Bioinformatic analysis of the Delta SARS-CoV-2 genome reveals a single nucleotide mutation (G15U) in the stem-loop II motif (s2m) relative to ancestral SARS-CoV-2. Despite sequence similarity, ...unexpected differences between SARS-CoV-2 and Delta SARS-CoV-2 s2m homodimerization experiments require the discovery of unknown structural and thermodynamic changes necessary to rationalize the data. Using our reported SARS-CoV-2 s2m model, we induced the G15U substitution and performed 3.5 microseconds of unbiased molecular dynamics simulation at 283 and 310 K. The resultant Delta s2m adopted a secondary structure consistent with our reported NMR data, resulting in significant deviations in the tertiary structure and dynamics from our SARS-CoV-2 s2m model. First, we find differences in the overall three-dimensional structure, where the characteristic 90° L-shaped kink of the SARS-CoV-2 s2m did not form in the Delta s2m resulting in a “linear” hairpin with limited bending dynamics. Delta s2m helical parameters are calculated to align closely with A-form RNA, effectively eliminating a hinge point to form the L-shape kink by correcting an upper stem defect in SARS-CoV-2 induced by a noncanonical and dynamic G:A base pair. Ultimately, the shape difference rationalizes the migration differences in reported electrophoresis experiments. Second, increased fluctuation of the Delta s2m palindromic sequence, within the terminal loop, compared to SARS-CoV-2 s2m results in an estimated increase of entropy of 6.8 kcal/mol at 310 K relative to the SARS-CoV-2 s2m. The entropic difference offers a unique perspective on why the Delta s2m homodimerizes less spontaneously, forming fewer kissing dimers and extended duplexes compared to SARS-CoV-2. In this work, both the L-shape reduction and palindromic entropic penalty provides an explanation of our reported in vitro electrophoresis homodimerization results. Ultimately, the structural, dynamical, and entropic differences between the SARS-CoV-2 s2m and Delta s2m serve to establish a foundation for future studies of the s2m function in the viral lifecycle.
Background
Parastomal hernias can be prevented or repaired using synthetic mesh; however, reported complications include infection, fibrosis and potential bowel erosion. The study aim was to assess ...the safety, feasibility and potential efficacy of using a prophylactic collagen implant.
Methods
Twenty patients undergoing defunctioning stomas were randomised to a conventional procedure or reinforcement with the implant. Follow-up included regular symptom questionnaires, clinical examination, stoma site ultrasound, and serum inflammatory markers.
Results
Ten patients (four males; mean BMI 26.3) had a conventional stoma, and ten (three males; mean BMI 26.3) received the implant. At a median of 6.5 months follow-up, a parastomal hernia was clinically evident in three of ten patients without the implant, and in none of ten patients with the implant. There were no clinical complications, ultrasound evidence of chronic seromas or serological evidence of a systemic inflammatory response.
Conclusions
Xenogeneic collagen has been demonstrated to aid soft tissue reinforcement. In this study, in contrast to published data relating to the use of conventional synthetic mesh, there were no complications related to infection or the implant’s proximity to the bowel. This trial demonstrates that the implant is safe, feasible to use and has the potential to prevent parastomal herniation.
Kudzu Pueraria montana variety lobata (Willd.) Maesen & S. M. Almeida plant architecture and growth were compared for plants subjected to 4 wk of simulated herbivory (75% leaf cutting) and no damage. ...Simulated herbivory reduced above-ground and root biomass by 40 and 47%, respectively, whereas total vine length and average length of the 10 longest vines were reduced by 48 and 43%, respectively, compared with control plants. Plant architecture was also affected, with damaged plants showing a significantly reduced proportion of primary vines, shorter secondary vines, and reduced average internode distances compared with the control plants. In natural situations, these changes would reduce the ability of kudzu to compete for light and other resources by affecting the plant's climbing habit.
The performance of the GlueX Forward Calorimeter was studied using a small version of the detector and a variable energy electron beam derived from the Hall B tagger at Jefferson Lab. For electron ...energies from 110MeV to 260MeV, which are near the lower-limits of the design sensitivity, the fractional energy resolution was measured to range from 20% to 14%, which meets the design goals. The use of custom 250MHz flash ADCs for readout allowed precise measurements of signal arrival times. The detector achieved timing resolutions of 0.38ns for a single 100mV pulse, which will allow timing discrimination of photon beam bunches and out-of-time background during the operation of the GlueX detector.
•A beam test was conducted for a miniature of the GlueX Forward Calorimeter.•The energy resolution at low energies was found to be consistent with design goals.•The timing resolution of the incidence of events was measured with flash ADCs.•The timing resolution was confirmed to be adequate for discriminating beam bunches.
To detect antimicrobial resistance genes in Salmonella isolates from turkey flocks using the microarray technology. A 775 gene probe oligonucleotide microarray was used to detect antimicrobial ...resistance genes in 34 isolates. All tetracycline-resistant Salmonella harboured tet(A), tet(C) or tet(R), with the exception of one Salmonella serotype Heidelberg isolate. The sul1 gene was detected in 11 of 16 sulfisoxazole-resistant isolates. The aadA, aadA1, aadA2, strA or strB genes were found in aminoglycoside-resistant isolates of Salm. Heidelberg, Salmonella serotype Senftenberg and untypeable Salmonella. The prevalence of mobile genetic elements, such as class I integron and transposon genes, in drug-resistant Salmonella isolates suggested that these elements may contribute to the dissemination of antimicrobial resistance genes in the preharvest poultry environment. Hierarchical clustering analysis demonstrated a close relationship between drug-resistant phenotypes and the corresponding antimicrobial resistance gene profiles. Salmonella serotypes isolated from the poultry environment carry multiple genes that can render them resistant to several antimicrobials used in poultry and humans. Multiple antimicrobial resistance genes in environmental Salmonella isolates could be identified efficiently by microarray analysis. Hierarchical clustering analysis of the data was also found to be a useful tool for analysing emerging patterns of drug resistance.
Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of this traditional usage, dietary supplements containing ...turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding antiarthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well-characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.
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