PACT - Prediction of amyloid cross-interaction by threading.

Amyloid proteins are often associated with the onset of diseases, including Alzheimer's, Parkinson's and many others. However, there is a wide class of functional amyloids that are involved in physiological functions, e.g., formation of microbial biofilms or storage of hormones. Recent studies showed that an amyloid fibril could affect the aggregation of another protein, even from a different species. This may result in amplification or attenuation of the aggregation process. Insight into amyloid cross-interactions may be crucial for better understanding of amyloid diseases and the potential influence of microbial amyloids on human proteins. However, due to the demanding nature of the needed experiments, knowledge of such interactions is still limited. Here, we present PACT (Prediction of Amyloid Cross-interaction by Threading) - the computational method for the prediction of amyloid cross-interactions. The method is based on modeling of a heterogeneous fibril formed by two amyloidogenic peptides. The resulting structure is assessed by the structural statistical potential that approximates its plausibility and energetic stability. PACT was developed and first evaluated mostly on data collected in the AmyloGraph database of interacting amyloids and achieved high values of Area Under ROC (AUC=0.88) and F1 (0.82). Then, we applied our method to study the interactions of CsgA - a bacterial biofilm protein that was not used in our in-reference datasets, which is expressed in several bacterial species that inhabit the human intestines - with two human proteins. The study included alpha-synuclein, a human protein that is involved in Parkinson's disease, and human islet amyloid polypeptide (hIAPP), which is involved in type 2 diabetes. In both cases, PACT predicted the appearance of cross-interactions. Importantly, the method indicated specific regions of the proteins, which were shown to play a central role in both interactions. We experimentally confirmed the novel results of the indicated CsgA fragments interacting with hIAPP based on the kinetic characteristics obtained with the ThT assay. PACT opens the possibility of high-throughput studies of amyloid interactions. Importantly, it can work with fairly long protein fragments, and as a purely physicochemical approach, it relies very little on scarce training data. The tool is available as a web server at https://pact.e-science.pl/pact/ . The local version can be downloaded from https://github.com/KubaWojciechowski/PACT .

Machine Learning Prediction Model for Inflammatory Bowel Disease Based on Laboratory Markers. Working Model in a Discovery Cohort Study.

Inflammatory bowel disease (IBD) is a chronic, incurable disease involving the gastrointestinal tract. It is characterized by complex, unclear pathogenesis, increased prevalence worldwide, and a wide spectrum of extraintestinal manifestations and comorbidities. Recognition of IBD remains challenging and delays in disease diagnosis still poses a significant clinical problem as it negatively impacts disease outcome. The main diagnostic tool in IBD continues to be invasive endoscopy. We aimed to create an IBD machine learning prediction model based on routinely performed blood, urine, and fecal tests. Based on historical patients' data (702 medical records: 319 records from 180 patients with ulcerative colitis (UC) and 383 records from 192 patients with Crohn's disease (CD)), and using a few simple machine learning classificators, we optimized necessary hyperparameters in order to get reliable few-features prediction models separately for CD and UC. Most robust classificators belonging to the random forest family obtained 97% and 91% mean average precision for CD and UC, respectively. For comparison, the commonly used one-parameter approach based on the C-reactive protein (CRP) level demonstrated only 81% and 61% average precision for CD and UC, respectively. Results of our study suggest that machine learning prediction models based on basic blood, urine, and fecal markers may with high accuracy support the diagnosis of IBD. However, the test requires validation in a prospective cohort.

Standardised Ileal Amino Acid Digestibility in Field Pea Seeds of Two Cultivars Differing in Flower Colour for Broiler Chickens: Effects of Bird Age and Microbial Protease.

This study aimed to determine and compare standardised ileal digestibility (SID) coefficients of amino acids (AA) in raw seeds of the white-(WF) and the coloured-flowered (CF) field pea cultivar as sole sources of AA in the diets fed to broiler chickens aged 14 or 28 days. An additional purpose was to check the influence of exogenous protease added to pea-based assay diets on AA SID in birds at both ages. Each assay diet was offered to six replicate pens. On both sampling days, the contents from the lower half of the ileum were collected for determination of the apparent digestibility values. The SID coefficients were calculated using ileal endogenous AA losses determined from birds fed an N-free diet. Results indicated a substantial advantage of WF pea over CF pea as a source of digestible Lys, Met, Cys, His, Ile, Leu, Phe, Val, Asp and Glu for 14-day-old chickens. With the exception of methionine and cysteine, there was no significant difference between these two cultivars in the SID values of AA in 28-day-old birds. The protease increased SID of nutritionally essential AA from WF pea-based diet at both ages, and from CF pea-based diet in chickens aged 28 days. In conclusion, the SID coefficients of indispensable AA determined at 14 days of age in low-tannin WF peas are not applicable to the formulation of grower-type feeds containing seeds of CF cultivars.

The Efficiency of Xylanase in Broiler Chickens Fed with Increasing Dietary Levels of Rye.

In this paper, we present a study on the evaluation of the effect of xylanase addition to a diet with an increasing content of modern hybrid rye (Brasetto variety) on the performance indices and viscosity of small intestine content in broiler chickens. A total of 560 1-day-old male Ross 308 chickens were randomly assigned to 1 of 10 treatments, each comprising 7 replicate cages, with 8 male birds per cage. A 5 × 2 factorial arrangement was employed, with five dietary levels of ground rye (0%, 5%, 10%, 15%, and 20%). All the diets were either unsupplemented or supplemented with xylanase (200 mg/kg of feed; with minimum xylanase activity 1000 FXU/g). In the starter rearing period (1⁻21 days of age), the inclusion of rye (without xylanase supplementation) to the diet, even at the lowest dietary level (5%), negatively affected body weight gain (p < 0.05); there was no effect on feed intake and feed conversion ratio. In older chickens (the grower-finisher rearing period; 22⁻42 days of age), none of the dietary levels of rye (5⁻20%) affected growth performance indices. Similarly, no significant effect of increasing dietary level of rye was found for the entire rearing period (1⁻42 days of age). Diet supplementation with xylanase improved body weight gain and feed conversion ratio in chickens from 1 to 21 days of age. No positive effect of enzyme was found in older birds. No significant effects of the experimental factors used were noticed on the results of slaughter analysis, i.e., the carcass yield, breast meat yield, abdominal fat, and relative weight of the liver and gizzard. A high dietary concentration of rye (20%) increased the viscosity of small intestine content (p < 0.05); however, diet supplementation with xylanase significantly alleviated this effect. The findings of this experiment indicated that modern hybrid rye grain may be used at a 20% dietary level in broiler diets during the second feeding phase, i.e., from 22 to 42 days of age, without any detrimental influence on growth performance indices, while enzyme (xylanase) positively affected body weight gain and feed conversion ratio in younger chicks (1⁻21 days of age).

Results of a 16-week Safety Assurance Study with Rats Fed Genetically Modified Bt Maize: Effect on Growth and Health Parameters.

INTRODUCTION: The influence of feeding genetically modified MON 810 hybrid maize on the growth and haematological and biochemical indices of rats was tested. MATERIAL AND METHODS: Two conventional (non-GM) and two test (MON 810) lines of maize were used in semi-purified diets at the level of 40% w/w. The non-GM I, MON 810 I, non-GM II, and MON 810 II maize lines were near-isogenic. A total of 40 male 6-week-old Wistar-derived rats were assigned to four equal feeding groups corresponding to the four maize lines for 16 weeks. Overall, health, body weight gain, clinical pathology parameters, gross changes, and appearance of tissues were compared between groups. RESULTS: There were no statistically significant differences in the weight gain or relative organ weights of rats, but there were some non diet-related histopathological changes in the liver, kidneys, and spleen. Except for creatinine level, no diet-related effects were observed in haematology or most of the biochemical indices. Transgenic DNA of MON 810 maize was not detected in the tissues or faeces nor in the DNA of E. coli isolated from the rectum digesta of rats given transgenic feeds. In our experiment, various metabolic indices of rats fed non-GM diets or genetically modified (MON 810) maize for 16 weeks were similar. No adverse nutrition-related health effects were detected. CONCLUSION: MON 810 maize seems to be as safe as the conventional maize lines.