Process-based growth model
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Photoautotrophic growth depends upon an optimal allocation of finite cellular resources to diverse intracellular processes. Commitment of a certain mass fraction of the proteome to a specific cellular function typically reduces the proteome available for other cellular functions. Here, we develop a semi-quantitative kinetic model of cyanobacterial phototrophic growth to describe such trade-offs of cellular protein allocation. The model is based on coarse-grained descriptions of key cellular processes, in particular carbon uptake, metabolism, photosynthesis, and protein translation. The model is parameterized using literature data and experimentally obtained growth curves. Of particular interest are the resulting cyanobacterial growth laws as fundamental characteristics of cellular growth. We show that the model gives rise to similar growth laws as observed for heterotrophic organisms, with several important differences due to the distinction between light energy and carbon uptake. We discuss recent experimental data supporting the model results and show that coarse-grained growth models have implications for our understanding of the limits of phototrophic growth and bridge a gap between molecular physiology and ecology.
Sledování individuálního růstu je v pediatrické praxi vyžadováno denně a často je doprovázeno potřebou podrobnějších analýz. Analýzu lidského růstu potřebují také sportovní antropologové a výzkumníci v oblasti biologie člověka. Přínosem by tedy byla pokročilá a zároveň snadno použitelná a bezplatná aplikace, která by pediatrům, auxologům a výzkumným pracovníkům v oblasti biologie člověka umožňovala provádět hloubkovou analýzu postnatálního růstu. Aplikace GROWTH byla vyvinuta na základě pochopení biologických procesů lidského růstu a matematických přístupů, které poskytují nejvhodnější model pro individuální (longitudinální) empirická data. Aplikace je navržena tak, aby ji bylo možné používat v každodenní pediatrické praxi. Poskytuje lékařům nástroje pro sledování růstu, předpovídání dosažené výšky a diagnostiku patologických růstových vzorců. Pokročilá analýza zahrnuje odhad časování hlavních růstových milníků. Současná verze je vyvrcholením několikastupňového vývoje aplikace a je založena na metodě FPCA (funkční analýza hlavních komponent) s numerickou optimalizací. Výstupní parametry jsou snadno použitelné a zobrazují se numericky i graficky.
Monitoring of individual growth is required on daily basis in paediatric practice, often accompanied by need for more in-depth analyses. Sports anthropologists and researchers in the fi eld of human biology also need to analyze human growth. To allow clinicians and researchers to monitor human growth and analyze it in advanced manner, easy-to-use free application would be beneficial. The application, GROWTH, was developed based on an understanding of the biological processes of human growth and mathematical approaches that provide the most appropriate model for individual (longitudinal) empirical data. The application is designed to be used in daily paediatric practice. It provides clinicians with tools to monitor growth, predict attained height and diagnose pathological growth patterns. Advanced analysis includes the timing of major growth milestones. The current version is the culmination of a multi-stage development of the application and is based on Functional Principal Components Analysis method with numerical optimization. The output parameters are easy to use and are displayed both numerically and graphically.
- Klíčová slova
- funkční analýza hlavních komponent, GROWTH,
- MeSH
- analýza dat MeSH
- biologické modely MeSH
- lidé MeSH
- růst MeSH
- software MeSH
- tělesná výška MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The mathematical prediction of cell proliferation in porous scaffold still remains a challenge. The analysis of existing models and experimental data confirms a need for a new solution, which takes into account cells" development on the scaffold pore walls as well as some additional parameters such as the pore size, cell density in cellular layers, the thickness of the growing cell layer and others. The simulations, presented below, are based on three main approaches. The first approach takes into account multilayer cell growth on the pore walls of the scaffold. The second approach is a simulation of cell proliferation in a discrete process as a continuous one. The third one is the representation of scaffold structure as a system of cylindrical channels. Oxygen (nutrient) mass transfer is realized inside these channels. The model, described below, proposes the new solution to time dependent description of cell proliferation in porous scaffold and optimized trophical conditions for tissue development.
Cartilaginous structures are at the core of embryo growth and shaping before the bone forms. Here we report a novel principle of vertebrate cartilage growth that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism of growth uncouples the lateral expansion of curved cartilaginous sheets from the control of cartilage thickness, a process which might be the evolutionary mechanism underlying adaptations of facial shape. In rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing limbs), the transverse integration of clonal columns determines the well-defined diameter and resulting rod-like morphology. We were able to alter cartilage shape by experimentally manipulating clonal geometries. Using in silico modeling, we discovered that anisotropic proliferation might explain cartilage bending and groove formation at the macro-scale.
- MeSH
- biologické modely MeSH
- chrupavka embryologie MeSH
- myši MeSH
- obratlovci embryologie MeSH
- počítačová simulace MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Most of the available crystal structures of epidermal growth factor receptor (EGFR) kinase domain, bound to drug inhibitors, originated from ligand-based drug design studies. Here, we used variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. The families shared similar mutational profiles and similarity in the ligand R-groups (chemical composition, geometry, and charge) facing the C-helix, mutation sites, and DFG domain. For structure-based drug design, we recommend a systematic decision-making process for choice of template, guided by appropriate pairwise fitting and clustering before the molecular docking step. Alternatively, the binding site shape/volume can be used to filter and select the compound libraries.
- MeSH
- erbB receptory antagonisté a inhibitory chemie genetika MeSH
- inhibitory proteinkinas farmakologie MeSH
- lidé MeSH
- ligandy MeSH
- mutace MeSH
- racionální návrh léčiv metody MeSH
- rozhodování MeSH
- simulace molekulového dockingu MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The pharmaceutical production of recombinant proteins, such as monoclonal antibodies, is rather complex and requires proper development work. Accordingly, it is essential to develop appropriate scale-down models, which can mimic the corresponding production scale. In this work, we investigated the impact of the bioreactor scale on intracellular micro-heterogeneities of a CHO cell line producing monoclonal antibodies in fed-batch mode, using a 10 mL micro-bioreactor (ambr™) scale-down model and the corresponding 300 L pilot-scale bioreactor. For each scale, we measured the time evolution of the proteome, which enabled us to compare the impact of the bioreactor scale on the intracellular processes. Nearly absolute accordance between the scales was verified by data mining methods, such as hierarchical clustering and in-detail analysis on a single protein base. The time response of principal enzymes related to N-glycosylation was discussed, emphasizing major dissimilarities between the glycan fractions adorning the heavy chain and the corresponding protein abundance. The enzyme expression displayed mainly a constant profile, whereas the resulting glycan pattern changed over time. It is concluded that the enzymatic activity is influenced by the changing environmental conditions present in the fed-batch processes leading to the observed time-dependent variation.
- MeSH
- biologické modely * MeSH
- bioreaktory * MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- glykosylace MeSH
- křečci praví MeSH
- monoklonální protilátky metabolismus MeSH
- proliferace buněk MeSH
- proteomika metody MeSH
- rekombinantní proteiny metabolismus MeSH
- shluková analýza MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In this paper, the decomposition reaction models and thermal hazard properties of 1,3,5-trinitro-1,3,5-triazinane (RDX) and its PBXs bonded by Formex P1, Semtex 1A, C4, Viton A and Fluorel polymer matrices have been investigated based on isoconversional and combined kinetic analysis methods. The established kinetic triplets are used to predict the constant decomposition rate temperature profiles, the critical radius for thermal explosion and isothermal behavior at a temperature of 82°C. It has been found that the effect of the polymer matrices on the decomposition mechanism of RDX is significant resulting in very different reaction models. The Formex P1, Semtex and C4 could make decomposition process of RDX follow a phase boundary controlled reaction mechanism, whereas the Viton A and Fluorel make its reaction model shifts to a two dimensional Avrami-Erofeev nucleation and growth model. According to isothermal simulations, the threshold cook-off time until loss of functionality at 82°C for RDX-C4 and RDX-FM is less than 500 days, while it is more than 700 days for the others. Unlike simulated isothermal curves, when considering the charge properties and heat of decomposition, RDX-FM and RDX-C4 are better than RDX-SE in storage safety at arbitrary surrounding temperature.
Bone and cartilage are tissues of a three-dimensional (3D) nature. Therefore, scaffolds for their regeneration should support cell infiltration and growth in all 3 dimensions. To fulfill such a requirement, the materials should possess large, open pores. Centrifugal spinning is a simple method for producing 3D fibrous scaffolds with large and interconnected pores. However, the process of bone regeneration is rather complex and requires additional stimulation by active molecules. In the current study, we introduced a simple composite scaffold based on platelet adhesion to poly-ε-caprolactone 3D fibers. Platelets were used as a natural source of growth factors and cytokines active in the tissue repair process. By immobilization in the fibrous scaffolds, their bioavailability was prolonged. The biological evaluation of the proposed system in the MG-63 model showed improved metabolic activity, proliferation and alkaline phosphatase activity in comparison to nonfunctionalized fibrous scaffold. In addition, the response of cells was dose dependent with improved biocompatibility with increasing platelet concentration. The results demonstrated the suitability of the system for bone tissue.
