Trapping by active sites on surfaces plays important roles in various chemical and biological processes, including catalysis, enzymatic reactions, and viral entry into host cells. However, the ...mechanisms of these processes remain not well understood, mostly because the existing theoretical descriptions are not fully accounting for the role of the surfaces. Here, we present a theoretical investigation on the dynamics of surface-assisted trapping by specific active sites. In our model, a diffusing particle can occasionally reversibly bind to the surface and diffuse on it before reaching the final target site. An approximate theoretical framework is developed, and its predictions are tested by Brownian dynamics computer simulations. It is found that the surface diffusion can be crucial in mediating trapping by active sites. Our theoretical predictions work reasonably well as long as the area of the active site is much smaller than the overall surface area. Potential applications of our approach are discussed.
Recent technological advances make it possible to deliver feeding strategies that can be tailored to the needs of individual pigs in order to optimise the allocation of nutrient resources and ...contribute toward reducing excess nutrient excretion. However, these efforts are currently hampered by the challenges associated with: (1) estimation of unobserved traits from the available data on bodyweight and feed consumption; and (2) characterisation of the distributions and correlations of these unobserved traits to generate accurate estimates of individual level variation among pigs. Here, alternative quantitative approaches to these challenges, based on the principles of inverse modelling and separately inferring individual level distributions within a Bayesian context were developed and incorporated in a proposed precision feeding modelling framework. The objectives were to: (i) determine the average and distribution of individual traits characterising growth potential and body composition in an empirical population of growing-finishing barrows and gilts; (ii) simulate the growth and excretion of nitrogen and phosphorus of the average pig offered either a commercial two-phase feeding plan, or a precision feeding plan with daily adjustments; and (iii) simulate the growth and excretion of nitrogen and phosphorus across the pig population under two scenarios: a two-phase feeding plan formulated to meet the nutrient requirements of the average pig or a precision feeding plan with daily adjustments for each and every animal in the population. The distributions of mature bodyweight and ratio of lipid to protein weights at maturity had median (IQR) values of 203 (47.8) kg and 2.23 (0.814) kg/kg, respectively; these estimates were obtained without any prior assumptions concerning correlations between the traits. Overall, it was found that a proposed precision feeding strategy could result in considerable reductions in excretion of nitrogen and phosphorus (average pig: 8.07 and 9.17% reduction, respectively; heterogenous pig population: 22.5 and 22.9% reduction, respectively) during the growing-finishing period from 35 to 120 kg bodyweight. This precision feeding modelling framework is anticipated to be a starting point toward more accurate estimation of individual level nutrient requirements, with the general aim of improving the economic and environmental sustainability of future pig production systems.
Although intrinsically disordered proteins and intrinsically disordered regions (IDRs) in folded proteins are not able to form stable structures, it is known that they play critically important roles ...in various biological processes. However, despite multiple studies, the molecular mechanisms of their functions remain not fully understood. In this work, we theoretically investigate the role of IDRs in acceleration of protein-protein association processes. Our hypothesis is that, in protein pairs with several independent binding sites, the association process goes faster if some of these binding sites are located on IDRs or connected by IDRs. To test this idea, we employed analytical modeling, numerical calculations, and Brownian dynamics computer simulations to calculate protein-protein association reaction rates for the ERK2-EtsΔ138 system, belonging to the RAS-RAF-MEK-ERK signaling pathway in living cells. It is found that putting a binding site on IDR accelerates the association process by a factor of 3 to 4. Possible molecular explanations for these observations are presented, and other systems that might use this mechanism are also mentioned.
Introduction: Colorectal cancer is one of the most common cancers occurring in Poland. Unfortunately, this cancer is most often diagnosed at the time of great advancement. This is caused by the ...appearance of specific symptoms only in the late stages of cancer. Also, such low detection of early stages of adenocarcinoma may be caused by disregarding of slight symptoms.
Purpose: To analyse symptoms in patients with colorectal cancer and correlate with chosen clinical-pathological parameters.
Materials and methods: The study group consisted of 46 patients diagnosed with colorectal cancer. Information on symptoms associated with cancer (subjective and objective) have been selected from patients' medical history. The presence of these symptoms was correlated with the age and sex of patients, tumor location, histological type of cancer, grade of histological malignancy (G), stage of tumor (T stage), presence of lymph node metastases and distant metastases.
Results: It has been shown that the presence of pain complaints described by the patient are associated with the occurrence of cancer in the colon. The painfulness and pathological resistance diagnosed by the physician are more often associated with cancer located in the colon. In the case of tumors located in the rectum, faecal admixtures appear more frequently. It has also been shown that the presence of admixtures of blood and mucus in the stool is associated with more advanced local tumors, infiltrating pericolorectal tissues (T3 + T4).
Conclusions: Familiarity with clinical symptoms of colorectal cancer could make patients more sensitive to more often screening for cancer. Analysis of these symptoms could indicate to the physician the location or stage of the cancer.
