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Actinomycetes constitute a large group of Gram-positive bacteria present in different habitats. One of these habitats involves the association of these bacteria with insects. In this work, we have studied twenty-four actinomycetes strains isolated from the intestinal tract and feces from larvae of the xylophagous coleopteran Cerambyx welensii and have shown that seventeen strains present hydrolytic activity of some of the following substrates: cellulose, hemicellulose, starch and proteins. Fourteen of the isolates produce antimicrobial molecules against the Gram-positive bacteria Micrococcus luteus . Analysis of seven strains led us to identify the production of a wide number of compounds including streptanoate, alpiniamide A, alteramides A and B, coproporphyrin III, deferoxamine, demethylenenocardamine, dihydropicromycin, nocardamine, picromycin, surugamides A, B, C, D and E, tirandamycins A and B, and valinomycin. A significant number of other compounds, whose molecular formulae are not included in the Dictionary of Natural Products (DNP), were also present in the extracts analyzed, which opens up the possibility of identifying new active antibiotics. Molecular identification of ten of the isolated bacteria determined that six of them belong to the genus Streptomyces , two of them are included in the genus Amycolatopsis and two in the genus Nocardiopsis.

Background: Geographic variation in male response to sex pheromone lures has been studied in the field in a number of moth species. However, only a few studies have investigated geographic variation in female calling and sex pheromone under field conditions. For an effective field implementation of sex pheromone lures, it is essential to know the local sex pheromone blend and local timing of sexual communication. We investigated the level and extent of geographic variation in the sexual communication of the important agricultural pest Helicoverpa armigera (Lepidoptera, Noctuidae) in three continents., Results: We found there is no genetic variation in the calling behavior of H. armigera. In the female sex pheromone, we found more between-population variation than within-population variation. In male response experiments, we found geographic variation as well. Strikingly, when adding the antagonistic compound Z11-16:OAc to the pheromone blend of H. armigera, significantly fewer males were caught in Australia and China, but not in Spain. This variation is likely not only due to local environmental conditions, such as photoperiod and temperature, but also to the presence of other closely related species with which communication interference may occur., Conclusion: Finding geographic variation in both the female sexual signal and the male response in this pest calls for region-specific pheromone lures. Our study shows that the analysis of geographic variation in moth female sex pheromones as well as male responses is important for effectively monitoring pest species that occur around the globe. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Objective: To evaluate the performance of the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) criteria in terms of earlier patients' classification in comparison to the 1982/1997 ACR or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria., Materials and Methods: Patients from a Latin America, multiethnic, multicentre cohort, where SLE was defined using the physicians' diagnosis, were included. To calculate the sensitivity of the 2019 EULAR/ACR criteria, the 1982/1997 ACR criteria were considered the gold standard. Additionally, comparison of the 1982/1997 ACR criteria and the 2012 SLICC criteria with the 2019 EULAR/ACR criteria was performed., Results: The sensitivity of the 2019 EULAR/ACR criteria when compared with the 1982/1997 ACR criteria as the gold standard was 91.3%. This new set of criteria allowed an earlier SLE patient classification in 7.4% (mean 0.67 years) and 0.6% (mean 1.47 years) than the 1982/1997 ACR and the 2012 SLICC criteria, respectively. Patients accruing the 2019 EULAR/ACR earlier than the 1982/1997 ACR criteria were more likely to have high anti-dsDNA titres; those accruing them later were less likely to have mucocutaneous and joint manifestations; this was not observed when comparing them with the 2012 SLICC criteria., Conclusions: The 2019 EULAR/ACR criteria classified earlier only a small proportion of Latin America patients than with the two other criteria sets in real-life clinical practice scenarios. Further studies in different patient populations are needed before these new criteria are adopted worldwide., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Systemic lupus erythematosus (SLE) predominantly affects women. Clinical phenotype and outcomes in SLE may vary by sex and are further complicated by unique concerns that are dependent upon sex-defined roles. We aimed to describe sex differences in disease-specific quality of life (QoL) assessment scores using the Lupus Patient-Reported Outcome (LupusPRO) tool in a large international study., Methods: Cross-sectional data from 1,803 patients with SLE on demographics, self-identified sex status, LupusPRO, and disease activity were analyzed. The LupusPRO tool has 2 constructs: health-related QoL (HRQoL) and non-HRQoL. Disease activity and damage were evaluated using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, respectively. Nonparametric tests were used to compare QoL and disease activity by sex., Results: A total of 122 men and 1,681 women with SLE participated. The mean age was similar by sex, but the damage scores were greater among men. Men fared worse on the non-HRQoL social support domain than women (P = 0.02). When comparing disease and QoL among men and women ages ≤45 years, men were found to have greater damage and worse social support than women. However, women fared significantly worse on lupus symptoms, cognition, and procreation domains with trends for worse functioning on physical health and pain-vitality domains., Conclusion: In the largest study of a diverse group of SLE patients, utilizing a disease-specific QoL tool, sex differences in QoL were observed on both HRQoL and non-HRQoL constructs. Although men performed worse in the social support domain, women (especially those in the reproductive age group) fared worse in other domains. These observations may assist physicians in appropriately addressing QoL issues in a sex-focused manner., (© 2018, American College of Rheumatology.)

