Caspase-dependent secondary lens fiber cell disintegration in alphaA-/alphaB-crystallin double-knockout mice

alphaB-crystallin has been demonstrated, in tissue culture experiments, to be a caspase 3 inhibitor; however, no animal model studies have yet been described. Here, we show that morphological abnormalities in lens secondary fiber cells of alphaA-/alphaB-crystallin gene double knockout (DKO) mice are consistent with, and probably result from, elevated DEVDase and VEIDase activities, corresponding to caspase 3 and caspase 6, respectively. Immunofluorescence microscopy revealed an increased amount of caspase 6, and the active form of caspase 3, in specific regions of the DKO lens, coincident with the site of cell disintegration. TUNEL labeling illustrated a higher level of DNA fragmentation in the secondary fiber lens cells of DKO mice, compared with wild-type mice. Using a pull-down assay, we show interaction between caspase 6 and alphaA- but not alphaB-crystallin. These studies suggest that alpha-crystallin plays a role in suppressing caspase activity, resulting in retention of lens fiber cell integrity following degradation of mitochondria and other organelles, which occurs during the apoptosis-like pathway of lens cell terminal differentiation.     

Exoskeletal Anomalies in Ixodes pavlovskyi pavlovskyi (Parasitiformes,Ixodidae)

Entomological Review - Types of exoskeleton anomalies and frequency of their occurrence were described in 437 females and 366 males of Ixodes pavlovskyi pavlovskyi Pomerantsev 1946, collected by...     

Revisiting the Role of Individual Variability in Population Persistence and Stability

Populations often exhibit a pronounced degree of individual variability and this can be important when constructing ecological models. In this paper, we revisit the role of inter-individual variability in population persistence and stability under predation pressure. As a case study, we consider interactions between a structured population of zooplankton grazers and their predators. Unlike previous structured population models, which only consider variability of individuals according to the age or body size, we focus on physiological and behavioural structuring. We first experimentally demonstrate a high degree of variation of individual consumption rates in three dominant species of herbivorous copepods (Calanus finmarchicus, Calanus glacialis, Calanus euxinus) and show that this disparity implies a pronounced variation in the consumption capacities of individuals. Then we construct a parsimonious predator-prey model which takes into account the intra-population variability of prey individuals according to behavioural traits: effectively, each organism has a ‘personality’ of its own. Our modelling results show that structuring of prey according to their growth rate and vulnerability to predation can dampen predator-prey cycles and enhance persistence of a species, even if the resource stock for prey is unlimited. The main mechanism of efficient top-down regulation is shown to work by letting the prey population become dominated by less vulnerable individuals when predator densities are high, while the trait distribution recovers when the predator densities are low.     

Approaches to the design of selective ligands for membrane progesterone receptor alpha

A number of progesterone derivatives were assayed in terms of their affinity for recombinant human membrane progesterone receptor alpha (mPRα) in comparison with nuclear progesterone receptor (nPR). The 16α,17α-cycloalkane group diminished an affinity of steroids for mPRα without significant influence on affinity for nPR, thus rendering a prominent selectivity of ligands for nPR. On the contrary, substitution of methyl at C10 for ethyl or methoxy group moderately increased the affinity for mPRα and significantly lowered the affinity for nPR. A similar but even more prominent effect was observed upon substitution of the 3-oxo group for the 3-O-methoxyimino group. A significant preference towards mPRα was also rendered by the 17α-hydroxy group and additional C6–C7-double bond. The data suggest that the modes of lig- and interaction with mPRα and nPR in the C3 region of the steroid molecule are different. One can speculate that combination of the above substitutions at C17, C10, C6, and C3 may give ligand(s) with high specificity towards mPRα over nPR.     

Talin1 and Rap1 Are Critical for Osteoclast Function

To determine talin1''s role in osteoclasts, we mated TLN1^fl/fl mice with those expressing cathepsin K-Cre (CtsK-TLN1) to delete the gene in mature osteoclasts or with lysozyme M-Cre (LysM-TLN1) mice to delete TLN1 in all osteoclast lineage cells. Absence of TLN1 impairs macrophage colony-stimulating factor (M-CSF)-stimulated inside-out integrin activation and cytoskeleton organization in mature osteoclasts. Talin1-deficient precursors normally express osteoclast differentiation markers when exposed to M-CSF and receptor activator of nuclear factor κB (RANK) ligand but attach to substrate and migrate poorly, arresting their development into mature resorptive cells. In keeping with inhibited resorption, CtsK-TLN1 mice exhibit an ∼5-fold increase in bone mass. Osteoclast-specific deletion of Rap1 (CtsK-Rap1), which promotes talin/β integrin recognition, yields similar osteopetrotic mice. The fact that the osteopetrosis of CtsK-TLN1 and CtsK-Rap1 mice is substantially more severe than that of those lacking αvβ3 is likely due to added failed activation of β1 integrins. In keeping with osteoclast dysfunction, mice in whom talin is deleted late in the course of osteoclastogenesis are substantially protected from ovariectomy-induced osteoporosis and the periarticular osteolysis attending inflammatory arthritis. Thus, talin1 and Rap1 are critical for resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss.     

Enantiospecificity of chloroperoxidase-catalyzed epoxidation: biased molecular dynamics study of a cis-β-methylstyrene/chloroperoxidase-compound I complex

Molecular dynamics simulations of an explicitly solvated cis-β-methylstyrene/chloroperoxidase-Compound I complex are performed to determine the cause of the high enantiospecificity of epoxidation. From the simulations, a two-dimensional free energy potential is calculated to distinguish binding potential wells from which reaction to 1S2R and 1R2S epoxide products may occur. Convergence of the free energy potential is accelerated with an adaptive biasing potential. Analysis of binding is followed by analysis of 1S2R and 1R2S reaction precursor structures in which the substrate, having left the binding wells, places its reactive double bond in steric proximity to the oxyferryl heme center. Structural analysis of binding and reaction precursor conformations is presented. We find that 1), a distortion of Glu(183) is important for CPO-catalyzed epoxidation as was postulated previously based on experimental results; 2), the free energy of binding does not provide significant differentiation between structures leading to the respective epoxide enantiomers; and 3), CPO's enantiospecificity toward cis-β-methylstyrene is likely to be caused by a specific group of residues which form a hydrophobic core surrounding the oxyferryl heme center.     

A study of bulky nanotube composites based on albumin by high-resolution microscopy

The structure of biocompatible nanocomposites formed by the action of laser radiation on an aqueous dispersion of albumin with carbon nanotubes has been studied by the high-resolution methods of atomic force and transmitting electron microscopy. It has been shown that the nanocomposites have a bulky structure consisting of conglomerates of nanotubes uniformly distributed in the albumin matrix. The results of the study may be useful in the production of filling nanomaterials for implants of biological tissues and organs and the control of their quality.