bluuebunny/crossref_metadata_2025 huggingface dataset:
Density dependence and climate effects in Rocky Mountain elk: an application of regression with instrumental variables for population time series with sampling error
Authors: Creel Scott , Creel Michael
Published: June 2009

1.
 Sampling error in annual estimates of population size creates two widely recognized problems for the analysis of population growth. First, if sampling error is mistakenly treated as process error, one obtains inflated estimates of the variation in true population trajectories (Staples, Taper & Dennis 2004). Second, treating sampling error as process error is thought to overestimate the importance of density dependence in population growth (Viljugrein et al. 2005; Dennis et al. 2006).

2.
 In ecology, state‐space models are used to account for sampling error when estimating the effects of density and other variables on population growth (Staples et al. 2004; Dennis et al. 2006). In econometrics, regression with instrumental variables is a well‐established method that addresses the problem of correlation between regressors and the error term, but requires fewer assumptions than state‐space models (Davidson & MacKinnon 1993; Cameron & Trivedi 2005).

3.
 We used instrumental variables to account for sampling error and fit a generalized linear model to 472 annual observations of population size for 35 Elk Management Units in Montana, from 1928 to 2004. We compared this model with state‐space models fit with the likelihood function of Dennis et al. (2006). We discuss the general advantages and disadvantages of each method. Briefly, regression with instrumental variables is valid with fewer distributional assumptions, but state‐space models are more efficient when their distributional assumptions are met.

4.
 Both methods found that population growth was negatively related to population density and winter snow accumulation. Summer rainfall and wolf (Canis lupus) presence had much weaker effects on elk (Cervus elaphus) dynamics [though limitation by wolves is strong in some elk populations with well‐established wolf populations (Creel et al. 2007; Creel & Christianson 2008)].

5.  Coupled with predictions for Montana from global and regional climate models, our results predict a substantial reduction in the limiting effect of snow accumulation on Montana elk populations in the coming decades. If other limiting factors do not operate with greater force, population growth rates would increase substantially.
Population genetics suggests effectiveness of habitat connectivity measures for the European tree frog in Switzerland
Authors: Angelone Sonia , Holderegger Rolf
Published: June 2009

1. Governmental authorities in many countries financially support the implementation of habitat connectivity measures to enhance the exchange of individuals among fragmented populations. The evaluation of the effectiveness of such measures is crucial for future management directions and can be accomplished by using genetic methods.

2. We retraced the population history of the European tree frog in two Swiss river valleys (Reuss and Thur), performed comprehensive population sampling to infer the genetic structure at 11 microsatellite markers, and used first‐generation migrant assignment tests to evaluate the contemporary exchange of individuals.

3. Compared with the Thur valley, the Reuss valley has lost almost double the number of breeding sites and exhibited a more pronounced genetic grouping. However, similar numbers of contemporary migrants were detected in both valleys. In the Reuss valley, 81% of the migration events occurred within the identified genetic groups, whereas in the Thur valley migration patterns were diffuse.

4. Our results show that the connectivity measures implemented in the Reuss valley facilitated effective tree frog migration among breeding sites within distances up to 4 km. Nevertheless, the Reuss valley exhibited high genetic differentiation, which reflected the impact of barriers to tree frog movement such as the River Reuss. By contrast in the Thur valley, a larger number of breeding sites have been preserved and high admixture indicated exchange of individuals at distances up to 16 km.

5. Synthesis and applications. We show that genetic methods can substantiate the effectiveness of connectivity measures taken in conservation management at the landscape scale. We urge responsible authorities from both river valleys to continue implementing connectivity measures and to create a dense network of breeding sites, as spatial gaps of 8 km are rarely traversed by tree frogs.
Responses of invertebrate trophic level, feeding guild and body size to the management of improved grassland field margins
Authors: Woodcock Ben A. , Potts Simon G. , Tscheulin Thomas , Pilgrim Emma , Ramsey Alex J. , Harrison‐Cripps Jennifer , Brown Valerie K. , Tallowin Jerry R.
Published: June 2009

1. Management of lowland mesotrophic grasslands in north‐west Europe often makes use of inorganic fertilizers, high stocking densities and silage‐based forage systems to maximize productivity. The impact of these practices has resulted in a simplification of the plant community combined with wide‐scale declines in the species richness of grassland invertebrates. We aim to identify how field margin management can be used to promote invertebrate diversity across a suite of functionally diverse taxa (beetles, planthoppers, true bugs, butterflies, bumblebees and spiders).

2. Using an information theoretic approach we identify the impacts of management (cattle grazing, cutting and inorganic fertilizer) and plant community composition (forb species richness, grass species richness and sward architecture) on invertebrate species richness and body size. As many of these management practices are common to grassland systems throughout the world, understanding invertebrate responses to them is important for the maintenance of biodiversity.

3. Sward architecture was identified as the primary factor promoting increased species richness of both predatory and phytophagous trophic levels, as well as being positively correlated with mean body size. In all cases phytophagous invertebrate species richness was positively correlated with measures of plant species richness.

4. The direct effects of management practices appear to be comparatively weak, suggesting that their impacts are indirect and mediated though the continuous measures of plant community structure, such as sward architecture or plant species richness.

