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X-linked adrenoleukodystrophy (X-ALD) is a demyelinating disease due to mutations in the ABCD1 (ALD) gene, encoding a peroxisomal ATP-binding cassette transporter (ALDP). Overexpression of adrenoleukodystrophy-related protein, an ALDP homologue encoded by the ABCD2 (adrenoleukodystrophy-related) gene, can compensate for ALDP deficiency. 4-Phenylbutyrate (PBA) has been shown to induce both ABCD2 expression and peroxisome proliferation in human fibroblasts. We show that peroxisome proliferation with unusual shapes and clusters occurred in liver of PBA-treated rodents in a PPARalpha-independent way. PBA activated Abcd2 in cultured glial cells, making PBA a candidate drug for therapy of X-ALD. The Abcd2 induction observed was partially PPARalpha independent in hepatocytes and totally independent in fibroblasts. We demonstrate that a GC box and a CCAAT box of the Abcd2 promoter are the key elements of the PBA-dependent Abcd2 induction, histone deacetylase (HDAC)1 being recruited by the GC box. Thus, PBA is a nonclassical peroxisome proliferator inducing pleiotropic effects, including effects at the peroxisomal level mainly through HDAC inhibition.

ABSTRACT An epidemiological model integrating three organizational scales of host plant populations (e.g., sites, leaves, and plants) is presented. At the lowest (site) scale, the model simulates the dynamics of vacant, latent, infectious, and removed sites. Three types of vacant sites are distinguished, depending on presence of infections at higher scales (leaf or plant). The rate of infection of each type of vacant site is computed according to ratios of autodeposition, allo-leaf-deposition, and allo-plantdeposition. At the leaf and plant scales, the rate of victimization is a function of the rate of infection of vacant sites. Sensitivity analyses showed that deposition patterns (the relative proportions of auto-, allo-leaf-, and allo-plant-depositions) and host structure (leaf size and number of leaves per plant) affected the speed of epidemics at the different scales. Model outputs conformed with results from other approaches in the case of random distribution of the disease. The model hypotheses concerning infection from autodeposited propagules, and their implications for disease epidemics, are discussed. The model can be used to derive relationships between allo-deposition ratios and disease incidences at the three scales. These relationships become simple when disease intensity is low. These relationships may be useful, e.g., to assess the potential efficiency of cultivar mixture to control epidemics. Integration of different organization scales and allo-deposition parameters enables the model to capture important features of epidemics developing in space without using explicitly spatialized variables. Such an approach could be useful to analyze other ecological processes that involve a variety of scales.

ABSTRACT A simulation study was conducted to assess the current and prospective efficiency of rice pest management and develop research priorities for lowland production situations in tropical Asia. Simulation modeling with the RICEPEST model provided the flexibility required to address varying production situations and diverse pest profiles (bacterial leaf blight, sheath blight, brown spot, leaf blast, neck blast, sheath rot, white heads, dead hearts, brown plant-hoppers, insect defoliators, and weeds). Operational definitions for management efficacy (injury reduction) and management efficiency (yield gain) were developed. This approach enabled the modeling of scenarios pertaining to different pest management strategies within the agroecological contexts of rice production and their associated pest injuries. Rice pests could be classified into two broad research priority-setting categories with respect to simulated yield losses and management efficiencies. One group, including weeds, sheath blight, and brown spot, consists of pests for which effective pest management tools need to be developed. The second group consists of leaf blast, neck blast, bacterial leaf blight, and brown plant-hoppers, for which the efficiency of current management methods is to be maintained. Simulated yield losses in future production situations indicated that a new type of rice plant with high-harvest index and high-biomass production ("New Plant Type") was more vulnerable to pests than hybrid rice. Simulations also indicated that the impact of deployment of host resistance (e.g., through genetic engineering) was much larger when targeted against sheath blight than when targeted against stem borers. Simulated yield losses for combinations of production situations and injury profiles that dominate current lowland rice production in tropical Asia ranged from 140 to 230 g m(-2). For these combinations, the simulated efficiency of current pest management methods, expressed in terms of relative yield gains, ranged from 0.38 to 0.74. Overall, the analyses indicated that 120 to 200 x 10(6) tons of grain yield are lost yearly to pests over the 87 x 10(6) ha of lowland rice in tropical Asia. This also amounts to the potential gain that future pest management strategies could achieve, if deployed.

