Release of integrin macroaggregates as a mechanism of rear detachment during keratinocyte migration

Cell-substrate adhesion can be mediated by the relatively short-lived focal complexes and focal adhesions and by the more stable hemidesmosomes. During cell migration both types of cell-substrate adhesions must be disrupted allowing the cell rear to detach. Rear detachment has been described to be accompanied by membrane ripping and the loss of cellular material in a variety of cell types including fibroblasts and chondrocytes, but also in fast moving cells such as keratinocytes. Here we show that migrating keratinocytes leave behind "migration tracks" of cellular remnants that can be classified due to their size, distribution and molecular composition. Type I macroaggregates appeared as spherical and tubular structures with a diameter of about 50-100 nm that were arranged like "pearls on a string". These structures apparently derived from fragmentation of long tubular extensions, the retracting fibers, at the cell rear and contained high amounts of beta1 integrin and different alpha integrins that are components of fibronectin and laminin receptors in migrating keratinocytes usually found in focal adhesions. Type II macroaggregates were recognized as spherical structures with a diameter of about 30 - 50 nm that were arranged in clusters scattered over the gaps between type I, macroaggregates. In contrast to type I type II macroaggregates contained high amounts of beta4 integrin and seemed to derive from former hemidesmosomes. Both types of macroaggregates were completely membrane covered, impermeable compartments devoid of cytosolic proteins. Our observations strongly support the concept that the release of macroaggregates represents a distinct cellular mechanism of rear detachment based on the loss of adhesive receptors embedded in membrane-covered cellular remnants.     

东北黑土水稳性团聚体及其结合碳分布特征

以东北黑土区32对自然和耕作黑土为研究对象,对比研究了两种土壤水稳性团聚体及其结合碳的分布特征.结果表明：自然土壤0～30 cm水稳性大团聚体（>0.25 mm）质量分数及其结合碳均高于微团聚体;随着土层深度的增加,大团聚体及其结合碳逐渐降低,而微团聚体（<0.25 mm）及其结合碳显著增加（P<0.01）.耕作土壤团聚体分布特征与自然土壤相反,与自然土壤相比,耕作土壤大团聚体数量及其结合碳急剧降低,且>1 mm的大团聚体降低幅度远大于其他粒级团聚体.自然土壤大团聚体质量分数与土壤有机碳（SOC）存在明显的正相关关系（P<0.01）,尤其是>1 mm大团聚体;耕作土壤>1 mm大团聚体质量分数与土壤总SOC相关不显著;自然与耕作土壤总SOC与各级团聚体结合碳呈极显著正相关（P<0.01）.与自然土壤相比,耕作土壤大团聚体结合碳明显降低,而微团聚体结合碳增加了37.1%,总SOC含量下降了29.5%,表明大团聚体在总SOC变化中起主要作用.水稳性大团聚体对管理措施响应迅速,可以作为评价农业管理措施转变对土壤肥力和土壤质量影响的指标.     

Effect of soil macroaggregates crushing on C mineralization in a tropical deciduous forest ecosystem

Soil aggregates strongly influence C dynamics by affecting microbial activity. Our study tested the effect of soil crushing on C mineralization by laboratory incubation experiments of soil samples from a tropical deciduous forest ecosystem in Western Mexico. Soil samples were taken in January (dry season) and in October (rainy season). For each sampling date, the incubation experiment had a two factorial design with litter and macroaggregates (>250 μm) crushing as the main factors, both with two levels (with and without). At both sampling dates, the soil samples with intact macroaggregates had significantly higher C mineralization than the soil samples in which macroaggregates were crushed. The pH of leached solution was higher in the crushed soil samples than in uncrushed soil samples. The reduction of C mineralization caused by the disruption of soil aggregates is explained by the disturbance of environmental conditions within macroaggregates. The effect of macroaggregates crushing also reduced the differences of C mineralization between both seasons. We concluded that macroaggregates promote microbial activity by reducing the impact of variations in soil chemical and physical environmental conditions.     

