Convection and the Extracellular Matrix Dictate Inter- and Intra-Biofilm Quorum Sensing Communication in Environmental Systems.

The mechanisms and impact of bacterial quorum sensing (QS) for the coordination of population-level behaviors are well studied under laboratory conditions. However, it is unclear how, in otherwise open environmental systems, QS signals accumulate to sufficient concentration to induce QS phenotypes, especially when quorum quenching (QQ) organisms are also present. We explore the impact of QQ activity on QS signaling in spatially organized biofilms in scenarios that mimic open systems of natural and engineered environments. Using a functionally differentiated biofilm system, we show that the extracellular matrix, local flow, and QQ interact to modulate communication. In still aqueous environments, convection facilitates signal dispersal while the matrix absorbs and relays signals to the cells. This process facilitates inter-biofilm communication even at low extracellular signal concentrations. Within the biofilm, the matrix further regulates the transport of the competing QS and QQ molecules, leading to heterogenous QS behavior. Importantly, only extracellular QQ enzymes can effectively control QS signaling, suggesting that the intracellular QQ enzymes may not have evolved to degrade environmental QS signals for competition

Temperature-scaling behavior of the Hall conductivity for Hg-based superconducting thin films

The Hall conductivities of HgBa_{2}CaCu_{2}O_{6+\delta}and HgBa_{2}Ca_{2}Cu_{3}O_{8+\delta} thin films are investigated for a magnetic field parallel to the c axis. The mixed-state Hall conductivity for these compounds is well described by \sigma_{xy}=C_{1}/H+C_{2}+C_{3}H. The prefactor C_1 shows a temperature dependence of the form C_1 = A(1-t)^n near T_c, where t=T/T_c is the reduced temperature. Contrary to the previous results, C_2 also follows a temperature-scaling behavior similar to that of the coefficient C_1. The observed value of n = 1.8 - 2.3 is comparable to the previously observed values for YBa_{2}Cu_{3}O_{7-\delta} and La_{2-x}Sr_{x}CuO_{4}.Comment: 5 pages, 4 eps figure

Expression of heterologous proteins flanked by NS3-4A cleavage sites within the hepatitis C virus polyprotein

AbstractHepatitis C virus (HCV) contributes substantially to human morbidity and mortality world-wide. The development of HCV genomes expressing heterologous proteins has enhanced the ability to study viral infection, but existing systems have drawbacks. Recombinant viruses often require adaptive mutations to compensate for reduced viral titers, or rely on an artificial genomic organization that uncouples viral protein expression from recombinant gene expression. Here, we sought to exploit the viral polyprotein processing machinery to express heterologous proteins within the context of the HCV polyprotein. We show that HCV genotypes 2a and 1b permit insertion of reporter proteins between NS5A and NS5B with minimal impact on viral fitness. Using this strategy we constructed reporter genomes exhibiting a wide dynamic range, simplifying analysis of HCV infection in primary hepatocytes. Expression of heterologous proteins within the HCV genome offers new opportunities to analyze HCV infection in experimental systems without perturbing functions of individual viral proteins

A rodent model of HIV protease inhibitor indinavir induced peripheral neuropathy

The research leading to these results is part of the EUROPAIN Collaboration, which has received support from the Innovative Medicines Initiative Joint Undertaking, under grant agreement no 115007, resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007‐2013) and EFPIA companies’ in kind contribution. We thank Pfizer for providing indinavir and gabapentin. MC received Conicyt grant (Folio 82130016),to complete this work.Peer reviewedPostprin

Giant Fibrovascular Polyp of the Hypopharynx: Surgical Treatment with the Biappoach

Fibrovascular polyps of the esophagus and hypopharynx are benign tumors of the upper digestive tract. The majority of these polyps are located in the upper part of the esophagus but the hypopharyngeal fibrovascular polyps are only rarely seen. Most of them are surgically treated and this is usually done through a cervical incision, although some of them have been removed endoscopically. The authors report here on a case of a 63-yr-old-man with a giant fibrovascular polyp of the hypopharynx that extended into the stomach; this polyp was removed through simultaneous transcervical and transabdominal approaches because of the huge size of the polyp. The man presented with progressive dysphagia of 1 yr duration. The preoperative assessment revealed a giant polyp arising from the left arytenoid and extending into the stomach. The dimension of the polyp was about 26×10×4 cm. The complete resection of the polyp with the simultaneous transcervical and transabdominal approaches was successful, and it was diagnosed as a fibrovascular polyp. The patient has been followed up without any recurrence for 6 month postoperatively

