Ecological assembly rules in plant communities--approaches, patterns and prospects.

Understanding how communities of living organisms assemble has been a central question in ecology since the early days of the discipline. Disentangling the different processes involved in community assembly is not only interesting in itself but also crucial for an understanding of how communities will behave under future environmental scenarios. The traditional concept of assembly rules reflects the notion that species do not co-occur randomly but are restricted in their co-occurrence by interspecific competition. This concept can be redefined in a more general framework where the co-occurrence of species is a product of chance, historical patterns of speciation and migration, dispersal, abiotic environmental factors, and biotic interactions, with none of these processes being mutually exclusive. Here we present a survey and meta-analyses of 59 papers that compare observed patterns in plant communities with null models simulating random patterns of species assembly. According to the type of data under study and the different methods that are applied to detect community assembly, we distinguish four main types of approach in the published literature: species co-occurrence, niche limitation, guild proportionality and limiting similarity. Results from our meta-analyses suggest that non-random co-occurrence of plant species is not a widespread phenomenon. However, whether this finding reflects the individualistic nature of plant communities or is caused by methodological shortcomings associated with the studies considered cannot be discerned from the available metadata. We advocate that more thorough surveys be conducted using a set of standardized methods to test for the existence of assembly rules in data sets spanning larger biological and geographical scales than have been considered until now. We underpin this general advice with guidelines that should be considered in future assembly rules research. This will enable us to draw more accurate and general conclusions about the non-random aspect of assembly in plant communities.

An improved trap design for decoupling multinuclear RF coils.

PURPOSE: Multinuclear magnetic resonance spectroscopy and imaging require a radiofrequency probe capable of transmitting and receiving at the proton and non-proton frequencies. To minimize coupling between probe elements tuned to different frequencies, LC (inductor-capacitor) traps blocking current at the (1) H frequency can be inserted in non-proton elements. This work compares LC traps with LCC traps, a modified design incorporating an additional capacitor, enabling control of the trap reactance at the low frequency while maintaining (1) H blocking. METHODS: Losses introduced by both types of trap were analysed using circuit models. Radiofrequency coils incorporating a series of LC and LCC traps were then built and evaluated at the bench. LCC trap performance was then confirmed using (1) H and (13) C measurements in a 7T human scanner. RESULTS: LC and LCC traps both effectively block interaction between non-proton and proton coils at the proton frequency. LCC traps were found to introduce a sensitivity reduction of 5±2%, which was less than half of that caused by LC traps. CONCLUSION: Sensitivity of non-proton coils is critical. The improved trap design, incorporating one extra capacitor, significantly reduces losses introduced by the trap in the non-proton coil. Magn Reson Med 72:584-590, 2014. © 2013 Wiley Periodicals, Inc.

Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design.

BACKGROUND: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. METHODS/DESIGN: In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. DISCUSSION: A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. TRIAL REGISTRATION: The TTM-trial is registered at ClinicalTrials.gov (NCT01020916).

The effects of dominance, regular inbreeding and sampling design on Q(ST), an estimator of population differentiation for quantitative traits.

To test whether quantitative traits are under directional or homogenizing selection, it is common practice to compare population differentiation estimates at molecular markers (F(ST)) and quantitative traits (Q(ST)). If the trait is neutral and its determinism is additive, then theory predicts that Q(ST) = F(ST), while Q(ST) > F(ST) is predicted under directional selection for different local optima, and Q(ST) < F(ST) is predicted under homogenizing selection. However, nonadditive effects can alter these predictions. Here, we investigate the influence of dominance on the relation between Q(ST) and F(ST) for neutral traits. Using analytical results and computer simulations, we show that dominance generally deflates Q(ST) relative to F(ST). Under inbreeding, the effect of dominance vanishes, and we show that for selfing species, a better estimate of Q(ST) is obtained from selfed families than from half-sib families. We also compare several sampling designs and find that it is always best to sample many populations (>20) with few families (five) rather than few populations with many families. Provided that estimates of Q(ST) are derived from individuals originating from many populations, we conclude that the pattern Q(ST) > F(ST), and hence the inference of directional selection for different local optima, is robust to the effect of nonadditive gene actions.

Rational design of indoleamine 2,3-dioxygenase inhibitors.

Indoleamine 2,3-dioxygenase (IDO) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. We have used the evolutionary docking algorithm EADock to design new inhibitors of this enzyme. First, we investigated the modes of binding of all known IDO inhibitors. On the basis of the observed docked conformations, we developed a pharmacophore model, which was then used to devise new compounds to be tested for IDO inhibition. We also used a fragment-based approach to design and to optimize small organic molecule inhibitors. Both approaches yielded several new low-molecular weight inhibitor scaffolds, the most active being of nanomolar potency in an enzymatic assay. Cellular assays confirmed the potential biological relevance of four different scaffolds.

