The proteasome system in infection: impact of β5 and LMP7 on composition, maturation and quantity of active proteasome complexes

Proteasomes are the major enzyme complexes for non-lysosomal protein degradation in eukaryotic cells. Mammals express two sets of catalytic subunits: the constitutive subunits β1, β2 and β5 and the immunosubunits LMP2 (β1i), MECL-1 (β2i) and LMP7 (β5i). The LMP7-propeptide (proLMP7) is required for optimal maturation of LMP2/MECL-1-containing precursors to mature immunoproteasomes, but can also mediate efficient integration into mixed proteasomes containing β1 and β2. In contrast, the β5-propeptide (proβ5) has been suggested to promote preferential integration into β1/β2-containing precursors, consequently favouring the formation of constitutive proteasomes. Here, we show that proβ5 predominantly promotes integration into LMP2/MECL-1-containing precursors in IFNγ-stimulated, LMP7-deficient cells and infected LMP7-deficient mice. This demonstrates that proβ5 does not direct preferential integration into β1/β2-containing precursors, but instead promotes the formation of mixed LMP2/MECL-1/β5 proteasomes under inflammatory conditions. Moreover, the propeptides substantially differ in their capacity to promote proteasome maturation, with proLMP7 showing a significantly higher chaperone activity as compared to proβ5. Increased efficiency of proteasome maturation mediated by proLMP7 is required for optimal MHC class I cell surface expression and is equally important as the catalytic activity of immunoproteasomes. Intriguingly, induction of LMP7 by infection not only results in rapid exchange of constitutive by immunosubunits, as previously suggested, but also increases the total proteasome abundance within the infected tissue. Hence our data identify a novel LMP7-dependend mechanism to enhance the activity of the proteasome system in infection, which is based on the high chaperone activity of proLMP7 and relies on accelerated maturation of active proteasome complexes.     

Testosterone and cortisol release among Spanish soccer fans watching the 2010 World Cup final

This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50) watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem.     

A mouse model to identify cooperating signaling pathways in cancer

We here establish a mouse cancer model called Multi-Hit that allows for the evaluation of oncogene cooperativities in tumor development. The model is based on the stochastic expression of oncogene combinations ('hits') that are mediated by Cre in a given tissue. Cells with cooperating hits are positively selected and give rise to tumors. We used this approach to evaluate the requirement of Ras downstream effector pathways in tumorigenesis.     

Molecular phylogeny of Pacific Archigregarines (Apicomplexa), including descriptions of Veloxidium leptosynaptae n. gen., n. sp., from the sea cucumber Leptosynapta clarki (Echinodermata), and two new species of Selenidium

Although archigregarines are poorly understood intestinal parasites of marine invertebrates, they are critical for understanding the earliest stages in the evolution of the Apicomplexa. Previous studies suggest that archigregarines are a paraphyletic stem group from which other lineages of gregarines, and possibly all other groups of apicomplexans, evolved. However, substantiating this inference is difficult because molecular phylogenetic data from archigregarines, in particular, and other gregarines, in general, are severely limited. In an attempt to help fill gaps in our knowledge of archigregarine diversity and phylogeny, we set out to discover and characterize novel lineages of archigregarines with high-resolution light and scanning electron microscopy and analyses of small subunit (SSU) rDNA sequences derived from single-cell (SC) PCR techniques. Here, we describe two novel species of Selenidium, namely Selenidium idanthyrsae n. sp. and S. boccardiellae n. sp., and demonstrate the surface morphology and molecular phylogenetic position of the previously reported species S. cf. mesnili. We also describe a novel genus of archigregarine, Veloxidium leptosynaptae n. gen., n. sp., which branches with an environmental sequence and, together, forms the nearest sister lineage to a diverse clade of marine eugregarines (i.e. lecudinids and urosporids). This molecular phylogenetic result is consistent with the hypothesis that archigregarines are deeply paraphyletic within apicomplexans, and suggests that convergent evolution played an important role in shaping the diversity of eugregarine trophozoites.     

The presence of a woman increases testosterone in aggressive dominant men

In line with the challenge hypothesis, this study investigated the effects of the presence of a woman on the testosterone (T) levels of young men. An informal contact with a woman of approximately 5 min resulted in an increase in salivary T among men. These effects occurred particularly in men with an aggressive dominant personality. In addition, higher salivary T levels were related to a more aggressively dominant personality, being sexual inactive for a month or more, and not being involved in a committed, romantic relationship. The most important findings of this study are that the short presence of a woman induces specific hormonal reactions in men, and that these effects are stronger for aggressively dominant men.     

Molecular Phylogeny and Description of the Novel Katablepharid Roombia truncata gen. et sp. nov., and Establishment of the Hacrobia Taxon nov

Background

Photosynthetic eukaryotes with a secondary plastid of red algal origin (cryptophytes, haptophytes, stramenopiles, dinoflagellates, and apicomplexans) are hypothesized to share a single origin of plastid acquisition according to Chromalveolate hypothesis. Recent phylogenomic analyses suggest that photosynthetic “chromalveolates” form a large clade with inclusion of several non-photosynthetic protist lineages. Katablepharids are one such non-photosynthetic lineage closely related to cryptophytes. Despite their evolutionary and ecological importance, katablepharids are poorly investigated.

