Evidence for a single glutamate receptor of the ionotropic kainate/quisqualate type

The kainate (KA) and the quisqualate (QUIS) receptors that activate cation channels in the central nervous system have previously been defined as two of the major glutamate receptor types. In amphibian brain, an exceptionally rich source of these sites, they can be coextracted by octylglucoside and shown to behave as one entity in all analyses made in solution. When partly purified by lectin affinity, ion-exchange chromatography or by sucrose gradient centrifugation, the two activities comigrate in a 1:1 ratio. When the QUIS component is bound to an immobilized specific QUIS agonist, the KA component is extracted in parallel with it. There are equivalent numbers of the QUIS and KA sites and the two sites show a single affinity series for the binding of glutamatergic agonists. We deduce that KA or QUIS select different conformations of a single KA/QUIS receptor binding site, leading thus to the different channel-opening events that have been reported for these two agonists.     

Pollination Ecophysiology of Mercurialis annua L. (Euphorbiaceae), an Anemophilous Species Flowering all Year Round

Mercurialis annua L. is a dioecious anemophilous species thatflowers all year round in central and southern Italy. The flowersof both sexes are dimorphic: the female flower has a vestigialcalyx; the male flower consists only of a calyx that opens atanthesis. The anthers always dehisce after anthesis. The anthesisof male flowers seems to be temperature dependent, whereas antherdehiscence is related to relative humidity. The pollen grainsvary in volume according to the season: they are smaller whenrelative humidity is low and vice versa. They always decreasein volume after anther dehiscence and have the capacity to varyin volume and reach equilibrium with a changing environment.Viability is high, but may drop suddenly during heavy rain orhail that damage the exposed male flowers. The number of pollengrains per stigma varies from 0 to 300. The data is discussedin relation to the type of pollination and environmental characteristics.Copyright1994, 1999 Academic Press Mercurialis annua, dioecism, anthesis, anther dehiscence, pollen volume, pollen viability, anemophilous pollination, pollination ecology     

Preferred conformation of peptides rich in Ac8c,a medium-ring alicyclic Cα,α-disubstituted glycine

A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C^α,α-disubstituted glycine 1-aminocyclooctane-1-carb oxylic acid (Ac₈c), and two Ala/Ac₈c tripeptides, were synthesized by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and ¹H-NMR. The molecular structures of the amino acid derivative Z-Ac₈c-OH, the dipeptide pBrBz- (Ac₈c)₂-OH and the tripeptide pBrBz-(Ac₈c)₃-OtBu were assessed in the crystal state by X-ray diffraction. Conformational energy computations were performed on the monopeptide Ac-Ac₈c-NHMe. Taken together, the results obtained strongly support the view that the Ac₈c residue is an effective β-turn and helix former. A comparison is also made with the conformational preferences of α-aminoisobutyric acid, the prototype of C^{α, α}-disubstituted glycines, and of the other members of the family of 1-aminocycloalkane-1-carboxylic acids (Ac_nc, with n=3, 5–7) investigated so far. The implications for the use of the Ac₈c residue in peptide conformational design are considered.     

Linear oligopeptides: 65′. Conformational analysis of the N-protected aromatic α-amino acid N-tert-butyloxycarbonyl-l-phenylalanine by X-ray diffraction and infrared absorption

The X-ray diffraction and i.r. absorption conformational analysis of $\text{N}\text{-tert-butyloxycarbonyl-}\text{l}\text{-phenylalanine}$ has showed the absence of intramolecularly hydrogen-bonded peptide conformations in the solid state. The molecules are held together in rows of ‘cyclic dimer’ motifs through intermolecular NH … OC (acid) and OH … OC {urethane} hydrogen bonds, the secondary amide-like group of the urethane moiety being in the unusual cis conformation, whereas the carboxylic acid group in the common syn conformation. The two molecules in the unit cell present a centrosymmetric set of ?, ψ¹, and ψ² values. In polar solvents solvated species largely predominate. In saturated hydrocarbon solution non-associated and associated (mostly involving the carboxylic acid CO as the proton acceptor) species simultaneously occur. The extent of association decreases with dilution. The amount of intramolecularly hydrogen-bonded oxy-C₇ and C₅ forms if any, should be extremely small. The type of association at saturation seems to differ from that found in the crystalline compound obtained by precipitation with saturated aliphatic hydrocarbons (from a diethyl ether solution).     

NMR studies of prebiotic polypeptides

Several polypeptides prepared by means of pyrocondensation have been the subject of structural investigations. Attention has been focused on the constitutional characterization of homo-and co-polymers containing Asp and Glu residues, whose role is essential for the formation of the so-called proteinoids. Contrary to the literature data based on chemical degradation, nmr studies show conclusively that in thermal poly-aspartic acid only β-peptide linkages are present. This result casts serious doubt on the role thermal condensation might have played in prebiotic polypeptide syntheses.     

