Harmful and Beneficial Role of ROS

Reactive oxygen species (ROS) are an unavoidable byproduct of oxygen metabolism and their cellular concentrations are determined by the balance between their rates of production and their rates of clearance by various antioxidant compounds and enzymes. For a long time ROS were thought to cause exclusively toxic effects which were associated with various pathologies, including carcinogenesis, neurodegeneration, atherosclerosis, diabetes, and aging. However, to date, it is known that while prolonged exposure to high ROS concentrations may lead to various disorders, low ROS concentrations exert beneficial effects regulating cell signaling cascades

Gate-Controlled Ionization and Screening of Cobalt Adatoms on a Graphene Surface

We describe scanning tunneling spectroscopy (STS) measurements performed on individual cobalt (Co) atoms deposited onto backgated graphene devices. We find that Co adatoms on graphene can be ionized by either the application of a global backgate voltage or by the application of a local electric field from a scanning tunneling microscope (STM) tip. Large screening clouds are observed to form around Co adatoms ionized in this way, and we observe that some intrinsic graphene defects display a similar behavior. Our results provide new insight into charged impurity scattering in graphene, as well as the possibility of using graphene devices as chemical sensors.Comment: 19 pages, 4 figure

Systematic reviews: a cross-sectional study of location and citation counts

BACKGROUND: Systematic reviews summarize all pertinent evidence on a defined health question. They help clinical scientists to direct their research and clinicians to keep updated. Our objective was to determine the extent to which systematic reviews are clustered in a large collection of clinical journals and whether review type (narrative or systematic) affects citation counts. METHODS: We used hand searches of 170 clinical journals in the fields of general internal medicine, primary medical care, nursing, and mental health to identify review articles (year 2000). We defined 'review' as any full text article that was bannered as a review, overview, or meta-analysis in the title or in a section heading, or that indicated in the text that the intention of the authors was to review or summarize the literature on a particular topic. We obtained citation counts for review articles in the five journals that published the most systematic reviews. RESULTS: 11% of the journals concentrated 80% of all systematic reviews. Impact factors were weakly correlated with the publication of systematic reviews (R(2 )= 0.075, P = 0.0035). There were more citations for systematic reviews (median 26.5, IQR 12 – 56.5) than for narrative reviews (8, 20, P <.0001 for the difference). Systematic reviews had twice as many citations as narrative reviews published in the same journal (95% confidence interval 1.5 – 2.7). CONCLUSIONS: A few clinical journals published most systematic reviews. Authors cited systematic reviews more often than narrative reviews, an indirect endorsement of the 'hierarchy of evidence'

Carbohydrate hydrogels with stabilized phage particles for bacterial biosensing: bacterium diffusion studies

Bacteriophage particles have been reported as potentially useful in the development of diagnosis tools for pathogenic bacteria as they specifically recognize and lyse bacterial isolates thus confirming the presence of viable cells. One of the most representative microorganisms associated with health care services is the bacterium Pseudomonas aeruginosa, which alone is responsible for nearly 15 % of all nosocomial infections. In this context, structural and functional stabilization of phage particles within biopolymeric hydrogels, aiming at producing cheap (chromogenic) bacterial biosensing devices, has been the goal of a previous research effort. For this, a detailed knowledge of the bacterial diffusion profile into the hydrogel core, where the phage particles lie, is of utmost importance. In the present research effort, the bacterial diffusion process into the biopolymeric hydrogel core was mathematically described and the theoretical simulations duly compared with experimental results, allowing determination of the effective diffusion coefficients of P. aeruginosa in the agar and calcium alginate hydrogels tested.Financial support to Victor M. Balcao, via an Invited Research Scientist fellowship (FAPESP Ref. No. 2011/51077-8) by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo, Brazil), is hereby gratefully acknowledged

The impact of decision aids to enhance shared decision making for diabetes (the DAD study): protocol of a cluster randomized trial

Background. Shared decision making contributes to high quality healthcare by promoting a patientcentered approach. Patient involvement in selecting the components of a diabetes medication program that best match the patient's values and preferences may also enhance medication adherence and improve outcomes. Decision aids are tools designed to involve patients in shared decision making, but their adoption in practice has been limited. In this study, we propose to obtain a preliminary estimate of the impact of patient decision aids vs. usual care on measures of patient involvement in decision making, diabetes care processes, medication adherence, glycemic and cardiovascular risk factor control, and resource utilization. In addition, we propose to identify, describe, and explain factors that promote or inhibit the routine embedding of decision aids in practice. Methods. We will be conducting a mixed-methods study comprised of a cluster-randomized, practical, multicentered trial enrolling clinicians and their patients (n = 240) with type 2 diabetes from rural and suburban primary care practices (n = 8), with an embedded qualitative study to examine factors that influence the incorporation of decision aids into routine practice. The intervention will consist of the use of a decision aid (Statin Choice and Aspirin Choice, or Diabetes Medication Choice) during the clinical encounter. The qualitative study will include analysis of video recordings of clinical encounters and in-depth, semi-structured interviews with participating patients, clinicians, and clinic support staff, in both trial arms. Discussion. Upon completion of this trial, we will have new knowledge about the effectiveness of diabetes decision aids in these practices. We will also better understand the factors that promote or inhibit the successful implementation and normalization of medication choice decision aids in the care of chronic patients in primary care practices

Enhancement of Allele Discrimination by Introduction of Nucleotide Mismatches into siRNA in Allele-Specific Gene Silencing by RNAi

Allele-specific gene silencing by RNA interference (RNAi) is therapeutically useful for specifically inhibiting the expression of disease-associated alleles without suppressing the expression of corresponding wild-type alleles. To realize such allele-specific RNAi (ASP-RNAi), the design and assessment of small interfering RNA (siRNA) duplexes conferring ASP-RNAi is vital; however, it is also difficult. In a previous study, we developed an assay system to assess ASP-RNAi with mutant and wild-type reporter alleles encoding the Photinus and Renilla luciferase genes. In line with experiments using the system, we realized that it is necessary and important to enhance allele discrimination between mutant and corresponding wild-type alleles. Here, we describe the improvement of ASP-RNAi against mutant alleles carrying single nucleotide variations by introducing base substitutions into siRNA sequences, where original variations are present in the central position. Artificially mismatched siRNAs or short-hairpin RNAs (shRNAs) against mutant alleles of the human Prion Protein (PRNP) gene, which appear to be associated with susceptibility to prion diseases, were examined using this assessment system. The data indicates that introduction of a one-base mismatch into the siRNAs and shRNAs was able to enhance discrimination between the mutant and wild-type alleles. Interestingly, the introduced mismatches that conferred marked improvement in ASP-RNAi, appeared to be largely present in the guide siRNA elements, corresponding to the ‘seed region’ of microRNAs. Due to the essential role of the ‘seed region’ of microRNAs in their association with target RNAs, it is conceivable that disruption of the base-pairing interactions in the corresponding seed region, as well as the central position (involved in cleavage of target RNAs), of guide siRNA elements could influence allele discrimination. In addition, we also suggest that nucleotide mismatches at the 3′-ends of sense-strand siRNA elements, which possibly increase the assembly of antisense-strand (guide) siRNAs into RNA-induced silencing complexes (RISCs), may enhance ASP-RNAi in the case of inert siRNA duplexes. Therefore, the data presented here suggest that structural modification of functional portions of an siRNA duplex by base substitution could greatly influence allele discrimination and gene silencing, thereby contributing to enhancement of ASP-RNAi

Mapping Dirac quasiparticles near a single Coulomb impurity on graphene

The response of Dirac fermions to a Coulomb potential is predicted to differ significantly from how non-relativistic electrons behave in traditional atomic and impurity systems. Surprisingly, many key theoretical predictions for this ultra-relativistic regime have not been tested. Graphene, a two-dimensional material in which electrons behave like massless Dirac fermions, provides a unique opportunity to test such predictions. Graphene’s response to a Coulomb potential also offers insight into important material characteristics, including graphene’s intrinsic dielectric constant, which is the primary factor determining the strength of electron–electron interactions in graphene. Here we present a direct measurement of the nanoscale response of Dirac fermions to a single Coulomb potential placed on a gated graphene device. Scanning tunnelling microscopy was used to fabricate tunable charge impurities on graphene, and to image electronic screening around them for a Q = +1|e| charge state. Electron-like and hole-like Dirac fermions were observed to respond differently to a Coulomb potential. Comparing the observed electron–hole asymmetry to theoretical simulations has allowed us to test predictions for how Dirac fermions behave near a Coulomb potential, as well as extract graphene’s intrinsic dielectric constant: ε[subscript g] = 3.0±1.0. This small value of ε[subscript g] indicates that electron–electron interactions can contribute significantly to graphene properties.United States. Office of Naval Research. Multidisciplinary University Research Initiative (Award N00014-09-1-1066)United States. Dept. of Energy. Office of Science (Contract DE-AC02-05CH11231)National Science Foundation (U.S.) (Award DMR-0906539