5. Synthesis and applications. By partitioning field margins from the remainder of the field, economically viable intensive grassland management can be combined with extensive management aimed at promoting native biodiversity. The absence of inorganic fertilizer, combined with a reduction in the intensity of both cutting and grazing regimes, promotes floral species richness and sward architectural complexity. By increasing sward architecture the total biomass of invertebrates also increased (byc.60% across the range of sward architectural measures seen in this study), increasing food available for higher trophic levels, such as birds and mammals.
Efficacy of prescribed grazing depends on timing intensity and frequency
Authors: Rinella Matthew J. , Hileman Benjamin J.
Published: June 2009

1. Exotic weeds and woody plants have invaded many grasslands, and prescribed grazing is one management technique used to combat these plants. Prescribed grazing entails introducing livestock such as sheep or goats that eat unwanted plants. It sometimes has desirable effects, but inconsistencies among study results discourage widespread use. Detailed studies that manipulate grazing timings, intensities and frequencies may explain inconsistencies among previous studies and identify effective weed control strategies.

2. We studied Euphorbia esula, an invasive forb avoided by cattle but eaten by sheep. We used simulated grazing (clipping) to estimate E. esula and resident plant responses to cattle and sheep grazing protocols.

3. Depending on timing, intensity and frequency, simulated grazing either: (i) did not dramatically affect the invader and/or resident species, (ii) increased the invader and decreased resident species or (iii) decreased the invader and increased resident species. These disparate results illustrate that successful prescribed grazing entails more than simply introducing animals that eat unwanted plants.

4. Our most promising finding was that removing small quantities of invader and resident species’ biomass at early growth stages reduced the invader and increased resident species over time. Defoliating more intensively at later growth stages often gave the opposite response. Forage availability is lowest in spring, so a given landmass can be prescription grazed with fewer animals (or in less time) in spring compared with later in the year.

5. Synthesis and applications. Our study illustrates that responses to prescribed grazing depend heavily on the specifics of the grazing regime. Our results show that some grazing strategies have the potential to exacerbate weed problems, while other strategies help to control the invader and restore desired species. In the case of E. esula, very light prescribed grazing can be beneficial when conducted early in the growing season.
Robust decisions for declaring eradication of invasive species
Authors: Rout Tracy M. , Thompson Colin J. , McCarthy Michael A.
Published: June 2009

1.
 Invasive species threaten biodiversity, and their eradication is desirable whenever possible. Deciding whether an invasive species has been successfully eradicated is difficult because of imperfect detection. Two previous studies [Regan et al., Ecology Letters, 9 (2006), 759; Rout et al., Journal of Applied Ecology, 46 (2009), 110] have used a decision theory framework to minimize the total expected cost by finding the number of consecutive surveys without detection (absent surveys) after which a species should be declared eradicated. These two studies used different methods to calculate the probability that the invasive species is present when it has not been detected for a number of surveys. However, neither acknowledged uncertainty in this probability, which can lead to suboptimal solutions.

2.   We use info‐gap theory to examine the effect of uncertainty in the probability of presence on decision‐making. Instead of optimizing performance for an assumed system model, info‐gap theory finds the decision among the alternatives considered that is most robust to model uncertainty while meeting a set performance requirement. This is the first application of info‐gap theory to invasive species management.

3.  We find the number of absent surveys after which eradication should be declared to be relatively robust to uncertainty in the probability of presence. This solution depends on the nominal estimate of the probability of presence, the performance requirement and the cost of surveying, but not the cost of falsely declaring eradication.

4.   More generally, to be robust to uncertainty in the probability of presence, managers should conduct at least as many surveys as the number that minimizes the total expected cost. This holds for any nominal model of the probability of presence.

5.
 Synthesis and applications. Uncertainty is pervasive in ecology and conservation biology. It is therefore crucial to consider its impact on decision‐making; info‐gap theory provides a way to do this. We find a simple expression for the info‐gap solution, which could be applied by eradication managers to make decisions that are robust to uncertainty in the probability of presence.
Molecular inference of a Late Pleistocene diversification shift inNigellas. lat. (Ranunculaceae) resulting from increased speciation in the Aegean archipelago
Authors: Bittkau Christiane , Comes Hans Peter
Published: June 2009

Aim To infer the temporal course and geographical mode of speciation in Mediterranean/Southwest AsianNigellas. lat.

Location Mediterranean Basin, Aegean archipelago.

Methods Phylogenies forNigellaL. andGaridellaL. (= Nigellas. lat.) were obtained from maximum‐likelihood analyses of internal transcribed spacer (ITS) sequences. Diversification through time was analysed by log lineages‐through‐time (LTT) plots and survival analyses. Relative node age estimates were regressed against the degree of sympatry between sister clades to infer the predominant mode of geographical speciation inNigellas. lat.

Results The Late Pleistocene radiation of theNigella arvensiscomplex in the Aegean region caused a significant departure from a stochastic speciation/extinction process of diversification during the evolution ofNigellas. lat., a lineage of (at least) Late Miocene origin. Speciation withinNigellas. lat. predominantly took place in allopatry.

