Facile one-pot synthesis of amoxicillin-coated gold nanoparticles and their antimicrobial activity

Nanomaterials have been the object of intense study due to promising applications in a number of different disciplines. In particular, medicine and biology have seen the potential of these novel materials with their nanoscale properties for use in diverse areas such as imaging, sensing and drug vectorisation. Gold nanoparticles (GNPs) are considered a very useful platform to create a valid and efficient drug delivery/carrier system due to their facile and well-studied synthesis, easy surface functionalization and biocompatibility. In the present study, stable antibiotic conjugated GNPs were synthesised by a one-step reaction using a poorly water soluble antibiotic, amoxicillin. Amoxicillin, a member of the penicillin family, reduces the chloroauric acid to form nanoparticles and at the same time coats them to afford the functionalised nanomaterial. A range of techniques including UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA) were used to ascertain the gold/drug molar ratio and the optimum temperature for synthesis of uniform monodisperse particles in the ca. 30-40 nm size range. Amoxicillin-conjugated gold showed an enhancement of antibacterial activity against Escherichia coli compared to the antibiotic alone

Identification and characterization of Dlc1 isoforms in the mouse and study of the biological function of a single gene trapped isoform

<p>Abstract</p> <p>Background</p> <p>The Dlc1 (deleted in liver cancer 1) tumour suppressor gene codes for a RhoGTPase activating protein that is found inactivated in many tumour types. Several transcriptional isoforms have been described but the functional significance and tissue distribution of each form is presently poorly understood. Also, differences in the number of isoforms and splice variants reported still exist between different mammalian species. In order to better understand the number and function of the different variants of the Dlc1 gene in the mouse, we have carried out a detailed analysis. Extensive 3' RACE experiments were carried out in order to identify all possible Dlc1 isoforms and splice variants in the mouse. In addition, we have generated a gene trapped mouse that targets one of these isoforms in order to study its biological function. The effect of this gene trap insertion on the splicing of other isoforms has also been studied.</p> <p>Results</p> <p>In addition to the known 6.1 and 6.2 Kb transcripts of Dlc1, our study revealed the existence of a novel 7.6 Kb transcriptional isoform in the mouse, which corresponds to the human 7.4 Kb (KIAA1723) cDNA transcript. A gene trapped embryonic cell line, with an insertion between Exon 1 and 2 of the 6.1 Kb transcriptional isoform, was used to generate a transgenic mouse. This line showed a significant reduction in the expression of the trapped isoform. However, reduced expression of the other isoforms was not seen. Mice heterozygous for the gene trapped allele were phenotypically normal, but homozygous mutant embryos did not survive beyond 10.5 days post coitum. Dlc1^gt/gtembryos showed defects in the brain, heart, and placental blood vessels. Cultured serum-free mouse embryo cells from Dlc1 deficient embryos had elevated RhoA activity and displayed alterations in the organization of actin filaments and focal adhesions. The Dlc1 deficient cells also exhibited increased wound closure in an <it>in vitro </it>scratch assay.</p> <p>Conclusions</p> <p>The mouse has three major transcriptional isoforms of the Dlc1 gene that are differentially expressed in various tissues. A mouse with exon 1 of the 6.1 Kb transcript gt resulted in hypomorphic expression of Dlc1 protein and an embryonic lethal phenotype in the homozygous condition, which indicates that this isoform plays a major role in mouse development. The Dlc1 deficient cells showed altered cytoskeleton structure, increased RhoA activity and cellular migration.</p

Mathematizing Darwin

Ernst Mayr called the first part of the evolutionary synthesis the ‘Fisherian synthesis’ on account of the dominant role played by R.A. Fisher in forging a mathematical theory of natural selection together with J.B.S. Haldane and Sewall Wright in the decade 1922–1932. It is here argued that Fisher’s contribution relied on a close reading of Darwin’s work to a much greater extent than did the contributions of Haldane and Wright, that it was synthetic in contrast to their analytic approach and that it was greatly influenced by his friendship with the Darwin family, particularly with Charles’s son Leonard

An inverse approach to determine complex modulus gradient of field-aged asphalt mixtures

This study develops a new mechanical-based method to determine the complex modulus and modulus gradient of field-aged asphalt mixtures using the direct tension test. Due to the non-uniform aging nature of the field cores, the mechanical responses must be measured at different depths. Meanwhile, the monotonic load is not applied at the neutral axis of the field core specimen due to the modulus gradient, the tensile part of the strain is used and should be separated from the measurement because of the eccentric loading. The modulus gradient parameters, the location of the neutral axis, and the stress distribution are first obtained using the elastic formulas for a series of loading times. Then the complex modulus is determined using the Laplace transform and the elastic–viscoelastic correspondence principle. An inverse approach and iteration are then proposed by using the pseudo strain to accurately calculate the modulus gradient parameters after the relaxation modulus and reference modulus are determined

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Semi-Markov Graph Dynamics

In this paper, we outline a model of graph (or network) dynamics based on two ingredients. The first ingredient is a Markov chain on the space of possible graphs. The second ingredient is a semi-Markov counting process of renewal type. The model consists in subordinating the Markov chain to the semi-Markov counting process. In simple words, this means that the chain transitions occur at random time instants called epochs. The model is quite rich and its possible connections with algebraic geometry are briefly discussed. Moreover, for the sake of simplicity, we focus on the space of undirected graphs with a fixed number of nodes. However, in an example, we present an interbank market model where it is meaningful to use directed graphs or even weighted graphs.Comment: 25 pages, 4 figures, submitted to PLoS-ON

Predicting performance using background characteristics of international medical graduates in an inner-city university-affiliated Internal Medicine residency training program

<p>Abstract</p> <p>Background</p> <p>IMGs constitute about a third of the United States (US) internal medicine graduates. US residency training programs face challenges in selection of IMGs with varied background features. However data on this topic is limited. We analyzed whether any pre-selection characteristics of IMG residents in our internal medicine program are associated with selected outcomes, namely competency based evaluation, examination performance and success in acquiring fellowship positions after graduation.</p> <p>Methods</p> <p>We conducted a retrospective study of 51 IMGs at our ACGME accredited teaching institution between 2004 and 2007. Background resident features namely age, gender, self-reported ethnicity, time between medical school graduation to residency (pre-hire time), USMLE step I & II clinical skills scores, pre-GME clinical experience, US externship and interest in pursuing fellowship after graduation expressed in their personal statements were noted. Data on competency-based evaluations, in-service exam scores, research presentation and publications, fellowship pursuance were collected. There were no fellowships offered in our hospital in this study period. Background features were compared between resident groups according to following outcomes: (a) annual aggregate graduate PGY-level specific competency-based evaluation (CBE) score above versus below the median score within our program (scoring scale of 1 – 10), (b) US graduate PGY-level specific resident in-training exam (ITE) score higher versus lower than the median score, and (c) those who succeeded to secure a fellowship within the study period. Using appropriate statistical tests & adjusted regression analysis, odds ratio with 95% confidence intervals were calculated.</p> <p>Results</p> <p>94% of the study sample were IMGs; median age was 35 years (Inter-Quartile range 25th – 75th percentile (IQR): 33–37 years); 43% women and 59% were Asian physicians. The median pre-hire time was 5 years (IQR: 4–7 years) and USMLE step I & step II clinical skills scores were 85 (IQR: 80–88) & 82 (IQR: 79–87) respectively. The median aggregate CBE scores during training were: PG1 5.8 (IQR: 5.6–6.3); PG2 6.3 (IQR 6–6.8) & PG3 6.7 (IQR: 6.7 – 7.1). 25% of our residents scored consistently above US national median ITE scores in all 3 years of training and 16% pursued a fellowship.</p> <p>Younger residents had higher aggregate annual CBE score than the program median (p < 0.05). Higher USMLE scores were associated with higher than US median ITE scores, reflecting exam-taking skills. Success in acquiring a fellowship was associated with consistent fellowship interest (p < 0.05) and research publications or presentations (p <0.05). None of the other characteristics including visa status were associated with the outcomes.</p> <p>Conclusion</p> <p>Background IMG features namely, age and USMLE scores predict performance evaluation and in-training examination scores during residency training. In addition enhanced research activities during residency training could facilitate fellowship goals among interested IMGs.</p