High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy

Damaged mitochondria can be eliminated in a process of organelle autophagy, termed mitophagy. In most cells, the organization of mitochondria in a network could interfere with the selective elimination of damaged ones. In principle, fission of this network should precede mitophagy; but it is unclear whether it is per se a trigger of autophagy. The pro-fission mitochondrial protein Fis1 induced mitochondrial fragmentation and enhanced the formation of autophagosomes which could enclose mitochondria. These changes correlated with mitochondrial dysfunction rather than with fragmentation, as substantiated by Fis1 mutants with different effects on organelle shape and function. In conclusion, fission associated with mitochondrial dysfunction stimulates an increase in autophagy.     

Moderate physical training increases brain insulin concentrations in experimental diabetic rats

Insulin is an important modulator of growth and metabolic function in the central nervous system. The aim of this study was to investigate the influence of swimming physical training (at 32 degrees +/- 1 degree C, 1 hr/day, 5 days/week, with an overload equivalent to 5% of the body weight, for 4 weeks) on brain insulin concentrations in alloxan induced type 1 diabetic rats. Training attenuated hyperglycemia but had no effect on insulinemia in diabetic rats. Hematocrit and blood albumin values remained without changes. Brain insulin did not change in diabetic rats. However, physical training increased the concentration in both control and diabetic rats. It is concluded that in the present experimental conditions, diabetes had no influence on brain insulin, however moderate physical training increased the hormone in both control and diabetic animals.     

Lysophosphatidic acid receptor-dependent secondary effects via astrocytes promote neuronal differentiation

Lysophosphatidic acid (LPA) is a simple phospholipid derived from cell membranes that has extracellular signaling properties mediated by at least five G protein-coupled receptors referred to as LPA(1)-LPA(5). In the nervous system, receptor-mediated LPA signaling has been demonstrated to influence a range of cellular processes; however, an unaddressed aspect of LPA signaling is its potential to produce specific secondary effects, whereby LPA receptor-expressing cells exposed to, or "primed," by LPA may then act on other cells via distinct, yet LPA-initiated, mechanisms. In the present study, we examined cerebral cortical astrocytes as possible indirect mediators of the effects of LPA on developing cortical neurons. Cultured astrocytes express at least four LPA receptor subtypes, known as LPA(1)-LPA(4). Cerebral cortical astrocytes primed by LPA exposure were found to increase neuronal differentiation of cortical progenitor cells. Treatment of unprimed astrocyte-progenitor cocultures with conditioned medium derived from LPA-primed astrocytes yielded similar results, suggesting the involvement of an astrocyte-derived soluble factor induced by LPA. At least two LPA receptor subtypes are involved in LPA priming, since the priming effect was lost in astrocytes derived from LPA receptor double-null mice (LPA(1)((-/-))/LPA(2)((-/-))). Moreover, the loss of LPA-dependent differentiation in receptor double-null astrocytes could be rescued by retrovirally transduced expression of a single deleted receptor. These data demonstrate that receptor-mediated LPA signaling in astrocytes can induce LPA-dependent, indirect effects on neuronal differentiation.     

c-Met must translocate to the nucleus to initiate calcium signals

Hepatocyte growth factor (HGF) is important for cell proliferation, differentiation, and related activities. HGF acts through its receptor c-Met, which activates downstream signaling pathways. HGF binds to c-Met at the plasma membrane, where it is generally believed that c-Met signaling is initiated. Here we report that c-Met rapidly translocates to the nucleus upon stimulation with HGF. Ca(2+) signals that are induced by HGF result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. Translocation of c-Met to the nucleus depends upon the adaptor protein Gab1 and importin beta1, and formation of Ca(2+) signals in turn depends upon this translocation. HGF may exert its particular effects on cells because it bypasses signaling pathways in the cytoplasm to directly activate signaling pathways in the nucleus.     

"Mushroom cloud": a giant left ventricular pseudoaneurysm after a myocardial infarction due to myocardial bridging – a case report

Left ventricular pseudoaneurysm is an uncommon complication after transmural myocardial infarction, occurring when a free wall rupture is contained by adhesions of the overlying pericardium preventing acute tamponade. In this report, an unusual case of a 61 year-old male with a giant apical left ventricular pseudoaneurysm after an unnoticed myocardial infarction is presented. On coronary angiogram myocardial bridging of the distal left anterior descending artery was judged to be the infarct related lesion. The echocardiographic diagnosis allowed for a timely surgical intervention which resulted in the patient's full recovery.     

Defense Proteins from Vigna Unguiculata Seed Exudates: Characterization and Inhibitory Activity Against Fusarium Oxysporum

Plants exude a variety of substances through their roots, germinating seeds and aerial parts. Some of these released compounds seem to have an inhibitory effect against pathogens. The aim of this work was to investigate and identify antifungal proteins present in exudates from imbibed cowpea seeds (Vigna unguiculata (L.) Walp). The obtained exudation was analyzed in regard to specific protein activities by enzymatic or immunological assays for plant defense proteins, from 4 h to 48 h of seed imbibition. Our results show that cowpea seeds exudates present several defense related proteins characterized as β-1,3-glucanases, cystatins, vicilins and lipid transfer proteins (LTPs), as well as a storage vacuole membrane α-TIP protein, since the very first hours of imbibition. These exudates also have an “in vitro” inhibitory effect on the growth of the fungus Fusarium oxysporum f. sp. phaseoli. Our results suggest that seed exudates should promote seed protection from soil pathogens.     

Localized contacts between hosts reduce pathogen diversity

We investigate the dynamics of a simple epidemiological model for the invasion by a pathogen strain of a population where another strain circulates. We assume that reinfection by the same strain is possible but occurs at a reduced rate due to acquired immunity. The rate of reinfection by a distinct strain is also reduced due to cross-immunity. Individual based simulations of this model on a 'small-world' network show that the proportion of local contacts in the host contact network structure significantly affects the outcome of such an invasion, and as a consequence will affect the patterns of pathogen evolution. In particular, hosts interacting through a 'small-world' network of contacts support lower prevalence of infection than well-mixed populations, and the region in parameter space for which an invading strain can become endemic and coexist with the circulating strain is smaller, reducing the potential to accommodate pathogen diversity. We discuss the underlying mechanisms for the reported effects, and we propose an effective mean-field model to account for the contact structure of the host population in 'small-world' networks.     

A crumpled surface having transverse attractive interactions as a simplified model with biological significance

Using extensive analogical simulations with square sheets of paper we investigate the influence of short-range transverse attractive interactions on the packing properties of a crumpled surface. These interactions are due to transverse connections or local bridges associated with a given number of binding sites localized on the two-dimensional surface and distributed in several patterns in the three-dimensional physical space. Geometrical relations and critical exponents describing the statistical properties of the crumpled surface are obtained as a function of the strength of the attractive interactions. Our model suggests how the presence of short-range interactions as, e.g. van der Waals forces can be important for the geometric plasticity of biological molecules, which in turn is important for biological function. The relevance of our results to the study of molecular conformation of proteins and membranes is discussed, and a comparison is also made between the behavior of the crumpled surface studied here and other important non-equilibrium fractal structures.