Granulomatosi sperimentali da specie del genere

Riassunto L'A. inocula il Monosporium apiospermum Saccardo (ceppo Tarozzi) in conigli, cavie e piccioni allo scopo di riprodurre sperimentalmente il micetoma monosporosico e di studiare l'infiammazione specifica. I tentativi di riprodurre nella zampa del piccione il micetoma monosporosico hanno avuto esito negativo. Nei conigli sono state studiate le modalità dell'infezione primaria e di quelle provocate con reinoculazioni in animali precedentemente preparati. L'A. ha messo in evidenza delle modificazioni umorali ed allergiche negli animali più volte trattati; al lume di questi reperti cerca di chiarire i meccanismi patogenetici della malattia sperimentale e di quella umana. Fa, infine, alcune considerazioni sulla forma parassitaria del Monosporium apiospermium.

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Summary The author injects the Monosporium apiospermum Saccardo (Tarozzi strain) into rabbits, guinea-pigs and pigeons in order to reproduce the monosporic mycetoma experimentally and to study specific inflammation. The attempts of reproducing the monosporic mycetoma in the pigeon's foot had a negative result. The modalities of primary infection and of those caused by reinoculation in animals previously prepared, have been studied in rabbits. The Author pointed out some humoral and allergical modifications in animals which had been treated many times; availing himself of these findings he tries to explain the pathogenic mechanism of the experimental and human disease. Finally he makes some consideration on the parasitical form of the Monosporium apiospermum.

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Zusammenfassung Verfasser impfo das Monosporium apiospermium Saccardo (stamm Tarozzi) Kaninchen, Meerschweinchen und Tauben zu dem Zwecke ein, das monosporosiche Mycetom experimentell zu erzeugen und die spezifische Entzündung zu studieren. Die Versuche, das monosporosische Mycetom am Taubenfuss hervorzurufen haben ein negatives Ergebnis gezeitigt. Bei den Kaninchen wurden die Modalitäten der primären und der mittels Wiedereinimpfung bei vorbehandelten Tieren hervorgerufenen Entzündungen untersucht. Verfasser konnte bei den mehrmals behandelten Tieren humorale und allergische Veränderungen zum Vorschein bringen; im Lichte dieser Befunde versucht er, die pathogenetischen Mechanismen der experimentellen und menschlichen Erkrankung zu klären. Schliesslich stellt Verfasser einige Betrachtungen über die parasitäre Form des Monosporium apiospermum an.

     

Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free,low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial

BackgroundWe compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression.Methods and findingsATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved. Primary endpoint was biopsy-proven CAN. Analysis was by intention to treat.Participants were included between June 2007 and July 2012 and followed up to August 2016. Between-group donor and recipient characteristics, donor/recipient mismatches, and follow-up CsA blood levels were similar. During a median (interquartile range (IQR)) follow-up of 47.7 (44.2 to 48.9) months, 29 of 87 biopsied patients on MMF (33.3%) versus 31 of 88 on AZA (35.2%) developed CAN (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595). Twenty and 21 patients on MMF versus 34 and 14 on AZA had clinical [HR (95% CI): 0.58 (0.34 to 1.02); p = 0.057) or biopsy-proven subclinical [HR (95% CI): 1.49 (0.76 to 2.92); p = 0.249] ACR, respectively. Combined events [HR (95% CI): 0.85 (0.56 to 1.29); p = 0.438], patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate (GFR) [53.8 (40.6;65.7) versus 49.8 (36.8;62.5) mL/min/1.73 m², p = 0.50], and adverse events (AEs) were not significantly different between groups.Chronicity scores other than CAN predict long-term graft outcome. Study limitations include small sample size and unblinded design.ConclusionsIn this study, we found that in deceased donor kidney transplant recipients on low-dose CsA and no steroids, MMF had no significant benefits over AZA. This finding suggests that AZA, due to its lower costs, could safely replace MMF in combination with minimized immunosuppression.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00494741","term_id":"NCT00494741"}}NCT00494741; EUDRACT 2006-005604-14.

Piero Ruggenenti and co-workers study maintenance immunosuppression in deceased-donor kidney transplantation.     

Breeding systems in two species of the genus Helleborus (Ranunculaceae)

ABSTRACT

The results of various types of manual and free pollination are reported in Helleborus bocconei and Helleborus foetidus, two sympatric species of the understorey of submediterranean woods that flower in January–March and are pollinated by bumble-bees of the genus Bombus. Both species were found to be partially self-compatible even if at different rates; geitonogamy seems to be more frequent in H. foetidus and spontaneous self-pollination does not usually occur for morphological reasons, and the species are not apomictic. Efficiency in seed production after free pollination was very high indicating that in spite of harsh climatic condition, there were no limitations imposed by pollen or pollinators.