A mechanobiological model to study upstream cell migration guided by tensotaxis

Biomechanics and Modeling in Mechanobiology - Cell migration is a process of crucial importance for the human body. It is responsible for important processes such as wound healing and tumor...     

Non-random distribution of individual genetic diversity along an environmental gradient

Improving our knowledge of the links between ecology and evolution is especially critical in the actual context of global rapid environmental changes. A critical step in that direction is to quantify how variation in ecological factors linked to habitat modifications might shape observed levels of genetic variability in wild populations. Still, little is known on the factors affecting levels and distribution of genetic diversity at the individual level, despite its vital underlying role in evolutionary processes. In this study, we assessed the effects of habitat quality on population structure and individual genetic diversity of tree swallows (Tachycineta bicolor) breeding along a gradient of agricultural intensification in southern Québec, Canada. Using a landscape genetics approach, we found that individual genetic diversity was greater in poorer quality habitats. This counter-intuitive result was partly explained by the settlement patterns of tree swallows across the landscape. Individuals of higher genetic diversity arrived earlier on their breeding grounds and settled in the first available habitats, which correspond to intensive cultures. Our results highlight the importance of investigating the effects of environmental variability on individual genetic diversity, and of integrating information on landscape structure when conducting such studies.     

Congenital dyserytropoietic anaemia, type II (HEMPAS) in three siblings

These siblings of a Czech family aged 21, 19 and 6 years, respectively, with congenital dyserythropoietic anemia, type II, (HEMPAS) are reported. In two elder siblings ferrokinetic studies revealed a rapid plasma 59Fe clearance, markedly decreased erythrocyte incorporation and shortened 51Cr red-cell survival. Direct anti-globulin test was found positive in one of them. Further investigations revealed low values of blood plasma cholesterol, total lipids, beta-lipoproteins, beta-carotine and vitamin E and A as well as low values of the prothrombin complex. Liver biopsy demonstrated siderosis and disseminated intravascular coagulation in the liver in both patients. The possible reasons for these humoral aberrations are discussed.     

Comparison of cobalamin-independent and cobalamin-dependent methionine synthases from Escherichia coli: two solutions to the same chemical problem.

In Escherichia coli, two enzymes catalyze the synthesis of methionine from homocysteine using methyltetrahydrofolate as the donor of the required methyl group: cobalamin-dependent and cobalamin-independent methionine synthases. Comparison of the mechanisms of these two enzymes offers the opportunity to examine two different solutions to the same chemical problem. We initiated the research described here to determine whether the two enzymes were evolutionarily related by comparing the deduced amino acid sequences of the two proteins. We have determined the nucleotide sequence for the metE gene, encoding the cobalamin-independent methionine synthase. Our results reveal an absence of similarity between the deduced amino acid sequences of the cobalamin-dependent and cobalamin-independent proteins and suggest that the two have arisen by convergent evolution. We have developed a rapid one-step purification of the recombinant cobalamin-independent methionine synthase (MetE) that yields homogeneous protein in high yield for mechanistic and structural studies. In the course of these studies, we identified a highly reactive thiol in MetE that is alkylated by chloromethyl ketones and by iodoacetamide. We demonstrated that alkylation of this residue, shown to be cysteine 726, results in complete loss of activity. While we are unable to deduce the role of cysteine 726 in catalysis at this time, the identification of this reactive residue suggests the possibility that this thiol functions as an intermediate methyl acceptor in catalysis, analogous to the role of cobalamin in the reaction catalyzed by the cobalamin-dependent enzyme.     

Comparative incidence of reticuloendothelial tumors in C57BL mice after exposure to tritiated water

A total of 2,377 C 57 Bl/6M mice were assigned to control groups and experimental groups exposed to tritiated water administered as a pulse injection or in drinking water, at a dose of 1.0 microCi per injection or per ml of drinking water. Weanlings were observed for the duration of life span. Data analysis was based on two coefficient estimates (1) individual carcinogenic induction coefficient and (2) specific tumorigenic induction coefficient. The carcinogenic potency of tritium was found to be dual in nature in enhancing the absolute induction of lymphocytic lymphomas in both sexes as well as their relative induction in competition with reticulo-endothelial tumors of other types.     

‘Mild mitochondrial uncoupling’ induced protection against neuronal excitotoxicity requires AMPK activity

The preconditioning response conferred by a mild uncoupling of the mitochondrial membrane potential (Δψ_m) has been attributed to altered reactive oxygen species (ROS) production and mitochondrial Ca^2 + uptake within the cells. Here we have explored if altered cellular energetics in response to a mild mitochondrial uncoupling stimulus may also contribute to the protection. The addition of 100 nM FCCP for 30 min to cerebellar granule neurons (CGNs) induced a transient depolarization of the Δψ_m, that was sufficient to significantly reduce CGN vulnerability to the excitotoxic stimulus, glutamate. On investigation, the mild mitochondrial ‘uncoupling’ stimulus resulted in a significant increase in the plasma membrane levels of the glucose transporter isoform 3, with a hyperpolarisation of Δψ_m and increased cellular ATP levels also evident following the washout of FCCP. Furthermore, the phosphorylation state of AMP-activated protein kinase (AMPK) (Thr 172) was increased within 5 min of the uncoupling stimulus and elevated up to 1 h after washout. Significantly, the physiological changes and protection evident after the mild uncoupling stimulus were lost in CGNs when AMPK activity was inhibited. This study identifies an additional mechanism through which protection is mediated upon mild mitochondrial uncoupling: it implicates increased AMPK signalling and an adaptive shift in energy metabolism as mediators of the preconditioning response associated with FCCP-induced mild mitochondrial uncoupling.