Band-selective Holstein polaron in Luttinger liquid material A0.3MoO3 (A = K, Rb).

(Quasi-)one-dimensional systems exhibit various fascinating properties such as Luttinger liquid behavior, Peierls transition, novel topological phases, and the accommodation of unique quasiparticles (e.g., spinon, holon, and soliton, etc.). Here we study molybdenum blue bronze A0.3MoO3 (A = K, Rb), a canonical quasi-one-dimensional charge-density-wave material, using laser-based angle-resolved photoemission spectroscopy. Our experiment suggests that the normal phase of A0.3MoO3 is a prototypical Luttinger liquid, from which the charge-density-wave emerges with decreasing temperature. Prominently, we observe strong renormalizations of band dispersions, which are recognized as the spectral function of Holstein polaron derived from band-selective electron-phonon coupling in the system. We argue that the strong electron-phonon coupling plays an important role in electronic properties and the charge-density-wave transition in blue bronzes. Our results not only reconcile the long-standing heavy debates on the electronic properties of blue bronzes but also provide a rare platform to study interesting excitations in Luttinger liquid materials.

[Detection of EDA gene mutation and phenotypic analysis in patients with hypohidrotic ectodermal dysplasia].

OBJECTIVE: To detect the ectodysplasin A (EDA) gene mutation in patients with hypohidro-tic ectodermal dysplasia (HED), and to analyze the distribution pattern of missing permanent teeth and the systemic manifestation of HED patients with EDA gene mutation. METHODS: Twelve HED families were enrolled from clinic for genetic history collection, systemic physical examination and oral examination. Peripheral blood or saliva samples were collected from the probands and the family members to extract genomic DNA. PCR amplification and Sanger sequencing were utilized to detect the EDA gene variations, which were compared with the normal sequence (NM_001399.5). The functional impact of EDA gene variants was then evaluated by functional prediction of mutation, conservation analysis and protein structure prediction. The pathogenicity of each EDA gene variation was assessed according to the stan-dards and guidelines of the American College of Medical Genetics and Genomics (ACMG). The systemic phenotype and missing permanent tooth sites of HED patients with EDA gene mutations were summarized, and the missing rate of each tooth position was analyzed and compared. RESULTS: Eight out of twelve HED families were identified to carry EDA gene mutations, including: c.164T>C(p.Leu55Pro); c.457C>T (p.Arg153Cys); c.466C>T(p.Arg156Cys); c. 584G>A(p.Gly195Glu); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys). Among them, c.164T>C(p.Leu55Pro); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys) were novel mutations. The HED patients with EDA gene mutations in this study were all male. Our results showed that the average number of missing permanent teeth was 13.86±4.49, the average number of missing permanent teeth in the upper jaw was 13.14±5.76, the missing rate was 73.02%. And in the lower jaw, the average number of missing permanent teeth was 14.57±3.05, the missing rate was 80.95%. There was no significant difference in the number of missing teeth between the left and right sides of the permanent dentition (P>0.05). Specifi-cally, the maxillary lateral incisors, the maxillary second premolars and the mandibular lateral incisors were more likely to be missing, while the maxillary central incisors, the maxillary and mandibular first molars had higher possibility of persistence. CONCLUSION: This study detected novel EDA gene pathogenic variants and summarized the distribution pattern of missing permanent teeth of HED patients, thus enriched the variation and phenotype spectrum of EDA gene, and provided new clinical evidence for genetic diagnosis and prenatal consultation.

Ground-to-satellite time and frequency synchronization link with active carrier phase compensation.

In this paper, a synchronization link between one ground station and one geostationary satellite is established. The ground station receives retransmitted signals from the satellite, measures phase delay along the propagation route, and actively compensates back to its sending signals, realizing real-time phase fluctuation compensation. The transmitted signal contains two frequencies to eliminate common-mode phase noise. The difference between their carrier phase delays is measured. Different modes of carrier phase variation are separated and compensated, achieving a remaining time jitter of ±200 ps. Major sources of error are analyzed, and potential methods for improvement are discussed. The proposed ground-to-satellite link and active compensation method has potential applications in frequency standard dissemination to remote receivers (including ground stations or satellites). These potential applications justify further study of this system.

