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The Mi locus of tomato confers resistance to root knot nematodes. Tomato DNA spanning the locus was isolated as bacterial artificial chromosome clones, and 52 kb of contiguous DNA was sequenced. Three open reading frames were identified with similarity to cloned plant disease resistance genes. Two of them, Mi-1.1 and Mi-1.2, appear to be intact genes; the third is a pseudogene. A 4-kb mRNA hybridizing with these genes is present in tomato roots. Complementation studies using cloned copies of Mi-1.1 and Mi-1.2 indicated that Mi-1.2, but not Mi-1.1, is sufficient to confer resistance to a susceptible tomato line with the progeny of transformants segregating for resistance. The cloned gene most similar to Mi-1.2 is Prf, a tomato gene required for resistance to Pseudomonas syringae. Prf and Mi-1.2 share several structural motifs, including a nucleotide binding site and a leucine-rich repeat region, that are characteristic of a family of plant proteins, including several that are required for resistance against viruses, bacteria, fungi, and now, nematodes

The root-knot nematode resistance gene Mi-1 in tomato has long been thought to be located in the pericentromeric heterochromatin region of the long arm of chromosome 6 because of its very tight genetic linkage (approx. 1cM) to the markers Aps-1 (Acid phosphatase 1) and yv (yellow virescent). Using Mi-BAC clones and an Aps-1 YAC clone in fluorescence in situ hybridisation (FISH) to pachytene chromosomes we now provide direct physical evidence showing that Mi-1 is located at the border of the euchromatin and heterochromatin regions in the short arm (6S) and Aps-1 in the pericentromeric heterochromatin of the long arm (6L) close to the euchromatin. Taking into account both the estimated DNA content of hetero-and euchromatin regions and the compactness of the tomato chromosomes at pachytene (2 Mb/µm), our data suggest that Mi-1 and Aps-1 are at least 40 Mb apart, a base pair-to-centiMorgan relationship that is more than 50-fold higher than the average value of 750 kb/cM of the tomato genome. An integrated cytogenetic-molecular map of chromosome 6 is presented that provides a framework for physical mapping.

ObjectiveTo determine the effect of helminth infection during pregnancy on the cognitive and motor functions of one-year-old children.MethodsSix hundred and thirty five singletons born to pregnant women enrolled before 29 weeks of gestation in a trial comparing two intermittent preventive treatments for malaria were assessed for cognitive and motor functions using the Mullen Scales of Early Learning, in the TOVI study, at twelve months of age in the district of Allada in Benin. Stool samples of pregnant women were collected at recruitment, second antenatal care (ANC) visit (at least one month after recruitment) and just before delivery, and were tested for helminths using the Kato-Katz technique. All pregnant women were administered a total of 600 mg of mebendazole (100 mg two times daily for 3 days) to be taken after the first ANC visit. The intake was not directly observed.ResultsPrevalence of helminth infection was 11.5%, 7.5% and 3.0% at first ANC visit, second ANC visit and at delivery, respectively. Children of mothers who were infected with hookworms at the first ANC visit had 4.9 (95% CI: 1.3–8.6) lower mean gross motor scores compared to those whose mothers were not infected with hookworms at the first ANC visit, in the adjusted model. Helminth infection at least once during pregnancy was associated with infant cognitive and gross motor functions after adjusting for maternal education, gravidity, child sex, family possessions, and quality of the home stimulation.ConclusionHelminth infection during pregnancy is associated with poor cognitive and gross motor outcomes in infants. Measures to prevent helminth infection during pregnancy should be reinforced.

ObjectivesMaternal depression occurs in 13–20% of women from low-income countries, which is associated with negative child health outcomes, including diarrheal disease. However, few studies have investigated its impact on child risk of infectious disease. We studied the impacts of maternal depressive symptoms and parent–child interactions, independently, on the risk of Plasmodium falciparum malaria and soil-transmitted helminth infection in Beninese children.MethodsOur population included mothers and children enrolled in a clinical trial during pregnancy (MiPPAD) in Benin. The Edinburgh Postnatal Depression Scale (EPDS) assessed maternal depressive symptoms and the home observation measurement of the environment (HOME) assessed parent–child interactions. Blood and stool sample analyses diagnosed child malaria and helminth infection at 12, 18, and 24 months. Negative binomial and Poisson regression models with robust variance tested associations.ResultsOf the 302 mother–child pairs, 39 (12.9%) mothers had depressive symptoms. Median number of malaria episodes per child was 3 (0–14) and 29.1% children had at least one helminth infection. Higher EPDS scores were associated with lower HOME scores; relative risk (RR) 0.97 (95% confidence interval (CI) 0.95, 0.99), particularly with lower acceptance, involvement, and variety subscales; RR 0.92 (95% CI 0.85, 0.99), RR 0.82 (95% CI 0.77, 0.88), RR 0.93 (95% CI 0.88, 0.99), respectively. However, neither exposure was associated with risk of parasitic infection in children.Conclusions for PracticeMaternal depressive symptoms are associated with poor parent–child interactions, particularly acceptance of behavior, involvement with children, and variety of interactions, but these exposures do not independently impact risk of parasitic infection in children.

