Lack of Significant Elevation of Myeloid-Derived Suppressor Cells in Peripheral Blood of Chronically Hepatitis C Virus-Infected Individuals

Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunosuppressive function. Compared to the level in healthy controls (HC), no elevation of MDSC in chronic hepatitis C (cHEP-C) patients was found, and there was no difference in MDSC based on genotype or viral load (P > 0.25). Moreover, MDSC of cHEP-C patients inhibited CD8 T cell function as efficiently as MDSC of HC did. Since we detected neither quantitative nor qualitative differences in MDSC of cHEP-C patients relative to those of HC, we postulate that MDSC in peripheral blood are most likely not significant regarding immune dysfunction in cHEP-C.     

Resistance to pathogens in terpene down-regulated orange fruits inversely correlates with the accumulation of D-limonene in peel oil glands

Volatile organic compounds (VOCs) are secondary metabolites acting as a language for the communication of plants with the environment. In orange fruits, the monoterpene D-limonene accumulates at very high levels in oil glands from the peel. Drastic down-regulation of D-limonene synthase gene expression in the peel of transgenic oranges harboring a D-limonene synthase transgene in antisense (AS) configuration altered the monoterpene profile in oil glands, mainly resulting in reduced accumulation of D-limonene. This led to fruit resistance against Penicillium digitatum (Pd), Xanthomonas citri subsp. citri (Xcc) and other specialized pathogens. Here, we analyze resistance to pathogens in independent AS and empty vector (EV) lines, which have low, medium or high D-limonene concentrations and show that the level of resistance is inversely related to the accumulation of D-limonene in orange peels, thus explaining the need of high D-limonene accumulation in mature oranges in nature for the efficient attraction of specialized microorganism frugivores.     

Docking and molecular dynamics studies of peripheral site ligand–oximes as reactivators of sarin-inhibited human acetylcholinesterase

In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.     

Seed germination traits of Ailanthus altissima,Phytolacca americana and Robinia pseudoacacia in response to different thermal and light requirements

Invasion of alien plant species (IAS) represents a serious environmental problem, particularly in Europe, where it mainly pertains to urban areas. Seed germination traits contribute to clarification of invasion dynamics. The objective of this research was to analyze how different light conditions (i.e., 12-hr light/12-hr darkness and continuous darkness) and temperature regimes (i.e., 15/6°C, 20/10°C and 30/20°C) trigger seed germination of Ailanthus altissima (AA), Phytolacca americana (PA) and Robinia pseudoacacia (RP). The relationship between seed germination and seed morphometric traits was also analyzed. Our findings highlight that temperature rather than light was the main environmental factor affecting germination. RP germinated at all tested temperatures, whereas at 15/6°C seeds of AA and PA showed physiological dormancy. RP had a higher germination capacity at a lower temperature, unlike AA and PA, which performed better at the highest temperatures. Light had a minor role in seed germination of the three species. Light promoted germination only for seeds of PA, and final germination percentage was 1.5-fold higher in light than in continuous darkness. Seed morphometric traits (thickness [T], area [A] and volume [V]) had a significant role in explaining germination trait variations. The results highlight the importance of increasing our knowledge on seed germination requirements to predict future invasiveness trends. The increase in global temperature could further advantage AA and PA in terms of germinated seeds, as well as RP by enhancing the germination velocity, therefore compensating for a lower germination percentage of this species at the highest temperatures.     

Statins and Antimicrobial Effects: Simvastatin as a Potential Drug against Staphylococcus aureus Biofilm

Statins are important lipid-lowering agents with other pleiotropic effects. Several studies have explored a possible protective effect of statins to reduce the morbidity and mortality of many infectious diseases. Staphylococcus aureus is one of the main pathogens implicated in nosocomial infections; its ability to form biofilms makes treatment difficult. The present study observed the MIC of atorvastatin, pravastatin and simvastatin against S. aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis. Simvastatin was the only agent with activity against clinical isolates and reference strains of methicilin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Thus, the effects of simvastatin on the growth, viability and biofilm formation of S. aureus were tested. In addition, a possible synergistic effect between simvastatin and vancomycin was evaluated. Simvastatin’s MIC was 15.65 µg/mL for S. aureus 29213 and 31.25 µg/mL for the other strains of S. aureus. The effect of simvastatin was bactericidal at 4xMIC and bacteriostatic at the MIC concentration. No synergistic effect was found between simvastatin and vancomycin. However, the results obtained against S. aureus biofilms showed that, in addition to inhibiting adhesion and biofilm formation at concentrations from 1/16xMIC to 4xMIC, simvastatin was also able to act against mature biofilms, reducing cell viability and extra-polysaccharide production. In conclusion, simvastatin showed pronounced antimicrobial activity against S. aureus biofilms, reducing their formation and viability.     