Retraction RETRACTION of "Efficacy and safety of nucleoside analogues in preventing vertical transmission of the hepatitis B virus from father to infant", by L.-H. Cao, P.-L. Zhao, Z.-M. Liu, S.-C. Sun, D.-B. Xu, J.-D. Zhang and Z.-H. Shao - Genet. Mol. Res. 14 (4): 15539-15546 (2015).

The retracted article is: Cao L-H, Zhao P-L, Liu Z-M, Sun S-C, et al. (2015). Efficacy and safety of nucleoside analogues in preventing vertical transmission of the hepatitis B virus from father to infant. Genet. Mol. Res. 14: 15539-15546. The article published in Genetics and Molecular Research 14 (4): 15539-15546 (2015) is a very good paper, but it appears that the authors' group submitted this manuscript to multiple journals, which is ethical misconduct. This manuscript (similar language and identical data) was published in the Experimental and Therapeutic Medicine Journal prior to being submitted to GMR. There are parts copied from "Efficacy and safety of nucleoside analogs on blocking father-to-infant vertical transmission of hepatitis B virus", by Li-Hau Cao, Pei-Li Zhao, Zhi-Min Liu, Shao-Chun Sun, et al. Exp. Ther. Med. 9 (6): 2251-2256 (2015) - DOI: 10.3892/etm.2015.2379. The GMR editorial staff was alerted and after a thorough investigation, there is strong reason to believe that the peer review process was failure. Also, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). The authors and their institutions were advised of this serious breach of ethics.

The antidepressant roles of Wnt2 and Wnt3 in stress-induced depression-like behaviors.

Wnts-related signaling pathways have been reported to play roles in the pathogenesis of stress-induced depression-like behaviors. However, there is relatively few direct evidence to indicate the effect of Wnt ligands on this process. Here, we investigated the role of Wnts in mediating chronic restraint stress (CRS)-induced depression-like behaviors. We found that CRS induced a significant decrease in the expression of Wnt2 and Wnt3 in the ventral hippocampus (VH) but not in the dorsal hippocampus. Knocking down Wnt2 or Wnt3 in the VH led to impaired Wnt/ß-catenin signaling, neurogenesis deficits and depression-like behaviors. In contrast, overexpression of Wnt2 or Wnt3 reversed CRS-induced depression-like behaviors. Moreover, Wnt2 and Wnt3 activated cAMP response element-binding protein (CREB) and there was CREB-dependent positive feedback between Wnt2 and Wnt3. Finally, fluoxetine treatment increased Wnt2 and Wnt3 levels in the VH and knocking down Wnt2 or Wnt3 abolished the antidepressant effect of fluoxetine. Taken together, our study indicates essential roles for Wnt2 and Wnt3 in CRS-induced depression-like behaviors and antidepressant.

Antiviral response and resistance analysis of treatment-naïve HCV-infected patients receiving single and multiple doses of GS-9190.

GS-9190 is a NS5B non-nucleoside analogue with demonstrated effectiveness in a Phase 1 monotherapy study and in combination with other DAAs for treatment of chronic HCV infection. Here, the resistance profile of GS-9190 monotherapy in a Phase 1b study was investigated. Resistance analysis was performed by population sequencing and allele-specific PCR (AS-PCR) for Y448H with an assay cut-off of 0.5%. Phenotypic susceptibility analyses were performed on patient isolates as well as site-directed mutagenesis of mutations selected during monotherapy. No resistance-associated variants were observed in patients before or after receiving single doses of GS-9190 by population sequencing. In contrast, in patients who received GS-9190 for 8 days, mutations Y448H and Y452H in NS5B were observed by population sequencing in 21/36 (58%) and 2/36 (5.6%) patients, respectively, at Day 8 or Day 14. Among the remaining 15 patients who had no detectable Y448H at Day 8 or Day 14 by population sequencing, low frequencies of Y448H ranging from 1.3 to 9.7% were detected in 14 of 15 patients by AS-PCR. By AS-PCR, Y448H remained detectable at reduced frequency in the majority of patients analysed through 4-6 months of follow-up. Chimeric HCV replicons constructed with the NS5B sequence from patients with Y448H and Y448H + Y452H/Y demonstrated 27-fold and 78.5-fold reduced susceptibility to GS-9190. In conclusion, Y448H was rapidly selected in the majority of patients receiving multiple doses of GS-9190 as monotherapy, despite undetectable levels in pretreatment samples. Y448H confers reduced susceptibility to GS-9190 and other NNIs and persisted in most patients for months post-treatment.

