The earliest known estuarine bivalve assemblage, Lower Ordovician of northwestern Argentina

The oldest known estuarine bivalve assemblage is documented from the Lower Ordovician (upper Arenig-lower Llanvirn) Alto del Cóndor Formation, which crops out in the Cordillera Oriental of northwestern Argentina. This unit displays most of the diagnostic sedimentary attributes of estuarine environments. Biotic components include low-diversity trace fossils and a peculiar bivalve fauna consisting of the new genera Konduria, Pseudoredonia, and Pucamya, and the new species Redonia condorensis. This constitutes the earliest known occurrence of bivalves in brackish waters, suggesting that the capability of this clade to colonize estuarine environments developed early in their radiation.     

The development and characterization of an E. coli O25B bioconjugate vaccine

Extraintestinal pathogenic Escherichia coli (ExPEC) cause a wide range of clinical diseases such as bacteremia and urinary tract infections. The increase of multidrug resistant ExPEC strains is becoming a major concern for the treatment of these infections and E. coli has been identified as a critical priority pathogen by the WHO. Therefore, the development of vaccines has become increasingly important, with the surface lipopolysaccharide constituting a promising vaccine target. This study presents genetic and structural analysis of clinical urine isolates from Switzerland belonging to the serotype O25. Approximately 75% of these isolates were shown to correspond to the substructure O25B only recently described in an emerging clone of E. coli sequence type 131. To address the high occurrence of O25B in clinical isolates, an O25B glycoconjugate vaccine was prepared using an E. coli glycosylation system. The O antigen cluster was integrated into the genome of E. coli W3110, thereby generating an E. coli strain able to synthesize the O25B polysaccharide on a carrier lipid. The polysaccharide was enzymatically conjugated to specific asparagine side chains of the carrier protein exotoxin A (EPA) of Pseudomonas aeruginosa by the PglB oligosaccharyltransferase from Campylobacter jejuni. Detailed characterization of the O25B-EPA conjugate by use of physicochemical methods including NMR and GC-MS confirmed the O25B polysaccharide structure in the conjugate, opening up the possibility to develop a multivalent E. coli conjugate vaccine containing O25B-EPA.

     

Mathematical models for excitable systems in biology and medicine.

The excitable systems play a very important role in Biology and Medicine. Phenomena such as the transmission of impulses between neurons, the cardiac arrhythmia, the aggregation of amoebas, the appearance of organized structures in the cortex of egg cells, all derive from the activity of excitable media. In the first part of this work a general definition of excitable system is given; we then analyze some cases of excitability, distinguishing between electrical and chemical excitability and comparing experimental observations with simulations carried out by appropriate mathematical models. Such models are almost always formulated by partial differential equations of "reaction-diffusion" type and they have the characteristic to describe propagations of electrical waves (neurons, pacemaker cardiac cells, pancreatic b-cells) or chemical and mechanical waves (propagation of Ca++ waves or mechanical waves in the endoplasmic reticulum). The aim is to put in evidence that the biological systems can show not only excitability of electrical type, but also excitability of chemical nature, which can be observed in the first steps of development of egg cells or, for example, in the formation of pigments in vertebrate skin or in clam shells.     

Free radical release in C6 glial cells enriched in hexacosanoic acid: implication for X-linked adrenoleukodystrophy pathogenesis

Free radicals have been implicated in the etiopathology of some neurological and demyelinating diseases. To evaluate their involvement in the cerebral form of X-linked adrenoleukodystrophy (cerALD) disorder, characterised by very long chain fatty acid (VLCFA) accumulation, we utilised an in vitro model using rat C6 glial cells, enriched in hexacosenoic acid (C26:0, HA). Modified cells were incubated in presence of oxidative stressors, such as bacterial endotoxin lipopolisaccharides (LPS) and human oxidised low-density lipoprotein (ox-LDL), and the production of proinflammatory cytokines, nitrite, nitrate and superoxide was determined in the supernatants. The results show that modified cells produce higher amounts of nitric oxide (NO) products and superoxide compared to native C6 cells, supporting the role of free radicals as important pathophysiological modulator of the neuroinflammatory response in ALD. This hypothesis suggests that the cerebral damage in ALD could be due to intracellular signalling activated by interaction of exogenous factors with the particular membrane fatty acid composition.     

