Prevalence of GB virus type C in urban Americans infected with human immunodeficiency virus type 1

Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980's. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica http://www.htlvconference.org.jm/. Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV.     

Fabrication of Nanosuspension Directly Loaded Fast-Dissolving Films for Enhanced Oral Bioavailability of Olmesartan Medoxomil: <Emphasis Type="Italic">In Vitro</Emphasis> Characterization and Pharmacokinetic Evaluation in Healthy Human Volunteers

Olmesartan medoxomil (OM) is an antihypertensive drug with poor water solubility and low oral bioavailability (28.6%). Accordingly, this study aimed to formulate and evaluate OM nanosuspension incorporated into oral fast-dissolving films (FDFs) for bioavailability enhancement. OM nanosuspension was prepared by antisolvent-precipitation-ultrasonication method and characterized regarding particle size (122.67?±?5.03 nm), span value (1.40?±?0.51), and zeta potential (??46.56?±?1.20 mV). Transmission electron microscopy (TEM) of the nanosuspension showed spherical non-aggregating nanoparticles. The nanosuspension was then directly loaded into FDFs by solvent casting technique. A full factorial design (2²?×?3¹) was implemented for optimization of the FDFs using Design-Expert® software. Physical and mechanical characteristics in addition to dissolution profiles of the FDFs were investigated. The optimum formula (FDF1) showed 0.43?±?0.02 kg/mm² tensile strength, 20.50?±?2.12 s disintegration time, and 87.53?±?2.50 and 95.99?±?0.25% OM dissolved after 6 and 10 min, respectively. Accelerated and long-term shelf stability studies confirmed the stability of FDF1. More than 75% OM was dissolved within 10 min from FDF1 compared with 9.80 and 47.80% for films prepared using coarse drug powder and market tablet, respectively. Relative bioavailability of FDF1 compared to market tablet was assessed in healthy human volunteers. The C_max value increased significantly from 66.62?±?14.95 to 179.28?±?23.96 ng/mL for market tablet and FDF1, respectively. Similarly, the AUC_0–72 value significantly increased from 498.36?±?217.46 to 1083.67?±?246.32 ng h/mL for market tablet and FDF1, respectively. Relative bioavailability of FDF1 was 209.28%. The highlighted results verified the effectiveness of OM nanosuspension-loaded FDFs in improving OM bioavailability.     

Biochemical Characterization of Chloromethane Emission from the Wood-Rotting Fungus Phellinus pomaceus

Many wood-rotting fungi, including Phellinus pomaceus, produce chloromethane (CH₃Cl). P. pomaceus can be cultured in undisturbed glucose mycological peptone liquid medium to produce high amounts of CH₃Cl. The biosynthesis of CH₃Cl is catalyzed by a methyl chloride transferase (MCT), which appears to be membrane bound. The enzyme is labile upon removal from its natural location and upon storage at low temperature in its bound state. Various detergents failed to solubilize the enzyme in active form, and hence it was characterized by using a membrane fraction. The enzyme had a sharp pH optimum between 7 and 7.2. Its apparent K_m for Cl⁻ (ca. 300 mM) was much higher than that for I⁻ (250 μM) or Br⁻ (11 mM). A comparison of these K_m values to the relative in vivo methylation rates for different halides suggests that the real K_m for Cl⁻ may be much lower, but the calculated value is high because the CH₃Cl produced is used immediately in a coupled reaction. Among various methyl donors tested, S-adenosyl-l-methionine (SAM) was the only one that supported significant methylation by MCT. The reaction was inhibited by S-adenosyl-l-homocysteine, an inhibitor of SAM-dependent methylation, suggesting that SAM is the natural methyl donor. These findings advance our comprehension of a poorly understood metabolic sector at the origin of biogenic emissions of halomethanes, which play an important role in atmospheric chemistry.Halogenated organic compounds are ubiquitous in nature (29). They participate in the depletion of stratospheric ozone and have a profound impact on atmospheric chemistry (4, 18, 24). Although the dominant sources of these compounds are biogenic emissions (12, 25, 26, 28), their significance to the emitter organisms is rather poorly understood, with only a few indications of the roles they might play. In fungi, halomethanes serve as methyl group donors for the biosynthesis of esters, anisoles, and veratryl alcohol (9, 11). In algae, halomethanes are by-products of reactions in which scavenging of H₂O₂ releases HOBr, which is presumed to be a defense molecule against bacteria, fungi, and herbivores (23, 27). A recent report (28) that a marine alga, Endocladia muricata, and a salt-tolerant plant, Mesembryanthemum crystallinum, could methylate Cl⁻ ions to chloromethane (CH₃Cl) triggered speculation that this may be a mechanism for Cl⁻ detoxification and salt tolerance. The S-adenosyl-l-methionine (SAM)-dependent methyl chloride transferase (MCT) that catalyzes this reaction was partially purified from E. muricata (28). The enzyme can also use I⁻ and Br⁻ as substrates.These results suggest possibilities for engineering a Cl⁻ detoxification capability into crop plants, many of which are sensitive to Cl⁻ (6, 17). Wood-rotting fungi of the family Hymenochaetaceae are the most efficient producers of CH₃Cl (5, 7, 13). Phellinus pomaceus converts Cl⁻ to CH₃Cl with over 90% efficiency, even at extremely low concentrations of the ion (7). A low MCT activity was detected in cell extracts of this fungus (28).Halomethanes are the primary carriers of halogens between the biosphere and the atmosphere (4, 18) and therefore play pivotal roles in the effect of halogens on atmospheric chemistry and the integrity of the ozone layer (24). Since biogenic sources are major contributors of atmospheric halomethanes (7, 12, 18, 25, 28), attempts to understand atmospheric composition must include an understanding of the metabolic processes underlying the generation of these gases. In addition, engineering a Cl⁻ detoxification capability into plants depends on the identification of novel metabolic pathways and an understanding of their regulation. Within this dual context, our objective was to determine the biochemical nature of the CH₃Cl-evolving system of P. pomaceus.     

