In situ analysis and structural elucidation of sainfoin (Onobrychis viciifolia) tannins for high-throughput germplasm screening

A rapid thiolytic degradation and cleanup procedure was developed for analyzing tannins directly in chlorophyll-containing sainfoin (Onobrychis viciifolia) plants. The technique proved suitable for complex tannin mixtures containing catechin, epicatechin, gallocatechin, and epigallocatechin flavan-3-ol units. The reaction time was standardized at 60 min to minimize the loss of structural information as a result of epimerization and degradation of terminal flavan-3-ol units. The results were evaluated by separate analysis of extractable and unextractable tannins, which accounted for 63.6−113.7% of the in situ plant tannins. It is of note that 70% aqueous acetone extracted tannins with a lower mean degree of polymerization (mDP) than was found for tannins analyzed in situ. Extractable tannins had between 4 and 29 lower mDP values. The method was validated by comparing results from individual and mixed sample sets. The tannin composition of different sainfoin accessions covered a range of mDP values from 16 to 83, procyanidin/prodelphinidin (PC/PD) ratios from 19.2/80.8 to 45.6/54.4, and cis/trans ratios from 74.1/25.9 to 88.0/12.0. This is the first high-throughput screening method that is suitable for analyzing condensed tannin contents and structural composition directly in green plant tissue.

Exposure to space radiation of high-performance infrared multilayer-filters and materials technology experiments

Infrared multilayer interference filters have been used extensively in satellite radiometers for about 15 years. Filters manufactured by the University of Reading have been used in Nimbus 5, 6, and 7, TIROS N, and the Pioneer Venus orbiter. The ability of the filters to withstand the space environment in these applications is critical; if degradation takes place, the effects would range from worsening of signal-to-noise performance to complete system failure. An experiment on the LDEF will enable the filters, for the first time, to be subjected to authoritative spectral measurements following space exposure to ascertain their suitability for spacecraft use and to permit an understanding of degradation mechanisms.

Simulating the impacts of global warming on wheat in China using a large area crop model

Temperature is one of the most prominent environmental factors that determine plant growth, devel- opment, and yield. Cool and moist conditions are most favorable for wheat. Wheat is likely to be highly vulnerable to further warming because currently the temperature is already close to or above optimum. In this study, the impacts of warming and extreme high temperature stress on wheat yield over China were investigated by using the general large area model (GLAM) for annual crops. The results showed that each 1±C rise in daily mean temperature would reduce the average wheat yield in China by about 4.6%{5.7% mainly due to the shorter growth duration, except for a small increase in yield at some grid cells. When the maximum temperature exceeded 30.5±C, the simulated grain-set fraction declined from 1 at 30.5±C to close to 0 at about 36±C. When the total grain-set was lower than the critical fractional grain-set (0.575{0.6), harvest index and potential grain yield were reduced. In order to reduce the negative impacts of warming, it is crucial to take serious actions to adapt to the climate change, for example, by shifting sowing date, adjusting crop distribution and structure, breeding heat-resistant varieties, and improving the monitoring, forecasting, and early warning of extreme climate events.

Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites

Understanding the cellular effects of flavonoid metabolites is important for predicting which dietary flavonoids might be most beneficial in vivo. Here we investigate the bioactivity in dermal fibroblasts of the major reported in vivo metabolites of quercetin, i.e. 3'-O-methyl quercetin, 4'-O-methyl quercetin and quercetin 7-O-beta-D-glucuronide, relative to that of quercetin, in terms of their further metabolism and their resulting cytotoxic and/or cytoprotective effects in the absence and presence of oxidative stress. Uptake experiments indicate that exposure to quercetin led to the generation of two novel cellular metabolites, one characterized as a 2'-glutathionyl quercetin conjugate and another product with similar spectral characteristics but 1 mass unit lower, putatively a quinone/quinone methide. A similar product was identified in cells exposed to 3'-O-methyl quercetin, but not in the lysates of those exposed to its 4'-O-methyl counterpart, suggesting that its formation is related to oxidative metabolism. There was no uptake or metabolism of quercetin 7-O-beta-D-glucuronide by fibroblasts. Formation of oxidative metabolites may explain the observed concentration-dependent toxicity of quercetin and 3'-O-methyl quercetin, whereas the formation of a 2'-glutathionyl quercetin conjugate is interpreted as a detoxification step. Both O -methylated metabolites conferred less protection than quercetin against peroxide-induced damage, and quercetin glucuronide was ineffective. The ability to modulate cellular toxicity paralleled the ability of the compounds to decrease the level of peroxide-induced caspase-3 activation. Our data suggest that the actions of quercetin and its metabolites in vivo are mediated by intracellular metabolites.

