Regulated costimulation in the thymus is critical for T cell development: dysregulated CD28 costimulation can bypass the pre-TCR checkpoint

Expression of CD28 is highly regulated during thymic development, with CD28 levels extremely low on immature thymocytes but increasing dramatically as CD4- CD8- cells initiate expression of TCRbeta. B7-1 and B7-2, the ligands for CD28, have a restricted distribution in the thymic cortex where immature thymocytes reside and are more highly expressed in the medulla where the most mature thymocytes are located. To determine the importance of this regulated CD28/B7 expression for T cell development, we examined the effect of induced CD28 signaling of immature thymocytes in CD28/B7-2 double-transgenic mice. Strikingly, we found that differentiation to the CD4+ CD8+ stage in CD28/B7-2 transgenics proceeds independent of the requirement for TCRbeta expression manifest in wild-type thymocytes, occurring even in Rag- or CD3epsilon- knockouts. These findings indicate that signaling of immature thymocytes through CD28 in the absence of TCR- or pre-TCR-derived signals can promote an aberrant pathway of T cell differentiation and highlight the importance of finely regulated physiologic expression of CD28 and B7 in maintaining integrity of the "beta" checkpoint for pre-TCR/TCR-dependent thymic differentiation.     

Costly apologies communicate conciliatory intention: an fMRI study on forgiveness in response to costly apologies

Reconciliation is an integral part of our social lives. Nevertheless, if a victim perceives the risk of further exploitation by his/her transgressor as non-negligible, the victim may well have difficulty forgiving the transgressor. Therefore, a key ingredient of reconciliation is the transgressor's sincere apology. Theoretical and empirical studies have shown that transgressors can make their apologies credible by incurring a substantial cost. Therefore, we hypothesized that costly apologies, compared to non-costly apologies (i.e., simply saying “sorry”), would effectively communicate a transgressor's conciliatory intention. In a functional magnetic resonance imaging (fMRI) study, participants were asked to imagine a friend committing a mild interpersonal transgression (e.g., standing up the participant) and then apologizing in a costly fashion, apologizing in a non-costly fashion, or not apologizing at all. Compared to non-costly apologies and non-apologies, costly apologies (signals of conciliatory intention) more strongly activated the theory-of-mind network (i.e., bilateral temporoparietal junction, precuneus, medial prefrontal cortex). Moreover, we did not observe any significant differences in brain responses to non-costly apologies and non-apology controls. These results underscore the importance of costly signals in human communication and in human peace-making in particular.     

Assignment of the human indoleamine 2,3-dioxygenase gene to chromosome 8 using the polymerase chain reaction

In order to identify the chromosomal assignment for the human indoleamine 2,3-dioxygenase (IDO) gene, we performed the polymerase chain reaction (PCR) using somatic cell hybrids and screened for the presence of amplified products. The results indicate that the human IDO gene can be assigned to chromosome 8.     

AGF1, an AT-hook protein, is necessary for the negative feedback of AtGA3ox1 encoding GA 3-oxidase

Negative feedback is a fundamental mechanism of organisms to maintain the internal environment within tolerable limits. Gibberellins (GAs) are essential regulators of many aspects of plant development, including seed germination, stem elongation, and flowering. GA biosynthesis is regulated by the feedback mechanism in plants. GA 3-oxidase (GA3ox) catalyzes the final step of the biosynthetic pathway to produce the physiologically active GAs. Here, we found that only the AtGA3ox1 among the AtGA3ox family of Arabidopsis (Arabidopsis thaliana) is under the regulation of GA-negative feedback. We have identified a cis-acting sequence responsible for the GA-negative feedback of AtGA3ox1 using transgenic plants. Furthermore, we have identified an AT-hook protein, AGF1 (for the AT-hook protein of GA feedback regulation), as a DNA-binding protein for the cis-acting sequence of GA-negative feedback. The mutation in the cis-acting sequence abolished both GA-negative feedback and AGF1 binding. In addition, constitutive expression of AGF1 affected GA-negative feedback in Arabidopsis. Our results suggest that AGF1 plays a role in the homeostasis of GAs through binding to the cis-acting sequence of the GA-negative feedback of AtGA3ox1.     

Tunicamycin-Induced Cell Death in the Trigeminal Ganglion is Suppressed by Nerve Growth Factor in the Mouse Embryo

The effect of nerve growth factor (NGF) on tunicamycin (Tm)-treated neurons in the trigeminal ganglion was investigated by use of caspase-3 immunohistochemistry. In intact embryos at embryonic day 16.5, only a few caspase-3-immunoreactivity were detected in the ganglion neurons. Mean ± SE of the density of the immunoreactivity was 0.22 ± 0.03%. In contrast, the number of the immunoreactive neurons was increased at 24 h after injection of 0.5 μg Tm in 1 μl of 0.05 N NaOH solution into mouse embryos at embryonic day 15.5. The density of immunoreactivity was also increased (mean ± SE = 1.44 ± 0.11%) compared to intact and 0.05 N NaOH-treated embryos (mean ± SE = 0.35 ± 0.03%). The Tm treatment caused increase of the number of trigeminal neurons representing apoptotic profiles (intact, mean ± SE = 79.3 ± 8.5; 0.05 N NaOH, mean ± SE = 132 ± 11.5; 0.5 μg Tm, mean ± SE = 370.2 ± 64.8). In addition, NGF significantly prevented the increase of density of the immunoreactivity (mean ± SE = 0.54 ± 0.16%) and the number of apoptotic cells (mean ± SE = 146.2 ± 11.3). Saline application (without NGF) had no effect on Tm-induced increase of the immunoreactivity (mean ± SE = 1.78 ± 0.23%) or the apoptotic profiles (mean ± SE = 431.9 ± 80.5). These results indicate that Tm-induced cell death in the trigeminal ganglion is suppressed by NGF in the mouse embryo.     