Feeding strategies for growing monogastric livestock (particularly pigs) must focus on maximising animal performance, while attempting to reduce environmental P load. Achieving these goals requires a ...comprehensive understanding of how different P feeding strategies affect animal responses and an ability to predict P retention. Although along with Ca, P is the most researched macromineral in pig nutrition, knowledge gaps still exist in relation to: (1) the effects of P feed content on feed intake (FI); (2) the impact of P intake on body composition; (3) the distribution of absorbed P to pools within the body. Here, we address these knowledge gaps by gathering empirical evidence on the effects of P-deficient feeds and by developing a predictive, mechanistic model of P utilisation and retention incorporating this evidence. Based on our statistical analyses of published literature data, we found: (1) no change in FI response in pigs given lower P feed contents; (2) the body ash–protein relationship to be dependent upon feed composition, with the isometric relationship only holding for pigs given balanced feeds and (3) the priority to be given towards P retention in soft tissue over P retention in bones. Subsequent results of the mechanistic model of P retention indicated that a potential reduction in P feeding recommendations could be possible without compromising average daily gain; however, such a reduction would impact P deposition in bones. Our study enhances our current knowledge of P utilisation and by extension excretion and could contribute towards developing more accurate P feeding guidelines.
ERK2 are protein kinases that during the enzymatic catalysis, in contrast to traditional enzymes, utilize additional interactions with substrates outside of the active sites. It is widely believed ...that these docking interactions outside of the enzymatic pockets enhance the specificity of these proteins. However, the molecular mechanisms of how the docking interactions affect the catalysis remain not well understood. Here, we develop a simple theoretical approach to analyze the enzymatic catalysis in ERK2 proteins. Our method is based on first-passage process analysis, and it provides explicit expressions for all dynamic properties of the system. It is found that there are specific binding energies for substrates in docking and catalytic domains that lead to maximal enzymatic reaction rates. Thus, we propose that the role of the docking interactions is not only to increase the enzymatic specificity but also to optimize the dynamics of the catalytic process. Our theoretical results are utilized to describe experimental observations on ERK2 enzymatic activities.
Ca digestibility and utilisation in growing pigs are not well understood, and are usually neglected in diet formulation. This has implications not only for the accurate determination of its ...requirements but also for its interactions with other nutrients. A systematic review and meta-analysis (meta-regression) of published trials was carried out to quantify factors affecting Ca absorption and utilisation, and to derive an estimate of Ca endogenous excretion. The analysis was carried out on the data from forty studies, corresponding to 201 treatments performed on 1204 pigs. The results indicated that although Ca absorption and retention (g/kg of body weight per d) increased with increasing Ca intake (P<0·001), non-phytate-P intake (P<0·001) and exogenous phytase supplementation (P<0·001), these values decreased with increasing phytate-P intake (P<0·05). Interactions between exogenous phytase and Ca intake, indicating reduced efficacy of this enzyme (P<0·001), and between phytate-P intake and exogenous phytase, counteracting the direct negative effect of phytate-P (P<0·05) on Ca absorption and retention, were also detected. There were no effects of animal-related characteristics, such as pig genotype in Ca absorption and retention. The large amount of variance explained in Ca absorption (90 %) and retention (91 %) supported our choice of independent variables. Endogenous Ca losses obtained via linear regression were 239 mg/kg of DM intake (95 % CI 114, 364). These outcomes advance the current understanding of Ca digestibility and utilisation, and should contribute towards establishing requirements for digestible Ca. Consequently, pig diets will be more correctly formulated if digestible Ca values are used in estimating requirements for Ca.
L,D-transpeptidase 2 from
plays a key role in the formation of the cell wall of a pathogen and catalyzes the cross-linking of growing peptidoglycan chains by non-classical 3-3 bonds, which causes ...resistance to a broad spectrum of penicillins. Molecular modeling of enzyme interactions with the N- and C-terminal tetrapeptide fragments of growing peptidoglycan chains has been performed for the first time and has allowed us to highlight the peculiarities of their binding at the formation of 3-3 cross-linkages, as well as to build a full-atom model of L,D-transpeptidase 2 for the screening and optimizing of inhibitors' structures.
Precision feeding and management of growing-finishing pigs typically require mathematical models to forecast individual pig performance from past data. The current approaches, namely double ...exponential smoothing (DES) and dynamic linear regression are likely to have some limitations in their applicability since they: (1) assume that responses can be forecasted linearly, which only holds in the short-term, and (2) often take insufficient account of uncertainty and correlations in the estimated traits. We developed and evaluated alternative approaches to forecasting individual growth or intake responses based on nonlinear models (allometric, monomolecular, rational) and Bayesian methodology to fit models to the data and generate probabilistic forecasts. We applied these approaches to individual data from two distinct pig populations, to parameterise the models (fitting based on a training dataset) and forecast performance (forecast horizons: 1–30 d tested on a validation dataset). We found that good fitting did not guarantee accurate forecasting, which is quantitatively relevant in the medium-to-long term. Forecasts from nonlinear models were more accurate compared to those from benchmark linear models, with the allometric model being more accurate for most pigs across considered forecast horizons. While DES was the best model at fitting, it was also the least accurate at forecasting for all forecast horizons. These results enhance the understanding of how underlying biological growth responses could be approximated using straightforward mathematical relationships. The approach could be utilised to formulate optimised feeding strategies and inform management decisions, including pen allocation or end-weight prediction.
•Nonlinear and linear predictive models of individual pig growth or intake were tested.•Bayesian forecasting offered key advantages relative to previous estimation methods.•Good fit of a model to the early data does not guarantee accurate forecasts.•Nonlinear model forecasts (1–30 d ahead) were the most accurate (≈0.5–8.0%).•Allometric models can be useful tools for forecasting pig growth responses.
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