Left- and right-handed LHC II macroaggregates revealed by circularly polarized chlorophyll luminescence

Circularly polarized chlorophyll luminescence (CPL) may serve as a measure of chiral macroaggregates of the light-harvesting chlorophyll-protein complexes (LHC II) in both isolated chloroplasts and intact leaves (Gussakovsky et al (2000) Photosynth Res 65: 83–92). In the present work, we applied the CPL approach to study the effect of fast (1–2 min) thermal impacts on LHC II macroaggregates. The results revealed unexpected temperature-response kinetics, composed of initial bell-shaped changes in the CPL signal, followed by degradation down to a steady state (equilibrium). The bell-shape effect was dependent upon illumination, and vanished in the dark. A mathematical analysis of the temperature-response kinetics uniquely indicated that LHC II chiral macroaggregates may persist in both left- and right-handed forms. These forms differ in their response to high temperatures. Both forms are more thermostable in leaves than in isolated chloroplasts. The cooperative degradation of LHC II macroaggregates, which is induced by the thermal impact, is irreversible. It is therefore suggested that the native LHC II macroaggregates are stable, stationary, non-equilibrium, spatially heterogeneous (dissipative) structures. The dissipative properties probably allow the interconversion between left- and right-handed forms under perturbation by certain factors. Illumination probably serves as one such perturbation factor, initiating the interconversion of dark-adapted, left-handed to light-dependent, right-handed LHC II macroaggregates. The chiral heterogeneity of the LHC II macroaggregates is a newly revealed aspect which needs to be taken into consideration in future circular dichroism or CPL studies.     

Production of macroaggregates from dissolved exopolymeric substances (EPS) of bacterial and diatom origin

Exopolymeric substances (EPS) isolated from a pure culture of the marine bacterium Marinobacter sp. and the marine diatom Skeletonema costatum (axenic) were partially purified, chemically characterized and used as dissolved organic matter (DOM) for the production of macroaggregates. The role of organic particles such as transparent exopolymeric particles (TEP) and Coomassie stained particles (CSP) in the production of macroaggregates was experimentally assessed. Three experimental rolling tanks containing sterile medium with: (1) EPS, (2) EPS + live diatom cells and (3) EPS + killed bacteria, and three control tanks without any added EPS were used for macroaggregate production. Changes in abundance and average size of macroaggregates were monitored using image analysis, whereas TEP and CSP were enumerated microscopically. In the presence of microbial EPS, macroaggregates of a size of 23-35 mm(2) were produced. Aggregate size and abundance considerably varied with both time and source of EPS. No correlation was observed for macroaggregate size and abundance with either TEP or CSP. One-way ANOVA demonstrated significant differences in the variance of particle abundance and size in tanks having only EPS or EPS in combination with live diatom cells. Our data suggest that production of macroaggregates was influenced by polymer chemistry and surface properties of colliding particles, whereas TEP and CSP concentrations were influenced by molecular weight of EPS and the presence of growing cells. Interestingly, macroaggregates were formed in the near absence of TEP and CSP, highlighting the role of other unknown processes in the transformation of DOM to particulate organic matter (POM) in aquatic environments.     

Research Commentary: Association of Zoonotic Pathogens with Fresh, Estuarine, and Marine Macroaggregates

Aquatic macroaggregates (flocs ≥0.5 mm) provide an important mechanism for vertical flux of nutrients and organic matter in aquatic ecosystems, yet their role in the transport and fate of zoonotic pathogens is largely unknown. Terrestrial pathogens that enter coastal waters through contaminated freshwater runoff may be especially prone to flocculation due to fluid dynamics and electrochemical changes that occur where fresh and marine waters mix. In this study, laboratory experiments were conducted to evaluate whether zoonotic pathogens (Cryptosporidium, Giardia, Salmonella) and a virus surrogate (PP7) are associated with aquatic macroaggregates and whether pathogen aggregation is enhanced in saline waters. Targeted microorganisms showed increased association with macroaggregates in estuarine and marine waters, as compared with an ultrapure water control and natural freshwater. Enrichment factor estimations demonstrated that pathogens are 2–4 orders of magnitude more concentrated in aggregates than in the estuarine and marine water surrounding the aggregates. Pathogen incorporation into aquatic macroaggregates may influence their transmission to susceptible hosts through settling and subsequent accumulation in zones where aggregation is greatest, as well as via enhanced uptake by invertebrates that serve as prey for marine animals or as seafood for humans.     

