Optimising and Communicating Options for the Control of Invasive Plant Disease When There Is Epidemiological Uncertainty

Although local eradication is routinely attempted following introduction of disease into a new region, failure is commonplace. Epidemiological principles governing the design of successful control are not well-understood. We analyse factors underlying the effectiveness of reactive eradication of localised outbreaks of invading plant disease, using citrus canker in Florida as a case study, although our results are largely generic, and apply to other plant pathogens (as we show via our second case study, citrus greening). We demonstrate how to optimise control via removal of hosts surrounding detected infection (i.e. localised culling) using a spatially-explicit, stochastic epidemiological model. We show how to define optimal culling strategies that take account of stochasticity in disease spread, and how the effectiveness of disease control depends on epidemiological parameters determining pathogen infectivity, symptom emergence and spread, the initial level of infection, and the logistics and implementation of detection and control. We also consider how optimal culling strategies are conditioned on the levels of risk acceptance/aversion of decision makers, and show how to extend the analyses to account for potential larger-scale impacts of a small-scale outbreak. Control of local outbreaks by culling can be very effective, particularly when started quickly, but the optimum strategy and its performance are strongly dependent on epidemiological parameters (particularly those controlling dispersal and the extent of any cryptic infection, i.e. infectious hosts prior to symptoms), the logistics of detection and control, and the level of local and global risk that is deemed to be acceptable. A version of the model we developed to illustrate our methodology and results to an audience of stakeholders, including policy makers, regulators and growers, is available online as an interactive, user-friendly interface at http://www.webidemics.com/. This version of our model allows the complex epidemiological principles that underlie our results to be communicated to a non-specialist audience.     

Cost-Effective Control of Infectious Disease Outbreaks Accounting for Societal Reaction

Background

Studies of cost-effective disease prevention have typically focused on the tradeoff between the cost of disease transmission and the cost of applying control measures. We present a novel approach that also accounts for the cost of social disruptions resulting from the spread of disease. These disruptions, which we call social response, can include heightened anxiety, strain on healthcare infrastructure, economic losses, or violence.

Methodology

The spread of disease and social response are simulated under several different intervention strategies. The modeled social response depends upon the perceived risk of the disease, the extent of disease spread, and the media involvement. Using Monte Carlo simulation, we estimate the total number of infections and total social response for each strategy. We then identify the strategy that minimizes the expected total cost of the disease, which includes the cost of the disease itself, the cost of control measures, and the cost of social response.

Conclusions

The model-based simulations suggest that the least-cost disease control strategy depends upon the perceived risk of the disease, as well as media intervention. The most cost-effective solution for diseases with low perceived risk was to implement moderate control measures. For diseases with higher perceived severity, such as SARS or Ebola, the most cost-effective strategy shifted toward intervening earlier in the outbreak, with greater resources. When intervention elicited increased media involvement, it remained important to control high severity diseases quickly. For moderate severity diseases, however, it became most cost-effective to implement no intervention and allow the disease to run its course. Our simulation results imply that, when diseases are perceived as severe, the costs of social response have a significant influence on selecting the most cost-effective strategy.     

The Epidemiological Modelling of Major Depressive Disorder: Application for the Global Burden of Disease Study 2010

Background

Although the detrimental impact of major depressive disorder (MDD) at the individual level has been described, its global epidemiology remains unclear given limitations in the data. Here we present the modelled epidemiological profile of MDD dealing with heterogeneity in the data, enforcing internal consistency between epidemiological parameters and making estimates for world regions with no empirical data. These estimates were used to quantify the burden of MDD for the Global Burden of Disease Study 2010 (GBD 2010).

Method

Analyses drew on data from our existing literature review of the epidemiology of MDD. DisMod-MR, the latest version of the generic disease modelling system redesigned as a Bayesian meta-regression tool, derived prevalence by age, year and sex for 21 regions. Prior epidemiological knowledge, study- and country-level covariates adjusted sub-optimal raw data.

Results

There were over 298 million cases of MDD globally at any point in time in 2010, with the highest proportion of cases occurring between 25 and 34 years. Global point prevalence was very similar across time (4.4% (95% uncertainty: 4.2–4.7%) in 1990, 4.4% (4.1–4.7%) in 2005 and 2010), but higher in females (5.5% (5.0–6.0%) compared to males (3.2% (3.0–3.6%) in 2010. Regions in conflict had higher prevalence than those with no conflict. The annual incidence of an episode of MDD followed a similar age and regional pattern to prevalence but was about one and a half times higher, consistent with an average duration of 37.7 weeks.

