Beta 2-receptors in the rat anterior pituitary mediate adrenergic stimulation of prolactin release

As previously shown, the beta-adrenergic agonists isoproterenol, epinephrine and norepinephrine stimulate prolactin (PRL) release from superfused rat anterior pituitary cell aggregates. In order to further characterize the beta-adrenergic response in this tissue preparation, the effects of various beta-adrenergic agents were investigated. The beta 2-agonist, zinterol, stimulated PRL release at concentrations more than 4 orders of magnitude lower than prenalterol, a beta 1-agonist with high potency in rat heart. The order of potency of the antagonists IPS 339 (beta 2), ICI 118.551 (beta 2), propranolol, sotalol, practolol (beta 1), metoprolol (beta 1) and H 35/25 for inhibition of beta-agonist-stimulated PRL release provided additional support for a beta 2-stimulatory effect. beta-Agonists were also capable of stimulating PRL release from superfused intact pituitaries. The beta-adrenergic response desensitized rapidly during prolonged exposure of the aggregates to beta-agonists.     

A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements.

We have identified and characterized a new orphan member of the nuclear hormone receptor superfamily, called MB67, which is predominantly expressed in liver. MB67 binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes, both of which consist of a direct repeat hexamers related to the consensus AGGTCA, separated by 5 bp. MB67 binds these elements as a heterodimer with the 9-cis-retinoic acid receptor, RXR. However, MB67 does not bind or activate other retinoic acid response elements with alternative hexamer arrangements or any of several other wild-type and synthetic hormone response elements examined. The transactivation of retinoic acid response elements by MB67 is weaker than that conferred by the retinoic acid receptors but does not require the presence of all-trans retinoic acid, 9-cis-retinoic acid, or any exogenously added ligand. We propose that MB67 plays an important role in the complex network of proteins that govern response to retinoic acid and its metabolites.     

Discovering lethal alleles across the turkey genome using a transmission ratio distortion approach

Deviation from Mendelian inheritance expectations (transmission ratio distortion, TRD) has been observed in several species, including the mouse and humans. In this study, TRD was characterized in the turkey genome using both allelic (specific- and unspecific-parent TRD) and genotypic (additive- and dominance-TRD) parameterizations within a Bayesian framework. In this study, we evaluated TRD for 23 243 genotyped Turkeys across 56 393 autosomal SNPs. The analyses included 500 sires, 2013 dams and 11 047 offspring (trios). Three different haplotype sliding windows of 4, 10 and 20 SNPs were used across the autosomal chromosomes. Based on the genotypic parameterizations, 14 haplotypes showed additive and dominance TRD effects highlighting regions with a recessive TRD pattern. In contrast, the allelic model uncovered 12 haplotype alleles with the allelic TRD pattern which showed an underrepresentation of heterozygous offspring in addition to the absence of homozygous animals. For regions with the allelic pattern, only one particular region showed a parent-specific TRD where the penetrance was high via the dam, but low via the sire. The gene set analysis uncovered several gene ontology functional terms, Reactome pathways and several Medical Subject Headings that showed significant enrichment of genes associated with TRD. Many of these gene ontology functional terms (e.g. mitotic spindle assembly checkpoint, DRM complex and Aneuploidy), Reactome pathways (e.g. Mismatch repair) and Medical Subject Headings (e.g. Adenosine monophosphate) are known to be related to fertility, embryo development and lethality. The results of this study revealed potential novel candidate lethal haplotypes, functional terms and pathways that may enhance breeding programs in Turkeys through reducing mortality and improving reproduction rate.     

ECHOLOCATION IN DOLPHINS WITH A DOLPHIN-BAT COMPARISON

ABSTRACT

Dolphins possess a highly sophisticated auditory system and a keen capability for echolocation. Signals are emitted in the form of high intensity, short duration, broadband exponentially decaying pulses. The frequency spectra of echolocation signals used by many dolphins are dependent on the output intensity of the signals and not on any fine tuning by the animals. When the output intensity is low, the center frequency of the click tends to be low. As the output intensity increases, the center frequency also tends to increase. The pulses propagate from the dolphin's melon in a relatively narrow beam, and echoes are received via the lower jaw, with a slightly wider beam. Echo- locating dolphins can detect targets at ranges of approximately 100 plus meters, depending on the size of the targets. Target discrimination experiments have shown that dolphins can discriminate the shape, size, material composition and internal structure of targets from the echoes. The broadband short duration properties of the signal allow the echoes to have high temporal resolution, so that within the structure of the echoes a considerable amount of information on the properties of the target can be conveyed. A brief comparison between the bat and dolphin sonar system will also be made. Bats typically emit much longer signals and a wider variety of different types of signals than dolphins. Signals used by some bats are suited to detecting Doppler shift, whereas the dolphin signal is designed to be tolerant of Doppler effects.     

