Cholecystokinin is not a major regulator in the digestive system in the chicken

To find out whether physiological concentrations of cholecystokinin (CCK), a gastrointestinal hormone in mammals, are also active in chickens, the pancreatic amylase secretory response to CCK-8 was investigated in vitro. Rat pancreatic acini responded to the physiological concentration of CCK-8, but in chickens amylase release was induced at a concentration of CCK-8 1000 times higher than that observed in rats. In another experiment, biliary flow was tested with several doses of CCK-8. The bile flow was stimulated in a dose-dependent fashion, but a significant enhancement was not obtained at a concentration of 0.5 g CCK-8/kg body weight, which was considerably higher than physiological ones. It is concluded that endogeneous CCK does not have an important role in the digestive system in the chicken.     

The role of Epac in the heart

As one of the most important second messengers, 3′,5′-cyclic adenosine monophosphate (cAMP) mediates various extracellular signals including hormones and neurotransmitters, and induces appropriate responses in diverse types of cells. Since cAMP was formerly believed to transmit signals through only two direct target molecules, protein kinase A and the cyclic nucleotide-gated channel, the sensational discovery in 1998 of another novel direct effecter of cAMP [exchange proteins directly activated by cAMP (Epac)] attracted a great deal of scientific interest in cAMP signaling. Numerous studies on Epac have since disclosed its important functions in various tissues in the body. Recently, observations of genetically manipulated mice in various pathogenic models have begun to reveal the in vivo significance of previous in vitro or cellular-level findings. Here, we focused on the function of Epac in the heart. Accumulating evidence has revealed that both Epac1 and Epac2 play important roles in the structure and function of the heart under physiological and pathological conditions. Accordingly, developing the ability to regulate cAMP-mediated signaling through Epac may lead to remarkable new therapies for the treatment of cardiac diseases.     

Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta

Protein kinase C (PKC), which comprises 11 closely related isoforms, has been implicated in a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis and tumour development. Among the PKC isotypes, PKC-delta is unique in that its overexpression results in inhibition of cell growth. Here we show that mice that lack PKC-delta exhibit expansion of the B-lymphocyte population with the formation of numerous germinal centres in the absence of stimulation. The rate of proliferation in response to stimulation was greater for B cells from PKC-delta-deficient mice than for those from wild-type mice. Adoptive transfer experiments suggested that the hyperproliferation phenotype is B-cell autonomous. Production of interleukin-6 was markedly increased in B cells of PKC-delta-null mice as a result of an increase in the DNA-binding activity of NF-IL6. Furthermore, the PKC-delta-deficient mice contain circulating autoreactive antibodies and display immune-complex-type glomerulonephritis, as well as lymphocyte infiltration in many organs. These results suggest that PKC-delta has an indispensable function in negative regulation of B-cell proliferation, and is particularly important for the establishment of B-cell tolerance.     

Factors influencing the intestinal phase of pancreatic exocrine secretion in the turkey

The present study was done to investigate the factors regulating the intestinal phase of exocrine pancreatic secretion in the turkey. The intestine of turkeys equipped with pancreatic fistulas was perfused with peptone solution, fat emulsion and hydrochloric acid (HCl), and pancreatic flow and protein output were measured. Neither peptone solution nor fat emulsion had any effects on pancreatic secretion. HCl enhanced the flow rate of pancreatic juice but not protein output. To clarify the neural mechanism of this phenomenon, the vagal postganglionic blocker atropine was continuously infused and pancreatic secretion in response to intestinal HCl was measured. Atropine completely suppressed both pancreatic flow and protein output. It is suggested that the avian intestinal phase of pancreatic secretion is mainly controlled by cholinergic action though HCl stimulation.     

CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast

In eukaryotic cells, cyclin-dependent kinases (CDKs) have an important involvement at various points in the cell cycle. At the onset of S phase, active CDK is essential for chromosomal DNA replication, although its precise role is unknown. In budding yeast (Saccharomyces cerevisiae), the replication protein Sld2 (ref. 2) is an essential CDK substrate, but its phospho-mimetic form (Sld2-11D) alone neither affects cell growth nor promotes DNA replication in the absence of CDK activity, suggesting that other essential CDK substrates promote DNA replication. Here we show that both an allele of CDC45 (JET1) and high-copy DPB11, in combination with Sld2-11D, separately confer CDK-independent DNA replication. Although Cdc45 is not an essential CDK substrate, CDK-dependent phosphorylation of Sld3, which associates with Cdc45 (ref. 5), is essential and generates a binding site for Dpb11. Both the JET1 mutation and high-copy DPB11 by-pass the requirement for Sld3 phosphorylation in DNA replication. Because phosphorylated Sld2 binds to the carboxy-terminal pair of BRCT domains in Dpb11 (ref. 4), we propose that Dpb11 connects phosphorylated Sld2 and Sld3 to facilitate interactions between replication proteins, such as Cdc45 and GINS. Our results demonstrate that CDKs regulate interactions between BRCT-domain-containing replication proteins and other phosphorylated proteins for the initiation of chromosomal DNA replication; similar regulation may take place in higher eukaryotes.     

Detection of a radio counterpart to the 27 December 2004 giant flare from SGR 1806-20

It was established over a decade ago that the remarkable high-energy transients known as soft gamma-ray repeaters (SGRs) are located in our Galaxy and originate from neutron stars with intense (< or = 10(15)G) magnetic fields-so-called 'magnetars'. On 27 December 2004, a giant flare with a fluence exceeding 0.3 erg cm(-2) was detected from SGR 1806-20. Here we report the detection of a fading radio counterpart to this event. We began a monitoring programme from 0.2 to 250 GHz and obtained a high-resolution 21-cm radio spectrum that traces the intervening interstellar neutral hydrogen clouds. Analysis of the spectrum yields the first direct distance measurement of SGR 1806-20: the source is located at a distance greater than 6.4 kpc and we argue that it is nearer than 9.8 kpc. If correct, our distance estimate lowers the total energy of the explosion and relaxes the demands on theoretical models. The energetics and the rapid decay of the radio source are not compatible with the afterglow model that is usually invoked for gamma-ray bursts. Instead, we suggest that the rapidly decaying radio emission arises from the debris ejected during the explosion.     

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.     

Lentinacin: a new hypocholesterolemic substance inLentinus edodes

Zusammenfassung Aus dem Speisepilz «Shiitake» (Lentinus edodes) wurde ein neues Adeninderivat isoliert und Lentinacin genannt. Seine chemische Struktur wurde mit 2(R), 3(R)-Dihydroxy-4-(9-adenyl)-buttersäure durch die vollständige Synthese identifiziert. Lentinacin senkt den Cholesterinspiegel bei Ratten.