Main conclusions No significant effect on diversification rate was found regarding the establishment of a Mediterranean‐type climate, or the onset of the Quaternary climatic oscillations. Rather, the accelerated rate of speciation in theN. arvensiscomplex is plausibly related toincreasedopportunities for allopatric speciation afforded by the (palaeo)geographical complexity of the Aegean archipelago combined with Late Pleistocene changes in climate and sea level. The evolution of self‐pollination and associated changes in habitat preference and flowering time further augmented speciation and niche differentiation within the complex, but these changes did not act as the primary promoters of the radiation process.
Floristic changes in the Iberian Peninsula and Balearic Islands (south‐west Europe) during the Cenozoic
Authors: Postigo Mijarra José M. , Barrón Eduardo , Gómez Manzaneque Fernando , Morla Carlos
Published: June 2009

Aim  The aim of this work was to identify the main changes in the flora and vegetation of the Iberian Peninsula over the Cenozoic Era, to record the disappearance of taxa associated with these changes and to determine the influence of climate and human activity on these events.

Location  The Iberian Peninsula and Balearic Islands.

Methods  A critical review was made of the palaeobotanical literature with the aims of detecting patterns of floristic change and extracting information on the disappearance of different taxa over the Cenozoic. These data are viewed alongside the most recent data for the climate of this period. A critical analysis is made of the role of Palaeotropical and Arctotertiary taxa in the forest communities of the Iberian Peninsula throughout the Cenozoic.

Results  Although the Eocene–Oligocene transition was a time when many taxa disappeared, the most outstanding events occurred between the end of the Oligocene and throughout the Miocene. Substantial floristic changes took place over this period, including the disappearance of 177 Palaeotropical taxa. This was probably related to acute cooling and aridification; no evidence exists that the Messinian Salinity Crisis had any important effect in the Iberian Peninsula. The last great disappearance of Palaeotropical taxa (36 in total) ended in the Middle–Late Piacenzian; Arctotertiary taxa were most affected during the Pleistocene. The Lower–Middle Pleistocene transition, best represented by marine isotopic stages (MIS) 36–34 and 20–18 and characterized by a change in glacial cyclicity, was the time of the last notable disappearance of taxa.

Main conclusions  This work provides the first chronogram of extinctions for the Iberian flora, and records the disappearance of 277 taxa during the Cenozoic. A clear relationship was detected between the main climatic events and the latest appearances of the different taxa.
Socio‐cultural aspects of prompting student reflection in Web‐based inquiry learning environments
Authors: Furberg A.
Published: June 2009

This paper reports on a qualitative study of students' engagement with a Web‐based inquiry environment aimed at prompting student reflection in processes of scientific inquiry. In order to demonstrate how prompts become structuring resources for students' scientific inquiry, detailed analyses of students' interaction processes are conducted. The students' written responses to the reflection prompts indicated a widespread use of a ‘copy and paste’ strategy. The analyses of student interaction deepen this finding and show that instead of participating in reflection activities, the students make use of these ‘copy and paste’ strategies in order to come up with ‘correct’ answers to the prompts. Further, the analyses indicate that the students' employment of these strategies can be seen as a response to what can be termed the institutional practices of schooling embedded within the design of the prompts. These findings are discussed and explored in accordance with findings from previous studies on prompting students' reflection in Web‐based inquiry environments. The study demonstrates the value of a socio‐cultural perspective for gaining a deeper understanding of students' engagement with Web‐based learning environments. Such a perspective can give valuable insight into how to (re)design prompts, and how prompts can be productive parts of students' learning.
An investigation of serum concentration of apoM as a potential MODY3 marker using a novel ELISA
Authors: Cervin C. , Axler O. , Holmkvist J. , Almgren P. , Rantala E. , Tuomi T. , Groop L. , Dahlbäck B. , Karlsson E.
Published: June 2009

Abstract.  Cervin C, Axler O, Holmkvist J, Almgren P, Rantala E, Tuomi T, Groop L, Dahlbäck B, Karlsson E (Lund University, Malmö, Sweden, Steno Diabetes Center, Gentofte, Denmark, University of Helsinki; and Folkhälsan Research Centre, Helsinki, Finland). An investigation of serum concentration of apoM as a potential MODY3 marker using a novel ELISA. J Intern Med 2010; 267: 316–321.

Objective.  To investigate the fitness of serum apolipoprotein M (apoM) concentration as a marker for maturity‐onset diabetes of the young 3 (MODY3).

Study design and subjects.  This study consisted of two parts. A family study included 71 carriers of the P291fsinsC mutation in hepatocyte nuclear factor‐1α (HNF‐1α) from the Finnish Botnia study, 53 of whom were diabetic, and 75 matched family controls. A second, case–control study included 24 MODY3 patients, 17 healthy MODY3 mutation carriers, 11 MODY1 patients, 18 type 2 diabetes patients and 19 healthy control individuals. Subjects in the case–control study were recruited from the Botnia study or the Clinic of Endocrinology, Malmö University Hospital. Serum apoM levels were measured using a novel ELISA based on two monoclonal apoM antibodies.

Results.  In the family study, mean serum apoM was 10% lower in female carriers of the P291fsinsC mutation compared to the family controls (P = 0.0058), a difference which remained significant after adjustment for diabetes status. There was no observed difference between groups for men. In the case–control study, no significant difference in apoM concentration was observed between MODY3 and type 2 diabetes patients, neither before nor after adjustment for total cholesterol.

