Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10.

Cytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection.     

施肥对柚木幼林生长及林下植被的影响

为探究施肥对柚木（Tectona grandis L. f.）幼林生长及林下植被多样性的影响,以广西4年生的柚木人工林为研究对象,采用随机区组试验设计,开展不同肥种配比组合试验（F1,0.5 kg氮磷钾复合肥+1.0 kg钙肥+1.0 kg硫酸镁肥;F2,1.0 kg氮磷钾复合肥+0.5 kg钙肥+0.5 kg硫酸镁肥;F3,1.0 kg氮磷钾复合肥+0.5 kg硫酸镁肥;F4,1.0 kg氮磷钾复合肥+0.5 kg钙镁磷肥;CK,不施肥）。结果表明：施肥显著加快了柚木树高、胸径和单株材积的生长,各指标年均增量分别比不施肥（CK）提高了0.13~0.32 m、0.17~0.26 cm和4.35~9.63 dm³,其中F3配比组合处理生长增量最大,且胸径和材积生长率比CK显著增加了10.35%、10.55%。幼林林下植物相对丰富,植被种类涉及25科39属42种,其中菊科（Compositae）与禾本科（Gramineae）植物为主要优势种。不同处理间林下植被物种Shannon-Wiener指数（H′）、Simpson指数（D）和Pielou均匀度指数（J_sw）差异显著（P<0.05）,F1、F3处理的3个物种指数显著高于CK,而各处理Gleason物种丰富度指数（D_g）差异不明显,不同处理间生长及林下植被多样性等12个指标综合评价得分由高到低依次为F3、F1、F4、F2、CK。4年生柚木幼林合理施肥,可以促进林木生长,还可提高林下物种丰富度和多样性;1.0 kg氮磷钾复合肥和0.5 kg硫酸镁肥的低投入配方施肥,更有利于促进柚木人工林生长和群落的稳定。     

安徽产大戟属药用植物资源及其生物活性

对安徽产大戟属药用植物的资源状况及其生物活性进行了综述。安徽产大戟属药用植物约有9种,具有抗肿瘤、抗菌、抗氧化等生物活性,有些具有一定的毒性。     

The composition and origins of genomic variation among individuals of the soybean reference cultivar Williams 82

Soybean (Glycine max) is a self-pollinating species that has relatively low nucleotide polymorphism rates compared with other crop species. Despite the low rate of nucleotide polymorphisms, a wide range of heritable phenotypic variation exists. There is even evidence for heritable phenotypic variation among individuals within some cultivars. Williams 82, the soybean cultivar used to produce the reference genome sequence, was derived from backcrossing a Phytophthora root rot resistance locus from the donor parent Kingwa into the recurrent parent Williams. To explore the genetic basis of intracultivar variation, we investigated the nucleotide, structural, and gene content variation of different Williams 82 individuals. Williams 82 individuals exhibited variation in the number and size of introgressed Kingwa loci. In these regions of genomic heterogeneity, the reference Williams 82 genome sequence consists of a mosaic of Williams and Kingwa haplotypes. Genomic structural variation between Williams and Kingwa was maintained between the Williams 82 individuals within the regions of heterogeneity. Additionally, the regions of heterogeneity exhibited gene content differences between Williams 82 individuals. These findings show that genetic heterogeneity in Williams 82 primarily originated from the differential segregation of polymorphic chromosomal regions following the backcross and single-seed descent generations of the breeding process. We conclude that soybean haplotypes can possess a high rate of structural and gene content variation, and the impact of intracultivar genetic heterogeneity may be significant. This detailed characterization will be useful for interpreting soybean genomic data sets and highlights important considerations for research communities that are developing or utilizing a reference genome sequence.     

S-nitrosylation of ApoE in Alzheimer's disease

The mechanism by which apolipoprotein E (ApoE) isoforms functionally influence the risk and progression of late-onset Alzheimer's disease (LOAD) remains hitherto unknown. Herein, we present evidence that all ApoE isoforms bind to nitric oxide synthase 1 (NOS1) and that such protein-protein interaction results in S-nitrosylation of ApoE2 and ApoE3 but not ApoE4. Our structural analysis at the atomic level reveals that S-nitrosylation of ApoE2 and ApoE3 proteins may lead to conformational changes resulting in the loss of binding to low-density lipoprotein (LDL) receptors. Collectively, our data suggest that S-nitrosylation of ApoE proteins may play an important role in regulating lipid metabolism and in the pathogenesis of LOAD.     

