Regression and persistence: remodelling in a tissue engineered axial vascular assembly

In later stages of vasculoangiogenesis a vascular network is going through a metamorphosis for optimal perfusion and economy of energy. In this study we make a quantitative approach to phenomena of remodelling in a bioartificial neovascular network and suggest variance of calibre as a parameter of neovascular maturation. For this study, 18 male Lewis rats were subjected to the AV loop operation in combination with a hard porous biogenic matrix and an isolation chamber. The animals were allocated into three groups for different explantation intervals set to 2, 4 and 8 weeks, respectively. Collective attributes like vascular density, percent fractional area and variance of calibre were evaluated for a predefined region of interest (ROI). Late morphogenesis was evaluated by means of scanning electron microscopy. After the fourth week the absolute number of vessels within the ROI decreased (P < 0.03) whereas, on the contrary, the fractional area of all segments increased (P < 0.02). The variance in calibre was significantly increased in the 8‐week group (P < 0.05). Lymphatic growth after week 4, early pericyte migration as well as intussusceptive angiogenesis were identified immunohistologically. Phenomena of remodelling were evaluated quantitatively in a neovascular network and variance could be proposed as a parameter of net vascular maturation.     

Angiotensin II-dependent loss of cardiac function: mechanisms and pharmacological targets attenuating this effect

Pharmacological inhibition of components of the renin-angiotensin-system is one of the major therapeutically options to treat patients with heart failure. This study hypothesized that angiotensin II (Ang II) directly depresses contractile function (cell shortening) by activation of transforming growth factor-beta(1) (TGF-beta(1)). Moreover, we hypothesized that an inhibition of glycogen synthase kinase 3-betaGSK will compensate for this depressive effect by increasing SERCA2 expression. Isolated adult ventricular rat cardiomyocytes were used and cultured in the presence of Ang II (100 nM) for 24 h. Cell shortening and contractile dynamics were recorded at 2 Hz. Immunoblot techniques and gel mobility shift assays were used to demonstrate NFAT activation caused by inhibition of GSK and to demonstrate increases in the expression of SERCA2. Ang-II caused a nearly 20% decrease in cell shortening. This Ang II-dependent effect was mimicked by TGF-beta(1) (10 ng/ml), attenuated by addition of aprotinin, that was used to block the proteolytic activation of TGF-beta(1), or by application of a neutralizing antibody directed against TGF-beta(1). Inhibition of GSK activated NFAT, increased SERCA2 expression and improved cell function. In conclusion, the study identified a paracrine mechanism for the Ang II-dependent loss of cardiac function that occurs independently of hemodynamic changes. Furthermore, it characterized the differences between Ang II and alpha-adrenoceptor stimulation with respect to the maintenance of cellular function explaining cellular events contributing to the difference between adaptive (physiological) and mal-adaptive (patho-physiological) hypertrophy.     

Selective extinction and rapid loss of evolutionary history in the bird fauna

The extinction of species results in a permanent loss of evolutionary history. Recent theoretical studies show that this loss may be proportionally much smaller than the loss of species, but under some conditions can exceed it. Such conditions occur when the phylogenetic tree that describes the evolutionary relationships among species is highly imbalanced due to differences between lineages in past speciation and/or extinction rates. I used the taxonomy by C. G. Sibley and B. L. Monroe Jr to estimate the global loss of bird evolutionary history from historical and predicted extinctions, and to quantify the ensuing changes in balance of the bird phylogenetic tree. In the global bird fauna, evolutionary history is being lost at a high rate, similar to the rate of species extinction. The bird phylogenetic tree is highly imbalanced, and the imbalance is increased significantly by anthropogenic extinction. Historically, the elevated loss of bird evolutionary history has been fuelled mostly by phylogenetic non-randomness in the extinction of species, but the direct effect of tree imbalance is substantial and could dominate in the future.     

NMDA and glycine regulate the affinity of the Mg2+-block site in NR1-1a/NR2A NMDA receptor channels expressed in Xenopus oocytes

NMDA receptors are glutamate-regulated ion channels of critical importance for many neurophysiological and neuropathological processes. Mg2+ blocks the NMDA receptor by binding to the channel pore with an apparent affinity that depends on the membrane potential. We have investigated the effect of NMDA and the required co-agonist glycine on the affinity of the Mg2+ block site in NR1-1a/NR2A NMDA receptors expressed in Xenopus oocytes. We found that NMDA and glycine increase the IC50 value of the Mg2+-block site at pH 7.4 and in the presence of physiological concentration of Ca2+. The increase the IC50 value may correspond to a decrease in Mg2+-block affinity. This effect may result in an increased influx of Ca2+, and this influx may constitute up to a third of the total Ca2+ influx induced by NMDA. At high pH, or at low concentrations of Ca2+, NMDA and glycine have an opposite effect and instead decreased the IC50 value of the Mg2+-block. These results indicate that glutamate and glycine can regulate the affinity of the Mg2+-block site. This effect may have implications for the understanding the role of NMDA receptors both under physiological and pathophysiological conditions.     

Effect of stressful conditions on the carotenogenic activity of a Colombian strain of Dunaliella salina

The objective was evaluate the carotenogenic activity of Dunaliella salina isolated from the artificial salt flats of municipality of Manaure (Department of La Guajira, Colombia). Two experimental testings were designed, in triplicate, to induce the reversibility of the cell tonality depending on the culture conditions. In the first test (A), to induce the reversibility from green to red tonality in D. salina cells, these were cultured in J/1 medium at a concentration of 4.0 M NaCl, 390 µmol m^?2 s^?1, 0.50 mM KNO₃. In the second test (B), to induce the reversibility from red to green cell tonality, the cultures were maintained in J/1 medium 1 M NaCl, 190 µmol m^?2 s^?1, 5.0 mM KNO₃ and pH 8.2. The population growth was evaluated by cell count and the pigment content was performed by spectrophotometric techniques. It was found that in both tests the culture conditions influenced the population growth and the pigments production of D. salina. There was a significant difference between the mean values of total carotenoids in the test A with 9.67 ± 0.19 μg/ml and second test with 1.54 ± 0.08 μg/ml at a significance level of p < 0.05. It was demonstrated that the culture conditions of test A induce the production of lipophilic antioxidants, among these carotenoids. The knowledge of the stressful conditions for the production of carotenoids from D. salina isolated from artificial saline of Manaure opens a field in implementation of this biotic resource for biotechnological purposes, production of new antibiotics, nutraceuticals and/or biofuels production.     

B cell tolerance checkpoints that restrict pathways of antigen-driven differentiation

Autoreactive B cells can be regulated by deletion, receptor editing, or anergy. Rheumatoid factor (RF)-expressing B lymphocytes in normal mice are not controlled by these mechanisms, but they do not secrete autoantibody and were presumed to ignore self-Ag. Surprisingly, we now find that these B cells are not quiescent, but instead are constitutively and specifically activated by self-Ag. In BALB/c mice, RF B cells form germinal centers (GCs) but few Ab-forming cells (AFCs). In contrast, autoimmune mice that express the autoantigen readily generate RF AFCs. Most interestingly, autoantigen-specific RF GCs in BALB/c mice appear defective. B cells in such GCs neither expand nor are selected as efficiently as equivalent cells in autoimmune mice. Thus, our data establish two novel checkpoints of autoreactive B cell regulation that are engaged only after initial autoreactive B cell activation: one that allows GCs but prevents AFC formation and one that impairs selection in the GC. Both of these checkpoints fail in autoimmunity.