Tremadoc (earliest Ordovician) brachiopods from Purmamarca and the Sierra de Mojotoro, Cordillera Oriental of northwestern Argentina

The Late Tremadoc storm-dominated shoreface to inner platform deposits exposed west of the Purmamarca village (Coquena Formation) contain a considerably more diverse brachiopod fauna than previously reported. Coquinite horizons from the lower heterolitic succession have yielded monospecific associations of Nanorthis purmamarcaensis nov. sp. (formerly assigned to N. christianiae KJERULF), which is also reported from the Late Tremadoc rocks of the Cerro San Bernardo area. The fine-grained Upper Member of the Coquena Formation contains a more diverse fauna composed by Nanorthis brachymyaria nov. sp., Astraborthis quebradensis nov. sp. and the new plectorthid genus Lipanorthis (type species L. andinus nov. sp.). A different species of Lipanorthis (L. santalaurae nov. sp.) from the Mid Tremadoc Floresta Formation of the Sierra de Mojotoro is also described.     

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.     

Effect of rIFN-gamma and IL-2 treatments in mouse and nude rat infections with Toxoplasma gondii.

Mice and nude rats lethally infected with T. gondii and treated with recombinant rat interferon-gamma (rIFN-gamma) or recombinant human interleukin-2 (rIL-2) were protected against death, when compared with untreated infected controls. In mice rIFN-gamma and rIL-2 played an important role in "prophylactic treatment", but not in "curative therapy". The survival rate was 42% in mice treated with 3 doses of 20,000 U of rIFN-gamma at days -2, -1, 0 before challenge and up to 66% in mice treated with 3 doses of 10,000 U of rIFN-gamma at days -2, 0, +2 before and after infection. Whereas the survival rate was 33% in mice that received 3 doses of 500 U rIL-2 at days -2, -1, 0 before infection, or -2, 0, +2 before and after infection respectively, up to 50% of the mice treated with 3 doses of 1,000 U rIL-2 at days -2, -1, 0 survived. In nude rats rIFN-gamma had a slight effect in "prophylactic treatment", whereas rIL-2 was active only in "curative treatment". The survival rate was 25% both in nude rats treated with doses of 400,000 U of rIFN-gamma at days -3, 0 before challenge, or with doses of 5,000 U of rIL-2 at days +2, +6, +9 after infection. These results lead us to hypothesise that the mechanism by which the lymphokine treatment exerts a protective effect on Toxoplasma infected mice is different from that on nu/nu rats. We conclude that these cytokines may play a notable role in modulating the host's immune defence against T. gondii infection.     

Anti‐inflammaging effects of human alpha‐1 antitrypsin

Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism underlying the anti‐aging effect of hAAT, we monitored the expression of aging‐associated genes and found that aging‐induced expressions of Relish (NF‐?B orthologue) and Diptericin were significantly lower in hAAT lines than in control lines. RNA‐seq analysis revealed that innate immunity genes regulated by NF‐kB were significantly and specifically inhibited in hAAT transgenic Drosophila lines. To confirm this anti‐inflammaging effect in human cells, we treated X‐ray‐induced senescence cells with hAAT and showed that hAAT treatment significantly decreased the expression and maturation of IL‐6 and IL‐8, two major factors of senescence‐associated secretory phenotype. Consistent with results from Drosophila,RNA‐seq analysis also showed that hAAT treatment significantly inhibited inflammation related genes and pathways. Together, our results demonstrated that hAAT significantly inhibited inflammaging in both Drosophila and human cell models. As hAAT is a FDA‐approved drug with a confirmed safety profile, this novel therapeutic potential may make hAAT a promising candidate to combat aging and aging‐related diseases.     

PLMItRNA, a database for tRNAs and tRNA genes in plant mitochondria: enlargement and updating

The current version of PLMItRNA has been realized to constitute a database for tRNA molecules and genes identified in the mitochondria of all green plants ( Viridiplantae ). It is the enlargement of a previous database originally restricted to seed plants [Ceci,L.R., Volpicella,M., Liuni,S., Volpetti,V., Licciulli,F. and Gallerani,R. (1999) Nucleic Acids Res., 27, 156-157]. PLMItRNA reports information and multialignments on 254 genes and 16 tRNA molecules detected in 25 higher plants (one bryophyta and 24 vascular plants) and seven green algae. PLMItRNA is accessible via the WWW at http://bio-WWW.ba.cnr.it:8000/srs6/