A model invalidation-based approach for elucidating biological signalling pathways,applied to the chemotaxis pathway in R. sphaeroides

Background  

Developing methods for understanding the connectivity of signalling pathways is a major challenge in biological research. For this purpose, mathematical models are routinely developed based on experimental observations, which also allow the prediction of the system behaviour under different experimental conditions. Often, however, the same experimental data can be represented by several competing network models.     

Poroelasticity of cartilage at the nanoscale

Atomic-force-microscopy-based oscillatory loading was used in conjunction with finite element modeling to quantify and predict the frequency-dependent mechanical properties of the superficial zone of young bovine articular cartilage at deformation amplitudes, δ, of ∼15 nm; i.e., at macromolecular length scales. Using a spherical probe tip (R ∼ 12.5 μm), the magnitude of the dynamic complex indentation modulus, |E^∗|, and phase angle, φ, between the force and tip displacement sinusoids, were measured in the frequency range f ∼ 0.2–130 Hz at an offset indentation depth of δ₀ ∼ 3 μm. The experimentally measured |E^∗| and φ corresponded well with that predicted by a fibril-reinforced poroelastic model over a three-decade frequency range. The peak frequency of phase angle, f_peak, was observed to scale linearly with the inverse square of the contact distance between probe tip and cartilage, 1/d², as predicted by linear poroelasticity theory. The dynamic mechanical properties were observed to be independent of the deformation amplitude in the range δ = 7–50 nm. Hence, these results suggest that poroelasticity was the dominant mechanism underlying the frequency-dependent mechanical behavior observed at these nanoscale deformations. These findings enable ongoing investigations of the nanoscale progression of matrix pathology in tissue-level disease.     

Respiration of sugar-beet leaves during illumination,with simultaneous photosynthesis

Auto?i sledovali sou?asně intensitu dýchání a intensitu fotosynthesy u list? cukrovky, neoddělených od rostliny. Několik hodin p?ed pokusem asimilovaly listy radioaktivní¹⁴CO₂, na?e? byly umístěny do normální listové komory k pr? tokovému gazometrickému stanovení intensity fotosynthesy podle změny koncentrace CO₂ v procházejícím vzduchu. Sou?asně s gazometrickým stanovením fotosynthesy mě?ili auto?i specifickou aktivitu kysli?níku uhli?itého ve vzduchu, který pro?el asimila?ní komorou. Podle hodnot specifické aktivity CO₂, kterou vylu?uje list v temnotě, je mo?no vypo?ítat intensitu dýchání v mg CO₂. Bylo zji?těno, ?e listy cukrovky vylu?ují na světle radioaktivní CO₂, a to jak první tak i druhý den po asimilaci zna?eného CO₂. P?i silném p?eh?ivání list? v komo?e, kdy gazometrickou metodou bylo zji?těno ji? jen dýchání, radiometricky byl stanoven výdej¹⁴CO₂, odpovídající vy??í intensitě dýchaní. Auto?i vysvětlují tuto skute?nost tím, ?e i p?i p?eh?ívaní list? probíha sou?asně s dýchaním fotosyntheticka asimilace kysli?níku uhli?itého, av?ak pasivní bilance CO₂ ve výměně plyn? vede ke zji?těnédýchaní, které je v podstatě rozdílem mezi intensitou piné fotosynthesy a plného dýchaní. Produkce kysli?níku uhli?itého celými listy cukrovky na světle není za normalních podmínek vý?ivy výjime?ným zjevem.     

Individual cartilage aggrecan macromolecules and their constituent glycosaminoglycans visualized via atomic force microscopy

Atomic force microscopy was used in ambient conditions to directly image dense and sparse monolayers of bovine fetal epiphyseal and mature nasal cartilage aggrecan macromolecules adsorbed on mica substrates. Distinct resolution of the non-glycosylated N-terminal region from the glycosaminoglycan (GAG) brush of individual aggrecan monomers was achieved, as well as nanometer-scale resolution of individual GAG chain conformation and spacing. Fetal aggrecan core protein trace length (398+/-57 nm) and end-to-end length (257+/-87 nm) were both larger than that of mature aggrecan (352+/-88 and 226+/-81 nm, respectively). Similarly, fetal aggrecan GAG chain trace length (41+/-7 nm) and end-to-end (32+/-8 nm) length were both larger than that of mature aggrecan GAG (32+/-5 and 26+/-7 nm, respectively). GAG-GAG spacing along the core protein was significantly smaller in fetal compared to mature aggrecan (3.2+/-0.8 and 4.4+/-1.2nm, respectively). Together, these differences between the two aggrecan types were likely responsible for the greater persistence length of the fetal aggrecan (110 nm) compared to mature aggrecan (82 nm) calculated using the worm-like chain model. Measured dimensions and polymer statistical analyses were used in conjunction with the results of Western analyses, chromatographic, and carbohydrate electrophoresis measurements to better understand the dependence of aggrecan structure and properties on its constituent GAG chains.