How citrullination invaded rheumatoid arthritis research

Citrullination and the immune response to citrullinated proteins have been fundamental for the early recognition of rheumatoid arthritis by serological tests and a better understanding of its pathophysiology. In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins. It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints. There is also accumulating evidence for a direct role of citrullination in tissue destruction in the rheumatoid synovium. Here we will discuss the development and importance of anti-citrullinated protein antibodies in rheumatoid arthritis as well as recent findings implicating citrullination in the pathophysiology of rheumatoid arthritis.The first indication that patients with rheumatoid arthritis (RA) produce antibodies to a specific autoantigen was published in 1964 by two Dutch scientists, Nienhuis and Mandema. The exact nature of this antigen, the so-called perinuclear factor, remained unclear for decades. In 1978, the target of seemingly unrelated RA-specific autoantibodies (that is, keratin) was identified. Almost 15 years later, Guy Serre’s group convincingly showed that both antigens were identical to the cytokeratin filament-aggregating protein filaggrin (reviewed in [1]). Our own previously published results had shown that the newly made precursor of filaggrin in cultured buccal mucosa cells (that is, profilaggrin) did not react with RA antibodies [2]. This prompted us to consider the possibility that a post-translational modification of filaggrin, absent on newly made profilaggrin, was required for the formation of the antigenic target of these antibodies. Since 1994, we have tested several likely modifications using synthetic peptides. Indeed, citrullination, the enzymatic conversion of peptidylarginine into peptidylcitrulline, turned out to be essential to make peptides reactive with RA autoantibodies. We subsequently developed an enzyme-linked immunosorbent assay with citrullinated peptides and confirmed that the anti-peptidylcitrulline activity was specific for RA [3]. Our further work was directed to the development of the CCP2 test, using cyclic citrullinated peptides (CCPs) selected from random peptide libraries [4].The discovery of CCP/protein as the most prominent RA-specific antigen had great impact on RA diagnostics and our understanding of RA pathophysiology. The following milestones can be noted (see [5] also).1. After decades of intensive research by many groups, a specific diagnostic test for RA had finally been developed. The CCP2 test has a specificity of more than 95%, is very sensitive (~75%), and is still considered the gold standard in RA autoantibody testing. Since 2010, anti-citrullinated protein antibodies (ACPAs) have been included in the new American College of Rheumatology/European League Against Rheumatism classification criteria for RA.2. Recently, an international reference preparation for ACPAs was evaluated by the International Committee for the Standardization of Autoantibodies in Rheumatic and Related Diseases [6]. It is available for the scientific community via the Centers for Disease Control and Prevention (Atlanta, GA, USA).3. A positive CCP2 test predicts the development of RA, often years before clinical confirmation (reviewed in [5]). It appears that time to RA diagnosis is shorter in patients with high anti-CCP2 titers at enrollment as compared with those with low titers [7].4. ACPA-positive RA is characterized by a more severe disease course. Early treatment of ACPA-positive individuals appears to be very effective.5. ACPA-negative patients (about 25% of the total RA population) generally display a much milder course of disease. About 35% of such ACPA-negative patients produce anti-carbamylated protein antibodies. Interestingly, the chemical product of carbamylation (that is, lysine converted to homocitrulline) is structurally very similar to citrulline [8].6. Specific human leukocyte antigen (HLA) genes (DRB1 shared epitope (SE) alleles) not only are the most important genetic risk factor for RA but also are strongly associated with the production of ACPAs.7. The best known environmental risk factor for RA, cigarette smoking, is a risk factor only for ACPA-positive and not for ACPA-negative RA [9]. There is increasing evidence that smoking acts as a trigger for anti-citrulline immunity and does so mainly in the context of certain HLA genes and certain other genetic risk factors.8. ACPAs and citrullinated antigens form immune complexes which stimulate the inflammatory process. Continuous production of such immune complexes ultimately results in the chronic inflammation, characteristic for RA (Figure 1).Open in a separate windowFigure 1Citrullination-related immunity and pathophysiology in rheumatoid arthritis. In genetically susceptible individuals, an environmental factor may initiate a primary inflammation, which can occur in various tissues, and trigger the immune response to citrullinated proteins (left). The resulting anti-citrullinated protein/peptide antibodies (ACPAs) are distributed through the circulation and may form immune complexes with citrullinated proteins produced in an inflamed synovium, thereby boosting the inflammatory process. This will be associated with the infiltration and activation of neutrophils, macrophages, and lymphocytes; cell death; extracellular DNA trap formation; the activation and release of peptidylarginine deiminases (PADs); de novo citrullination; and diversification of the ACPA response. Besides the common inflammation-associated mediators of tissue destruction (not shown), ACPAs and PADs can be directly involved in these processes. HLA, human leukocyte antigen.     