Unidirectional potentiation of binding between two anti-FBP MAbs: Evaluation of involved mechanisms

The monoclonal antibody MOv19 directed to a folate binding protein shows temperature-dependent potentiation of binding of the noncompeting monoclonal antibody MOv18 to the relevant antigen, but the mechanism involved in this phinomenon had remained unclear. Use of chimeric versions of both monoclonal antibodies and the F(ab′)₂ and fan fragments of MOv19 revealed an increment in MOv18 binding in all combinations irrespective of the orgin of the Fc portin of the monoclonal antibody. The potentiating effect of bivalent MOv19 fragments on ¹²⁵l-MOv18 binding was similar to that of the entire monoclonal antibody and occurred at saturating concentrations of both reagents at which monovalent binding prevails. Similarly, the monovalent fragment also induced a significant increase in MOv18 bunding. Howener, the potentiation sccurred only at very high concentrations of antibody fragment. Homologous inhibition was drastically reduced using MOv19 Fab fragment, suggesting a low binding stability of the monovalent reagent. Immunoblotting analysis and binding in the presence of exogenous purified folate binding protein indicated a cross-linking between soluble and cell surface molecules mediated by the bivalent monoclonal antibodies. The extentof the increase in MOv18 binging at O°C with high amounts of exogenous folate binding protein was lower than that obtained at 37⁰C in the absence of added molecule. Release of ¹²⁵l-MOv18 from the cell surface was significantly higher in the absence of MOv19 than in its presence. Affinity constant values of ¹²⁵l-MOv18 binding evaluated in the presence of MOv19 or control monoclonal antibody MINT5 were comparable, whereas the number of binding sites per cell detected by ¹²⁵l-MOv18 was significantly higher in the presence of MOv19 than MINT5. Together, the data suggest that monoclonal antibody MOv19 induces a conformational change of the molecule it binds that increases the number of antigenic sites anvailable for MOv18 binding and, in turn, the binding stability of the latter, MOv19 bivalency also contributes to the MOv18 binding increment by cross-linking released and cell surface–anchored folate binding protein molecules. © Wiley-Liss, Inc.     

Advanced phenology of intraguild predators shifts herbivore host plant preference and performance

1. The abundance of insect herbivores is mediated by interactions with higher and lower trophic levels. This research asks (i) how phenological change across trophic levels affects host plant quality and selection for aphids, and (ii) what higher trophic level mechanisms drive aphid abundance. 2. Ligusticum porteri is a perennial host for the sap-feeding aphid Aphis asclepiadis and intraguild mirid predators (chiefly Lygus hesperus) in Colorado. We used long-term observational data to discover that aphids and mirids respond differently to phenological cues. These unique responses can impact aphid abundance through changes to host plant selection and quality. 3. We used behavioural choice assays to assess how advanced mirid phenology influences aphid host plant selection. More alates landed and reproduced on mirid-free control plants relative to host plants with prior mirid feeding. However, this preference did not correlate with aphid performance when we compared aphid relative growth rates between treatments. This suggests that advanced mirid phenology would impact aphid populations more through host plant choice, rather than reductions in host quality. The addition of mirids to experimental aphid colonies also demonstrated reduced aphid colony growth via predation. 4. We measured plant cues involved in host selection and found differences in volatile composition between plants with prior mirid feeding compared to control plants, providing the potential for aphids to detect enemy-free space using volatile cues.     

Diversity of spiders and orthopterans respond to intra-seasonal and spatial environmental changes

Our understanding of arthropod responses to environmental pressures is limited, especially for the poorly studied Mediterranean region. In the light of likely further environmental change and the need for protocols for rapid biodiversity assessment, we measured how the abundance and species richness of two taxa, ground spiders and Orthoptera, belonging to different functional groups, fluctuates intra- seasonally (early-mid-late summer) and across habitat types (grasslands, maquis, forests). We also tested their surrogate value. Spiders were found to have higher species richness and abundance almost throughout the investigation. Orthoptera had lower species richness and abundance in forests compared to grasslands and maquis, while no significant difference between habitats was revealed for spiders. Early-summer was the richest period for spiders while mid-summer was the richest for Orthoptera. Canopy cover was found to significantly influence community composition of both groups, while herb height and cover of stones was a determinant factor for Orthoptera only. There was a significant congruence between the two groups and Orthoptera provided the best complementary network. Our results show that diversity patterns of both spiders and Orthoptera are sensitive to environmental changes even over short time-scales (e.g. within the summer period) and space (e.g. across different habitat types), suggesting that small inexpensive experimental designs may still reveal community dynamics. For conservation purposes, we advise a focus on variables regulating habitat heterogeneity and microhabitat characteristics. We provide a list of the most influential species and propose the most effective network for obtaining information on the local fauna.     

Orexinergic Neurotransmission in Temperature Responses to Methamphetamine and Stress: Mathematical Modeling as a Data Assimilation Approach

Experimental Data

Orexinergic neurotransmission is involved in mediating temperature responses to methamphetamine (Meth). In experiments in rats, SB-334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg decreases late temperature responses (t>60 min) to an intermediate dose of Meth (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates early responses (t<60 min) to intermediate and high doses (5 and 10 mg/kg) of Meth. As pretreatment with SB also inhibits temperature response to the stress of injection, traditional statistical analysis of temperature responses is difficult.

Mathematical Modeling

We have developed a mathematical model that explains the complexity of temperature responses to Meth as the interplay between excitatory and inhibitory nodes. We have extended the developed model to include the stress of manipulations and the effects of SB. Stress is synergistic with Meth on the action on excitatory node. Orexin receptors mediate an activation of on both excitatory and inhibitory nodes by low doses of Meth, but not on the node activated by high doses (HD). Exaggeration of early responses to high doses of Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and lowers the activation threshold, while the higher dose suppresses the inhibitory component. Using a modeling approach to data assimilation appears efficient in separating individual components of complex response with statistical analysis unachievable by traditional data processing methods.