Invariant sets for discontinuous parabolic area-preserving torus maps

We analyze a class of piecewise linear parabolic maps on the torus, namely those obtained by considering a linear map with double eigenvalue one and taking modulo one in each component. We show that within this two parameter family of maps, the set of noninvertible maps is open and dense. For cases where the entries in the matrix are rational we show that the maximal invariant set has positive Lebesgue measure and we give bounds on the measure. For several examples we find expressions for the measure of the invariant set but we leave open the question as to whether there are parameters for which this measure is zero.Comment: 19 pages in Latex (with epsfig,amssymb,graphics) with 5 figures in eps; revised version: section 2 rewritten, new example and picture adde

Structure of the cystathionine γ-synthase MetB from Mycobacterium ulcerans

Cystathionine γ-synthase (CGS) is a transferase that catalyzes the reaction between O 4-succinyl-l-homoserine and l-cysteine to produce l-­cystathionine and succinate. The crystal structure of CGS from M. ulcerans is presented covalently linked to the cofactor pyridoxal phosphate (PLP). A second structure contains PLP as well as a highly ordered HEPES molecule in the active site acting as a pseudo-ligand. This is the first structure ever reported from the pathogen M. ulcerans

Bound Water at Protein-Protein Interfaces: Partners, Roles and Hydrophobic Bubbles as a Conserved Motif

Background There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. Methodology A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed Relevance was used to classify the general roles of the water molecules. Results The water molecules were found to be involved in: a) (bridging) interactions with both proteins (21%), b) favorable interactions with only one protein (53%), and c) no interactions with either protein (26%). This trend is shown to be independent of the crystallographic resolution. Interactions with residue backbones are consistent for all classes and account for 21.5% of all interactions. Interactions with polar residues are significantly more common for the first group and interactions with non-polar residues dominate the last group. Waters interacting with both proteins stabilize on average the proteins\u27 interaction (−0.46 kcal mol−1), but the overall average contribution of a single water to the protein-protein interaction energy is unfavorable (+0.03 kcal mol−1). Analysis of the waters without favorable interactions with either protein suggests that this is a conserved phenomenon: 42% of these waters have SASA ≤ 10 Å2 and are thus largely buried, and 69% of these are within predominantly hydrophobic environments or “hydrophobic bubbles”. Such water molecules may have an important biological purpose in mediating protein-protein interactions

Semiquantitative Analysis of Clinical Heat Stress in Clostridium difficile Strain 630 Using a GeLC/MS Workflow with emPAI Quantitation.

<div><p><i>Clostridium difficile</i> is considered to be the most frequent cause of infectious bacterial diarrhoea in hospitals worldwide yet its adaptive ability remains relatively uncharacterised. Here, we used GeLC/MS and the exponentially modified protein abundance index (emPAI) calculation to determine proteomic changes in response to a clinically relevant heat stress. Reproducibility between both biological and technical replicates was good, and a 37°C proteome of 224 proteins was complemented by a 41°C proteome of 202 proteins at a 1% false discovery rate. Overall, 236 <i>C. difficile</i> proteins were identified and functionally categorised, of which 178 were available for comparative purposes. A total of 65 proteins (37%) were modulated by 1.5-fold or more at 41°C compared to 37°C and we noted changes in the majority of proteins associated with amino acid metabolism, including upregulation of the reductive branch of the leucine fermentation pathway. Motility was reduced at 41°C as evidenced by a 2.7 fold decrease in the flagellar filament protein, FliC, and a global increase in proteins associated with detoxification and adaptation to atypical conditions was observed, concomitant with decreases in proteins mediating transcriptional elongation and the initiation of protein synthesis. Trigger factor was down regulated by almost 5-fold. We propose that under heat stress, titration of the GroESL and dnaJK/grpE chaperones by misfolded proteins will, in the absence of trigger factor, prevent nascent chains from emerging efficiently from the ribosome causing translational stalling and also an increase in secretion. The current work has thus allowed development of a heat stress model for the key cellular processes of protein folding and export.</p></div

Isozyme-Specific Ligands for O-acetylserine sulfhydrylase, a Novel Antibiotic Target

Conceived and designed the experiments: FS PC BC ES AM. Performed the experiments: FS RS ES PF SR. Analyzed the data: FS BC ES PF GEK PFC AM. Contributed reagents/materials/analysis tools: PC PB GC. Wrote the paper: FS GEK BC AM.The last step of cysteine biosynthesis in bacteria and plants is catalyzed by O-acetylserine sulfhydrylase. In bacteria, two isozymes, O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, have been identified that share similar binding sites, although the respective specific functions are still debated. O-acetylserine sulfhydrylase plays a key role in the adaptation of bacteria to the host environment, in the defense mechanisms to oxidative stress and in antibiotic resistance. Because mammals synthesize cysteine from methionine and lack O-acetylserine sulfhydrylase, the enzyme is a potential target for antimicrobials. With this aim, we first identified potential inhibitors of the two isozymes via a ligand- and structure-based in silico screening of a subset of the ZINC library using FLAP. The binding affinities of the most promising candidates were measured in vitro on purified O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B from Salmonella typhimurium by a direct method that exploits the change in the cofactor fluorescence. Two molecules were identified with dissociation constants of 3.7 and 33 µM for O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, respectively. Because GRID analysis of the two isoenzymes indicates the presence of a few common pharmacophoric features, cross binding titrations were carried out. It was found that the best binder for O-acetylserine sulfhydrylase-B exhibits a dissociation constant of 29 µM for O-acetylserine sulfhydrylase-A, thus displaying a limited selectivity, whereas the best binder for O-acetylserine sulfhydrylase-A exhibits a dissociation constant of 50 µM for O-acetylserine sulfhydrylase-B and is thus 8-fold selective towards the former isozyme. Therefore, isoform-specific and isoform-independent ligands allow to either selectively target the isozyme that predominantly supports bacteria during infection and long-term survival or to completely block bacterial cysteine biosynthesis.Yeshttp://www.plosone.org/static/editorial#pee

Pi&#249; convenuti, pi&#249; colpe e un danno da &#8220;spartire&#8221; : il perimetro del medico legale

La presente riflessione, dagli interessanti spunti di carattere medico-legale, ortopedico ed infettivologico, trae origine da una complessa vicenda clinica che vede coinvolte diverse strutture e figure professionali sanitarie, sviluppatasi in un complesso iter clinico della durata di circa 5 anni: un soggetto di 58 anni, presso due diverse strutture, si sottopose a due interventi di artroprotesi al ginocchio sinistro, le quali ebbero entrambe ad infettarsi con due diversi agenti patogeni. L'iter clinico sfoci\uf2 poi in un intervento finale di artrosi di ginocchio che port\uf2 ad una stabilizzazione con postumi

Recreational inhalation of butane and propane in adolescents: two forensic cases of accidental death

The recreational use of inhalants is a fairly widespread habit among adolescents because of the ease of availability and methods of assumption. Their use is however not free of risks, both for direct toxicity on several target organs and for a mechanism of gas replacement with lack of oxygen. The first case concerns a 12-year-old boy who died suddenly after sniffing a mix of butane and propane contained in a can of air freshener. The second case concerns a 14-year-old boy who died by acute poisoning by the same mixture contained in a refill for lighters. High concentrations of the compounds were found in the tissues by analysis with gas chromatography-mass spectrometry. The compounds found in tissues and biological fluids were perfectly compatible with those contained in the containers used for the inhalation. The mechanisms of death were therefore assessed in a combination of the direct toxicity of the compound and oxygen replacement, thus highlighting the crucial help that toxicological analyses can provide in such cases

Aqua Virgo: first characterization of mortars and plasters from the inner duct

Aqua Virgo is the ancient Roman aqueduct, inaugurated in 19 BC, that today still carries water to Fontana di Trevi. It is the only aqueduct built by ancient Romans for their capital that never stopped working, even when all the other aqueducts have been damaged during barbarian invasions (Pace, 2010). Two sectors of the inner underground duct of the aqueduct have been explored in this research: one still functioning area located under Pincian Hill, from San Sebastianello reservoir to the spiral staircase of Villa Medici, and one segment (now in disuse) between Via del Nazareno, Via dei Due Macelli and Via del Tritone. A total of 17 mortars and plasters samples have been collected from different parts of the inner duct (vault, lateral walls, inner part of walls, covering plasters) and 3 samples also from the cocciopesto of a duct that intersect Aqua Virgo just before Via del Nazareno, named “Y” (Baumgartner, 2017). A multi-analytical approach has been applied for the archaeometric characterization of the materials constituting the binder and the aggregate, and the reactions occurred between them: optical microscopy in thin section (OM), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM-EDS), and thermogravimetric analysis on the binder fraction (TGA). As Aqua Virgo has a millenary working history, the aim of this work is to characterize what are supposed to be original materials from the Roman period and compare them with subsequent restorations; also, to compare the samples from aqueduct “Y”, whom attribution is still unknown (but it is supposed to be antecedent), with the ones of Aqua Virgo. REFERENCES Baumgartner M. (2017) - Roma rinascente: la città antica tra Quirinale e Pincio. De Luca editori d'arte, 295 pp. Pace P. (2010) - Acquedotti di Roma e il De aquaeductu di Frontino. Consiglio Nazionale delle Ricerche (CNR), 326 pp