Life-history evolution when Lestes damselflies invaded vernal ponds

We know little about the macroevolution of life-history traits along environmental gradients, especially with regard to the directionality compared to the ancestral states and the associated costs to other functions. Here we examine how age and size at maturity evolved when Lestes damselflies shifted from their ancestral temporary pond habitat (i.e., ponds that may dry once every decade or so) to extremely ephemeral vernal ponds (ponds that routinely dry completely each year). Larvae of three species were reared from eggs until emergence under different levels of photoperiod and transient starvation stress. Compared to the two temporary-pond Lestes, the phylogenetically derived vernal-pond Lestes dryas developed more rapidly across photoperiod treatments until the final instar, and only expressed plasticity in development time in the final instar under photoperiod levels that simulated a later hatching date. The documented change in development rate can be considered adaptive and underlies the success of the derived species in vernal ponds. Results suggest associated costs of faster development are lower mass at maturity and lower immune function after transient starvation stress. These costs may not only have impeded further evolution of the routine development rate to what is physiologically maximal, but also maintained some degree of plasticity to time constraints when the habitat shift occurred.     

Phenotypes of Two Generations of Sporobolus airoides Seedlings Derived from Acroptilon repens‐invaded and Non‐invaded Grass Populations

Although the ecological impacts of invasive species are well known, the evolutionary impacts on recipient native grass communities are not. We suggest that remnant native plants may provide desirable seed sources for restoration and native plant production. Native populations exposed to the selective pressures associated with exotic invasion may retain traits that increase their ability to coexist with invasive species. Two generations of Sporobolus airoides Torr. (Alkali sacaton) plants derived from lineages collected from within long‐term invaded areas of Acroptilon repens (L.) DC (Russian knapweed) and from adjacent non‐invaded areas were propagated in a greenhouse to evaluate generational changes in phenotypic traits from the production environment. Given the difference in invasion history of the two populations, we hypothesized that invaded and non‐invaded subpopulations would differ phenotypically. Phenotypic measurements revealed that invaded subpopulations had greater vegetative growth, whereas non‐invaded subpopulations had increased sexual reproduction. Phenotypic expression changed from the first to the second generation, predominantly in the invaded subpopulation. Generational phenotypic shifts are disadvantageous for native seed production which requires a standard product to sell commercially. However, phenotypic variation may improve field seed survival. This research demonstrates the potential value of targeting post‐invasion remnant grass populations for restoration.     

Status of coastal dune communities invaded by Chrysanthemoides monilifera

It has often been assumed that the introduced species Chrysanthemoides monilifera is displacing native species in invaded coastal communities in Australia but no direct evidence has been presented that this displacement is occurring and, if so, to what extent. At an invaded site near Moruya, New South Wales, we found strong negative correlations between the presence (measured as cover, frequency or volume of shrub) of C. monilifera and Acacia longifolia, the hitherto dominant native species, and of C. monilifera and Lomandra longifolia. The negative correlations are partly accounted for by differences in the amounts of each species on different zones on the dune, but the negative correlations remain even within these zones. Also a comparison with uninvaded sites indicates that C. monilifera is displacing A. longifolia from the fore-dune and mid-dune but is having less effect in the swale. In addition, there is a trend towards reduced seed production of A. longifolia when growing in proximity to C. monilifera. There is no significant difference in the presence of L. longifolia in the uninvaded and invaded sites. In invaded sites, significantly fewer C. monilifera seedlings occur in the presence of L. longifolia. Thus it appears that the observed negative associations arise from different causes. Chrysanthemoides monilifera is displacing the structurally similar, and previously dominant A. longifolia, while the tussock-forming L. longifolia is locally hindering the invasion.     

