Le api svelano il mistero delle fonti di emissione di particolato inquinante

Si tratta di una ricerca che è durata due anni, ed è stata pubblicata sul numero di luglio 2015 della Rivista scientifica internazionale Plos One. Gli autori: Ilaria Negri, Marco Pellecchia (Koiné - Consulenze Ambientali S.n.c., Parma, Italy), Christian Mavris (Department of Earth Sciences, Natural History Museum, London, United Kingdom), Gennaro Di Prisco, Emilio Caprio (Dipartimento di Agraria, Laboratorio di Entomologia E. Tremblay, Università degli Studi di Napoli Federico II, Portici - Napoli). Nello studio scientifico i ricercatori dimostrano che le api si comportano anche come “campionatori” attivi di particolato atmosferico, i cosiddetti PM (dall’inglese “Particulate Matter”), di cui sono ricche le nostre città come troppo spesso avvertono i dati dell’Agenzia Regionale di Protezione dell’Ambiente (ARPA). Dice che l’Iglesiente (Iglesias, Sardegna) è inquinato, fortemente contaminato da metalli pesanti come il piombo e il bario. E svela poi che la salute di chi ci vive potrebbe essere compromessa, se non lo è già, anche dall’alta concentrazione di ferro, silicio e alluminio. Rivela ancora, con scientifica precisione, da dove provengono le micro particelle di queste impercettibilissime polveri: dalle miniere dell’Iglesiente e dalle industrie di Portovesm

Honey Bees (Apis mellifera, L.) as Active Samplers of Airborne Particulate Matter

© 2015 Negri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. [CC by 4.0] The attached file is the published version of the article

The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities

E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities

ATPase Subdomain IA Is a Mediator of Interdomain Allostery in Hsp70 Molecular Chaperones

The versatile functions of the heat shock protein 70 (Hsp70) family of molecular chaperones rely on allosteric interactions between their nucleotide-binding and substrate-binding domains, NBD and SBD. Understanding the mechanism of interdomain allostery is essential to rational design of Hsp70 modulators. Yet, despite significant progress in recent years, how the two Hsp70 domains regulate each other's activity remains elusive. Covariance data from experiments and computations emerged in recent years as valuable sources of information towards gaining insights into the molecular events that mediate allostery. In the present study, conservation and covariance properties derived from both sequence and structural dynamics data are integrated with results from Perturbation Response Scanning and in vivo functional assays, so as to establish the dynamical basis of interdomain signal transduction in Hsp70s. Our study highlights the critical roles of SBD residues D481 and T417 in mediating the coupled motions of the two domains, as well as that of G506 in enabling the movements of the α-helical lid with respect to the β-sandwich. It also draws attention to the distinctive role of the NBD subdomains: Subdomain IA acts as a key mediator of signal transduction between the ATP- and substrate-binding sites, this function being achieved by a cascade of interactions predominantly involving conserved residues such as V139, D148, R167 and K155. Subdomain IIA, on the other hand, is distinguished by strong coevolutionary signals (with the SBD) exhibited by a series of residues (D211, E217, L219, T383) implicated in DnaJ recognition. The occurrence of coevolving residues at the DnaJ recognition region parallels the behavior recently observed at the nucleotide-exchange-factor recognition region of subdomain IIB. These findings suggest that Hsp70 tends to adapt to co-chaperone recognition and activity via coevolving residues, whereas interdomain allostery, critical to chaperoning, is robustly enabled by conserved interactions. © 2014 General et al

Growth hormone secretion is correlated with neuromuscular innervation rather than motor neuron number in early-symptomatic male amyotrophic lateral sclerosis mice

GH deficiency is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, therapy with GH and/or IGF-I has not shown benefit. To gain a better understanding of the role of GH secretion in ALS pathogenesis, we assessed endogenous GH secretion in wild-type and hSOD1(G93A) mice throughout the course of ALS disease. Male wild-type and hSOD1(G93A) mice were studied at the presymptomatic, onset, and end stages of disease. To assess the pathological features of disease, we measured motor neuron number and neuromuscular innervation. We report that GH secretion profile varies at different stages of disease progression in hSOD1(G93A) mice; compared with age-matched controls, GH secretion is unchanged prior to the onset of disease symptoms, elevated at the onset of disease symptoms, and reduced at the end stage of disease. In hSOD1(G93A) mice at the onset of disease, GH secretion is positively correlated with the percentage of neuromuscular innervation but not with motor neuron number. Moreover, this occurs in parallel with an elevation in the expression of muscle IGF-I relative to controls. Our data imply that increased GH secretion at symptom onset may be an endogenous endocrine response to increase the local production of muscle IGF-I to stimulate reinnervation of muscle, but that in the latter stages of disease this response no longer occurs

Are Well Performing Catalysts for the Ring Opening Polymerization of l -Lactide under Mild Laboratory Conditions Suitable for the Industrial Process? the Case of New Highly Active Zn(II) Catalysts

Poly(lactic acid) (PLA) is one of the best candidates as a sustainable plastic material for a circular economy, being biodegradable, bio-based, recyclable, and displaying good thermal and mechanical properties. The industrial production of PLA is mainly based on the ring opening polymerization (ROP) of l-lactide (l-LA) promoted by tin(II) 2-ethylhexanoate [Sn(Oct)2] in a continuous solvent-free process operating at temperatures between 180 and 200 °C, above the melting point of the resulting isotactic polymer. Despite the huge efforts in the research of alternative catalysts based on less toxic metals, resulting in a plethora of highly active catalysts under laboratory mild conditions, very few candidates can compete with Sn(Oct)2 under industrially relevant conditions. We report a family of new Zn(II) complexes, bearing variously substituted monoanionic [N,O-] (imidazole[1,5-a]pyrid-3-yl)phenolate ligands, as catalysts for the ROP of l-LA under both mild (20 °C, solvent) and industrially relevant (190 °C, in the melt, technical grade unpurified monomer, very low catalyst loading) conditions. Interestingly, the best performing catalyst under mild conditions is the worst performing under harsh conditions, and, on the contrary, the less active catalysts under mild conditions compete well with Sn(Oct)2 under industrially relevant conditions. Kinetic and DFT mechanistic investigations shed light on the non-trivial role of the 2-pyridine substituent in the catalytic performances at different temperatures. Preliminary depolymerization tests on commercial PLLA samples suggested that the new catalysts can also be a suitable candidate for the chemical recycling of PLA under mild conditions

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Objectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated.Results:Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions:The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss