Movement of IS26-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS26 and Preferentially Inserts Adjacent to Another IS26

TheinsertionsequenceIS26playsakeyroleindisseminatingantibioticresistancegenesinGram-negativebacteria, forming regions containing more than one antibiotic resistance gene that are flanked by and interspersed with copies of IS26. A model presented for a second mode of IS26 movement that explains the structure of these regions involves a translocatable unit consisting of a unique DNA segment carrying an antibiotic resistance (or other) gene and a single IS copy. Structures resembling class I transposons are generated via RecA-independent incorporation of a translocatable unit next to a second IS26 such that the ISs are in direct orientation. Repeating this process would lead to arrays of resistance genes with directly oriented copies of IS26 at each end and between each unique segment. This model requires that IS26 recognizes another IS26 as a target, and in transpo- sition experiments, the frequency of cointegrate formation was 60-fold higher when the target plasmid contained IS26. This re- action was conservative, with no additional IS26 or target site duplication generated, and orientation specific as the IS26s in the cointegrates were always in the same orientation. Consequently, the cointegrates were identical to those formed via the known mode of IS26 movement when a target IS26 was not present. Intact transposase genes in both IS26s were required for high- frequency cointegrate formation as inactivation of either one reduced the frequency 30-fold. However, the IS26 target specificity was retained. Conversion of each residue in the DDE motif of the Tnp26 transposase also reduced the cointegration frequency

Effects of diabetes family history and exercise training on the expression of adiponectin and leptin and their receptors

The daughters of patients with diabetes have reduced insulin sensitivity index (ISI) scores compared with women with no family history of diabetes, but their ISI increase more in response to exercise training(1). The present study aimed to determine whether differences between these groups in exercise-induced changes in circulating adiponectin and leptin concentrations and expression of their genes and receptors in subcutaneous adipose tissue (SAT), could explain differences in the exercise-induced changes in ISI between women with and without a family history of diabetes

Field responsive mechanical metamaterials.

Typically, mechanical metamaterial properties are programmed and set when the architecture is designed and constructed, and do not change in response to shifting environmental conditions or application requirements. We present a new class of architected materials called field responsive mechanical metamaterials (FRMMs) that exhibit dynamic control and on-the-fly tunability enabled by careful design and selection of both material composition and architecture. To demonstrate the FRMM concept, we print complex structures composed of polymeric tubes infilled with magnetorheological fluid suspensions. Modulating remotely applied magnetic fields results in rapid, reversible, and sizable changes of the effective stiffness of our metamaterial motifs

Acute Effects of Ballistic and Non-ballistic Bench Press on Plyometric Push-up Performance

The purpose of this study was to examine the effects of a ballistic or non-ballistic concentric-only bench press (COBP) on subsequent plyometric push-up performance. Fourteen resistance trained men completed two separate one-repetition-maximum (1RM) testing sessions followed by three randomized experimental explosive push-up sessions. These sessions combined a heavy concentric bench press with plyometric push-ups. Using a series of 3 × 10 (condition × time) repeated measures ANOVA, comparisons were made between the effects of ballistic and non-ballistic bench presses on performance of plyometric push-ups to investigate push-up performance variables. Compared with the control condition, both ballistic and non-ballistic bench presses produced lower net impulse and take-off velocity data. No differences were found between ballistic and non-ballistic conditions comparing net impulse and take-off velocity. We conclude that the magnitude of loading used in the current investigation may have caused acute fatigue which led to lower push-up performance characteristics. This information can be used to alter loading protocols when designing complexes for the upper body, combining the bench press and plyometric push-ups

Acetarsol Suppositories: Effective Treatment for Refractory Proctitis in a Cohort of Patients with Inflammatory Bowel Disease.

