The Mechanical Behaviour of Chondrocytes Predicted with a Micro-structural Model of Articular Cartilage

The integrity of articular cartilage depends on the proper functioning and mechanical stimulation of chondrocytes, the cells that synthesize extracellular matrix and maintain tissue health. The biosynthetic activity of chondrocytes is influenced by genetic factors, environmental influences, extracellular matrix composition, and mechanical factors. The mechanical environment of chondrocytes is believed to be an important determinant for joint health, and chondrocyte deformation in response to mechanical loading is speculated to be an important regulator of metabolic activity. In previous studies of chondrocyte deformation, articular cartilage was described as a biphasic material consisting of a homogeneous, isotropic, linearly elastic solid phase, and an inviscid fluid phase. However, articular cartilage is known to be anisotropic and inhomogeneous across its depth. Therefore, isotropic and homogeneous models cannot make appropriate predictions for tissue and cell stresses and strains. Here, we modelled articular cartilage as a transversely isotropic, inhomogeneous (TI) material in which the anisotropy and inhomogeneity arose naturally from the microstructure of the depth-dependent collagen fibril orientation and volumetric fraction, as well as the chondrocyte shape and volumetric fraction. The purpose of this study was to analyse the deformation behaviour of chondrocytes using the TI model of articular cartilage. In order to evaluate our model against experimental results, we simulated indentation and unconfined compression tests for nominal compressions of 15%. Chondrocyte deformations were analysed as a function of location within the tissue. The TI model predicted a non-uniform behaviour across tissue depth: in indentation testing, cell height decreased by 43% in the superficial zone and between 11 and 29% in the deep zone. In unconfined compression testing, cell height decreased by 32% in the superficial zone, 25% in the middle, and 18% in the deep zones. This predicted non-uniformity is in agreement with experimental studies. The novelty of this study is the use of a cartilage material model accounting for the intrinsic inhomogeneity and anisotropy of cartilage caused by its microstructure.     

Single and combined effects of two trace elements (Cd and Cu) on the asexual reproduction of Aurelia sp. polyps

Aquatic Ecology - Jellyfish blooms are an increasingly common event in our seas. Occurring via polyps’ asexual reproduction induced by human stresses, they represent a hazard for ecosystems...     

A New Species of Ctenomys (Rodentia: Ctenomyidae) from Patagonia Related to C. sociabilis

The genus Ctenomys includes a high number of taxa, with at least ten species from Patagonia and three recently described species for northeastern Chubut Province (Argentina). Ctenomys sociabilis is a social species of the genus Ctenomys and is currently distributed in the surrounding area of Sierra Cuyin Manzano (Neuquén Province), with a recently extinct population that occurred in Laguna Nahuelquir (Cushamen, Chubut Province). Molecular analyses have placed C. sociabilis at the base of Ctenomys clade, as the sister species to all other Ctenomys. Based on a morphological assessment (qualitative and quantitative) and DNA sequencing, we describe a new species of Ctenomys from Esquel, Chubut Province. Phylogenetic analysis shows the new species to be closely related to C. sociabilis, with evidence of solitary behavior. This new species is the first reported to be closely related phylogenetically to Ctenomys sociabilis at the base of the Ctenomys phylogeny. We provide anatomical comparisons between the new species and other species of Ctenomys from Patagonia, especially C. sociabilis.

     

Oligopeptide Signaling through TbGPR89 Drives Trypanosome Quorum Sensing

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Consumer attitudes toward food crops developed by CRISPR/Cas9 in Costa Rica

Plant Cell, Tissue and Organ Culture (PCTOC) - In the original publication, only affiliation number 2 was indicated as the last author’s affiliation. In fact, the author works for both...     

FtsZ filament structures in different nucleotide states reveal the mechanism of assembly dynamics

Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling filaments that hydrolyse GTP at an active site formed upon subunit association. We determined high-resolution filament structures of FtsZ from the pathogen Staphylococcus aureus in complex with different nucleotide analogs and cations, including mimetics of the ground and transition states of catalysis. Together with mutational and biochemical analyses, our structures reveal interactions made by the GTP γ-phosphate and Mg²⁺ at the subunit interface, a K⁺ ion stabilizing loop T7 for co-catalysis, new roles of key residues at the active site and a nearby crosstalk area, and rearrangements of a dynamic water shell bridging adjacent subunits upon GTP hydrolysis. We propose a mechanistic model that integrates nucleotide hydrolysis signaling with assembly-associated conformational changes and filament treadmilling. Equivalent assembly mechanisms may apply to more complex tubulin and actin cytomotive filaments that share analogous features with FtsZ.