Development, design and validation of solid reference samples.

We developed a method of sample preparation using epoxy compound, which was validated in two steps. First, we studied the homogeneity within samples by scanning tubes filled with radioactive epoxy. We found within-sample homogeneity better than 2%. Then, we studied the homogeneity between samples during a 4.5 h dispensing time. The homogeneity between samples was found to be better than 2%. This study demonstrates that we have a validated method, which assures the traceability of epoxy samples.

Cost-effective experimental design to support modeling of concentration-response functions

Modeling concentration-response function became extremely popular in ecotoxicology during the last decade. Indeed, modeling allows determining the total response pattern of a given substance. However, reliable modeling is consuming in term of data, which is in contradiction with the current trend in ecotoxicology, which aims to reduce, for cost and ethical reasons, the number of data produced during an experiment. It is therefore crucial to determine experimental design in a cost-effective manner. In this paper, we propose to use the theory of locally D-optimal designs to determine the set of concentrations to be tested so that the parameters of the concentration-response function can be estimated with high precision. We illustrated this approach by determining the locally D-optimal designs to estimate the toxicity of the herbicide dinoseb on daphnids and algae. The results show that the number of concentrations to be tested is often equal to the number of parameters and often related to the their meaning, i.e. they are located close to the parameters. Furthermore, the results show that the locally D-optimal design often has the minimal number of support points and is not much sensitive to small changes in nominal values of the parameters. In order to reduce the experimental cost and the use of test organisms, especially in case of long-term studies, reliable nominal values may therefore be fixed based on prior knowledge and literature research instead of on preliminary experiments

Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: study design and baseline characteristics.

OBJECTIVE: Intervention during the pre-psychotic period of illness holds the potential of delaying or even preventing the onset of a full-threshold disorder, or at least of reducing the impact of such a disorder if it does develop. The first step in realizing this aim was achieved more than 10 years ago with the development and validation of criteria for the identification of young people at ultra-high risk (UHR) of psychosis. Results of three clinical trials have been published that provide mixed support for the effectiveness of psychological and pharmacological interventions in preventing the onset of psychotic disorder. METHOD: The present paper describes a fourth study that has now been undertaken in which young people who met UHR criteria were randomized to one of three treatment groups: cognitive therapy plus risperidone (CogTher + Risp: n = 43); cognitive therapy plus placebo (CogTher + Placebo: n = 44); and supportive counselling + placebo (Supp + Placebo; n = 28). A fourth group of young people who did not agree to randomization were also followed up (monitoring: n = 78). Baseline characteristics of participants are provided. RESULTS AND CONCLUSION: The present study improves on the previous studies because treatment was provided for 12 months and the independent contributions of psychological and pharmacological treatments in preventing transition to psychosis in the UHR cohort and on levels of psychopathology and functioning can be directly compared. Issues associated with recruitment and randomization are discussed.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

BACKGROUND AND OBJECTIVES: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. PROTOCOL DESIGN: The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125 mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8 mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. OUTCOMES: Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. SAMPLE SIZE CALCULATION: It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

Design, data management, and population baseline characteristics of the PERFORM magnetic resonance imaging project.

Quantitative information from magnetic resonance imaging (MRI) may substantiate clinical findings and provide additional insight into the mechanism of clinical interventions in therapeutic stroke trials. The PERFORM study is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke. We report on the design of an exploratory longitudinal MRI follow-up study that was performed in a subgroup of the PERFORM trial. An international multi-centre longitudinal follow-up MRI study was designed for different MR systems employing safety and efficacy readouts: new T2 lesions, new DWI lesions, whole brain volume change, hippocampal volume change, changes in tissue microstructure as depicted by mean diffusivity and fractional anisotropy, vessel patency on MR angiography, and the presence of and development of new microbleeds. A total of 1,056 patients (men and women ≥ 55 years) were included. The data analysis included 3D reformation, image registration of different contrasts, tissue segmentation, and automated lesion detection. This large international multi-centre study demonstrates how new MRI readouts can be used to provide key information on the evolution of cerebral tissue lesions and within the macrovasculature after atherothrombotic stroke in a large sample of patients.