侵入性害虫——蔗扁蛾

近几年 ,在某些宾馆、饭店、写字楼以及家庭中的观赏植物香龙血树 (巴西铁 ) ,树身有虫孔虫粪或虫蛹壳 ,像辫子一样的马拉巴栗 (发财树 )枯死了一根或几根。剥开树皮检查 ,原来是虫危害的 (图版Ⅰ 1 ,2 ,封 4)。经中国农业大学杨集昆教授鉴定 ,是侵入性害虫蔗扁蛾Ｏｐｏｇｏ ｎａｓａｃｃｈａｒｉ (Ｂｏｊｅｒ)。该虫属鳞翅目Ｌｅｐｉｄｏｐｔｅｒａ扁蛾属Ｏｐｏｇｏｎａ ,是中国新记录种、新记录属、新记录科 (辉蛾科Ｈｉｅｒｏｘｅｓｔｉｄａｅ) ,是一种侵入我国的危险性害虫[1,2 ] 。此虫是改革开放后随花卉进口带入 ,具体何时何地传入广…     

A role for the sampling effect in invaded ecosystems

Species loss and invasion of exotic species are two components of global biodiversity change that are expected to influence ecosystem functioning. Yet how they interact in natural settings remains unclear. Experiments have revealed two major mechanisms for the observed increase in primary productivity with plant species richness. Plant productivity may rise with species richness due to the increased amount of resources used by more diverse communities (niche complementarity) or through the increased probability of including a highly productive, dominant species in the community (sampling effect). Current evidence suggests that niche complementarity is the most relevant mechanism, whereas the sampling effect would only play a minor and transient role in natural systems. In turn, exotic species can invade by using untapped resources or because they possess a fitness advantage over resident species allowing them to dominate the community. We argue that the sampling effect can be a significant biodiversity mechanism in ecosystems invaded by dominant exotic species, and that the effect can be persistent even after decades of succession. We illustrate this idea by analyzing tree species richness–productivity relationships in a subtropical montane forest (NW Argentina) heavily invaded by Ligustrum lucidum, an evergreen tree from Asia. We found that the forest biomass increased along a natural gradient of tree species richness whether invaded by L. lucidum or not. Consistent with the sampling effect, L. lucidum invasion tripled total tree biomass irrespective of species richness, and monocultures of L. lucidum were more productive than any of the most species‐rich, uninvaded communities. Hence, the sampling effect may not be restricted to randomly assembled, synthetic communities. We emphasize that studying invaded ecosystems may provide novel insights on the mechanisms underlying the effect of biodiversity on ecosystem function.     

北美地区一新外来入侵种——花曲柳窄吉丁

介绍了原产亚洲的北美地区的一种新的入侵种——花曲柳窄吉丁AgrilusplanipennisFairmaire的国内外研究进展,对该虫的分类地位、形态特征、分布与起源、寄主、生物学特性等进行了综述,提出了作为入侵种需要进一步研究的方向。     

