Catecholamines inhibit Ca(2+)-dependent proteolysis in rat skeletal muscle through beta(2)-adrenoceptors and cAMP

Overall proteolysis and the activity of skeletal muscle proteolytic systems were investigated in rats 1, 2, or 4 days after adrenodemedullation. Adrenodemedullation reduced plasma epinephrine by 95% and norepinephrine by 35% but did not affect muscle norepinephrine content. In soleus and extensor digitorum longus (EDL) muscles, rates of overall proteolysis increased by 15-20% by 2 days after surgery but returned to normal levels after 4 days. The rise in rates of protein degradation was accompanied by an increased activity of Ca(2+)-dependent proteolysis in both muscles, with no significant change in the activity of lysosomal and ATP-dependent proteolytic systems. In vitro rates of Ca(2+)-dependent proteolysis in soleus and EDL from normal rats decreased by ~35% in the presence of either 10(-5) M clenbuterol, a beta(2)-adrenergic agonist, or epinephrine or norepinephrine. In the presence of dibutyryl cAMP, proteolysis was reduced by 62% in soleus and 34% in EDL. The data suggest that catecholamines secreted by the adrenal medulla exert an inhibitory control of Ca(2+)-dependent proteolysis in rat skeletal muscle, mediated by beta(2)-adrenoceptors, with the participation of a cAMP-dependent pathway.     

Homocysteine and vitamin therapy in stroke prevention and treatment: a review

Homocysteine (Hcy), a sulfur amino acid, is the only direct precursor for L-methionine synthesis through a reaction that requires vitamin B??, representing a connection with "one-carbon" units metabolism. Hcy catabolism requires vitamin B? and as a consequence, alteration in folic acid and B vitamins status impairs Hcy biotransformation. Numerous studies have indicated that Hcy is an independent risk factor for cardio- and cerebrovascular diseases. In the last decade, several clinical trials have investigated the possible correlation between the use of folic acid and vitamins B? and B?? for lowering Hcy plasma concentration and the reduced risk of stroke or its recurrence. This review is aimed to present some aspects of Hcy biochemistry, as well as the mechanisms through which it exerts the toxic effects on the vascular endothelium. We also discuss the results of some of the clinical trials developed to investigate the beneficial effects of vitamin therapy in the prevention and management of stroke.     

Living with primary ciliary dyskinesia: a prospective qualitative study of knowledge sharing, symptom concealment, embarrassment, mistrust, and stigma

Background

Primary ciliary dyskinesia (PCD) is a chronic respiratory disease for which there is little psycho-social research and no qualitative studies of individuals living with the condition. A questionnaire-based survey in 2003 found evidence of stigmatisation in some individuals with PCD. Although the questionnaire had face and construct validity, stigmatisation was not cross-validated against interviews. The present study had the twin aims of carrying out a qualitative study of the adult patients living with PCD, and using a structured design to validate the questionnaire measure of stigma.

Methods

Interviews were carried out with six pairs of individuals with PCD, matched for sex, situs, and age, one with a high stigma score in 2003 and the other with a low stigma score. Depth-qualitative interviews were conducted by one author to explore themes surrounding the psycho-social impact of PCD using a grounded theory analysis. The interviewer was blind to the stigma scores of participants, and after the qualitative analysis was completed, the interviewer made an assessment of which member of each pair seemed the more stigmatised, after which the code was broken.

Results

Interviews revealed a number of themes, including other people's knowledge of PCD, the sharing of knowledge about PCD, the concealment of symptoms of PCD, embarrassment at symptoms, changes of behaviour in response to PCD, mistrust of medical care, in particular in relation to problems in diagnosis, a mistrust of general practitioners who were seen as poorly informed, and the importance of expert care at tertiary referral centres. Although stigmatisation as such was rarely mentioned directly by respondents, when the interviewer's judgement on level of stigmatisation was correlated with stigma scores from 2003, it was found that the more stigmatised member had been correctly identified in all six pairs (p = .016).

Conclusion

Our results suggest that some people with PCD feel isolated through mistrust in medicine, and lack of knowledge surrounding PCD. Many responses to PCD can be explained in terms of stigmatisation, and in particular felt stigma. The correlation between questionnaire used several years previously, and the interviewer's judgements of stigmatisation suggest that the stigma questionnaire had both predictive validity and long-term stability. As in other chronic conditions, stigmatisation occurs only in some individuals with PCD, and the present study explores the basis of stigmatisation, and validate the questionnaire as a measure of difference in stigma.     

Marmoset phylogenetics, conservation perspectives, and evolution of the mtDNA control region

Marmosets (genus Callithrix) are a diverse group of platyrrhine primates with 13-15 purported taxa, many of them considered endangered. Morphological analyses constitute most of the basis for recognition of these forms as distinct taxa. The purpose of this study was to provide a molecular view, based on mitochondrial control region sequences, of the evolutionary history of the marmosets, concomitant with a molecular phylogenetic perspective on species diversity within the group. An additional purpose was to provide the first comparative examination of a complete New World monkey control region sequence with those of other mammals. The phylogenetic analyses provide convincing support for a split between the Atlantic forest and Amazonian marmosets, with the inclusion of the pygmy marmoset (Cebuella pygmaea) at the base of the Amazonian clade. The earliest branch of the Atlantic forest group was C. aurita. In the Amazonian group, the analyses do not support the recognition of C. humeralifer and the recently described C mauesi as distinct taxa. They do, however, support a clear distinction between C. argentata and a strongly supported mixed clade of C. humeralifer and C. mauesi. In the Atlantic forest group, the phylogenetic tree suggests mixing between C. penicillata, C. kuhli, and possibly C. jacchus. Most of the sequence features characteristic of other mammal control regions were also evident in marmosets, with the exception that conserved sequence blocks (CSBs) 2 and 3 were not clearly identifiable. Tandem repeat units often associated with heteroplasmy in a variety of other mammals were not evident in the marmoset sequences.      

Role of L-histidine in conferring tolerance to Ni2+ in Sacchromyces cerevisiae cells

Ni(2+) toxicity can be alleviated in yeast cells by exogenous L-histidine, but not by its enantiomer, D-histidine, nor by other natural L-amino acids tested. We studied the effect of L-histidine upon the accumulation and intracellular distribution of Ni(2+) and found that moderate L-histidine concentrations (less than or equal to those of Ni(2+)) increased cell tolerance without decreasing Ni(2+) accumulation. Although excess L-histidine appeared to lower Ni(2+) accumulation, the concomitant presence of Ni(2+) and L-histidine in the growth medium stimulated each other's uptake.     

The European Renal Genome Project: An Integrated Approach Towards Understanding the Genetics of Kidney Development and Disease

Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a three-dimensional reconstruction of the organ. We will seek proof of concept for the organ atlas by elucidating genetic pathways involved in development and pathophysiology of the kidney. Such a kidney atlas may provide a paradigm for a new systems-biology approach in functional genome research aimed at understanding the genetic bases of organ development, physiology and disease.Key Words: EuReGene, kidney, genome, development, pathophysiology, genetics     

Status of research in stock enhancement and sea ranching

Reviews in Fish Biology and Fisheries -     

Neural mechanisms of context-dependent processing of CO2 avoidance behavior in fruit flies

The fruit fly, Drosophila melanogaster, innately avoids even low levels of CO₂. CO₂ is part of the so-called Drosophila stress odor produced by stressed flies, but also a byproduct of fermenting fruit, a main food source, making the strong avoidance behavior somewhat surprising. Therefore, we addressed whether feeding states might influence the fly’s behavior and processing of CO₂. In a recent report, we showed that this innate behavior is differentially processed and modified according to the feeding state of the fly. Interestingly, we found that hungry flies require the function of the mushroom body, a higher brain center required for olfactory learning and memory, but thought to be dispensable for innate olfactory behaviors. In addition, we anatomically and functionally characterized a novel bilateral projection neuron connecting the CO₂ sensory input to the mushroom body. This neuron was essential for processing of CO₂ in the starved fly but not in the fed fly. In this Extra View article, we provide evidence for the potential involvement of the neuromodulator dopamine in state-dependent CO₂ avoidance behavior. Taken together, our work demonstrates that CO₂ avoidance behavior is mediated by alternative neural pathways in a context-dependent manner. Furthermore, it shows that the mushroom body is not only involved in processing of learned olfactory behavior, as previously suggested, but also in context-dependent innate olfaction.     

Removing heavy metals from synthetic effluents using “kamikaze” Saccharomyces cerevisiae cells

One key step of the bioremediation processes designed to clean up heavy metal contaminated environments is growing resistant cells that accumulate the heavy metals to ensure better removal through a combination of biosorption and continuous metabolic uptake after physical adsorption. Saccharomyces cerevisiae cells can easily act as cation biosorbents, but isolation of mutants that are both hyperaccumulating and tolerant to heavy metals proved extremely difficult. Instead, mutants that are hypersensitive to heavy metals due to increased and continuous uptake from the environment were considered, aiming to use such mutants to reduce the heavy metal content of contaminated waters. In this study, the heavy metal hypersensitive yeast strain pmr1∆ was investigated for the ability to remove Mn²⁺, Cu²⁺, Co²⁺, or Cd²⁺ from synthetic effluents. Due to increased metal accumulation, the mutant strain was more efficient than the wild-type in removing Mn²⁺, Cu²⁺, or Co²⁺ from synthetic effluents containing 1–2 mM cations, with a selectivity $ {\text{Mn}}^{{{\text{2}} + }} > {\text{Co}}^{{{\text{2}} + }} ~ > {\text{Cu}}^{{{\text{2}} + }} $ {\text{Mn}}^{{{\text{2}} + }} > {\text{Co}}^{{{\text{2}} + }} ~ > {\text{Cu}}^{{{\text{2}} + }} and also in removing Mn²⁺ and Cd²⁺ from synthetic effluents containing 20–50 μM cations, with a selectivity Mn²⁺ > Cd²⁺.     

Calcium signaling mediates the response to cadmium toxicity in Saccharomyces cerevisiae cells

The involvement of Ca²⁺ in the response to high Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, and Hg²⁺ was investigated in Saccharomyces cerevisiae. The yeast cells responded through a sharp increase in cytosolic Ca²⁺ when exposed to Cd²⁺, and to a lesser extent to Cu²⁺, but not to Mn²⁺, Co²⁺, Ni²⁺, Zn²⁺, or Hg²⁺. The response to high Cd²⁺ depended mainly on external Ca²⁺ (transported through the Cch1p/Mid1p channel) but also on vacuolar Ca²⁺ (released into the cytosol through the Yvc1p channel). The adaptation to high Cd²⁺ was influenced by perturbations in Ca²⁺ homeostasis. Thus, the tolerance to Cd²⁺ often correlated with sharp Cd²⁺-induced cytosolic Ca²⁺ pulses, while the Cd²⁺ sensitivity was accompanied by the incapacity to rapidly restore the low cytosolic Ca²⁺.