Bacterial sensors: synthetic design and application principles

Bacterial reporters are live, genetically engineered cells with promising application in bioanalytics. They contain genetic circuitry to produce a cellular sensing element, which detects the target compound and relays the detection to specific synthesis of so-called reporter proteins (the presence or activity of which is easy to quantify). Bioassays with bacterial reporters are a useful complement to chemical analytics because they measure biological responses rather than total chemical concentrations. Simple bacterial reporter assays may also replace more costly chemical methods as a first line sample analysis technique. Recent promising developments integrate bacterial reporter cells with microsystems to produce bacterial biosensors. This lecture presents an in-depth treatment of the synthetic biological design principles of bacterial reporters, the engineering of which started as simple recombinant DNA puzzles, but has now become a more rational approach of choosing and combining sensing, controlling and reporting DNA 'parts'. Several examples of existing bacterial reporter designs and their genetic circuitry will be illustrated. Besides the design principles, the lecture also focuses on the application principles of bacterial reporter assays. A variety of assay formats will be illustrated, and principles of quantification will be dealt with. In addition to this discussion, substantial reference material is supplied in various Annexes.

Transcriptional potentiation of the vitellogenin B1 promoter by a combination of both nucleosome assembly and transcription factors: an in vitro dissection.

The Xenopus laevis vitellogenin B1 promoter was assembled into nucleosomes in an oocyte extract. Subsequent RNA polymerase II-dependent transcription from these DNA templates fully reconstituted in chromatin in a HeLa nuclear extract was increased 50-fold compared with naked DNA. Remarkably, under specific conditions, production of a high level of transcripts occurred at very low DNA (1 ng/microliter) and HeLa nuclear protein (1.6 micrograms/microliters) concentrations. When partially reconstituted templates were used, transcription efficiency was intermediate between that of fully reconstituted and naked DNA. These results implicate chromatin in the process of the transcriptional activation observed. Depletion from the oocyte assembly extract of an NF-I-like factor which binds in the promoter region upstream of the TATA box (-114 to -101) or deletion from the promoter of the region interacting with this factor reduced the transcriptional efficiency of the assembled templates by a factor of 5, but transcription of these templates was still 10 times higher than that of naked DNA. Together, these results indicate that the NF-I-like factor participates in the very efficient transcriptional potentiation of the vitellogenin B1 promoter which occurs during nucleosome assembly.

Human immunoglobulins and Fc fragments promote microtubule assembly via tau proteins and induce conformational changes of neuronal microtubules in vitro.

The influence of human immunoglobulins (Ig) in neuronal cytoskeleton stability was studied in vitro. Here we show that human Ig and Fc fragments stimulate animal and human microtubule assembly by binding to microtubules via tau isoforms. In presence of Ig, microtubules show increased aggregation, twisting and rigidity. Non-immune Ig and Fc fragments promote microtubule assembly in temperature-dependent manner and stabilize microtubules at a molecular ratio of 1 Ig per 4 tubulin dimers. These in vitro data provide an experimental support for an immuno-mediated modulation of the cytoskeleton. In conjunction with previous neuropathological data, they suggest that Ig could participate in early stages of neurodegeneration by affecting the microtubule stability in vivo.

Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low molecular weight inhibitors, the most active being of nanomolar potency both in an enzymatic and in a cellular assay, while showing no cellular toxicity and a high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quantitative structure-activity relationship based on the electrostatic ligand-protein interactions in the docked binding modes and on the quantum chemically derived charges of the triazole ring demonstrated a good explanatory power for the observed activities.

Life design: Un paradigma per la costruzione della vita professionale nel XXI secolo

In questo inizio di secolo, la nuova organizzazione sociale del lavoro pone una serie di domande e di sfide ai ricercatori che intendono aiutare le persone a progettare la loro vita lavorativa. Nell'era della globalizzazione anche per quanto riguarda il career counseling, abbiamo deciso di affrontare queste problematiche e di dare delle risposte che si caratterizzassero come innovative attraverso la costituzione di un forum di discussione internazionale. Si è proceduto in questo modo per evitare le difficoltà che generalmente si incontrano quando si mettono a punto dei modelli e dei metodi in un Paese e poi si esportano in altre culture con l'intento di adattarli alle stesse. Questo articolo presenta i primi risultati della collaborazione che si è registrata - un modello e dei metodi per la consulenza di orientamento. Il modello per l'intervento nell'ambito dell'approccio Life Design si caratterizza per cinque presupposti relativi al modo di vedere le persone e la loro vita lavorativa. Essi riguardano le possibilità contestuali, i processi dinamici, i progressi non-lineari, le molteplici prospettive e la presenza di pattern personali. Partendo da questi cinque presupposti abbiamo messo a punto un modello basato sull'epistemologia del costruzionismo sociale, che sostiene che la conoscenza e l'identità di un individuo sono i prodotti dell'interazione sociale e che il significato è costruito attraverso il discorso. Questo approccio fa riferimento anche alla teoria della costruzione di sé di Guichard (2005) e della costruzione della vita professionale di Savickas (2005), che descrivono le azioni utili a facilitare la progettazione del proprio futuro. Particolare attenzione viene data agli interventi nel corso dell'arco di vita, olistici, contestuali e preventivi.