Chronic Food Deprivation Decreases Extracellular Dopamine in the Nucleus Accumbens: Implications for a Possible Neurochemical Link Between Weight Loss and Drug Abuse

In rats reduced to 80% of normal body weight (n=9), the basal levels of extracellular dopamine (DA) in the nucleus accumbens (NAC), as determined by microdialysis, decreased significantly to 33 % (mean ± SEM) of their normal baseline (p<.01). Basal extracellullar DA did not change significantly over a matching 3-week period in controls (n=7). No changes were observed in NAC serotonin after weight reduction. These results indicate that parts of the mesolimbic DA system are depressed in underweight rats. The observed decrease in basal DA may be responsible for a variety of behavioral changes observed in undernourished humans and animals including the tendency to eat and gain weight when food becomes available. Given that DA can be released in the NAC when rats self-inject drugs of abuse, the present findings may help explain why animals increase drug intake when they are underweight.     

Control of leaf and chloroplast development by the Arabidopsis gene pale cress.

Leaf plastids of the Arabidopsis pale cress (pac) mutant do not develop beyond the initial stages of differentiation from proplastids or etioplasts and contain only low levels of chlorophylls and carotenoids. Early in development, the epidermis and mesophyll of pac leaves resemble those of wild-type plants. In later stages, mutant leaves have enlarged intercellular spaces, and the palisade layer of the mesophyll can no longer be distinguished. To study the molecular basis of this phenotype, we cloned PAC and determined that this gene is regulated by light and has the capacity to encode an acidic, predominantly alpha-helical protein. The PAC gene appears to be a novel component of a light-induced regulatory network that controls the development of leaves and chloroplasts.     

A method for single pair mating in an obligate parasitic nematode

Parasitic nematode species have extremely high levels of genetic diversity, presenting a number of experimental challenges for genomic and genetic work. Consequently, there is a need to develop inbred laboratory strains with reduced levels of polymorphism. The most efficient approach to inbred line development is single pair mating, but this is challenging for obligate parasites where the adult sexual reproductive stages are inside the host, and thus difficult to experimentally manipulate. This paper describes a successful approach to single pair mating of a parasitic nematode, Haemonchus contortus. The method allows for polyandrous mating behaviour and involves the surgical transplantation of a single adult male worm with multiple immature adult females directly into the sheep abomasum. We used a panel of microsatellite markers to monitor and validate the single pair mating crosses and to ensure that the genotypes of progeny and subsequent filial generations were consistent with those expected from a mating between a single female parent of known genotype and a single male parent of unknown genotype. We have established two inbred lines that both show a significant overall reduction in genetic diversity based on microsatellite genotyping and genome-wide single nucleotide polymorphism. There was an approximately 50% reduction in heterozygous SNP sites across the genome in the MHco3.N1 line compared with the MoHco3(ISE) parental strain. The MHco3.N1 inbred line has subsequently been used to provide DNA template for whole genome sequencing of H. contortus. This work provides proof of concept and methodologies for forward genetic analysis of obligate parasitic nematodes.     

Isolation of a random cosmid clone,cX5, which defines a new polymorphic locus DXS148 near the locus for Duchenne muscular dystrophy

Summary We have isolated a random cosmid cX5 (DXS148), which maps into a small Xp21 deletion associated with Duchenne muscular dystrophy (DMD), chronic granulomatous disease (CGD), retinitis pigmentosa (RP) and McLeod syndrome. cX5 maps proximally outside several other deletions associated with DMD, glycerol kinase deficiency (GK) and adrenal hypoplasia (AHC). The following order of loci is proposed: centromere-OTC-cX5 (DXS148)-754 (DXS84)-PERT87 (DXS164)/DMD-telomere. A subclone cX5.7, isolated from this cosmid, identifies an MspI RFLP, with a minor allele frequency of 35%. This probe forms an important adjunct to the existing RFLPs for family studies in Duchenne muscular dystrophy.