The Potassium Channel Interacting Protein 3 (DREAM/KChIP3) Heterodimerizes with and Regulates Calmodulin Function

Downstream regulatory element antagonistic modulator (DREAM/KChIP3), a neuronal EF-hand protein, modulates pain, potassium channel activity, and binds presenilin 1. Using affinity capture of neuronal proteins by immobilized DREAM/KChIP3 in the presence and absence of calcium (Ca²⁺) followed by mass spectroscopic identification of interacting proteins, we demonstrate that in the presence of Ca²⁺, DREAM/KChIP3 interacts with the EF-hand protein, calmodulin (CaM). The interaction of DREAM/KChIP3 with CaM does not occur in the absence of Ca²⁺. In the absence of Ca²⁺, DREAM/KChIP3 binds the EF-hand protein, calcineurin subunit-B. Ca²⁺-bound DREAM/KChIP3 binds CaM with a dissociation constant of ∼3 μm as assessed by changes in DREAM/KChIP3 intrinsic protein fluorescence in the presence of CaM. Two-dimensional ¹H,¹⁵N heteronuclear single quantum coherence spectra reveal changes in chemical shifts and line broadening upon the addition of CaM to ¹⁵N DREAM/KChIP3. The amino-terminal portion of DREAM/KChIP3 is required for its binding to CaM because a construct of DREAM/KChIP3 lacking the first 94 amino-terminal residues fails to bind CaM as assessed by fluorescence spectroscopy. The addition of Ca²⁺-bound DREAM/KChIP3 increases the activation of calcineurin (CN) by calcium CaM. A DREAM/KChIP3 mutant incapable of binding Ca²⁺ also stimulates calmodulin-dependent CN activity. The shortened form of DREAM/KChIP3 lacking the NH₂-terminal amino acids fails to activate CN in the presence of calcium CaM. Our data demonstrate the interaction of DREAM/KChIP3 with the important EF-hand protein, CaM, and show that the interaction alters CN activity.     

Development and Evaluation of Intron and Insertion–Deletion Markers for Gossypium barbadense

A total of 588 Gossypium barbadense coding sequences (CDSs) from nucleotide databases were selected for marker development. After selection, 125 CDSs were used to design 126 markers, including 39 intron polymorphisms (GbIPs) and 87 insertion?Cdeletion polymorphisms (GbIDPs). These markers were evaluated by analyzing the genetic diversity of 66 tetraploid cotton accessions including 56 G. barbadense accessions and 10 Gossypium hirsutum accessions. The amplification efficiencies of the GbIPs and GbIDPs were 0.560 and 0.489 for polymorphism information content, 0.744 and 0.690 for effective multiplex ratio (E), 0.653 and 0.438 for qualitative of nature of data, and 0.272 and 0.148 for effective marker index. Principal coordinate analysis showed profound differences between G. hirsutum and G. barbadense accessions. In addition, most of the G. barbadense accessions of Xinjiang, China were clearly different from foreign and other Chinese G. barbadense accessions. The 126 markers were also evaluated for their ability to enrich genetic maps, and 16 polymorphic loci were mapped on nine chromosomes with six loci on A subgenome and 10 loci on D subgenome. The mapping efficiencies of GbIPs and GbIDPs primers were 15.38% and 11.49%, respectively. This study well proves that GbIPs and GbIDPs can be successfully applied to the analysis of genetic diversity and construction of genetic maps.     

Replication-mediated disassociation of replication protein A-XPA complex upon DNA damage: implications for RPA handing off

RPA (replication protein A), the eukaryotic ssDNA (single-stranded DNA)-binding protein, participates in most cellular processes in response to genotoxic insults, such as NER (nucleotide excision repair), DNA, DSB (double-strand break) repair and activation of cell cycle checkpoint signalling. RPA interacts with XPA (xeroderma pigmentosum A) and functions in early stage of NER. We have shown that in cells the RPA-XPA complex disassociated upon exposure of cells to high dose of UV irradiation. The dissociation required replication stress and was partially attributed to tRPA hyperphosphorylation. Treatment of cells with CPT (camptothecin) and HU (hydroxyurea), which cause DSB DNA damage and replication fork collapse respectively and also leads to the disruption of RPA-XPA complex. Purified RPA and XPA were unable to form complex in vitro in the presence of ssDNA. We propose that the competition-based RPA switch among different DNA metabolic pathways regulates the dissociation of RPA with XPA in cells after DNA damage. The biological significances of RPA-XPA complex disruption in relation with checkpoint activation, DSB repair and RPA hyperphosphorylation are discussed.     

Ni and Co Segregations on Selective Surface Facets and Rational Design of Layered Lithium Transition‐Metal Oxide Cathodes

The chemical processes occurring on the surface of cathode materials during battery cycling play a crucial role in determining battery's performance. However, the understanding of such surface chemistry is far from clear due to the complexity of redox chemistry during battery charge/discharge. Through intensive aberration corrected STEM investigation on ten layered oxide cathode materials, two important findings on the pristine oxides are reported. First, Ni and Co show strong plane selectivity when building up their respective surface segregation layers (SSLs). Specifically, Ni‐SSL is exclusively developed on (200)_m facet in Li–Mn‐rich oxides (monoclinic C2/m symmetry) and on (012)_h facet in Mn–Ni equally rich oxides (hexagonal R‐3m symmetry), while Co‐SSL has a strong preference to (20?2)_m plane with minimal Co‐SSL also developed on some other planes in Li–Mn‐rich cathodes. Structurally, Ni‐SSLs tend to form spinel‐like lattice while Co‐SSLs are in a rock‐salt‐like structure. Second, by increasing Ni concentration in these layered oxides, Ni and Co SSLs can be suppressed and even eliminated. The findings indicate that Ni and Co SSLs are tunable through controlling particle morphology and oxide composition, which opens up a new way for future rational design and synthesis of cathode materials.