Variables of Microbial Response in Natural Soil Aggregates for Soil Characterization in Different Fluvial Land Shapes

The main objective of this study was to determine changes in microbial response in natural soil aggregates for soil characterization in different fluvial land shapes. This study was carried out in fluvial lands formed on accumulated sediment depositions carried by K?z?l?rmak River. The majority soils of the study area were classified as Typic Ustifluvent and Typic Haplustept in Soil Taxonomy. It was found that macroaggregates (especially >6300 μm and 2000–4750 μm diameters) of all soil samples were higher than microaggregate of soils. In addition, it was determined that the C_org content varies between 0.41–0.91% in soil samples. C_mic content was also found higher level in aggregates involved <250 and 250–425 μm diameters as compared to other aggregate size classes. Moreover, we detected that C_org:C_mic ratio was much higher in macroaggregates than in microaggregate fractions. BR levels were also greater in macroaggregates of >6,300, 4,750–6,300 and 2,000–4,750 μm than in the other macroaggregates sizes and microaggregates. Consequently, macroaggregates have relatively more C_org level than the C_org level in microaggregates, even if the absolute values of C_mic were the lower. This study thus evidenced contrasting microbial habitats and their response in different soil aggregate size formed in various developed soils.     

The Use of Macro-Aggregates of Radioiodinated Human Serum Albumin in Brain Scanning

Intra-arterially injected macroaggregates of radioiodinated human serum albumin were used in the detection of brain tumours in mice and in human subjects. The mean size of particle used was 29 μ. Brain-to-tumour ratios in ependymoblastoma-bearing mice ranged from 43.5:1 to 2.8:1. Autoradiographs of brain and tumour from sacrificed mice indicated that most of the macroaggregates were trapped within cerebral and cerebellar grey matter. Tumour retained little activity. Particles within small vessels did not cause complete obstruction, although temporary vessel spasm, cessation and reversal of flow were observed. Twelve patients with clinically evident brain tumours received carotid or vertebral injections of macroaggregates. Ten had histologically proved tumours, and six of these were correctly localized by external scanning. The quality of the scans was not superior to that obtained with other tracers currently in use. Because four patients developed transient neurological complications that could be attributed to the procedure, the clinical pilot study was terminated.     

Structural and compositional analysis of the keratinocyte migration track

Slowly migrating cells such as fibroblasts leave behind a "migration track," which has been assumed not to occur in fast-moving cells such as keratinocytes. Here we show that keratinocytes left behind "migration tracks" of cellular remnants consisting of membranous patches or macroaggregates that were anchored to a meshwork of extracellular matrix proteins consisting of collagen type IV, fibronectin, laminin, and laminin 5. According to their origin and localisation, two types of macroaggregates could be distinguished : (1) Spherical and elongated tubular structures (diameter about 50-110 nm) both of which were arranged like "pearls on a string" and that apparently derived from fragmentation of retracting fibres. (2) Spherical structures (diameter about 50 nm) left behind in the gaps between the retracting fibres and presumably derived from former focal adhesion sites. Both types of macroaggregates did not contain cytoplasmic proteins but carried on their surface adhesion proteins, particularly high amounts of integrins : type 1 macroaggregates contained alpha3beta1-integrins, whereas type 2 macroaggregates contained other types of integrins such as alpha6beta4-integrins. Modulation of keratinocyte adhesion by using poly-L-lysine coated cover slips resulted in an increased application of inhibitory beta1-antibodies and slightly reduced migration velocity and track formation. Within 24 h of migration, we observed a migration velocity-dependent loss of cellular beta1-integrin by macroaggregate formation of about 11% for fast and about 4% for slowly migrating keratinocytes. The physiological role of the migration track is unclear. However, with its multiple adhesion sites it may serve as a provisional basement membrane during reepithelialization of epidermal wounds.     

