Dynamics of Influenza Virus and Human Host Interactions During Infection and Replication Cycle

The replication and life cycle of the influenza virus is governed by an intricate network of intracellular regulatory events during infection, including interactions with an even more complex system of biochemical interactions of the host cell. Computational modeling and systems biology have been successfully employed to further the understanding of various biological systems, however, computational studies of the complexity of intracellular interactions during influenza infection is lacking. In this work, we present the first large-scale dynamical model of the infection and replication cycle of influenza, as well as some of its interactions with the host’s signaling machinery. Specifically, we focus on and visualize the dynamics of the internalization and endocytosis of the virus, replication and translation of its genomic components, as well as the assembly of progeny virions. Simulations and analyses of the models dynamics qualitatively reproduced numerous biological phenomena discovered in the laboratory. Finally, comparisons of the dynamics of existing and proposed drugs, our results suggest that a drug targeting PB1:PA would be more efficient than existing Amantadin/Rimantaine or Zanamivir/Oseltamivir.     

The peptide motif of the single dominantly expressed class I molecule of the chicken MHC can explain the response to a molecular defined vaccine of infectious bursal disease virus (IBDV)

In contrast to typical mammals, the chicken MHC (the BF-BL region of the B locus) has strong genetic associations with resistance and susceptibility to infectious pathogens as well as responses to vaccines. We have shown that the chicken MHC encodes a single dominantly expressed class I molecule whose peptide-binding motifs can determine resistance to viral pathogens, such as Rous sarcoma virus and Marek’s disease virus. In this report, we examine the response to a molecular defined vaccine, fp-IBD1, which consists of a fowlpox virus vector carrying the VP2 gene of infectious bursal disease virus (IBDV) fused with β-galactosidase. We vaccinated parental lines and two backcross families with fp-IBD1, challenged with the virulent IBDV strain F52/70, and measured damage to the bursa. We found that the MHC haplotype B15 from line 15I confers no protection, whereas B2 from line 6₁ and B12 from line C determine protection, although another locus from line 6₁ was also important. Using our peptide motifs, we found that many more peptides from VP2 were predicted to bind to the dominantly expressed class I molecule BF2*1201 than BF2*1501. Moreover, most of the peptides predicted to bind BF2*1201 did in fact bind, while none bound BF2*1501. Using peptide vaccination, we identified one B12 peptide that conferred protection to challenge, as assessed by bursal damage and viremia. Thus, we show the strong genetic association of the chicken MHC to a T cell vaccine can be explained by peptide presentation by the single dominantly expressed class I molecule.     

Description of a new species of Neralsia Cameron with a wide distribution in the American continent: N. incompleta n. sp. (Hymenoptera: Figitidae: Figitinae)

In this study a new species of Neralsia is described, N. incompleta n. sp. The radial cell shape allows to distinguish it clearly from the rest of species of the genus. The distribution of Neralsia incompleta n. sp. is probably the entire American continent, having been collected from Canada to Paraguay. In spite of its abundance, the associated biology is unknown, although it should be related with parasitism of Diptera Cyclorrhapha.     

Fine genetic mapping of RXopJ4, a bacterial spot disease resistance locus from Solanum pennellii LA716

The RXopJ4 resistance locus from the wild accession Solanum pennellii (Sp) LA716 confers resistance to bacterial spot disease of tomato (S. lycopersicum, Sl) caused by Xanthomonas perforans (Xp). RXopJ4 resistance depends on recognition of the pathogen type III effector protein XopJ4. We used a collection of Sp introgression lines (ILs) to narrow the RXopJ4 locus to a 4.2-Mb segment on the long arm of chromosome 6, encompassed by the ILs 6-2 and 6-2-2. We then adapted or developed a collection of 14 molecular markers to map on a segregating F₂ population from a cross between the susceptible parent Sl FL8000 and the resistant parent RXopJ4 8000 OC₇. In the F₂ population, a 190-kb segment between the markers J350 and J352 cosegregated with resistance. This fine mapping will enable both the identification of candidate genes and the detection of resistant plants using cosegregating markers. The RXopJ4 resistance gene(s), in combination with other recently characterized genes and a quantitative trait locus (QTL) for bacterial spot disease resistance, will likely be an effective tool for the development of durable resistance in cultivated tomato.     

