Does Male Circumcision Prevent HIV Infection?

Siegfried discusses the first reported randomized controlled trial of whether circumcision protects against HIV, published in PLoS Medicine

Cereulide synthetase gene cluster from emetic Bacillus cereus: Structure and location on a mega virulence plasmid related to Bacillus anthracis toxin plasmid pXO1

BACKGROUND: Cereulide, a depsipeptide structurally related to valinomycin, is responsible for the emetic type of gastrointestinal disease caused by Bacillus cereus. Recently, it has been shown that this toxin is produced by a nonribosomal peptide synthetase (NRPS), but its exact genetic organization and biochemical synthesis is unknown. RESULTS: The complete sequence of the cereulide synthetase (ces) gene cluster, which encodes the enzymatic machinery required for the biosynthesis of cereulide, was dissected. The 24 kb ces gene cluster comprises 7 CDSs and includes, besides the typical NRPS genes like a phosphopantetheinyl transferase and two CDSs encoding enzyme modules for the activation and incorporation of monomers in the growing peptide chain, a CDS encoding a putative hydrolase in the upstream region and an ABC transporter in the downstream part. The enzyme modules responsible for incorporation of the hydroxyl acids showed an unusual structure while the modules responsible for the activation of the amino acids Ala and Val showed the typical domain organization of NRPS. The ces gene locus is flanked by genetic regions with high homology to virulence plasmids of B. cereus, Bacillus thuringiensis and Bacillus anthracis. PFGE and Southern hybridization showed that the ces genes are restricted to emetic B. cereus and indeed located on a 208 kb megaplasmid, which has high similarities to pXO1-like plasmids. CONCLUSION: The ces gene cluster that is located on a pXO1-like virulence plasmid represents, beside the insecticidal and the anthrax toxins, a third type of B. cereus group toxins encoded on megaplasmids. The ces genes are restricted to emetic toxin producers, but pXO1-like plasmids are also present in emetic-like strains. These data might indicate the presence of an ancient plasmid in B. cereus which has acquired different virulence genes over time. Due to the unusual structure of the hydroxyl acid incorporating enzyme modules of Ces, substantial biochemical efforts will be required to dissect the complete biochemical pathway of cereulide synthesis

The birth of the Alps: Ediacaran to Paleozoic accretionary processes and crustal growth along the northern Gondwana margin

New whole-rock geochemical and coupled U–Pb and Lu–Hf LA-ICP-MS zircon data of metasedimentary rocks of the Austroalpine, South Alpine and Penninic basement domains are presented, to disentangle the pre-Variscan tectonic evolution of the proto-Alps. The studied units seem to record distinct stages of protracted Late Ediacaran to Carboniferous tectonosedimentary processes prior to the Variscan collision. In the case of Austroalpine and South Alpine units, nevertheless, no major differences in terms of provenance are observed, since most detrital zircon samples are characterized by a major Pan-African peak. Their detrital zircon spectra record a provenance from the northeastern Saharan Metacraton and the Sinai basement at the northern Arabian-Nubian Shield, being thus located along the eastern Early Paleozoic northern Gondwana margin, whereas sources located further west are inferred for the Penninic Unit, which might have been placed close to the Moldanubian Unit of the Bohemian Massif. In any case, it is thus clear that the Alpine basement remained in a close position to the Gondwana mainland at least during the Early Paleozoic. The Late Ediacaran to Silurian tectonic evolution, which includes Cadomian and Cenerian tectonometamorphic and magmatic processes, seem thus to record a continuum related to a retreating-mode accretionary orogen, with diachronous back-arc basin opening and possibly discrete compressional/transpressional pulses linked to changes in subduction zone dynamics. On the other hand, it is inferred that the Alpine basement essentially comprises Pan-African metasedimentary and subordinate metaigneous rocks, possibly with very few Early Neoproterozoic relics. This basement was significantly reworked during the protracted Paleozoic orogenic evolution, due to anatexis and/or assimilation by mantle-derived juvenile magmatism.Fil: Siegesmund, Siegfried. Universität Göttingen; AlemaniaFil: Oriolo, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Schulz, Bernhard. Technische Universitat Bergakademie Freiberg; AlemaniaFil: Heinrichs, T.. Universität Göttingen; AlemaniaFil: Basei, M. A. S.. Universidade de Sao Paulo; BrasilFil: Lammerer, Bernd. Ludwig Maximilians Universitat; Alemani