A synthetic route to fully substituted chiral cyclopentylamine derivatives: precursors of carbanucleosides

Removal of silyl protection from D-glucose derived substrate 6 afforded 7, which upon acetonide deprotection followed by reaction with N-benzylhydroxylamine furnished two isomeric isoxazolidinocyclopentane derivatives via spontaneous cyclization of an in situ generated nitrone. The methyl xanthate derivative of the tertiary hydroxyl group of one isomer was isolated and subjected to radical deoxygenation reaction to form epimeric products, while with the other isomer it underwent spontaneous 1,2-elimination to form a mixture of the two possible endocyclic olefins. Hydrogenolytic cleavage of the isoxazolidine rings of the purified products followed by insertion of 5-amino-4-chloropyrimidine moiety and purine ring construction smoothly afforded structurally unique carbanucleoside analogues. Various spectroscopic methods on the synthesized compounds and X-ray analysis on one important intermediate were used to assign the structures and stereochemistry of the products.

Reaction of 1,1′-diacetylferrocene with hydrazine hydrate: Synthesis and X-ray crystal structures of bis(hydrazine)bis(hydrazinecarboxylato-N′,O)iron(II), [Fe(N2H4)2(O2CNHNH2)2], and the cyclic biferrocene diazine, [N(Me)CC5H4FeC5H4C(Me)N]2

1,1′-Diacetylferrocene reacts with neat hydrate over a period of 72 h at 20°C to give the dihydrazone [H2NN(Me)CC5H4FeC5H4C(Me)NNH2] (6) in almost quantitative yield. Either prolonging the reaction time or reacting 6 with fresh hydrazine causes the iron to be stripped from the metallocene and bis(hydrazine)bis(hydrazinecarboxylato-N′,O) iron(II), [Fe(N2H4)2(OOCNHNH2)2] (11), crystallizes. In the presence of Ba2+ or Mo2+ ions two molecules of complex 6 react to give the cyclic diazine [N(Me)CC5H4FeC5H4C (Me)N]2 (7) in high yield. Hydrazine is liberated in this reaction. Complexes 6 and 11 have been characterized crystallographically. The cyclic voltammograms of complexes 6 and 7 contain essentially non-reversible oxidation peaks.

The effect of exogenous gonadotropins on ovarian function in goats actively immunized against inhibin

The aim of this investigation was to compare the ovarian response to superovulatory treatments in does before and after inhibin immunization, with a view to optimizing the superovulatory potential of the caprine ovary. To avoid interference by the ovarian cycle, the experiment was conducted out-of-season. At the onset of the experiment 48 does were subjected to treatment with an sc implant of the progestogen norgestomet, combined with a gonadotropin; eight does each received a single injection of 1200 IU eCG, 400 IU eCG or 2 mL physiological saline (control) or six injections (at 12 h intervals) constituting 16 or 5.4 AU pFSH. The does were mated and subjected to embryo collection 6 to 7 d later. Throughout the experiment ovarian function (by ultrasonography) and plasma levels of inhibin antibodies and progesterone were monitored. Of 40 does treated during the first part of the experiment, 48% showed estrus. The ovarian response in does treated with a high or low dose of eCG or a low dose of pFSH was barely in excess of the ovarian response in the saline-treated controls, whereas a superovulatory dose of pFSH (16 AU) gave a satisfactory response of, on average, 14.5 ovulations (yielding 8.8 flushed ova and embryos). Immediately after the does had been subjected to embryo collection they were actively immunized against inhibin by administering two injections of a recombinant α-subunit of ovine inhibin at four week intervals. All immunized does produced antibodies with the maximal titer reached two weeks after the second injection. Groups of immunized does were subjected to the same gonadotropin treatments as before (avoiding allocation of individuals to the same treatments). This time all does showed estrous symptoms. The ovulatory response to the various treatments, including the saline controls, was virtually identical, the overall average being 21.8 follicles and 9.1 ovulations. The average embryo yield per doe was 5.7. The results imply that inhibin acted as the key factor in determining the ovulatory response since no impact of any of the supplementary gonadotropins was noted in inhibin-immunized does. This finding gives rise to the notion that inhibin antibodies may act primarily by an intraovarian paracrine action rather than by reducing the suppressive action of inhibin on pituitary FSH release. Further, these findings confirm earlier reports that eCG is less suitable than FSH for inducing superovulation in goats, and indicate that active immunization against inhibin may be considered a viable alternative to using exogenous gonadotropin for inducing superovulation in goats.

Anion-directed template synthesis and hydrolysis of mono-condensed Schiff base of 1,3-pentanediamine ando-hydroxyacetophenone in NiII and CuII Complexes

Bis(o-hydroxyacetophenone)nickel(II) dihydrate, on reaction with 1,3-pentanediamine, yields a bis-chelate complex [NiL2]·2H2O (1) of mono-condensed tridentate Schiff baseligand HL {2-[1-(3-aminopentylimino)ethyl]phenol}. The Schiff base has been freed from the complex by precipitating the NiII as a dimethylglyoximato complex. HL reacts smoothly with Ni(SCN)2·4H2O furnishing the complex [NiL(NCS)] (2) and with CuCl2·2H2O in the presence of NaN3 or NH4SCN producing [CuL(N3)]2 (3) or [CuL(NCS)] (4). On the other hand, upon reaction with Cu(ClO4)2·6H2O and Cu(NO3)2·3H2O, the Schiff base undergoes hydrolysis to yield ternary complexes [Cu(hap)(pn)(H2O)]ClO4 (5) and [Cu(hap)(pn)(H2O)]NO3 (6), respectively (Hhap = o-hydroxyacetophenone and pn = 1,3-pentanediamine). The ligand HL undergoes hydrolysis also on reaction with Ni(ClO4)2·6H2O or Ni(NO3)2·6H2O to yield [Ni(hap)2] (7). The structures of the complexes 2, 3, 5, 6, and 7 have been confirmed by single-crystal X-ray analysis. In complex 2, NiII possesses square-planar geometry, being coordinated by the tridentate mono-negative Schiff base, L and the isothiocyanate group. The coordination environment around CuII in complex 3 is very similar to that in complex 2 but here two units are joined together by end-on, axial-equatorial azide bridges to result in a dimer in which the geometry around CuII is square pyramidal. In both 5 and 6, the CuII atoms display the square-pyramidal environment; the equatorial sites being coordinated by the two amine groups of 1,3-pentanediamine and two oxygen atoms of o-hydroxyacetophenone. The axial site is coordinated by a water molecule. Complex 7 is a square-planar complex with the Ni atom bonded to four oxygen atoms from two hap moieties. The mononuclear units of 2 and dinuclear units of 3 are linked by strong hydrogen bonds to form a one-dimensional network. The mononuclear units of 5 and 6 are joined together to form a dimer by very strong hydrogen bonds through the coordinated water molecule. These dimers are further involved in hydrogen bonding with the respective counteranions to form 2-D net-like open frameworks.

