Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration

Netrins, axon guidance cues in the CNS, have also been detected in epithelial tissues. In this study, using the embryonic pancreas as a model system, we show that Netrin-1 is expressed in a discrete population of epithelial cells, localizes to basal membranes, and specifically associates with elements of the extracellular matrix. We demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of CK19+/PDX1+ putative pancreatic progenitors on Netrin-1. These results provide evidence for the activation of epithelial cell adhesion and migration by a neural chemoattractant, and identify Netrin-1/integrin interactions as adhesive/guidance cues for epithelial cells.     

Disturbances, elevation, topography and spatial proximity drive vegetation patterns along an altitudinal gradient of a top biodiversity hotspot

The correlation between vegetation patterns (species distribution and richness) and altitudinal variation has been widely reported for tropical forests, thereby providing theoretical basis for biodiversity conservation. However, this relationship may have been oversimplified, as many other factors may influence vegetation patterns, such as disturbances, topography and geographic distance. Considering these other factors, our primary question was: is there a vegetation pattern associated with substantial altitudinal variation (10–1,093 m a.s.l.) in the Atlantic Rainforest—a top hotspot for biodiversity conservation—and, if so, what are the main factors driving this pattern? We addressed this question by sampling 11 1-ha plots, applying multivariate methods, correlations and variance partitioning. The Restinga (forest on sandbanks along the coastal plains of Brazil) and a lowland area that was selectively logged 40 years ago were floristically isolated from the other plots. The maximum species richness (>200 spp. per hectare) occurred at approximately 350 m a.s.l. (submontane forest). Gaps, multiple stemmed trees, average elevation and the standard deviation of the slope significantly affected the vegetation pattern. Spatial proximity also influenced the vegetation pattern as a structuring environmental variable or via dispersal constraints. Our results clarify, for the first time, the key variables that drive species distribution and richness across a large altitudinal range within the Atlantic Rainforest.     

Effect of 1-MCP and low-temperature storage on postharvest conservation of camu–camu

Camu–camu, a native fruit from the Amazon region, is a rich source of bioactive compounds. However, its intense metabolic activity and high-water content limit the fruit’s postharvest storage and marketing. The aim of this study, conducted in two parts, was to evaluate the effects of 1-MCP and storage temperature on the physiology and postharvest preservation of camu–camu fruit. In part 1 of the study, fruit harvested at maturity stage 3 were divided into groups: control, 1-methylcyclopropene (1-MCP; 900 nL L^?1; 12 h) and ethylene (1000 µL L^?1; 24 h) and were stored at 22?±?1 °C and 85?±?5% RH for 9 days. In part 2, fruit harvested at maturity stage 3 were stored at 5, 10, 15, 20, or 25?±?1 °C and 85?±?5% RH for 9 days. During storage, fruit were evaluated daily for decay, mass loss, respiratory activity, and ethylene production, and every 3 days they were evaluated for peel color, pulp firmness, soluble solids content, total titratable acidity, ascorbic acid, total chlorophyll, and total anthocyanins. Fruit treated with 1-MCP exhibited delayed ripening due to lower metabolic activity, as evidenced by delay to softening, reduced mass loss and no decay. Storage at 5 °C prevented ethylene production, mass loss, color changes, and maintained pulp firmness, while did not affect soluble solids content. The results indicated that storage of camu–camu fruit at 5 °C or at 25 °C following application of 900 nL L^?1 1-MCP were effective strategies to delay ripening and maintain fruit quality up to 9 days.     

Speciation-rate dependence in species–area relationships

The general tendency for species number (S) to increase with sampled area (A) constitutes one of the most robust empirical laws of ecology, quantified by species–area relationships (SAR). In many ecosystems, SAR curves display a power-law dependence, S∝A^z. The exponent z is always less than one but shows significant variation in different ecosystems. We study the multitype voter model as one of the simplest models able to reproduce SAR similar to those observed in real ecosystems in terms of basic ecological processes such as birth, dispersal and speciation. Within the model, the species–area exponent z depends on the dimensionless speciation rate ν, even though the detailed dependence is still matter of controversy. We present extensive numerical simulations in a broad range of speciation rates from ν=10^-3 down to ν=10^-11, where the model reproduces values of the exponent observed in nature. In particular, we show that the inverse of the species–area exponent linearly depends on the logarithm of ν. Further, we compare the model outcomes with field data collected from previous studies, for which we separate the effect of the speciation rate from that of the different species lifespans. We find a good linear relationship between inverse exponents and logarithm of species lifespans. However, the slope sets bounds on the speciation rates that can hardly be justified on evolutionary basis, suggesting that additional effects should be taken into account to consistently interpret the observed exponents.     