Two invasive acacia species secure generalist pollinators in invaded communities

Exotic entomophilous plants need to establish effective pollinator interactions in order to succeed after being introduced into a new community, particularly if they are obligatory outbreeders. By establishing these novel interactions in the new non-native range, invasive plants are hypothesised to drive changes in the composition and functioning of the native pollinator community, with potential impacts on the pollination biology of native co-flowering plants. We used two different sites in Portugal, each invaded by a different acacia species, to assess whether two native Australian trees, Acacia dealbata and Acacia longifolia, were able to recruit pollinators in Portugal, and whether the pollinator community visiting acacia trees differed from the pollinator communities interacting with native co-flowering plants. Our results indicate that in the invaded range of Portugal both acacia species were able to establish novel mutualistic interactions, predominantly with generalist pollinators. For each of the two studied sites, only two other co-occurring native plant species presented partially overlapping phenologies. We observed significant differences in pollinator richness and visitation rates among native and non-native plant species, although the study of β diversity indicated that only the native plant Lithodora fruticosa presented a differentiated set of pollinator species. Acacias experienced a large number of visits by numerous pollinator species, but massive acacia flowering resulted in flower visitation rates frequently lower than those of the native co-flowering species. We conclude that the establishment of mutualisms in Portugal likely contributes to the effective and profuse production of acacia seeds in Portugal. Despite the massive flowering of A. dealbata and A. longifolia, native plant species attained similar or higher visitation rates than acacias.     

Recruitment limitation of native species in invaded coastal dune communities

Recruitment limitation may limit the ability of sites to regenerate after disturbances such as weed invasion and weed management. We investigated seed bank constraints and dispersal limitation in coastal dune communities on the east coast of Australia. The ability of sites to regenerate naturally following weed removal was assessed in coastal dune communities invaded by the invasive alien, bitou bush (Chrysanthemoides monilifera subsp. rotundata). To investigate recruitment limitation, seed banks and vegetation of invaded, native, intensively managed (selective application of herbicide and some re-vegetation) and extensively managed (large-scale, non-selective herbicide application) sites were compared. We investigated the dispersal mechanisms of species in the seed bank and vegetation to determine if communities might be dispersal-limited, i.e. contain significant numbers of species with only short-distance dispersal capabilities. Species richness and composition of soil seed banks differed from the vegetation in foredunes and hinddunes. Invasion depleted seed banks further. About half of the species had short-distance dispersal mechanisms indicating the potential for dispersal limitation. Secondary weed invasion following management was evident although alien species occurred in both seed banks and vegetation. Our results indicated that coastal dune communities suffer recruitment limitation. Native, managed and invaded dune communities appear to be both seed bank and dispersal-limited although management and invasion exacerbates recruitment. Regeneration of coastal dune communities will require active reintroduction of species, particularly those with short-distance dispersal mechanisms.     

Evidence that Kenyan House Sparrows Passer domesticus invaded from multiple sites

Here we characterize genetic patterns across the range of House Sparrows in Kenya using six microsatellite markers. We screened House Sparrows from two remote locations in northern Kenya, Marsabit (n = 24) and Wajir (n = 27), which are separated from other colonized areas in Kenya by minimally developed, arid habitat, and then compared these birds with House Sparrows in 10 more central and longer established Kenyan cities (n = 233) in this range. House Sparrows from Marsabit and Wajir originated from a separate source, probably Somalia and/or Ethiopia, from other Kenyan House Sparrows, probably Mombasa. Furthermore, the genetic characteristics of northern and southern populations indicate that they have not yet mixed, supporting a hypothesis that the large, minimally (human) developed, arid landscape spanning nearly all of northern Kenya, including the 100 000 km² Chalbi Desert, is a barrier to dispersal for House Sparrows.     

Evidence for pollen limitation of a native plant in invaded communities

Animal-pollinated invasive species have frequently been demonstrated to outcompete native species for pollinator attention, which can have detrimental effects on the reproductive success and population dynamics of native species. Many animal-pollinated invasive species exhibit showy flowers and provide substantial rewards, allowing them to act as pollinator ‘magnets’, which, at a large scale, can attract more pollinators to an area, but, at a smaller scale, may reduce compatible pollen flow to local native species, possibly explaining why most studies detect competition. By performing pollen limitation experiments of populations in both invaded and uninvaded sites, we demonstrate that the invasive plant Lythrum salicaria appears to facilitate, rather than hinder, the reproductive success of native confamilial Decodon verticillatus, even at a small scale, in a wetland habitat in southeastern Ontario. We found no evidence for a magnet species effect on pollinator attraction to invaded sites. Germination experiments confirmed that seeds from invaded sites had similar germination rates to those from uninvaded sites, making it unlikely that a difference in inbreeding was masking competitive effects. We describe several explanations for our findings. Notably, there were no differences in seed set among populations at invaded and uninvaded sites. Our results underscore the inherent complexity of studying the ecological impacts of invasive species on natives.     

