Jasione sphaerocephala sp.nov. (Campanulaceae) from Italy

Jasione sphaerocephala Brullo, Marcend et Pavone sp.nov. is described from Calabria, S Italy. It grows in rocky places and has some resemblance to J. laevis and J. montana. The chromosome number is 2n = 14.     

Integrin receptors play a role in the internalin B-dependent entry of <Emphasis Type="Italic">Listeria monocytogenes</Emphasis> into host cells

Listeria monocytogenes enters non-phagocytic cells by binding its surface proteins inlA (internalin) and inlB to the host’s E-cadherin and Met, respectively. The two internalins play either separate or cooperative roles in the colonization of infected tissues. Here, we studied bacterial uptake into HeLa cells using an L. monocytogenes mutant strain (ΔinlA) carrying a deletion in the gene coding for inlA. The ΔinlA mutant strain showed the capability to invade HeLa cells. The monoclonal anti-β₃- and anti-β₁-integrin subunit antibodies prevented bacterial uptake into the cells, while the anti-β₂- and anti-β₄-integrin subunit antibodies failed to affect L. monocytogenes entry into HeLa cells. Three structurally distinct disintegrins (kistrin, echistatin and flavoridin) also inhibited bacterial uptake, showing different potencies correlated to their selective affinity for the β₃- and β₁-integrin subunits. In addition to inducing Met phosphorylation, infection of cells by the L. monocytogenes ΔinlA mutant strain promoted the tyrosine phosphorylation of the focal adhesion-associated proteins FAK and paxillin. Our findings provide the first evidence that β₃- and β₁-integrin receptors play a role in the inlB-dependent internalization of L. monocytogenes into host cells.     

Critical role of the N-loop and beta1-strand hydrophobic clusters of RANTES-derived peptides in anti-HIV activity

HIV initiates its infectious cycle by docking to CD4 and a chemokine receptor, most commonly CCR5. RANTES, a natural CCR5 ligand, is a potent inhibitor of HIV-1. Despite the lack of structural information on the RANTES-CCR5 complex, determinants of HIV blockade were previously identified within the RANTES N-loop and beta1-strand regions. A prototype N-loop/beta1-strand peptide, named R11-29, contains two terminal hydrophobic stretches separated by a central hydrophilic region. Here, the role of the terminal hydrophobic clusters was investigated by means of amino acid substitutions or deletions. Most hydrophobic residues in these clusters were shown to be fundamental for the anti-HIV activity. However, increasing the hydrophobicity of the two clusters using non-natural amino acids did not significantly improve the potency of the peptides. These results may provide instrumental knowledge for the rational design of RANTES-derivative molecules with increased anti-HIV activity.     

Long,Chiral Polypeptide 310-Helices at Atomic Resolution

Abstract

The crystal-state preferred conformation of the terminally blocked hepta- and octapeptides with the general formula -(Aib)_n L-Leu-(Aib)₂- (n=4 and 5, respectively), determined by X-ray diffraction, was found to be a right-handed 3₁₀-helix stabilized by five and six consecutive intramolecular NH···0=C H-bonds of the C₁₀-III type, respectively. The octapeptide structure represents the first observation at atomic resolution of a regular, chiral 3₁₀-helix larger than two complete turns. In both cases the right handed screw sense of the helix is dictated by the presence of the single, internal L-residue. This study confirms the propensity of short peptides rich in Aib, the prototype of the amino acid residues dialkylated at the α carbon, to adopt a 3₁₀- helical structure and is expected to help our understanding of the conformational preferences of the membrane-active, channel-forming, ion-transporting peptaibol antibiotics.     

Molecular Structure of Peptaibol Antibiotics: Solution Conformation and Crystal Structure of the Octapeptide Corresponding to the 2–9 Sequence of Emerimicins III and IV

Abstract

The infrared absorption and ¹H nuclear magnetic resonance analyses of chloroform solutions of the terminally-blocked segment corresponding to the 2–9 sequence of emerimicins III and IV, -(Aib)₃-L-Val-Gly-L-Leu-(Aib)_2-, are consistent with the presence of a 3₁₀-helical structure of high thermal stability. The crystal structure of the octapeptide, obtained by X-ray diffraction indicates the formation of a right-handed 3₁₀-helix, stabilized by six consecutive intramolecular N-H OC H-bonds, slightly distorted at the level of the L-Leu residue.     

