Natural product libraries: Assembly, maintenance, and screening

This review discusses successful strategies and potential pitfalls to assembling a natural product-based library suitable for high-throughput screening. Specific extraction methods for plants, microorganisms, and marine invertebrates are detailed, along with methods for generating a fractionated sub-library. The best methods to store, maintain and prepare the library for screening are addressed, as well as recommendations on how to develop a robust high-throughput assay. Finally, the logistics of moving from an assay hit to pure bioactive compound are discussed

Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.

BACKGROUND:Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain. METHODS AND FINDINGS:This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration. CONCLUSIONS:We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain

Large-effect flowering time mutations reveal conditionally adaptive paths through fitness landscapes in Arabidopsis thaliana.

Contrary to previous assumptions that most mutations are deleterious, there is increasing evidence for persistence of large-effect mutations in natural populations. A possible explanation for these observations is that mutant phenotypes and fitness may depend upon the specific environmental conditions to which a mutant is exposed. Here, we tested this hypothesis by growing large-effect flowering time mutants of Arabidopsis thaliana in multiple field sites and seasons to quantify their fitness effects in realistic natural conditions. By constructing environment-specific fitness landscapes based on flowering time and branching architecture, we observed that a subset of mutations increased fitness, but only in specific environments. These mutations increased fitness via different paths: through shifting flowering time, branching, or both. Branching was under stronger selection, but flowering time was more genetically variable, pointing to the importance of indirect selection on mutations through their pleiotropic effects on multiple phenotypes. Finally, mutations in hub genes with greater connectedness in their regulatory networks had greater effects on both phenotypes and fitness. Together, these findings indicate that large-effect mutations may persist in populations because they influence traits that are adaptive only under specific environmental conditions. Understanding their evolutionary dynamics therefore requires measuring their effects in multiple natural environments

Prismatine: Revalidation for Boron-Rich Compositions in the Kornerupine Group

Kornerupine and prismatine were introduced independently by Lorenzen in 1884 (but published in 1886 and 1893) and by Sauer in 1886, respectively. Ussing (1889) showed that the two minerals were sufficiently close crystallographically and chemically to be regarded as one species. However, recent analyses of boron using the ion microprobe and crystal structure refinement, indicate that the boron content of one tetrahedral site in kornerupine ranges from 0 to 1. Kornerupine and prismatine, from their respective type localities of Fiskenaesset, Greenland and Waldheim, Germany, are distinct minerals, members of an isomorphic series differing in boron content. For this reason, we re-introduce Sauer\u27s name prismatine for kornerupines with B \u3e 0.5 atoms per formula unit (p.f.u.) of 22(O,OH,F), and restrict the name kornerupine sensu stricto to kornerupines with B \u3c 0.5 p.f.u. Kornerupine sensu lato is an appropriate group name for kornerupine of unknown boron content. Kornerupine sensu stricto and prismatine from the type localities differ also in Fe2+/Mg ratio, Si - (Mg + Fe2+ + Mn) content, Al content, F content, colour, density, cell parameters, and paragenesis. Both minerals formed under granulite-facies conditions with sapphirine and phlogopite, but kornerupine sensu stricto is associated with anorthite and homblende or gedrite, whereas prismatine is found with oligoclase (An9-13), sillimanite, garnet, and/or tourmaline. Occurrences at other localities suggest that increasing boron content extends the stability range of prismatine relative to that of kornerupine sensu stricto

Henry Cadell’s Experimental Researches in Mountain Building : their lessons for interpreting thrust systems and fold-thrust structures

Funding The Fold-Thrust Research Group has been funded by InterOil, Santos, OilSearch and NAGRA. The original compilation of Cadell’s researches was part of an outreach programme funded by BP. Acknowledgements RWHB is indebted to the late John Mendum for arranging access to Cadell’s notebooks and his field maps that were lodged in the then offices of the British Geological Survey in Murchison House, Edinburgh. This formed part of a collaboration with BGS and the development of the “Assynt’s Geology” website in the early 2000s. Many of the images from Cadell’s notebooks, including his experimental results, were part of this site. Regrettably it has not been maintained and is no longer accessible. Rectifying this loss of resource forms the motivation for this contribution. We thank Juergen Adam and an anonymous referee for construct reviews, together with James Hammerstein for shepherding the manuscript through the editing process, although of course the views expressed in this paper remain the responsibility of the authors alone.Peer reviewedPostprin

Reliability of Sprint Acceleration Performance and Three Repetition Maximum Back Squat Strength in Hurling Players