Three large saproxylic cerambycids with different pest/legal status co-occur in the Iberian oak woodlands, Cerambyx welensii (Cw), Cerambyx cerdo (Cc) and Prinobius myardi (Pm): Cw is an emerging pest, Cc is a protected but sometimes harmful species and Pm is a secondary/minor pest. A precise taxonomic diagnosis is necessary for research, management or protection purposes, but may be problematic mainly because Cw and Cc larvae are morphologically indistinguishable. To resolve this constraint, we genotyped adults, larvae and eggs collected over a wide geographical range using the mitochondrial barcoding of the cytochrome c oxidase subunit I (COI). A Neighbour-Joining tree phylogram revealed three distinct clusters corresponding to Cw, Cc and Pm. We further first sequenced for Cw and Cc two mitochondrial (12S rRNA and 16S rRNA) and one nuclear (28S rRNA) gene fragments. For the first two genes, interspecific divergence was lower than in COI, and for the 28S (lower mutation rate), the two species shared identical haplotypes. Two approaches for species delimitation (General Mixed Yule Coalescent (GMYC), Barcode Index Number (BIN)) confirmed the species distinctiveness of Cc and Cw. The Bayesian COI gene tree showed a remarkable genetic divergence between Cc populations from Iberia and the rest of Europe. Such divergence has relevant taxonomic connotations and stresses the importance of a wide geographical scale sampling for accurate DNA barcoding species identification. Incongruities between morphology/lineage and COI barcodes in some individuals revealed natural hybridization between Cw and Cc. Natural hybridization is important from a phylogenetic/evolutionary perspective in these cerambycids, but the prevalence of (and the behavioural/ecological factors involved in) interspecific cross-breeding remain to be investigated.

We analysed electroantennogram (EAG) responses of male and female adults of the European grapevine moth Lobesiabotrana (Denis et Schiffermüller) (Lepidoptera: Tortricidae) collected as larvae from grapevine ( Vitis vinifera L.) and flax-leaved daphne ( Daphne gnidium L.). The host-plant odorants tested were either V. vinifera -specific [1-octen-3-ol, ( E )-β-farnesene, ( E )-4,8-dimethyl-1,3,7-nonatriene], D. gnidium -specific (2-ethyl-hexan-1-ol, benzothiazole, linalool-oxide, ethyl benzanoate), or were shared by both host-plants (linalool, methyl salicylate). Sex pheromone compounds were also tested. The male response to the major pheromone component ( E 7, Z 9-12:Ac) was higher than to any other stimuli, whereas the response to the minor pheromone components ( E 7, Z 9-12:OH and Z 9-12:Ac) was not different from the response to the plant odorants. The female response to pheromone was lower or not different from that to plant odorants. Methyl salicylate elicited a higher response in females and ( E )-β-farnesene elicited a higher response than several other plant odorants in both sexes. Non-significant interactions between host-plant odorant and sex indicated an absence of sex specialization for host-plant volatile detection. The lack of a significant interaction between plant volatiles and larval host-plants suggested that there was no specialization for plant-volatile detection between V. vinifera and D. gnidium individuals., Competing Interests: The authors declare no conflict of interest.