Conclusion

We were able to integrate available data, including those from high quality surveys and sub-optimal studies, into a model adjusting for known methodological sources of heterogeneity. We were also able to estimate the epidemiology of MDD in regions with no available data. This informed GBD 2010 and the public health field, with a clearer understanding of the global distribution of MDD.     

生防细菌在植物病害防治中的应用

生防细菌资源极为丰富,因其具有对环境友好的优点使之成为植物病害防控技术研究的热点。本文阐述了植物内生细菌和根际细菌的筛选、鉴定和活性测定技术,介绍了芽孢杆菌、假单胞菌和其它生防细菌的应用概况和作用机理,论述了生防细菌制剂商业化生产与大田应用可能遇到的问题,提出生防细菌的基因改造和制剂复配可能成为今后技术研发的关键。     

Facilitating Goal-Oriented Behaviour in the Stroop Task: When Executive Control Is Influenced by Automatic Processing

A portion of Stroop interference is thought to arise from a failure to maintain goal-oriented behaviour (or goal neglect). The aim of the present study was to investigate whether goal- relevant primes could enhance goal maintenance and reduce the Stroop interference effect. Here it is shown that primes related to the goal of responding quickly in the Stroop task (e.g. fast, quick, hurry) substantially reduced Stroop interference by reducing reaction times to incongruent trials but increasing reaction times to congruent and neutral trials. No effects of the primes were observed on errors. The effects on incongruent, congruent and neutral trials are explained in terms of the influence of the primes on goal maintenance. The results show that goal priming can facilitate goal-oriented behaviour and indicate that automatic processing can modulate executive control.     

GUN4 Is Required for Posttranslational Control of Plant Tetrapyrrole Biosynthesis

In aerobic photosynthetic organisms, GUN4 binds the chlorophyll intermediates protoporphyrin and Mg protoporphyrin, stimulates Mg chelatase activity, and is implicated in plastidic retrograde signaling. GUN4 expression is most abundant in young and greening tissues and parallels the activity of 5-aminolevulinic acid （ALA） ALA and Mg porphyrin biosynthesis during photoperiodic growth. We explored function and mode of action of GUN4 using GUN4- deficient and overexpressing plants. GUN4 overexpression leads to a general activation of the enzymes of chlorophyll biosynthesis. During photoperiodic growth GUN4 deficiency prevents ALA synthesis and chlorophyll accumulation. All these metabolic changes do not correlate with altered gene expression or changes of protein abundance in tetrapyrrole biosynthesis. While ALA feeding fails to compensate GUN4 deficiency during light-dark growth, this approach results in chlorophyll accumulation under continuous dim light. A new model defines the involvement of GUN4 in posttranslational regulation of ALA and Mg porphyrin synthesis, to sustain chlorophyll synthesis, namely under varying environmental conditions.     

The Scaling of Plant Height: A Comparison Among Major Plant Clades and Anatomical Grades

The scaling plant height h (m) with respect to stem diameterd (m) was determined for a total 610 species (mosses, n = 40;pteridophytes, n = 16; dicotyledonous herbs, n = 117; palms,n = 17; gymnosperms, n = 105; dicotyledonous trees, n = 315);axial length or mass vs. d was determined for the pteridophytePsilotum nudum ; and the scaling of critical buckling heighth_crit of gymnosperm and dicotyledonous trees was calculatedbased on the record trunk d and average Young's modulus E anddensity p of 33 wood species. The scaling exponents (based onleast squares and reduced major axis regressions;     

Patchy Distributions of Competitors Affect the Growth of a Clonal Plant When the Competitor Density Is High

Environments are patchy in not only abiotic factors but also biotic ones. Many studies have examined effects of spatial heterogeneity in abiotic factors such as light, water and nutrients on the growth of clonal plants, but few have tested those in biotic factors. We conducted a greenhouse experiment to examine how patchy distributions of competitors affect the growth of a rhizomatous wetland plant Bolboschoenus planiculmis and whether such effects depend on the density of the competitors. We grew one ramet of B. planiculmis in the center of each of the experimental boxes without competitors (Schoenoplectus triqueter), with a homogeneous distribution of the competitors of low or high density, and with a patchy distribution of the competitors of low or high density. The presence of competitors markedly decreased the growth (biomass, number of ramets, number of tubers and rhizome length) of the B. planiculmis clones. When the density of the competitors was low, the growth of B. planiculmis did not differ significantly between the competitor patches and competitor-free patches. However, when the density of the competitors was high, the growth of B. planiculmis was significantly higher in the competitor-free patches than in the competitor patches. Therefore, B. planiculmis can respond to patchy distributions of competitors by placing more ramets in competition-free patches when the density of competitors is high, but cannot do so when the density of competitors is low.     

