Regulation of cardiac AMP-specific 5'-nucleotidase during ischemia mediates ATP resynthesis on reflow

The ability toresynthesize ATP during recovery from ischemia is limited tothe size of endogenous pool of adenine nucleotides. CytosolicAMP-specific 5'-nucleotidase (5'-NT) plays a key role inATP degradation and hence the capacity for ATP resynthesis. We havesuggested (J. Clin. Invest. 93:40-49, 1994) that intracellular acidosis [intracellular pH(pH_i)] is a potentinhibitor of 5'-NT under in vivo conditions. To test thishypothesis further, we used the hyperthyroid rat heart because we couldalter pH_i during ischemiaand determine the consequences of lowerpH_i on AMPaccumulation (by chemical assay) and ATP resynthesis (by³¹P nuclear magnetic resonancespectroscopy) during reperfusion. Global no-flow ischemiacaused pH_i to decrease from 7.1 under well-oxygenated control perfusion to 6.7. We found thatdecreasing pH_i further from pH 6.7 to 6.4 leads to increased accumulation (30%) of AMP duringischemia and to a 2.5-fold increase in ATP resynthesis duringreperfusion. Analysis of all known substrates, products, activators,and inhibitors of the 5'-NT suggests that 5'-NT isactivated primarily by Mg²⁺ andADP and is inhibited by H⁺. Thusthese observations provide evidence for a salutary effect ofintracellular acidosis on preserving the AMP pool due to inhibition of5'-NT and suggest a novel role ofH⁺ in protecting ischemic tissue.

     

Genetic and endocrine control of renin activity in the submaxillary gland of the mouse

Basal activity of submaxillary gland (SMG) renin is high in female mice that carry the Rnr ^s allele and is induced to higher levels by treatment with dihydrotestosterone (DHT). To determine whether the difference in basal activity between high (Rnr ^s/Rnr^s) and low (Rnr ^b/Rnr^b) strains is due to enhanced sensitivity of Rnr ^s/Rnr^s strains to endogenous androgen, we first studied the effect of several types of endocrine ablation on SMG renin in young female mice, and second, we removed normal androgen receptor protein by introducing the X-linked Tfm gene. Adrenalectomy with or without castration had no effect on basal SMG renin; hypophysectomy decreased basal renin activity 400-fold but did not abolish responsiveness to DHT. Loss of androgen receptor did not affect basal renin activity but did prevent enhancement by DHT. Basal and induced renin activities in L.AKR(Alll)/Cy, a congenic strain homozygous for Rnr ^s introduced from AKR/J into the background of C57L/J, an Rnr ^b/Rnr^b type strain, are intermediate between levels observed in the original strains. We conclude that (1) the basal level of SMG renin is regulated directly or indirectly by some pituitary hormone(s) but not by androgen, (2) androgen induction of renin activity requires a normal androgen receptor, and (3) major gene(s) that regulate basal as well as induced SMG renin are in a circumscribed region of chromosome 1.This work has been aided by Grants GM26414 and AM03892 from the National Institutes of Health, a grant from the Texas affiliate of the American Heart Association, and by research contract NO1-CP33255 from the Division of Cancer Cause and Prevention, the National Cancer Institute. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.     

Habitat discrimination of juvenile sardines in the Aegean Sea using remotely sensed environmental data

Despite the importance of the recruitment process for small pelagic fish and the high economic importance of European sardine (Sardina pilchardus, Walbaum 1792) in the Mediterranean Sea, knowledge on the distribution and environmental characteristics of its nursery grounds is very limited. In the present study, we used pelagic trawl data collected during 1995–2006 to explore the spatial distribution of sardine juveniles in the Aegean Sea in early summer. Based on sardine abundance per length class, a cluster analysis was initially used to define hauls dominated by juveniles. In a subsequent step, Discriminant Function Analysis (DFA) was applied to discriminate stations with high relative abundance of juveniles using satellite environmental data and bottom depth. The parameters contributing mostly to the discrimination of juvenile grounds were sea level anomaly, photosynthetically active radiation, sea surface temperature, chlorophyll-α and bottom depth. The classification functions of DFA were finally used to post classify unsampled areas in the Greek Seas and the Mediterranean Sea in order to map grounds that meet characteristic environmental conditions for young sardine. Such areas were mostly located inshore, in semi-closed productive areas and often in proximity to river mouths, a pattern that is generally supported by existing information. Guest editor: V. D. Valavanis Essential Fish Habitat Mapping in the Mediterranean     

Pre-processing Agilent microarray data

Background  

Pre-processing methods for two-sample long oligonucleotide arrays, specifically the Agilent technology, have not been extensively studied. The goal of this study is to quantify some of the sources of error that affect measurement of expression using Agilent arrays and to compare Agilent's Feature Extraction software with pre-processing methods that have become the standard for normalization of cDNA arrays. These include log transformation followed by loess normalization with or without background subtraction and often a between array scale normalization procedure. The larger goal is to define best study design and pre-processing practices for Agilent arrays, and we offer some suggestions.