Renal imaging: a comparison of radionuclide,ultrasound, and computed tomographic scanning in investigation of renal space-occupying lesions.

Two studies were carried out in which 27 and 23 patients respectively with renal space-occupying lesions were assessed by different techniques and the results compared. Instead of proceeding to renal arteriography after the lesion had been found on urography, radionuclide and ultrasound scanning were used in the first study to clarify the nature of the lesions, while in the second study computed tomography was used as well. Results were good with all three methods, although ultrasonography and radionuclide scanning cannot resolve lesions of under 2 cm in diameter and the radiation dose with computed tomography is similar to that used in renal arteriography. Probably the best method of evaluating renal space-occupying lesions after urography is to use both ultrasound and radionuclide scanning. If further information is required computed tomography or arteriography is indicated.     

黄土高原不同土壤质地农田土壤碳、氮、磷及团聚体分布特征

结合野外观测和室内分析,研究了黄土高原不同土壤质地农田土壤碳、氮、磷含量及其生态计量学特征,以及土壤团聚体分布状况,以揭示土壤质地对区域农田土壤肥力的影响,以及土壤团聚体对肥力的调控作用.结果表明: 黄土高原农田土壤大团聚体含量、主要养分含量及其生态计量比值均随土壤质地由细变粗(壤质黏土→黏壤土→砂质壤土)逐渐降低;土壤pH值和微团聚体含量则呈现出相反的变化趋势. 随土壤黏粒含量增加,大团聚体含量、有机碳、全氮和全磷含量,以及C/P和N/P显著增加,土壤pH和微团聚体含量显著降低. 土壤有机碳、全氮和全磷含量,以及C/P和N/P随大团聚体含量的增加显著增加.表明区域尺度上农田土壤肥力状况取决于土壤质地,并受土壤大团聚体的调节.     

Dispersal of proteolipid macroaggregates with trifluoroacetic acid and analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis

The propensity of highly purified proteolipids to form macroaggregates in aqueous solutions, especially when heated with sodium dodecyl sulfate (SDS), with or without thiol reagents, has made qualitative and quantitative analyses of individual species by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) difficult and unreliable. Comparisons of proteolipid profiles from liver, brain, and cultured human keratinocytes demonstrate that 40-72% of the total proteolipid in SDS-PAGE sample buffer is in the form of macroaggregates. Treatment of proteolipids with neat trifluoroacetic acid (TFA) followed by removal of the TFA and incubation in cold SDS-PAGE sample buffer causes complete dispersal of the macroaggregates and allows recovery of virtually all of the proteolipid applied to gels (increasing yields by as much as 3.6 times, depending on tissue type). Gels of TFA-treated samples display differences not only in the relative amounts of individual species but also in novel species not found in untreated samples. Eluted macroaggregates treated with TFA display the same SDS-PAGE banding profiles as TFA-treated whole proteolipids. Hence, routine TFA treatment of proteolipids prior to SDS-PAGE increases total proteolipid yields, allows reliable quantitation of individual apoprotein species, and reveals species previously obscured by the formation of macroaggregates.     

Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation

The formation of collagen fibrils, fibril bundles, and tissue-specific collagen macroaggregates by chick embryo tendon fibroblasts was studied using conventional and high voltage electron microscopy. During chick tendon morphogenesis, there are at least three extracellular compartments responsible for three levels of matrix organization: collagen fibrils, bundles, and collagen macroaggregates. Our observations indicate that the initial extracellular events in collagen fibrillogenesis occur within narrow cytoplasmic recesses, presumably under close cellular regulation. Collagen fibrils are formed within these deep, narrow recesses, which are continuous with the extracellular space. Where these narrow recesses fuse with the cell surface, it becomes highly convoluted with folds and processes that envelope forming fibril bundles. The bundles laterally associate and coalesce, forming aggregates within a third cell-defined extracellular compartment. Our interpretation is that this third compartment forms as cell processes retract and cytoplasm is withdrawn between bundles. These studies define a hierarchical organization within the tendon, extending from fibril assembly to fascicle formation. Correlation of different levels of extracellular compartmentalization with tissue architecture provides insight into the cellular controls involved in collagen fibril and higher order assembly and a better understanding of how collagen fibrils are collected into structural groups, positioned, and woven into functional tissue-specific collagen macroaggregates.     