Endothelial preconditioning by transient oxidative stress reduces inflammatory responses of cultured endothelial cells to TNF-α

Brief episodes of ischemia can render an organ resistant to subsequent severe ischemia. This ‘ischemic preconditioning’ is ascribed to various mechanisms, including oxidative stress. We investigated whether preconditioning exists on an endothelial level. Human umbilical vein endothelial cells (HUVECs) were transiently confronted with oxidative stress (1 mM H2O2, 5 min). Adhesion molecules ICAM-1 and E-selectin and release of cytokines IL-6 and IL-8 to subsequent stimulation with TNF-α (2.5 ng/ml, 4 h) were measured (flow cytometry and immunoassay), as were nuclear translocation of the transcription factor NFkB (Western blotting, confocal microscopy) and redox status of HUVECs (quantification of glutathione by HPLC). TNF-α elevated IL-6 in the cell supernatant from 8.8 ± 1 to 41 ± 3 pg/ml and IL-8 from 0.5 ± 0.03 to 3 ± 0.2 ng/ml. ICAM-1 was increased threefold and E-selectin rose eightfold. Oxidative stress (decrease of glutathione by 50%) reduced post-TNF-α levels of IL-6 to 14 ± 3 and IL-8 to 1 ± 0.2; the rise of ICAM-1 was completely blocked and E-selectin was only doubled. The anti-inflammatory effects of preconditioning via oxidative stress were paralleled by reduction of the translocation of NFkB on stimulation with TNF-α, and antagonized by the intracellular radical scavenger N-acetylcysteine. ‘Anti-inflammatory preconditioning’ of endothelial cells by oxidative stress may account for the inhibitory effects of preconditioning on leukocyte adhesion in vivo

Metabolites from the fungus Phoma sp. 7210, associated with Aizoon canariense.

A new metabolite, 3,16-diketoaphidicolan (1), was isolated together with four known compounds: aphidicolin (2), 17-acetyl-aphidicolin (3), (+)-eupenoxide (4), and phomoxanthone A (5) from the endophytic fungus Phoma sp. The structure of the new compound 1 was determined by spectroscopic methods (mainly extensive 1D and 2D NMR experiments and by mass spectral measurements) and confirmed by X-ray crystallography. Its absolute configuration was assigned by means of the solid-state CD/TDDFT approach comparing the solid-state CD spectrum with the TDDFT-calculated one on the X-ray geometry

Effects of Ozone Oxidative Preconditioning on TNF-α Release and Antioxidant-Prooxidant Intracellular Balance in Mice During Endotoxic Shock

Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of cell redox state by the increase of antioxidant endogenous systems in both in vivo and in vitro experimental models. Our aim is to analyze the effect of ozone oxidative preconditioning on serum TNF-α levels and as a modulator of oxidative stress on hepatic tissue in endotoxic shock model (mice treated with lipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which was administered intraperitoneally (0.2, 0.4, and 1.2 mg/kg) once daily for five days before LPS (0.1 mg/kg, intraperitoneal). TNF-α was measured by cytotoxicity on L-929 cells. Biochemical parameters such as thiobarbituric acid reactive substances (TBARS), enzymatic activity of catalase, glutathione peroxidase, and glutathione-S transferase were measured in hepatic tissue. One hour after LPS injection there was a significant increase in TNF-α levels in mouse serum. Ozone/oxygen gaseous mixture reduced serum TNF-α levels in a dose-dependent manner. Statistically significant decreases in TNF-α levels after LPS injection were observed in mice pretreated with ozone intraperitoneal applications at 0.2 (78%), 0.4 (98%), and 1.2 (99%). Also a significant increase in TBARS content was observed in the hepatic tissue of LPS-treated mice, whereas enzymatic activity of glutathion-S transferase and glutathione peroxidase was decreased. However in ozone-treated animals a significant decrease in TBARS content was appreciated as well as an increase in the activity of antioxidant enzymes. These results indicate that ozone oxidative preconditioning exerts inhibitory effects on TNF-α production and on the other hand it exerts influence on the antioxidant-prooxidant balance for preservation of cell redox state by the increase of endogenous antioxidant systems

Early Paleozoic accretionary orogens along the Western Gondwana margin

Early Paleozoic accretionary orogens dominated the Western Gondwana margin and were characterized by nearly continuous subduction associated with crustal extension and back-arc basin development. The southwestern margin is represented by Famatinian and Pampean basement realms exposed in South America, both related to the protracted Paleozoic evolution of the Terra Australis Orogen, whereas the northwestern margin is mainly recorded in Cadomian domains of Europe and adjacent regions. However, no clear relationships between these regions were so far established. Based on a compilation and reevaluation of geological, paleomagnetic, petrological, geochronological and isotopic evidence, this contribution focuses on crustal-scale tectonic and geodynamic processes occurring in Western Gondwana accretionary orogens, aiming at disentangling their common Early Paleozoic evolution. Data show that accretionary orogens were dominated by high-temperature/low-pressure metamorphism and relatively high geothermal gradients, resulting from the development of extended/hyperextended margins and bulk transtensional deformation. In this sense, retreating-mode accretionary orogens characterized the Early Paleozoic Gondwana margin, though short-lived pulses of compression/transpression also occurred. The existence of retreating subduction zones favoured mantle-derived magmatism and mixing with relatively young (meta)sedimentary sources in a thin continental crust. Crustal reworking of previous forearc sequences due to trenchward arc migration thus took place through assimilation and anatexis in the arc/back-arc regions. Therefore, retreating-mode accretionary orogens were the locus of Early Paleozoic crustal growth in Western Gondwana, intimately associated with major flare-up events, such as those related to the Cadomian and Famatian arcs. Slab roll back, probably resulting from decreasing convergence rates and plate velocities after Gondwana assembly, was a key factor for orogen-scale geodynamic processes. Coupled with synchronous oblique subduction and crustal-scale dextral deformation, slab roll back might trigger toroidal mantle flow, thus accounting for bulk dextral transtension, back-arc extension/transtension and a large-scale anticlockwise rotation of Gondwana mainland.Fil: Oriolo, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Schulz, Bernhard. Technische Universität Bergakademie Freiberg; AlemaniaFil: Geuna, Silvana Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Gonzalez, Pablo Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Negro. Sede Alto Valle. Instituto de Investigaciones en Paleobiología y Geología; ArgentinaFil: Otamendi, Juan Enrique. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente; ArgentinaFil: Sláma, Jiří. The Czech Academy of Sciences. Institute of Geology; República ChecaFil: Druguet, Elena. Universitat Autònoma de Barcelona; EspañaFil: Siegesmund, Siegfried. Universität Göttingen; Alemani

From genome to toxicity: a combinatory approach highlights the complexity of enterotoxin production in Bacillus cereus

