Viremia and antibody response in green monkeys (Chlorocebus aethiops sabaeus) infected with dengue virus type 2: A potential model for vaccine testing

The increasingly limited availability and high cost of the hitherto most commonly used monkey species in dengue vaccine research has augmented the importance of identifying alternative suitable models for these studies. In this study we examined the capacity of green monkeys ( Chlorocebus aethiops sabaeus ) to develop dengue viremia, and thus provide a potential model for dengue vaccine testing. Monkeys were inoculated with two different doses of dengue virus type 2. All animals in both groups became viremic after inoculation of the virus. In the lower dose group, mean viremia duration of 5.66 days was detected, whereas in the group that received the 10⁶ PFU dose, viremia had a mean duration of only 1.66 days. Antibody titers were similar to those obtained in previous experiments with rhesus and cynomolgus macaques. We conclude that green monkeys develop viremia and antibody responses and therefore provide a potential model for the preclinical evaluation of novel candidates for dengue vaccines.     

Species-Specific Viromes in the Ancestral Holobiont Hydra

Recent evidence showing host specificity of colonizing bacteria supports the view that multicellular organisms are holobionts comprised of the macroscopic host in synergistic interdependence with a heterogeneous and host-specific microbial community. Whereas host-bacteria interactions have been extensively investigated, comparatively little is known about host-virus interactions and viral contribution to the holobiont. We sought to determine the viral communities associating with different Hydra species, whether these viral communities were altered with environmental stress, and whether these viruses affect the Hydra-associated holobiont. Here we show that each species of Hydra harbors a diverse host-associated virome. Primary viral families associated with Hydra are Myoviridae, Siphoviridae, Inoviridae, and Herpesviridae. Most Hydra-associated viruses are bacteriophages, a reflection of their involvement in the holobiont. Changes in environmental conditions alter the associated virome, increase viral diversity, and affect the metabolism of the holobiont. The specificity and dynamics of the virome point to potential viral involvement in regulating microbial associations in the Hydra holobiont. While viruses are generally regarded as pathogenic agents, our study suggests an evolutionary conserved ability of viruses to function as holobiont regulators and, therefore, constitutes an emerging paradigm shift in host-microbe interactions.     

Objectively Measured Physical Activity in European Adults: Cross-Sectional Findings from the Food4Me Study

Background

Comparisons of objectively measured physical activity (PA) between residents of European countries measured concurrently with the same protocol are lacking. We aimed to compare PA between the seven European countries involved in the Food4Me Study, using accelerometer data collected remotely via the Internet.

Methods

Of the 1607 participants recruited, 1287 (539 men and 748 women) provided at least 3 weekdays and 2 weekend days of valid accelerometer data (TracmorD) at baseline and were included in the present analyses.

Results

Men were significantly more active than women (physical activity level = 1.74 vs. 1.70, p < 0.001). Time spent in light PA and moderate PA differed significantly between countries but only for women. Adherence to the World Health Organization recommendation to accumulate at least 150 min of moderate-equivalent PA weekly was similar between countries for men (range: 54–65%) but differed significantly between countries for women (range: 26–49%). Prevalence estimates decreased substantially for men and women in all seven countries when PA guidelines were defined as achieving 30 min of moderate and vigorous PA per day.

Conclusions

We were able to obtain valid accelerometer data in real time via the Internet from 80% of participants. Although our estimates are higher compared with data from Sweden, Norway, Portugal and the US, there is room for improvement in PA for all countries involved in the Food4Me Study.     

E1a gene expression blocks the ERK1/2 signaling pathway by promoting nuclear localization and MKP up-regulation: implication in v-H-Ras-induced senescence

In response to oncogenic signals, cells have developed safe mechanisms to avoid transformation through activation of a senescence program. Upon v-H-Ras overexpression, normal cells undergo senescence through several cellular processes, including activation of the ERK1/2 pathway. Interestingly, the E1a gene from adenovirus 5 has been shown to rescue cells from senescence by a yet unknown mechanism. We investigated whether E1a was able to interfere with the ERK1/2 signaling pathway to rescue cells from v-H-Ras-mediated senescence. Our results show that, E1a overexpression blocks v-H-Ras-mediated ERK1/2 activation by two different and concomitant mechanisms. E1a through its ability to interfere with PKB/Akt activation induces the down-regulation of the PEA15 protein, an ERK1/2 nuclear export factor, leading to nuclear accumulation of ERK1/2. In addition to this, we show that E1a increases the expression of the inducible ERK1/2 nuclear phosphatases (MAPK phosphatases) MKP1/DUSP1 and DUSP5, which leads to ERK1/2 dephosphorylation. We confirmed our observations in the human normal diploid fibroblasts IMR90, in which we could also show that an E1a mutant, unable to bind retinoblastoma protein (pRb), cannot rescue cells from v-H-Ras-induced senescence. In conclusion, E1a is able to rescue from Ras-induced senescence by affecting ERK1/2 localization and phosphorylation.     

LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons

In this study, we examined the subcellular distribution and functions of LIMK1 in developing neurons. Confocal microscopy, subcellular fractionation, and expression of several epitope-tagged LIMK1 constructs revealed that LIMK1 is enriched in the Golgi apparatus and growth cones, with the LIM domain required for Golgi localization and the PDZ domain for its presence at neuritic tips. Overexpression of wild-type LIMK1 suppresses the formation of trans-Golgi derived tubules, and prevents cytochalasin D-induced Golgi fragmentation, whereas that of a kinase-defective mutant has the opposite effect. Transfection of wild-type LIMK1 accelerates axon formation and enhances the accumulation of Par3/Par6, insulin-like growth factor (IGF)1 receptors, and neural cell adhesion molecule (NCAM) at growth cones, while inhibiting the Golgi export of synaptophysin-containing vesicles. These effects were dependent on the Golgi localization of LIMK1, paralleled by an increase in cofilin phosphorylation and phalloidin staining in the region of the Golgi apparatus, and prevented by coexpression of constitutive active cofilin. The long-term overexpression of LIMK1 produces growth cone collapse and axon retraction, an effect that is dependent on its growth cone localization. Together, our results suggest an important role for LIMK1 in axon formation that is related with its ability to regulate Golgi dynamics, membrane traffic, and actin cytoskeletal organization.     

High yield of endoreduplication induced by ICRF-193: a topoisomerase II catalytic inhibitor

Previous studies have demonstrated that phenolic compounds, including genistein (4',5,7-trihydroxyisoflavone) and resveratrol (3,4',5-trihydroxystilbene), are able to protect against carcinogenesis in animal models. This study was undertaken to examine the ability of genistein and resveratrol to inhibit reactive oxygen species (ROS)-mediated strand breaks in phi X-174 plasmid DNA. H(2)O(2)/Cu(II) and hydroquinone/Cu(II) were used to cause oxidative DNA strand breaks in the plasmid DNA. We demonstrated that the presence of genistein at micromolar concentrations resulted in a marked inhibition of DNA strand breaks induced by either H(2)O(2)/Cu(II) or hydroquinone/Cu(II). Genistein neither affected the Cu(II)/Cu(I) redox cycle nor reacted with H(2)O(2) suggest that genistein may directly scavenge the ROS that participate in the induction of DNA strand breaks. In contrast to the inhibitory effects of genistein, the presence of resveratrol at similar concentrations led to increased DNA strand breaks induced by H(2)O(2)/Cu(II). Further studies showed that in the presence of Cu(II), resveratrol, but not genistein was able to cause DNA strand breaks. Moreover, both Cu(II)/Cu(I) redox cycle and H(2)O(2) were shown to be critically involved in resveratrol/copper-mediated DNA strand breaks. The above results indicate that despite their similar in vivo anticarcinogenic effects, genistein and resveratrol appear to exert different effects on oxidative DNA damage in vitro.     

Seasonal cycles,phylogenetic assembly,and functional diversity of orchid bee communities

Neotropical rainforests sustain some of the most diverse terrestrial communities on Earth. Euglossine (or orchid) bees are a diverse lineage of insect pollinators distributed throughout the American tropics, where they provide pollination services to a staggering diversity of flowering plant taxa. Elucidating the seasonal patterns of phylogenetic assembly and functional trait diversity of bee communities can shed new light into the mechanisms that govern the assembly of bee pollinator communities and the potential effects of declining bee populations. Male euglossine bees collect, store, and accumulate odoriferous compounds (perfumes) to subsequently use during courtship display. Thus, synthetic chemical baits can be used to attract and monitor euglossine bee populations. We conducted monthly censuses of orchid bees in three sites in the Magdalena valley of Colombia – a region where Central and South American biotas converge – to investigate the structure, diversity, and assembly of euglossine bee communities through time in relation to seasonal climatic cycles. In particular, we tested the hypothesis that phylogenetic community structure and functional trait diversity changed in response to seasonal rainfall fluctuations. All communities exhibited strong to moderate phylogenetic clustering throughout the year, with few pronounced bursts of phylogenetic overdispersion that coincided with the transition from wet‐to‐dry seasons. Despite the heterogeneous distribution of functional traits (e.g., body size, body mass, and proboscis length) and the observed seasonal fluctuations in phylogenetic diversity, we found that functional trait diversity, evenness, and divergence remained constant during all seasons in all communities. However, similar to the pattern observed with phylogenetic diversity, functional trait richness fluctuated markedly with rainfall in all sites. These results emphasize the importance of considering seasonal fluctuations in community assembly and provide a glimpse to the potential effects that climatic alterations may have on both pollinator communities and the ecosystem services they provide.