Distinct effects of IL-18 on the engraftment and function of human effector CD8 T cells and regulatory T cells

IL-18 has pleotropic effects on the activation of T cells during antigen presentation. We investigated the effects of human IL-18 on the engraftment and function of human T cell subsets in xenograft mouse models. IL-18 enhanced the engraftment of human CD8(+) effector T cells and promoted the development of xenogeneic graft versus host disease (GVHD). In marked contrast, IL-18 had reciprocal effects on the engraftment of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in the xenografted mice. Adoptive transfer experiments indicated that IL-18 prevented the suppressive effects of Tregs on the development of xenogeneic GVHD. The IL-18 results were robust as they were observed in two different mouse strains. In addition, the effects of IL-18 were systemic as IL-18 promoted engraftment and persistence of human effector T cells and decreased Tregs in peripheral blood, peritoneal cavity, spleen and liver. In vitro experiments indicated that the expression of the IL-18Ralpha was induced on both CD4 and CD8 effector T cells and Tregs, and that the duration of expression was less sustained on Tregs. These preclinical data suggest that human IL-18 may have use as an adjuvant for immune reconstitution after cytotoxic therapies, and to augment adoptive immunotherapy, donor leukocyte infusions, and vaccine strategies.     

Visualization of bacteriophage T3 capsids with DNA incompletely packaged in vivo

The tightly packaged double-stranded DNA (dsDNA) genome in the mature particles of many tailed bacteriophages has been shown to form multiple concentric rings when reconstructed from cryo-electron micrographs. However, recent single-particle DNA packaging force measurements have suggested that incompletely packaged DNA (ipDNA) is less ordered when it is shorter than ∼ 25% of the full genome length. The study presented here initially achieves both the isolation and the ipDNA length-based fractionation of ipDNA-containing T3 phage capsids (ipDNA-capsids) produced by DNA packaging in vivo; some ipDNA has quantized lengths, as judged by high-resolution gel electrophoresis of expelled DNA. This is the first isolation of such particles among the tailed dsDNA bacteriophages. The ipDNA-capsids are a minor component (containing ∼ 10^− 4 of packaged DNA in all particles) and are initially detected by nondenaturing gel electrophoresis after partial purification by buoyant density centrifugation. The primary contaminants are aggregates of phage particles and empty capsids. This study then investigates ipDNA conformations by the first cryo-electron microscopy of ipDNA-capsids produced in vivo. The 3-D structures of DNA-free capsids, ipDNA-capsids with various lengths of ipDNA, and mature bacteriophage are reconstructed, which reveals the typical T = 7l icosahedral shell of many tailed dsDNA bacteriophages. Though the icosahedral shell structures of these capsids are indistinguishable at the current resolution for the protein shell (∼ 15 Å), the conformations of the DNA inside the shell are drastically different. T3 ipDNA-capsids with 10.6 kb or shorter dsDNA (< 28% of total genome) have an ipDNA conformation indistinguishable from random. However, T3 ipDNA-capsids with 22 kb DNA (58% of total genome) form a single DNA ring next to the inner surface of the capsid shell. In contrast, dsDNA fully packaged (38.2 kb) in mature T3 phage particles forms multiple concentric rings such as those seen in other tailed dsDNA bacteriophages. The distance between the icosahedral shell and the outermost DNA ring decreases in the mature, fully packaged phage structure. These results suggest that, in the early stage of DNA packaging, the dsDNA genome is randomly distributed inside the capsid, not preferentially packaged against the inner surface of the capsid shell, and that the multiple concentric dsDNA rings seen later are the results of pressure-driven close-packing.     

Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication

Background  

Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis.     

Organization of the pronephric kidney revealed by large-scale gene expression mapping

Background

The pronephros, the simplest form of a vertebrate excretory organ, has recently become an important model of vertebrate kidney organogenesis. Here, we elucidated the nephron organization of the Xenopus pronephros and determined the similarities in segmentation with the metanephros, the adult kidney of mammals.

Results

We performed large-scale gene expression mapping of terminal differentiation markers to identify gene expression patterns that define distinct domains of the pronephric kidney. We analyzed the expression of over 240 genes, which included members of the solute carrier, claudin, and aquaporin gene families, as well as selected ion channels. The obtained expression patterns were deposited in the searchable European Renal Genome Project Xenopus Gene Expression Database. We found that 112 genes exhibited highly regionalized expression patterns that were adequate to define the segmental organization of the pronephric nephron. Eight functionally distinct domains were discovered that shared significant analogies in gene expression with the mammalian metanephric nephron. We therefore propose a new nomenclature, which is in line with the mammalian one. The Xenopus pronephric nephron is composed of four basic domains: proximal tubule, intermediate tubule, distal tubule, and connecting tubule. Each tubule may be further subdivided into distinct segments. Finally, we also provide compelling evidence that the expression of key genes underlying inherited renal diseases in humans has been evolutionarily conserved down to the level of the pronephric kidney.

Conclusion

The present study validates the Xenopus pronephros as a genuine model that may be used to elucidate the molecular basis of nephron segmentation and human renal disease.     