Conclusions.  Female carriers of the P291fsinsC mutation in HNF‐1α displayed slightly lower apoM serum levels. This difference is too small for apoM to be reliably employed as a biomarker for HNF‐1α mutation status.
Impact of a high‐dose nitrate strategy on cardiac stress in acute heart failure: a pilot study
Authors: Breidthardt T. , Noveanu M. , Potocki M. , Reichlin T. , Egli P. , Hartwiger S. , Socrates T. , Gayat E. , Christ M. , Mebazaa A. , Mueller C.
Published: June 2009

Abstract.  Breidthardt T, Noveanu M, Potocki M, Reichlin T, Egli P, Hartwiger S, Socrates T, Gayat E, Christ M, Mebazaa A, Mueller C (University Hospital, Basel, Switzerland, University Paris, Paris, France, and Klinikum Nürnberg, Nürnberg, Germany). Impact of a high‐dose nitrate strategy on cardiac stress in acute heart failure: a pilot study. J Intern Med 2010; 267: 322–330.

Background.  Intravenous nitrate therapy has been shown to improve short‐term outcome of acute heart failure patients treated in the intensive care unit. The potential of a noninvasive high‐dose nitrate strategy in the Emergency Department and the general ward remains unknown.

Methods.  A total of 128 consecutive acute heart failure patients were either treated with standard therapy or high‐dose sublingual and transdermal nitrates on top of standard of care treatment. Cardiac recovery, quantified by B‐type natriuretic peptide (BNP) levels during the first 48 h, was the primary endpoint. Secondary endpoints ascertained the safety of the nitrate therapy.

Results.  The high nitrate group received higher doses of nitrates during the first 48 h compared to the standard therapy group [82.4 mg (46.2–120.6) vs. 20 mg (10–30) respectively, P < 0.001]. The amount of diuretics given in both groups was similar. BNP levels decreased in all patients (P < 0.0001). However, the BNP decrease was larger in the high‐dose nitrate group (P < 0.0001). The larger decrease in BNP in the high‐dose nitrate group was already apparent 12 h after the initiation of treatment. After 48 h BNP values decreased by an average of 29 ± 4.9% in the high‐dose nitrate strategy group compared to 15 ± 5.4% during standard therapy. There was a strong trend towards fewer ICU admissions in the high‐dose nitrate group [high‐dose nitrates: 2 cases (4%) vs. standard therapy: 9 cases (13%); P = 0.06]. During the study period, no intergroup changes were observed in blood pressure, RIFLE classes of acute kidney injury or troponin T. In‐hospital and 90‐day outcome was similar amongst the two groups.

Conclusions.  A noninvasive high‐dose nitrate strategy on top of standard therapy is safe and notably accelerates cardiac recovery in patients observed on the general ward.
Halton sampling for autofocus
Authors: PENGO T. , MUÑOZ‐BARRUTIA A. , ORTIZ‐DE‐SOLÓRZANO C.
Published: June 2009

Reliable autofocusing is a critical part of any automated microscopy system: by precisely positioning the sample in the focal plane, the acquired images are sharp and can be accurately segmented and quantified. The three main components of an autofocus algorithm are a contrast function, an optimization algorithm and a sampling strategy. The latter has not been given much attention in the literature. It is however a very important part of the autofocusing algorithm, especially in high content and high throughput image‐based screening. It deals with the problem of sampling the focus surface as sparsely as possible to reduce bleaching and computation time while with sufficient detail as to permit a faithful interpolation. We propose a new strategy that has higher performance compared to the classical square grid or the hexagonal lattice, which is based on the concept of low discrepancy point sets and in particular on the Halton point set. We tested the new algorithm on nine different focus surfaces, each under 24 different combinations of Signal‐to‐Noise ratio (SNR) and sampling rate, obtaining that in 88% of the tested conditions, Halton sampling outperforms its counterparts.
TEM foil preparation of sub‐micrometre sized individual grains by focused ion beam technique
Authors: HOLZAPFEL C. , SOLDERA F. , VOLLMER C. , HOPPE P. , MÜCKLICH F.
Published: June 2009

Analysis of presolar silicate grains provides new knowledge on interstellar and circumstellar environments and can be used to test models of the Galactic chemical evolution. However, structural information of these grains is rare because sample preparation for transmission electron microscopy is very difficult due to the small dimensions of these grains (<0.5 μm). With the use of the focused ion beam technique thin foils from these grains for transmission electron microscopy analysis can be prepared. Nevertheless, reaching the required precision of some tens of nanometres for the preparation of the transmission electron microscopy foil in the place of interest is not trivial. Furthermore, in the current samples, the grain of interest can only be identified by its different isotopic composition; i.e. there is no contrast difference in scanning electron microscopy or transmission electron microscopy images which allow the identification of the grain. Therefore, the grain has to be marked in some way before preparing the transmission electron microscopy foil. In the present paper, a method for transmission electron microscopy foil preparation of grains about 200 to 400 nm in diameter is presented. The method utilizes marking of the grain by Pt deposition and milling of holes to aid in the exact orientation of the transmission electron microscopy foil with respect to the grain. The proposed method will be explained in detail by using an example grain.
EBSD for analysing the twinning microstructure in fine‐grained TWIP steels and its influence on work hardening
Authors: BARBIER D. , GEY N. , BOZZOLO N. , ALLAIN S. , HUMBERT M.
Published: June 2009