In recent years Bacillus cereus has gained increasing importance as a food poisoning pathogen. It is the eponymous member of the Bacillus cereus sensu lato group that consists of eight closely related species showing impressive diversity of their pathogenicity. The high variability of cytotoxicity and the complex regulatory network of enterotoxin expression have complicated efforts to predict the toxic potential of new Bacillus cereus isolates. In this study, comprehensive analyses of enterotoxin gene sequences, transcription, toxin secretion and cytotoxicity were performed. For the first time, these parameters were compared in a whole set of Bacillus cereus strains representing isolates of different origin (food or food poisoning outbreaks) and of different toxic potential (enteropathogenic and apathogenic) to elucidate potential starting points of strain-specific differential toxicity. While toxin gene sequences were highly conserved and did not allow for differentiation between high and low toxicity strains, comparison of nheB and hblD enterotoxin gene transcription and Nhe and Hbl protein titers revealed not only strain-specific differences but also incongruence between toxin gene transcripts and toxin protein levels. With one exception all strains showed comparable capability of protein secretion and so far, no secretion patterns specific for high and low toxicity strains were identified. These results indicate that enterotoxin expression is more complex than expected, possibly involving the orchestrated interplay of different transcriptional regulator proteins, as well as posttranscriptional and posttranslational regulatory mechanisms plus additional influences of environmental conditions

The Conlara metamorphic complex: Lithology, provenance, metamorphic constraints on the metabasic rocks, and chime monazite dating

The Conlara Metamorphic Complex, the easternmost complex of the Sierra de San Luis, is a key unit to understand the relationship between the late Proterozoic-Early Cambrian Pampean and the Upper Cambrian-Middle Ordovician Famatinian orogenies of the Eastern Sierras Pampeanas. The Conlara Metamorphic Complex extends to the east to the foothills of the Sierra de Comechingones and to the west up the Río Guzmán shear zone. The main rock types of the CMC are metaclastic and metaigneous rocks that are intruded by Ordovician and Devonian granitoids. The metaclastic units comprise fine to medium-grained metagreywackes and scarce metapelites with lesser amounts of tourmaline schists and tourmalinites whereas the metaigneous rocks encompass basic and granitoids rocks. The former occur as rare amphibolite interlayered within the metasedimentary rocks. The granitic component corresponds to a series of orthogneisses and migmatites (stromatite and diatexite). The CMC is divided in four groups based on the dominant lithological associations: San Martin and La Cocha correspond mainly to schists and some gneisses and Santa Rosa and San Felipe encompass mainly paragneisses, migmatites and orthogneisses. The Conlara Metamoprphic Complex underwent a polyphase metamorphic evolution. The penetrative D2-S2 foliation was affected by upright, generally isoclinal, N-NE trending D3 folds that control the NNE outcrop patterns of the different groups. An earlier, relic S1 is preserved in microlithons. Discontinuous high-T shear zones within the schists and migmatites are related with D4 whereas some fine-grained discontinuous shear bands attest for a D5 deformation phase. Geochemistry of both non-migmatitic metaclastic units and amphibolites suggest that the Conlara Metamorphic Complex represents an arc related basin. Maximun depositional ages indicate a pre- 570 Ma deposition of the sediments. An ample interval between sedimentation and granite emplacement in the already metamorphic complex is indicated by the 497 ± 8 Ma age of El Peñon granite. D1-D2 history took place at 564 ± 21 Ma as indicated by one PbSL age calculated for the M2 garnet of La Cocha Group. D3 is constrained by the pervasively solid-state deformed Early Ordovician granitoids which exhibits folded xenoliths of the D1-D2 deformed metaclastic rocks. Pressure-temperature pseudosections were calculated for one amphibolite using the geologically realistic system MnNCKFMASHTO (MnO–Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–Fe2O3). Peak metamophic conditions (M2) indicate 6 kbar and 620 °C. Late chlorite on the rims and in cracks of garnet, along with titanite rims on ilmenite and matrix plagioclase breaking down to albite suggests that the P-T path moved back down. Monazite analyses yield isochron Th–U–Pb ages ranging from 446 to 418 Ma. The oldest age of 446 ± 5 Ma correspond to a migmatite from the Santa Rosa Group. Monazites in samples from the La Cocha and the San Martin group crystallized at decreasing temperatures, followed by the 418 ± 10 Ma low-Y2O3 monazites in one sample of the la Cocha Group that was also obtained from a migmatite, and would likely mark a later stage of a retrograde metamorphism New CHIME monazite ages presented here likely represent post-peak fluid assisted recrystallization that are similar to amphibole and muscovite cooling ages. Therefore the monazite ages may represent a re-equilibration of the monazite on the cooling path of the basement complex.Fil: López de Luchi, Mónica G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Martínez Dopico, Carmen Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Cutts, Kathryn Ann. Universidade do Estado de Rio do Janeiro; BrasilFil: Schulz, Bernhard. Institute of Mineralogy; AlemaniaFil: Siegesmund, Siegfried. Universität Göttingen; AlemaniaFil: Wemmer, Klaus. Universität Göttingen; AlemaniaFil: Montenegro, Teresita Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; Argentin