Optomotor course control in flies with largely asymmetric visual input

We have studied freely flying and walking flies as well as flies flying in a flight simulator in order to discover how functionally blinding one of the eyes affects the fly's ability to move straight. It is hard to tell just by observing the animals' movements whether they have been deprived of vision in one eye. Statistical analysis is need to show that there are differences in the locomotory paths of monocular and binocular flies: monocular flies tend to turn slightly towards the side of the seeing eye. It is possible that the superimposed translational and rotational optic flow fields, generated on the trajectory of monocular flies, sum to zero net flow. This overall flow over the retina of the open eye might lead to a state of optomotor equilibrium. Accepted: 11 October 1999     

Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)-1Phenylethanone and its Protective Effect Against DNA Damage

Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities.     

Thermal specialization across large geographical scales predicts the resilience of mangrove crab populations to global warming

The broad prediction that ectotherms will be more vulnerable to climate change in the tropics than in temperate regions includes assumptions about centre/edge population effects that can only be tested by within‐species comparisons across wide latitudinal gradients. Here, we investigated the thermal vulnerability of two mangrove crab species, comparing populations at the centre (Kenya) and edge (South Africa) of their distributions. At the same time, we investigated the role of respiratory mode (water‐ versus air‐breathing) in determining the thermal tolerance in amphibious organisms. To do this, we compared the vulnerability to acute temperature fluctuations of two sympatric species with two different lifestyle adaptations: the free living Perisesarma guttatum and the burrowing Uca urvillei, both pivotal to the ecosystem functioning of mangroves. The results revealed the air‐breathing U. urvillei to be a thermal generalist with much higher thermal tolerances than P. guttatum. Importantly, however, we found that, while U. urvillei showed little difference between edge and centre populations, P. guttatum showed adaptation to local conditions. Equatorial populations had elevated tolerances to acute heat stress and mechanisms of partial thermoregulation, which make them less vulnerable to global warming than temperate conspecifics. The results reveal both the importance of respiratory mode to thermal tolerance and the unexpected potential for low latitude populations/species to endure a warming climate. The results also contribute to a conceptual model on the latitudinal thermal tolerance of these key species. This highlights the need for an integrated population‐level approach to predict the consequences of climate change.     

S-100 B Concentrations Are a Predictor of Decreased Survival in Patients with Major Trauma,Independently of Head Injury

Background

Major trauma remains one of the principle causes of disability and death throughout the world. There is currently no satisfactory risk assessment to predict mortality in patients with major trauma. The aim of our study is to examine whether S-100 B protein concentrations correlate with injury severity and survival in patients with major trauma, with special emphasis on patients without head injury.

Methods

Our retrospective data analysis comprised adult patients admitted to our emergency department between 1.12. 2008 and 31.12 2010 with a suspected major trauma. S-100 B concentrations were routinely assessed in major trauma patients.

Results

A total of 27.7% (378) of all patients had major trauma. The median ISS was 24.6 (SD 8.4); 16.6% (63/378) of the patients died. S-100 B concentrations correlated overall with the ISS (p<0.0001). Patients who died had significantly higher S-100 B concentrations than survivors (8.2 μg/l versus 2.2 μg/l, p<0.0001). Polytraumatised patients with and without head trauma did not differ significantly with respect to S-100 B concentration (3.2 μg/l (SD 5.3) versus 2.9 μg/l (SD 3.8), respectively, p = 0.63) or with respect to Injury Severity Score (24.8 (SD 8.6) versus 24.2 (SD 8.1), respectively, p = 0.56). S-100 B concentrations correlated negatively with survival (p<0.0001) in all patients and in both subgroups (p = 0.001 and p = 0.006, respectively)

Conclusions

S-100 concentrations on admission correlate positively with greater injury severity and decreased survival in major trauma patients, independently of the presence of a head injury. S-100 B protein levels at admission in patients with major trauma may therefore be used to assess outcome in all polytraumatised patients. These measurements should be subject to further evaluation.     

Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2-phenylbenzimidazole derivatives

Seventy-six 2-phenylbenzimidazole derivatives were synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. The most commonly affected viruses were, in decreasing order, CVB-2, BVDV, Sb-1, HSV-1, and YFV, while HIV-1 and VSV were not affected, and RSV, VV and Reo-1 were only susceptible to a few compounds. Thirty-nine compounds exhibited high activity (EC₅₀ = 0.1–10 μM) against at least one virus, and four of them were outstanding for their high and selective activity against VV (24, EC₅₀ = 0.1 μM) and BVDV (50, 51, and 53 with EC₅₀ = 1.5, 0.8, and 1.0 μM, respectively). The last compounds inhibited at low micromolar concentrations the NS5B RdRp of BVDV and also of HCV, the latter sharing structural similarity with the former. The considered compounds represent attractive leads for the development of antiviral agents against poxviruses, pestiviruses and even HCV, which are important human and veterinary pathogens.     

Synthesis,semipreparative HPLC separation,biological evaluation,and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors

The present study reports on synthesis in high yields (70–99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1–45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds.