No description available.

No description available.

The purpose of this study was to correlate the extent of myofibrillar disruption with muscle protein synthetic rate (MPS) following an isolated bout of concentric or eccentric elbow flexor resistance exercise. Six strength-trained males performed 8 unilateral sets of 8 repetitions at 80% concentric 1RM. The absolute amount of work performed by each arm was controlled by having both the concentrically-exercised (CON) and eccentrically-exercised (ECC) arms lift or lower the same weight through the same range and magnitude. Biopsies from biceps brachii of each arm, extracted ~21 h post -exercise, were analyzed electron microscopically to quantify myofibrillar disruption. The severity of disruption was classified as focal (FOC), moderate (MOD), or extreme (EXT). MPS of both arms was calculated from the increment in L- [1,2-¹³C₂] leucine abundance in biopsy samples relative to the mean plasma [1, 2-¹³C₂] -α-KIC enrichment at isotopic plateau using the primed-constant infusion technique over ~10 h so that the midpoint of the assessment period was ~24 h post-exercise. The severity of disruption was significantly (P < 0.001) greater in both the FOC (11.2%) and MOD (12.2%) compared to the EXT (1.6%) rating. Absolute disruption of fibers was significantly greater (P = 0.007) in the ECC (44.7%) as compared to baseline (BASE) samples (3.9%), obtained following 5 d where no arm training had occurred. In addition, ECC samples showed ~40% greater total disruption than CON samples (44.7% vs. 26.7%). Despite this, a positive correlation (r = 0.89) was found between individual values for MPS and the percentage of disrupted fibers in tissue from the ECC but not CON arm. These findings indicate that, in strength-trained males, residual myofibrillar disruption from a previous training session is essentially repaired within 5 d, but that resistance exercise induced muscle damage did not appear to provide the activating signal for elevating MPS between -21-29 h post-exercise. / Thesis / Master of Science (MSc)

Multiple antibiotic resistant bacteria continue to be a threat to the health of the world's population. Glycopeptide antibiotics are one type of drug that are used to treat these serious pathogens. Increased usage over the years has led to the emergence of bacteria which are resistant to these glycopeptide antibiotics and now the need for altered antibiotics with an increased effectiveness has arisen. 𝘚𝘵𝘳𝘦𝘱𝘵𝘰𝘮𝘺𝘤𝘦𝘴 𝘵𝘰𝘺𝘰𝘤𝘢𝘦𝘯𝘴𝘪𝘴 NRRL 15009 produces the glycopeptide antibiotic A47934. Here, the biosynthetic gene cluster for A47934 was sequenced in its entirety. All enzymes encoded by assigned open reading frames were analyzed and functions assigned where possible. The resulting biosynthesis cluster encodes all the enzymes necessary to produce A47934, as well as confer resistance and regulate the resistance response. In addition to sequencing the biosynthetic gene cluster, enzymatic studies were attempted on the two-component regulatory system (VanR and VanS) which confers resistance to A47934. Finally, inactivation of 𝘴𝘵𝘢𝘓 was attempted. Overall, the results presented here should help us to further understand how these chemically complex glycopeptide antibiotics are made and lend further insight into how we can attempt to produce new semi-synthetic versions. / Thesis / Master of Science (MSc)

Thesis / Master of Science (MS)

The synthesis and characterization of phosphorus containing poly(arylene ether)s were investigated to determine the effect of phosphorus upon the thermal stability, mechanical strength, and fire resistance of thermoplastics. Phosphorus containing activated aromatic dihalides and bisphenols were synthesized in high purity. These monomers were successfully polymerized via nucleophilic aromatic substitution to afford high molecular weight polymers. It was determined that by incorporating the phosphine oxide moiety into the polymer backbone certain properties of the resulting poly(arylene ether)s were substantially improved, such as an increase in T_g, thermal stability in air, modulus, and char yield, compared with control poly(arylene ether sulfone)s. The high char yields obtained for these polymers in air, along with observed intumescence indicates that these materials have improved fire resistance. Preliminary cone calorimetry measurements support this conclusion. In addition, the phosphine oxide group in the backbone was reduced to a phosphine and successfully converted to a phosphonium bromide ionomer. The resulting system was further chemically modified to ionically bond second-order nonlinear optical chromophores to the backbone of selected poly(arylene ether)s. Initial results on corona poling of cast film at low temperature produced stable second harmonic generation in these materials, indicating that they may have promise in nonlinear optical applications. / Ph. D.

