A Role of Glutathione-Encoding Gene (gshA) in Oxidative Stress and Antibiotic Susceptibility in Multidrug Resistant Pseudomonas aeruginosa: A Possible Drug Target

Background: Pseudomonas aeruginosa is a major causative agent of hospital- and community-acquired infections. Antibacterial treatment of the infections is often difficult due to presence of antibiotic resistant P. aeruginosa. A number of intrinsic and acquired antibiotic resistance mechanisms reported in P. aeruginosa. Recently, scavenging intracellular reactive oxygen species (ROS) has suggested as an intrinsic antibiotic resistance mechanism to all bacterial species since antibiotics induce oxidative stress in the bacterial species. However, this intrinsic resistance mechanism is currently controversial and further clarification requires. Glutathione is a sulfuhydryl (-SH)-containing tri-peptide intracellular antioxidant and serves as a scavenger of the intracellular ROS. Aim: In this study, a mutant P. aeruginosa knocked-out a gene (gshA) encoding glutathione synthetase, a gshA-complemented mutant P. aeruginosa, and their parental wild type (MPAO1) used to understand the role of glutathione in the neutralization of oxidative stress (H2O2) and antibiotic susceptibility. Approaches and Results: Bacterial killing assays showed that the mutant strain (gshA::Tn-Tc) was completely killed at 0.005% of H2O2 while the gshA-complemented and their parental strains were both completely killed at 0.01% of H2O2. Antibiotic susceptibility testing showed that the mutant strain was at least 2-fold more susceptible to all tested antibiotics than that of its parental strain. The gshA-complemented strain fully restored the susceptibility to the same antibiotics as the same levels of the parental strain. Conclusions and Discussion: The results indicate that i) glutathione is associated with neutralization of oxidative stress, ii) antibiotics induce the oxidative stress, and iii) the antibiotic-induced oxidative stress in the mutant strain may have more ROS than its parental strain which results in the increased-susceptibility to antibiotics. Overall, the results suggest that glutathione is one of the intrinsic antibiotic resistance mechanisms and may be a possible drug target to treat the untreatable multidrug resistant P. aeruginosa

Effect of Electron Beam Irradiation and Storage on the Quality Attributes of Sausages with Different Fat Contents

Sausages with different fat contents (16 or 29%) were purchased from local stores, vacuum-packaged in oxygen-impermeable bags, and irradiated at 0 or 5 kGy using a linear accelerator. The changes in quality attributes of irradiated sausages were determined during storage at 4°C. The 2-thiobarbituric acid-reactive substance values of sausages were not affected by fat content but were increased after irradiation (5 kGy). Storage for 60 d increased the 2-thiobarbituric acid-reactive substance values of nonirradiated sausages (P \u3c 0.05) but had no effect on irradiated sausages. The numbers of volatile compounds and the amounts of total volatiles were increased by irradiation in both the high-fat (29% fat) and low-fat (16% fat) sausages. Dimethyl sulfide was detected only in irradiated sausages, regardless of fat content (P \u3c 0.05), but it disappeared after 60 d of storage. Pentane and 1-heptene were detected only in irradiated samples after 60 d of storage. Low-fat sausages had greater L* values, but had lesser a* and b* values than high-fat sausages. Irradiation and storage had little effect on either the exterior or interior color (L*, a*, and b* values) of sausages. Fat content had no effect on the sensory variables of sausages, regardless of irradiation and storage. However, irradiated sausages had significantly stronger off-odors and off-flavors than nonirradiated sausages regardless of fat content (P \u3c 0.05). This indicated that fat content in sausages had a minimal effect on the quality of irradiated sausages during storage

Non-equilibrium fluctuations for linear diffusion dynamics

We present the theoretical study on non-equilibrium (NEQ) fluctuations for diffusion dynamics in high dimensions driven by a linear drift force. We consider a general situation in which NEQ is caused by two conditions: (i) drift force not derivable from a potential function and (ii) diffusion matrix not proportional to the unit matrix, implying non-identical and correlated multi-dimensional noise. The former is a well-known NEQ source and the latter can be realized in the presence of multiple heat reservoirs or multiple noise sources. We develop a statistical mechanical theory based on generalized thermodynamic quantities such as energy, work, and heat. The NEQ fluctuation theorems are reproduced successfully. We also find the time-dependent probability distribution function exactly as well as the NEQ work production distribution $P({\mathcal W})$ in terms of solutions of nonlinear differential equations. In addition, we compute low-order cumulants of the NEQ work production explicitly. In two dimensions, we carry out numerical simulations to check out our analytic results and also to get $P({\mathcal W})$. We find an interesting dynamic phase transition in the exponential tail shape of $P({\mathcal W})$, associated with a singularity found in solutions of the nonlinear differential equation. Finally, we discuss possible realizations in experiments.Comment: 13 page

The Microbe-Derived Short Chain Fatty Acid Butyrate Targets miRNA-Dependent p21 Gene Expression in Human Colon Cancer

