Evaluating periocidities in peat-based climate proxy records.

Proxy records derived from ombrotrophic peatlands provide important insights into climate change over decadal to millennial timescales. We present mid- to late- Holocene humification data and testate amoebae-derived water table records from two peatlands in Northern Ireland. We examine the repli- cation of periodicities in these proxy climate records, which have been precisely linked through teph- rochronology. Age-depth models are constructed using a Bayesian piece-wise linear accumulation model and chronological errors are calculated for each profile. A Lomb-Scargle Fourier transform-based spectral analysis is used to test for statistically significant periodicities in the data. Periodicities of c. 130, 180, 260, 540 and 1160 years are present in at least one proxy record at each site. The replication of these peri- odicities provides persuasive evidence that they are a product of allogenic climate controls, rather than internal peatland dynamics. A technique to estimate the possible level of red-noise in the data is applied and demonstrates that the observed periodicities cannot be explained by a first-order autoregressive model. We review the periodicities in the light of those reported previously from other marine and terrestrial climate proxy archives to consider climate forcing parameters. © 2012 Elsevier Ltd. All rights reserved.

Energy levels, wavefunction compositions and electric dipole transitions in neutral Ca

A configuration-interaction approach, based on the use of B-spline basis sets combined with a model potential including monoelectronic and dielectronic core polarization effects, is employed to calculate term energies and wavefunctions for neutral Ca. Results are reported for singlet and triplet bound states, and some quasi-bound states above the lowest ionization limit, with angular momentum up to L = 4. Comparison with experiment and with other theoretical results shows that this method yields the most accurate energy values for neutral Ca obtained to date. Wavefunction compositions, necessary for labelling the levels, and the effects of semi-empirical polarization potentials on the wavefunctions are discussed, as are some recent identifications of doubly-excited states. It is shown that taking into account dielectronic core polarization changes the energies of the lowest terms in Ca significantly, in general by a few hundred cm(-1), the effect decreasing rapidly for the higher bound states. For Rydberg states with n approximate to 7 the accuracy of the results is often better than a few cm(-1). For series members (or perturbers) with a pronounced 3d character the error can reach 150 cm(-1). The wavefunctions are used to calculate oscillator strengths and lifetimes for a number of terms and these are compared with existing measurements. The agreement is good but points to a need for improved measurements.

A plasma membrane Ca<sup>2+-ATPase (PMCA) from the liver fluke, Fasciola hepatica</em>

Fasciolosis is a parasitic infection by the liver fluke Fasciola hepatica, which costs the global agricultural community over US $2 billion per year. Its prevalence is rising due to factors such as climate change and drug resistance. ATP-dependent membrane transporters are considered good potential drug targets as they are essential for cellular processes and are in an exposed, accessible position in the cell. Immunolocalisation studies demonstrated that a plasma membrane calcium ATPase (PMCA) was localised to the parenchymal tissue in F. hepatica. The coding sequence for a F. hepatica PMCA (FhPMCA) has been obtained. This sequence encodes a 1,163 amino acid protein which contains motifs which are commonly conserved in PMCAs. Molecular modelling predicted that the protein has 10 transmembrane segments which include a potential calcium ion binding site and phosphorylation motif. FhPMCA interacts with the calmodulin-like protein FhCaM1, but not the related proteins FhCaM2 or FhCaM3, in a calcium-ion dependent manner. This interaction occurs through a region in the C-terminal region of FhPMCA which most likely adopts an a-helical conformation. When FhPMCA was heterologously expressed in a budding yeast strain deleted for its PMCA (Pmc1p), it restored viability. Microsomes prepared from these yeast cells had calcium ion stimulated ATPase activity which was inhibited by the known PMCA inhibitors, bisphenol and eosin. The potential of FhPMCA as a new drug target is discussed.

INFLUENCE OF CORE POLARIZATION ON THE ELECTRON-AFFINITY OF CA

We have developed a method, based on the use of B-spline basis sets and model potentials, for determining properties of systems with two or three electrons outside a polarizable closed-shell core. It is applied to the calculation of the electron affinity of Ca and the resulting value of 17.7 meV is in excellent agreement with the most recent experiments. It is found that the dielectronic core-valence interaction reduces the electron affinity by 39.5 meV.

Pharmacological profiling of store-operated Ca(2+) entry in retinal arteriolar smooth muscle

Objective: Pharmacological profiling of store-operated Ca(2+) entry (SOCE) and molecular profiling of ORAI and TRPC expression in arterioles. 
Methods: Fura-2 based microfluorimetry was used to assess CPA-induced SOCE in rat retinal arteriolar myocytes. Arteriolar ORAI and TRP transcript expression were screened using RT-PCR. 
Results: SKF96365 and LOE908 blocked SOCE (IC(50) s of 1.2µM and 1.4µM, respectively). Gd(3+) and La(3+) potently inhibited SOCE (IC(50) s of 21nM and 42nM, respectively), but Ni(2+) showed lower potency (IC(50) = 11.6µM). 2-aminoethyldiphenyl borate (2APB) inhibited SOCE (IC(50) = 3.7µM) but enhanced basal influx (>100µM). Verapamil and nifedipine had no effect at concentrations that inhibit L-type Ca(2+) channels, but diltiazem inhibited SOCE by approximately 40% (=0.1µM). RT-PCR demonstrated transcript expression for ORAI 1, 2 and 3, and TRPC1, 3, 4 and 7. Transcripts for TRPV1 and 2, which are activated by 2APB, were also expressed. 
Conclusion: The pharmacological profile of SOCE in retinal arteriolar smooth muscle appears unique when compared to other vascular tissues. This suggests that the molecular mechanisms underlying SOCE can differ, even in closely related tissues. Taken together, the pharmacological and molecular data are most consistent with involvement of TRPC1 in SOCE, although involvement of ORAI or other TRPC channels cannot be excluded. © 2012 John Wiley & Sons Ltd.

Decomposing the mid-holocene Tsuga decline in eastern North America

The mid-Holocene decline of Tsuga canadensis (hereafter Tsuga) populations across eastern North America is widely perceived as a synchronous event, driven by pests/pathogens, rapid climate change, or both. Pattern identification and causal attribution are hampered by low stratigraphic density of pollen-sampling and radiometric dates at most sites, and by absence of highly resolved, paired pollen and paleoclimate records from single sediment cores, where chronological order of climatic and vegetational changes can be assessed. We present an intensely sampled (contiguous 1-cm intervals) record of pollen and water table depth (inferred from testate amoebae) from a single core spanning the Tsuga decline at Irwin Smith Bog in Lower Michigan, with high-precision chronology. We also present an intensively sampled pollen record from Tower Lake in Upper Michigan. Both sites show high-magnitude fluctuations in Tsuga pollen percentages during the pre-decline maximum. The terminal decline is dated at both sites ca. 5000 cal yr BP, some 400 years later than estimates from other sites and data compilations. The terminal Tsuga decline was evidently heterochronous across its range. A transient decline ca. 5350 cal yr BP at both sites may correspond to the terminal decline at other sites in eastern North America. At Irwin Smith Bog, the terminal Tsuga decline preceded an abrupt and persistent decline in water table depths by;200 years, suggesting the decline was not directly driven by abrupt climate change. The Tsuga decline may best be viewed as comprising at least three phases: a long-duration predecline maximum with high-magnitude and high-frequency fluctuations, followed by a terminal decline at individual sites, followed in turn by two millennia of persistently low Tsuga populations. These phases may not be causally linked, and may represent dynamics taking place at multiple temporal and spatial scales. Further progress toward understanding the phenomenon requires an expanded network of high-resolution pollen and paleoclimate chronologies.

Possible interactions between environmental factors in determining species optima

Questions: 1. Indicator values, such as those of Ellenberg, for different environmental factors are seen as independent. We tested for the presence of interactions between environmental factors ( soil moisture and reaction) to see if this assumption is simplistic. 2. How close are Ellenberg indicator values (IVs) related to the observed optima of species response curves in an area peripheral to those where they have been previously employed and 3. Can the inclusion of bryophytes add to the utility of IVs?

