Synthesis and anti-HCMV activity of 1-[ω-(phenoxy)alkyl]uracil derivatives and analogues thereof

HCMV infection represents a life-threatening condition for immunocompromised patients and newborn infants and novel anti-HCMV agents are clearly needed. In this regard, a series of 1-[ω-(phenoxy)alkyl]uracil derivatives were synthesized and examined for antiviral properties. Compounds 17, 20, 24 and 28 were found to exhibit highly specific and promising inhibitory activity against HCMV replication in HEL cell cultures with EC₅₀ values within 5.5–12 μM range. Further studies should be undertaken to elucidate the mechanism of action of these compounds and the structure–activity relationship for the linker region.     

Is Pain Intensity Really That Important to Assess in Chronic Pain Patients? A Study Based on the Swedish Quality Registry for Pain Rehabilitation (SQRP)

Background

Incorporating the patient''s view on care and treatment has become increasingly important for health care. Patients describe the variety of consequences of their chronic pain conditions as significant pain intensity, depression, and anxiety. We hypothesised that intensities of common symptoms in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. This study has three aims: 1) to determine the importance of different symptoms with respect to participation and ill-health; 2) to identify subgroups based on data concerning important symptoms; and 3) to determine the secondary consequences for the identified subgroups with respect to participation and health factors.

Methods and Subjects

This study is based on a cohort of patients referred to a multidisciplinary pain centre at a university hospital (n = 4645, participation rate 88%) in Sweden. The patients answered a number of questionnaires concerning symptoms, participation, and health aspects as a part of the Swedish Quality Registry for Pain Rehabilitation (SQRP).

Results

Common symptoms (such as pain intensity, depression, and anxiety) in patients with chronic pain showed great variability across subjects and 60% of the cohort had normal values with respect to depressive and anxiety symptoms. Pain intensity more than psychological symptoms showed stronger relationships with participation and health. It was possible to identify subgroups based on pain intensity, depression, and anxiety. With respect to participation and health, high depressive symptomatology had greater negative consequences than high anxiety.

Conclusions

Common symptoms (such as pain intensity and depressive and anxiety symptoms) in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups.     

MOR Is Not Enough: Identification of Novel mu-Opioid Receptor Interacting Proteins Using Traditional and Modified Membrane Yeast Two-Hybrid Screens

The mu-opioid receptor (MOR) is the G-protein coupled receptor primarily responsible for mediating the analgesic and rewarding properties of opioid agonist drugs such as morphine, fentanyl, and heroin. We have utilized a combination of traditional and modified membrane yeast two-hybrid screening methods to identify a cohort of novel MOR interacting proteins (MORIPs). The interaction between the MOR and a subset of MORIPs was validated in pulldown, co-immunoprecipitation, and co-localization studies using HEK293 cells stably expressing the MOR as well as rodent brain. Additionally, a subset of MORIPs was found capable of interaction with the delta and kappa opioid receptors, suggesting that they may represent general opioid receptor interacting proteins (ORIPS). Expression of several MORIPs was altered in specific mouse brain regions after chronic treatment with morphine, suggesting that these proteins may play a role in response to opioid agonist drugs. Based on the known function of these newly identified MORIPs, the interactions forming the MOR signalplex are hypothesized to be important for MOR signaling and intracellular trafficking. Understanding the molecular complexity of MOR/MORIP interactions provides a conceptual framework for defining the cellular mechanisms of MOR signaling in brain and may be critical for determining the physiological basis of opioid tolerance and addiction.     

Synthesis and Bioactivity of Novel Trisubstituted Triazole Nucleosides

A series of novel trisubstituted 1,2,3-triazole purine nucleosides were efficiently synthesized via Huisgen 1,3-dipolar cycloaddition in good yields. Bioactivity against cytomegalovirus (CMV) and varicella-zoster virus (VZV) in human embryonic lung cell cultures was evaluated and all compounds show low antiviral activity.     

To Smell you Better: Prior Food Deprivation Increases Herbivore Insect Responsiveness to Host Plant Odor Cues

Hunger plays a crucial role in insect feeding behavior, however food deprivation is rarely considered when insect responses to plant host and related chemical stimuli are investigated. Here we assessed, by means of experiments with Y-tube olfactometer, the effect of food deprivation time on the response of a specialist (Xanthogaleruca luteola) and a generalist (Diabrotica speciosa) herbivore beetle species (Coleoptera: Chrysomelidae) to odor cues of their respective host plants. Increasing food deprivation periods enhanced responses to host plant odor in both species, with insects remaining for longer in the olfactometer arm carrying plant odor than in the control, moving less frequently between olfactometer arms, and being more efficient in moving towards the plant odor as their first choice. These trends were less significant in the generalist species, which also required a longer fasting threshold (48 h) in comparison with the specialist (8 h). Our results, showing that prior food deprivation time can influence insect herbivore responsiveness to plant stimuli and that those effects may vary between species, highlight the risk of neglecting this factor in studies involving insect responses to host or chemical stimuli.     

Rapid method to obtain high quality nuclear and chromosome images directly from living cells in the Characeae

This study focused on a method based on the capacity of cationic dyes to stain only the nucleus and chromosomes in cells subjected to either acid or alkaline hydrolysis. The method and the squash were optimized for the Characeae and were described in detail. Nuclei from vegetative shoot apices and antheridial filament cells of unfixed, fixed and herbarium material of Nitella opaca were investigated using the Azure A or Toulidine Blue stains. Comparisons with some other staining methods, used in the previous studies, were also reported. The Azure A/Toulidine Blue method is useful to obtain clear images of chromosome morphology comparable or higher to that obtained with Feulgen or Aceto‐Orcein. It requires little time and a less complicated procedure in comparison with other staining methods.     

Identification of flavonoids as regulators of YbeY activity in Liberibacter asiaticus

Liberibacter asiaticus is the prevalent causative pathogen of Huanglongbing or citrus greening disease, which has resulted in a devastating crisis in the citrus industry. A thorough understanding of this pathogen's physiology and mechanisms to control cell survival is critical in the identification of therapeutic targets. YbeY is a highly conserved bacterial RNase that has been implicated in multiple roles. In this study, we evaluated the biochemical characteristics of the L. asiaticus YbeY (CLIBASIA_01560) and assessed its potential as a target for antimicrobials. YbeY_Las was characterized as an endoribonuclease with activity on 3′ and 5′ termini of 16S and 23S rRNAs, and the capacity to suppress the E. coli ΔybeY phenotype. We predicted the YbeY_Las protein:ligand interface and subsequently identified a flavone compound, luteolin, as a selective inhibitor. Site-directed mutagenesis was subsequently used to identify key residues involved in the catalytic activity of YbeY_Las. Further evaluation of naturally occurring flavonoids in citrus trees indicated that both flavones and flavonols had potent inhibitory effects on YbeY_Las. Luteolin was subsequently examined for efficacy against L. asiaticus in Huanglongbing-infected citrus trees, where a significant reduction in L. asiaticus gene expression was observed.     

Virulence potential and genetic diversity of Aeromonas caviae, Aeromonas veronii, and Aeromonas hydrophila clinical isolates from Mexico and Spain: a comparative study

A comparative study of 109 Aeromonas clinical isolates belonging to the 3 species most frequently isolated from patients with diarrhea in Mexico and Spain was performed to investigate the distribution of 3 prominent toxin genes and the gene encoding flagellin of lateral flagella; 4 well-established virulence factors in the genus Aeromonas. The aerolysin-hemolysin toxin genes were the most prevalent, being present in 89% of the total isolates. The ast toxin gene was conspicuously absent from the Aeromonas caviae and Aeromonas veronii groups but was present in 91% of the Aeromonas hydrophila isolates. Both the alt toxin gene and the lafA flagellin gene also had a low incidence in A. caviae and A. veronii. Differences in the prevalence of alt and lafA were observed between isolates from Mexico and Spain, confirming genus heterogeneity according to geographic location. Carriage of multiple toxin genes was primarily restricted to A. hydrophila isolates, suggesting that A. caviae and A. veronii isolates circulating in Mexico and Spain possess a limited array of virulence genes. Enterobacterial repetitive intergenetic consensus - polymerase chain reaction showed that the Aeromonas populations sampled lack dominant clones and were genetically heterogeneous, with A. caviae being the most diverse species. Further surveys of virulence determinants in genetically heterogeneous populations of Aeromonas isolates circulating worldwide are required to enhance the understanding of their capacity to cause disease.     

The use of systems analysis methods in the sustainable management of wetlands

The management of the utilisation of natural resources from wetland ecosystems is a multiobjective and complex task. The creation of innovative decision making tools for sustainable wetland resource utilisation is an important challenge for the future. This is particularly crucial in the light of the growing shortages for high quality freshwater and the vanishing habitat for a large number of wetland fauna and flora species. Because wetlands combine attributes of both aquatic and terrestrial ecosystems, wetlands are often at the crossroads of a number of disciplines with no specific discipline of its own. Therefore, management programmes require a multidisciplinary approach founded on a systematic monitoring of key biological and physical parameters. A European Commission DG XII research project dedicated to the development of management tools for wetland resources in Latin America is being developed by a multidisciplinary team of researchers from eight universities, located in four EU member states, Argentina and Brazil. The study sites that will be utilised for this analysis are two shallow lakes in Northeast Argentina within the large (13000 km²) wetland `Esteros del Ibera'. Continuous and periodic in-situ monitoring instrumentation has been installed in a long term monitoring programme of hydrological and meteorological factors, coupled with monthly biological and ecological data gathering. Potential future scenarios for wetland resource use are being discussed in a series of public meetings with key provincial and local actors (teachers, university professors, clergymen, local business persons and politicians). These meetings address both the small scale modifications of wetland use (water extraction for agriculture, tourism, controlled hunting) as well as regional projects related to the creation of large scale economic development (forestation, modification of nearby waterways for hydroelectric production and increased river transportation). Models are developed relating the chemical, physical, biological and ecological parameters monitored. These models will be dedicated to analysing the effects of development on wetland functions and resource quality. An economic model will be created to evaluate potential modifications in wetland functions in the local and regional socio-economic context. Evaluation instruments are developed and tested which include; qualitative models using loop analysis, goal functions based on the aquatic trophic web and the overall energy flux in the lagoon, and a geographical information system utilising satellite images. The purpose of these instruments is to examine the overall impacts of development alternatives on resource quality and ecosystem integrity, as well as demonstrating key parameters that should be more closely monitored. The final package will include an evaluation of the potential impacts of the development scenarios proposed by the key actors, recommendations to reduce specific impacts through alternative technologies, together with a monitoring programme and analysis tools for improved decision making in wetland resource management.