The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration

The 5-hydroxytryptamine (5-HT₄) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT₄ receptor [³H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5-HT transporter ( S )-[ N -methyl-³H]citalopram binding. We also determined the regulation of 5-HT₄ receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5-HT depletion, and compared this with changes in 5-HT_2A receptor [³H]MDL100907 binding. In the Flinders Sensitive Line, the 5-HT₄ receptor and 5-HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16–47% down-regulation of 5-HT₄ receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5-HT₄ receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT_2A receptor binding was decreased in the frontal and cingulate cortices after chronic paroxetine administration, and markedly reduced in several regions after 5-HT depletion. Thus, the 5-HT₄ receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration.     

Gravitropic responses of the Avena coleoptile in space and on clinostats. IV. The clinostat as a substitute for space experiments

Gravitropic responses of dark grown oat coleoptiles were measured in weightlessness and under clinorotation on earth. The tests in microgravity were conducted in Spacelab during the IML-1 mission and those on clinostats were conducted in laboratories on earth. The same apparatus was used for both kinds of tests. In both cases autotropism and gravitropic responsiveness were determined. This allowed a quantitative comparison between the plants' responses after receiving the same tropistic stimulations either in weightlessness or on clinostats.
Autotropism was observed with oat coleoptiles responding in weightlessness but it did not occur on clinostats. Gravitropic responsiveness was measured as the ratio between the incremental bending response (degrees curvature) and the corresponding incremental g-dose (stimulus intensity times duration for which it was applied). Plants were tested at either of two stages of coleoptile development (i.e. different coleoptile lengths). From a total of six different kinds of critical comparisons that could be made from our tests that provided data for clinorotated vs weightless plants, three showed no significant difference between responses in simulated vs authentic weightlessness. Three other comparisons showed highly significant differences. Therefore, the validity of clinorotation as a general substitute for space flight was not supported by these results.     

Identification of 27-oxo-octacosanoic acid and heptacosane-1,27-dioic acid in Legionella pneumophila

A strain of Escherichia coli having elevated levels of cytochrome bo and lacking the cytochrome bd quinol oxidase was grown in chemostat culture at low copper levels. Such cells had lowered levels of copper and of total cytochrome b. Cytochrome o concentration was unchanged when assayed by conventional CO difference spectroscopy, but apparently diminished by 80% in copper-deficient cells as determined by photodissociation of bound CO at 193 K. This is attributed to depletion of copper in the oxidase of copper-deficient cells, causing rapid recombination of photodissociated CO to haem O. CO recombination was also more sensitive to low intensities of actinic light in copper-depleted oxidase. The results illustrate a further similarity between the active sites of o- and aa3-type terminal oxidases.     

The helicase CaHmi1p is required for wild-type mitochondrial DNA organization in Candida albicans

The mechanistic details of mtDNA maintenance in petite-negative yeasts have remained largely unexplored. We report here that the DNA helicase Hmi1p plays a crucial role in mtDNA stability in Candida albicans. Like its counterpart in Saccharomyces cerevisiae, Hmi1p in C. albicans (CaHmi1p) contains a C-terminal mitochondrial targeting signal that is functional in both organisms. Biochemical analysis demonstrates that CaHmi1p is a protein possessing ATP-dependent 3'-5' DNA-unwinding activity. Deletion of both HMI1 alleles does not lead to complete loss of mtDNA in C. albicans; however, substantial fragmentation of the wild-type mitochondrial genome, reduction of mtDNA mass and loss of wild-type nucleoid distribution occur. Specific regions of the mitochondrial genome give rise to mtDNA molecule populations with altered characteristics upon CaHMI1 deletion. Fragmentation of the mitochondrial genome can be reversed by reintroduction of CaHmi1p. This is the first time that a gene required for wild-type mtDNA maintenance in S. cerevisiae has been demonstrated to be nonessential in a petite-negative yeast.     

