AMPK and PGC-α following maximal and supramaximal exercise in men and women: a randomized cross-over study.

We tested the hypothesis that AMPK activation and peroxisome proliferator gamma coactivator 1 alpha (PGC-1α) expression are not augmented as exercise intensity (power output) increases from maximal to supramaximal intensities and conducted an exploratory analysis comparing AMPK activation and PGC-1α expression in males and females. Seventeen (n = 9 males; n = 8 females) recreationally active, healthy, young individuals volunteered to participate in the current study. Participants completed work matched interval exercise at 100% (Max) and 133% (Supra) of peak work rate (WRpeak). Intervals were 1 min in duration and participants were prescribed 6 and 8 intervals of Max and Supra, respectively, to equate external work across protocols. PGC-1α mRNA expression and activation of AMPK (p-ACC) were examined in muscle biopsy samples. Interval WR (watts; W), intensity (%WRpeak) and average HR (bpm), blood lactate (mmol/L) and rating of perceived exertion were all higher (all p < 0.05) in Supra. Fatigue was greater (p < 0.05) in Supra. PGC-1α mRNA expression significantly increased after exercise in Max (p < 0.01) and Supra (p < 0.01), but was not significantly different (p = 0.71) between intensities. A main effect of time (Pre - 0 h) (p < 0.01) was observed for p-ACC; however, no effect of intensity (p = 0.08) or interaction (p = 0.97) was observed. No significant effects of time (p = 0.05) intensity (p = 0.42), or interaction (p = 0.97) were observed for p-AMPK (Thr172). Exploratory sex analysis demonstrated a main effect of sex for p-ACC (greater p-ACC in males; p < 0.05) but not for p-AMPK or PGC-1α expression. Our results confirm that AMPK-PGC-1α signalling is not augmented following supramaximal exercise and provide novel data demonstrating a decrease in AMPK activation (p-ACC) in females compared to men. Trial registration: https://doi.org/10.17605/OSF.IO/U7PX9.

The charm-quark contribution to light-by-light scattering in the muon ( g - 2 ) from lattice QCD.

We compute the hadronic light-by-light scattering contribution to the muon g - 2 from the charm quark using lattice QCD. The calculation is performed on ensembles generated with dynamical (u, d, s) quarks at the SU(3) f symmetric point with degenerate pion and kaon masses of around 415 MeV. It includes the connected charm contribution, as well as the leading disconnected Wick contraction, involving the correlation between a charm and a light-quark loop. Cutoff effects turn out to be sizeable, which leads us to use lighter-than-physical charm masses, to employ a broad range of lattice spacings reaching down to 0.039 fm and to perform a combined charm-mass and continuum extrapolation. We use the η c meson to define the physical charm-mass point and obtain a final value of a µ HLbL , c = ( 2.8 ± 0.5 ) × 10 - 11 , whose uncertainty is dominated by the systematics of the extrapolation. Our result is consistent with the estimate based on a simple charm-quark loop, whilst being free of any perturbative scheme dependence on the charm mass. The mixed charm-light disconnected contraction contributes a small negative amount to the final value.

Quantification of calcium in infant formula using laser-induced breakdown spectroscopy (LIBS), Fourier transform mid-infrared (FT-IR) and Raman spectroscopy combined with chemometrics including data fusion.

Laser-induced breakdown spectroscopy (LIBS), Fourier transform mid-infrared (FT-IR) and Raman spectroscopy combined with chemometrics were investigated to quantify calcium (Ca) content in infant formula powder (INF). INF samples (n = 51) with calcium content levels (ca. 6.5-30 mg Ca/100 kJ) were prepared in accordance with the guidelines of Commission Directive 2006/125/EC. Atomic absorption spectroscopy (AAS) was used as the reference method for Ca content determination. To predict Ca content in INF samples, partial least squares regression (PLSR) models that developed based on LIBS, Raman and FT-IR spectral data, respectively. The model developed using LIBS data achieved the best performance for the quantification of Ca content in INF (R2 (cross-validation (CV))-0.99, RMSECV-0.29 mg/g; R2 (prediction (P))-1, RMSEP-0.63 mg/g). PLSR models that developed based on data fusion of Raman and FT-IR spectral features obtained the second best performance (R2CV-0.97, RMSECV-0.38 mg/g; R2P-0.97, RMSEP-0.36 mg/g). This study demonstrated the potential of LIBS, FT-IR and Raman spectroscopy to accurately quantify Ca content in INF.