Type I Interferon Induction Is Detrimental during Infection with the Whipple's Disease Bacterium,Tropheryma whipplei

Macrophages are the first line of defense against pathogens. Upon infection macrophages usually produce high levels of proinflammatory mediators. However, macrophages can undergo an alternate polarization leading to a permissive state. In assessing global macrophage responses to the bacterial agent of Whipple''s disease, Tropheryma whipplei, we found that T. whipplei induced M2 macrophage polarization which was compatible with bacterial replication. Surprisingly, this M2 polarization of infected macrophages was associated with apoptosis induction and a functional type I interferon (IFN) response, through IRF3 activation and STAT1 phosphorylation. Using macrophages from mice deficient for the type I IFN receptor, we found that this type I IFN response was required for T. whipplei-induced macrophage apoptosis in a JNK-dependent manner and was associated with the intracellular replication of T. whipplei independently of JNK. This study underscores the role of macrophage polarization in host responses and highlights the detrimental role of type I IFN during T. whipplei infection.     

Phenotypic and Genotypic Analysis of Newly Obtained Interspecific Hybrids in the Campanula Genus

Interspecific hybridisation creates new phenotypes within several ornamental plant species including the Campanula genus. We have employed phenotypic and genotypic methods to analyse and evaluate interspecific hybridisation among cultivars of four Campanula species, i.e. C. cochleariifolia, C. isophylla, C. medium and C. formanekiana. Hybrids were analysed using amplified fragment length polymorphism (AFLP), flow cytometry and biometrical measurements. Results of correlation matrices demonstrated heterogeneous phenotypes for the parental species, which confirmed our basic premise for new phenotypes of interspecific hybrids. AFLP assays confirmed the hybridity and identified self-pollinated plants. Limitation of flow cytometry analysis detection was observed while detecting the hybridity status of two closely related parents, e.g. C. cochleariiafolia × C. isophylla. Phenotypic characteristics such as shoot habitus and flower colour were strongly influenced by one of the parental species in most crosses. Rooting analysis revealed that inferior rooting quality occurred more often in interspecific hybrids than in the parental species. Only interspecific hybrid lines of C. formanekiana ‘White’ × C. medium ‘Pink’ showed a high rooting level. Phenotype analyses demonstrated a separation from the interspecific hybrid lines of C. formanekiana ‘White’ × C. medium ‘Pink’ to the other clustered hybrids of C. formanekiana and C. medium. In our study we demonstrated that the use of correlation matrices is a suitable tool for identifying suitable cross material. This study presents a comprehensive overview for analysing newly obtained interspecific hybrids. The chosen methods can be used as guidance for analyses for further interspecific hybrids in Campanula, as well as in other ornamental species.     

PtaRHE1, a Populus tremula × Populus alba RING‐H2 protein of the ATL family,has a regulatory role in secondary phloem fibre development

REALLY INTERESTING NEW GENE (RING) proteins play important roles in the regulation of many processes by recognizing target proteins for ubiquitination. Previously, we have shown that the expression of PtaRHE1, encoding a Populus tremula × Populus alba RING‐H2 protein with E3 ubiquitin ligase activity, is associated with tissues undergoing secondary growth. To further elucidate the role of PtaRHE1 in vascular tissues, we have undertaken a reverse genetic analysis in poplar. Within stem secondary vascular tissues, PtaRHE1 and its corresponding protein are expressed predominantly in the phloem. The downregulation of PtaRHE1 in poplar by artificial miRNA triggers alterations in phloem fibre patterning, characterized by an increased portion of secondary phloem fibres that have a reduced cell wall thickness and a change in lignin composition, with lower levels of syringyl units as compared with wild‐type plants. Following an RNA‐seq analysis, a biological network involving hormone stress signalling, as well as developmental processes, could be delineated. Several candidate genes possibly associated with the altered phloem fibre phenotype observed in amiRPtaRHE1 poplar were identified. Altogether, our data suggest a regulatory role for PtaRHE1 in secondary phloem fibre development.     