Care homes’ use of medicines study: prevalence, causes and potential harm of medication errors in care homes for older people

Introduction: Care home residents are at particular risk from medication errors, and our objective was to determine the prevalence and potential harm of prescribing, monitoring, dispensing and administration errors in UK care homes, and to identify their causes. Methods: A prospective study of a random sample of residents within a purposive sample of homes in three areas. Errors were identified by patient interview, note review, observation of practice and examination of dispensed items. Causes were understood by observation and from theoretically framed interviews with home staff, doctors and pharmacists. Potential harm from errors was assessed by expert judgement. Results: The 256 residents recruited in 55 homes were taking a mean of 8.0 medicines. One hundred and seventy-eight (69.5%) of residents had one or more errors. The mean number per resident was 1.9 errors. The mean potential harm from prescribing, monitoring, administration and dispensing errors was 2.6, 3.7, 2.1 and 2.0 (0 = no harm, 10 = death), respectively. Contributing factors from the 89 interviews included doctors who were not accessible, did not know the residents and lacked information in homes when prescribing; home staff’s high workload, lack of medicines training and drug round interruptions; lack of team work among home, practice and pharmacy; inefficient ordering systems; inaccurate medicine records and prevalence of verbal communication; and difficult to fill (and check) medication administration systems. Conclusions: That two thirds of residents were exposed to one or more medication errors is of concern. The will to improve exists, but there is a lack of overall responsibility. Action is required from all concerned.

Anthropogenic natal environmental effects on life histories in a wild bird population

Recent work suggests that the environment experienced in early life can alter life histories in wild populations [1, 2, 3, 4 and 5], but our understanding of the processes involved remains limited [6 and 7]. Since anthropogenic environmental change is currently having a major impact on wild populations [8], this raises the possibility that life histories may be influenced by human activities that alter environmental conditions in early life. Whether this is the case and the processes involved remain unexplored in wild populations. Using 23 years of longitudinal data on the Mauritius kestrel (Falco punctatus), a tropical forest specialist, we found that females born in territories affected by anthropogenic habitat change shifted investment in reproduction to earlier in life at the expense of late life performance. They also had lower survival rates as young adults. This shift in life history strategy appears to be adaptive, because fitness was comparable to that of other females experiencing less anthropogenic modification in their natal environment. Our results suggest that human activities can leave a legacy on wild birds through natal environmental effects. Whether these legacies have a detrimental effect on populations will depend on life history responses and the extent to which these reduce individual fitness.

Centennial variations in sunspot number, open solar flux and streamer belt width: 1. correction of the sunspot number record since 1874

We analyse the widely-used international/ Zürich sunspot number record, R, with a view to quantifying a suspected calibration discontinuity around 1945 (which has been termed the “Waldmeier discontinuity” [Svalgaard, 2011]). We compare R against the composite sunspot group data from the Royal Greenwich Observatory (RGO) network and the Solar Optical Observing Network (SOON), using both the number of sunspot groups, N{sub}G{\sub}, and the total area of the sunspots, A{sub}G{\sub}. In addition, we compare R with the recently developed interdiurnal variability geomagnetic indices IDV and IDV(1d). In all four cases, linearity of the relationship with R is not assumed and care is taken to ensure that the relationship of each with R is the same before and after the putative calibration change. It is shown the probability that a correction is not needed is of order 10{sup}−8{\sup} and that R is indeed too low before 1945. The optimum correction to R for values before 1945 is found to be 11.6%, 11.7%, 10.3% and 7.9% using A{sub}G{\sub}, N{sub)G{\sub}, IDV, and IDV(1d), respectively. The optimum value obtained by combining the sunspot group data is 11.6% with an uncertainty range 8.1-14.8% at the 2σ level. The geomagnetic indices provide an independent yet less stringent test but do give values that fall within the 2σ uncertainty band with optimum values are slightly lower than from the sunspot group data. The probability of the correction needed being as large as 20%, as advocated by Svalgaard [2011], is shown to be 1.6 × 10{sup}−5{\sup}.