Aims: To determine whether the proportion of time systemic lupus erythematosus patients achieve remission/low disease activity state (LDAS) is associated with a better quality of life (QoL)., Patients and Methods: Patients from a well-established multiethnic, multicentre US cohort were included: remission: Systemic Lupus Activity Measure (SLAM) score=0, prednisone≤5 mg/day and no immunosuppressants); LDAS not in remission, SLAM score≤3, prednisone≤7.5 mg/day, no immunosuppressants; the combined proportion of time patients were in these states was the independent variable. The endpoints were the Physical and Mental Components Summary measures (PCS and MCS, respectively) and the individual subscales of the Short Form (SF)-36 at the last visit. Linear regression was used to estimate the association between the proportion of follow-up time in remission/LDAS and the SF-36 measures with and without adjustment for possible confounders., Results: Four hundred and eighty-three patients were included. The per cent of time on remission/LDAS was associated with better QoL after adjusting for potential confounders; for the PCS the parameter estimate was 9.47 (p<0.0001), for the MCS 5.89 (p=0.0027), and for the subscales they ranged between 7.51 (p=0.0495) for mental health and 31.79 (p<0.0001) for role physical., Conclusions: The per cent of time lupus patients stay on remission/LDAS is associated with a better QoL as measured by SF-36., Competing Interests: Competing interests: None declared.

Cerambyx cerdo (Cc) is a protected saproxylic beetle in Europe, although it is increasingly reported as an oak 'pest'. Cc ecological features are relatively well known, but, its reproductive biology is still poorly understood. Hence, we investigated the reproductive traits of Cc under laboratory conditions. In females, body length was 44.1 ± 0.9 mm, 28-53 (mean ± SE, range); fecundity 143 ± 11 eggs, 33-347; fertility 78 ± 1%, 65-93; oviposition period 44 ± 3 days, 13-128 and longevity 59 ± 5 days, 16-157. Fecundity was positively correlated with female size, longevity and oviposition period. Daily fecundity was 3.5 ± 0.2 eggs/day, 0.9-6.5 showing a fluctuating synovigenic pattern with a slight decreasing trend over time. Egg length was 3.74 ± 0.01 mm, 2.3-6.0 and egg volume 5.45 ± 0.04 mm3, 2.4-9.6. Egg size was correlated with female size, but, the relative size of eggs was larger in smaller females. Incubation time was 13.5 ± 0.1 days, 7-28. Hatching was superior in larger eggs and neonate size was positively correlated to egg volume. Females were polyandrous (up to 19 matings), but, multiple mating did not enhance fecundity or fertility. In males, body length was 41.8 ± 0.8 mm, 29-53 and longevity 49 ± 3 days, 9-124. Male longevity was unrelated to body size. Males were polygynous (up to 16 matings) and mating number did not affect male longevity. Overall, females were larger and lived longer than males. Cc reproductive traits are compared with those other Cerambycidae, especially with the congeneric pest Cerambyx welensii. Our data may be valuable to improve the protection/management measures of Cc in dehesa woodlands and other oak forests.

The longhorn beetle Cerambyx welensii is an emerging pest involved in oak decline episodes, whose damage is increasingly reported in dehesa open woodlands. Knowledge of the reproductive biology of C. welensii is a crucial goal due to its new pest status. In this study, we assess the reproductive traits of both sexes in the laboratory (25°C and 60% relative humidity ). In females, body length was 44.9 ± 0.9 mm (mean ± SE), fecundity 132 ± 12 eggs, fertility 70 ± 1 %, longevity 70 ± 3 days, preoviposition period 2 ± 0.2 days, oviposition period 44 ± 3 days and postoviposition period 19 ± 3 days. Fecundity was positively correlated with female size, longevity and oviposition period. Daily fecundity was 3.0 ± 0.2 eggs/day and showed a fluctuating synovigenic pattern with a slight decreasing trend over time. Egg length was 4.24 ± 0.01 mm and egg volume 8.14 ± 0.04 mm3. Egg size was correlated with female size but the relative size of eggs was larger in smaller females. Incubation time was 13.9 ± 0.1 days and hatching did not depend on egg size. Neonate size was positively correlated with egg length. Females were polyandrous (more than 20 lifetime matings) but multiple mating did not increase fecundity, fertility or longevity. In males, body length was 43.7 ± 0.6 mm and longevity 52 ± 3 days. Unlike with females, longevity was positively correlated with male size. Males were polygynous (up to 30 lifetime matings) but mating history did not affect male longevity. Rather to the contrary, long-lived males mated more times because they had more mating chances. Lastly, C. welensii reproductive traits were compared with those other Cerambycidae species and discussed from an adaptive perspective. Our data will be useful to improve management of C. welensii in order to prevent or mitigate its impact in dehesa woodlands and other oak forests.

Background: A binary co-occluded mixture (HearSP1B:LB6) of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) variants was previously found to be highly pathogenic under laboratory conditions. The insecticidal efficacy and persistence of this mixture were determined in greenhouse and field-grown tomato crops in Spain and Portugal., Results: Concentrations of 10(9) -10(11) occlusion bodies (OBs) L(-1) of HearSP1B:LB6 resulted in 89-100% mortality of larvae on treated tomato plants in growth chambers. In protected tomato crops, application of 10(10) OBs L(-1) of HearSP1B:LB6 was as effective as Bacillus thuringiensis (Bt) and spinosad in reducing the percentage of damaged fruits, and resulted in higher larval mortality than the Bt treatment. In open-field tomato crops, virus treatments were as effective in reducing the percentage of damaged fruit as spinosad, Bt and chlorpyrifos treatments. The persistence of the insecticides on tomato plants was negatively correlated with solar radiation in both field and greenhouse settings. Residual insecticidal activity of OBs on protected tomato crops at 6 days post-application was 55 and 35% higher than that of Bt and spinosad respectively. On field-grown tomato, OB persistence was significantly lower than with spinosad or chlorpyrifos., Conclusion: The efficacy and persistence of HearSP1B:LB6 OBs were comparable with those of commercial insecticides in both field and greenhouse tomato crops. Future studies should focus on reducing application rates to determine insecticidal efficacy at lower OB concentrations. © 2015 Society of Chemical Industry., (© 2015 Society of Chemical Industry.)

The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-κB and mitogen-activated protein kinase activity.

Polyandry is perhaps the most puzzling component of mating systems because the fitness benefits for females of mating with more than one male during lifetime are poorly understood. The occurrence and extent of polyandry varies considerably both among and within species, and a positive association between polyandry and fecundity is widespread but not universal. The scenario is further complicated because the scientific literature on this issue includes studies that are often inconclusive or contradictory even for the same target species. A previous meta-analysis detected the crucial importance of two usually neglected aspects that potentially bias the interpretation of primary studies about the polyandry-fecundity relationship: the methodological approach--experimental or descriptive--and the polyandry concept itself--realized or potential. In this paper, we experimentally test the effect of these aspects with the moth Lobesia botrana. We used an innovative protocol in which the experimental and the descriptive methods were conducted simultaneously on the same target population and the results were then interpreted from the perspective of both concepts of polyandry. The results clearly showed that 1) the conclusions about the polyandry-fecundity relationship were strongly dependent on the methodological approach used and 2) the concept of polyandry invoked by the researcher was a confounding effect that potentially biases data interpretation. We suggest that greater attention must be paid to intraspecific variation among females in their propensity to remate. The differentiation in experimental studies between potentially polyandrous and monandrous phenotypes could greatly improve our knowledge about the maintenance of female mating polymorphism in most species and the adaptive significance of polyandry., (© 2012 The Author. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.)

Objective: The increased risk of thrombosis in systemic lupus erythematosus (SLE) may be partially explained by interrelated genetic pathways for thrombosis and SLE. The present study was undertaken to investigate whether 33 established and novel single-nucleotide polymorphisms (SNPs) in 20 genes involved in hemostasis pathways that have been associated with deep venous thrombosis (DVT) in the general population are risk factors for SLE among Asian subjects., Methods: Patients in the discovery cohort were enrolled in 1 of 2 North American SLE cohorts. Patients in the replication cohort were enrolled in 1 of 4 Asian or 2 North American cohorts. We first genotyped 263 Asian patients with SLE and 357 healthy Asian control subjects for 33 SNPs in the discovery phase, and then genotyped 5 SNPs in up to an additional 1,496 patients and 993 controls in the replication phase. Patients were compared to controls for bivariate association with minor alleles. Principal components analysis was used to control for intra-Asian ancestry in the replication cohort., Results: Two genetic variants in the gene VKORC1 were highly significant in both the discovery and replication cohorts: rs9934438 (in the discovery cohort, odds ratio [OR] 2.45, P=2×10(-9); in the replication cohort, OR 1.54, P=4×10(-6)) and rs9923231 (in the discovery cohort, OR 2.40, P=6×10(-9); in the replication cohort, OR 1.53, P=5×10(-6)). These associations were significant in the replication cohort after adjustment for intra-Asian ancestry: for rs9934438, OR 1.34, P=0.0029; for rs9923231, OR 1.34, P=0.0032., Conclusion: Genetic variants in VKORC1, which are involved in vitamin K reduction and associated with DVT, correlate with SLE development in Asian subjects. These results suggest that there may be intersecting genetic pathways for the development of SLE and thrombosis., (Copyright © 2013 by the American College of Rheumatology.)

Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p(meta-Euro) = 2.08 × 10(-10)), transmembrane protein 39A (TMEM39A; rs1132200; p(meta-all) = 8.62 × 10(-9)), and 17q21 (rs1453560; p(meta-all) = 3.48 × 10(-10)) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 × 10(-8) < p(meta-Euro) < 9.99 × 10(-5)) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation., (Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in ∼8370 patients with SLE and ∼7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P=2.99E-13, OR=5.2, 95% CI=3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis.

Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 × 10(-8), odds ratio = 1.70) and Korean (P = 8.33 × 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-κB subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.

Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10(-8)) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10(-8), OR = 0.83) and rs387619 (p = 7.7 × 10(-7), OR = 0.83) in the European samples with p(meta) = 1.82 × 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10(-3), OR = 0.81 and p = 4.3 × 10(-4), OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p(meta) = 2.36 × 10(-13). This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.

A combined forward and reverse genetic approach was undertaken to test the candidacy of IRAK1 (interleukin-1 receptor associated kinase-1) as an X chromosome-encoded risk factor for systemic lupus erythematosus (SLE). In studying approximately 5,000 subjects and healthy controls, 5 SNPs spanning the IRAK1 gene showed disease association (P values reaching 10(-10), odds ratio >1.5) in both adult- and childhood-onset SLE, in 4 different ethnic groups, with a 4 SNP haplotype (GGGG) being strongly associated with the disease. The functional role of IRAK1 was next examined by using congenic mouse models bearing the disease loci: Sle1 or Sle3. IRAK1 deficiency abrogated all lupus-associated phenotypes, including IgM and IgG autoantibodies, lymphocytic activation, and renal disease in both models. In addition, the absence of IRAK1 reversed the dendritic cell "hyperactivity" associated with Sle3. Collectively, the forward genetic studies in human SLE and the mechanistic studies in mouse models establish IRAK1 as a disease gene in lupus, capable of modulating at least 2 key checkpoints in disease development. This demonstration of an X chromosome gene as a disease susceptibility factor in human SLE raises the possibility that the gender difference in SLE may in part be attributed to sex chromosome genes.

Tobacco (Nicotiana tabaccum L.) is among the most important crops in La Vera Region (Cáceres, west-central Spain) where, since 2001, flue-cured tobacco plants showing typical symptoms of a vascular disease associated to the cyst nematode (Globodera tabacum) complex have been frequently observed (2). Symptoms observed were wilting, yellowing, and drying of the leaves, usually on one side of the plant; stunted and distorted leaves with curved midribs due to the unequal growth; and brown vascular discoloration of stems and midribs. Several diseased plants were collected during the summers of 2003 and 2004, and F. oxysporum was consistently isolated from sections of necrotic midribs. To confirm the pathogenicity of F. oxysporum isolates, plants of flue-cured tobacco (cv. Ct-681) were inoculated. Since Fusarium wilt of tobacco may be caused by F. oxysporum f. sp. vasinfectum or F. oxysporum f. sp. batatas (1), plants of cotton (cv. Acala) and sweet potato (cvs. Nemagold and Nancy Hall) were also inoculated to determine the forma specialis designation. Twenty plants per cultivar and isolate were inoculated with six isolates at the two to four true-leaf stage by pouring into the substrate 200 ml of a conidial suspension (1 × 10 5 CFU/ml). After inoculation, plants were incubated in a growth chamber at 28°C (day) and 24°C (night) with a 16-h photoperiod. All six F. oxysporum isolates were pathogenic to tobacco and sweet potato, but there were differences among isolates in time from inoculation to appearance of first disease symptoms (7 to 15 days after inoculation in tobacco and sweet potato) and also in disease severity 30 days after inoculation (60 to 100% wilt or mortality in tobacco and 50 to 100% in sweet potato). F. oxysporum was reisolated from stems of inoculated plants. No disease symptom was observed in cotton plants 60 days after inoculation, and F. oxysporum was not reisolated from them. Results of inoculation on the differential hosts indicated that disease symptoms in tobacco were caused by F. oxysporum f. sp. batatas. To our knowledge, this is the first report of F. oxysporum f. sp. batatas causing disease in flue-cured tobacco in Spain. References: (1) G. M. Armstrong and J. K. Armstrong. Phytopathology 58:1242, 1968. (2) G. Espárrago and I. Blanco. Plant Dis. 86:1402, 2002.