Acrolein induces differentiation of infection structures in the wheat stem rust fungus.

A chemical factor from wheat stem rust uredospores that induces infection structure formation has been identified as acrolein (2-propenal). This compound is the active component of distillates from uredospore extracts previously shown to induce infection structure formation.

Linkage of lactate dehydrogenase B and C loci in pigeons.

Synthesis of lactate dehydrogenase in somatic and gametic tissues of certain avian and mammalian species is controlled by alleles at three loci, A, B, and C. We report breeding experiments with pigeons that conclusively demonstrate linkage between the B and C structural loci in this species. The most probable recombination fraction is zero, and contiguity is not excluded. The upper 95 percent probability limit is 4.5 percent. This tight linkage of two loci that produce closely similar polypeptides suggests that the loci acquired their separate identities through a duplication event. Further-more, the existence of recognizable B- and C-type polypeptides in both the bird and the mammal suggests that the event and the resulting linkage preceded the separation of these fauna. If so, then the linkage has persisted for a very long time.

Selective production of cis- and trans-verbenol from (-)-and (+)-alpha by a bark beetle.

A unique biological system whereby optical isomers are selectively transformed to geometrical isomers is demonstrated in Ips paraconfusus. Exposure of adult male and female beetles to vapor of (-)-alpha-pinene resulted in the production of (+)-cis-verbenol, a pheromone of this species, whereas (+)-alpha-pinene was oxidized to (+)-trans-verbenol. It appears, therefore, that the ability of a bark beetle to produce its aggregation pheromone can be governed by the chirality of a precursor in the host tree.

Self-inhibitor of bean rust uredospores: methyl 3,4-dimethoxycinnamate.

Two germination inhibitors from bean rust uredospores were identified as the cis and trans isomers of methyl 3,4-dimethoxycinnamate. They appear to be the "self-inhibitors" previously described from these spores.

Identification of the germination self-inhibitor from wheat stem rust uredospores.

Two germination inhibitors from wheat rust uredospores were identified as the cis and trans isomers of methyl 4-hydroxy-3-methoxycinnamate (methyl ferulate). They are the self-inhibitors from these spores described previously.

Long-term survival data from a phase 3 study of Filgrastim as an adjunct to chemotherapy in adults with de novo acute myeloid leukemia.

We previously reported the results of a double-blind, placebo-controlled study of Filgrastim in patients with de novo AML undergoing induction and consolidation chemotherapy. The study demonstrated that Filgrastim was effective and well tolerated and had no impact on complete remission or survival. We now report follow-up data on these patients, assessing long-term effects with emphasis on prognostic indicators. After a median follow-up of 7 years, 434 (83%) patients were dead, 73 (14%) were alive, and 14 (3%) were lost to follow-up. The proportions of deaths were similar in the Filgrastim (83%) and placebo (84%) groups. No differences in median time to death (1.04 years Filgrastim, 1.13 years placebo; P = 0.97) or median disease-free survival (0.86 years Filgrastim, 0.79 years placebo; P = 0.52) were evident. Proportional hazard modeling identified age, performance status, and French-American-British subtype as independent predictors for survival (P < 0.001, P = 0.005, and P = 0.036, respectively), whereas cytogenetic status was not (P = 0.118). Filgrastim had no effect on overall survival in any of these subgroup analyses as none of the treatment comparisons were statistically significant. These findings indicate that Filgrastim can be effectively used to support patients with AML undergoing induction and consolidation chemotherapy without worsening long-term disease outcome.

A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis.

Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 microg/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 x 10(6)/kg CD34+ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34+ cells and CFU-GM. One patient in the 5 microg/kg/day group and two patients in the 10 microg/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 microg/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 microg/kg/day was more efficient with all patients (n = 5) achieving target CD34+ cell counts with a single leukapheresis (median = 2.8, range = 2.3-4.8 x 10(6)/kg, median CFU-GM = 22.1, range = 4.2-102.9 x 10(4)/kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 microg/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 microg/kg/day. However, on balance, 10 microg/kg/day remains the dose of choice in view of more efficient CD34+ cell mobilisation.