RAB23 coordinates early osteogenesis by repressing FGF10-pERK1/2 and GLI1

Mutations in the gene encoding Ras-associated binding protein 23 (RAB23) cause Carpenter Syndrome, which is characterized by multiple developmental abnormalities including polysyndactyly and defects in skull morphogenesis. To understand how RAB23 regulates skull development, we generated Rab23-deficient mice that survive to an age where skeletal development can be studied. Along with polysyndactyly, these mice exhibit premature fusion of multiple sutures resultant from aberrant osteoprogenitor proliferation and elevated osteogenesis in the suture. FGF10-driven FGFR1 signaling is elevated in Rab23(-/-) sutures with a consequent imbalance in MAPK, Hedgehog signaling and RUNX2 expression. Inhibition of elevated pERK1/2 signaling results in the normalization of osteoprogenitor proliferation with a concomitant reduction of osteogenic gene expression, and prevention of craniosynostosis. Our results suggest a novel role for RAB23 as an upstream negative regulator of both FGFR and canonical Hh-GLI1 signaling, and additionally in the non-canonical regulation of GLI1 through pERK1/2.Peer reviewe

HAltORF: a database of predicted out-of-frame alternative open reading frames in human

Human alternative open reading frames (HAltORF) is a publicly available and searchable online database referencing putative products of out-of-frame alternative translation initiation (ATI) in human mRNAs. Out-of-frame ATI is a process by which a single mRNA encodes independent proteins, when distinct initiation codons located in different reading frames are recognized by a ribosome to initiate translation. This mechanism is largely used in viruses to increase the coding potential of small viral genomes. There is increasing evidence that out-of-frame ATI is also used in eukaryotes, including human, and may contribute to the diversity of the human proteome. HAltORF is the first web-based searchable database that allows thorough investigation in the human transcriptome of out-of-frame alternative open reading frames with a start codon located in a strong Kozak context, and are thus the more likely to be expressed. It is also the first large scale study on the human transcriptome to successfully predict the expression of out-of-frame ATI protein products that were previously discovered experimentally. HAltORF will be a useful tool for the identification of human genes with multiple coding sequences, and will help to better define and understand the complexity of the human proteome

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al

Effect of stress-triaxiality on void growth in dynamic fracture of metals: a molecular dynamics study

The effect of stress-triaxiality on growth of a void in a three dimensional single-crystal face-centered-cubic (FCC) lattice has been studied. Molecular dynamics (MD) simulations using an embedded-atom (EAM) potential for copper have been performed at room temperature and using strain controlling with high strain rates ranging from 10^7/sec to 10^10/sec. Strain-rates of these magnitudes can be studied experimentally, e.g. using shock waves induced by laser ablation. Void growth has been simulated in three different conditions, namely uniaxial, biaxial, and triaxial expansion. The response of the system in the three cases have been compared in terms of the void growth rate, the detailed void shape evolution, and the stress-strain behavior including the development of plastic strain. Also macroscopic observables as plastic work and porosity have been computed from the atomistic level. The stress thresholds for void growth are found to be comparable with spall strength values determined by dynamic fracture experiments. The conventional macroscopic assumption that the mean plastic strain results from the growth of the void is validated. The evolution of the system in the uniaxial case is found to exhibit four different regimes: elastic expansion; plastic yielding, when the mean stress is nearly constant, but the stress-triaxiality increases rapidly together with exponential growth of the void; saturation of the stress-triaxiality; and finally the failure.Comment: 35 figures, which are small (and blurry) due to the space limitations; submitted (with original figures) to Physical Review B. Final versio

Single Particle and Fermi Liquid Properties of He-3/--He-4 Mixtures: A Microscopic Analysis

We calculate microscopically the properties of the dilute He-3 component in a He-3/--He-4 mixture. These depend on both, the dominant interaction between the impurity atom and the background, and the Fermi liquid contribution due to the interaction between the constituents of the He-3 component. We first calculate the dynamic structure function of a He-3 impurity atom moving in He-3. From that we obtain the excitation spectrum and the momentum dependent effective mass. The pole strength of this excitation mode is strongly reduced from the free particle value in agreement with experiments; part of the strength is distributed over high frequency excitations. Above k > 1.7$\AA$^{-1}$ the motion of the impurity is damped due to the decay into a roton and a low energy impurity mode. Next we determine the Fermi--Liquid interaction between He-4 atoms and calculate the pressure-- and concentration dependence of the effective mass, magnetic susceptibility, and the He-3--He-3 scattering phase shifts. The calculations are based on a dynamic theory that uses, as input, effective interactions provided by the Fermi hypernetted--chain theory. The relationship between both theories is discussed. Our theoretical effective masses agree well with recent measurements by Yorozu et al. (Phys. Rev. B 48, 9660 (1993)) as well as those by R. Simons and R. M. Mueller (Czekoslowak Journal of Physics Suppl. 46, 201 (1996)), but our analysis suggests a new extrapolation to the zero-concentration limit. With that effective mass we also find a good agreement with the measured Landau parameter F_0^a.Comment: 47 pages, 15 figure