Efficacy and safety of nucleoside analogues in preventing vertical transmission of the hepatitis B virus from father to infant.

We examined the efficacy and safety of nucleoside analogues in preventing the vertical transmission of hepatitis B virus (HBV) from father to infant. We included 201 patients who visited the liver clinic of our hospital. The patients were positive for HBV surface antigen (HBsAg), HBeAg, anti-HBc, and HBV DNA; 189 patients (94%) had abnormal liver function. In all couples, the fathers were HBV DNA-negative and had normal liver function, and the mothers were anti-HB-positive before pregnancy. The control group comprised 188 couples who visited our hospital during the same time period. The fathers in the control group were positive for HBsAg, HBeAg, anti-HBc, and HBV DNA. The mothers were HBsAg-negative and anti-HBs-positive. No infants in the case group were HBsAg-positive and HBV DNA-positive, and all were anti-HBs-positive, indicating that father to infant HBV vertical transmission was prevented in the case group. In the control group, 147 of 188 newborns (78.2%) were anti-HBs-positive at birth, 28 (14.9%) were HBV DNA-positive, and 19 (10.1%) were HBsAg-positive. A significant difference was observed between the two groups. No statistically significant difference was observed in the gestational age, birth weight, birth length, 1-min and 8-min Apgar score, jaundice, other internal and surgical diseases, delivery mode, and other birth information between the neonates born to couples in the case and control groups; there were no fetal malformations and stillbirths in the two groups. Our results showed that administration of antiretroviral therapy to HBV DNA-positive fathers before pregnancy can cause a decrease in the viral load and prevent father to infant HBV vertical transmission. The use of antiviral nucleoside analogues before pregnancy was safe in fathers, and the fathers who wanted children could continue to use anti-viral therapy. The sample size in our study was small, and further studies with a large sample size and longer follow-up time are required for determining the use of nucleoside analogues from the point view of prenatal and postnatal care.

Proteomic analysis revealed the altered kidney protein profile of a Cyld knockout mouse model.

The aim of this study was to compare the proteomics pattern of the kidneys from Cyld knockout mice with that from normal mouse kidneys and establish a preliminary understanding of the role of Cyld in the kidney. Proteins from the kidneys of knockout Cyld mice and wild-type mice were extracted, isobaric tags for relative and absolute quantitation (iTRAQ) was performed, and the proteomics patterns of the two groups were compared. The genotypes of the mice were verified by polymerase chain reaction. A total of 1748 proteins with a local false discovery rate of ≤5% were identified, among which 1437 proteins were reliably recognized and quantified. The expression of two dysregulated proteins was confirmed by Western blotting. Gene ontology and pathway analyses indicated that the proteins identified were involved in biological processes, cell components, and molecular functions, and participated in different pathways. Some of the proteins identified were relevant to renal function or kidney diseases. The difference between the proteomics profiles of kidneys from Cyld knockout mice and wild-type mice was prominent, which correlates to kidney dysfunction and the development of renal diseases.

Efficacy of combined hepatitis B immunoglobulin and hepatitis B vaccine in blocking father-infant transmission of hepatitis B viral infection.

The aim of this study was to examine the efficacy of combined immunization of hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine (HBVac) in blocking father-infant transmission of hepatitis B virus (HBV). Newborns positive at birth for blood HBV sur-face antigen (HBsAg) and/or HBV DNA were selected and immunized with HBIG combination HBVac. At 7 months, HBV markers and HBV DNA of each neonate were measured using electrochemiluminescence with the Cobas-e-411 Automatic Electrochemiluminescence Immuno-assay Analyzer and fluorescence quantitative polymerase chain reaction. Among all 7-month-old subjects, the negative conversion rates of HBV DNA and HBsAg were 48/61 (78.7%) and 19/41 (46.3%), respectively. Therefore, this study demonstrated that prompt combination injection of HBIG and HBVac can protect some of the HBV DNA- and/ or HBsAg-positive newborns from HBV.

HTLV-1 Tax deregulates autophagy by recruiting autophagic molecules into lipid raft microdomains.

The retroviral oncoprotein Tax from human T-cell leukemia virus type 1 (HTLV-1), an etiological factor that causes adult T-cell leukemia and lymphoma, has a crucial role in initiating T-lymphocyte transformation by inducing oncogenic signaling activation. We here report that Tax is a determining factor for dysregulation of autophagy in HTLV-1-transformed T cells and Tax-immortalized CD4 memory T cells. Tax facilitated autophagic process by activating inhibitor of κB (IκB) kinase (IKK) complex, which subsequently recruited an autophagy molecular complex containing Beclin1 and Bif-1 to the lipid raft microdomains. Tax engaged a crosstalk between IKK complex and autophagic molecule complex by directly interacting with both complexes, promoting assembly of LC3+ autophagosomes. Moreover, expression of lipid raft-targeted Bif-1 or Beclin1 was sufficient to induce formation of LC3+ autophagosomes, suggesting that Tax recruitment of autophagic molecules to lipid rafts is a dominant strategy to deregulate autophagy in the context of HTLV-1 transformation of T cells. Furthermore, depletion of autophagy molecules such as Beclin1 and PI3 kinase class III resulted in impaired growth of HTLV-1-transformed T cells, indicating a critical role of Tax-deregulated autophagy in promoting survival and transformation of virally infected T cells.

Involvement of FoxO1 in the effects of follicle-stimulating hormone on inhibition of apoptosis in mouse granulosa cells.

In mammalian ovaries, follicular atresia occurs periodically and destroys almost all the follicles in the ovary. Follicle-stimulating hormone (FSH) acts as the primary survival factor during follicular atresia by preventing apoptosis in granulosa cells. FoxO1 is a critical factor in promoting follicular atresia and granulosa cell apoptosis. FSH inhibits the induction of FoxO1. In this report, we investigated the role of FSH-FoxO1 pathway in mouse follicular atresia. FSH dampened stress-induced apoptosis and the expression of FoxO1 and pro-apoptosis genes in mouse granulosa cells (MGCs). In contrast, overexpression of FoxO1 inhibited the viability of MGCs and induced the expression of endogenous FoxO1. The signaling cascades involved in regulating FoxO1 activity upon FSH treatment were identified using FSH signaling antagonists. Blocking protein kinase A (PKA), phosphatidylinositol-3 kinase (PI3K) or protein kinase B (AKT) restored the upregulation of FoxO1 and apoptotic signals, which was suppressed by FSH. Moreover, inhibition of PKA or PI3K impaired FSH-induced AKT activity, but inactivation of PI3K or AKT had little effect on PKA activity in the presence of FSH. Correspondingly, constitutive activation of FoxO1 (all three AKT sites were replaced by alanines) also promoted MGC apoptosis despite FSH administration. Furthermore, both luciferase reporter assays and chromatin immunoprecipitation assays showed that FoxO1 directly bound to a FoxO-recognized element site within the FoxO1 promoter and contributed to the regulation of FoxO1 expression in response to FSH. Taken together, we propose a novel model in which FSH downregulates FoxO1-dependent apoptosis in MGCs by coordinating the PKA-PI3K-AKT-FoxO1 axis and FoxO1-FoxO1 positive feedback.

Single nucleotide polymorphism analysis of exons 3 and 4 of IGF-1 gene in pigs.

