Attentional Stimulus Selection through Selective Synchronization between Monkey Visual Areas

A central motif in neuronal networks is convergence, linking several input neurons to one target neuron. In visual cortex, convergence renders target neurons responsive to complex stimuli. Yet, convergence typically sends multiple stimuli to a target, and the behaviorally relevant stimulus must be selected. We used two stimuli, activating separate electrocorticographic V1 sites, and both activating an electrocorticographic V4 site equally strongly. When one of those stimuli activated one V1 site, it gamma synchronized (60-80?Hz) to V4. When the two stimuli activated two V1 sites, primarily the relevant one gamma synchronized to V4. Frequency bands of gamma activities showed substantial overlap containing the band of interareal coherence. The relevant V1 site had its gamma peak frequency 2-3?Hz higher than the irrelevant V1 site and 4-6?Hz higher than V4. Gamma-mediated interareal influences were predominantly directed from V1 to V4. We propose that selective synchronization renders relevant input effective, thereby modulating effective connectivity.     

NADPH Oxidase NOX4 Mediates Stellate Cell Activation and Hepatocyte Cell Death during Liver Fibrosis Development

A role for the NADPH oxidases NOX1 and NOX2 in liver fibrosis has been proposed, but the implication of NOX4 is poorly understood yet. The aim of this work was to study the functional role of NOX4 in different cell populations implicated in liver fibrosis: hepatic stellate cells (HSC), myofibroblats (MFBs) and hepatocytes. Two different mice models that develop spontaneous fibrosis (Mdr2^−/−/p19^ARF−/−, Stat3^Δhc/Mdr2^−/−) and a model of experimental induced fibrosis (CCl₄) were used. In addition, gene expression in biopsies from chronic hepatitis C virus (HCV) patients or non-fibrotic liver samples was analyzed. Results have indicated that NOX4 expression was increased in the livers of all animal models, concomitantly with fibrosis development and TGF-β pathway activation. In vitro TGF-β-treated HSC increased NOX4 expression correlating with transdifferentiation to MFBs. Knockdown experiments revealed that NOX4 downstream TGF-β is necessary for HSC activation as well as for the maintenance of the MFB phenotype. NOX4 was not necessary for TGF-β-induced epithelial-mesenchymal transition (EMT), but was required for TGF-β-induced apoptosis in hepatocytes. Finally, NOX4 expression was elevated in patients with hepatitis C virus (HCV)-derived fibrosis, increasing along the fibrosis degree. In summary, fibrosis progression both in vitro and in vivo (animal models and patients) is accompanied by increased NOX4 expression, which mediates acquisition and maintenance of the MFB phenotype, as well as TGF-β-induced death of hepatocytes.     

Biomass and water storage dynamics of epiphytes in old-growth and secondary montane cloud forest stands in Costa Rica

The way competition structures plant communities has been investigated intensely over many decades. Dominance structures due to competitive hierarchies, with consequences for species richness, have not received as much experimental attention, since their manipulation is a large logistic undertaking. Here the data from a model system based on bryophytes are presented to investigate competition structure in a three-species system. Grown in monocultures, pairwise and three-species mixtures under no and high nitrogen supply, the three moss species responded strongly to treatment conditions. One of them suffered from nitrogen fertilisation and hence performed better in mixtures, where the dominant species provided physical shelter from apparently toxic nitrogen spray. Accordingly, no linear competitive hierarchy emerged and qualitative transitivity remains restricted to the unfertilised treatments. Faciliation also affected other properties of the competition structure. The reciprocity of competition effects could not be observed. Moreover, the performances in three-species mixtures were not well predictable from the knowledge of monocultures and pairwise mixtures because competitive effects were not additive. This had implications for community stability at equilibrium: all two-species systems were stable, both fertilised and unfertilised, while the three-species system was only stable when fertilised. This stability under fertilisation has probably to do with the facilitative effect of the two dominant species on the third. In this experiment, little support for commonly held ideas was found about the way competition in plant communities is structured. On the other hand, this study shows that moss communities are ideal model systems to test predictions of theoretical models concerning properties and consequences of competition in plant communities.     

