Immunosuppressive effect of a human serum ferroprotein of hepatic origin, alpha 2 H globulin. Study on blastic transformation of normal lymphocytes in the presence of phytohemagglutinin]

The alpha2 H globulin, a glycoferroprotein, has been found in the serum of patients with malignant diseases. Its level varies according to the evolution of the disease. The activity of this protein has been studied on the normal lymphocytes cultivated in presence of phytohemagglutinin. This study has showed that 5 mug/ml of alpha2 H globulin can inhibit the blastic transformation. The inhibitory effect is proportional to the amount of alpha2 H globulin added as judged by the tritiated thymidin incorporation. The study of morphological aspects of the lymphocytes shows that alpha2 H globulin acts upon the synthesis of the cytoplasmic proteins.     

Transthyretin: the servant of many masters

Transthyretin (TTR) (formerly, thyroxine binding prealbumin) is an evolutionarily conserved serum and cerebrospinal fluid protein that transports holo-retinol-binding protein and thyroxine. Its serum concentration has been widely used to assess clinical nutritional status. It is also well known that wild-type transthyretin and approximately 100 different mutants give rise to a variety of forms of systemic amyloid deposition. It has been suspected and recently established that TTR can suppress the Alzheimer’s disease phenotype in transgenic animal models of cerebral Aβ deposition. Thus, while TTR is a systemic amyloid precursor, in the brain it seems to have an anti-amyloidogenic effect. TTR is found in other organs as a result of local synthesis or transport, suggesting that it may have other, as yet undiscovered, functions. It is possible that its capacity to bind many classes of compounds allows it to serve as an endogenous detoxifier of molecules with potential pathologic effects.     

Chitotriosidase: the yin and yang

The enzyme chitotriosidase (ChT), the human analogue of chitinases from non-vertebrate species, is one of the most abundant and indicative proteins secreted by activated macrophages. Its enzymatic activity is elevated in serum of patients suffering from Gaucher’s disease type 1 and in some other inherited lysosomal storage disorders, as well as in diseases in which macrophages are activated. The last decade has witnessed the appearance of a substantial number of studies attempting to unravel its cellular functions, which have yet not been fully defined. A great deal of progress has been made in the study of the physiological roles of ChT. This review is looks at the key areas of investigations addressed to further illuminate whether ChT activation might have different functional meanings in various diseases. Received 7 June 2006; received after revision 24 July 2006; accepted 21 September 2006     

Characterization of the partial inhibition, by deficiency in serum factors, of multiplication of SV3T3 transformed fibroblasts]

Partial inhibition, by serum starvation, of multiplication of SV3T3 transformed fibroblasts was studied by cultivating cells in a medium containing 1% of serum. Two different and successive states are described: a first step, with a rate of multiplication for 24 hrs, which is lowered (2 instead of 3 in a normal medium containing 10% of serum) but which remains constant (i.e. exponential multiplication), the observed inhibition being reversed by normal medium; a second step, where the rate of multiplication for 24 hrs, decreases very fast, and which is not reversible.     

Calcitonin-like peptide in the shrimpPalaemon serratus (Crustacea,Decapoda) during the intermolt cycle

Summary A molecule immunologically related to salmon calcitonin has been detected in the hemolymph of the shrimpPalaemon serratus. Its concentration varies inversely with the calcium level during the molt cycle; a maximum (14 ng/ml) is found in the post-molt stage and a minimum (0.5 ng/ml) during the premolt stage.     

Naturalness,the autonomy of scales,and the 125 GeV Higgs

The recent discovery of the Higgs at 125 GeV by the ATLAS and CMS experiments at the LHC has put significant pressure on a principle which has guided much theorizing in high energy physics over the last 40 years, the principle of naturalness. In this paper, I provide an explication of the conceptual foundations and physical significance of the naturalness principle. I argue that the naturalness principle is well-grounded both empirically and in the theoretical structure of effective field theories, and that it was reasonable for physicists to endorse it. Its possible failure to be realized in nature, as suggested by recent LHC data, thus represents an empirical challenge to certain foundational aspects of our understanding of QFT. In particular, I argue that its failure would undermine one class of recent proposals which claim that QFT provides us with a picture of the world as being structured into quasi-autonomous physical domains.     