Effect of large magnetotactic bacteria with polyphosphate inclusions on the phosphate profile of the suboxic zone in the Black Sea

The Black Sea is the world’s largest anoxic basin and a model system for studying processes across redox gradients. In between the oxic surface and the deeper sulfidic waters there is an unusually broad layer of 10–40 m, where neither oxygen nor sulfide are detectable. In this suboxic zone, dissolved phosphate profiles display a pronounced minimum at the upper and a maximum at the lower boundary, with a peak of particulate phosphorus in between, which was suggested to be caused by the sorption of phosphate on sinking particles of metal oxides. Here we show that bacterial polyphosphate inclusions within large magnetotactic bacteria related to the genus Magnetococcus contribute substantially to the observed phosphorus peak, as they contain 26–34% phosphorus compared to only 1–5% in metal-rich particles. Furthermore, we found increased gene expression for polyphosphate kinases by several groups of bacteria including Magnetococcaceae at the phosphate maximum, indicating active bacterial polyphosphate degradation. We propose that large magnetotactic bacteria shuttle up and down within the suboxic zone, scavenging phosphate at the upper and releasing it at the lower boundary. In contrast to a passive transport via metal oxides, this bacterial transport can quantitatively explain the observed phosphate profiles.We are grateful for the competent technical assistance of Ronny Baaske, Christian Burmeister, Christin Laudan and Christian Meeske. We are greatly indebted to Cindy Lee and Bo Barker Jørgensen for providing extremely helpful comments on an earlier version of the manuscript. Horst D. Schulz and René Friedland are acknowledged for stimulating discussions on the modeling approach. We thank the captain and the crew of the R/V “Maria S. Merian” for the excellent support on board and the DFG (MSM33) and BMBF (01DK12043) for financing the cruise. The particle analysis was funded by the BMBF (03F0663A). S.B. was funded by a BONUS BLUEPRINT project (03F0679A awarded to KJ; http://blueprint- project.org), supported by BONUS (Art 185), funded jointly by the EU and the German Federal Ministry of Education and Research (BMBF). T. S. was funded by the German research foundation (DFG) (awarded to K.J., JU 367/16-1). Metagenome sequencing was done at the Swedish National Genomics Infrastructure (NGI) at SciLifeLab (Sweden).We are grateful for the competent technical assistance of Ronny Baaske, Christian Burmeister, Christin Laudan and Christian Meeske. We are greatly indebted to Cindy Lee and Bo Barker Jørgensen for providing extremely helpful comments on an earlier version of the manuscript. Horst D. Schulz and René Friedland are acknowledged for stimulating discussions on the modeling approach. We thank the captain and the crew of the R/V “Maria S. Merian” for the excellent support on board and the DFG (MSM33) and BMBF (01DK12043) for financing the cruise. The particle analysis was funded by the BMBF (03F0663A). S.B. was funded by a BONUS BLUEPRINT project (03F0679A awarded to KJ; http://blueprint- project.org), supported by BONUS (Art 185), funded jointly by the EU and the German Federal Ministry of Education and Research (BMBF). T. S. was funded by the German research foundation (DFG) (awarded to K.J., JU 367/16-1). Metagenome sequencing was done at the Swedish National Genomics Infrastructure (NGI) at SciLifeLab (Sweden)