Temporal dynamics and resilience of fine litterfall in relation to typhoon disturbances over 14 years in an old-growth lucidophyllous forest in southwestern Japan

We examined fine litterfall fluctuations on a seasonal and annual scale for 14 years (1992–2005) in a 1.2-ha plot in an old-growth lucidophyllous (evergreen broad-leaved) forest within the Aya Research Site, southwestern Japan. The average total litterfall input was 6.32 Mg ha^–1, of which leaf litter accounted for 60% of the total. Two high-impact typhoons struck the study area in 1993 (T9313) and 2004 (T0416) during the observation period; however, the subsequent pattern of litterfall after disturbance was different between the two typhoons. T9313 disturbance caused a reduction of biomass (ca. 10% of basal area (BA)) and a sharp decrease in litterfall input following a massive input in 1993. On the other hand, T0416 caused a minor decline in litterfall input, accompanied by a relatively small reduction of BA (5.2% of the 2001 BA). In spite of large fluctuations, litterfall input increased year by year after the T9313 disturbance. In 2000, 7 years after T9313, leaf input showed no significant differences and recorded more than 90% of pre-T9313 levels. Re-leafing from typhoon survivors may play an important role in the recovery of litterfall input in this forest. This study demonstrated how one high-impact typhoon can alter the temporal fluctuations in fine litterfall in lucidophyllous forest ecosystems.     

Maternal inheritance of mitochondria: multipolarity, multiallelism and hierarchical transmission of mitochondrial DNA in the true slime mold Physarum polycephalum

Direct evidence of digestion of paternal mitochondrial DNA (mtDNA) has been found in the true slime mold Physarum polycephalum. This is the first report on the selective digestion of mtDNA inside the zygote, and is striking evidence for the mechanism of maternal inheritance of mitochondria. Moreover, two mitochondrial nuclease activities were detected in this organism as candidates for the nucleases responsible for selective digestion of mtDNA. In the true slime mold, there is an additional feature of the uniparental inheritance of mitochondria. Although mitochondria are believed to be inherited from the maternal lineage in nearly all eukaryotes, the mating types of the true slime mold P. polycephalum is not restricted to two: there are three mating loci—matA, matB, and matC—and these loci have 16, 15, and 3 alleles, respectively. Interestingly, the transmission patterns of mtDNA are determined by the matA locus, in a hierarchical fashion (matA hierarchy) as follows: matA7 > matA2 > matA11 > matA12 > matA15/matA16 > matA1 > matA6. The strain possessing the higher status of matA would be the mtDNA donor in crosses. Furthermore, we have found that some crosses showed biparental inheritance of mitochondria. This review describes the phenomenon of hierarchical transmission of mtDNA in true slime molds, and discusses the presumed molecular mechanism of maternal and biparental inheritance.     

The genome of Erysipelothrix rhusiopathiae, the causative agent of swine erysipelas, reveals new insights into the evolution of firmicutes and the organism's intracellular adaptations

Erysipelothrix rhusiopathiae is a Gram-positive bacterium that represents a new class, Erysipelotrichia, in the phylum Firmicutes. The organism is a facultative intracellular pathogen that causes swine erysipelas, as well as a variety of diseases in many animals. Here, we report the first complete genome sequence analysis of a member of the class Erysipelotrichia. The E. rhusiopathiae genome (1,787,941 bp) is one of the smallest genomes in the phylum Firmicutes. Phylogenetic analyses based on the 16S rRNA gene and 31 universal protein families suggest that E. rhusiopathiae is phylogenetically close to Mollicutes, which comprises Mycoplasma species. Genome analyses show that the overall features of the E. rhusiopathiae genome are similar to those of other Gram-positive bacteria; it possesses a complete set of peptidoglycan biosynthesis genes, two-component regulatory systems, and various cell wall-associated virulence factors, including a capsule and adhesins. However, it lacks many orthologous genes for the biosynthesis of wall teichoic acids (WTA) and lipoteichoic acids (LTA) and the dltABCD operon, which is responsible for d-alanine incorporation into WTA and LTA, suggesting that the organism has an atypical cell wall. In addition, like Mollicutes, its genome shows a complete loss of fatty acid biosynthesis pathways and lacks the genes for the biosynthesis of many amino acids, cofactors, and vitamins, indicating reductive genome evolution. The genome encodes nine antioxidant factors and nine phospholipases, which facilitate intracellular survival in phagocytes. Thus, the E. rhusiopathiae genome represents evolutionary traits of both Firmicutes and Mollicutes and provides new insights into its evolutionary adaptations for intracellular survival.