X-linked adrenoleukodystrophy (X-ALD) is a demyelinating disorder associated with impaired very-long-chain fatty-acid (VLCFA) beta-oxidation caused by mutations in the ABCD1 (ALD) gene that encodes a peroxisomal membrane ABC transporter. ABCD2 (ALDR) displays partial functional redundancy because when overexpressed, it is able to correct the X-ALD biochemical phenotype. The ABCD2 promoter contains a putative thyroid hormone-response element conserved in rodents and humans. In this report, we demonstrate that the element is capable of binding retinoid X receptor and 3,5,3'-tri-iodothyronine (T3) receptor (TRbeta) as a heterodimer and mediating T3 responsiveness of ABCD2 in its promoter context. After a T3 treatment, an induction of the ABCD2 gene was observed in the liver of normal rats but not that of TRbeta-/- mice. ABCD2 was not induced in the brain of the T3-treated rats. However, we report for the first time that induction of the ABCD2 redundant gene is feasible in myelin-producing cells (differentiated CG4 oligodendrocytes). The induction was specific for this cell type because it did not occur in astrocytes. Furthermore, we observed T3 induction of ABCD2 in human and mouse ABCD1-deficient fibroblasts, which was correlated with normalization of the VLCFA beta-oxidation. Finally, ABCD3 (PMP70), a close homolog of ABCD2, was also induced by T3 in the liver of control rats, but not that of TRbeta-/- mice, and in CG4 oligodendrocytes.

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease due to a defect in the ABCD1 (ALD) gene. ABCD1, and the two close homologues ABCD2 (ALDR) and ABCD3 (PMP70), are genes encoding ATP-binding cassette half-transporters of the peroxisomal membrane. As overexpression of the ABCD2 or ABCD3 gene can reverse the biochemical phenotype of X-ALD (reduced beta-oxidation of very-long-chain fatty acids), pharmacological induction of these partially redundant genes may represent a therapeutic approach to X-ALD. We previously reported that the ABCD2 and ABCD3 genes could be strongly induced by fibrates, which are hypolipidaemic drugs and peroxisome-proliferators in rodents. We provide evidence that the induction is dependent on peroxisome proliferator-activated receptor (PPARalpha) as both genes were not induced in fenofibrate-treated PPARalpha -/- knock-out mice. To further characterize the PPARalpha pathway, we cloned and analysed the promoter of the ABCD2 gene, the closest homologue of the ABCD1 gene. The proximal region (2 kb) of the rat promoter displayed a high conservation with the human and mouse cognate sequences suggesting an important role of the region in regulation of the ABCD2 gene. Classically, fibrate-induction involves interaction of PPARalpha with a response element (PPRE) characterized by a direct repeat of the AGGTCA-like motif. Putative PPRE motifs of the rat ABCD2 promoter were studied in the isolated form or in their promoter context by gel-shift assay and transfection of COS-7 cells. We failed to characterize a functional PPRE, suggesting a different mechanism for the PPARalpha-dependent regulation of the ABCD2 gene.