转几丁质酶基因防植物病害研究:进展、问题与展望

综合评述了近几年转几丁质酶基因防植物病害研究中的发现与进展：（１）至少３１种病原真菌（含变种和专化型）可诱导植物几丁质酶,（２）据称已提纯的植物几丁质酶对立枯丝核菌等真菌呈现了体外抑菌活性;（３）一些生防细菌的防病作用依赖于其几丁质酶基因的存在;（４）数种植物几丁质酶基因和一种细菌几丁质酶基因已被转入水稻、烟草、番茄等植物,一些转基因株系抗病性显著增强;（５）粘质沙雷氏菌的一种几丁质酶基因已被转入荧光假单胞菌和根瘤菌中,转基因细菌对立枯丝核菌有显著抑制作用。就几丁质酶抑菌谱、转基因的策略和研究中存在的疑点进行了分析讨论。建议今后的研究方向应集中在以下几方面：（１）加速转几丁质酶基因或几丁质酶基因与其它基因组合的植物实用化;（２）进一步研究不同基因组合的增效作用及增效机理;（３）查明个别几丁质酶基因的抑菌谱及选择性抑菌机制;（４）转几丁质酶基因或与其它基因的组合于植物内生细菌。     

Modelling the Components of Plant Respiration: Some Guiding Principles

Respiration is poorly represented in whole plant or ecosystemmodels relative to photosynthesis. This paper reviews the principlesunderlying the development of a more mechanistic approach tomodelling plant respiration and the criteria by which modelbehaviour might be judged. The main conclusions are as follows:(1) Models should separate C substrate from structure so thatdirect or indirect C substrate dependence of the componentsof respiration can be represented. (2) Account should be takenof the fact that some of the energy for leaf respiration isdrawn from the light reactions of photosynthesis. (3) It ispossible to estimate respiration associated with growth, nitratereduction, symbiotic N₂fixation, N-uptake, other ion uptakeand phloem loading, because reasonable estimates are availableof average specific unit respiratory costs and the rates ofthese processes can be quantified. (4) At present, it is lesseasy to estimate respiration associated with protein turnover,maintenance of cell ion concentrations and gradients and allforms of respiration involving the alternative pathway and futilecycles. (5) The growth-maintenance paradigm is valuable but‘maintenance ' is an approximate concept and there isno rigorous division between growth and maintenance energy-requiringprocesses. (6) An alternative ‘process-residual’approach would be to estimate explicitly respiratory fluxesassociated with the six processes listed in (3) above and treatthe remainder as a residual with a phenomenological ‘residual maintenance’ coefficient. (7) Maintenance or‘residual maintenance’ respiration rates are oftenmore closely related to tissue N content than biomass, volumeor surface area. (8) Respiratory fluxes associated with differentprocesses vary independently, seasonally and during plant development,and so should be represented separately if possible. (9) Anunforced outcome of mechanistic models should be a constrained,but non-constant, ratio between whole plant gross photosynthesisand respiration. Copyright 2000 Annals of Botany Company Respiration, photosynthesis, growth, maintenance, substrate, N uptake, nitrate reduction, symbiotic N₂fixation, phloem loading, model.     

Modelling the Components of Plant Respiration: Representation and Realism

This paper outlines the different ways in which plant respirationis modelled, with reference to the principles set out in Cannelland Thornley (Annals of Botany85: 55–67, 2000), firstin whole-plant ‘toy’ models, then within ecosystemor crop models using the growth-maintenance paradigm, and finallyrepresenting many component processes within the Hurley Pasture(HPM) and Edinburgh Forest Models (EFM), both of which separateC and N substrates from structure. Whole-plant models can beformulated so that either maintenance or growth respirationtake priority for assimilates, or so that growth respirationis the difference between total respiration and maintenanceassociated with the resynthesis of degraded tissues. All threeschemes can be converted to dynamic models which give similar,reasonable predictions of plant growth and respiration, butall have limiting assumptions and scope. Ecosystem and cropmodels which use the growth-maintenance respiration paradigmwithout separating substrates from structure, implicitly assumethat maintenance respiration is a fixed cost, uncoupled to assimilatesupply, and use fixed rate coefficients chosen from a rangeof measured values. Separation of substrates in the HPM andEFM enables estimates to be made of respiration associated withlocal growth, phloem loading, ammonium and nitrate N uptake,nitrate reduction, N₂fixation and other mineral ion uptake,leaving a ‘residual maintenance’ term. The lattercan be explicitly related to C substrate supply. Simulated changesin grassland respiration over a season and forest respirationover a rotation show that the ratio of total respiration togross canopy photosynthesis varies within the expected limitedrange, that residual maintenance accounts for 46–48% oftotal respiration, growth 36–42%, phloem loading 10–12%and the other components for the small remainder, with the ratiosbetween components varying during a season or forest rotation.It is concluded that the growth-maintenance approach to respiration,extended to represent many of the component processes, has considerablemerit. It can be connected to reality at many points, it givesmore information, it can be examined at the level of assumptionsas well as at the level of predictions, and it is open to modificationas more knowledge emerges. However, currently, there are stillparameters that require adjustment so that the predictions ofthe model are acceptable. Copyright 2000 Annals of Botany Company Respiration, photosynthesis, growth, maintenance, substrate, N uptake, mineral uptake, phloem loading, model.     

植物内生细菌在防治植物病害中的应用研究

许多报道已证明在不同的植物体内都存在多种内生细菌。本文综述了内生细菌的概念、种群密度等方面的内容 ,着重叙述了内生细菌在生物防治植物病害上的作用 ,并对内生细菌的研究现状及应用提出了自己的见解。     

Modeling Disease Vector Occurrence When Detection Is Imperfect II: Drivers of Site-Occupancy by Synanthropic Triatoma brasiliensis in the Brazilian Northeast

Background

Understanding the drivers of habitat selection by insect disease vectors is instrumental to the design and operation of rational control-surveillance systems. One pervasive yet often overlooked drawback of vector studies is that detection failures result in some sites being misclassified as uninfested; naïve infestation indices are therefore biased, and this can confound our view of vector habitat preferences. Here, we present an initial attempt at applying methods that explicitly account for imperfect detection to investigate the ecology of Chagas disease vectors in man-made environments.

Methodology

We combined triplicate-sampling of individual ecotopes (n = 203) and site-occupancy models (SOMs) to test a suite of pre-specified hypotheses about habitat selection by Triatoma brasiliensis. SOM results were compared with those of standard generalized linear models (GLMs) that assume perfect detection even with single bug-searches.

Principal Findings

Triatoma brasiliensis was strongly associated with key hosts (native rodents, goats/sheep and, to a lesser extent, fowl) in peridomestic environments; ecotope structure had, in comparison, small to negligible effects, although wooden ecotopes were slightly preferred. We found evidence of dwelling-level aggregation of infestation foci; when there was one such focus, same-dwelling ecotopes, whether houses or peridomestic structures, were more likely to become infested too. GLMs yielded negatively-biased covariate effect estimates and standard errors; both were, on average, about four times smaller than those derived from SOMs.

Conclusions/Significance

Our results confirm substantial population-level ecological heterogeneity in T. brasiliensis. They also suggest that, at least in some sites, control of this species may benefit from peridomestic rodent control and changes in goat/sheep husbandry practices. Finally, our comparative analyses highlight the importance of accounting for the various sources of uncertainty inherent to vector studies, including imperfect detection. We anticipate that future research on infectious disease ecology will increasingly rely on approaches akin to those described here.     

When It Is Better to Regress: Dynamics of Vascular Pruning

Blood vascular networks in vertebrates are essential to tissue survival. Establishment of a fully functional vasculature is complex and requires a number of steps including vasculogenesis and angiogenesis that are followed by differentiation into specialized vascular tissues (i.e., arteries, veins, and lymphatics) and organ-specific differentiation. However, an equally essential step in this process is the pruning of excessive blood vessels. Recent studies have shown that pruning is critical for the effective perfusion of blood into tissues. Despite its significance, vessel pruning is the least understood process in vascular differentiation and development. Two recently published PLOS Biology papers provide important new information about cellular dynamics of vascular regression.Vascular biology is a rapidly emerging field of research. Given the critical role the vasculature frequently plays in a wide range of common and serious diseases such as arteriosclerosis, ischemic diseases, cancer, and chronic inflammatory diseases, a better understanding of the formation, maintenance, and remodeling of blood vessels is of major importance.A mature vascular network is a highly anisotropic, hierarchical, and dynamic structure that has evolved to provide optimal oxygen delivery to tissues under a variety of conditions. Whilst much has been learned about early steps in vascular development such as vasculogenesis and angiogenesis, we still know relatively little about how such anatomical and functional organization is achieved. Furthermore, the dynamic nature of mature vascular networks, with its potential for extensive remodeling and a continuing need for stability and maintenance, is even less understood. The issue of optimal vascular density in tissue is of particular importance as several recent studies demonstrated that excessive vascularity may, in fact, reduce effective perfusion [1–3]. Since all neovascularization processes initially result in the formation of excessive amounts of vasculature, be that capillaries, arterioles, or venules, pruning must occur to return the vascular density to its optimal value in order to achieve effective tissue perfusion.Yet despite its functional importance, little is known about how regression of the once formed vasculature actually happens. While several potential mechanisms have been proposed including apoptosis of endothelial cells, intussusception vascular pruning, and endothelial cell migration away from the regressing vessel, cellular and molecular understanding of how this might happen is conspicuously lacking. Two articles recently published in PLOS Biology describe migration of endothelial cells as the key mechanism of apoptosis-independent vascular pruning and place it in a specific biologic context. This important advance offers not only a new understanding of a poorly understood aspect of vascular biology but may also prove to be of considerable importance in the development of pro- and anti-angiogenic therapies.To put vessel regression in context, it helps to briefly outline the current understanding of vessel formation. During embryonic development, vasculature forms in several distinct steps that begin with vasculogenesis, a step that involves differentiation of stem cells into primitive endothelial cells that then form initial undifferentiated and nonhierarchically organized lumenized vascular structures termed the primary plexus [4]. The primary plexus is then remodeled, by the process termed angiogenesis, into a more mature vascular network [5]. This remodeling event involves both formation of new vessels accomplished either by branching angiogenesis, a process dependent on tip cell-driven formation of new branches [6], or intussusception, a poorly understood process of splitting an existing vessel into two [7]. This incompletely differentiated and still nonhierarchical vasculature then further remodels into a number of distinctly different types of vessels such as capillaries, arteries, and veins. This requires fate specification, differentiation, and incorporation of various mural cells into evolving vascular structures. Finally, additional specialization of the vascular network occur in an organ-specific manner.Once formed, vascular networks require active maintenance as withdrawal of key signals, such as of ongoing fibroblast growth factor (FGF) or vascular endothelial growth factor (VEGF) stimulation, can lead to a rapid loss of vascular integrity and even changes in endothelial cell fate [8–12]. In addition, mature vessels retain the capacity for extensive remodeling and new growth as can be seen in a number of conditions from cancer to myocardial infarction and wound healing responses, among many others [5].A key issue common to both embryonic and adult vessel remodeling is how an existing lumenized vessel connected to the rest of the vasculature undergoes a change that results in its remodeling into something else. Such a change may involve either a new branch formation or regression of an existing branch, while the patency and integrity of the remaining circulation is maintained. Two types of cellular process leading to branching have been described—sprouting and intussusception. Formation of vascular branches by sprouting involves VEGF-A-induced expression of high levels of delta-like ligand 4 (Dll4) in a subset of endothelial cells at the leading edge of the vascular sprouts that are lying closest to the source of VEGF, thus converting them to a “tip cell” phenotype. Some of the key features of tip cells include the presence of cytoplasmic processes that extend into avascular (or hypoxic) tissue that form nascent branches. Dll4 expressed on tip cells binds Notch-1 receptor in neighboring endothelial cells, thereby activating their downstream Notch signaling. In turn, Notch signaling shuts down the formation of additional filopodia processes, converting these cells to a “stalk cell” phenotype and thereby avoiding excessive branching [13–15]. The bone morphogenetic protein signaling pathway provides further input in determining stalk cell fate [16]. Importantly, tip cells are only partially lumenized; only once they have converted to a stalk phenotype does the lumen extend to what was a tip cell and its sprouts.An alternative mechanism of branching involves intussusception, a process by which a tissue pillar from the surrounding tissue splits the existing endothelial tube into two along its long axis, creating two adjusting vessels. While this process has been described morphologically, virtually nothing is known about its molecular and cellular regulation. In development, angiogenesis by intussusception occurs in vessels previously formed by sprouting angiogenesis [17,18]. Importantly, however, both sprouting angiogenesis and intussusception allow growth and remodeling of vascular network without any integrity compromise, thereby avoiding bleeding and related complications.There are certain parallels between vessel formation and branching and vessel regression. While growth occurs either via sprouting (a process linked to endothelial cell-migration) or intussusception, regression involves either “reverse intussusception,” endothelial migration-dependent regression, or apoptosis. The latter is the primary means of regression of the hyaloid vasculature in the eye and of the vascular loss seen in oxygen-induced retinopathy (OIR). In the case of hyaloid vasculature, secretion of WNT7b by macrophages invading the hyaloid membrane induces apoptosis of hyaloid endothelial cells leading to the regression of the entire hyaloid vasculature [19]. This total apoptosis-induced loss of hyaloid blood vessels contrasts with a less extensive vascular regression seen in the setting of OIR. In this condition, exposure of the developing retinal vasculature to abnormally high oxygen levels leads to vascular damage characterized by capillary pruning [20]. The pruning is the consequence of apoptosis of endothelial cells due to the toxic effect of a combination of high oxygen and low VEGF level. Interestingly, larger vessels and mature capillaries are not sensitive to hyperoxia [21].Intussusception vascular pruning was also described in a low VEGF level context in the chick chorioallantoic membrane. Application of VEGF-releasing hydrogels to the membrane surface results in formation of an excessive vasculature. Removal or degradation of the hydrogel induces an abrupt VEGF withdrawal. In this context, formation of transluminal pillars, similar to the ones seen in intussusception angiogenesis, is observed in vessels undergoing pruning [22]. The same process is observed in the tumor vasculature in the setting of anti-angiogenic therapy [23]. Finally, apoptosis-independent vascular regression, driven by endothelial cell migration, has been described in the mouse retina, yolk vessels of the chick and mouse embryos, branchial arches, and the zebrafish brain [24–28].In all of these cases, only a subset of vessels is designated for pruning, and the selection of these vessels is highly regulated. Yet, factors involved in choosing a particular vascular branch for pruning remain ill-defined. One such factor is low blood flow [27,28]. Another is Notch signaling that has been shown to at least partially control vascular pruning in mouse retina and in intersegmental vessels (ISVs) in zebrafish [24]. Loss of Notch-regulated ankyrin repeat protein (Nrarp), target gene of Notch signaling, leads to an increase in vascular regression in these tissues due to a decrease in Wnt signaling-induced stalk cell proliferation. Similarly, in Dll4 ^+/- mice, developmental retinal vascular regression and OIR-induced vascular pruning are reduced [29], confirming the involvement of the Notch pathway in the control of vascular regression.The two factors may be linked, as low flow can affect endothelial shear stress and lead to a decrease in Notch activation. Such a link is suggested by studies on vascular regression in mice with endothelial expression of dominant negative NFκB pathway inhibitor that demonstrate excessive vascular growth but reduced tissue perfusion [2]. Molecular studies showed inhibition of flow- or cytokine-induced NFκB activation results in decreased Dll4 expression [2].Another important issue is the fate of endothelial cells from vessels undergoing pruning. In PLOS Biology, two groups recently described endothelial cell behavior during vascular pruning in three different models: the mouse retina, the ISVs in zebrafish, and the subintestinal vessel in zebrafish [30,31]. Using a high resolution time-lapse microscopy technique, Lenard and collaborators showed that vascular pruning during the subintestinal vessel formation occurs in two different ways. In type I pruning, the first step is the collapse of the lumen. Once that occurs, endothelial cells migrate and incorporate into the neighboring vessels. In type II pruning, the lumen is maintained. One endothelial cell in the center of the pruning vessel undergoes self-fusion, leading to a unicellular lumenized vessel. At the same time, other endothelial cells migrate away and incorporate into the neighboring vessels. The eventual lumen collapse is the last step after which the remaining single endothelial cell migrates and incorporates into one of the major vessels.Franco and collaborators described a pruning mechanism similar to the type I pruning described by Lenard et al., showing lumen disruption as an initial step in pruning of retinal vasculature in mice and ISVs in zebrafish [31]. By analyzing the first axial polarity map of endothelial cells in these models, they demonstrated that axial orientation predicts endothelial cell migration, and that migration-driven pruning occurs in vessels with low flow. Interestingly, migrating endothelial cells in regressing vessel display a tip cell phenotype with filopodia.The cellular dynamic of vessel pruning described here is the reverse of the cellular dynamic during anastomosis and angiogenesis [32]. Given the crucial role of factors as VEGF for the migration of endothelial cells during angiogenesis, can we go further and propose that other cytokines or cell–cell signaling may be involved in the migration of these endothelial cells? Indeed, low blood flow seems to be the cause of vessel pruning, but how can we explain the direction of endothelial cell migration, moreover with a tip cell morphology? Also, what determines the choice between type I and type II pruning? The collapse of lumen suggests a reorganization of the cytoskeleton, and a loss of polarity and electrostatic repulsion of endothelial cells. Molecular mechanisms leading from low shear stress to loss of endothelial cell polarity need further investigation. As defective vascular pruning could be involved in poor recovery after injury or ischemic accident, a better understanding of the molecular control of this phenomenon appears to have medical consequences. Another question that is still unanswered is the fate of mural cells that surrounded the pruned vessels. Small vessels are covered by pericytes, which have strong interaction with endothelial cells. How and when are these interactions disrupted? Are pericytes integrated into the neighboring vessel, or do they undergo apoptosis? Further studies are needed to understand the molecular and cellular mechanisms by which vasculature can adapt, even at the adult stage, to support the nutrient and oxygen needs of each cell.Overall, taking the results of these studies together with other recent developments in this field, the following picture is emerging (Fig 1). Under conditions of low blood flow in certain vascular tree branches, pruning will occur via endothelial cell migration out of these branches to the neighboring (presumably higher blood flow) vessels. This results in decreased total vascular cross-sectional area and increased average blood flow, thereby terminating further pruning. Importantly, this occurs without the loss of luminal integrity and without reduction in the total endothelial cell mass. At the same time, vessels that suddenly find themselves in a low VEGF environment will regress either by apoptosis of endothelial cells or by intussusception. In both cases, there is a reduction in the total vasculature without an increase in blood flow to this tissue. Thus, the local context determines the mechanism: migratory regression and remodeling in low shear stress versus apoptotic pruning in low VEGF milieu.Open in a separate windowFig 1Vessel regression under low flow versus low VEGF conditions.Vessel regression under low flow conditions proceeds by endothelial cell (EC) migration-driven regression, resulting in a decrease in total vessel areas but an increase in blood flow (left panel). Vessel regression under low VEGF conditions proceeds by EC apoptosis or intussusception regression, resulting in decreased vessel number and decreased flow to tissues subtended by the regressing vasculature (right panel). Image credit: Nicolas Ricard & Michael Simons.This distinction is likely to be of a significant practical importance, in particular in the context of therapies designed to facilitate vessel normalization in tumors after VEGF-targeting treatments and therapies designed to promote vascularization of mildly ischemic tissues as occurs, for example, in the setting of chronic stable angina and other similar conditions. In the former case, a precipitous drop in VEGF levels is likely to induce vascular regression by induction of endothelial apoptosis, and further promotion of apoptosis may facilitate this process. In contrast, in the latter case, low flow in newly formed collateral arteries may induce their regression by stimulating outmigration of endothelial cells, thereby limiting their beneficial functional impact. Therapies designed to inhibit this mechanism, therefore, may promote growth of the new functional vasculature.     

