Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents

We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote “healthy” chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects.     

Architectonics of GABAergic inhibitory network in the sensorimotor area of the rat neocortex in the early postnatal period under normal conditions and after acute perinatal hypoxia

The distribution of GABAergic interneurons as well as terminal and synaptic networks in different layers of the rat sensorimotor neocortex were studied at different stages of the postnatal period under normal conditions and after exposure to perinatal hypoxia. In control animals, the architectonics of the inhibitory network in different layers of the sensorimotor neocortex was shown to display distinctive features at different stages of the postnatal development. At early postnatal stages, a significant portion of neurons in layers II–V are immunopositive for GAD-67, indicative of a high level of GABA expression, however, GABA transmission is extremely weak, thus supporting the presence in the neuropil of only sporadic GABAergic terminals and synapses. By the juvenile age, a dramatic drop in the number of GABAergic neurons and an increase in the density of the network of GABA-immunopositive processes and synaptic structures occur in the neuropil, suggesting a considerable increase in GABA transmission. A higher level of GABA transmission is revealed in layers IV and V, persisting over the prepubertal period. Our results demonstrate that acute perinatal hypoxia affects the state of the inhibitory GABAergic network in the rat sensorimotor neocortex during the postnatal period. GABA expression and transmission were shown to change virtually in all layers.     

How Multidisciplinary Are the Multidisciplinary Journals Science and Nature?

Interest in cross-disciplinary research knowledge interchange runs high. Review processes at funding agencies, such as the U.S. National Science Foundation, consider plans to disseminate research across disciplinary bounds. Publication in the leading multidisciplinary journals, Nature and Science, may signify the epitome of successful interdisciplinary integration of research knowledge and cross-disciplinary dissemination of findings. But how interdisciplinary are they? The journals are multidisciplinary, but do the individual articles themselves draw upon multiple fields of knowledge and does their influence span disciplines? This research compares articles in three fields (Cell Biology, Physical Chemistry, and Cognitive Science) published in a leading disciplinary journal in each field to those published in Nature and Science. We find comparable degrees of interdisciplinary integration and only modest differences in cross-disciplinary diffusion. That said, though the rate of out-of-field diffusion might be comparable, the sheer reach of Nature and Science, indicated by their potent Journal Impact Factors, means that the diffusion of knowledge therein can far exceed that of leading disciplinary journals in some fields (such as Physical Chemistry and Cognitive Science in our samples).     

Efficacy of intermittent or continuous administration of GnRH in inducing ovulation in early and late seasonal anoestrus in the Père David's deer hind (Elaphurus davidianus)

Père David's deer hinds were treated with GnRH, administered as intermittent i.v. injections (2.0 micrograms/injection at 2-h intervals) for 4 days, or as a continuous s.c. infusion (1.0 micrograms/h) for 14 days. These treatments were given early (February-March) and late (May-June) in the period of seasonal anoestrus. The administration of repeated injections of GnRH increased mean LH concentrations from pretreatment values of 0.54 +/- 0.09 to 2.10 +/- 0.25 ng/ml over the first 8 h of treatment in early anoestrus, and from 0.62 +/- 0.11 to 2.73 +/- 0.49 ng/ml in late anoestrus. The mean amplitude of GnRH-induced LH episodes was greater (P less than 0.01) in late (4.03 +/- 0.28 ng/ml) than in early (3.12 +/- 0.26 ng/ml) anoestrus, but within each replicate (early or late anoestrus), neither mean LH episode amplitude nor mean plasma LH concentrations differed significantly between the four periods of intensive blood sampling. On the basis of their progesterone profiles, 6/12 hinds had ovulated in response to treatment with injections of GnRH (1/6 in early anoestrus and 5/6 in late anoestrus), and oestrus and a preovulatory LH surge were recorded in all of these animals. Oestrus and a preovulatory LH surge were also recorded in one other animal treated in early anoestrus in which progesterone concentrations remained low. The mean times of onset of oestrus (91.0 +/- 1.00 and 62.4 +/- 0.98 h) and of the preovulatory LH surge (85.8 +/- 3.76 and 59.4 +/- 0.25 h) both occurred significantly earlier (P less than 0.001) in animals treated in late anoestrus. Continuous infusion of GnRH to seasonally anoestrous hinds resulted in an increase in mean plasma LH concentrations, but this response did not differ significantly between early (2.15 +/- 0.28 ng/ml) and late (2.48 +/- 0.26 ng/ml) anoestrus. Ovulation, based on progesterone profiles, occurred in 2/7 hinds in early anoestrus and in 4/6 hinds in late anoestrus. Oestrus was detected in all except one of these hinds. The mean time of onset of oestrus occurred earlier in animals treated in late anoestrus (66.2 +/- 0.32 h and 46.7 +/- 0.67 h, P less than 0.01). The administration of GnRH, given either intermittently or continuously, will induce ovulation in a proportion of seasonally anoestrous Père David's deer. However, more animals ovulate in response to this treatment in late than in early anoestrus (75% compared with 23%).     