X-linked adrenoleukodystrophy (X-ALD) is an inherited demyelinating disorder due to mutations in the ALD gene, which encodes a peroxisomal ABC half-transporter (ALDP). It has been suggested that ALDP assembles with ALDRP (adrenoleukodystrophy-related protein), a close homologous half-transporter, to form a functional heterodimer. For the first time full-length ALDRP cDNA (5.5 kb) was cloned, and 5' and 3' RACE analysis revealed that alternative usage of polyadenylation sites generates the two transcripts of 3.0 and 5.5 kb observed in the rat in Northern blot analysis. Southern blotting and chromosomal mapping demonstrated one ALDR locus in the rat genome. Characterisation of the 3' flanking region suggested that an ID sequence might be responsible for high expression of the 5.5 kb ALDRP transcript in rat brain. ALDR gene expression was found to be high in the liver of rats before weaning and very low in adult rats; the reverse developmental regulation was observed in the brain. Fenofibrate, which is a potent inducer of the ALDR gene in the liver of adult rats, could not induce the ALDR gene in suckling rats. The exact significance of this result with regard to development of an efficient pharmacological gene therapy for X-ALD is discussed.

A protocol for characterizing patterns of rice cropping practices and injuries due to pathogens, insects, and weeds was developed and used in six sites in tropical Asia covering a wide range of environments where lowland rice is cultivated. The data collected in a total population of 456 individual farmers' fields were combined to site-specific weather data and analyzed using non-parametric multivariate techniques: cluster analyses with chi-square distance and correspondence analyses. The main results are: (i) patterns of cropping practices that are common across sites can be identified; (ii) conversely, injury profiles that are common across sites can be determined; (iii) patterns of cropping practices and injury profiles are strongly associated at the regional scale; (iv) weather patterns are strongly associated with patterns of cropping practices and injury profiles; (v) patterns of cropping practices and injury profiles allow for a good description of the variation in actual yield; and (vi) patterns of cropping practices and injury profiles provide a framework that accurately reflects weather variation and site diversity, and reliably accounts for variation in yield. The mean estimated yield across sites (4.12 t ha -1 ) corresponds to commonly cited averages in the region and indicates the potential for increased productivity with better management practices, especially an improved water supply. Injuries due to pests are secondary compared with other yield-limiting factors. Injury profiles were dominated by stem rot and sheath blight (IN1); bacterial leaf blight, plant hoppers, and leaf folder (IN2); and sheath rot, brown spot, leaf blast, and neck blast (IN3). IN1 was associated with high (mineral) fertilizer inputs, long fallow periods, low pesticide use, and good water management in (mostly) transplanted rice crops of a rice-rice rotation. IN2 was associated with direct-seeded rice crops in an intensive rice-rice rotation, where fertilizer and pesticide inputs are low and water management is poor, or where fertilizer and pesticide inputs are high and water management is adequate. IN3 corresponds to low input, labor intensive (hand weeding and transplanting) rice crops in a diverse rotation system with uncertain water supply. Weed infestation was an omnipresent constraint. This study shows the potential for developing pest management strategies that can be adapted throughout the region, rather than being site-specific.

A series of experiments was conducted where a range of injuries due to rice pests (pathogens, insects, and weeds) was manipulated simultaneously with a range of production factors (fertilizer input, water supply, crop establishment method, variety) in different seasons and years. These factors were chosen to represent lowland rice production situations characterized in surveys conducted in tropical Asia and their corresponding range of attainable yield. Experiments complemented one another in exploring the response surface of rice yields to yield-limiting and yield-reducing factors. The resulting experimental data base consisted of 445 individual plots and involved 11 manipulated injuries in a range of attainable yields of 2 to 11 t ha -1 . A first, nonparametric, multivariate analysis led to a hierarchy of potential injuries, from marginally (e.g., bacterial leaf blight) to extremely harmful (e.g., rice tungro disease). A second, parametric, multivariate approach resulted in a multiple regression model involving factors generated by principal component analysis on injuries that adequately described the variation in actual yield. One major finding was that some (attainable yield × injury factors) interactions significantly contributed to the description of variation in actual yield, indicating that some injuries (or their combinations) had a stronger or weaker yield-reducing effect, depending on the level of attainable yield. For instance, yield losses due to sheath blight, weed infestation, and rice tungro disease tend to increase, remain stable, and decrease, respectively, with increasing attainable yields. Back-computations using the principal component regression model estimated yield losses caused by individual injuries, using the mean injury levels in a population of farmers' fields surveyed across tropical Asia. The results indicate that sheath blight, brown spot, and leaf blast are diseases that cause important losses (between 1 and 10%) regionally. Among the insect injuries, only white heads caused by stem borers appear of relevance (2.3% yield losses). These injuries, however, do not match in importance those caused by weeds, whether outgrowing the rice crop canopy (WA) or not (WB), both types of injuries causing about 20% yield losses when considered individually. When all mean injuries were combined into one mean injury profile occurring at a regional attainable yield of 5.5 t ha -1 , a mean yield loss of 37.2% was estimated, indicating that injuries were less than additive in their yield-reducing effects. Scenario analyses were conducted in a set of (production situations × injury profiles) combinations characterized from surveys in farmers' fields in tropical Asia. Depending on the scenario chosen, losses ranging from 24 to 41% were found.