There appears to be an incompressible high rate of preterm births among populations of African origin irrespective of their geographic location. The objective of this study was to assess the risk factors for preterm birth in a French Caribbean population of African descent, offered medical care comparable to that on the French mainland, but presenting a higher rate of preterm birth. The study was based on a birth cohort at maternity hospitals in Guadeloupe (French West Indies) including 911 singleton pregnancies enrolled during their third trimester check-up visits. Associations between risk factors and the risk of preterm delivery (spontaneous and induced) were assessed using a multivariate Cox model. In addition, prevalences of sociodemographic and medical factors in Guadeloupe were compared with those on the French mainland. 144 women (15.8 %) delivered preterm, medically induced in 52 %. Women delivering preterm were more often over 35 years old (37 %), single (54 %), and had higher prevalence of prior preterm birth (20 %), prior miscarriage (37 %), lupus (3 %), asthma (14 %), gestational hypertension (26 %), gestational diabetes (13 %) and urinary tract infection (24 %) than women with term births. In the whole cohort, these risk factors were also more frequent than in mainland France. Our results suggest highly prevalent medical risk factors for preterm births in Guadeloupe. This observation combined with specific social risk factors (older maternal age, single living) less frequent on the French mainland probably explains a large part of a higher prevalence of preterm births in this population despite similar medical provision.

Apolipoprotein E is a monomeric protein secreted by the liver and responsible for the transport of plasma cholesterol and triglycerides. The APOE gene encodes 3 isoforms Ɛ4, Ɛ3 and Ɛ2 with APOE Ɛ4 associated with higher plasma cholesterol levels and increased pathogenesis in several infectious diseases (HIV, HSV). Given that cholesterol is an important nutrient for malaria parasites, we examined whether APOE Ɛ4 was a risk factor for Plasmodium infection, in terms of prevalence or parasite density. A cross sectional survey was performed in 508 children aged 1 to 12 years in Gabon during the wet season. Children were screened for Plasmodium spp. infection, APOE and hemoglobin S (HbS) polymorphisms. Median parasite densities were significantly higher in APOE Ɛ4 children for Plasmodium spp. densities compared to non-APOE Ɛ4 children. When stratified for HbS polymorphisms, median Plasmodium spp. densities were significantly higher in HbAA children if they had an APOE Ɛ4 allele compared to those without an APOE Ɛ4 allele. When considering non-APOE Ɛ4 children, there was no quantitative reduction of Plasmodium spp. parasite densities for HbAS compared to HbAA phenotypes. No influence of APOE Ɛ4 on successful Plasmodium liver cell invasion was detected by multiplicity of infection. These results show that the APOE Ɛ4 allele is associated with higher median malaria parasite densities in children likely due to the importance of cholesterol availability to parasite growth and replication. Results suggest an epistatic interaction between APOE and HbS genes such that sickle cell trait only had an effect on parasite density in APOE Ɛ4 children. This suggests a linked pathway of regulation of parasite density involving expression of these genes. These findings have significance for understanding host determinants of regulation of malaria parasite density, the design of clinical trials as well as studies of co-infection with Plasmodium and other pathogens.

Objective:To study recent trends in the cumulative incidence of visual impairment in childhood over a 15-year period and to assess progress against WHO goals for prevention.Design, setting and participants:Data from a population-based register of visual impairment in southern England were used to estimate cumulative incidence and trends in visual impairment (VI) and severe visual impairment/blindness (SVI/BL) for children born in 1984–1998. Causes were classified by anatomical site(s), timing of insult(s) and whether the visual impairment was potentially preventable or treatable.Results:Of 691 eligible children, 358 (53%) had VI and 323 (47%) SVI/BL. The cumulative incidence of VI to age 12 years was 7.1 (95% CI 6.4 to 7.8) per 10 000 live births and for SVI/BL was 6.2 (95% CI 5.6 to 6.9); the incidence of both decreased significantly over time. There was an inverse relationship with gestational age and birth weight, although the risk of visual impairment associated with prematurity and low birth weight decreased substantially over time. 55% of children with VI and 77% with SVI/BL had other impairments; the proportion of associated impairments among children with VI decreased over time. 130 (19%) of the children have died, with over half dying before the age of 5.Conclusions:There is evidence of a temporal decline in the incidence of VI and SVI/BL in births from 1984 to 1998 especially in very preterm and low birthweight infants. Early childhood mortality was high. The causes of visual impairment in UK children are numerous, complex and often part of a wider picture of childhood disability.

Objective To determine the effect of helminth infection during pregnancy on the cognitive and motor functions of one-year-old children. Methods Six hundred and thirty five singletons born to pregnant women enrolled before 29 weeks of gestation in a trial comparing two intermittent preventive treatments for malaria were assessed for cognitive and motor functions using the Mullen Scales of Early Learning, in the TOVI study, at twelve months of age in the district of Allada in Benin. Stool samples of pregnant women were collected at recruitment, second antenatal care (ANC) visit (at least one month after recruitment) and just before delivery, and were tested for helminths using the Kato-Katz technique. All pregnant women were administered a total of 600 mg of mebendazole (100 mg two times daily for 3 days) to be taken after the first ANC visit. The intake was not directly observed. Results Prevalence of helminth infection was 11.5%, 7.5% and 3.0% at first ANC visit, second ANC visit and at delivery, respectively. Children of mothers who were infected with hookworms at the first ANC visit had 4.9 (95% CI: 1.3-8.6) lower mean gross motor scores compared to those whose mothers were not infected with hookworms at the first ANC visit, in the adjusted model. Helminth infection at least once during pregnancy was associated with infant cognitive and gross motor functions after adjusting for maternal education, gravidity, child sex, family possessions, and quality of the home stimulation. Conclusion Helminth infection during pregnancy is associated with poor cognitive and gross motor outcomes in infants. Measures to prevent helminth infection during pregnancy should be reinforced.

In 2000, at its fifty-second session, the International Law Commission (ILC) completed an initial reconsideration of part 2 of the draft articles on state responsibility, as adopted on first reading in 1996. The Drafting Committee provisionally adopted a complete text of the draft articles and referred it to the General Assembly for comment. The intention is to adopt a final text, together with commentaries, in 2001. In the meantime the ILC itself has taken no substantive decision on the Drafting Committee's text, which remains open to further revisions in the light of any comments made.