissues. For the need of experimental research, three groups of 40 day old chicken, hybrid line Cobb 500 were formed. Every group had five replicates, in total amount of 200 chickens per treatment. Control group were fed with diet in addition of 4% soybean oil, while the experimental groups were fed with addition of 4 and 8% of linseed oil in the diet. Addition of linseed oil had a statistically high (P<0.01) influence on chicken body weight reduction in treatments T2 and T3, compared to the body weights of chicken in control group T1. Feed conversion ratio in chicken in experimental groups T2 and T3 was 1.84 and 1.82 kg of feed/kg of gain. Introduction of linseed oil in amounts of 4 and 8% in chicken nutrition led to statistically high (P<0.01) differences in content of linoleic acid (C18:2) in treatments T2 and T3, compared to control group T1, which leads to a conclusion that linseed oil significantly reduces linoleic acid in tissue. Compared to linoleic acid, content of α-linolenic acid (C18:3) was statistically significantly increased (P<0.05) in treatment T2 and highly significantly (P<0.01) in treatment T3, compared to control. Negative values of regression (b) and correlation (r) also confirm the fact that introduction of linseed oil in the diet significantly reduces content of linoleic acid in fat tissue of chickens (b=-0.551; r=-0.79), while the same coefficients show positive dependence between added linseed oil in the diet and deposited linolenic acid in tissues (b=1.081 and r=0.87). Based on the gained results it can be concluded that addition of linseed oil in the amount of 4 and 8% could be successfully used in chicken nutrition for fatty acid composition improvement and for lowering the ratio between n-6/n-3 polyunsaturated fatty acid in tissues of broilers

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.

BACKGROUND: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. METHODS: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. RESULTS: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. CONCLUSIONS: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors

NONTRIVIAL VARIATIONS OF MORPHO-ANATOMICAL LEAF TRAITS IN NATURAL SOUTH-EASTERN POPULATIONS OF VACCINIUM SPECIES FROM CENTRAL BALKANS

Morpho-anatomical characteristics of Vaccinium myrtillus, V. uliginosum and V. vitis-idaea leaves from several sites of the Central Balkans were examined. The aim of this study was to investigate for the first time morpho-anatomical leaf traits of these species in the studied populations and to identify traits that follow a specific trend along the gradients of climate factors. Leaf traits that discriminate Vaccinium species were as follows: Depth of the adaxial cuticule (AdC), thickness of the palisade tissue (PT), thickness of the spongy tissue (ST), height of the abaxial epidermal cells (AbE), height of the abaxial cuticule (AbC) and leaf thickness (LT). Populations of V. myrtillus were characterized by the smallest, and populations of V. vitis-idaea by the highest values for AdC, PT, ST, AbE and LT. Additionally, AbC was significantly larger for V. uliginosum in comparison to two other species. On the basis of morpho-anatomical traits, intraspecific variability of the studied species was explored by Principal Component Analysis (PCA), Cluster Analysis (CA) and Analysis of Variance (ANOVA). CA based on 10 morpho-anatomical traits showed that populations of V. myrtillus and V. uliginosum that grew at lower altitudes (characterized by higher mean annual temperature) are more similar to each other. Especially V. myrtillus was responsive to the elevational gradient and exhibited the highest plasticity in morpho-anatomical leaf traits. Populations of V. vitis-idaea had a different pattern of differentiation along the elevational gradient. CA showed that the populations at the lowest and at the highest altitudes were more similar according to the morpho-anatomical leaf traits, meaning that evergreen leaves were more resistant to environmental conditions. © Polish Academy of Sciences and Jagiellonian University, Cracow 2021

Increased fidelity of protein synthesis extends lifespan

Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life, in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies. These findings pave the way for identifying novel translation accuracy interventions to improve aging

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

A triple drug combination targeting components of the nutrient-sensing network maximizes longevity

Increasing life expectancy is causing the prevalence of age-related diseases to rise, and there is an urgent need for new strategies to improve health at older ages. Reduced activity of insulin/insulin-like growth factor signaling (IIS) and mechanistic target of rapamycin (mTOR) nutrient-sensing signaling network can extend lifespan and improve health during aging in diverse organisms. However, the extensive feedback in this network and adverse side-effects of inhibition imply that simultaneous targeting of specific effectors in the network may most effectively combat the effects of aging. We show that the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, the mTOR complex 1 (mTORC1) inhibitor rapamycin, and the glycogen synthase kinase-3 (GSK-3) inhibitor lithium act additively to increase longevity in Drosophila. Remarkably, the triple drug combination increased lifespan by 48%. Furthermore, the combination of lithium with rapamycin cancelled the latter’s effects on lipid metabolism. In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health

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