An open-loop approach to calculate noise-induced transitions

Bistability permits the co-existence of two distinct cell fates in a population of genetically identical cells. Noise induced transitions between two fates of a bistable system are difficult to calculate due to the intricate interplay between nonlinear dynamics and noise in bistable positive feedback loops. Here we opened multivariable feedback loops at the slowest variable to obtain the open-loop function and the fluctuations in the open-loop output. By the subsequent reclosing of the loop, we calculated the mean first passage time (MFPT) using the Fokker-Planck equation in good agreement with the exact stochastic simulation. When an external component interacts with a feedback component, it amplifies the extrinsic noise in the loop. Consequently, the open-loop function is shifted and the transition rates between the two states in the closed loop are increased. Despite this shift, the open-loop output reflects the system faithfully to predict the MFPT in the feedback loop. Therefore, the open-loop approach can help theoretical analysis. Furthermore, the measurement of the mean value, variance, and the reaction time-scale of the open-loop output permits the prediction of MFPT simply from experimental data, which underscores the practical value of the stochastic open-loop approach

Biology inspires engineering

A report of the Cold Spring Harbor Laboratory/Wellcome Trust Meeting on Engineering Principles in Biology, Cambridge, UK, 14-16 October 2009

Impact of Methods on the Measurement of mRNA Turnover

The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study RNA turnover since the beginnings of molecular biology. Here we summarize the main methods to measure RNA half-life: transcription inhibition, gene control, and metabolic labelling. These methods were used to detect the cellular activity of the mRNAs degradation machinery, including the exo-ribonuclease Xrn1 and the exosome. On the other hand, the study of the differential stability of mature RNAs has been hampered by the fact that different methods have often yielded inconsistent results. Recent advances in the systematic comparison of different method variants in yeast have permitted the identification of the least invasive methodologies that reflect half-lives the most faithfully, which is expected to open the way for a consistent quantitative analysis of the determinants of mRNA stability

Measurement of in vivo protein binding affinities in a signaling network with mass spectrometry

Protein interaction networks play a key role in signal processing. Despite the progress in identifying the interactions, the quantification of their strengths lags behind. Here we present an approach to quantify the in vivo binding of proteins to their binding partners in signaling-transcriptional networks, by the pairwise genetic isolation of each interaction and by varying the concentration of the interacting components over time. The absolute quantification of the protein concentrations was performed with targeted mass spectrometry. The strengths of the interactions, as defined by the apparent dissociation constants ranged from subnanomolar to micromolar values in the yeast galactose signaling network. The weak homodimerization of the Gal4 activator amplifies the signal elicited by glucose. Furthermore, combining the binding constants in a feedback loop correctly predicted cellular memory, a characteristic network behavior. Thus, this genetic-proteomic binding assay can be used to faithfully quantify how strongly proteins interact with proteins, DNA and metabolites

Gene Families With Stochastic Exclusive Gene Choice Underlie Cell Adhesion in Mammalian Cells

Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single-cell RNA-seq data with a simple metric. This metric can detect exclusivity independently of the mean value and the monoallelic nature of gene expression. Chromosomal segments and gene families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions

Nutritivni kvalitet hraniva koja se koriste u ishrani mlečnih koza u Vojvodini

The study was to conduct to evaluate the chemical composition and nutritive values of feedstuffs (forages and concentrate mixtures) used for dairy goats nutrition in Vojvodina. Samples were collected from six farms, including one organic farm. The results showed that the relative feed values of analyzed forages were in the range of good, medium to lower quality. Average protein content from lowest to highest for investigated forages was: corn silage (Zea Mays) (65.37-82.57g kgˉ¹DM), alfalfa haylage (Medicago sativa L.) (159.99-184.17g kgˉ¹DM), pasture (185.30g kgˉ¹ DM), and alfalfa hay (Medicago sativa L.) (167.48-203.60g kgˉ¹DM). The non-fibre carbohydrates and protein content most varied in organic hay samples (cv: 29.25% and 19.09%, respectively). Generally, feedstuffs used in organic nutrition, including organic concentrate, were of lower nutritional quality and moreover contained higher amounts of crude fibre and lignin. Especially, a high source of variation was observed in investigated concentrate mixtures for the crude protein content (p lt 0.0001), ranged from 135.32 to 209.87g kgˉ¹DM. Corn silages also varied substantially in their chemical composition and significant difference (p lt 0.05) was observed in regard to acid detergent fibre (ADF) and lignin content (ranged: ADF: 242.20-319.24g kg‾¹DM; ADL: 27.98-52.54g kg‾¹DM, respectively). Furthermore, pasture contained the most soluble materials during May and June and their content was related inversely to crude fibre amount. This survey highlights that investigated farms still pay insufficient attention to the quality of the feedstuff. For the development of intensive goat farming, greater emphasis should be placed on using higher quality feedstuffs, as well, standards for feed quality must be considered and established.Istraživanje je bilo sprovedeno sa ciljem procene hemijskog sastava i nutritivne vrednosti kabastih hraniva i smeša koncentrata koja se koriste u ishrani mlečnih koza u Vojvodini. Ispitivano je ukupno šest farmi,uključujući i organsku farmu. Dobijeni rezultati su pokazali da se relativna hranibena vrednost analiziranih kabastih hraniva kretala od dobrog, srednjeg do slabijeg kvaliteta. Prosečan sadržaj proteina od najmanjih do najviših vrednosti se kretao u opsegu: kukuruzna silaža (Zea Mays) (65.37-82.50g kg‾¹DM), senaža lucerke (Medigao sativa L.) (159.99-184.17g kg‾¹DM), pašnjak (185.30g kg‾¹DM ) i seno lucerke (Medigao sativa L.) (167.48-203.60g kg‾¹DM). Sadržaj nestrukturnih ugljenih hidrata i proteina pokazao je najveće varijacije u uzorcima organskog sena (cv: 29.25% и 19.09%, pojedinačno). Generalno, hraniva koja su bila ispitivana na organskoj farmi, uključujući organske smeše koncentrata, su pokazale lošiji nutritivni kvalitet usled većeg sadržaja sirovih vlakana i lignina. Posebno su utvrdjene velike varijacije u ispitivanim smešama koncentrata u pogledu sadržaja proteina (p lt 0.0001), koji je bio rangiran od 135.32 do 209.87g kg‾¹DM. Kukuruzne silaže su takodje značajno varirale u njihovom hemijskom sastavu i signifikantna razlika (p lt 0.05) je utvrdjena u pogledu sadržaja kiselih deteržent vlakana (ADF) i lignina (u opsegu: ADF: 242.20-319.24g kg‾¹DM; ADL: 27.98-52.54g kg‾¹DM, pojedinačno). Osim toga, utvrdjeno je da je pašnjak posedovao najviše rastvorljivih materija tokom Maja i Juna meseca a njihov sadržaj je bio obrnuto povezan sa sadržajem sirovih vlakana. Ovo istraživanje je pokazalo da ispitivane farme još uvek ne posvećuju dovoljno pažnje kvalitetu hraniva. Za razvoj intenzivnog uzgoja koza, veći naglasak treba staviti na upotrebu kvalitetnijih hraniva i istovremeno standardi kvaliteta hrane moraju biti razmotreni i utvrđeni

Biodiverzitet i tradicionalni način ispaše ovaca u Južnobanatskom regionu

In this paper the capacity for reintroduction of traditional sheep breeds as key resources for biodiversity conservation systems in HNV farming system of the South Banat region was analyzed. Taking the vulnerability of the ecosystem into consideration when creating the optimal grazing system based on traditional rearing breeds, can contribute to the protection of biodiversity in the South Banat region. The representatives of Fabaceae, Poaceae, Lamiaceae, Rosaceae and Apiaceae family were described. Basic nutritive components of pasture and mixed hay: crude moisture, crude ash, crude protein, crude fat, crude cellulose, calcium (Ca), magnesium (Mg), phosphorous (P), copper (Cu), iron (Fe), manganese (Mn) and zinc (Zn) were measured. Botanical analysis has confirmed the presence of plant diversity, as well as the nutritive value of sheep pastures. Chemical analyses of samples pointed out that the levels of crude proteins, cellulose, fats, macro and trace elements are sufficient to satisfy the requirements of low input sheep farming system and therefore can be considered a solid base for reintroduction of autochthonous sheep breeds in the peripheral parts of the Deliblato Sands area.Imajući u vidu osetljivost ekosistema, primena izbalansirane ispaše, bazirana na gajenju autohtonih rasa ovaca mogla bi da doprinese očuvanju biodiverziteta. U ovom radu ispitivane su mogućnosti za reintrodukciju tradicionalnih rasa ovaca, kao ključnog resursa za zaštitu biodiverziteta u okviru poljoprivrednih sistema visoke prirodne vrednosti južnobanatskog regiona. U tom cilju ispitivan je botanički sastav i hranljiva vrednost paše i mešanog sena sa područja južnog Banata. Utvrđeno je prisustvo familija: Fabaceae, Poaceae, Lamiaceae, Rosaceae i Apiaceae. Određen je sadržaj osnovnih hranljivih materija u mešovitom senu i paši: vlaga, pepeo, proteini, mast i celuloza. Takođe je utvrđen sadržaj Ca, Mg, P, Cu, Fe, Mn i Zn. Utvrđeni nivo štetnih materija (mikotoksina i pesticida) bio je u propisanim granicama. Botanički sastav je pokazao visok stepen diverziteta kao i visoku hranljivu vrednost biljaka, koja može u potpunosti da zadovolji potrebe ovaca u ekstenzivnom načinu gajenja i predstavlja dobru osnovu za reintrodukciju autohtonih rasa ovaca na rubnim delovima Deliblatske peščare

When kinases meet mathematics: the systems biology of MAPK signalling

The mitogen activated protein kinase/extracellular signal regulated kinase pathway regulates fundamental cellular function such as cell proliferation, survival, differentiation and motility, raising the question how these diverse functions are specified and coordinated. They are encoded through the activation kinetics of the pathway, a multitude of feedback loops, scaffold proteins, subcellular compartmentalisation, and crosstalk with other pathways. These regulatory motifs alone or in combination can generate a multitude of complex behaviour. Systems biology tries to decode this complexity through mathematical modelling and prediction in order to gain a deeper insight into the inner works of signalling networks