Methodology/Principal Findings

Here, we report a newly discovered flagellate, Roombia truncata gen. et sp. nov., that is related to katablepharids, but is morphologically distinct from othermembers of the group in the following ways: (1) two flagella emerge from a papilla-like subapical protrusion, (2) conspicuous ejectisomes are aligned in multiple (5–11) rows, (3) each ejectisome increases in size towards the posterior end of the rows, and (4) upon feeding, a part of cytoplasm elastically stretch to engulf whole prey cell. Molecular phylogenies inferred from Hsp90, SSU rDNA, and LSU rDNA sequences consistently and strongly show R. truncata as the sister lineage to all other katablepharids, including lineages known only from environmental sequence surveys. A close association between katablepharids and cryptophytes was also recovered in most analyses. Katablepharids and cryptophytes are together part of a larger, more inclusive, group that also contains haptophytes, telonemids, centrohelids and perhaps biliphytes. The monophyly of this group is supported by several different molecular phylogenetic datasets and one shared lateral gene transfer; therefore, we formally establish this diverse clade as the “Hacrobia.”

Conclusions/Significance

Our discovery of R. truncata not only expands our knowledge in the less studied flagellate group, but provide a better understanding of phylogenetic relationship and evolutionary view of plastid acquisition/losses of Hacrobia. Being an ancestral to all katablepharids, and readily cultivable, R. truncata is a good candidate for multiple gene analyses that will contribute to future phylogenetic studies of Hacrobia.     

Morphology and molecular phylogeny of Haplozoon praxillellae n. sp. (Dinoflagellata): a novel intestinal parasite of the maldanid polychaete Praxillella pacifica Berkeley

The genus Haplozoon comprises a group of endoparasites infecting the intestines of polychaete worms. Comparative studies using light microscopy, scanning and transmission electron microscopy, and small subunit rDNA have shown that these organisms are very unusual dinoflagellates. To date, there is only one species known from the Pacific Ocean, namely Haplozoon axiothellae Siebert. In this study, we describe Haplozoon praxillellae n. sp. from the intestine of the Pacific maldanid polychaete Praxillella pacifica Berkeley. The parasites are relatively small, oblong and about 35-125mum in length, consisting of the trophocyte (anterior-most compartment), rectangular gonocytes and bulbous sporocytes. The trophocyte bears an attachment apparatus with a prominent 'suction disc' and numerous stylets. We were able to detect spherical vesicles near the ventral surface of each gonocyte. The whole organism is covered with thecal barbs of different shape and size, except for the caudal end of the posterior-most sporocyte, which is instead covered with hexagonal or pentagonal alveoli. A continuous membrane encloses the whole pseudocolony. Molecular phylogenetic data, host specificity and morphological differences clearly distinguish H. praxillellae n. sp. from H. axiothellae.     

Symbiotic innovation in the oxymonad Streblomastix strix

Streblomastix strix is an enigmatic oxymonad found exclusively in the hindgut of the damp-wood termite Zootermopsis. Streblomastix has a number of unusual morphological characters and forms a complex but poorly understood symbiosis with epibiotic bacteria. Here we described the ultrastructure of S. strix, with emphasis on the axial cytoskeleton and cell-cell associations, in its normal state and when treated with antibiotics. In untreated cells, epibiotic bacteria were orderly arranged end-to-end on six or seven longitudinal vanes, giving S. strix a stellate appearance in transverse section. The epibiotic bacteria were unusually long bacilli of at least three different morphotypes. Bacteria adhered to the oxymonad host by distinct cell-cell junctions that protruded between the poles of adjacent epibiotic bacteria. Treating termites with the antibiotic carbenicillin led to the loss of most (but not all) of the bacteria and the transformation of S. strix from a long slender cell to a teardrop-shaped cell, where the axostyle was compacted and became bifurcated near the posterior end.     

Characterisation of a non-canonical genetic code in the oxymonad Streblomastix strix

The genetic code is one of the most highly conserved characters in living organisms. Only a small number of genomes have evolved slight variations on the code, and these non-canonical codes are instrumental in understanding the selective pressures maintaining the code. Here, we describe a new case of a non-canonical genetic code from the oxymonad flagellate Streblomastix strix. We have sequenced four protein-coding genes from S.strix and found that the canonical stop codons TAA and TAG encode the amino acid glutamine. These codons are retained in S.strix mRNAs, and the legitimate termination codons of all genes examined were found to be TGA, supporting the prediction that this should be the only true stop codon in this genome. Only four other lineages of eukaryotes are known to have evolved non-canonical nuclear genetic codes, and our phylogenetic analyses of alpha-tubulin, beta-tubulin, elongation factor-1 alpha (EF-1 alpha), heat-shock protein 90 (HSP90), and small subunit rRNA all confirm that the variant code in S.strix evolved independently of any other known variant. The independent origin of each of these codes is particularly interesting because the code found in S.strix, where TAA and TAG encode glutamine, has evolved in three of the four other nuclear lineages with variant codes, but this code has never evolved in a prokaryote or a prokaryote-derived organelle. The distribution of non-canonical codes is probably the result of a combination of differences in translation termination, tRNAs, and tRNA synthetases, such that the eukaryotic machinery preferentially allows changes involving TAA and TAG.