AZD2184: a radioligand for sensitive detection of β-amyloid deposits

The presence of β‐amyloid plaques in brain is a hallmark of Alzheimer’s disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Positron emission tomography (PET) radioligands such as Pittsburgh compound B ([¹¹C]‐2‐(3‐fluoro‐4‐methylamino‐phenyl)‐benzothiazol‐6‐ol) (PIB) binds selectively to β‐amyloid and are promising new tools supporting the clinical diagnoses of AD. In addition, such methodology may be useful for evaluation of new drugs aiming at reduction of amyloid plaque load. The objective of this study is to develop a new amyloid selective PET radioligand with higher signal‐to‐background ratio when compared with existing amyloid PET ligands. The lead compound, AZD2184, (2‐[6‐(methylamino)pyridin‐3‐yl]‐1,3‐benzothiazol‐6‐ol) was found to have high affinity for amyloid fibrils in vitro (K_d: 8.4 ± 1.0 nM). Two minutes after i.v. administration in rats, about 1% of the dose was in brain. In vitro autoradiography on cortical brain sections from amyloid‐beta precursor protein/presenilin 1 (APP/PS1) mice and AD patients showed that while [³H]AZD2184 and [³H]PIB are mutually displaceable, [³H]AZD2184 displays a higher signal‐to‐background ratio primarily by virtue of lower background binding levels. The ratio of binding ability in prefrontal cortex (high plaque load) to subcortical white matter (background) was 4.5 for [³H]AZD2184 and 0.8 for [³H]PIB at 1 nM. In adjacent cortical sections from APP/PS1 mouse as well as from AD cortical tissue, [³H]AZD2184 and antibodies to human β‐amyloid labeled identical structures. In vivo administration of [³H]AZD2184 to APP/PS1 mice further showed that [³H]AZD2184 labels amyloid deposits with low non‐specific background binding. Taken together, the pre‐clinical profile of AZD2184 in relation to the reference ligand PIB, suggests that ¹¹C‐labeled AZD2184 is a potential radioligand for PET‐visualization of β‐amyloid deposits in the living human brain.     

Species composition and vegetation structure of an upper montane forest at the summit of Mt. Doi Inthanon, Thailand

Upper montane forest (UMF) within Doi Inthanon National Park, Northern Thailand, was investigated by means of fifty, 40 × 40 m stratified random plots situated between 2080 and 2565 m altitude. The aim was to address a number of community ecological questions concerning woody species composition and structural heterogeneity of the forest. A total of 7474 individuals of trees and woody climbers ≥ 15 cm gbh (girth at breast height) were included in the study and these were identified to 47 species, 39 genera and 26 families. The average density was 934 individuals/ha and the average stem basal area was 71.8 m²/ha. The most important species were: Quercus eumorpha, Sjzygium angkae, Litsea martabanica, Helicia nilagirica, Lindera caudata, Schima wallichii, Osmanthus fiagrans, Eurya acuminata, Myrsine semiserrata and Ilex umbellulata and the most important families were Fagaceae, Lauraceae, Theaceae and Myrtaceae. Altitude was the most important environmental variable explaining species composition and vegetation structure. Most of the calculated vegetation variables showed significant correlation with altitude: species richness, family richness, diversity, density and crown cover declined with altitude, average tree height was uncorrelated with altitude and basal area increased with altitude. An analysis of size class distributions indicated good forest conditions and reverse-J-shaped age class distribution of most species.     

NMR imaging of roots: effects after root freezing of containerised conifer seedlings

Seedlings of Scots pine ( Pinus sylvestris L.) and Norway spruce [ Picea abies (L) Karst.] were subjected to low root temperatures, and 10 days later the roots were examined by NMR imaging. The amount of NMR detectable roots decreased with decreasing temperature, with the signal from the younger roots at the bottom of the container being the first to disappear. The origin of the loss of NMR signal is unclear but may be due to changes in the NMR properties of root water after cold damage. A recent method is discussed for obtaining unbiased estimates of root lengths from a series of total vertical projections; the method is particularly suited to evaluating NMR projection images. Since NMR imaging methods can apparently distinguish between control and cold damaged roots, it may be possible to design more routine applications using low resolution NMR methods.