Male rock sparrows adjust their breeding strategy according to female ornamentation: parental or mating investment?

We investigated the relations between female quality and ornamentation and between male breeding investment and female ornamentation in the rock sparrow, Petronia petronia, a passerine in which both sexes have a yellow breast patch. Breast patch size in females was positively correlated with body mass and breeding status; double-brooding and primary females of polygynous males had a larger patch, and patch size could therefore be an indicator of female phenotypic quality. We conducted a field experiment to test whether males allocate their parental effort in relation to female quality, as predicted by the differential allocation hypothesis. We increased and reduced the ornament sizes of paired females and compared the behaviour of their males before and after manipulation. Frequency of brood feeding by the male was not affected by female ornament manipulation; there was a nonsignificant trend for females with enlarged ornaments, contrary to predictions, to increase their feeding rate. Reducing female ornaments resulted in a decrease in male nest attendance, a measure of passive brood defence, whereas enlarging the ornament had no effect. Males concurrently reduced their territorial (song output) and sexual activity (courtship and copulation). The reduction in sexual activity suggests that males may have changed their nest attendance in response to their mate's renesting probability. Whatever the interpretation, these results provide some of the first evidence that not only female, but also male, birds change breeding strategy according to their mate's phenotype in the wild. Copyright 2003 Published by Elsevier Ltd on behalf of The Association for the Study of Animal Behaviour.      

Apoptosis meets proteasome, an invaluable therapeutic target of anticancer drugs

This report reviews the current status of extensive efforts directed towards the interpretation of crosstalk between apoptosis and proteasome to understanding the molecular mechanism of anticancer agents targeting proteasome, with particular focus on MG132 and PS-341. The discovery that all cancer cells have retained the apoptotic death program has offered to the researchers new biochemical targets to design anticancer drugs. Moreover, the demonstration that proteasome inhibition induces apoptosis and sensitizes cancer cells to traditional tumoricidal agents has proposed the proteasome as an attractive target for development of new anticancer drugs. Since then, a number of both naturally occurring and synthetic inhibitors of the proteasome have been identified. The best characterized and most widely used inhibitors of the proteasome are the peptide aldehydes; among these MG132, due to its broad spectrum of action, low cost and rapid reversibility of action, still remains the first choice to study proteasome function in cell and tissue cultures. Recently, a very potent new class of selective and reversible proteasome inhibitors which contains an inhibitory boronate group has been described. PS-341 represent the first of this promising class of agents that could have application in cancer therapy and it is the only that has progressed to clinical trials.     

Mechanisms transducing the aldosterone secretagogue signal of endothelins in the human adrenal cortex

Evidence has been provided that the 21-amino acid hypertensive peptide endothelin (ET)-1 exerts a potent secretagogue effect on human adrenocortical zona glomerulosa (ZG), acting through two receptor subtypes, called ET(A) and ET(B), the signaling mechanism(s) of which has (have) not yet been investigated. Collagenase dispersed human ZG cells were obtained from normal adrenals of patients undergoing nephrectomy/adrenalectomy for renal cancer. The selective ET(A)- and ET(B)-receptor activation was obtained by exposing dispersed cells to ET-1 plus the ET(B)-receptor antagonist BQ-788 and to the ET(B)-receptor agonist BQ-3020, respectively. The phospholipase (PL) C inhibitor U-73122 abolished ET(A) receptor-mediated secretory response, but only partially prevented the ET(B) receptor-mediated one. The phosphatidylinositol 3-kinase inhibitor wortmannin, the calmodulin inhibitor W-7 and the protein kinase (PK) C inhibitor calphostin-C significantly blunted the secretory responses ensuing from the activation of both receptor subtypes. When added together, calphostin-C and wortmannin or W-7 abolished ET(A)-mediated secretory response, but only decreased ET(B)-mediated one. The ET(B) receptor-, but not the ET(A) receptor-mediated aldosterone response was partially reversed by the cyclooxygenase (COX) inhibitor indomethacin, which when added together with U-73122 abolished it. ET(A)-receptor activation raised inositol triphosphate (IP(3)) production from dispersed ZG cells, while ET(B)-receptor stimulation enhanced both IP(3) and prostaglandin-E(2) production. Collectively, our findings indicate that ETs stimulate aldosterone secretion from human ZG cells, acting through ET(A) receptors exclusively coupled to PLC/PKC-dependent pathway and ET(B) receptors coupled to both PLC/PKC- and COX-dependent cascades.     

K+ channel cAMP activated in guinea pig gallbladder epithelial cells

In guinea pig gallbladder epithelial cells, an increase in intracellular cAMP levels elicits the rise of anion channel activity. We investigated by patch-clamp techniques whether K(+) channels were also activated. In a cell-attached configuration and in the presence of theophylline and forskolin or 8-Br-cAMP in the cellular incubation bath, an increase of the open probability (P(o)) values for Ca(2+)-activated K(+) channels with a single-channel conductance of about 160 pS, for inward current, was observed. The increase in P(o) of these channels was also seen in an inside-out configuration and in the presence of PKA, ATP, and cAMP, but not with cAMP alone; phosphorylation did not influence single-channel conductance. In the inside-out configuration, the opioid loperamide (10(-5) M) was able to reduce P(o) when it was present either in the microelectrode filling solution or on the cytoplasmic side. Detection in the epithelial cells by RT-PCR of the mRNA corresponding to the alpha subunit of large-conductance Ca(2+)-activated K(+) channels (BK(Ca)) indicates that this gallbladder channel could belong to the BK family. Immunohistochemistry experiments confirm that these cells express the BK alpha subunit, which is located on the apical membrane. Other K(+) channels with lower conductance (40 pS) were not activated either by 8-Br-cAMP (cell-attached) or by PKA + ATP + cAMP (inside-out). These channels were insensitive to TEA(+) and loperamide. The data demonstrate that under conditions that induce secretion, phosphorylation activates anion channels as well as Ca(2+)-dependent, loperamide-sensitive K(+) channels present on the apical membrane.     

Metal chelates of 2-hydroxy-4-methylthiobutanoic acid in animal feeding: preliminary investigations on stability and bioavailability

The alpha-hydroxyacid 2-hydroxy-4-methylthiobutanoic acid (the so-called methionine hydroxy-analogue, MHA), largely used in animal nutrition as a source of methionine, forms stable metal chelates with divalent metals of formula [[CH(3)SCH(2)CH(2)CH(OH)COO](2)M].ZnH(2)O. Protonation and zinc(II) complex formation constants have been determined by pH-metry at 25 degrees C; the ternary system Zn(2+)/MHA/glycine was also studied by pH-metry and the formation constant of the species [ZnLA] was determined [log beta=6.57(11)]. Experiments in vitro with human intestinal CACO-2 cells indicated that the MHA/Fe chelate was taken up by the cells without any apparent toxic effect.     

Melatonin,melanogenesis, and hypoxic stress in the newt,Triturus carnifex

Groups of 6 specimens each of the newt Triturus carnifex were treated with melatonin to see if the hormone inhibited melanogenesis in the Kupffer cells of the liver (melanomacrophages), a process markedly stimulated by hypoxia. A dose of 500 microg/g in 27% ethanol, injected intraperitoneally, induced loss of consciousness and tetany of all the skeletal muscles, which on the contrary appeared relaxed in animals pre-anesthetised by immersion in chlorbutol at 0.2%. Anesthetised specimens injected with melatonin showed a significantly lower increase in hepatic pigmentation after acute hypoxia, a condition attained by sealing each specimen in a 620 mL respiratory chamber with water containing 1.1 ppm of oxygen for the time needed to consume it all (about two hours). If hypoxia is reached gradually, beginning with 8 ppm of oxygen (normoxic condition), the increase in hepatic pigmentation after melatonin injection does not differ significantly from that of non-hormone treated specimens: thus melatonin does not seem to play a direct part in controlling hepatic melanogenesis. Instead, the hormone induces significant increase in oxygen consumption, marked general steatosis of the liver and the almost total disappearance of glycogen. Intraperitoneal injection of 500 microg/g of melatonin in anesthetised animals exposed to the air (normoxic) also causes severe steatosis and an unexpected increase in the hepatic deposits of melanin, as after hypoxic treatment. A dose of 100 ng/g in 1% ethanol, ineffective when injected intraperitoneally, also induces these effects if injected directly into the arterial blood-stream through the conus arteriosus, thus avoiding the hepatic filter. The phenomena observed appear to be induced by a powerful endocrine mechanism that provokes metabolic hypoxia by consuming all the available ATP for synthesizing fat. A less intense form of steatosis can also be observed in animals subjected to hypoxia but without prior hormone treatment, indicating that a natural process triggered by hypoxic stress is pushed to the extreme by exogenous melatonin: the hormone changes the entire energy metabolism of the organism so that it can survive for a long time under adverse environmental conditions.     

Proteomics application exercise of the Swiss Proteomics Society: report of the SPS'02 session

After the success of the mass spectrometry (MS) round table that was held at the first Swiss Proteomics Society congress (SPS'01) in Geneva, the SPS has organized a proteomics application exercise and allocated a full session at the SPS'02 congress. The main objective was to encourage the exchange of expertise in protein identification, with a focus on the use of mass spectrometry, and to create a bridge between the users' questions and the instrument providers' solutions. Two samples were sent to fifteen interested labs, including academic groups and MS hardware providers. Participants were asked to identify and partially characterize the samples. They consisted of a complex mixture of peptide/proteins (sample A) and an almost pure recombinant peptide carrying post-translational modifications (sample B). Sample A was an extract of snake venom from the species Bothrops jararaca. Sample B was a recombinant and modified peptide derived from the shrimp Penaeus vannamei penaeidin 3a. The eight labs that returned results reported the use of a wide range of MS instrumentation and techniques. They mentioned a variety of time and manpower allocations. The origin of sample A was generally identified together with a number of database protein entries. The difficulty of the sample identification lay in the incomplete knowledge of the Bothrops species genome sequence and is discussed. Sample B was generally and correctly identified as penaeidin. However, only one group reported the full primary structure. Interestingly, the approaches were again varied and are discussed in the text.