Formation of fluorinated nonionic surfactant microemulsions in hydrofluorocarbon 134a (HFC 134a)

A structurally related series of fluorinated nonionic oxyethylene glycol surfactants of the type C(m)F(2m+1)(CH(2))(n)O[(CH(2)CH(2)O)(p)H], denoted C(m.n)E(p) (where m=4, 6, or 7, m=1 or 2, and p=4 or 6) were synthesized and their surface behavior in aqueous solution was characterized. The ability of these surfactants to form water-in-hydrofluorocarbon (HFC) propellant 134a microemulsions suitable for use in the aerosolized delivery of water-soluble drugs has been investigated. Phase studies showed that, regardless of the composition used, clear one-phase systems could not be prepared if a fluorinated nonionic surfactant was used alone, or in combination with a short or medium fluorocarbon alcohol cosurfactant. Clear one-phase systems could, however, be prepared if a short-chain hydrocarbon alcohol, such as ethanol, n-propanol, or n-pentanol, was used as cosurfactant, with the extent of the one-phase region increasing with decreased chain length of the alcohol cosurfactant. Light-scattering studies on a number of the hydrocarbon-alcoholcontaining systems in the propellant-rich part of the phase diagram showed that only systems prepared with C(4.2)E(6) and propanol contained microemulsion droplets (all other systems investigated were considered to be cosolvent systems).

Propagation of the Madden–Julian Oscillation and scale interaction with the diurnal cycle in a high-resolution GCM

The Madden–Julian Oscillation (MJO) is the chief source of tropical intra-seasonal variability, but is simulated poorly by most state-of-the-art GCMs. Common errors include a lack of eastward propagation at the correct frequency and zonal extent, and too small a ratio of eastward- to westward-propagating variability. Here it is shown that HiGEM, a high-resolution GCM, simulates a very realistic MJO with approximately the correct spatial and temporal scale. Many MJO studies in GCMs are limited to diagnostics which average over a latitude band around the equator, allowing an analysis of the MJO’s structure in time and longitude only. In this study a wider range of diagnostics is applied. It is argued that such an approach is necessary for a comprehensive analysis of a model’s MJO. The standard analysis of Wheeler and Hendon (Mon Wea Rev 132(8):1917–1932, 2004; WH04) is applied to produce composites, which show a realistic spatial structure in the MJO envelopes but for the timing of the peak precipitation in the inter-tropical convergence zone, which bifurcates the MJO signal. Further diagnostics are developed to analyse the MJO’s episodic nature and the “MJO inertia” (the tendency to remain in the same WH04 phase from one day to the next). HiGEM favours phases 2, 3, 6 and 7; has too much MJO inertia; and dies out too frequently in phase 3. Recent research has shown that a key feature of the MJO is its interaction with the diurnal cycle over the Maritime Continent. This interaction is present in HiGEM but is unrealistically weak.

Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial

Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (<35yrs) and 20 elderly (50-80yrs) healthy, male non- smokers consumed either a CF-containing drink (450mg CF) or nutrient-matched, CF-free control drink bi-daily for 14 days. The primary endpoint was endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints included cardiac output, vascular stiffness, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Following 2 weeks of CF intake, FMD improved in young (6.1±0.7% vs. 7.6±0.7%, p<0.001) and elderly (4.9±0.6% vs. 6.3±0.9%, p<0.001). Secondary outcomes demonstrated in both groups that CF intake decreased pulse wave velocity and lowered total peripheral resistance, increased arteriolar- and microvascular vasodilator capacity, red cell deformability, and diastolic blood pressure, while cardiac output remained affected. In the elderly, baseline systolic blood pressure was elevated, driven by an arterial stiffness-related augmentation. CF intake decreased aortic augmentation index (-9%), and thus systolic blood pressure (-7mmHg). (Clinicaltrials.gov:NCT01639781) CF intake reverses age-related burden of cardiovascular risk in healthy elderly, highlighting the potential of dietary flavanols to maintain cardiovascular health.