Uncovering the Lactobacillus plantarum WCFS1 Gallate Decarboxylase Involved in Tannin Degradation

Lactobacillus plantarum is a lactic acid bacterium able to degrade tannins by the subsequent action of tannase and gallate decarboxylase enzymes. The gene encoding tannase had previously been identified, whereas the gene encoding gallate decarboxylase is unknown. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of gallic-acid induced L. plantarum extracts showed a 54-kDa protein which was absent in the uninduced cells. This protein was identified as Lp_2945, putatively annotated UbiD. Homology searches identified ubiD-like genes located within three-gene operons which encoded the three subunits of nonoxidative aromatic acid decarboxylases. L. plantarum is the only bacterium in which the lpdC (lp_2945) gene and the lpdB and lpdD (lp_0271 and lp_0272) genes are separated in the chromosome. Combination of extracts from recombinant Escherichia coli cells expressing the lpdB, lpdC, and lpdC genes demonstrated that LpdC is the only protein required to yield gallate decarboxylase activity. However, the disruption of these genes in L. plantarum revealed that the lpdB and lpdC gene products are essential for gallate decarboxylase activity. Similar to L. plantarum tannase, which exhibited activity only in esters derived from gallic and protocatechuic acids, purified His6-LpdC protein from E. coli showed decarboxylase activity against gallic and protocatechuic acids. In contrast to the tannase activity, gallate decarboxylase activity is widely present among lactic acid bacteria. This study constitutes the first genetic characterization of a gallate decarboxylase enzyme and provides new insights into the role of the different subunits of bacterial nonoxidative aromatic acid decarboxylases.     

Occurrence of Poecilochirus austroasiaticus (Acari: Parasitidae) in forensic autopsies and its application on postmortem interval estimation

Despite the fact that mites were used at the dawn of forensic entomology to elucidate the postmortem interval, their use in current cases remains quite low for procedural reasons such as inadequate taxonomic knowledge. A special interest is focused on the phoretic stages of some mite species, because the phoront-host specificity allows us to deduce in many occasions the presence of the carrier (usually Diptera or Coleoptera) although it has not been seen in the sampling performed in situ or in the autopsy room. In this article, we describe two cases where Poecilochirus austroasiaticus Vitzthum (Acari: Parasitidae) was sampled in the autopsy room. In the first case, we could sample the host, Thanatophilus ruficornis (Küster) (Coleoptera: Silphidae), which was still carrying phoretic stages of the mite on the body. That attachment allowed, by observing starvation/feeding periods as a function of the digestive tract filling, the establishment of chronological cycles of phoretic behavior, showing maximum peaks of phoronts during arrival and departure from the corpse and the lowest values in the phase of host feeding. From the sarcosaprophagous fauna, we were able to determine in this case a minimum postmortem interval of 10 days. In the second case, we found no Silphidae at the place where the corpse was found or at the autopsy, but a postmortem interval of 13 days could be established by the high specificity of this interspecific relationship and the departure from the corpse of this family of Coleoptera.     

Comparison of historical bottleneck effects and genetic consequences of re‐introduction in a critically endangered island passerine

Re‐introduction is an important tool for recovering endangered species; however, the magnitude of genetic consequences for re‐introduced populations remains largely unknown, in particular the relative impacts of historical population bottlenecks compared to those induced by conservation management. We characterize 14 microsatellite loci developed for the Seychelles paradise flycatcher and use them to quantify temporal and spatial measures of genetic variation across a 134‐year time frame encompassing a historical bottleneck that reduced the species to ~28 individuals in the 1960s, through the initial stages of recovery and across a second contemporary conservation‐introduction‐induced bottleneck. We then evaluate the relative impacts of the two bottlenecks, and finally apply our findings to inform broader re‐introduction strategy. We find a temporal trend of significant decrease in standard measures of genetic diversity across the historical bottleneck, but only a nonsignificant downward trend in number of alleles across the contemporary bottleneck. However, accounting for the different timescales of the two bottlenecks (~40 historical generations versus <1 contemporary generation), the loss of genetic diversity per generation is greater across the contemporary bottleneck. Historically, the flycatcher population was genetically structured; however, extinction on four of five islands has resulted in a homogeneous contemporary population. We conclude that severe historical bottlenecks can leave a large footprint in terms of sheer quantity of genetic diversity lost. However, severely depleted genetic diversity does not render a species immune to further genetic erosion upon re‐introduction. In some cases, the loss of genetic diversity per generation can, initially at least, be greater across re‐introduction‐induced bottlenecks.     

