Estrogen therapy and brain muscarinic receptor density in healthy females: a SPET study

Estrogen Therapy (ET) may protect against age-related cognitive decline and neuropsychiatric disorders (e.g. Alzheimer's disease). The biological basis for this putative neuroprotective effect is not fully understood, but may include modulation of cholinergic systems. Cholinergic dysfunction has been implicated in age-related memory impairment and Alzheimer's disease. However, to date no one has investigated the effect of long-term ET on brain cholinergic muscarinic receptor aging, and related this to cognitive function. We used Single Photon Emission Tomography (SPET) and (R,R)[(123)I]-I-QNB, a novel ligand with high affinity for m(1)/m(4) muscarinic receptors, to examine the effect of long-term ET and age on brain m(1)/m(4) receptors in healthy females. We included 10 younger premenopausal subjects and 22 postmenopausal women; 11 long-term ET users (all treated following surgical menopause) and 11 ET never-users (surgical menopause, n=2). Also, verbal memory and executive function was assessed in all postmenopausal subjects. Compared to young women, postmenopausal women (ET users and never-users combined) had significantly lower muscarinic receptor density in all brain regions examined. ET users also had higher muscarinic receptor density than ET never-users in all the brain regions, and this reached statistical significance in left striatum and hippocampus, lateral frontal cortex and thalamus. Moreover, in ET users, (R,R)[(123)I]-I-QNB binding in left hippocampus and temporal cortex was significantly positively correlated with plasma estradiol levels. We also found evidence for improved executive function in ET users as compared to ET never-users. However, there was no significant relationship between receptor binding and cognitive function within any of the groups. In healthy postmenopausal women use of long-term ET is associated with reduced age-related differences in muscarinic receptor binding, and this may be related to serum estradiol levels.     

Environmental stresses inhibit splicing in the aquatic fungus Blastocladiella emersonii

Background  

Exposure of cells to environmental stress conditions can lead to the interruption of several intracellular processes, in particular those performed by macromolecular complexes such as the spliceosome.     

Differential Phosphorylation of Smad1 Integrates BMP and Neurotrophin Pathways through Erk/Dusp in Axon Development

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The historical biogeography of Mammalia

Palaeobiogeographic reconstructions are underpinned by phylogenies, divergence times and ancestral area reconstructions, which together yield ancestral area chronograms that provide a basis for proposing and testing hypotheses of dispersal and vicariance. Methods for area coding include multi-state coding with a single character, binary coding with multiple characters and string coding. Ancestral reconstruction methods are divided into parsimony versus Bayesian/likelihood approaches. We compared nine methods for reconstructing ancestral areas for placental mammals. Ambiguous reconstructions were a problem for all methods. Important differences resulted from coding areas based on the geographical ranges of extant species versus the geographical provenance of the oldest fossil for each lineage. Africa and South America were reconstructed as the ancestral areas for Afrotheria and Xenarthra, respectively. Most methods reconstructed Eurasia as the ancestral area for Boreoeutheria, Euarchontoglires and Laurasiatheria. The coincidence of molecular dates for the separation of Afrotheria and Xenarthra at approximately 100 Ma with the plate tectonic sundering of Africa and South America hints at the importance of vicariance in the early history of Placentalia. Dispersal has also been important including the origins of Madagascar's endemic mammal fauna. Further studies will benefit from increased taxon sampling and the application of new ancestral area reconstruction methods.     

The origin of chloroplastic acetyl coenzyme A

Pyruvic dehydrogenase activity has been examined in a number of highly purified leaf organelles. In spinach leaf cell, the major activity is in the mitochrondrion with low activity in isolated chloroplasts. The major source of CO₂ derived from pyruvic acid metabolism in the isolated chloroplast is via the acetolactic synthase reaction localized in the chloroplast. Evidence is presented that the leaf mitochondrion contains both the pyruvic acid dehydrogenase and an acetyl coenzyme A hydrolase. It is suggested that free acetic acid is generated in the mitochrondrion and then moves to the chloroplast where acetyl coenzyme synthetase converts it from the metabolically inert acid to the very metabolically active acetyl coenzyme A.     

External morphology of the short-beaked common dolphin, Delphinus delphis: growth, allometric relationships and sexual dimorphism

Growth, allometric relationships and sexual dimorphism are described from measurements of 105 male, 149 female and 38 unsexed specimens of short‐beaked common dolphin, Delphinus delphis, stranded along the Irish coastline (53.8% of the sample) or by‐caught in fisheries (46.2% of the sample), from 1990 to 2003. For each dolphin, 24 external body length measurements were recorded. Ages were determined for 183 dolphins by analysis of growth layer groups in the dentine. Males ranged in total body length (TBL) from 105 to 231 cm and females from 93 to 230 cm, with a maximum age of 25 years obtained for both sexes. Using a single Gompertz growth curve, asymptotic values obtained for TBL were 211.6 cm and 197.4 cm for males and females, respectively. Asymptotic lengths were attained at 11 years in males and 9 years in females. The gestation period was estimated to last approximately 11.5 months. Sexual size dimorphism (SSD) was evident, with males being significantly larger than females for 20 of the characters measured, and an SSD ratio of 1.06 was obtained. Sexual shape dimorphism was lacking, except for the presence of prominent postanal humps in mature males.     

Synthetic analgesics and other phenylpiperidines: effects on uptake and storage of dopamine and other monoamines mouse forebrain tissue

The neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce degeneration of dopamine (DA) and other central monoamine neurons, leading to Parkinson's disease-like effects in man, monkey, and mouse. MPTP and other substituted phenylpiperidines related to synthetic analgesics including alphaprodine and meperidine were evaluated for potency vs. uptake of 0.1 microM tritiated DA, norepinephrine (NE), or serotonin (5HT) in synaptosomal preparations of mouse striatum or cerebral cortex. The most potent inhibitor of the uptake of 3H-DA was N-methyl-4-phenylpyridinium ion (MPP+; IC50 = 1 microM, Ki = 0.4 microM), a metabolite of MPTP; its effect was competitive and reversible. Other analogs of MPTP: the N-ethylindole AHR-1709, N,N-dimethyl-MPTP, and N-methyl-4-phenylpiperidine were all more potent than MPTP against 3H-DA uptake. N-dealkylation and N-propyl substitution, as well as pyridine ring substitution, decreased affinity for DA uptake while 3',4'-dihydroxyphenyl substitution increased potency and selectivity for catecholamine uptake, and quarternarization of the pyridine ring also increased potency against DA uptake. Active compounds showed higher potency against the uptake of NE than of DA. MPP+ was also more potent than MPTP in releasing endogenous DA from striatal synaptosomes (EC50 = 3 vs. 30 microM), but did not release the cytoplasmic markers tyrosine hydroxylase and lactate dehydrogenase (LDH). In contrast to MPTP, synthetic phenylpiperidine analgesics, their potential metabolites and the experimental neuroleptic agent AHR-1709 all failed to deplete striatal DA in vivo, even if active in vitro against DA uptake.