Antimicrobial GL13K Peptide Coatings Killed and Ruptured the Wall of Streptococcus gordonii and Prevented Formation and Growth of Biofilms

Infection is one of the most prevalent causes for dental implant failure. We have developed a novel antimicrobial peptide coating on titanium by immobilizing the antimicrobial peptide GL13K. GL13K was developed from the human salivary protein BPIFA2. The peptide exhibited MIC of 8 µg/ml against planktonic Pseudonomas aeruginosa and their biofilms were reduced by three orders of magnitude with 100 µg/ml GL13K. This peptide concentration also killed 100% of Streptococcus gordonii. At 1 mg/ml, GL13K caused less than 10% lysis of human red blood cells, suggesting low toxicity to mammalian cells. Our GL13K coating has also previously showed bactericidal effect and inhibition of biofilm growth against peri-implantitis related pathogens, such as Porphyromonas gingivalis. The GL13K coating was cytocompatible with human fibroblasts and osteoblasts. However, the bioactivity of antimicrobial coatings has been commonly tested under (quasi)static culture conditions that are far from simulating conditions for biofilm formation and growth in the oral cavity. Oral salivary flow over a coating is persistent, applies continuous shear forces, and supplies sustained nutrition to bacteria. This accelerates bacteria metabolism and biofilm growth. In this work, the antimicrobial effect of the coating was tested against Streptococcus gordonii, a primary colonizer that provides attachment for the biofilm accretion by P. gingivalis, using a drip-flow biofilm bioreactor with media flow rates simulating salivary flow. The GL13K peptide coatings killed bacteria and prevented formation and growth of S. gordonii biofilms in the drip-flow bioreactor and under regular mild-agitation conditions. Surprisingly the interaction of the bacteria with the GL13K peptide coatings ruptured the cell wall at their septum or polar areas leaving empty shell-like structures or exposed protoplasts. The cell wall rupture was not detected under regular culture conditions, suggesting that cell wall rupture induced by GL13K peptides also requires media flow and possible attendant biological sequelae of the conditions in the bioreactor.     

Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages

Recognition and internalisation of intracellular pathogens by host cells is a multifactorial process, involving both stable and transient interactions. The plasticity of the host cell plasma membrane is fundamental in this infectious process. Here, the participation of macrophage lipid microdomains during adhesion and internalisation of the fungal pathogen Histoplasma capsulatum (Hc) was investigated. An increase in membrane lateral organisation, which is a characteristic of lipid microdomains, was observed during the first steps of Hc–macrophage interaction. Cholesterol enrichment in macrophage membranes around Hc contact regions and reduced levels of Hc–macrophage association after cholesterol removal also suggested the participation of lipid microdomains during Hc–macrophage interaction. Using optical tweezers to study cell‐to‐cell interactions, we showed that cholesterol depletion increased the time required for Hc adhesion. Additionally, fungal internalisation was significantly reduced under these conditions. Moreover, macrophages treated with the ceramide‐glucosyltransferase inhibitor (P4r) and macrophages with altered ganglioside synthesis (from B4galnt1^?/? mice) showed a deficient ability to interact with Hc. Coincubation of oligo‐GM1 and treatment with Cholera toxin Subunit B, which recognises the ganglioside GM1, also reduced Hc association. Although purified GM1 did not alter Hc binding, treatment with P4 significantly increased the time required for Hc binding to macrophages. The content of CD18 was displaced from lipid microdomains in B4galnt1^?/? macrophages. In addition, macrophages with reduced CD18 expression (CD18^low) were associated with Hc at levels similar to wild‐type cells. Finally, CD11b and CD18 colocalised with GM1 during Hc–macrophage interaction. Our results indicate that lipid rafts and particularly complex gangliosides that reside in lipid rafts stabilise Hc–macrophage adhesion and mediate efficient internalisation during histoplasmosis.     

The Interplay between Natural Selection and Susceptibility to Melanoma on Allele 374F of SLC45A2 Gene in a South European Population

We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and intron 5 of the 34 most and the 34 least pigmented individuals according to the reflectance distribution, we observed that the polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In particular, allele 374F was significantly more frequent among the individuals with lighter skin. Further genotyping an independent set of 558 individuals of a geographically wider population with known ancestry in the Spanish population also revealed that the frequency of L374F was significantly correlated with the incident UV radiation intensity. Selection tests suggest that allele 374F is being positively selected in South Europeans, thus indicating that depigmentation is an adaptive process. Interestingly, by genotyping 119 melanoma samples, we show that this variant is also associated with an increased susceptibility to melanoma in our populations. The ultimate driving force for this adaptation is unknown, but it is compatible with the vitamin D hypothesis. This shows that molecular evolution analysis can be used as a useful technology to predict phenotypic and biomedical consequences in humans.     