A new procedure to produce lignocellulosic anion exchangers from agricultural waste materials

Two lignocellulosic agricultural waste materials (LCM), sugarcane bagasse (BG) and rice hull (RH), were converted into weak-base anion exchanger and evaluated for their exchanger capacity for nitrate. Pure cellulose (PC) and pure alkaline lignin (PL) were also used as reference materials to elucidate possible reactivity in LCM. Epoxy and amino groups were introduced into BG, RH, PC and PL substrates after the reaction with epichlorohydrin and dimethylamine in the presence of pyridine and an organic solvent N,N-dimethylformamide (DMF). Amino group incorporation into cellulose decreased with the presence of water in the reaction mixture and increased with the reaction time and presence of a catalyst (pyridine). The highest maximum nitrate exchange capacity (Qmax) and yields of the prepared exchangers was obtained from PL (1.8 mmol g(-1) and 412.5%), followed by BG (1.41 mmol g(-1) and 300%), PC (1.34 mmol g(-1) and 166%) and RH (1.32 mmol g(-1) and 180%). The proposed synthetic procedure was effective in modifying PL, PC and LCM chemically resulting in a higher yield and nitrate removal capacity.     

Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model

The mammalian multifunctional protein-2 (MFP-2, also called multifunctional enzyme 2, D-bifunctional enzyme or 17-beta-estradiol dehydrogenase type IV) was identified by several groups about a decade ago. It plays a central role in peroxisomal beta-oxidation as it handles most, if not all, peroxisomal beta-oxidation substrates. Deficiency of this enzyme in man causes a severe developmental syndrome with abnormalities in several organs but in particular in the brain, leading to death within the first year of life. Accumulation of branched-long-chain fatty acids and very-long-chain fatty acids and a disturbed synthesis of bile acids were documented in these patients. A mouse model with MFP-2 deficiency only partly phenocopies the human disease. Although the expected metabolic abnormalities are present, no neurodevelopmental aberrations are observed. However, the survival of these mice into adulthood allowed to document the importance of this enzyme for the normal functioning of the brain, eyes and testis. In the present review, the identification and biochemical characteristics of MFP-2, and the consequences of MFP-2 dysfunction in humans and in mice will be discussed.     

Do sphingoid bases interact with the peroxisome proliferator activated receptor alpha (PPAR-alpha)?

In a search for possible endogenous ligands of nuclear receptors that are activated by peroxisome proliferators (PPARs), a solid phase binding assay was developed employing recombinant mouse PPAR-alpha, containing a myc-epitope, a histidine repeat and a kinase A domain. After in vitro labelling with 32P-gamma-ATP, the binding of purified 32P-PPAR-alpha to a panel of different natural and synthetic lipids, immobilized on silica layers, was evaluated. Autoradiographs of the silica layers revealed binding to two main classes of lipophilic compounds. A first class comprised (poly)unsaturated fatty acids. Compounds belonging to a second class were characterized by the presence of an overall positive charge such as long chain amines, sphingoid bases (sphingenine), and lysoglycosphingolipids (psychosine). PPAR-alpha did not bind to N-acylated sphingoid bases (ceramides) or to sphingenine phosphorylated at the primary hydroxy group (sphingenine-1-phosphate). The binding of PPAR-alpha to sphingoid bases might be of interest given the role of PPAR-alpha and sphingolipids in various cellular processes.     

Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice

Mice with inactivation of the D-specific multifunctional protein 2 (MFP2), a crucial enzyme of peroxisomal beta-oxidation, develop multiple pathologies in diverse tissues already starting in the postnatal period. Gene expression profiling performed on liver of 2-day-old pups revealed up-regulation of PPAR alpha responsive genes in knockout mice. Surprisingly, also genes involved in cholesterol biosynthesis were markedly induced. Real-time PCR confirmed the induction of PPAR alpha target genes and of HMGCR and SREBP2, both involved in cholesterol synthesis, in lactating and in adult MFP2 knockout mice. In accordance, the rate of cholesterol biosynthesis was significantly increased in liver of knockout mice but the hepatic cholesterol concentration was unaltered. In MFP2/PPAR alpha double knockout mice, up-regulations of SREBP2 and HMGCR were markedly attenuated. These data demonstrate a tight interrelationship between induction of PPAR alpha by endogenous ligands and up-regulation of genes of cholesterol biosynthesis through increased expression of SREBP2.     

Mouse models for peroxisome biogenesis disorders

The gene knockout technology has been applied to generate mice lacking functional peroxisomes. These mice are a model for Zellweger syndrome and other peroxisome biogenesis disorders that are lethal in early life. Extensive biochemical, ultrastructural, and neurodevelopmental analyses indicate that the peroxisome deficient mice closely mimic the pathology in Zellweger patients and will be a very useful tool to elucidate the pathogenesis of this disease.