Postnatal development of the suprachiasmatic hypothalamic nucleus of the rat

Summary Light and electron microscopy of newborn, four day, one, two, three and five week old rats revealed principally a progressive increase in the diversity and number of synaptic contacts in the suprachiasmatic nucleus (SCN). The major increase in synaptic diversity occurred between four days and one week of age. Correlation between this finding and the adult synaptic morphology of SCN (Güldner, 1976) on the one hand, and the ontogeny of circadian rhythms on the other were made. This suggested that the retinal afferents arriving on day four form asymmetrical contacts with dendrites. While increase in synaptic number was progressive, it was most marked between three and five weeks of age. By five weeks, most features of the adult SCN were present. No significant morphological effects were evident as a result of neonatal retinal lesions.Supported in part by grants NS-12265, NS-12267, HD04583 and HD-08658 from the National Institutes of Health, USPHS. The electron microscopic facilities of the California Regional Primate Center, supported by NIH grant RR-00169, were utilized. The technical assistance of Mrs. Viviana Wong is gratefully acknowledged. A preliminary report of a portion of this data was given at the Society for Neuroscience, November, 1974 in St. Louis, Missouri.     

Discriminative insulin antagonism of stimulatory effects of various cAMP analogs on adipocyte lipolysis and hepatocyte glycogenolysis

Although insulin effectively blocked hormone-stimulated glycerol output in adipocytes or phosphorylase activation in hepatocytes, the inhibitory effect of insulin on cAMP analog-stimulated cells depended on the cAMP analog used. Of the 20 analogs tested in adipocytes and 13 tested in hepatocytes, the effects of about half of them were effectively blocked by insulin, whereas the effects of many of them were not inhibited at all. In order to approach the explanation for this discriminative insulin action, the inhibitory effects of insulin on the responses to the analogs in the intact cells were correlated with the in vitro cAMP analog specificity for the hepatocyte cAMP-dependent protein kinase isozymes and the low Km, hormone-sensitive phosphodiesterases from both cell types. No correlation was found between insulin resistance of analog-stimulated hepatocyte phosphorylase and the concentration of analog required in vitro for half-maximal activation of either type I or type II cAMP-dependent protein kinase from hepatocytes. However, a good correlation was found between insulin resistance of cAMP analog-stimulated responses and the analog I50 values for the phosphodiesterase from both cell types. Using a new method capable of measuring hydrolysis at low analog concentrations, several of those analogs which had relatively low, but not high, phosphodiesterase I50 values were shown to be directly hydrolyzed by the low Km adipocyte phosphodiesterase. The insulin inhibition of cell responses when stimulated by hydrolyzable analogs, but not by poorly hydrolyzable analogs, is best explained by insulin stimulation of the low Km phosphodiesterases from both cell types.     

Bacteremia due to Bifidobacterium,Eubacterium or Lactobacillus; twenty-one cases and review of the literature.

Twenty-one cases of bacteremia due to Bifidobacterium, Eubacterium and Lactobacillus are described. Transient bacteremic episodes with these organisms may follow trauma to the mouth, intestine, or vagina. The majority of the patients were female and most had an underlying condition that may have predisposed to bacteremia. Ten of the patients died despite antibiotic treatment.     

Transport Alterations in a Phosphatidylethanolamine-Deficient Mutant of Bacillus subtilis

A mutant of Bacillus subtilis ATCC 6051, demonstrated to be deficient in phosphatidylethanolamine, was found to differ from the parent strain in the rate of uptake of a variety of metabolites.     

Design and SAR of thienopyrimidine and thienopyridine inhibitors of VEGFR-2 kinase activity

Novel classes of thienopyrimidines and thienopyridines have been identified as potent inhibitors of VEGFR-2 kinase. The synthesis and SAR of these compounds is presented, along with successful efforts to diminish EGFR activity present in the lead series.     

The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS)

Interleukin-10 (IL-10) is an immunoregulatory cytokine that plays a crucial role in inflammatory and immune reactions. It has potent anti-inflammatory and immunosuppressive activities on myeloid cell functions which forms a solid basis for its use in acute and chronic inflammatory diseases. Here, we discuss the role of IL-10 in autoimmune diseases and examine its beneficial effects in cellular-based autoimmune diseases such as multiple sclerosis (MS) or its involvement in humoral-based autoimmune diseases such as systemic lupus erythematosus (SLE). Inhibition of the immune stimulatory activities of IL-10 may provide novel approaches in the treatment of humoral autoimmune diseases, infectious diseases and cancer.     

Inheritance of seed iron and zinc concentrations in common bean (Phaseolus vulgaris L.)

Micronutrients are essential elements needed in small amounts for adequate human nutrition and include the elements iron and zinc. Both of these minerals are essential to human well-being and an adequate supply of iron and zinc help to prevent iron deficiency anemia and zinc deficiency, two prevalent health concerns of the developing world. The objective of this study was to determine the inheritance of seed iron and zinc accumulation in a recombinant inbred line (RIL) population of common beans from a cross of low × high mineral genotypes (DOR364 × G19833) using a quantitative trait locus (QTL) mapping approach. The population was grown over two trial sites and two analytical methods (Inductively Coupled Plasma Spectrometry and Atomic Absorption Spectroscopy) were used to determine iron and zinc concentration in the seed harvested from these trials. The variability in seed mineral concentration among the lines was larger for iron (40.0–84.6 ppm) than for zinc (17.7–42.4 ppm) with significant correlations between trials, between methods and between minerals (up to r = 0.715). A total of 26 QTL were identified for the mineral × trial × method combinations of which half were for iron concentration and half for zinc concentration. Many of the QTL (11) for both iron (5) and zinc (6) clustered on the upper half of linkage group B11, explaining up to 47.9% of phenotypic variance, suggesting an important locus useful for marker assisted selection. Other QTL were identified on linkage groups B3, B6, B7, and B9 for zinc and B4, B6, B7, and B8 for iron. The relevance of these results for breeding common beans is discussed especially in light of crop improvement for micronutrient concentration as part of a biofortification program.     

The actin regulatory protein HS1 interacts with Arp2/3 and mediates efficient neutrophil chemotaxis

HS1 is an actin regulatory protein and cortactin homolog that is expressed in hematopoietic cells. Antigen receptor stimulation induces HS1 phosphorylation, and HS1 is essential for T cell activation. HS1 is also expressed in neutrophils; however, the function of HS1 in neutrophils is not known. Here we show that HS1 localizes to the neutrophil leading edge, and is phosphorylated in response to the chemoattractant formyl-Met-Leu-Phe (fMLP) in adherent cells. Using live imaging in microchannels, we show that depletion of endogenous HS1 in the neutrophil-like PLB-985 cell line impairs chemotaxis. We also find that HS1 is necessary for chemoattractant-induced activation of Rac GTPase signaling and Vav1 phosphorylation, suggesting that HS1-mediated Rac activation is necessary for efficient neutrophil chemotaxis. We identify specific phosphorylation sites that mediate HS1-dependent neutrophil motility. Expression of HS1 Y378F, Y397F is sufficient to rescue migration of HS1-deficient neutrophils, however, a triple phospho-mutant Y222F, Y378F, Y397F did not rescue migration of HS1-deficient neutrophils. Moreover, HS1 phosphorylation on Y222, Y378, and Y397 regulates its interaction with Arp2/3. Collectively, our findings identify a novel role for HS1 and its phosphorylation during neutrophil directed migration.