Conservation status of habitats (Directive 92/43 EEC) of coastal and low hill belts in a Mediterranean biodiversity hot spot (Gargano – Italy)

The Gargano is one of the richest Mediterranean areas in biodiversity. The work reports an assessment of the presence and conservation status of the habitats according to the 92/43/EEC Directive of Gargano coastal and low hill belts, their relationships with plant communities, threatened species, phytoclimatology, threats, and suggestions for management purposes. The field surveys revealed 33 habitats of Directive, and 6 of them are priority (1150^* Coastal lagoons, 2250^* Coastal dunes with Juniperus ssp., 2270^* Wooded dunes with Pinus pinea and/or Pinus pinaster, 6220^* pseudo-steppe with grasses and annuals of the Thero-Brachypodietea, 7210^* Calcareous fens with Cladium mariscus and species of the Caricion davallianae, 91AA^* Eastern white oak woods). The updates of six Special Areas Conservation and three Special Protection Areas of Natura 2000 network are provided.     

Protein-protein interaction heterogeneity of plasma apolipoprotein A1 in nephrotic syndrome

Apolipoprotein A1 (apoA1) is a component of the high density lipoproteins (HDL) that regulates the transport of cholesterol between the liver and peripheral cells and modulates the removal of any excess of cholesterol from membranes. Any variation in apoA1 composition may modify the plasma lipid profile and be involved in atherogenesis. We investigated apoA1 composition in plasma of 6 children with nephrotic syndrome, a condition characterized by high levels of cholesterol in plasma and by a high risk to develop atherosclerosis. Non-denaturing two-dimensional electrophoresis (Nat/SDS-PAGE), mass spectrometry, western blot and pull down experiments were done to characterize proteins and define putative interactions. ApoA1 was resolved in 12 variants, 6 of which had a slightly lower molecular weight (18-19 KDa) and migrated on the same axes of the β chain of haptoglobin (Hp). Low molecular weight apoA1 were observed in carriers of different Hp haplotypes (including one homozygous for the rare ββα1α1) ruling out any contaminant effect of co-migration of apoA1 with Hp α2 chain. Overall, apoA1 isoforms were much more present in plasma of nephrotic patients compared to a normal profile. These findings show that apoA1 plasma in nephrotic syndrome is heterogeneous in terms of molecular weight. Low molecular weight fragments lack internal structural domains and likely form macro-aggregates with Hp. Fragmentation and transport of apoA1 may be involved in the general disorder of lipid metabolism that characterizes nephrotic syndrome.     

Intranasal "painless" human Nerve Growth Factors slows amyloid neurodegeneration and prevents memory deficits in App X PS1 mice

Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that "painless" hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n?=?8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of "painless" hNGF variants as a new generation of therapeutics for neurodegenerative diseases.     

And Yet They Act Together: Interpersonal Perception Modulates Visuo-Motor Interference and Mutual Adjustments during a Joint-Grasping Task

Prediction of “when” a partner will act and “what” he is going to do is crucial in joint-action contexts. However, studies on face-to-face interactions in which two people have to mutually adjust their movements in time and space are lacking. Moreover, while studies on passive observation have shown that somato-motor simulative processes are disrupted when the observed actor is perceived as an out-group or unfair individual, the impact of interpersonal perception on joint-actions has never been directly addressed. Here we explored this issue by comparing the ability of pairs of participants who did or did not undergo an interpersonal perception manipulation procedure to synchronise their reach-to-grasp movements during: i) a guided interaction, requiring pure temporal reciprocal coordination, and ii) a free interaction, requiring both time and space adjustments. Behavioural results demonstrate that while in neutral situations free and guided interactions are equally challenging for participants, a negative interpersonal relationship improves performance in guided interactions at the expense of the free interactive ones. This was paralleled at the kinematic level by the absence of movement corrections and by low movement variability in these participants, indicating that partners cooperating within a negative interpersonal bond executed the cooperative task on their own, without reciprocally adapting to the partner''s motor behaviour. Crucially, participants'' performance in the free interaction improved in the manipulated group during the second experimental session while partners became interdependent as suggested by higher movement variability and by the appearance of interference between the self-executed actions and those observed in the partner. Our study expands current knowledge about on-line motor interactions by showing that visuo-motor interference effects, mutual motor adjustments and motor-learning mechanisms are influenced by social perception.