Road Traffic Injury Prevention Initiatives: A Systematic Review and Metasummary of Effectiveness in Low and Middle Income Countries

Background

Road traffic injuries (RTIs) are a growing but neglected global health crisis, requiring effective prevention to promote sustainable safety. Low- and middle-income countries (LMICs) share a disproportionately high burden with 90% of the world’s road traffic deaths, and where RTIs are escalating due to rapid urbanization and motorization. Although several studies have assessed the effectiveness of a specific intervention, no systematic reviews have been conducted summarizing the effectiveness of RTI prevention initiatives specifically performed in LMIC settings; this study will help fill this gap.

Methods

In accordance with PRISMA guidelines we searched the electronic databases MEDLINE, EMBASE, Scopus, Web of Science, TRID, Lilacs, Scielo and Global Health. Articles were eligible if they considered RTI prevention in LMICs by evaluating a prevention-related intervention with outcome measures of crash, RTI, or death. In addition, a reference and citation analysis was conducted as well as a data quality assessment. A qualitative metasummary approach was used for data analysis and effect sizes were calculated to quantify the magnitude of emerging themes.

Results

Of the 8560 articles from the literature search, 18 articles from 11 LMICs fit the eligibility and inclusion criteria. Of these studies, four were from Sub-Saharan Africa, ten from Latin America and the Caribbean, one from the Middle East, and three from Asia. Half of the studies focused specifically on legislation, while the others focused on speed control measures, educational interventions, enforcement, road improvement, community programs, or a multifaceted intervention.

Conclusion

Legislation was the most common intervention evaluated with the best outcomes when combined with strong enforcement initiatives or as part of a multifaceted approach. Because speed control is crucial to crash and injury prevention, road improvement interventions in LMIC settings should carefully consider how the impact of improvements will affect speed and traffic flow. Further road traffic injury prevention interventions should be performed in LMICs with patient-centered outcomes in order to guide injury prevention in these complex settings.     

New contributions to propagation of pineapple (<Emphasis Type="Italic">Ananas comosus</Emphasis> L. Merr) in temporary immersion bioreactors

Summary Plantlets propagated in temporary immersion bioreactors (TIB) have better performance than those propagated by conventional methods such as micropropagation. This is as a result of a better handling of the in vitro atmosphere and the nutrition. The object of this study to further improve the cultivation conditions by introducting photomixotrophism as an intermediate link of photoautotrophic growth during ex vitro acclimatization. For this purpose the effects of light were evaluated by different parameters such as photosynthetic photon flux density (PPF), sucrose concentration, and CO₂ enrichment levels on CO₂ evolution inside the culture vessels. It was observed that CO₂ diminished upon light exposure and increased in the dark according to the photoperiod during each cycle of immersion. With this approach it was possible to increase the photomixotrophism in the pineapple plantlets propagated in TIB. It was demonstrated that light is the factor with more influence on plant quality, although under these conditions they seem to use more of the nutrients of the medium than their photoassimilates. The propagation of pineapple in TIB involves three phases: proliferation, pre-elongation, and final growth of the buds. In each phase the cultivation conditions were determined to substitute for sterilization by autoclaving, to improve the quality of the plants, to elevate the efficiency of the process, and to reduce production costs. The buds that grew in the temporary immersion bioreactor with the presence of Vitrofural (G-1) achieved the best indicators of growth. Significant increases were observed in the leaf area, dry mass of the buds, and chlorophyll contents.     

Förster energy-transfer studies between Trp residues of alpha1-acid glycoprotein (orosomucoid) and the glycosylation site of the protein

Energy-transfer studies between Trp residues of alpha(1)-acid glycoprotein and the fluorescent probe Calcofluor White were performed. Calcofluor White interacts with carbohydrate residues of the protein, while the three Trp residues are located at the surface (Trp-160) and in hydrophobic domains of the protein (Trp-25 and Trp-122). Binding of Calcofluor to the protein induces a decrease in the fluorescence intensity of the Trp residues accompanied by an increase of that of Calcofluor White. Efficiency (E) of Trp fluorescence quenching was determined to be equal to 45%, and the F?rster distance R(o), at which the efficiency of energy transfer is 50%, was calculated to be 18.13 A. This low distance and the value of the efficiency clearly indicate that energy transfer between Trp residues and Calcofluor White is weak.     

A comparison between methods for linkage disequilibrium fine mapping of quantitative trait loci

We present a maximum likelihood method for mapping quantitative trait loci that uses linkage disequilibrium information from single and multiple markers. We made paired comparisons between analyses using a single marker, two markers and six markers. We also compared the method to single marker regression analysis under several scenarios using simulated data. In general, our method outperformed regression (smaller mean square error and confidence intervals of location estimate) for quantitative trait loci with dominance effects. In addition, the method provides estimates of the frequency and additive and dominance effects of the quantitative trait locus.