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Inositol pyrophosphates are signaling molecules containing at least one phosphoanhydride bond that regulate a wide range of cellular processes in eukaryotes. With a cyclic array of phosphate esters and diphosphate groups around myo-inositol, these molecular messengers possess the highest charge density found in nature. Recent work deciphering inositol pyrophosphate biosynthesis in Arabidopsisrevealed important functions of these messengers in nutrient sensing, hormone signaling, and plant immunity. However, despite the rapid hydrolysis of these molecules in plant extracts, very little is known about the molecular identity of the phosphohydrolases that convert these messengers back to their inositol polyphosphate precursors. Here, we investigate whether ArabidopsisPlant and Fungi Atypical Dual Specificity Phosphatases (PFA-DSP1-5) catalyze inositol pyrophosphate phosphohydrolase activity. We find that recombinant proteins of all five ArabidopsisPFA-DSP homologues display phosphohydrolase activity with a high specificity for the 5-β-phosphate of inositol pyrophosphates and only minor activity against the β-phosphates of 4-InsP7and 6-InsP7. We further show that heterologous expression of ArabidopsisPFA-DSP1-5 rescues wortmannin sensitivity and deranged inositol pyrophosphate homeostasis caused by the deficiency of the PFA-DSP-type inositol pyrophosphate phosphohydrolase Siw14 in yeast. Heterologous expression in Nicotiana benthamianaleaves provided evidence that ArabidopsisPFA-DSP1 also displays 5-β-phosphate-specific inositol pyrophosphate phosphohydrolase activity in planta. Our findings lay the biochemical basis and provide the genetic tools to uncover the roles of inositol pyrophosphates in plant physiology and plant development.

We establish local input-to-state stability and asymptotic gain results for a class of nonlinear infinite-dimensional systems with respect to the global attractor of the respective undisturbed system. We apply our results to a large class of reaction-diffusion equations with nontrivial global attractors.

In this paper we consider countable couplings of finite-dimensional input-to-state stable systems. We consider the whole interconnection as an infinite-dimensional system on the ℓ∞state space. We develop stability conditions of the small-gain type to guarantee that the whole system remains ISS and highlight the differences between finite and infinite couplings by means of examples. We show that using our methodology it is possible to study uniform global asymptotic stability of nonlinear spatially invariant systems by solving a finite number of nonlinear algebraic inequalities.

We present well-posedness - along with global stability - results for non-autonomous semilinear input-output systems, the central assumption being that the considered system is scattering-passive. We consider both systems with distributed control and observation and systems with boundary control and observation.

Four alginates possessing different guluronic/mannuronic acid ratios and one acetylated alginate were investigated with respect to their behaviour during intercalation into layered double hydroxides (LDHs). Two alginates were commercial products while the others were synthesised by way of bacterial fermentation and in one sample followed by enzymatic treatment. Intercalation was performed by way of co-precipitation of aluminium nitrate and zinc nitrate in alginate solution at a pH of 8·5–9. The products were characterised by powder X-ray diffraction, elemental analysis, wide-angle X-ray scattering, scanning electron microscopy and magic angle spinning (MAS) NMR spectroscopy. All alginates intercalate well into the Zn2Al-LDH host structure. With an increase in the content of guluronic acid in the alginate, the d-spacing (interlayer distance) in the alginate-LDH compound increases from 1·28 to 1·85 nm. Similarly, acetylation of the carboxylic groups leads to an increased steric volume of such alginate and therefore to a higher d-spacing (1·72 nm). The results indicate that different guluronic/mannuronic acid ratios can be used to trigger the steric size of the alginates and consequently the d-spacing of the alginate-LDHs. 13C CP MAS NMR spectroscopy confirmed an interaction between the carboxylic groups present in the alginate with the inorganic main layer.

Four alginates possessing different guluronic/mannuronic acid ratios and one acetylated alginate were investigated with respect to their behaviour during intercalation into layered double hydroxides (LDHs). Two alginates were commercial products while the others were synthesised by way of bacterial fermentation and in one sample followed by enzymatic treatment. Intercalation was performed by way of co-precipitation of aluminium nitrate and zinc nitrate in alginate solution at a pH of 8·5–9. The products were characterised by powder X-ray diffraction, elemental analysis, wide-angle X-ray scattering, scanning electron microscopy and magic angle spinning (MAS) NMR spectroscopy. All alginates intercalate well into the Zn2Al-LDH host structure. With an increase in the content of guluronic acid in the alginate, the d-spacing (interlayer distance) in the alginate-LDH compound increases from 1·28 to 1·85 nm. Similarly, acetylation of the carboxylic groups leads to an increased steric volume of such alginate and therefore to a higher d-spacing (1·72 nm). The results indicate that different guluronic/mannuronic acid ratios can be used to trigger the steric size of the alginates and consequently the d-spacing of the alginate-LDHs. 13C CP MAS NMR spectroscopy confirmed an interaction between the carboxylic groups present in the alginate with the inorganic main layer.

The study was conducted in healthy male volunteers to evaluate the absorption, metabolic pattern, and mode of elimination of telmisartan, a nonpeptide angiotensin II receptor antagonist. [14C]telmisartan was administered orally in solution as a single 40 mg dose to 5 subjects. A further 5 subjects received short‐term intravenous infusion of [14C]telmisartan 40 mg. Measurement of total 14C radioactivity in plasma showed that about 50% was absorbed following oral administration, with maximum plasma concentration observed after 0.5 to 1 hour. Absolute bioavailability was 43%. On average, 84% of total radioactivity in plasma reflected the parent compound. The remainder of total radioactivity could be ascribed to the glucuronide conjugate of telmisartan, which represented the only metabolite in man. About 99.5% of telmisartan was bound to plasma protein, mainly to albumin and α‐1‐acid glycoprotein. Telmisartan was reversibly distributed into erythrocytes. More than 90% of administered dose was excreted within 120 hours, and the excretion balance was complete 144 hours after dosing. Radioactivity was almost exclusively (> 98%) excreted via the feces; urinary excretion accounted for < 1% of the dose, irrespective of the route of administration. In the small fraction excreted into urine, the glucuronide conjugate of telmisartan was predominant. Although some telmisartan glucuronide was detected in plasma, only unchanged drug was identified in the feces. No changes in vital signs, electrocardiogram, or clinical laboratory tests were detected following telmisartan administration, and adverse events, predominantly unrelated to treatment and of mild intensity, were infrequent. One subject fainted and, on another occasion, reported faintness; these events were probably due to the antihypertensive action of the intravenous study medication.

Methoxsalen, administered orally shows a strong, albeit saturable first-pass effect, as demonstrated by classical dose linearity testing and by a new method, using stable isotopes and gas chromatographic mass spectrometric analysis. The therapeutic consequences of the first-pass effect are discussed.

Scientists have combined functional and computational analysis to predict the substrate specificity of a family of glycosyltransferases from Arabidopsis thaliana, creating a tool that enables researchers to classify the donor and acceptor specificity of glycosyltransferase enzymes.