Viral Biology and Immune Privilege in the Development of Extrahepatic Manifestations During Hepatitis E Virus Infection.

Hepatitis E virus (HEV) exhibits tropism toward hepatocytes and thus affects the liver; however, HEV may also affect other tissues, including the heart, kidneys, intestines, testicles, and central nervous system. To date, the pathophysiological links between HEV infection and extrahepatic manifestations have not yet been established. Considering that HEV infects multiple types of cells, the direct effects of virus replication in peripheral tissues represent a plausible explanation for extrahepatic manifestations. In addition, since the immune response is crucial in the development of the disease, the immune characteristics of affected tissues should be revisited to identify commonalities explaining the effects of the virus. This review summarizes the most recent advances in understanding the virus biology and immune-privileged status of specific tissues as major elements for HEV replication in diverse organs. These discoveries may open avenues to explain the multiple extrahepatic manifestations associated with HEV infection and ultimately to design effective strategies for infection control.

Rhodium and ruthenium complexes of methylene-bridged, P-stereogenic, unsymmetrical diphosphanes.

Enantiopure P-stereogenic methylphosphane-boranes (SP)-P(BH3)PhArMe (ArMe; Ar = 1-naphthyl (NpMe), and 2-biphenylyl (BiphMe)) have been used to prepare diphosphanes of the type ArPhPCH2PR2 (R = Ph, iPr or tBu; ArR). The ligands have been reacted with [Rh(COD)2]BF4 to furnish the corresponding six monochelated [Rh(COD)(ArR)]BF4 organometallic compounds (RhArR) or, depending on the reaction conditions, the bis(chelated) coordination compound [Rh(BiphiPr)2]BF4 as a mixture of cis and trans isomers. The crystal structure of cis-[Rh(BiphiPr)2]BF4 was obtained. The coordination of the BiphR with [RuCl(µ-Cl)(η6-p-cymene)2]2 under different conditions produced cationic chelated complexes of the type [RuCl(η6-p-cymene)(κ2-BiphR)]PF6 (RuBiphR) and the neutral monocoordinated complex [RuCl2(η6-p-cymene)(κ1-BiphPh)] (RuBiphPh') with the uncoordinated P-stereogenic moiety. The Rh(I) complexes were used in the catalytic hydrogenation of functionalized olefins and the Ru(II) complexes were tested in the transfer hydrogenation of acetophenone. Both precursors displayed good activities with moderate enantioselectivities.

Trophic state alters the mechanism whereby energetic coupling between photosynthesis and respiration occurs in Euglena gracilis.

The coupling between mitochondrial respiration and photosynthesis plays an important role in the energetic physiology of green plants and some secondary-red photosynthetic eukaryotes (diatoms), allowing an efficient CO2 assimilation and optimal growth. Using the flagellate Euglena gracilis, we first tested if photosynthesis-respiration coupling occurs in this species harbouring secondary green plastids (i.e. originated from an endosymbiosis between a green alga and a phagotrophic euglenozoan). Second, we tested how the trophic state (mixotrophy and photoautotrophy) of the cell alters the mechanisms involved in the photosynthesis-respiration coupling. Energetic coupling between photosynthesis and respiration was determined by testing the effect of respiratory inhibitors on photosynthesis, and measuring the simultaneous variation of photosynthesis and respiration rates as a function of temperature (i.e. thermal response curves). The mechanism involved in the photosynthesis-respiration coupling was assessed by combining proteomics, biophysical and cytological analyses. Our work shows that there is photosynthesis-respiration coupling and membrane contacts between mitochondria and chloroplasts in E. gracilis. However, whereas in mixotrophy adjustment of the chloroplast ATP/NADPH ratio drives the interaction, in photoautotrophy the coupling is conditioned by CO2 limitation and photorespiration. This indicates that maintenance of photosynthesis-respiration coupling, through plastic metabolic responses, is key to E. gracilis functioning under changing environmental conditions.

De Novo Transcriptome Meta-Assembly of the Mixotrophic Freshwater Microalga Euglena gracilis.

Euglena gracilis is a well-known photosynthetic microeukaryote considered as the product of a secondary endosymbiosis between a green alga and a phagotrophic unicellular belonging to the same eukaryotic phylum as the parasitic trypanosomatids. As its nuclear genome has proven difficult to sequence, reliable transcriptomes are important for functional studies. In this work, we assembled a new consensus transcriptome by combining sequencing reads from five independent studies. Based on a detailed comparison with two previously released transcriptomes, our consensus transcriptome appears to be the most complete so far. Remapping the reads on it allowed us to compare the expression of the transcripts across multiple culture conditions at once and to infer a functionally annotated network of co-expressed genes. Although the emergence of meaningful gene clusters indicates that some biological signal lies in gene expression levels, our analyses confirm that gene regulation in euglenozoans is not primarily controlled at the transcriptional level. Regarding the origin of E. gracilis, we observe a heavily mixed gene ancestry, as previously reported, and rule out sequence contamination as a possible explanation for these observations. Instead, they indicate that this complex alga has evolved through a convoluted process involving much more than two partners.

Functional and transcriptional characterization of a barley mutant with impaired photosynthesis.

Chemical mutagenesis induces variations that may assist in the identification of targets for adaptation to growth under atmospheric CO2 enrichment. The aim of this work was to characterize the limitations causing reduced photosynthetic capacity in G132 mutagenized barley (Hordeum vulgare L. cv. Graphic) grown in a glasshouse. Compared to the wild type (WT) G132 showed increased transcript levels for the PSII light harvesting complex, but lower levels of chlorophyll, transcripts for protochlorophyllide oxidoreductase A and psbQ, and PSII quantum efficiency in young leaves. Rubisco limitation had an overriding influence on G132 photosynthesis, and was due to strong and selective decreases in Rubisco protein and activity. These reductions were accompanied by enhanced Rubisco transcripts, but increased levels of a Rubisco degradation product. G132 showed lower levels of carbohydrates, amino acids and corresponding transcripts, and proteins, but not of nitrate. Many of the measured parameters recovered in the mutant as development progressed, or decreased less than in the WT, indicating that senescence was delayed. G132 had a longer growth period than the WT and similar final plant dry matter. The reduced resource investment in Rubisco of G132 may prove useful for studies on barley adaptation to elevated CO2 and climate change.

Photosynthesis-dependent/independent control of stomatal responses to CO2 in mutant barley with surplus electron transport capacity and reduced SLAH3 anion channel transcript.

The mechanisms of stomatal sensitivity to CO2 are yet to be fully understood. The role of photosynthetic and non-photosynthetic factors in stomatal responses to CO2 was investigated in wild-type barley (Hordeum vulgare var. Graphic) and in a mutant (G132) with decreased photochemical and Rubisco capacities. The CO2 and DCMU responses of stomatal conductance (gs), gas exchange, chlorophyll fluorescence and levels of ATP, with a putative transcript for stomatal opening were analysed. G132 had greater gs than the wild-type, despite lower photosynthesis rates and higher intercellular CO2 concentrations (Ci). The mutant had Rubisco-limited photosynthesis at very high CO2 levels, and higher ATP contents than the wild-type. Stomatal sensitivity to CO2 under red light was lower in G132 than in the wild-type, both in photosynthesizing and DCMU-inhibited leaves. Under constant Ci and red light, stomatal sensitivity to DCMU inhibition was higher in G132. The levels of a SLAH3-like slow anion channel transcript, involved in stomatal closure, decreased sharply in G132. The results suggest that stomatal responses to CO2 depend partly on the balance of photosynthetic electron transport to carbon assimilation capacities, but are partially regulated by the CO2 signalling network. High gs can improve the adaptation to climate change in well-watered conditions.

[Cyclooxygenase-2 polymorphisms and bronchoalveolar lavage cellularity of sarcoidosis]. / El polimorfismo COX2.8473t>C del gen de la ciclooxigenasa-2 está asociado al cociente CD4/CD8 del lavado broncoalveolar en la sarcoidosis.

OBJECTIVES: Recent studies have found cyclooxygenase-2 (COX-2) and its polymorphisms to be associated with sarcoidosis, being it significantly decreased in alveolar macrophages, with no information on the relationship between these polymorphisms and the rest of cells in bronchoalveolar layage (BAL). The present study aimed to investigate the potential association between COX-2 gene polymorphisms and the BAL cell profile including the CD4/CD8 ratio. MATERIAL AND METHODS: This observational cross-sectional study involved six hospitals in Spain. Patients diagnosed with sarcoidosis with a BAL performed were included. The following variables were recorded: age, gender, initial diagnostic methods, serum angiotensin-converting enzyme levels, pulmonary function tests, radiological stage, and the cellularity and CD4/CD8 ratio from BAL. Genotyping of four COX-2 polymorphisms (COX2.5909T>G, COX2.8473T>C, COX2.926G>C, and COX2.3050G>C) was undertaken on DNA extracted from peripheral blood lymphocytes using fluorescent hybridization probes. The relationship between the polymorphisms and the cellularity was done by means of a multiple linear regression, adjusting for gender. RESULTS: A total of 51 sarcoid patients (23 males, mean age: 45 +/- 15 years) were studied. CD4/CD8 ratio was significantly higher among homozygote allele C carriers of the polymorphism COX2.8473T>C (CC 11.2 +/- 5.5 vs. CT+TT 4.4 +/- 3.5; p = 0.022; beta = 7.43; 95% CI 1.38 - 13.48). Although several differences were observed in other cell groups, they did not reach the statistical significance level. CONCLUSIONS: In patients diagnosed with sarcoidosis, there seems to be a relationship between COX2.8473 polymorphism and CD4/CD8 ratio from BAL.