The objective of this study was to determine the factors predictive of time to the occurrence of pulmonary damage in systemic lupus erythematosus (SLE). Six-hundred and twenty-six SLE patients from a multiethnic (Hispanics, African Americans and Caucasians) longitudinal study of outcome were studied. Pulmonary damage was defined as per the Systemic Lupus International Collaborating Clinics Damage Index. Socioeconomic-demographic, clinical, genetic, serological features, pharmacologic treatments, behavioural, psychological and disease activity [as per the Systemic Lupus Activity Measure-Revised (SLAM-R)] were examined. Factors associated with time to the occurrence of pulmonary damage were examined by Cox proportional hazards regressions. A Kaplan-Meier survival curve was also examined. Forty-six (7.3%) patients had pulmonary damage after a mean (SD) total disease duration of 5.3 (3.6) years. Among those patients, 25 had pulmonary fibrosis, 12 pulmonary hypertension, eight pleural fibrosis, four pulmonary infarction and four shrinking lung syndrome. Seven patients had more than one type of lung damage. Cumulative rates of pulmonary damage at five and 10 years were 7.6% and 11.6%, respectively. In the multivariable analyses, age (HR = 1.033, 95% CI 1.006-1.060; P = 0.0170), pneumonitis (HR = 2.307, 95% CI 1.123-4.739; P = 0.0229) and anti-RNP antibodies (HR = 2.344, 95% CI 1.190-4.618; P = 0.0138) were associated with a shorter time to the occurrence of pulmonary damage while photosensitivity (HR = 0.388, 95% CI 0.184-0.818; P = 0.0128) and oral ulcers (HR = 0.466, 95% CI 0.230-0.942; P = 0.0335) with a longer time. Pulmonary damage is relatively common in SLE. Age, pneumonitis and anti-RNP antibodies were associated with a shorter time to the development of permanent lung disease.

Virgin females of Lobesia botrana Denis & Schiffermüller were mated at ages of 1, 3, 5, 8, 12 and 16 days and the effect of mating delay on reproductive output assessed. Delayed mating did not affect female mating success but fertilization was reduced in 16-day-old females. Increased mating delays substantially affected daily oviposition pattern and resulted in a significant reduction of both fecundity and fertility, so that mean number of viable eggs laid decreased from 150 to 22 in 1- and 16-day-old mated females, respectively. Heavier females were more constrained than lighter ones by mating delays and female reproductive efficiency (no. viable eggs/female body weight) was also significantly reduced. Female longevity significantly increased and oviposition period gradually declined with mating delay. The number of viable eggs was positively correlated with both female weight and oviposition period; female longevity and female weight were also significantly correlated. However, the significance of these correlations declined with increased mating delay. Results overall indicated that mating delay drastically reduces female L. botrana reproductive output. The implications of delayed mating of females are discussed from an ecological perspective in relation to L. botrana control using mating disruption.