The IGF-1 gene has been implicated as a candidate gene for the regulation of pig growth traits. We analyzed exons 3 and 4 of IGF-1 gene polymorphisms of the Banna mini-pig (28), the Tibetan mini-pig (30), the Junmu pig (55), and L. Yorkshire species (50) using PCR-SSCP. Three genotypes in exon 3 and 6 genotypes in exon 4 were observed, among which, one single nucleotide polymorphism, G201A, on exon 3 and two single nucleotide polymorphisms, A440G and T455C, on exon 4 were found. Statistical analysis of genotype frequencies revealed that the A allele was dominant in the large pig at the G201A locus (PIC = 0.20-0.34), and the AT alleles were dominant in the large pig at the A440G and T455C loci (PIC = 0.30-0.60). The genotype distribution between the various groups was significantly different (P< 0.01), with the highest heterozygosity seen in Junmu pigs at 0.223 and the lowest seen in L. Yorkshire at 0.098. The genetic distance of the Junmu pig from the L. Yorkshire is the smallest, the distance from the Tibetan miniature pigs is larger, and the distance from the Banna mini-pig is the largest. The IGF-1 gene polymorphism and heterozygosity results from various pig breeds indicate that IGF-1 is substantially polymorphic with significant difference of the polymorphic distribution and expression levels among various pig breeds. This information provides a theoretical basis for the genetic background of miniature pigs but also provides means to breed improved pig varieties.

Polyphenols from Parabarium huaitingii and their positive inotropic and anti-myocardial infarction effects in rats.

Eight phenolic compounds, including (-)-epicatechin (1) and seven proanthocyanidins (2-8), were obtained from the butanol extract of Parabarium huaitingii (PHB). Their chemical structures were identified based on analyses of mass spectra (MS), NMR, CD spectra, and partial acid catalyzed thiolytic degradation. The observation made by laser scanning confocal microscope found a significant increase of the concentration of intracellular Ca²+ ([Ca²+](i)) in single myocytes when the PHB was added, while compounds 1 and 3 had the same physiological effect. Further investigations showed PHB had a dose-dependent positive inotropic effect on isolated right atria and papillary muscle of left ventricle of the rat, while having no significant influence on the spontaneous beating rate of the isolated right atria. The inotropic effect of PHB could be greatly abolished by pretreating the myocardium in Ca²+-free solution. These findings indicated that PHB could significantly increase [Ca²+](i) in myocytes, which was greatly dependent on the influx of extracellular Ca²+. Compounds 1 and 3 might be the effective ingredients of the inotropic effect of PHB. In addition, PHB could also significantly decrease the infarct size of the heart on acute myocardial infarction (AMI) model rats, which suggested its myocardial protective effect on ischemic myocardium. The positive inotropic effect of PHB, together with its myocardial protective effect on AMI, suggested that PHB had a promising potential for the prevention and treatment of heart failure, especially the one that was caused by AMI.

Estimation of inhibitory quotient using a comparative equilibrium dialysis assay for prediction of viral response to hepatitis C virus inhibitors.

The relationship of inhibitory quotient (IQ) with the virologic response to specific inhibitors of human hepatitis C virus (HCV) and the best method to correct for serum protein binding in calculating IQ have not been addressed. A common method is to determine a fold shift by comparing the EC(50) values determined in cell culture in the absence and presence of human serum (fold shift in EC(50) ), but this method has a number of disadvantages. In the present study, the fold shifts in drug concentrations between 100% human plasma (HP) and cell culture medium (CCM) were directly measured using a modified comparative equilibrium dialysis (CED) assay for three HCV protease inhibitors (PIs) and for a novel HCV inhibitor GS-9132. The fold shift values in drug concentration between the HP and CCM (CED ratio) were ∼1 for SCH-503034, VX-950 and GS-9132 and 13 for BILN-2061. These values were ∼3-10-fold lower than the fold shift values calculated from the EC(50) assay for all inhibitors except BILN-2061. Using the CED values, a consistent pharmacokinetic and pharmacodynamic relationship was observed for the four HCV inhibitors analysed. Specifically, an approximate 1 log(10) reduction in HCV RNA was achieved with an IQ close to 1, while 2-3 and greater log(10) reductions in HCV RNA were achieved with IQ values of 3-5 and greater, respectively. Thus, use of CED to define IQ provides a predictive and quantitative approach for the assessment of the in vivo potency of HCV PIs and GS-9132. This method provides a framework for the evaluation of other classes of drugs that are bound by serum proteins but require the presence of serum for in vitro evaluation.

Natural variation in drug susceptibility to HCV polymerase inhibitors in treatment-naïve HCV patient isolates.

Summary. To assess the natural variation in drug susceptibility among treatment-naïve hepatitis C virus (HCV) patient isolates, the susceptibilities of chimeric replicons carrying the HCV NS5B polymerase from up to 51 patient isolates against a panel of diverse HCV nonnucleoside polymerase inhibitors were evaluated using a replicon-based transient replication assay. Some patient to patient variation in susceptibility to the panel of three HCV nonnucleoside polymerase inhibitors was observed. Linear regression and correlation analyses revealed no correlations among the susceptibilities to the polymerase inhibitors tested. Our results suggest that variable antiviral responses to HCV nonnucleoside polymerase inhibitors may be observed because of the natural variation in baseline susceptibility. In addition, the lack of correlation among the susceptibilities to three classes of HCV polymerase inhibitors evaluated here supports their possible combined use in a combination therapy strategy.

CYLD: a tumor suppressor deubiquitinase regulating NF-kappaB activation and diverse biological processes.

Protein ubiquitination is a reversible reaction, in which the ubiquitin chains are deconjugated by a family of deubiquitinases (DUBs). The presence of a large number of DUBs suggests that they likely possess certain levels of substrate selectivity and functional specificity. Indeed, recent studies show that a tumor suppressor DUB, cylindromatosis (CYLD), has a predominant role in the regulation of NF-kappaB, a transcription factor that promotes cell survival and oncogenesis. NF-kappaB activation involves attachment of K63-linked ubiquitin chains to its upstream signaling factors, which is thought to facilitate protein-protein interactions in the assembly of signaling complexes. By deconjugating these K63-linked ubiquitin chains, CYLD negatively regulates NF-kappaB activation, which may contribute to its tumor suppressor function. CYLD also regulates diverse physiological processes, ranging from immune response and inflammation to cell cycle progression, spermatogenesis, and osteoclastogenesis. Interestingly, CYLD itself is subject to different mechanisms of regulation.

Distal trisomy of 10q with distal monosomy of 15q due to a paternal translocation.

Distal trisomy of 10q is a rare chromosomal abnormality. Distal deletions of the terminal long arm of chromosome 15 have rarely been described. We report on a male infant with low birth weight and microcephaly, a flat face with a spacious forehead, low-set ears, blepharophimosis, microphthalmia, a small nose, and a depressed nasal bridge. Microarray comparative genomic hybridization identified that he had the karyotype 46, XY, der (15) t (10;15) (q25.2;q26.2) pat, with chromosomal breakpoints at 10q25.2 and 15q26.2. This male neonatal case had an unbalanced translocation inherited from his father who was a balanced carrier with the karyotype 46, XY, t (10;15) (q25;q26). The neonate had a partial trisomy of the long arm of chromosome 10 with a partial monosomy of distal 15q. The clinical features were in agreement with previous descriptions and allowed us to propose a growth retardation phenotype for this neonate case.

Species-specific in vitro pharmacological effects of the cannabinoid receptor 2 (CB2) selective ligand AM1241 and its resolved enantiomers.

