Melting temperatures, T(m), were systematically studied for a set of 92 DNA duplex oligomers in a variety of sodium ion concentrations ranging from 69 mM to 1.02 M. The relationship between T(m) and ln [Na(+)] was nonlinear over this range of sodium ion concentrations, and the observed melting temperatures were poorly predicted by existing algorithms. A new empirical relationship was derived from UV melting data that employs a quadratic function, which better models the melting temperatures of DNA duplex oligomers as sodium ion concentration is varied. Statistical analysis shows that this improved salt correction is significantly more accurate than previously suggested algorithms and predicts salt-corrected melting temperatures with an average error of only 1.6 degrees C when tested against an independent validation set of T(m) measurements obtained from the literature. Differential scanning calorimetry studies demonstrate that this T(m) salt correction is insensitive to DNA concentration. The T(m) salt correction function was found to be sequence-dependent and varied with the fraction of G.C base pairs, in agreement with previous studies of genomic and polymeric DNAs. The salt correction function is independent of oligomer length, suggesting that end-fraying and other end effects have little influence on the amount of sodium counterions released during duplex melting. The results are discussed in the context of counterion condensation theory.

Technologies that enable the rapid detection and localization of bacterial infections in living animals could address an unmet need for infectious disease diagnostics. We describe a molecular imaging approach for the specific, non-invasive detection of S. aureus based on the activity of its secreted nuclease, micrococcal nuclease (MN). Several short, synthetic oligonucleotides, rendered resistant to mammalian serum nucleases by various chemical modifications, flanked with a fluorophore and quencher, were activated upon degradation by recombinant MN and in S. aureus culture supernatants. A probe consisting of a pair of deoxythymidines flanked by several 2′-O-methyl-modified nucleotides was activated in culture supernatants of S. aureus but not in culture supernatants of several other pathogenic bacteria. Systemic administration of this probe to mice bearing bioluminescent S. aureus muscle infections resulted in probe activation at the infection sites in an MN-dependent manner. This novel bacterial imaging approach has potential clinical applicability for S. aureus and several other medically significant pathogens.

BackgroundDyslipidemia is an important and common cardiovascular risk factor in the general population. The lipid-lowering effects of turmeric and curcumin are unconfirmed. We performed a meta-analysis to assess the efficacy and safety of turmeric and curcumin in lowering blood lipids in patients at risk of cardiovascular disease (CVD).MethodsA comprehensive literature search was conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to identify randomized controlled trials (published as of November 2016) that assessed the effect of turmeric and curcumin on blood lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effect.ResultsThe analysis included 7 eligible studies (649 patients). Turmeric and curcumin significantly reduced serum LDL-C (SMD = −0.340, 95% confidence interval [CI]: −0.530 to −0.150, P < 0.0001) and TG (SMD = −0.214, 95% CI: −0.369 to −0.059, P = 0.007) levels as compared to those in the control group. These may be effective in lowering serum TC levels in patients with metabolic syndrome (MetS, SMD = −0.934, 95% CI: −1.289 to −0.579, P < 0.0001), and turmeric extract could possibly have a greater effect on reducing serum TC levels (SMD = −0.584, 95% CI: −0.980 to −0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies.ConclusionsTurmeric and curcumin may protect patients at risk of CVD through improving serum lipid levels. Curcumin may be used as a well-tolerated dietary adjunct to conventional drugs. Further research is required to resolve uncertainties related to dosage form, dose and medication frequency of curcumin.Electronic supplementary materialThe online version of this article (10.1186/s12937-017-0293-y) contains supplementary material, which is available to authorized users.

Dicer-substrate small interfering RNAs (DsiRNAs) are synthetic RNA duplexes that are processed by Dicer into 21-mer species and show improved potency as triggers of RNA interference, particularly when used at low dose. Chemical modification patterns that are compatible with high potency 21-mer small interfering RNAs have been reported by several groups. However, modification patterns have not been studied for Dicer-substrate duplexes. We therefore synthesized a series of chemically modified 27-mer DsiRNAs and correlated modification patterns with functional potency. Some modification patterns profoundly reduced function although other patterns maintained high potency. Effects of sequence context were observed, where the relative potency of modification patterns varied between sites. A modification pattern involving alternating 2'-O-methyl RNA bases was developed that generally retains high potency when tested in different sites in different genes, evades activation of the innate immune system, and improves stability in serum.

BackgroundAlthough Tai Ji Quan has been shown to relieve pain and improve functional mobility in people with knee osteoarthritis (OA), little is known about its potential benefits on gait characteristics among older Chinese women who have a high prevalence of both radiographic and symptomatic knee OA. This study aims to assess the efficacy of a tailored Tai Ji Quan intervention on gait kinematics for older Chinese women with knee OA.MethodsA randomized controlled trial involving 46 older women in Shanghai, China, with clinically diagnosed knee OA. Randomized (1:1) participants received either a 60 min Tai Ji Quan session (n = 23) 3 times weekly or a 60 min bi-weekly educational session (n = 23) for 24 weeks. Primary outcomes were changes in gait kinematic measures from baseline to 24 weeks. Secondary outcomes included changes in scores on the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Short Physical Performance Battery (SPPB).ResultsAfter 24 weeks the Tai Ji Quan group demonstrated better performance in gait velocity (mean difference, 8.40 cm/s, p = 0.01), step length (mean difference, 3.52 cm, p = 0.004), initial contact angle (mean difference, 2.19°, p = 0.01), and maximal angle (mean difference, 2.61°, p = 0.003) of flexed knees during stance phase compared to the control group. In addition, the Tai Ji Quan group showed significant improvement in WOMAC scores (p < 0.01) (mean difference, −4.22 points in pain, p = 0.002; −2.41 points in stiffness, p < 0.001; −11.04 points in physical function, p = 0.006) and SPPB scores (mean difference, 1.22 points, p < 0.001).ConclusionAmong older Chinese women with knee OA, a tailored Tai Ji Quan intervention improved gait outcomes. The intervention also improved overall function as indexed by the WOMAC and SPPB. These results support the use of Tai Ji Quan for older Chinese adults with knee OA to both improve their functional mobility and reduce pain symptomatology.