Kidneys extract BNP and NT-proBNP in healthy young men.

Renal metabolism of the cardiac marker NH2-terminal-pro-brain natriuretic peptide (NT-proBNP) has been suggested. Therefore, we determined the renal extraction ratios of NT-proBNP and its bioactive coproduct brain natriuretic peptide (BNP) at rest and during exercise. In addition, the cerebral ratios were evaluated. Ten young healthy men were investigated at baseline, during moderate cycle exercise (heart rate: 140, Borg scale: 14-15), and in the recovery with BNP and NT-proBNP measured from the brachial artery and the jugular and renal veins, and the renal and cerebral extraction ratios (Ext-Ren and Ext-Cer, respectively) were calculated. Cardiac output, stroke volume, heart rate, mean arterial pressures, and estimated glomerular filtration were determined. BNP and NT-proBNP were extracted by the kidneys but not by the brain. We observed no effect of exercise. The mean values (+/- SE) of Ext-Ren of NT-proBNP were similar (0.19 +/- 0.05, 0.21 +/- 0.06, and 0.12 +/- 0.03, respectively) during the three sessions (P > 0.05). Also the Ext-Ren of BNP were similar (0.18 +/- 0.07, 0.15 +/- 0.11, and 0.14 +/- 0.06, respectively; P > 0.05). There were no significant differences between Ext-Ren of BNP and NT-proBNP during the three sessions (P > 0.05). The Ext-Cer of both peptides varied insignificantly between -0.21 +/- 0.15 and 0.11 +/- 0.08. The renal extraction ratio of both BNP and NT-proBNP is approximately 0.15-0.20. There is no cerebral extraction, and short-term moderate exercise does not affect these values. Our findings suggest that the kidneys extract BNP and NT-proBNP to a similar extent in healthy young men.     

Antigen-specific,MHC-unrestricted T cells

The published record suggests that in the majority of cases the antigen is recognized by the T cell receptor (TCR) as a complex of a foreign antigen and amino acid residues contributed by the major histocompatibility complex (MHC) antigens, and the antigen-specific, MHC-restricted effector function is an unambiguous result of this process. Alternatively, the T cell receptor may recognize a particular conformational form of the antigen which is dictated by the allelic differences in the MHC, resulting also in MHC-restricted recognition. When, however, a T cell which phenotypically fulfills all the requirements necessary to perform antigen specific, MHC-restricted function, shows a lack of MHC restriction, there are two possible explanations: 1) In addition to the MHC-restricted, antigen-specific T cell receptor the cell expresses, or has newly acquired the expression of another, MHC-unrestricted (NK-like) receptor, or 2) The specific antigen recognized by the T cell receptor, is able to bind to the receptor and activate the T cell without being presented by the MHC molecule. While the first possibility has been extensively described in the literature as well as other articles in this issue, the second possibility has not been dealt with to the same extent and is the primary focus of this review.     

Staggered Flowering in Four Sympatric Varieties of Geonoma cuneata (Palmae)1

Phenology, flowering biology, and pollination were studied for one year in four sympatric varieties of the polymorphic palm Geonoma cuneata in Ecuador. Flowering seasons of the three most common varieties were significantly staggered resulting in minimal temporal overlap. No marked differences were found with respect to flowering biology or pollination. The implication of these findings for explaining the complicated morphological variation pattern found in G. cuneata and similar species complexes is discussed.     

Female mate choice of male signals is unlikely to promote ecological adaptation in Enchenopa treehoppers (Hemiptera: Membracidae)

A key question in speciation research is how ecological and sexual divergence arise and interact. We tested the hypothesis that mate choice causes local adaptation and ecological divergence using the rationale that the performance~signal trait relationship should parallel the attractiveness~signal trait relationship. We used female fecundity as a measure of ecological performance. We used a species in the Enchenopa binotata treehopper complex, wherein speciation involves adaptation to novel environments and divergence in sexual communication. We used a full‐sibling, split‐family rearing design to estimate genetic correlations (r_G) between fecundity and signal traits, and compared those relationships against population‐level mate preferences for the signal traits. Animal model estimates for r_G between female fecundity and male signal traits overlapped zero—rejecting the hypothesis—but could reflect sample size limitations. The magnitude of r_G correlated with the strength of the mate preferences for the corresponding signal traits, especially for signal frequency, which has the strongest mate preference and the most divergence in the complex. However, signal frequencies favored by the population‐level mate preference are not associated with high fecundity. Therefore, mate preferences do not appear to have been selected to favor high‐performance genotypes. Our findings suggest that ecological and sexual divergence may arise separately, but reinforce each other, during speciation.     

Synthetic tools for adrenocorticotropin receptor identification

Biotinylated photoaffinity derivatives of adrenocorticotropin (ACTH) are potentially useful tools for the identification of ACTH receptors. The hormone can be attached covalently to its receptor by photoactivation, and the presence of biotin in the molecule facilitates isolation of the solubilized hormone-receptor complex on columns of immobilized succinoylavidin (Suc-avidin). Six photoprobes of ACTH1-24 have been prepared by reacting ACTH1-24, [25-biocytin]ACTH1-25 amide, and [25-dethiobiocytin]ACTH1-25 amide with either 4- or 5-azido-2-nitrophenylsulfenyl (4-NAPS and 5-NAPS, respectively) chlorides in acetic acid. The homogeneity of the photoprobes was carefully monitored by thin-layer chromatography and amino acid analyses of acid hydrolysates. The presence of underivatized starting material in the photoprobes was critically scrutinized by high-pressure liquid chromatography and was estimated to be less than 0.5%. Both the 4- and 5-NAPS derivatives stimulated maximal steroidogenesis (as compared with ACTH1-24) in calf adrenal cortical cells. However, the potencies of the two isomers differed significantly. The ED50 for steroidogenesis with 5-NAPS-ACTH1-24 was 100-fold greater than the standard (ACTH1-24) while that for 4-NAPS-ACTH1-24 was only approximately 7 times greater. Although 4-NAPS-ACTH1-24 was capable of stimulating maximal adenosine cyclic 3',5'-phosphate (cAMP) production, the 5-NAPS derivative was usually not. The level of stimulation with the 5-NAPS derivative varied considerably from cell preparation to cell preparation. ACTH1-24-induced cAMP production was inhibited by 5-NAPS-ACTH1-24 or 5-NAPS-[25-dethiobiocytin]ACTH1-25 amide.(ABSTRACT TRUNCATED AT 250 WORDS)     

A series of spirocyclic analogues as potent inhibitors of bacterial phenylalanyl-tRNA synthetases

We have identified a series of spirocyclic furan and pyrrolidine inhibitors of Enterococcus faecalis and Staphylococcus aureus phenylalanyl-tRNA synthetases. The most potent analogue 1b showed IC50=5 nM (E. faecalis PheRS) and IC50=2 nM (S. aureus PheRS) with high selectivity over the human enzyme. The crystal X-ray structure of analogue 1b was determined.     

Overlapping and specific patterns of GDNF,c-ret and GFR alpha mRNA expression in the developing chicken retina

GDNF and the GDNF receptors, c-Ret, GFR alpha 1 and 2 mRNA is expressed in the developing chicken retina. GDNF labelling was mainly found in embryonic day 4-5 retina but weak labelling could also be found over scattered retinal cells at later stages. c-ret labelling was found over ganglion cells, amacrine and horizontal cells; the preferred GDNF receptor (GFR alpha 1) over amacrine and horizontal cells; and the less preferred GDNF receptor (GFR alpha 2) over ganglion cells, amacrine cells and photoreceptors.     

In vivo and in vitro effect of naloxone on prolactin response to TRH in rat

In adult male Wistar rats submitted to a standardized noise stress, intravenous TRH induced a prolactin (PRL) secretory response. Prior IV naloxone administration not only lowered plasma PRL levels in those stressed rats but abolished also the stimulatory action of TRH. This effect was further studied by superfusion experiments on enriched PRL cell suspensions (70% lactotrophs) from female adult Wistar rats. Naloxone kept unaffected the basal PRL secretion but lowered significantly that induced by TRH. These experiments suggest a dual effect of naloxone on rat PRL secretion, one exerted on central opioid receptors lowering stress-related increased basal PRL levels, the other inhibiting the TRH-dependent PRL secretion exerted at the lactotroph level itself.     

The effect of bombesin on basal, alpha-methyl-p-tyrosine, haloperidol, morphine, bremazocine and stress-induced prolactin secretion

Intravenously administered bombesin lowered basal PRL levels in conscious male rats and prevented the morphine, bremazocine and stress-induced PRL secretion. The same dose of bombesin had no effect on PRL levels in alpha-methyl-p-tyrosine pretreated rats and did not affect haloperidol-stimulated PRL release. These results show that bombesin given intravenously acts as an inhibitor of PRL secretion and suggests that it does not act on the lactotrope itself but rather by an increase of the inhibitory dopaminergic tone.