Bacterial cell division critically relies on the tubulin homolog FtsZ, which assembles into filaments that treadmill, fuelled by GTP hydrolysis. This structural and biochemical study of FtsZ from Staphylocuccus aureus reveals the mechanism of GTP hydrolysis and its connection with filament dynamics.     

A spectrofluorometric analysis to evaluate transcutaneous biodistribution of fluorescent nanoparticulate gel formulations

The investigation of the absorption of drug delivery systems, designed for the transport of therapeutic molecules inside the body, could be relatively simplified by the fluorophore association and tracking by means of bio-imaging techniques (i.e., optical in vivo imaging or confocal and multiphoton microscopy). However, when a fluorescence signal comes out from the skin, its specific detection can be problematic. Skin high autofluorescence can hinder the observation of administered exogenous fluorophores conjugated to drug delivery systems, making it more challenging to detect their biodistribution. In the present study, we have developed a method based on the spectrofluorometric analysis of skin samples to discriminate the fluorescent signal coming from administered fluorescent molecules from the background. Moreover, we gave a semi-quantitative evaluation of the signal intensity. Thus, we distinguished two gel formulations loading the fluorophore rhodamine B (called GEL RHO and GEL SLN-RHO). The two formulations of gels, one of which containing solid lipid nanoparticles (GEL RHO-SLN), were administered on skin explants incubated in a bioreactor, and the penetration was evaluated at different time points (2 and 6 hours). Cryostatic sections of skin samples were observed with confocal laser scanning microscopy, and a spectrofluorometric analysis was performed. Significantly higher signal intensity in the samples administered with SLN-RHO GEL, with a preferential accumulation in the hair bulbs, was found. Reaching also the deeper layers of the hair shaft after 6 hours, the solid lipid nanoparticles thickened with polymer represent a suitable drug delivery system for transcutaneous administration.Key words: Organ culture, bioreactor, transcutaneous biodistribution, spectrofluorimetric analysis     

Biochemical changes in prostanoids and cerebral expression of cyclooxygenase (COX)-1 and COX-2 during morphine sulfate infusion in the newborn piglet

To examine the biochemical regulation of morphine sulfate (MS) on prostanoid synthesis, conscious newborn piglets received a bolus dose of 100 microg/kg followed by a continuous infusion dose of 100 microg/kg/h. The control group received equivalent volume bolus and continuous infusion of 5% dextrose. Blood samples were drawn from the femoral artery and sagittal sinus vein before, during and after infusion for measurement of prostanoids. The expression of mRNAs encoding cyclooxygenases (COX)-1 and -2 in the brainstem, thalamus, cortex, and cerebellum of the newborn piglets were also examined. Systemic PGE2 levels declined substantially during and post MS infusion (p < 0.01), whereas sagittal sinus vein PGE2 levels increased following the bolus dose (p < 0.01) and at 4 h of continuous infusion (p < 0.01). MS infusion did not affect systemic 6-ketoPGF1alpha levels, however, in the cerebral circulation 6-ketoPGF1alpha levels increased 146% (p < 0.01) following the bolus dose and remained elevated throughout the infusion and post infusion times. Systemic TxB2 levels increased transiently at 4 h (p < 0.01) and sagittal sinus vein TxB2 increased at 0.5 and 1 h (p < 0.01) during continuous infusion. RT-PCR assays revealed a 1.5- (p < 0.001) to 4-fold (p < 0.001) increased expression of COX-1 mRNA in the MS-infused brain samples. In contrast, no differences in COX-2 mRNA were detected between the groups. These data imply that MS may have significant effects on prostanoid synthesis in the newborn. The data further show that the MS-induced prostanoid responses appear to be mediated via COX-1.     

Cerebellar dysgenesis and mental retardation associated with a complex chromosome rearrangement

Cerebellar hypoplasia, mild mental retardation, skeletal abnormalities, and ataxia were present in a 40 years old patient with a complex chromosome rearrangement (CCR). Chromosomes 2, 5, 16, and 17 were involved in the CCR. For the definition of the eight breakpoints leading to the rearrangement FISH with whole chromosomes paintings and specific telomeric probes was employed. Gene disruption, positional effect variegation, and sub-microscopic deletions are all possible causes for the abnormal phenotype observed in the patient.