- MeSH
- adhezivita trombocytů účinky léků MeSH
- alkalická fosfatasa metabolismus MeSH
- kinetika MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- mezibuněčné signální peptidy a proteiny aplikace a dávkování farmakologie MeSH
- nádorové buněčné linie MeSH
- osteoblasty cytologie účinky léků ultrastruktura MeSH
- osteogeneze účinky léků MeSH
- polyestery chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury chemie MeSH
- trombocyty účinky léků metabolismus ultrastruktura MeSH
- tvar buňky účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The oogenesis and folliculogenesis are closely linked and occur simultaneously in the growing ovarian follicles. Biochemical and morphological changes in oocytes (OC) and surrounding granulosa cells (GCs) are highly complex and depend on many factors, including intercellular communication. GCs are cells with many functions, often crucial for the proper viability of the oocyte and subsequent positive fertilization. The purpose of this study was to analyze gene expression in porcine GCs, to define differentially expressed genes belongs to the "cell growth", "aging", "positive regulation of cell death", "apoptotic process", "regulation of cell death", "cell death" and "negative regulation of cell death" ontology groups during the short - term primary in vitro culture. Microarrays were employed to study the transcriptome contained in the total RNA of the cultured GCs. Ovaries were obtained after slaughter, from 40 gilts of swine aged 170 days. The cells were obtained through puncture of the ovaries, collection of follicular fluid, removal of the cumulus - oocyte complexes and centrifugation. The cells were then cultured in vitro. The RNA material was obtained before the culture was established (0h) and then after 48h, 96h and 144h of its course. From 182 differently expressed genes belonging to the these ontology groups, we have selected POSTN, FN1, FMOD, ITGB3, DCN, SERPINB2, SFRP2, IGFBP5, EMP1, and CCL2 which were upregulated, as well as DAPL1, ESR1, IHH, TGFBR3, PPARD, PDK4, TXNIP, IFIT3, CSRNP3, and TNFSF10 genes whose expression was downregulated during the time of in vitro culture of the GCs. The significance of the differential gene expression is to provide new information on the molecular aspects of in vitro granulosa cell culture.
- MeSH
- apoptóza fyziologie MeSH
- čipová analýza proteinů MeSH
- down regulace MeSH
- folikulární buňky fyziologie MeSH
- kultivované buňky MeSH
- prasata MeSH
- regulace genové exprese fyziologie MeSH
- transkriptom MeSH
- upregulace MeSH
- viabilita buněk fyziologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The enzymes involved in de novo purine synthesis (DNPS), one of the basic processes in eukaryotic cells, transiently and reversibly form a dynamic multienzyme complex called the purinosome in the cytoplasm. The purinosome has been observed in a broad spectrum of cells, but some studies claim that it is an artefact of the constructs used for visualization or stress granules resulting from the exposure of cells to nutrient-reduced growth media. Both may be true depending on the method of observation. To clarify this point, we combined two previously used methods, transfection and immunofluorescence, to detect purinosomes in purinosome-free cells deficient in particular DNPS steps (CR-DNPS cells) and in cells deficient in the salvage pathway, which resulted in construction of the purinosome regardless of purine level (CR-HGPRT cells). METHODS AND FINDINGS: To restore or disrupt purinosome formation, we transiently transfected CR-DNPS and CR-HGPRT cells with vectors encoding BFP-labelled wild-type (wt) proteins and observed the normalization of purinosome formation. The cells also ceased to accumulate the substrate(s) of the defective enzyme. The CR-DNPS cell line transfected with a DNA plasmid encoding an enzyme with zero activity served as a negative control for purinosome formation. No purinosome formation was observed in these cells regardless of the purine level in the growth medium. CONCLUSION: In conclusion, both methods are useful for the detection of purinosomes in HeLa cells. Moreover, the cell-based models prepared represent a unique system for the study of purinosome assembly with deficiencies in DNPS or in the salvage pathway as well as for the study of purinosome formation under the action of DNPS inhibitors. This approach is a promising step toward the treatment of purine disorders and can also provide targets for anticancer therapy.
- MeSH
- biologické modely * MeSH
- HeLa buňky MeSH
- lidé MeSH
- multienzymové komplexy genetika metabolismus MeSH
- puriny biosyntéza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