桉树枝瘿姬小蜂入侵海南省

桉树枝瘿姬小蜂Leptocybe invasa Fisher ＆ La Salle是一种新入侵的有害生物,专一危害桉属植物。近几年在地中海、非洲、中东和东南亚陆续发生,2007年中国大陆首次发现该虫,2008年7月发现其在海南发生。通过调查,目前在海南省分布在以三亚市、东方市和儋州市为中心的2个圆弧形区域,中心点危害较为严重,植株生长严重受阻。文章介绍桉树枝瘿姬小蜂的鉴别特征、生物学特性、在海南的发现及扩散过程和防控建议。     

Amphibian richness patterns in Atlantic Forest areas invaded by American bullfrogs

The relationship between invasion success and native biodiversity is central to biological invasion research. New theoretical and analytical approaches have revealed that spatial scale, land‐use factors and community assemblages are important predictors of the relationship between community diversity and invasibility and the negative effects of invasive species on community diversity. In this study we assess if the abundance of Lithobates catesbeianus, the American bullfrog, negatively affects the richness of native amphibian species in Atlantic Forest waterbodies in Brazil. Although this species has been invading Atlantic Forest areas since the 1930s, studies that estimate the invasion effects upon native species diversity are lacking. We developed a model to understand the impact of environmental, spatial and species composition gradients on the relationships between bullfrogs and native species richness. We found a weak positive relationship between bullfrog abundance and species richness in invaded areas. The path model revealed that this is an indirect relationship mediated by community composition gradients. Our results indicate that bullfrogs are more abundant in certain amphibian communities, which can be species‐rich. Local factors describing habitat heterogeneity were the main predictors of amphibian species richness and composition and bullfrog abundance. Our results reinforce the important role of habitats in determining both native species diversity and potential invasibility.     

金钟藤入侵群落的种间联结及生态位特征

金钟藤(Decalobanthus boisianus)是林业有害植物, 其暴发生长和扩散对森林生态系统造成了严重破坏。本文以海南岛48个金钟藤典型分布群落为研究对象, 用方差比率法和贡献定律法探究群落的稳定性; 用χ ²统计量、联结系数(AC)、共同出现百分率(PC)、Ochiai指数和Dice指数分析金钟藤与伴生物种的种间联结关系; 用生态位宽度、生态位相似性系数和生态位重叠指数研究群落中各物种的生态位特征, 以期为金钟藤生物防治的植物物种筛选提供借鉴。结果表明: (1)金钟藤所在48个群落共有156种伴生植物, 其中大戟科、茜草科、桑科、无患子科和樟科植物占优势; (2)群落中优势物种呈正联结关系, 植物种类累积倒数百分比与累积相对频度交点坐标为(44.53, 55.47), 远离稳定交点坐标(20, 80), 说明群落处于不稳定状态; (3)金钟藤与芳槁润楠(Machilus suaveolens)、黄椿木姜子(Litsea variabilis)、岭南山竹子(Garcinia oblongifolia)、显脉杜英(Elaeocarpus dubius)、鸭脚木(Schefflera octophylla)和银柴(Aporusa dioica)都紧密关联, 说明金钟藤与这些物种的资源利用方式较相似; (4)金钟藤的生态位宽度最大, 与伴生物种间的生态位重叠度较高, 但伴生物种间的生态位重叠度较低。金钟藤的入侵导致群落处于不稳定状态, 并与伴生物种间存在激烈的竞争关系。因此, 建议在金钟藤已入侵的群落中大量栽种芳槁润楠、黄椿木姜子、显脉杜英、鸭脚木和银柴, 以遏制其蔓延; 大量栽种翻白叶树(Pterospermum heterophyllum)、海南菜豆树(Radermachera hainanensis)、九节(Psychotria rubra)和肉实树(Sarcosperma laurinum)用于金钟藤入侵群落的植被恢复。     