Electroacupuncture Effects in a Rat Model of Complete Freund’s Adjuvant-Induced Inflammatory Pain: Antinociceptive Effects Enhanced and Tolerance Development Accelerated

We have previously shown that electroacupuncture (EA) produced antinociception through the release of endogenous opioid peptides to activate opioid receptors during acute nociception. EA produced tolerance after its prolonged application. It has reported that 100 Hz EA could reduce mechanical hyperalgesia in complete Freund’s adjuvant (CFA)-induced inflammatory nociception rats. The present study aims to investigate the antinociceptive effect of EA and the development of EA tolerance in chronic inflammatory nociception rats with CFA injection into the hind paw plantar. The results showed that the antinociceptive effect of 100 Hz EA was significantly enhanced in CFA-induced inflammatory nociception rats. Naloxone at 20 mg/kg could significantly block this antinociceptive effect. Chronic tolerance to EA was developed faster in CFA-induced inflammatory nociception rats than in normal rats. Therefore, 100 Hz EA could enhance antinociceptive effects and accelerate tolerance development in CFA-induced inflammatory nociception rats. The enhancement of EA antinociceptive effect in CFA-induced inflammatory nociception rats might involve the endogenous opioid peptides such as dynorphin. Special issue article in honor of Dr. Ji-Sheng Han.     

Permineralized rhizomes of the Osmundaceae (Filicales): Diversity and tempo-spatial distribution pattern

The family Osmundaceae is among the most primitive ferns of the Filicales, with an extensive fossil record dating back to the Late Paleozoic. Numerous fossil osmundaceous rhizomes have been documented in the geological history. However, the diversity, variation and distribution pattern of permineralized rhizomes remain poorly known. Here we intend to analyze the fossil records with regard to the diversity and distribution pattern of the osmundaceous rhizomes based on available data. To date, about 83 species ascribed to 14 genera of fossil osmundaceous rhizomes have been described worldwide, assigned to two subfamilies, namely, Thamnopteroideae and Osmundoideae. Geologically, two groups (i.e., Thamnopteroideae and Palaeosmunda) have been reported in the Permian. All the Triassic taxa are from the southern hemisphere. Jurassic osmundaceous rhizomes are abundant and widespread throughout the world, most dominant in the southern hemisphere. During the transition of Jurassic to Cretaceous, the diversity of osmundaceous rhizomes declined rapidly. In the Cretaceous, however, the osmundaceous rhizomes from the northern hemisphere surpass those from the southern hemisphere in generic level for the first time. The Cenozoic taxa diversified in the northern hemisphere with the rise of angiosperms. Geographically, the osmundaceous fossil rhizomes have been found in both hemispheres; the major localities include Ural area of the former USSR, Tasmania of Australia, southern Argentina, Antarctica, northern India, central and western part of North America and northern China. We discuss the origin, radiation, and development of the Osmundaceae based on rhizomes, to help further understand the systematic relation and evolutionary history of the family Osmundaceae.     

Effect of Cd on growth, photosynthetic gas exchange, and chlorophyll fluorescence of wild and Cd-sensitive mutant rice

Growth, photosynthetic gas exchange, and chlorophyll fluorescence characteristics were investigated in wild type (WT) and Cd-sensitive mutant rice (Oryza sativa L.) plants using 50 μM Cd treatment for 12 d followed by a 3-d recovery. Under Cd stress, net dry mass and pigment contents were significantly lower in the mutant plants than in the WT. The mutant had lower net photosynthetic rate (P _N), transpiration rate (E), and stomatal conductance (g _s) than WT rice, however, it had higher intercellular CO₂ concentration (C _i), indicating that non-stomatal factors accounted for the inhibition of P _N. Maximal photochemical efficiency of photosystem 2 (F_v/F_m), effective quantum yield of PS2 (Φ_PS2), and photochemical quenching (q_P) decreased much in the mutant under Cd stress. Cd content in roots and leaves of the mutant was significantly higher than those in the WT. Hence Cd toxicity was associated with the marked increases in Cd contents of plant tissue. After the recovery for 3 d, the WT rice had higher capacity to recover from Cd injury than the mutant.     

TEMPO-mediated selective oxidation of substituted polysaccharides--an efficient approach for the determination of the degree of substitution at C-6

2,2,6,6-Tetramethyl-1-piperidinyloxy radical (TEMPO)-mediated oxidations of substituted polysaccharides were studied at pH 10.2 and at a temperature of 0 °C with NaOCl as the oxidant. The reaction is highly selective, and it was shown that the oxidation can proceed to a yield of nearly 100%. The oxidation process was investigated for several substituted polysaccharides, especially for a series of hydroxypropyl guar gums with different molar degrees of substitution. It was shown that this oxidation can be used for the determination of the degree of substitution at C-6 of the polysaccharide by comparing the difference in oxidation yield between substituted and natural polysaccharides. Studies on several hydroxypropyl guar gums showed that the degrees of substitution at C-6—for MS of 0.08, 0.34, 0.62, and 1.08—are 0.06, 0.24, 0.40, and 0.44, respectively. The results were extended to other polysaccharides such as carboxymethyl cellulose, cationic guar gum, carboxymethyl pullulan, and methyl cellulose. It can be concluded that the TEMPO-mediated oxidation is a useful method for the determination of the DS at the substituted C-6 position for different kinds of modified polysaccharides.