BACKGROUND: Management of proctitis refractory to conventional therapies presents a common clinical problem. The use of acetarsol suppositories, which are derived from organic arsenic, was first described in 1965. Data concerning clinical efficacy and tolerability are very limited. AIM: To examine the efficacy of acetarsol suppositories for the treatment of refractory proctitis. METHODS: A retrospective analysis was performed on patients with inflammatory bowel disease treated with acetarsol suppositories between 2008 and 2014 at Addenbrooke's Hospital, Cambridge, United Kingdom. Clinical response was defined as resolution of symptoms back to baseline at the time of next clinic review. RESULTS: Thirty-nine patients were prescribed acetarsol suppositories between March 2008 and July 2014 (29 patients with ulcerative colitis, nine with Crohn's disease, and one with indeterminate colitis). Thirty-eight were included for analysis. The standard dose of acetarsol was 250 mg twice daily per rectum for 4 weeks. Clinical response was observed in 26 patients (68%). Of the 11 patients who had endoscopic assessment before and after treatment, nine (82%) showed endoscopic improvement and five (45%) were in complete remission (Wilcoxon signed-rank test p = 0.006). One patient developed a macular skin rash 1 week after commencing acetarsol, which resolved within 4 weeks of drug cessation. CONCLUSION: Acetarsol was effective for two out of every three patients with refractory proctitis. This cohort had failed a broad range of topical and systemic treatments, including anti-TNFα therapy. Clinical efficacy was reflected in significant endoscopic improvement. Adverse effects of acetarsol were rare

Temperature-dependent phenotypic variation of Campylobacter jejuni lipooligosaccharides

<p>Abstract</p> <p>Background</p> <p><it>Campylobacter jejuni </it>is a major bacterial cause of food-borne enteritis, and its lipooligosaccharide (LOS) plays an initiating role in the development of the autoimmune neuropathy, Guillain-Barré syndrome, by induction of anti-neural cross-reactive antibodies through ganglioside molecular mimicry.</p> <p>Results</p> <p>Herein we describe the existence and heterogeneity of multiple LOS forms in <it>C. jejuni </it>strains of human and chicken origin grown at 37°C and 42°C, respectively, as determined on sodium dodecyl sulphate-polyacrylamide electrophoresis gels with carbohydrate-specific silver staining and blotting with anti-ganglioside ligands, and confirmed by nuclear magnetic resonance (NMR) spectroscopy. The <it>C. jejuni </it>NCTC 11168 original isolate (11168-O) was compared to its genome-sequenced variant (11168-GS), and both were found to have a lower-M_rLOS form, which was different in size and structure to the previously characterized higher-M_rform bearing GM₁mimicry. The lower-M_rform production was found to be dependent on the growth temperature as the production of this form increased from ~5%, observed at 37°C to ~35% at 42°C. The structure of the lower-M_rform contained a β-D-Gal-(1→3)-β-D-GalNAc disaccharide moiety which is consistent with the termini of the GM₁, asialo-GM₁, GD₁, GT₁and GQ₁gangliosides, however, it did not display GM₁mimicry as assessed in blotting studies but was shown in NMR to resemble asialo-GM₁. The production of multiple LOS forms and lack of GM₁mimicry was not a result of phase variation in the genes tested of NCTC 11168 and was also observed in most of the human and chicken isolates of <it>C. jejuni </it>tested.</p> <p>Conclusion</p> <p>The presence of differing amounts of LOS forms at 37 and 42°C, and the variety of forms observed in different strains, indicate that LOS form variation may play a role in an adaptive mechanism or a stress response of the bacterium during the colonization of different hosts.</p

Centile reference chart for resting metabolic rate through the life course

OBJECTIVE: Reference centile charts are widely used for the assessment of growth and have progressed from describing height and weight to include body composition variables such as fat and lean mass. Here, we present centile charts for an index of resting energy expenditure (REE) or metabolic rate, adjusted for lean mass versus age, including both children and adults across the life course. DESIGN, PARTICIPANTS AND INTERVENTION: Measurements of REE by indirect calorimetry and body composition using dual-energy X-ray absorptiometry were made in 411 healthy children and adults (age range 6-64 years) and serially in a patient with resistance to thyroid hormone α (RTHα) between age 15 and 21 years during thyroxine therapy. SETTING: NIHR Cambridge Clinical Research Facility, UK. RESULTS: The centile chart indicates substantial variability, with the REE index ranging between 0.41 and 0.59 units at age 6 years, and 0.28 and 0.40 units at age 25 years (2nd and 98th centile, respectively). The 50th centile of the index ranged from 0.49 units (age 6 years) to 0.34 units (age 25 years). Over 6 years, the REE index of the patient with RTHα varied from 0.35 units (25th centile) to 0.28 units (<2nd centile), depending on changes in lean mass and adherence to treatment. CONCLUSION: We have developed a reference centile chart for an index of resting metabolic rate in childhood and adults, and shown its clinical utility in assessing response to therapy of an endocrine disorder during a patient's transition from childhood to adult