Colonic microbiota ferment non-absorbed dietary fiber to produce prodigious amounts of short chain fatty acids (SCFAs) that benefit the host through a myriad of metabolic, trophic, and chemopreventative effects. The chemopreventative effects of the SCFA butyrate are, in part, mediated through induction of p21 gene expression. In this study, we assessed the role of microRNA(miRNA) in butyrate's induction of p21 expression. The expression profiles of miRNAs in HCT-116 cells and in human sporadic colon cancers were assessed by microarray and quantitative PCR. Regulation of p21 gene expression by miR-106b was assessed by 3′ UTR luciferase reporter assays and transfection of specific miRNA mimics. Butyrate changed the expression of 44 miRNAs in HCT-116 cells, many of which were aberrantly expressed in colon cancer tissues. Members of the miR-106b family were decreased in the former and increased in the latter. Butyrate-induced p21 protein expression was dampened by treatment with a miR-106b mimic. Mutated p21 3′UTR-reporter constructs expressed in HCT-116 cells confirmed direct miR-106b targeting. Butyrate decreased HCT-116 proliferation, an effect reversed with the addition of the miR-106b mimic. We conclude that microbe-derived SCFAs regulate host gene expression involved in intestinal homeostasis as well as carcinogenesis through modulation of miRNAs

The Microbe-Derived Short Chain Fatty Acid Butyrate Targets miRNA-Dependent p21 Gene Expression in Human Colon Cancer

Colonic microbiota ferment non-absorbed dietary fiber to produce prodigious amounts of short chain fatty acids (SCFAs) that benefit the host through a myriad of metabolic, trophic, and chemopreventative effects. The chemopreventative effects of the SCFA butyrate are, in part, mediated through induction of p21 gene expression. In this study, we assessed the role of microRNA(miRNA) in butyrate's induction of p21 expression. The expression profiles of miRNAs in HCT-116 cells and in human sporadic colon cancers were assessed by microarray and quantitative PCR. Regulation of p21 gene expression by miR-106b was assessed by 3′ UTR luciferase reporter assays and transfection of specific miRNA mimics. Butyrate changed the expression of 44 miRNAs in HCT-116 cells, many of which were aberrantly expressed in colon cancer tissues. Members of the miR-106b family were decreased in the former and increased in the latter. Butyrate-induced p21 protein expression was dampened by treatment with a miR-106b mimic. Mutated p21 3′UTR-reporter constructs expressed in HCT-116 cells confirmed direct miR-106b targeting. Butyrate decreased HCT-116 proliferation, an effect reversed with the addition of the miR-106b mimic. We conclude that microbe-derived SCFAs regulate host gene expression involved in intestinal homeostasis as well as carcinogenesis through modulation of miRNAs.</p

Calorimetric Evidence for Nodes in the Overdoped Ba(Fe0.9_{0.9}Co0.1_{0.1})2_{2}As2_{2}

We present low-temperature specific heat of the electron-doped Ba(Fe$_{0.9}$Co$_{0.1}$)$_{2}$As$_{2}$, which does not show any indication of an upturn down to 400 mK, the lowest measuring temperature. The lack of a Schottky-like feature at low temperatures or in magnetic fields up to 9 Tesla enables us to identify enhanced low-temperature quasiparticle excitations and to study anisotropy in the linear term of the specific heat. Our results can not be explained by a single or multiple isotropic superconducting gap, but are consistent with multi-gap superconductivity with nodes on at least one Fermi surface sheet.Comment: 5 pages 4 figure

Directed Ising type dynamic preroughening transition in one dimensional interfaces

We present a realization of directed Ising (DI) type dynamic absorbing state phase transitions in the context of one-dimensional interfaces, such as the relaxation of a step on a vicinal surface. Under the restriction that particle deposition and evaporation can only take place near existing kinks, the interface relaxes into one of three steady states: rough, perfectly ordered flat (OF) without kinks, or disordered flat (DOF) with randomly placed kinks but in perfect up-down alternating order. A DI type dynamic preroughening transition takes place between the OF and DOF phases. At this critical point the asymptotic time evolution is controlled not only by the DI exponents but also by the initial condition. Information about the correlations in the initial state persists and changes the critical exponents.Comment: 12 pages, 10 figure

Novel universality class of absorbing transitions with continuously varying critical exponents

The well-established universality classes of absorbing critical phenomena are directed percolation (DP) and directed Ising (DI) classes. Recently, the pair contact process with diffusion (PCPD) has been investigated extensively and claimed to exhibit a new type of critical phenomena distinct from both DP and DI classes. Noticing that the PCPD possesses a long-term memory effect, we introduce a generalized version of the PCPD (GPCPD) with a parameter controlling the memory effect. The GPCPD connects the DP fixed point to the PCPD point continuously. Monte Carlo simulations show that the GPCPD displays novel type critical phenomena which are characterized by continuously varying critical exponents. The same critical behaviors are also observed in models where two species of particles are coupled cyclically. We suggest that the long-term memory may serve as a marginal perturbation to the ordinary DP fixed point.Comment: 13 pages + 10 figures (Full paper version

Can disordered mobile phone use be considered a behavioral addiction? An update on current evidence and a comprehensive model for future research

Despite the many positive outcomes, excessive mobile phone use is now often associated with potentially harmful and/or disturbing behaviors (e.g., symptoms of deregulated use, negative impact on various aspects of daily life such as relationship problems, and work intrusion). Problematic mobile phone use (PMPU) has generally been considered as a behavioral addiction that shares many features with more established drug addictions. In light of the most recent data, the current paper reviews the validity of the behavioral addiction model when applied to PMPU. On the whole, it is argued that the evidence supporting PMPU as an addictive behavior is scarce. In particular, it lacks studies that definitively show behavioral and neurobiological similarities between mobile phone addiction and other types of legitimate addictive behaviors. Given this context, an integrative pathway model is proposed that aims to provide a theoretical framework to guide future research in the field of PMPU. This model highlights that PMPU is a heterogeneous and multi-faceted condition