Engineering plants to reflect light: strategies for engineering water‐efficient plants to adapt to a changing climate

Population growth and globally increasing standards of living have put a significant strain on the energy–food–water nexus. Limited water availability particularly affects agriculture, as it accounts for over 70% of global freshwater withdrawals (Aquastat). This study outlines the fundamental nature of plant water consumption and suggests a >50% reduction in renewable freshwater demand is possible by engineering more reflective crops. Furthermore, the decreased radiative forcing resulting from the greater reflectivity of crops would be equivalent to removing 10–50 ppm CO₂ from the atmosphere. Recent advances in engineering optical devices and a greater understanding of the mechanisms of biological reflectance suggest such a strategy may now be viable. Here we outline the challenges involved in such an effort and suggest three potential approaches that could enable its implementation. While the local benefits may be straightforward, determining the global externalities will require careful modelling efforts and gradually scaled field trials.     

Litterflow chemistry and nutrient uptake from the forest floor in northwest Amazonian forest ecosystems

Samples of the fraction of net rainfall passing through the forest floor collected at monthly intervals in four pristine forests in Colombian Amazonia, during the period between 1995–1997 were analysed for solute concentrations to estimate the element fluxes from the forest floor into the mineral soil and root nutrient uptake from these forest floors. Results were compared with inputs by throughfall, stemflow, litterfall and fine root decay. Element concentrations were tested for their relationship with litterflow amounts, rainfall intensity and length of the antecedent dry period and differences in element fluxes between ecosystems were assessed. Concentrations of elements in litterflow followed a similar pattern as those in throughfall, which indicates that element outputs from the forest floor are strongly related to those inputs in throughfall. In the forests studied, the average concentrations of elements as K, Mg, orthoP and the pH of the litterflow decreased relative to that in throughfall in most events, while the concentration of elements such as dissolved organic carbon, H, SO₄ and Si increased in litterflow from these forests. Element concentrations in litterflow showed a poor correlation with variables such as litterflow amounts, rainfall intensity and antecedent dry period, except for K which showed a significant correlation (p>0.95) with analysed variables in all forests. Outputs were significantly different between forests (p>0.95); these fluxes, which particularly concerned cations, being the largest in the flood plain, while for anions outputs increased from the flood plain to the sedimentary plain. After adding the nutrient contributed by litter decomposition and fine root decay, the net outputs of main elements from the forest floors were still smaller than inputs by net precipitation (throughfall+stemflow) indicating that the litter layers clearly acted as a sink for most nutrients. Accordingly, the element balances confirm that the forest floors acted as a sink for nutrients coming in by throughfall, stemflow, litterfall and fine root decomposition. P, Mg and N appeared to be the most limiting nutrients and the forests studied efficiently recycled these nutrients.     

Effect of melatonin on vascular reactivity in pancreatectomized rats

The present study was undertaken to assess whether the improvement of contractile performance of aortic rings by melatonin described in streptozotocin diabetic rats also occurs in another model of type I diabetes, the pancreatectomized rats. Adult male Wistar rats submitted to a subtotal pancreatectomy and exhibiting altered levels of fasting glucose and an abnormal tolerance glucose test, were used. Sham-operated laparotomized rats were employed as controls. Dose-response curves for acetylcholine-induced, endothelium-related relaxation of aortic rings (after previous exposure to phenylephrine) and for phenylephrine-induced vasoconstriction were conducted. This protocol was repeated with rings pre-incubated in a high glucose solution (44 mmol/l). Pancreatectomy decreased significantly acetylcholine-induced relaxation of aortic rings, but not phenylephrine-induced vasoconstriction, the effect being amplified by preincubation in high glucose solution. The deleterious effect of a high glucose medium was more pronounced in pancreatectomized rats. Melatonin (10(-5) M) did not modify acetylcholine-induced relaxation in normal glucose concentration but was effective to prevent the impairment of relaxation brought about by exposure to high glucose solution. The contractile response to phenylephrine of aortic rings obtained from pancreatectomized rats was not affected by melatonin. The results further support the improvement by melatonin of endothelial-mediated relaxation in blood vessels of diabetic rats.