A 22 Mn–0.6 C twinning induced plasticity steel with an average grain size of 2.6 μm was deformed in tension at room temperature. The electron backscattered diffraction technique was used to characterize the twinning structure in relation with the local texture evolution. For nanoscale analysis, additional transmission electron microscopy analysis was performed. Nanotwins were activated in the largest grains from the beginning of the deformation. They interacted with a well‐developed dislocation structure that induced detectable intragranular orientation variations. With increasing deformation, dense bundles of nanotwins preferentially developed in grains oriented close to the <111>//tensile direction fibre (promoted by the deformation) as well as medium to high angle sub‐boundaries. These key features of the twinned microstructure were finally related to the remarkably high strain hardening, which evolved according to different stages.
Chromatic two‐photon excitation fluorescence imaging
Authors: XU Q. , SHI K. , YIN S. , LIU Z.
Published: June 2009

We report on a chromatic axial scanning method for two‐photon excitation fluorescence imaging. Effective axial scanning is achieved by incorporating a Fresnel lens in the system, which has large chromatic aberration and can therefore focus the excitation beam to different axial positions depending on its wavelength. We experimentally demonstrated this technique and used it to image the cross‐section of fluorescent microspheres.
High‐aperture cryogenic light microscopy
Authors: LE GROS M.A. , McDERMOTT G. , UCHIDA M. , KNOECHEL C.G. , LARABELL C.A.
Published: June 2009

We report here the development of instruments and protocols for carrying out high numerical aperture immersion light microscopy on cryogenic specimens. Imaging by this modality greatly increases the lifetimes of fluorescence probes, including those commonly used for protein localization studies, while retaining the ability to image the specimen with high fidelity and spatial resolution. The novel use of a cryogenic immersion fluid also minimizes the refractive index mismatch between the sample and lens, leading to a more efficient coupling of the light from the sample to the image forming system. This enhancement is applicable to both fluorescence and transmitted light microscopy techniques. The design concepts used for the cryogenic microscope can be applied to virtually any existing light‐based microscopy technique. This prospect is particularly exciting in the context of ‘super‐resolution’ techniques, where enhanced fluorescence lifetime probes are especially useful. Thus, using this new modality it is now possible to observe dynamic events in a live cell, and then rapidly vitrify the specimen at a specific time point prior to carrying out high‐resolution imaging. The techniques described can be used in conjunction with other imaging modalities in correlated studies. We have also developed instrumentation to perform cryo‐light imaging together with soft X‐ray tomography on the same cryo‐fixed specimen as a means of carrying out high content, quantifiable correlated imaging analyses. These methods are equally applicable to correlated light and electron microscopy of frozen biological objects.
Live cell tracking based on cellular state recognition from microscopic images
Authors: SUN Y.‐N. , LIN C.‐H. , KUO C.‐C. , HO C.‐L. , LIN C.‐J.
Published: June 2009

The analysis of cell motion is an essential process in fundamental medical studies because most active cellular functions involve motion. In this paper, a computer‐assisted motion analysis system is proposed for cell tracking. In the proposed tracking process, unlike in conventional tracking methods, cellular states referring to the cellular life cycle are defined and appropriate strategies are adopted for cells at different states. The use of cellular state recognition allows detection of possible cell division and hence can improve the robustness of cell tracking. Experimental results show that cells can be successfully segmented and tracked over a long period of time, and the proposed system is found to be as accurate as manual tracking. Various quantitative analyses and visualizations are used to represent cell motion, which demonstrates the usefulness of the proposed system in the study of cell dynamics.
Daytime Gating in the Syrian Hamster Pineal Gland
Authors: Salingre A. , Klosen P. , Pévet P. , Simonneaux V.
Published: June 2009

Melatonin synthesis in rodents is tightly regulated at the transcriptional level by stimulatory and inhibitory transcription factors. Among them, phosphorylated cAMP‐related element binding protein (pCREB) and inducible cAMP early repressor (ICER), a strong inhibitor of cAMP‐related element‐driven genes, have an antagonistic action in activating/inhibiting the transcription of theAa‐natgene, which is an important enzyme in melatonin synthesis. In the Syrian hamster, a rodent displaying a seasonal control of reproduction, melatonin synthesis is strongly gated to the second part of the night. Indeed, exogenous adrenergic stimulation is unable to stimulateAa‐natgene transcription and melatonin synthesis during daytime. In the present study, we investigated whether ICER may be the cause of this daytime repression by comparing the dynamic of ICER and the adrenergic regulation of two genes whose expression is rapidly activated by cAMP‐dependant mechanisms, c‐fosandIcer. Adrenergic induction of c‐fosandIcerexpression was not possible during daytime, except at early day. ICER immunoreactivity was elevated throughout the daily cycle but reached the highest levels at early day, when gene expression can be induced by adrenergic agonists. Additionally, CREB phosphorylation was subjected to the same daily gating with an adrenergic induction occurring in the early but not in the late day. Taken together, our results indicate that the diurnal gating of pineal activity in the Syrian hamster is not caused by the repressor ICER and that it may occur at the level of noradrenergic receptor signalling.
Continuous positive airway pressure treatment for obstructive sleep apnoea reduces resting heart rate but does not affect dysrhythmias: a randomised controlled trial
Authors: CRAIG SONYA , PEPPERELL JUSTIN C. T. , KOHLER MALCOLM , CROSTHWAITE NICKY , DAVIES ROBERT J. O. , STRADLING JOHN R.
Published: June 2009

Obstructive sleep apnoea (OSA) is associated with cardiovascular morbidity and may precipitate cardiac dysrhythmias. Uncontrolled reports suggest that continuous positive airway pressure (CPAP) may reduce dysrhythmia frequency and resting heart rate. We undertook a randomised controlled trial of therapeutic CPAP and compared with a subtherapeutic control which included an exploration of changes in dysrhythmia frequency and heart rate. Values are expressed as mean (SD). Eighty‐three men [49.5 (9.6) years] with moderate–severe OSA [Oxygen Desaturation Index, 41.2 (24.3) dips per hour] underwent 3‐channel 24‐h electrocardiograms during normal daily activities, before and after 1 month of therapeutic (n = 43) or subtherapeutic (n = 40) CPAP. Recordings were manually analysed for mean heart rate, pauses, bradycardias, supraventricular and ventricular dysrhythmias. The two groups were well matched for age, body mass index, OSA severity, cardiovascular risk factors and history. Supraventricular ectopics and ventricular ectopics were frequently found in 95.2% and 85.5% of patients, respectively. Less common were sinus pauses (42.2%), episodes of bradycardia (12%) and ventricular tachycardias (4.8%). Compared with subtherapeutic control, CPAP reduced mean 24‐h heart rate from 83.0 (11.5) to 79.7 (9.8) (P < 0.002) in the CPAP group compared with a non‐significant rise (P = 0.18) from 79.0 (10.4) to 79.9 (10.4) in the subtherapeutic group; this was also the case for the day period analysed separately. There was no significant change in the frequencies of dysrhythmias after CPAP. Four weeks of CPAP therapy reduces mean 24‐h heart rate possibly due to reduced sympathetic activation but did not result in a significant decrease in dysrhythmia frequency.
Highway driving performance and cognitive functioning the morning after bedtime and middle‐of‐the‐night use of gaboxadol, zopiclone and zolpidem
Authors: LEUFKENS TIM R. M. , LUND JESPER S. , VERMEEREN ANNEMIEK
Published: June 2009

Gaboxadol is a selective extrasynaptic GABAA receptor agonist previously in development for the treatment of insomnia. Due to its short half‐life (1.5–2 h) it is expected to be free from residual effects the next morning. The present study assessed the residual effects of evening and middle‐of‐the‐night administration of 15 mg of gaboxadol on cognitive, psychomotor and driving performance. Twenty‐eight healthy volunteers entered the study with 25 (12 women; mean age 31.4 years) completing a double‐blind, placebo‐controlled, active‐referenced five‐way cross‐over study. Each treatment night subjects ingested one capsule at 23:00 hours and one at 04:00 hours. Treatments were placebo at both times, 15 mg gaboxadol or 7.5 mg zopiclone followed by placebo, and placebo followed by 15 mg gaboxadol or 10 mg zolpidem. Effects on cognition and psychomotor performance were assessed between 07:30 and 08:30 hours and on driving between 09:00 and 10:00 hours. Driving, as measured by standard deviation of lateral position in an on‐the‐road driving test, was almost significantly (P < 0.07) impaired after evening administration of gaboxadol for the all‐subjects‐completed set (n = 25) but significantly (P < 0.05) in the full analysis set (n = 28). Effects of all other active treatments on driving were significant. Evening administration of gaboxadol had minor effects on divided attention only, whereas middle‐of‐the‐night administration impaired performance significantly in all tests except memory. Zolpidem and zopiclone impaired performance significantly in every test except tracking after zopiclone; 15 mg of gaboxadol can produce minor residual effects on driving after evening administration. Administration later at night is associated with moderately impairing residual effects on driving and psychomotor performance but not on memory.
Evidence for divergent natural selection of a Lake Tanganyika cichlid inferred from repeated radiations in body size
Authors: TAKAHASHI T. , WATANABE K. , MUNEHARA H. , RÜBER L. , HORI M.
Published: June 2009

Divergent natural selection is thought to play a vital role in speciation, but clear, measurable examples from nature are still few. Among the many possible sources of divergent natural selection, predation pressure may be important because predators are ubiquitous in food webs. Here, we show evidence for divergent natural selection in a Lake Tanganyika cichlid,Telmatochromis temporalis, which uses burrows under stones or empty snail shells as shelters. This species contains normal and dwarf morphs at several localities. The normal morph inhabits rocky shorelines, whereas the dwarf morph invariably inhabits shell beds, where empty snail shells densely cover the lake bottom. Genetic evidence suggested that the dwarf morph evolved independently from the normal morph at two areas, and morphological analysis and evaluation of habitat structure revealed that the body sizes of morphs closely matched the available shelter sizes in their habitats. These findings suggest that the two morphs repeatedly evolved through divergent natural selection associated with the strategy for sheltering from predators.
Influence of clinical parameters on the results of 13C‐octanoic acid breath tests: examination of different mathematical models in a large patient cohort
Authors: Keller J. , Andresen V. , Wolter J. , Layer P. , Camilleri M.
Published: June 2009