On the use of weighting in LCA: translating decision makers’ preferences into weights via linear programming

Purpose

The main goal of any life cycle assessment (LCA) study is to identify solutions leading to environmental savings. In conventional LCA studies, practitioners select from some alternatives the one which better matches their preferences. This task is sometimes simplified by ranking these alternatives using an aggregated indicator defined by attaching weights to impacts. We address here the inverse problem. That is, given an alternative, we aim to determine the weights for which that solution becomes optimal.

Methods

We propose a method based on linear programming (LP) that determines, for a given alternative, the ranges within which the weights attached to a set of impact metrics must lie so that when a weighting combination of these impacts is optimized, the alternative can be optimal, while if the weights fall outside this range, it is guaranteed that the solution will be suboptimal. A large weight value implies that the corresponding LCA impact is given more importance, while a low value implies the converse. Furthermore, we provide a rigorous mathematical analysis on the implications of using weighting schemes in LCA, showing that this practice guides decision-making towards the adoption of some specific alternatives (those lying on the convex envelope of the resulting trade-off curve).

Results and discussion

A case study based on the design of hydrogen infrastructures is taken as a test bed to illustrate the capabilities of the approach presented. Given are a set of production and storage technologies available to produce and deliver hydrogen, a final demand, and cost and environmental data. A set of designs, each achieving a unique combination of cost and LCA impact, is considered. For each of them, we calculate the minimum and maximum weight to be given to every LCA impact so that the alternative can be optimal among all the candidate designs. Numerical results show that solutions with lower impact are selected when decision makers are willing to pay larger monetary penalties for the environmental damage caused.

Conclusions

LP can be used in LCA to translate the decision makers’ preferences into weights. This information is rather valuable, particularly when these weights represent economic penalties, as it allows screening and ranking alternatives on the basis of a common economic basis. Our framework is aimed at facilitating decision making in LCA studies and defines a general framework for comparing alternatives that show different performance in a wide variety of impact metrics.     

Structures of Novel Sesquiterpene Alcohols from Chloranthus japonicus (Chloranthaceae)

Three novel sesquiterpene alcohols, shizuka-acoradienol (2), shizukafuranol (3) and shizukol-idol (4), were isolated from Chloranthus japonicus Sieb. (Japanese name: Hitori-shizuka, Chloranthaceae). Their structures were elucidated on the basis of their physicochemical properties and some chemical reactions. Furanodienone (5), scopoletin (6a) and isoscopoletin (6b) were also isolated from this plant.     

Antioxidant and prebiotic effects of dietary fiber co-travelers from sugar Kombu in healthy rats

The edible brown seaweed sugar Kombu (Saccharina latissima) is a good source of dietary fiber (DF) and associated compounds. Besides it presents antioxidant capacity in vitro due to their sulfated polysaccharides and polyphenols. The effect of a DF-rich sugar Kombu diet on biochemical parameters and antioxidant and prebiotic effects in healthy rats was evaluated. Thus, rats were fed either a basal diet or a supplemented one with 10 % sugar Kombu for 4 weeks. Several health-promoting effects were found such as a decrease in triglycerides (TGL) and uric acid (UrA), and an increase in antioxidant status both in serum and cecum. Regarding prebiotic effect, higher cecum weight and total short chain fatty acid (SCFA) content were evidenced in the seaweed-fed group, without significant differences on total bacterial count of feces. Sugar Kombu and sulfated polysaccharides from its DF could be used as functional ingredients for further nutraceutical applications.