BACKGROUND AND PURPOSE: Racemic (R,S) AM1241 is a cannabinoid receptor 2 (CB(2))-selective aminoalkylindole with antinociceptive efficacy in animal pain models. The purpose of our studies was to provide a characterization of R,S-AM1241 and its resolved enantiomers in vitro and in vivo. EXPERIMENTAL APPROACH: Competition binding assays were performed using membranes from cell lines expressing recombinant human, rat, and mouse CB(2) receptors. Inhibition of cAMP was assayed using intact CB(2)-expressing cells. A mouse model of visceral pain (para-phenylquinone, PPQ) and a rat model of acute inflammatory pain (carrageenan) were employed to characterize the compounds in vivo. KEY RESULTS: In cAMP inhibition assays, R,S-AM1241 was found to be an agonist at human CB(2), but an inverse agonist at rat and mouse CB(2) receptors. R-AM1241 bound with more than 40-fold higher affinity than S-AM1241, to all three CB(2) receptors and displayed a functional profile similar to that of the racemate. In contrast, S-AM1241 was an agonist at all three CB(2) receptors. In pain models, S-AM1241 was more efficacious than either R-AM1241 or the racemate. Antagonist blockade demonstrated that the in vivo effects of S-AM1241 were mediated by CB(2) receptors. CONCLUSIONS AND IMPLICATIONS: These findings constitute the first in vitro functional assessment of R,S-AM1241 at rodent CB(2) receptors and the first characterization of the AM1241 enantiomers in recombinant cell systems and in vivo. The greater antinociceptive efficacy of S-AM1241, the functional CB(2) agonist enantiomer of AM1241, is consistent with previous observations that CB(2) agonists are effective in relief of pain.

Molecular cytogenetic discrimination and reaction to wheat streak mosaic virus and the wheat curl mite in Zhong series of wheat--Thinopyrum intermedium partial amphiploids.

Thinopyrum intermedium (2n = 6x = 42, JJJsJsSS) is potentially a useful source of resistance to wheat streak mosaic virus (WSMV) and its vector, the wheat curl mite (WCM). Five partial amphiploids, namely Zhong 1, Zhong 2, Zhong 3, Zhong 4, and Zhong 5, derived from Triticum aestivum x Thinopyrum intermedium crosses produced in China, were screened for WSMV and WCM resistance. Zhong 1 and Zhong 2 had high levels of resistance to WSMV and WCM. The other three partial amphiploids, Zhong 3, 4, and 5, were resistant to WSMV, but were susceptible to WCM. Genomic in situ hybridization (GISH) using a genomic DNA probe from Pseudoroegneria strigosa (SS, 2n = 14) demonstrated that two partial amphiploids, Zhong 1 and Zhong 2, have almost the identical 10 Th. intermedium chromosomes, including four Js, four J, and two S genome chromosomes. Both of them carry two pairs of J and a pair of Js genome chromosomes and two different translocations that were not observed in the other three Zhong lines. The partial amphiploids Zhong 3, 4, and 5 have another type of basic genomic composition, which is similar to a reconstituted alien genome consisting of four S and four Js genome chromosomes of Th. intermedium (Zhong 5 has two Js chromosomes plus two Js-W translocations) with six translocated chromosomes between S and Js or J genomes. All three lines carry a specific S-S-Js translocated chromosome, which might confer resistance to barley yellow dwarf virus (BYDV-PAV). The present study identified a specific Js2 chromosome present in all five of the Zhong lines, confirming that a Js chromosome carries WSMV resistance. Resistance to WCM may be linked with J or Js chromosomes. The discovery of high levels of resistance to both WSMV and WCM in Zhong 1 and Zhong 2 offers a useful source of resistance to both the virus and its vector for wheat breeding programs.

Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha.

IkappaB kinase (IKK) is a key mediator of NF-kappaB activation induced by various immunological signals. In T cells and most other cell types, the primary target of IKK is a labile inhibitor of NF-kappaB, IkappaBalpha, which is responsible for the canonical NF-kappaB activation. Here, we show that in T cells infected with the human T-cell leukemia virus (HTLV), IKKalpha is targeted to a novel signaling pathway that mediates processing of the nfkappab2 precursor protein p100, resulting in active production of the NF-kappaB subunit, p52. This pathogenic action is mediated by the HTLV-encoded oncoprotein Tax, which appears to act by physically recruiting IKKalpha to p100, triggering phosphorylation-dependent ubiquitylation and processing of p100. These findings suggest a novel mechanism by which Tax modulates the NF-kappaB signaling pathway.