Location: South Uist, Outer Hebrides, Scotland, UK.

Methods: Two grids (ca. 2000 m x 2000 m) were sampled at 50-m intervals across the transition from machair to upland communities covering an orthogonal gradient of both soil pH ( reaction) and soil moisture content. Percentage cover data for vascular plants, bryophytes and lichens were recorded, along with pH and moisture content of the underlying sand/soil/peat. Reaction optima, derived from species response curves calculated using HOF models, were compared between wet and dry sites, and moisture optima between acidic and basic samples. Optima for the whole data set were compared to Ellenberg IVs to assess their performance in this area, with and without the inclusion of bryophytes.

Results: A number of species showed substantially different pH optima at high and low soil moisture contents (18% of those tested) and different soil moisture optima at high and low pH (49%). For a number of species the IVs were poor predictors of their actual distribution across the sampled area. Bryophytes were poor at explaining local variation in the environmental factors and also their inclusion with vascular plants negatively affected the strength of relationships.

Conclusions: A substantial number of species showed an interaction between soil moisture and reaction in determining their optima on the two respective gradients. It should be borne in mind that IVs such as Ellenberg's may not be independent of one another.

Ca(2+) sparks promote myogenic tone in retinal arterioles

Background and Purpose: Ca(2+) imaging reveals subcellular Ca(2+) sparks and global Ca(2+) waves/oscillations in vascular smooth muscle. It is well established that Ca(2+) sparks can relax arteries, but we have previously reported that sparks can summate to generate Ca(2+) waves/oscillations in unpressurized retinal arterioles, leading to constriction. We have extended these studies to test the functional significance of Ca(2+) sparks in the generation of myogenic tone in pressurized arterioles.

Experimental Approach: Isolated retinal arterioles (25-40 μm external diameter) were pressurized to 70 mmHg, leading to active constriction. Ca(2+) signals were imaged from arteriolar smooth muscle in the same vessels using Fluo4 and confocal laser microscopy.

Key Results: Tone development was associated with an increased frequency of Ca(2+) sparks and oscillations. Vasomotion was observed in 40% of arterioles and was associated with synchronization of Ca(2+) oscillations, quantifiable as an increased cross-correlation coefficient. Inhibition of Ca(2+) sparks with ryanodine, tetracaine, cyclopiazonic acid or nimodipine, or following removal of extracellular Ca(2+) , resulted in arteriolar relaxation. Cyclopiazonic acid-induced dilatation was associated with decreased Ca(2+) sparks and oscillations but with a sustained rise in the mean global cytoplasmic [Ca(2+) ] ([Ca(2+) ]c ), as measured using Fura2 and microfluorimetry.

Conclusions and Implications: This study provides direct evidence that Ca(2+) sparks can play an excitatory role in pressurized arterioles, promoting myogenic tone. This contrasts with the generally accepted model in which sparks promote relaxation of vascular smooth muscle. Changes in vessel tone in the presence of cyclopiazonic acid correlated more closely with changes in spark and oscillation frequency than global [Ca(2+) ]c , underlining the importance of frequency-modulated signalling in vascular smooth muscle.

Can Certain Genotypes Predispose to Poor Asthma Control in Children? A Pharmacogenetic Study of 9 Candiate Genes in Children with Difficult Asthma

Objective: We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control.

Methods: A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma.

Key Results: The results indicated that LTA4H A-9188.G, TNFa G-308.A and IL-4Ra A1727.G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p,0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Ra A1199.C, IL-4Ra T1570.C and IL- 4Ra A1727.G and CA haplotype of TNFa C-863.A and TNFa G-308.A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively).

Conclusions and Clinical Relevance: The study revealed multiple SNPs and haplotypes in LTA4H, TNFa and IL4-Ra genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A- 9188.G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit. ©2013 Almomani et al.