Demonstration of a receptor for 5 alpha-androstane-3 beta, 17 beta-diol in the cytosol of the anterior pituitary of prepubertal male rats]

The presence of a specific receptor for 5alpha-androstan-3beta, 17beta-diol (3beta-diol) in the pituitary cytosol from prepubertal male rats was demonstrated. Its characteristics were: Ka = 5.2.10(7) M-1 KD = 1.9 X 10(-8) M, number of specific binding = 8.7 10(-14) moles per mg of proteins. Its sedimentation constant was 3 S. Competition assays showed that only 3beta-diol itself and estrogens were able to compete for the binding sites for 3beta-diol. Androgens, including 3alpha-diol, were inefficient. This receptor was found only in pituitary cytosol, it was missing from hypothalamic or cortical cytosols. This special localization seemed to foreshadow a specific role for 3beta-diol in the anterior hypophysis.     

Action of an ATP analog, adenosine 5'-hyophosphophosphate in the reactions catalysed by hexokinase and fructose-6-phosphate kinase]

Adenosine 5'-hypoposphate phosphorylates glucose and fructose 6-phosphate in the presence of hexokinase and fructose 6-phosphate kinase respectively. It behaves as a competitive inhibitor versus ATP in the hexokinase reaction. Its affinity for the two enzymes is similar to that of ATP, the maximal velocities being however much lower.     

Prolactin inducible protein in cancer, fertility and immunoregulation: structure, function and its clinical implications

Prolactin inducible protein (PIP) is a 17- kDa single polypeptide chain, known by various names due to its versatile nature and function in human reproductive and immunological systems. It is expressed in several exocrine tissues such as the lacrimal, salivary, and sweat glands. Its expression is up regulated by prolactin and androgens, and estrogens down regulate it. Due to its over-expression in metastatic breast and prostate cancer, presently PIP is considered as a prognostic biomarker. Moreover, its aspartyl-proteinase nature suggests its role in tumor progression. PIP has unique features because it is small in size and plays multiple important functions. Its ability to bind potentially with CD4-T cell receptor, immunoglobulin G (IgG), actin, zinc α2-glycoprotein (ZAG), fibronectin and enamel pellicle, reveals its important biological functions. This is the first comprehensive review on the structure and functional analysis of PIP and its clinical applications. Received 04 August 2008; received after revision 09 September 2008; accepted 15 September 2008     

Structure of furasterin,a chlorinated metabolite from the fungusPhialophora asteris (downson) burge et isaac

Summary Furasterin, 4-chloro-7-hydroxy-5-methoxy-2-methyl-benzofuran, a new naturally occurring mono-chlorinated fungal metabolite was isolated fromPhialophora Asteris (Downson) Burge et Isaac. Its possible relationship with the biosynthetical pathway of the fungitoxic dichlorinated fungal metabolite cryptosporiopsin is discussed.This work was supported by a combined grant from the French C. N. R. S. and the Dutch foundation Z. W. O.     

Ribonuclease 4, an evolutionarily highly conserved member of the superfamily

The structural and enzymatic properties of RNase 4 are reviewed. This RNase shows a much higher interspecies similarity (approximately 90%) than the other members of the RNase A superfamily. The enzyme is ubiquitous, with the highest amounts present in liver and lung. Its unique uridine specificity results from alterations in and around the pyrimidine-binding site. In particular, the shortened C-terminus and the side chains of Phe-42, Asp-80 and Arg-101 appear to be involved. RNase 4 binds tightly to the intracellular RNase inhibitor, with a K _d of 4 × 10⁻¹⁵ M.     

Structure and stereochemistry of brianolide, a new antiinflammatory diterpenoid from the Okinawan gorgonian Briareum sp.

Brianolide (1), a new antiinflammatory diterpenoid of the briarein class, possessing a beta substituent at C-12 (R), has been isolated from the Okinawan gorgonian Briareum sp. Its structure has been established from spectral data in conjunction with a single crystal X-ray analysis.     

Lens regeneration from the dorsal iris inEurycea bislineata,the two-lined salamander

Summary Following lens removal from the eye of adultEurycea bislineata, the northern (USA) 2-lined salamander, it was found that this salamander has the capacity for lens regeneration. Its widespread distribution and high percentage of regenerative success suggests it as a suitable organism for the study of this differentiative phenomenon.This research was supported by N.I.H. grant EY-02534 from the National Eye Institute. We thank S.M. DiRienzo for excellent technical assistance.     

The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity

The PREPL (previously called KIAA0436) gene encodes a putative serine peptidase from the prolyl oligopeptidase family. A chromosomal deletion involving the PREPL gene leads to a severe syndrome with multiple symptoms. Homology with oligopeptidase B suggested that the enzyme cleaves after an arginine or lysine residue. Several PREPL splice variants have been identified, and a 638-residue variant (PREPL A) was expressed in Escherichia coli and purified. Its secondary structure was similar to that of oligopeptidase B, but differential-scanning calorimetry indicated a higher conformational stability. Dimerization may account for the enhanced stability. Unexpectedly, the PREPL A protein did not cleave peptide substrates containing a P1 basic residue, but did slowly hydrolyse an activated ester substrate, and reacted with diisopropyl fluorophosphate. These results indicated that the catalytic serine is a reactive residue. However, the negligible hydrolytic activity suggests that the function of PREPL A is different from that of the other members of the prolyl oligopeptidase family.     

Effect of cell proliferation on the condensation of X chromosomes in the form of Barr-bodies, in human 46 XX fibroblast cultures with different serum concentrations]

The frequency of Barr-bodies in cultivated 46 XX human fibroblasts considerably increases when in confluent monolayer cultures the cells no longer divide. Or, independently of cell contact, when the cells are grown in medium with low serum content, which will slow down or entirely arrest further growth. The frequency of Barr-bodies again diminishes when after the administration of culture medium with sufficient serum concentration, the cells start growing again, indicating that the condensation of the X chromosome is reversible under control of the cell proliferation.     

A p-menthane derivative isolated from culture filtrates ofFusicoccum amygdali,Del.

Summary From culture filtrates ofFusicoccum amygdali, Del., a new compound, whose structure corresponds to 1,2,3-trihydroxy-p-menthane, has been isolated. Its discovery is of some interest since, to our knowledge, it is the first time that a monoterpenoid is isolated from a microorganism.     

Phallolysin,ein hochmolekulares toxin ausAmanita phalloides

Summary Phallolysin, a toxic hemolysin of high molecular weight, was isolated from aqueous extracts ofAmanita phalloides. Its properties are discussed.     

Effects of repeated administration of potassium canrenoate (SC-14266) on serum gonadotrophin,prolactin, testosterone and progesterone in male rats

Summary Chronic administration of potassium canrenoate (SC-14266), a water-soluble anti-aldosterone agent, increased serum LH levels in male rats without altering serum levels of FSH, prolactin, testosterone and progesterone. The increase in serum LH may be due to the anti-androgenic effect of potassium canrenoate.Acknowledgments. The authors thank the Rat Pituitary Hormone Distribution Program, NIAMDD, NIH and Dr A.F. Parlow for radioimmunoassay materials.     

The halophilic properties of pyruvate kinase from Vibrio costicola, a moderate halophile.

Pyruvate kinase from Vibrio costicola, a moderate halophile, appears to be adapted to functioning in the presence of salt. Its stability depends on the ionic strength of the medium. The amino acid composition resembles that of other halophilic enzymes. It is proposed that the halophilic pyruvate kinase utilizes preferentially the Mn++ cofactor which forms more stable complexes in the presence of physiological concentrations of salt.     

Thiarubrine A, a bioactive constituent of Aspilia (Asteraceae) consumed by wild chimpanzees

Two African species of Aspilia (Asteraceae), which are used medicinally by man and which are eaten by wild chimpanzees in an unusual manner, were found to contain the potent antibiotic thiarubrine A as a major leaf phytochemical. Its presence in leaf material strengthens the view that the feeding behavior of wild chimpanzees is related to special physiological or pharmacological effects on the animals.