There is significant concern that agricultural use of antimicrobials leads to spill over of antimicrobial resistance (AMR) into the general population. Animal manures contain a large and diverse reservoir of AMR genes. While poultry litter is a rich source of nitrogen, it contains an abundance of AMR genes and genetic elements associated with its dissemination. Reduce this reservoir and its potential to transmit AMR to pathogens is diminished. Methods. The ability of litter microbiota to transmit AMR was assessed using a rifampicin (Rp)-resistant Salmonella Typhimurium LT2 strain, as the recipient, and an Escherichia coli pR100, plasmid donor strain. Autoclaved poultry litter served as a negative control in plasmid transfer studies. Abundance of phenotypic AMR was assessed for litter microbiota to the antibiotics: ampicillin (Ap; 25 ï ­g/ml), chloramphenicol (Cm; 25 ï ­g/ml), streptomycin (Sm; 100 ï ­g/ml), and tetracycline (Tc; 25 ï ­g/ml). qPCR was used to estimate gene load of streptomycin-resistance and sulfonamide-resistance genes aadA and sul, respectively in the poultry litter community. AMR gene load was determined relative to total population; using 16S rRNA qPCR to estimate the total bacterial load. Different growth conditions (temperature, media) and cell densities (filter vs liquid matings) were assessed to determine conditions optimal for AMR transfer from the litter community to the recipient Salmonella strain. Results. Poultry litter contained 108 CFU/g, with Gram-negative enterics representing a minor population (< 103 CFU/g). There was high abundance of resistance to Sm (106 CFU/g) and tetracycline (107 CFU/g); and a sizeable antimicrobial resistance gene (aadA- 2.63 E+6; sul- 7.01 E+10) load in poultry litter. Autoclaving reduced viable bacterial counts by >6 log10 and the antimicrobial resistance gene load was undetectable and by 4 log10 for aadA and sul, respectively. While plasmid transfer was observed between the Salmonella recipient with R100 plasmid, no AMR Salmonella were observed in matings with live or dead, poultry litter microbiota under conditions optimal for F-plasmid transfer. Conclusions. While poultry litter microbiota contains a significant AMR gene load, potential to transmit resistance is low, under conditions commonly used to assess plasmid conjugation. Autoclaving poultry litter significantly reduces the litter resistome. Several processes (ex. composting) are currently being examined to identify one that ameliorates poultry litter. / Master of Science / There is significant concern that agricultural use of antimicrobials leads to spill over of antimicrobial resistance (AMR) into the general population. Animal manures contain a large and diverse reservoir of AMR genes. While poultry litter is a rich source of nitrogen, it contains an abundance of AMR genes and genetic elements associated with its dissemination. Reduce this reservoir and its potential to transmit AMR to pathogens is diminished. Methods. The ability of litter microbiota to transmit AMR was assessed using a rifampicin (Rp)-resistant Salmonella Typhimurium LT2 strain, as the recipient, and an Escherichia coli pR100, plasmid donor strain. Autoclaved poultry litter served as a negative control in plasmid transfer studies. Abundance of phenotypic AMR was assessed for litter microbiota to the antibiotics: ampicillin (Ap; 25 ï ­g/ml), chloramphenicol (Cm; 25 ï ­g/ml), streptomycin (Sm; 100 ï ­g/ml), and tetracycline (Tc; 25 ï ­g/ml). qPCR was used to estimate gene load of streptomycin-resistance and sulfonamide-resistance genes aadA and sul, respectively in the poultry litter community. AMR gene load was determined relative to total population; using 16S rRNA qPCR to estimate the total bacterial load. Different growth conditions (temperature, media) and cell densities (filter vs liquid matings) were assessed to determine conditions optimal for AMR transfer from the litter community to the recipient Salmonella strain. Results. Poultry litter contained 108 CFU/g, with Gram-negative enterics representing a minor population (< 103 CFU/g). There was high abundance of resistance to Sm (106 CFU/g) and tetracycline (107 CFU/g); and a sizeable antimicrobial resistance gene (aadA- 2.63 E+6; sul- 7.01 E+10) load in poultry litter. Autoclaving reduced viable bacterial counts by >6 log10 and the antimicrobial resistance gene load was undetectable and by 4 log10 for aadA and sul, respectively. While plasmid transfer was observed between the Salmonella recipient with R100 plasmid, no AMR Salmonella were observed in matings with live or dead, poultry litter microbiota under conditions optimal for F-plasmid transfer. Conclusions. While poultry litter microbiota contains a significant AMR gene load, potential to transmit resistance is low, under conditions commonly used to assess plasmid conjugation. Autoclaving poultry litter significantly reduces the litter resistome. Several processes (ex. composting) are currently being examined to identify one that ameliorates poultry litter.

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Antibiotic-resistant bacterial strains continually arise and their increasing prevalence poses significant clinical and societal challenges. Functional analyses of resistant mutants and the study of general stress responses perturbed by antibiotic treatment have yielded valuable insights into how resistance arises through mutations. However, less is known about the population dynamics and communal interactions that underlie the development of resistance through mutations. In this work, we utilize systems approaches to study the functional dynamics of bacterial populations evolving antibiotic resistance. We follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the populations less resistant constituents, in part, by producing indole, a signaling molecule generated by actively growing and unstressed cells. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and wholegenome sequencing reveals that this bacterial altruism is enabled by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other more vulnerable cells, enhancing the survival capacity of the overall population in stressful environments. Deeper studies into cooperative strategies bacteria use to evade antibiotics may prove critical for the rational design of more effective antimicrobial interventions. / 2999-01-01

Yes / The purpose of this workshop was to promote interdisciplinary learning and collaborations between UK and India in the area of bacteria and wounds, particularly when bacteria are increasingly antibiotic resistant. To this end we invited colleagues from India with clinical experience ofmanaging bacterially infected wounds in patients, particularly when antibiotic resistant (Dr Prashant Garg) and colleagues from India with expertise in developing new drug delivery systems (Prof Nikhil Singh and Dr Vamsi Venuganti) and together with UK delegates, spanning those with international experience in investigating bacterial infections (Prof Simon Foster), investigating how biofilms communicate (Prof Paul Williams), international expertise in discovering materials for antimicrobial resistance and for instruction of macrophages (Prof Morgan Alexander), expertise in developing responsive films for detecting infection in wounds using a visible signal (Prof Toby Jenkins) and other scientists working on the axis of detecting and treating infection in wounds. / MRC/DBT

Yes / During January 15th – 17th, 2017 a group of scientists met, under the auspices of the UK-India Centre for Advanced Technology for Minimizing Indiscriminate Use of Antibiotics, to discuss the further developments and potential solutions to antimicrobial resistance. This was the third work shop under this funding stream held in Hyderabad. The presentations and outcomes of the workshop are released here. Key out comes included the need to address improved treatment and detection of TB, delivery of antimicrobial peptides, potential strategies for combating beta-lactam resistance. / Medical Research Council