Split of HLA-DRw2 into subtypic specificities closely correlated to two HLA-D products

Two B-lymphocyte-specific human alloantisera were studied, PA59 and 51.23. They identify two new HLA-DR alleles, which are both subtypic to HLA-DRw2. Moreover, they are closely correlated with two HLA-D products, Dw2 and tb24 (tb24 is a new specificity described by our group). Thus, DRw2 can be split into two subtypic specificities that have been named TO60 and TO61, which appear more strongly correlated with HLA-D antigens. Absorption studies demonstrated cytotoxicity-negative, absorption-positive (CYNAP) reactions, and cross-reactive groups of antibodies.     

Conformational behaviour of Cα,α-diphenylglycine: folded vs. extended structures in DϕG-containing tripeptides

The crystal structures of three fully protected tripeptides containing the Dϕg residue (C^α,α-diphenylglycine) in the central position are reported, namely Z-Gly-Dϕg-Gly-OMe ( a ), Z-Gly-Dϕg-Aib-OMe ( b ) and Z-Aib-Dϕg-Aib-OMe ( c ). The molecular conformations are quite unusual because the Dϕg residue adopts a folded conformation in the 3₁₀-helical region when the following residue adopts a folded conformation of opposite handedness (peptides b and c ). In contrast, the Dϕg residue adopts the more frequently observed fully extended conformation when the following residue adopts a semi-extended conformation (peptide a ). These findings are in agreement with the theoretical calculations on Ac-Dϕg-Aib-NHCH₃ and Ac-Aib-Dϕg-NHCH₃ also reported in this work. © 1998 European Peptide Society and John Wiley & Sons, Ltd.     

Ulteriori indagini sul rapporto tra nichel e acidi malico e malonico in Alyssum

Abstract

Further contribution on the relationship between nickel and malic and malonic acids in Alyssum.—Further research has been carried out on extracts of leaves and seeds of A. bertolonii Desv., grown on serpentine and normal garden soil, in order to investigate the nature of the nickel compounds present in this plant. On the purified extracts, obtained with water and formic acid, malic and malonic acids have been determined through gas-chromatography of the trimethyl-sililderivatives; Ni, Ca, Mg and K have been analysed by atomic absorption spectrophotometry.

Both malic and malonic acids are present in the leaves of the plants collected on serpentine and therefore rich in nickel, whilst they are present only in small amounts in the plants grown in garden soil. Seeds contain mainly high levels of malic acid. Remarkable amounts of malic acid, related to a high nickel content, have been observed also in the leaves of another nickel accumulator in the genus Alyssum, i.e. A. serpyllifolium Desf. ssp. lusitanicum Dudley et P. Silva, endemic of Portugal serpentines.     

Identification of proteins associated with ligand-activated estrogen receptor α in human breast cancer cell nuclei by tandem affinity purification and nano LC-MS/MS

Estrogen receptor α (ER-α) is a key mediator of estrogen actions in breast cancer (BC) cells. Understanding the effects of ligand-activated ER-α in target cells requires identification of the molecular partners acting in concert with this nuclear receptor to transduce the hormonal signal. We applied tandem affinity purification (TAP), glycerol gradient centrifugation and MS analysis to isolate and identify proteins interacting with ligand-activated ER-α in MCF-7 cell nuclei. This led to the identification of 264 ER-associated proteins, whose functions highlight the hinge role of ER-α in the coordination of multiple hormone-regulated nuclear processes in BC cells.     

Role of drugs in recovery of metabolic function of rat brain following severe hypoglycemia

Severe hypoglycemia with isoelectric EEG induced extensive deterioration of the energy state and gross alteration of amino acid contents on the rat cerebral and cerebellar cortex. During recovery, tissue glucose concentration returned to normal, while both lactate and pyruvate concentrations increased to above normal. In the recovery period, the ATP concentration increased but the adenine nucleotide pool remained reduced, even if the ADP and AMP contents were close to normal. Phosphocreatine was restored to normal concentration with reciprocal changes in creatine content. During recovery there was a rise in glutamate and glutamine concentrations, gamma-aminobutyrate content returning to normal value. Ammonia and aspartate decreased below normal, while alanine increased above normal. The effect of some pharmacological agents on the posthypoglycemic recovery was tested: (a) Ergot alkaloids (dihydroergocristine, dihydroergocriptine, dihydroergocornine); (b) Vinca minor alkaloids (vincamine TPS, (–) eburnamonine); (c) Rauwolfia serpentina alkaloids (reserpine, raubasine); (d) synthetic agent (piracetam). During the posthypoglycemic recovery, these different agents exhibited different, or even contrasting, interferences on glycolytic metabolites, amino acids and energy-rich phosphates. The metabolic alterations in the cerebellar cortex were qualitatively of the same character of those in neocortex. However, the metabolic alterations were less extensive and more sensitive to drug action.     

Synthesis and biological evaluation of novel tamoxifen analogues

A collection of compounds, structurally related to the anticancer drug tamoxifen, used in breast cancer therapy, were designed and synthesized as potential anticancer agents. McMurry coupling reaction was used as the key synthetic step in the preparation of these analogues and the structural assignment of E, Z isomers was determined on the basis of 2D-NOESY experiments. The compounds were evaluated for their antiproliferative activity on breast cancer (MCF-7), cervix adenocarcinoma (HeLa) and biphasic mesothelioma (MSTO-211H) human tumor cell lines. The estrogen like properties of the novel compounds were compared with those of the untreated controls using an estrogen responsive element-based (ERE) luciferase reporter assay and compared to 17β-estradiol (E2). Finally, with the aim to correlate the antiproliferative activity with an intracellular target(s), the effect on relaxation activity of DNA topoisomerases I and II was assayed.     

An Artiodactyl Tracksite at Musandam Peninsula,Sultanate of Oman

Here we report an artiodactyl trackway from Musandam Peninsula, Sultanate of Oman. Epireliefs of the tracks are preserved in poorly consolidated aeolian deposits now making up the ceiling of a coastal cave. As an interesting morphological feature, the trackway documents the trackmaker negotiating a slippery dune slope at an angle.     

Hormonal steroidogenesis in liver and small intestine of the green frog, Rana esculenta L.

We have investigated the potential of autonomous hormonal steroidogenesis in liver and small intestine of male and female frogs, Rana esculenta, during the recovery phase. After incubation of mitochondrial fractions with [4-14C]cholesterol, female liver and intestine formed pregnenolone at a rate of 0.63 and 2.3 pmol/mg protein/h, respectively, whereas conversion by male organs was only c. 0.03 pmol/mg protein/h. Minced tissues preparations transformed [4-14C]pregnenolone into progesterone and 17alpha-hydroxypregnenolone, the former prevailing in the liver, the latter in the intestine. Moreover, both tissues produced 20alpha-dihydropregnenolone, 20alpha-dihydroprogesterone and dehydroepiandrosterone. From incubates with [4-14C]dehydroepiandrosterone, androstenedione and androst-5-ene-3beta, 17beta-diol were identified, the former being more abundant in the liver, the latter in the intestine. These results indicate that both liver and intestine in frog can be independent sources of hormonally active steroids in both sexes.     

Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole

Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure.