Uptake of Exogenous Glutamate and Aspartate by Circumventricular Organs but Not Other Regions of Brain

Abstract: Glutamate (Glu) and aspartate (Asp) concentrations in blood and selected regions of brain were measured at sequential intervals over a 3-h period following subcutaneous administration of Glu, Asp, or Glu plus Asp (2 mg/g body wt) to 4-day-old mouse or rat pups. Marked serum elevations of the administered amino acids (peak values exceeding 200 times control levels) were detected within 1 h. In circumventricular organ (CVO) regions of brain, which are thought to have no blood-brain barriers, a sharp and steady increase in tissue concentrations of the administered amino acids (peak values 4–10 times higher than control levels) occurred during a 15–120 min interval, whereas no appreciable increases were detected in other brain regions. When 2 mg/g Glu plus 2 mg/g Asp were administered, CVO tissue concentrations of each amino acid rose to approximately the same level obtained when the individual amino acids were given. It is concluded that blood-brain barriers preventing net entry of Glu or Asp into brain proper are relatively well established by the 4th postnatal day in rodents, but that CVO brain regions lack such barriers; selective access of blood-borne Glu or Asp to CVO neurons explains why these neurons are selectively destroyed by systemic administration of these neurotoxic amino acids.     

An improved enzymatic cycle for nicotinamide-adenine dinucleotide phosphate.

We describe the use of column chromatography on the nonpolar adsorbent. Amberlite XAD-2, and on silanized silica gel in the desalting and partial purification of cobalamins. These techniques are both simpler and more versatile than phenol extraction, without sacrificing efficiency. In addition, a solvent system for thin-layer chromatography on silanized silica gel is described which rapidly separates naturally occurring cobalamins.     

Down syndrome in British Columbia, 1952-73: incidence and mean maternal age.

Records of children with Down syndrome (DS) at the BC Health Surveillance Registry were linked to their Birth Registrations to derive maternal ages. Incidence and maternal-age specific rates were calculated for 1952-73. Mean maternal age has declined both for normal and DS children, the latter to a marked degree, so that in 1972-73 80% were born to women under 35 years. Using maternal age of 40 and over as an indication for amniocentesis would only detect 10% of DS children. The crude incidence rate (mean 1.28/1000 livebirths) has not changed appreciably over the study period except for 1969 in which a statistically significant peak occurred. The standarized rate showed an increasing trend but it is not clear whether this was a true biological increase or resulted from better ascertainment.     

The effects of dogfish MSH''s and of corticotrophin-like intermediate lobe peptides (CLIP''s) on avoidance behavior in rats

Recently purified melanocyte-stimulating hormones (MSH's) from dogfish pituitary tissue were tested on extinction of a conditioned avoidance response (CAR). Corticotrophin like intermediate lobe peptides (CLIP's) from dogfish and porcine origin were tested for an effect on avoidance extinction as well. All peptides appeared to delay extinction of the CAR.The results suggest that the pituitary contains various peptides which influence adaptive behavior. The observation that MSH is more potent in delaying extinction of the CAR then CLIP leads to the conclusion that the behavioral active sequence of the ACTH molecules is located in the N terminal part rather than in the C terminal part of the polypetide.     

Indirect Evolution of Hybrid Lethality Due to Linkage with Selected Locus in Mimulus guttatus

Most species are superbly and intricately adapted to the environments in which they live. Adaptive evolution by natural selection is the primary force shaping biological diversity. Differences between closely related species in ecologically selected characters such as habitat preference, reproductive timing, courtship behavior, or pollinator attraction may prevent interbreeding in nature, causing reproductive isolation. But does ecological adaptation cause reproductive incompatibilities such as hybrid sterility or lethality? Although several genes causing hybrid incompatibilities have been identified, there is intense debate over whether the genes that contribute to ecological adaptations also cause hybrid incompatibilities. Thirty years ago, a genetic study of local adaptation to copper mine soils in the wildflower Mimulus guttatus identified a locus that appeared to cause copper tolerance and hybrid lethality in crosses to other populations. But do copper tolerance and hybrid lethality have the same molecular genetic basis? Here we show, using high-resolution genome mapping, that copper tolerance and hybrid lethality are not caused by the same gene but are in fact separately controlled by two tightly linked loci. We further show that selection on the copper tolerance locus indirectly caused the hybrid incompatibility allele to go to high frequency in the copper mine population because of hitchhiking. Our results provide a new twist on Darwin''s original supposition that hybrid incompatibilities evolve as an incidental by-product of ordinary adaptation to the environment.     

Fish Assemblages on Estuarine Artificial Reefs: Natural Rocky-Reef Mimics or Discrete Assemblages?

If the primary goal of artificial reef construction is the creation of additional reef habitat that is comparable to adjacent natural rocky-reef, then performance should be evaluated using simultaneous comparisons with adjacent natural habitats. Using baited remote underwater video (BRUV) fish assemblages on purpose-built estuarine artificial reefs and adjacent natural rocky-reef and sand-flat were assessed 18 months post-deployment in three south-east Australian estuaries. Fish abundance, species richness and diversity were found to be greater on the artificial reefs than on either naturally occurring reef or sand-flat in all estuaries. Comparisons within each estuary identified significant differences in the species composition between the artificial and natural rocky-reefs. The artificial reef assemblage was dominated by sparid species including Acanthopagrus australis and Rhabdosargus sarba. The preference for a range of habitats by theses sparid species is evident by their detection on sand-flat, natural rocky reef and artificial reef habitats. The fish assemblage identified on the artificial reefs remained distinct from the adjacent rocky-reef, comprising a range of species drawn from naturally occurring rocky-reef and sand-flat. In addition, some mid-water schooling species including Trachurus novaezelandiae and Pseudocaranx georgianus were only identified on the artificial reef community; presumably as result of the reef''s isolated location in open-water. We concluded that estuarine artificial reef assemblages are likely to differ significantly from adjacent rocky-reef, potentially as a result of physical factors such as reef isolation, coupled with species specific behavioural traits such as the ability of some species to traverse large sand flats in order to locate reef structure, and feeding preferences. Artificial reefs should not be viewed as direct surrogates for natural reef. The assemblages are likely to remain distinct from naturally occurring habitat comprised of species that reside on a range of adjacent natural habitats.     

Secondary Structure and Dynamics of an Intrinsically Unstructured Linker Domain

Abstract

The transient secondary structure and dynamics of an intrinsically unstructured linker domain from the 70 kDa subunit of human replication protein A was investigated using solution state NMR. Stable secondary structure, inferred from large secondary chemical shifts, was observed for a segment of the intrinsically unstructured linker domain when it is attached to an N-terminal protein interaction domain. Results from NMR relaxation experiments showed the rotational diffusion for this segment of the intrinsically unstructured linker domain to be correlated with the N-terminal protein interaction domain. When the N-terminal domain is removed, the stable secondary structure is lost and faster rotational diffusion is observed. The large secondary chemical shifts were used to calculate phi and psidihedral angles and these dihedral angles were used to build a backbone structural model. Restrained molecular dynamics were performed on this new structure using the chemical shift based dihedral angles and a single NOE distance as restraints. In the resulting family of structures a large, solvent exposed loop was observed for the segment of the intrinsically unstructured linker domain that had large secondary chemical shifts.