ALDR is one of the four genes encoding an ATP Binding Cassette (ABC) hemi-transporter of the peroxisomal membrane so far identified in mammalian cells. The best known of these is X-ALD, whose dysfunction has been causally associated with X-linked adrenoleukodystrophy. ALDR and X-ALD protein product are closely related and we show here that this striking conservation is maintained at the genomic level. Although extending to a larger genomic region, the organisation of the mouse ALDR gene mirrors exactly that of X-ALD. This supports further the hypothesis that among the four known peroxisomal ABC hemi-transporters ALDRP is the most likely candidate as a modifier contributing to the phenotypic variability of X-linked adrenoleukodystrophy.

The representativeness of information on yield losses due to rice diseases in tropical Asia was studied. Published studies involving different groups of diseases (viral, bacterial, and fungal) and conducted in different rice production ecosystems were compared to help identify research gaps, the filling of which could improve current disease management in rice and help in developing strategies that fit the management needs of fast-evolving rice production systems in the future. Four criteria of representativeness of yield loss information were used: representativeness over time (the proportion of studies conducted over more than one crop cycle), representativeness over space (the proportion of studies conducted in more than one location), representativeness of scale (the proportion of studies conducted on the scale of plots or fields), and representativeness of injury (the standard deviation of the proportion of studies using inoculation, spontaneous infection, or chemical control). A strong imbalance in both the number and the representativeness of studies dealing with fungal, viral, and bacterial diseases was found. Most of the few studies of yield loss due to viral diseases (mainly rice tungro disease) were conducted on the scale of individual (potted) plants or were based on one-year data sets, often reflecting strong epidemics only. Studies of bacterial diseases were conducted in single locations only, and whether such results can be extrapolated still needs to be addressed. There is an acute need to better document yield losses in rice ecosystems other than the irrigated ecosystem. While studies conducted in the upland, rain-fed lowland, and deep-water rice ecosystems seem to have a high degree of representativeness, this cannot compensate for their small number in view of the great diversity of these environments. Studies of irrigated rice tend to concentrate on one year and one location. This approach may be based on the erroneous view that the irrigated ecosystem is homogeneous, and possible extrapolation of data from these studies needs to be examined.

We report here on the identification and genomic mapping of a novel member of the family of the ATP-binding cassette (ABC) transporters, ABC7, conserved in mouse and in humans. The ABC7 gene encodes a protein with the typical features of half-transporters, such as those involved in translocation of antigenic peptides or in peroxisomal disorders. ABC7 shows a ubiquitous expression pattern and maps to the X chromosome both in mouse and in humans. The high sequence similarity to those of two yeast half-transporters supports once again the extreme evolutionary conservation of this family of proteins.

We report here on the chromosomal mapping of the adrenoleukodystrophy-related (ALDR) gene on both the human and the mouse genomes. This gene encodes a peroxisomal ATP binding cassette transporter, closely related to the transporter identified as responsible for the adrenoleukodystrophy phenotype. ALDR maps on the syntenic region on murine and human autosomes. In addition, we could determine its position in relation to known microsatellite framework markers; this will allow to test its role in Zellweger syndrome and/ or related peroxisomal disorders.