The genetic basis as well as the mode of inheritance of polyandry in Spodoptera exigua Hübner was studied in the laboratory by using a simple divergent selection experiment followed by F1 reciprocal crosses, F2 and backcrosses. There was an effective response to artificial selection for high (H line) and low (L line) female mating frequency with significant separation of the lines by the second generation of selection. The mean female mating frequency in the parental generation (1.57 matings per female) reached plateaus of 2.50 and 1.25 matings per female in the H and L lines, respectively, after six generations of selection. Selection response becomes saturated at about 90% and 25% levels of polyandry (percentage females re-mating) in the H and L lines, respectively, and consequently mono- and polyandric pure strains were not obtained. Polyandry levels in offspring from the H and L lines and their hybrids in F1, F2 and backcrosses consistently indicate that female mating frequency was more or less proportional to the relative amounts of genes derived from the H and L lines. Such a clear pattern of hybrid responses, together with the gradual selective changes under artificial selection, suggests the involvement of a polygenic system. Female mating frequencies from progeny of the two reciprocal F1 crosses were not significantly different, which suggest that the trait was autosomally inherited. Moreover, female mating frequency of F1 (pooled) progeny was not significantly different from the mid-parental value, which suggest no dominance. The computation of the Cavalli's joint scaling test consistently confirmed these results yielding values of d = 0.51 +/- 0.10 and h = 0.12 +/- 0.21. The broad sense heritability estimate was H2 = 0.73. It is concluded that polyandry in S. exigua is a polygenic, autosomal heritable trait and that additive genetic variance is available for selection for female mating frequency. The implications of the genetic basis of polyandry are briefly discussed in the context of current theories about this crucial insect mating system.

Activation of CD4+ cells is a prerequisite for infection by the human immunodeficiency virus (HIV). Thus, any agent capable of suppressing CD4+ cell proliferation could create a refractory stage that would impede viral infection. We have reported, in a previous publication, that a biological response modifier (BRM), polyantigenic immunomodulator (PAI) substantially reduces HIV-1 titer (from 20 to 100%) in peripheral mononuclear cells (PBMC) cultures with high viral titer (p24 = 10(2)-10(5) pg/ml). We are presenting data suggesting that the reported reduction in virus titer seems to be associated with a suppressive activity of PAI on the proliferation of PBMC from intravenous drug users (IVDU) infected and non-infected with HIV-1. PAI, a well characterized BRM, is a mixture of inactivated bacterial and influenza virus vaccines. PBMC from healthy donors and IVDU individuals were exposed to PAI, phytohemagglutinin (PHA), interleukin-2 (IL-2) and to combinations of PAI with either PHA or IL-2. Appropriate controls were included. 3H-thymidine pulsing was used as indicator of cell proliferation. The stimulation index and the difference between mean cpm of test sample and control were used to measure proliferative activity. There was a low proliferative response in the PBMC cultures from IVDU and HIV-1 positive patients, but it was substantially lower in the later group. When PBMC cultures from the same group of individuals were exposed to PAI, PHA and IL-2, and to the combination of either PAI plus PHA or IL-2, the response observed in the PAI treated group was uniformly lower than in the other treated cultures. Moreover, when PAI was combined with PHA, it exerted a significant reduction in the measured parameters. The effect of PAI on IL-2 activity was negligible. A suppressive effect of a PAI has been detected on the proliferation of PBMC from IVDA and HIV-1 positive individuals. This activity may be associated with the capacity of PAI to reduce HIV titers in infected PBMC cultures.

Human gamma delta T cells expressing the V gamma 9/V delta 2 T-cell receptor have been previously found to proliferate in response to certain microorganisms and to expand throughout life, presumably because of extrathymic activation by foreign antigens. In vitro expansion of V gamma 9/V delta 2 cells by mycobacteria has been previously shown to be dependent on accessory cells. In order to gain an insight into the mechanisms involved in the expansion of these cells, we have undertaken to identify the peripheral blood subset of cells on which proliferation of V gamma 9/V delta 2 cells in response to mycobacteria is dependent. Contrary to their role in antigen presentation to alpha beta T cells, professional antigen-presenting cells, such as monocytes, B cells, and dendritic cells, were unable to provide the cellular support for the expansion of V gamma 9/V delta 2 cells. Selective depletion of T-cell subsets, as well as the use of highly purified T-cell populations, indicated that the only subset of peripheral blood cells that could expand V gamma 9/V delta 2 cells were CD4+ CD45RO+ CD7- alpha beta T cells. These cells underwent distinct intracellular signaling events after stimulation with the mycobacterial antigen. Expansion of V gamma 9/V delta 2 cells by alpha beta T cells was dependent on cell-cell contact. This is the first evidence that a small subset of the memory helper T-cell population is exclusively responsible for the peripheral expansion of V gamma 9/V delta 2 cells. These data illustrate a unique aspect of antigen recognition by gamma delta T cells and provide new means to study their immune defense role.