Depression in general practice: a comparison of flupenthixol dihydrochloride and dothiepin hydrochloride.

A single-blind, parallel group, general practice study was carried out in 153 patients with mild to moderate depression to compare the efficacy and tolerability of flupenthixol dihydrochloride and dothiepin hydrochloride. Patients were allocated at random to receive single daily doses of either 1 mg flupenthixol in the morning or 75 mg dothiepin in the evening, and this dose could be doubled at the end of 2 weeks in the event of inadequate response. Assessments were made on entry and after 1, 2, 4 and 6 weeks of treatment using the Hamilton Depression Rating Scale, a 4-point severity scale and an unwanted symptoms checklist. The results showed that both treatments significantly improved the patients' condition over 6 weeks, and there was a significant difference in favour of flupenthixol at end-point. Both drugs were well tolerated, although persistence of anticholinergic side-effects in the dothiepin group resulted in a trend favouring flupenthixol. One patient in the flupenthixol group attempted suicide by overdose but made a complete recovery.

Oviposition stimulants for the monarch butterfly: flavonol glycosides from Asclepias curassavica.

The monarch butterfly, Danaus plexippus oviposits on milkweed plants, primarily within the Asclepiadaceae. Oviposition stimulants responsible for host plant recognition were isolated from Asclepias curassavica. Six flavonoid glycosides-quercetin 3-O-(2",6"-alpha-L-dirhamnopyranosyl)-beta-D-galactopyranoside, quercetin 3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-galactopyranoside, quercetin 3-O-(2"-O-alpha-L-rhamnopyranosyl)-beta-D-galactopyranoside, quercetin 3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside, quercetin 3-O-beta-D-galactopyranoside, quercetin 3-O-beta-D-glucopyranoside, and an unidentified flavonoid mixture were isolated and characterized from this plant. An additional glycoside, possibly quercetin 3-O-(2",6"-alpha-L-dirhamnopyranosyl)-beta-D-glucopyranoside, which could not be separated from the first triglycoside, was also found in some batches of plant extract. The two dirhamnosyl glycosides, the glucosylgalactose and the rutinoside were found to be active as oviposition stimulants at 0.5 g leaf equivalents.

Effects of plant nutrition on the balance of insect relevant cardenolides and glucosinolates in Erysimum cheiranthoides.

The possible effects of environmental stress on plant chemistry that are important to herbivorous insects were examined by growing a wild crucifer, Erysimum cheiranthoides, under different nutrient regimes. Oviposition by the cabbage butterfly, Pieris rapae, is thought to be affected by the balance of glucosinolates (stimulants) and cardenolides (deterrents) at the surface of leaves. E. cheiranthoides seedlings were provided with three levels of nitrogen and two levels of sulfur for a period of 15 days before analysis of semiochemicals in whole leaf tissue and at the surface of the foliage. The ratio of cardenolides to glucosinolates in the plants at elevated C/N ratios followed the carbon/nutrient balance hypothesis. However, a high nitrogen supply enhanced biomass production to the extent that concentrations of secondary compounds were unchanged or reduced. The concentration of glucosinolates (glucoiberin and glucocheirolin) at the surface was positively related to whole tissue levels. However, cardenolide (erysimoside and erychroside) concentrations, which were highest in leaf tissue of nitrogen-deficient plants, had the lowest surface levels on foliage of these plants. Possible reasons for differential expression of cardenolides and glucosinolates in a plant as a result of nutrient deficiency are discussed.

Ethanol-sensitive times for the human conceptus.

The world's literature has been scoured to obtain data on 492 examples of the fetal alcohol syndrome (FAS) in the Northern Hemisphere. The seasonally pattern of FAS birth prevalence rates is compared with the seasonality pattern of ethanol intakes to estimate the time-lag between them and hence the timing of ethanol damage during development. It is tentatively suggested, in the light of the data, that this timing might be as late as the 18th-20th week. If this can be substantiated, it would alloy opportunities for preventive measures to be feasible even during pregnancy. Seasonality data have never previously been used to estimate the timing of a sensitive period in prenatal development. The present estimate for ethanol is, however, tentative and should be regarded only as an interesting indicator for future studies.