NH resonances of Ribonuclease S-peptide in aqueous solution. Low temperature n.m.r. study

A detailed study of the NH resonances of Ribonuclease-S-peptide (1-19 N-terminal fragment of Ribonuclease A) has been carried out in H2O, pH 3.0, in the temperature range 1-31 degrees, and ionic strength 0-1 M. Individual assignments of all NH amide signals have been achieved by means of extensive double resonance experiments. The folding of S-peptide at low temperature has been monitored by examination of the several NH resonance parameters: first, the nonlinearity of chemical shift vs. temperature plots; second, the selective broadening observed for signals assigned to residues 3-13; and third, the decrease of 3JHNCH coupling constants belonging to this region of the polypeptide chain. All these results are in agreement with the formation of a folded structure at low temperature, which is similar to the one found for the S-peptide in the RNase S crystal.     

5''-Nucleotidases in rat heart. Evidence for the occurrence of two soluble enzymes with different substrate specificities.

Chromatography of soluble proteins from rat heart on phosphocellulose columns separates two 5'-nucleotidases. The first to emerge from the column shows a preference for AMP over IMP as substrate, whereas the second shows a preference for IMP over AMP. The properties of the IMP-preferring enzyme, including the conditions under which it is eluted from phosphocellulose columns, show it to be the enzyme studied by Itoh, Oka & Ozasa [Biochem. J. (1986) 235, 847-851]. The kinetic properties of the AMP-preferring enzyme indicate that it is likely to be the enzyme responsible for the production of adenosine under conditions of hypoxia and increased work load, and with metabolic stresses such as a high load of acetate.     

Calorimetric and Fourier transform infrared spectroscopic studies on the interaction of glycophorin with phosphatidylserine/dipalmitoylphosphatidylcholine-d62 mixtures

Glycophorin has been isolated in pure form from human erythrocyte membranes and reconstituted into lipid vesicles composed of binary mixtures of bovine brain phosphatidylserine (PS) and acyl-chain perdeuterated dipalmitoylphosphatidylcholine (DPPC-d62). The effect of protein on lipid melting behavior and order has been monitored with differential scanning calorimetry and Fourier transform infrared spectroscopy (FT-IR). The phase diagram for PS/DPPC-d62 is consistent with that previously reported for PS/DPPC (Stewart et al. (1979) Biochim. Biophys. Acta 556, 1-16) and indicates that acyl chain perdeuteration does not greatly alter the lipid mixing characteristics. The use of deuterated lipid allows the examination of lipid order by FT-IR of each lipid component in the binary mixtures as well as in the ternary (lipid/lipid/protein) systems. Addition of glycophorin to a 30:70 PS/DPPC-d62 binary lipid mixture results in a preferential glycophorin/PS interaction leading to bulk lipid enriched in DPPC-d62. This is revealed in two ways: first, through cooperative calorimetric transitions increased in temperature from the binary lipid system and second, through FT-IR melting curves of the DPPC-d62 component which shows transitions increased in both onset and completion temperatures in the presence of protein. In addition, non-cooperative melting events are observed at temperatures below the onset of phase separation. The FT-IR data are used to assign these non-cooperative events to the melting of the PS component. For the 50:50 lipid mixture with protein, two transitions are observed in the DSC experiments. The IR results indicate that both lipid components are involved with the lower temperature event.     

Immunoenzyme analysis of the fertility alpha 2-microglobulin in the blood serum of men and women

It has been found that fertility alpha 2-microglobulin content in male and female serum does not exceed 20 ng/ml and 40 ng/ml, respectively. A high level of fertility alpha 2-microglobulin was found in the serum in early pregnancy, with its concentration decreased by parturition.