The majority of human peripheral gamma delta T cells express antigen receptors using the V gamma 9 and V delta 2 gene products. Cells of this subset have been previously shown to uniformly recognize mycobacteria regardless of their V-(D)-J junctional sequences in an MHC-unrestricted manner. This reactivity superficially resembles activation of alpha beta cells by bacterial superantigens, which are thought to be presented by monomorphic regions of MHC class II molecules. It is not known whether presentation of the mycobacterial antigen to V gamma 9/V delta 2 T cells is also mediated by class II MHC molecules. In order to examine the similarity between presentation of bacterial superantigens to alpha beta T cells and the presentation of mycobacteria to gamma delta T cells we have studied the role of class II MHC molecules in presentation of the mycobacterial antigen AP-MT to V gamma 9/V delta 2 clones. Activation of gamma delta T cells by AP-MT required direct contact with antigen presenting cells, indicating that an interaction with cell surface molecules on antigen presenting cells is required. Class II MHC molecules were neither sufficient nor necessary for effective presentation of AP-MT to the gamma delta T cells, as transfectants expressing class II MHC molecules were unable to present, whereas cell lines lacking expression of MHC class II molecules could present this mycobacterial antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

The function of gamma delta T cells is still elusive. The nature of the antigens that they recognize and the mode of presentation of these antigens are largely unknown. The majority of human peripheral gamma delta T cells bear a V gamma 9/V delta 2 T cell receptor, and display nonclonal reactivity to mycobacteria, without restriction by MHC. It is unknown whether these cells have clonal antigenic specificity as well. Here we describe rheumatoid arthritis-derived V gamma 9/V delta 2 T cell clones, displaying dual antigenic recognition: a nonclonal, MHC-unrestricted recognition of mycobacteria, and a clonal recognition of a short tetanus toxin peptide presented by HLA-DRw53, a nonpolymorphic class II MHC molecule associated with susceptibility to rheumatoid arthritis. This is the first evidence that V gamma 9/V delta 2 T cells can recognize nominal antigenic peptides presented by class II MHC molecules. These results suggest that much like alpha beta T cells, V gamma 9/V delta 2 cells may contribute to the immune response against foreign antigens in an antigen-specific and MHC-restricted manner. The reactivity of these gamma delta T cells to mycobacteria may represent a superantigen-like phenomenon.

The value of adenosine deaminase activity (ADA) in ascitic fluid was examined in 12 patients with confirmed peritoneal tuberculosis and compared with that of 96 patients with ascites of other different etiologies as an age-matched control group, to determine the diagnostic value of the ADA activity in tuberculous ascites. The mean adenosine deaminase activity (ADA) value in ascitic fluid of the tuberculous peritonitis group was 47.9 +/- 21.9 IU/L and in the control group 9.6 +/- 5 U/L (mean +/- SD); p less than 0.01. A different method than that usually reported in tuberculous peritonitis was used for ascites ADA estimation. The best sensitivity and specificity was obtained when greater than 32 U/L was used as a cutoff point. The ascites ADA activity correlated with the ascites total protein concentration in the tuberculosis group (r = 0.842). Our findings confirm other results and support the ADA activity determination in ascitic fluid as a useful noninvasive screening test in the diagnosis of peritoneal tuberculosis in endemic areas or in high risk patients. However, false-negative results may occur in those patients in which ascites total protein concentration is low.

A group of pregnant women living in the south of the province of Pontevedra (Spain) have been studied in order to determine the prevalence of hepatitis B virus biological markers. For that respect we have prospectively studied HBsAg and other markers in 535 pregnant women from June 1987 to March 1988. The prevalence of HBsAg was 0.75%, and in 6.12% certain biological markers were detected. Only one carrier fulfilled the current criteria recommended by the Advisory Committee on Immunization Practices (ACIP) for selective screening of pregnant women. Although the prevalence and costs of the detection are similar to those for voluntary blood donors of the same region (1%), the frequency with which infected neonates develop chronic antigenemia along with the low sensitivity of the selective screening justifies the systematized serological study of the pregnant women.