The purpose of this study was to estimate the inter-day reliability of 5, 10 and 20-meter sprint time and three repetition maximum back squat strength in male hurling players. Eighteen male hurling players volunteered to participate and performed 20- meter sprint trials and a three repetition maximum back squat strength test at each test session, on three separate occasions, a minimum of 48 hours apart. Participants performed three sprints over 20-meters, including split times at 5 and 10-meters. The three repetition back squat strength test was performed after the sprint test. The results displayed acceptable levels of reliability for sprint performance times (Intra class correlation coefficient single measure range: 0.76-0.89; Coefficient of variance range: 1.0 – 2.0%) and absolute and relative three repetition maximum back squat strength (Intra class correlation coefficient single measure: 0.98; CV 0.8%). Furthermore, sprint performance times and three repetition maximum back squat strength measures estimated feasible minimum a priori sample sizes from limits of agreement (5-meter:0.01 ± 0.08 s; 10-meter:-0.01 ± 0.12; 20-meter:-0.007 ± 0.15s; three repetition maximum (kg): 1.11 ± 4.19kg; three repetition maximum (kg/BW): 0.01 ± 0.06) random error therefore showing acceptable reliability. Sprint performance over 5, 10 and 20-meters and three repetition maximum back squat strength are reliable measures in male hurling players and can be used to estimate feasible minimum a priori sample sizes for sport science research

Criterion Intervals for Pretreatment Drinking Measures in Treatment Evaluation

Drinking during a 30-day pretreatment period was found not to be representative of longer pretreatment intervals, especially in a population of seriously impaired inpatient alcoholic

Neuromuscular and Bounce Drop-Jump Responses to Different Inter-Repetition Rest Intervals during A Composite Training Session in Hurling Players

The purposes of this study were to a) compare a 4-min to an 8-min rest interval between composite training (jump-sprint combination) repetitions in a single session to allow for the recovery of neuromuscular and bounce drop-jump (BDJ) performance and b) investigate if super compensation would occur after 168hrs of rest. Twelve players were randomly assigned to either a 4-min or an 8-min rest interval group. Participants first completed a BDJ test to identify individual BDJ drop heights followed by a 20m sprint test. Seventy-two hours later, a composite training session of two repetitions (three BDJs followed by a 20m sprint after a 15s rest) with either a 4-min or an 8-min rest interval was performed. A three repetition maximum (3RM) back squat strength test, a BDJ, countermovement jump (CMJ) and a sprint performance test were completed 10-mins pre- and immediately post-session, and 168 hrs post-session. CMJ force (8-min group) and BDJ (height and reactive strength index (RSI)) measures decreased significantly post-session (4-min and 8-min groups; P ≤ 0.05). Pre-session to 168 hrs post-session, relative 3RM back squat strength and 20m sprint performance increased significantly for the 4-min group only (P ≤ 0.05). In conclusion, a 4-min composite training inter-repetition rest interval leads to a significant decline in BDJ measures (RSI and jump height) which may act as fatigue markers for monitoring. However, 4-mins provides sufficient recovery during the session which, in conjunction with 168 hrs of recovery, causes super compensation in neuromuscular performance in hurling players

The Reliability of Countermovement Jump Performance and the Reactive Strength Index in Identifying Drop-Jump Drop Height in Hurling Players

The purpose of this study was to estimate the inter-day reliability of countermovement jump performance (CMJ) and the reactive strength index (RSI) in identifying drop-jump drop height in male hurling players. Eighteen male hurling players volunteered to participate. Subjects performed the CMJ and drop-jump test for RSI during the same sessions on three separate occasions a minimum of 48 hours apart. Subjects performed three CMJs and two drop-jumps from five different heights in an incremental manner (0.20, 0.30, 0.40, 0.50, 0.60 m). The results displayed acceptable levels of relative and absolute reliability for the following CMJ measures: height, velocity, force, power and average eccentric rate of force development measures (RFD). Absolute and relative peak concentric rate of force development from the CMJ test were found to have low levels of absolute reliability due to high CV% values. RSI and identified drop height from the drop-jump test displayed acceptable reliability (ICC single measure = 0.88 and 0.92 respectively; CV% = 6% and 10% respectively). Furthermore, limits of agreement random error displayed acceptable reliability for CMJ and drop-jump measures from estimated feasible minimum a priori sample sizes based upon limits of agreement. In conclusion, CMJ force-time measures (excluding peak concentric RFD measures), RSI and the identified drop height have acceptable absolute and relative reliability. For the sport science practitioner involved in hurling and for hurling players, this means that the CMJ test is reliable for kinetic and kinematic variables and the drop-jump test provides a means of developing a reactive strength profile and a means of individualizing drop height for drop-jump training