Abstract  It is assumed, although not proven, that 13CO2‐excretion following ingestion of 13C‐octanoic acid (13C‐OA) does not only depend on gastric emptying (GE) but also on absorption and metabolism of 13C‐OA and endogenous CO2‐production. Our aims were (i) to test the effects of patient characteristics and of diseases that may impair 13C‐OA‐metabolism on GE parameters. (ii) To compare different GE endpoints. Therefore, we investigated effects of age, gender, BMI and diseases with potential impact on 13C‐OA‐metabolism (including pancreatic, liver and lung disease, diabetes, IBD) on cumulative 4h‐13CO2‐excretion (4h‐CUM) and T½ calculated by non‐linear regression model (NL, determined by shape of breath test curve) and generalized linear regression model (GLR, reflects absolute 13CO2‐excretion) in 1279 patients and 19 healthy controls who underwent a standardized 13C‐OA‐breath test. Digestive and metabolic disturbances hardly influenced 4h‐CUM or T½ calculated by NL or GLR models. In the multivariate linear regression models, 4h‐CUM was significantly predicted by diabetes adjusted for age, gender and IBD but influence of these parameters was small (R2 = 0.028, P < 0.0001). T½NL and 4h‐CUM were weakly correlated, even after exclusion of tests with unrealistically high estimates for T½NL (n = 1095, R2 = 0.029, P < 0.0001). Conversely, 4h‐CUM was closely associated with T½GLR (exponential correlation, R2 = 0.774, P < 0.00001, n = 1279). We conclude that influences of digestive and metabolic disturbances on 13CO2‐excretion following 13C‐OA‐application are generally low. Thus, our findings resolve an important criticism of methods using absolute 13CO2‐excretion for evaluation of 13C‐OA‐breath tests and suggest that such models may correctly identify T½ in a mixed patient population.
How might infant and paediatric immune responses influence malaria vaccine efficacy?
Authors: MOORMANN A. M.
Published: June 2009

Naturally acquired immunity to malaria requires repeat infections yet does not engender sterile immunity or long‐lasting protective immunologic memory. This renders infants and young children the most susceptible to malaria‐induced morbidity and mortality, and the ultimate target for a malaria vaccine. The prevailing paradigm is that infants initially garner protection due to transplacentally transferred anti‐malarial antibodies and other intrinsic factors such as foetal haemoglobin. As these wane infants have an insufficient immune repertoire to prevent genetically diverse Plasmodium infections and an inability to control malaria‐induced immunopathology. This Review discusses humoral, cell‐mediated and innate immune responses to malaria and how each contributes to protection – focusing on how deficiencies in infant and paediatric immune responses might influence malaria vaccine efficacy in this population. In addition, burgeoning evidence suggests a role for inhibitory receptors that limit immunopathology and guide the development of long‐lived immunity. Precisely how age or malaria infections influence the function of these regulators is unknown. Therefore the possibility that infants may not have the immune‐dexterity to balance effective parasite clearance with timely immune‐regulation leading to protective immunologic memory is considered. And thus, malaria vaccines tested in adults and older children may not be predictive for trials conducted in infants.
Genetic diversity and malaria vaccine design, testing and efficacy: preventing and overcoming ‘vaccine resistant malaria’
Authors: TAKALA S. L. , PLOWE C. V.
Published: June 2009

The development of effective malaria vaccines may be hindered by extensive genetic diversity in the surface proteins being employed as vaccine antigens. Understanding of the extent and dynamics of genetic diversity in vaccine antigens is needed to guide rational vaccine design and to interpret the results of vaccine efficacy trials conducted in malaria endemic areas. Molecular epidemiological, population genetic, and structural approaches are being employed to try to identify immunologically relevant polymorphism in vaccine antigens. The results of these studies will inform choices of which alleles to include in multivalent or chimeric vaccines; however, additional molecular and immuno‐epidemiological studies in a variety of geographic locations will be necessary for these approaches to succeed. Alternative means of overcoming antigenic diversity are also being explored, including boosting responses to critical conserved regions of current vaccine antigens, identifying new, more conserved and less immunodominant antigens, and developing whole‐organism vaccines. Continued creative application and integration of tools from multiple disciplines, including epidemiology, immunology, molecular biology, and evolutionary genetics and genomics, will likely be required to develop broadly protective vaccines against Plasmodium and other antigenically complex pathogens.
The development of the RTS,S malaria vaccine candidate: challenges and lessons
Authors: BALLOU W. R.
Published: June 2009

RTS,S is the world’s most advanced malaria vaccine candidate and is intended to protect infants and young children living in malaria endemic areas of sub‐Saharan Africa against clinical disease caused by Plasmodium falciparum. Recently, a pivotal Phase III efficacy trial of RTS,S began in Africa. The goal of the programme has been to develop a vaccine that will be safe and effective when administered via the Expanded Program for Immunization (EPI) and significantly reduce the risk of clinically important malaria disease during the first years of life. If a similar reduction in the risk of severe malaria and other important co‐morbidities associated with malaria infection can be achieved, then the vaccine could become a major new tool for reducing the burden of malaria in sub‐Saharan Africa. Encouraging data from the ongoing phase II programme suggest that these goals may indeed be achievable. This review discusses some of the unique challenges that were faced during the development of this vaccine, highlights the complexity of developing new vaccine technologies and illustrates the power of partnerships in the ongoing fight against this killer disease.
Malaria vaccine trial endpoints – bridging the gaps between trial design, public health and the next generation of vaccines
Authors: O’MEARA W. P. , LANG T.
Published: June 2009