Pigmentation of Drosophila eyes requires the concerted action of several genes, most of which have been cloned and characterized. Three of them, white, brown, and scarlet, have been directly implicated in the import of pigment precursors into the cells. These three genes encode similar proteins, belonging to the evolutionary conserved family of ATP Binding Cassette transporters. The identification of a novel mouse gene, ABC8, closely related to white is reported here, together with an analysis of its expression profile and its comparative mapping in mouse and human genome.

The family of ATP binding cassette (ABC) transporters or traffic ATPases is composed of several membrane-associated proteins that transport a great variety of solutes across cellular membranes. Two novel mammalian members of the family, ABC1 and ABC2, have been identified by a PCR-based approach. They belong to a group of traffic ATPases encoded as a single multifunctional protein, such as CFTR, STE 6, and P-glycoproteins. Their peculiar structural features and close relationship to ABC transporters involved in nodulation suggest that ABC1 and ABC2 define a novel subgroup of mammalian traffic ATPases.

Correspondence analyses were used to explore the relationships between yield and populations of Pratylenchus zeae in an upland rice field and in a greenhouse experiment. Initial soil (Pi) and final root (Pf) population densities of P. zeae, and yield (Y) of rice cv. UPL Ri5 were determined at 490 spots in the field. Very low Y was linked to very high Pf. Low Y was linked to medium or high Pi and medium Pf. Medium to very high Y were clustered with undetectable Pi and very low or high Pf. All yield levels were independent of very high Pi. In the greenhouse experiment where seven nematode inoculum levels and three fertilizer levels were evaluated, low Y was associated with medium or high Pf and high Y with high or low Pf. The analyses indicated that nematode-yield interaction involved a complex, dynamic process, in which the root-carrying capacity probably was a determining factor. Correspondence analysis, which does not require assumptions on the shape of nematode population-yield relationships or on variable distributions, revealed meaningful associations in these complex data sets.

A framework for associating pest management with farming systems may be characterized by a cropping index (number of crop cycles per year); a plant species homogeneity rank, described as the degree of monoculture or polyculture and intensity of use of modern, high-yielding varieties versus land races or traditional varieties; intensity of use of synthetic agrochemicals; the availability of societal infrastructure to support agriculture, such as irrigation and roads; and availability of support services such as credit, public/private sector research and extension services. Traditional methods of plant protection in the tribal areas of the Philippines rely heavily on ritual-based cultural practices that recognize the crop calendar and its activities as part of a larger social agenda. Most groundnut growers in West Africa utilize minimal inputs with little infrastructural support but they have often adopted improved varieties. Extensive farming systems with modern inputs are exemplified by wheat in the mid-western USA, where pests are managed mainly through host plant resistance. In intensive farming systems--vegetables in South-East Asia, wheat in The Netherlands and orchards in the USA--crop intensification is greatest and pest problems arising from overuse of pesticides are most noticeable. Unsustainable farming systems evolve if realistic plant protection is not taken into consideration.

Four field experiments were conducted to study the effect of Sesbania rostrata and Aeschynomene afraspera as rotational and green manure crops on the population dynamics of Hirschmanniella mucronata and H. oryzae, and subsequent rice yields. The sequential cropping of the legumes with rice controlled both nematode species. In two experiments, yield of rice was related to the nematode population denisites at planting and harvesting of the second rice crop (R(2) = 0.391, P < 0.001, and R(2) = 0.57, P < 0.001), regardless of the treatments. Rice yield increases were attributed to nutritional effect of the green manure and the reduction of the nematode populations or the modification of a factor(s) linked to the nematode populations induced by their cropping. As the two leguminous crops do not generate direct return, using them to control the rice-root nematodes was not economical, despite the significant yield increase obtained.