When Less Is More: Evolutionary Origins of the Affect Heuristic

The human mind is built for approximations. When considering the value of a large aggregate of different items, for example, we typically do not summate the many individual values. Instead, we appear to form an immediate impression of the likeability of the option based on the average quality of the full collection, which is easier to evaluate and remember. While useful in many situations, this affect heuristic can lead to apparently irrational decision-making. For example, studies have shown that people are willing to pay more for a small set of high-quality goods than for the same set of high-quality goods with lower-quality items added [e.g. 1]. We explored whether this kind of choice behavior could be seen in other primates. In two experiments, one in the laboratory and one in the field, using two different sets of food items, we found that rhesus monkeys preferred a highly-valued food item alone to the identical item paired with a food of positive but lower value. This finding provides experimental evidence that, under certain conditions, macaque monkeys follow an affect heuristic that can cause them to prefer less food. Conservation of this affect heuristic could account for similar ‘irrational’ biases in humans, and may reflect a more general complexity reduction strategy in which averages, prototypes, or stereotypes represent a set or group.     

Safety of Microorganisms Intended for Pest and Plant Disease Control: A Framework for Scientific Evaluation

Microorganisms are enormous but largely untapped natural resources for biological control of pests and diseases. There are two primary reasons for their underployment for pest or disease control: (1) the technical difficulties of using microorganisms for biological control, owing to a lack of fundamental information on them and their ecology, and (2) the costs of product development and regulatory approvals required for each strain, formulation, and use. Agriculture and forestry benefit greatly from the resident communities of microorganisms responsible for naturally occurring biological control of pest species, but additional benefits are achieved by introducing/applying them when or where needed. This can be done as (1) an inoculative release, (2) an augmentative application, or (3) an inundative application. Because of their specificity, different microbial biocontrol agents typically are needed to control different pests or the same pest in different environments. Four potential adverse effects are identified as safety issues (hazards) associated with the use of microorganisms for the biological control of plant pests and diseases. These are: (1) displacement of nontarget microorganisms, (2) allergenicity to humans and other animals, (3) toxigenicity to nontarget organisms, and (4) pathogenicity to nontarget organisms. Except for allergenicity, these are the same attributes that contribute to the efficacy of microbial biocontrol agents toward the target pest species. The probability of occurrence of a particular adverse nontarget effect of a microbial biocontrol agent may be a function of geographic origin or a specific trait genetically added or modified, but the safety issues are the still the same, including whether the microorganism intended for pest or disease control is indigenous, nonindigenous (imported and released), or genetically modified by traditional or recombinant DNA (rDNA) technology. Likewise, the probability of occurrence of a particular adverse nontarget effect may vary with method of application, e.g., whether as an aerosol, soil treatment, baits, or seed treatment, and may increase with increased scale of use, but the safety issues are still the same, including whether the microorganism is used for an inoculative release or augmentative or inundative application. Existing practices for managing microorganisms in the environment (e.g., plant pathogens,Rhizobium,plant inoculants) provide experience and options for managing the risks of microorganisms applied for pest and disease control. Moreover, experience to date indicates that any adverse nontarget effects, should they occur, are likely to be short-term or transitory effects that can, if significant, be eliminated by terminating use of the microbial biocontrol agent. In contrast, production agriculture as currently practiced, such as the use of tillage and crop rotations, has significant and long-term effects on nontarget organisms, including the intentional and unintentional displacement of microorganisms. Even the decision to leave plant pests and diseases unmanaged could have significant long-term environmental effects on nontarget organisms. Potential safety issues associated with the use of microbial biocontrol must therefore be properly identified and compared with the impact of other options for managing the pest or leaving the pest unmanaged. This paper provides a scientific framework for this process.     

Anticipatory Modulation of Digit Placement for Grasp Control Is Affected by Parkinson's Disease

Background

Successful object manipulation relies on the ability to form and retrieve sensorimotor memories of digit forces and positions used in previous object lifts. Past studies of patients affected by Parkinson''s disease (PD) have revealed that the basal ganglia play a crucial role in the acquisition and/or retrieval of sensorimotor memories for grasp control. Whereas it is known that PD impairs anticipatory control of digit forces during grasp, learning deficits associated with the planning of digit placement have yet to be explored. This question is motivated by recent work in healthy subjects revealing that anticipatory control of digit placement plays a crucial role for successful manipulation.

Methodology/Principal Findings

We asked ten PD patients off medication and ten age-matched controls to reach, grasp and lift an object whose center of mass (CM) was on the left, right or center. The only task requirement was to minimize object roll during lift. The CM remained the same across consecutive trials (blocked condition) or was altered from trial to trial (random condition). We hypothesized that impairment of the basal ganglia-thalamo-cortical circuits in PD patients would reduce their ability to anticipate digit placement appropriate to the CM location. Consequently, we predicted that PD patients would exhibit similar digit placement in the blocked vs. random conditions and produce larger peak object rolls than that of control subjects. In the blocked condition, PD patients exhibited significantly weaker modulation of fingertip contact points to CM location and larger object roll than controls (p<0.05 and p<0.01, respectively). Nevertheless, both controls and PD patients minimized object roll more in the blocked than in the random condition (p<0.01).

Conclusions/Significance

Our findings indicate that, even though PD patients may have a residual ability of anticipatory control of digit contact points and forces, they fail to implement a motor plan with the same degree of effectiveness as controls. We conclude that intact basal ganglia-thalamo-cortical circuits are necessary for successful sensorimotor learning of both grasp kinematics and kinetics required for dexterous hand-object interactions.     

Association of Plant p40 Protein with Ribosomes Is Enhanced When Polyribosomes Form during Periods of Active Tissue Growth

p40s are acidic proteins of eukaryotic cells occurring either free in the cytoplasm or in association with ribosomes, the latter occurring in both monosomes and polysomes. p40s may play a role in the regulation of protein synthesis, although the exact mechanism is not known. Leaves of all 10 plant species examined here, including both monocots and dicots, contained proteins detected on immunoblots with Arabidopsis thaliana p40 antiserum. The number and apparent size of the protein bands were variable even among closely related species. Abundance of p40 relative to ribosomal content during soybean (Glycine max L.) seed germination and during seed and leaf development was examined. p40 abundance correlated with periods of active tissue growth and high polysome content. The plant growth regulator indole acetic acid caused an increase in polysome formation in etiolated pea (Pisum sativum L.) plants and a concomitant recruitment of p40 into polysomes. Subcellular localization at the microscopy level indicated that the pattern of p40 staining is very similar to that for RNA, except that p40 is excluded from the nucleus. These data suggest that p40 is an accessory protein of the ribosome that might play a role in plant growth and development.