A recent working group convened by the World Health Organization recommended that time to first or only episode of clinical malaria should be used to evaluate vaccine efficacy in phase III trials. However, calculating vaccine efficacy based on this endpoint misses important aspects of malaria disease and transmission. Here, we discuss the gaps that this approach leaves in predicting the potential public health impact of a vaccine and the challenges faced by vaccine trial designers. We examine the implications of current vaccine trial design on effectiveness studies and the next generation of malaria vaccines.
Acclimation of leaf hydraulic conductance and stomatal conductance of Pinus taeda (loblolly pine) to long‐term growth in elevated CO2 (free‐air CO2 enrichment) and N‐fertilization
Authors: DOMEC JEAN‐CHRISTOPHE , PALMROTH SARI , WARD ERIC , MAIER CHRIS A. , THÉRÉZIEN M. , OREN RAM
Published: June 2009

We investigated how leaf hydraulic conductance (Kleaf) of loblolly pine trees is influenced by soil nitrogen amendment (N) in stands subjected to ambient or elevated CO2 concentrations (CO2a and CO2e, respectively). We also examined how Kleaf varies with changes in reference leaf water potential (Ψleaf‐ref) and stomatal conductance (gs‐ref) calculated at vapour pressure deficit, D of 1 kPa. We detected significant reductions in Kleaf caused by N and CO2e, but neither treatment affected pre‐dawn or midday Ψleaf. We also detected a significant CO2e‐induced reduction in gs‐ref and Ψleaf‐ref. Among treatments, the sensitivity of Kleaf to Ψleaf was directly related to a reference Kleaf (Kleaf‐ref computed at Ψleaf‐ref). This liquid‐phase response was reflected in a similar gas‐phase response, with gs sensitivity to D proportional to gs‐ref. Because leaves represented a substantial component of the whole‐tree conductance, reduction in Kleaf under CO2e affected whole‐tree water use by inducing a decline in gs‐ref. The consequences of the acclimation of leaves to the treatments were: (1) trees growing under CO2e controlled morning leaf water status less than CO2a trees resulting in a higher diurnal loss of Kleaf; (2) the effect of CO2e on gs‐ref was manifested only during times of high soil moisture.
Thermogenesis of three species of Arum from Crete
Authors: SEYMOUR ROGER S. , GIBERNAU MARC , PIRINTSOS STERGIOS ARG.
Published: June 2009

Inflorescences of arum lilies have a three‐part spadix with a scent‐producing, sterile appendix above two bands of fertile male and female florets. The appendix and male florets are thermogenic, but with different temporal patterns. Heat‐production was measured in Arum concinnatum, A. creticum and A. idaeum. The male florets of A. concinnatum showed a 3 d continuous episode of thermogenesis with three waves, and the appendix warmed in a single, 6 h episode. Maximum fresh‐mass‐specific CO2 production rate was 0.17 µmol s−1 g−1 to achieve a 10.9 °C temperature elevation by the appendix, and 0.92 µmol s−1 g−1 to achieve a 4.8 °C elevation by male florets. Reversible, physiological temperature regulation was not evident in either tissue. Respiration increased with tissue temperatures with Q10 values of 1.8–3.9, rather than less than 1.0 as occurs in thermoregulatory flowers. Experimental step changes in temperature of appendix and male floret tissues also failed to show thermoregulatory responses. The patterns of thermogenesis therefore appear to be fixed by the temporal sequence of blooming. Thermogenesis in the alpine species, A. creticum and A. idaeum, was significantly lower than in the lowland A. concinnatum, possibly related to difficulty in raising floral temperature in their cold and windy habitat.
Theoretical reconsiderations when estimating the mesophyll conductance to CO2 diffusion in leaves of C3 plants by analysis of combined gas exchange and chlorophyll fluorescence measurements
Authors: YIN XINYOU , STRUIK PAUL C.
Published: June 2009

Existing methods to estimate the mesophyll conductance to CO2 diffusion (gm) are often based on combined gas exchange and chlorophyll fluorescence measurements. However, estimations of average gm by these methods are often unreliable either because the range of usable data is too narrow or because the estimations are very sensitive to measurement errors. We describe three method variants to estimate gm, for which a wider range of data are usable. They use curve‐fitting techniques, which minimise the sum of squared model deviations from the data for A (CO2 assimilation rate) or for J (linear electron transport rate). Like the existing approaches, they are all based on common physiological principles assuming that electron transport limits A. The proposed variants were far less sensitive than the existing approaches to ‘measurement noise’ either created randomly in the generated data set or inevitably existing in real data sets. Yet, the estimates of gm from the three variants differed by approximately 15%. Moreover, for each variant, a stoichiometric uncertainty in linear electron transport‐limited photosynthesis can cause another 15% difference. Any estimation of gm using gas exchange and chlorophyll fluorescence measurements should be considered with caution, especially when gm is high.