Alternative splicing directs the expression of two D2 dopamine receptor isoforms

Dopamine receptors are classified into D1 and D2 subtypes on the basis of their pharmacological properties and the intracellular responses they mediate. The cerebral D2 dopamine receptor is the target of drugs used to alleviate the main symptoms of schizophrenia. Although it is considered to be a single molecular entity, there is evidence that multiple D2-receptor subtypes exist. A complementary DNA encoding a D2 receptor has recently been cloned and the deduced 415-amino-acid sequence indicates that it belongs to the large superfamily of receptors coupled to G proteins, and that its topology consists of seven transmembrane domains. In this family, the genes are frequently without introns and each is believed to encode a unique polypeptide product. Here we show that the gene for the D2 receptor produces two receptor isoforms by alternative messenger RNA splicing, providing a route to receptor diversity in this family. One isoform corresponds to the D2(415) receptor, but the second contains an additional sequence encoding a 29-amino-acid fragment, defining a novel D2(444) receptor isoform. Expression of the two isoforms is tissue-specific, and both are regulated by guanyl nucleotides. As the extra sequence is located within a putative cytoplasmic loop that binds to G proteins, the two isoforms might interact with different G proteins and thereby initiate distinct intracellular signals.     

Water balance and fluid consumption in the southern grasshopper mouse, Onychomys torridus

Weight loss was rapid and fluid consumption decreased sharply when Onychomys torridus were exposed to salinities greater than 0.3 Molar. The southern grasshopper mouse is physiologically unspecialized for maintaining water balance in its xeric habitat. The southern grasshopper mouse is capable of weight maintenance on smaller daily water rations than is the northern grasshopper mouse ( Onychomys leucogaster ) . Differences in the water balance of O. torridus and O. leucogaster may influence their local distributions in areas of sympatry.     

Loss of the SKI proto-oncogene in individuals affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice.

Experiments involving overexpression of Ski have suggested that this gene is involved in neural tube development and muscle differentiation. In agreement with these findings, Ski-/- mice display a cranial neural tube defect that results in exencephaly and a marked reduction in skeletal muscle mass. Here we show that the penetrance and expressivity of the phenotype changes when the null mutation is backcrossed into the C57BL6/J background, with the principal change involving a switch from a neural tube defect to midline facial clefting. Other defects, including depressed nasal bridge, eye abnormalities, skeletal muscle defects and digit abnormalities, show increased penetrance in the C57BL6/J background. These phenotypes are interesting because they resemble some of the features observed in individuals diagnosed with 1p36 deletion syndrome, a disorder caused by monosomy of the short arm of human chromosome 1p (refs. 6-9). These similarities prompted us to re-examine the chromosomal location of human SKI and to determine whether SKI is included in the deletions of 1p36. We found that human SKI is located at distal 1p36.3 and is deleted in all of the individuals tested so far who have this syndrome. Thus, SKI may contribute to some of the phenotypes common in 1p36 deletion syndrome, and particularly to facial clefting.     

Highly potent and selective ligands for histamine H3-receptors

New drugs selective for histamine H3-receptors can be used to establish that these receptors are involved in the feedback control of histamine synthesis and release, and to demonstrate their distribution in the brain and peripheral tissues. These drugs provide new tools for affecting physiological and possibly pathological conditions in which histamine is involved.     

GABA and GAD immunoreactivity of photoreceptor terminals in primate retina

Within the vertebrate retina, two types of photoreceptor cells--the rods and cones--transduce visual signals and convey this information through synapses with bipolar and horizontal cells. Although the neurotransmitter at these first-order synapses has not been identified, electrophysiological studies suggest that it might be excitatory. In the present study, however, we have found photoreceptor terminals in the rhesus monkey retina which are immunoreactive with antibodies to either gamma-aminobutyric acid (GABA) or L-glutamic acid decarboxylase (GAD, an enzyme involved in the synthesis of GABA). In the perifoveal region of the retina, approximately 25% of presynaptic profiles having ultrastructural characteristics of either rod or cone terminals are immunoreactive with one or the other antibody. This evidence for a putatively inhibitory neurotransmitter in photoreceptor terminals challenges present understanding of retinal synaptic function.     

Diffusion of new products in risk-sensitive markets

Diffusion of new products may be deterred by consumers' uncertainties about how they will perform. This paper introduces a decision-theoretic framework for modeling the diffusion of consumables, in which consumers choose between a current and new product so as to maximize expected utility. Consumers that are sufficiently risk-averse delay adoption, and change their prior uncertainties in a Bayesian fashion using information generated by early adopters. Under certain assumptions about the underlying consumer choice process and the market dynamics, the result is logistic growth in the share of consumers that choose the new product. The model can be generalized by allowing for consumer heterogeneity with respect to performance of the new product. The paper concludes with a discussion of applications for market forecasting, design of market trials and other extensions.