Seed characteristics and regeneration of some species in invaded coastal communities

The seed production, germination and regeneration characteristics of two native species (Acacia longifolia var. sophorae and Banksia integrifolia) and two invasive subspecies (Chrysanthemoides monilifera ssp. monilifera and ssp. rotundata) were compared. C. monilifera ssp. rotundata was similar in seed characteristics and regeneration to B. integrifolia in that: (1) seed production was over an extended period each year; (2) seed longevity was low (0–2% viable after burial for 3 years), but increased with depth of burial; and (3) regeneration from 26 to 28% of mature plants occurred after fire. By contrast, C. monilifera ssp. monilifera was similar to A. Iongifolia var. sophorae in that; (1) seed production was over a short period each year; (2) of the total buried, 6–13% of seeds were viable after 3 years, and again numbers increased with depth of burial (percentages of missing seeds of A. longifolia were high but all remaining seeds were viable after 3 years); and (3) regeneration after fire occurred only from seed, hence their seed longevity is an important factor for long-term survival. However, growth habit and niche occupation by ssp. rotundata is similar to that of A. longifolia and the above differences may contribute to the observed displacement of the native by the invasive species. The distribution of the two invasive subspecies is at present largely in separate areas in Australia and it is predicted this situation will continue because of their differing climatic preferences, morphology and regeneration from fire.     

紫茎泽兰入侵地区土壤种子库特征

土壤种子库是植物潜在的种群,其时空分布格局对植物群落的动态与稳定性有着举足轻重的影响,尤其是在受外来种入侵危害地区,土壤种子库的特征对生态系统的恢复和未来植被的结构、功能、组成与动态等更为重要。本文通过野外调查与萌发实验相结合的方法研究了四川攀枝花市紫茎泽兰（Eupatorium adenophorum）入侵地区的植被组成和紫茎泽兰种子雨前后土壤种子库的变化,初步探讨了受入侵地区种子库中包括紫茎泽兰在内的物种的种类与储量情况。结果表明：（1）在紫茎泽兰危害严重的地带,群落组成比较简单,草本层以紫茎泽兰最为丰富,种群构成为1–4年生植株及其荫庇下大量的实生幼苗,Drude多度极大,频度达100%;（2）在土壤种子库中有13种高等植物出现,与植被组成的相似度为0.31;土壤种子库总储量为3,180粒/m^2,其中紫茎泽兰1,950粒/m^2,占总储量的61.3%。种子库各层种子储量不同,上层种子少于中下层,差异不显著（P〉0.05）,在土壤下层（5–10cm层）的紫茎泽兰种子仍然可以萌发;（3）种子雨后,表层土中（0–2cm）紫茎泽兰种子总储量为4,733粒/m^2;紫茎泽兰种子雨后种子萌发出现2个峰值,分别为第9天与第17天,表明土壤中的紫茎泽兰种子会阶段性打破休眠。紫茎泽兰在当地植被和土壤种子库中都占绝对优势,其他物种从种子阶段就开始亏缺,是紫茎泽兰不断更新和难以彻底控制的重要原因。     

Mortality of exotic and native seeds in invaded and uninvaded habitats

We examined seed survival in exotic- and native-dominated grasslands by placing seeds of a once-pervasive native grass species, Nassella pulchra, and two of the most common, widespread exotic grass species, Avena fatua and Bromus hordeaceus, in mesh bags in the field for 3 months. Compared to germination of unexposed seeds not placed in the field, exotic species experienced an approximately 40% reduction in viability, whereas the mortality experienced by the native species was <20%. Despite these differences, germination rates of exposed seeds were similar between native and exotic species because native N. pulchra seeds had lower initial viability prior to entering the seed bank. Seed mortality did not differ based on whether seeds were placed in habitats dominated by exotic or native grasses. Rather, our results suggest that re-establishment of native N. pulchra must focus on maximizing seed viability and survival, and that A. fatua and B. hordeaceus overcome relatively higher losses of viable seeds in the seed bank, potentially by producing large numbers of highly viable seeds.