Engineering cartilage tissues with the shape of human nasal alar by using chondrocyte macroaggregate--Experiment study in rabbit model

Despite of progresses in tissue engineering based on cell/scaffold strategy, uneven cell distribution as well as tissue formation in the scaffold, limited cell seeding efficiency and inflammatory reaction triggered by the degradation of scaffold remain problems to be resolved. In this study, we proposed a novel cell-macroaggregate cultivation system, and explored a feasible strategy to construct three-dimensional cartilage tissue with shape of human nasal alar by using cell macroaggregate. Isolated chondrocytes was cultured at high density to form a monolayer chondrocyte sheet as well as expanded for seeding on the sheet to produce mechanically operable cell macroaggregate. Chondrocyte macroaggregates were then fabricated into transplants with shape of nasal alar by using Internal support or External scaffold techniques; results of in vivo chondrogenesis were investigated in immunocompetent animal. Chondrocyte macroaggregates presented long survival time and good viability; constructs fabricated using both techniques can develop into tissues with characteristic structure of native cartilage, glycosaminoglycans as well as type II collagen were highly produced in the ECM of engineered cartilages. By placing hyaluronan ester film as Internal support, the predetermined shape of the chondrocyte macroaggregate can be well maintained. In contrast, due to the poor mechanical stability of grafts fabricated in External scaffold group, obvious deformation occurred in harvested specimens. The experiment proved the usefulness of chondrocyte macroaggregate in cartilage regeneration, and provided a new strategy to engineer cartilage with special shape by using cell macroaggregate/biodegradable support.     

Macroaggregates and their phytoplanktonic components in the Southern California Bight

The abundances of phytoplankton associated with scuba-collected,visible macroaggregates (i e. ‘marine Snow’) fromvarious euphotic zone depths of several nearshore and offshoresites sampled in late winter/early spring and summer were determinedby microscopic study. Such phytoplankters have a different potentialfor predator/prey interactions than they would as separate individuals.Mean macroaggregate concentrations of 1.7–7 6 1^–1and mean individual macroaggregate sizes of 27–175 mm³were observed at the different sites. Phytoplankters associatedwith the macroaggregates were generally a few percent or lessof the total phytoplankton (range for numbers. 0.2–2.5%.range for carbon, 0.2–7.1%. n = 11). Of the taxonomicgroups, pennate diatoms in general showed high relative associationwith macroaggregates. Compared to the mean abundance of phytoplanktonin an equivalent volume of surrounding water, macroaggregateswere algal-enriched by factors ranging from 6.2–1300 (median,65) for numbers and 6.3–2500 (median. 110) for carbon(n = 11). ATP and chlorophyll a showed degrees of associationwith, and enrichment in. macroaggregates similar to that ofphytoplankton carbon. Before assessing the overall importanceof phytoplanktonic associations with aggregates in terms ofpelagic food web consequences, the abundances and algal compositionof the smaller microaggregates must also be known     

Aggregation and C and N contents of soil organic matter fractions in a permanent raised-bed planting system in the Highlands of Central Mexico

Permanent raised bed planting with crop residue retention is a form of conservation agriculture that has been proposed as an alternative to conventional tillage for wheat production systems in the Central Highlands of Mexico. A field experiment comparing permanent and tilled raised beds with different residue management under rainfed conditions was started at El Batán (State of Mexico, Mexico) in 1999. The percentage of small and large macroaggregates and mean weight diameter (MWD) was significantly larger in permanent raised beds compared to conventionally tilled raised beds both with full crop residue retention (average for maize and wheat), while the percentages free microaggregates was lower. The percentages of small and large macroaggregates and mean weight diameter (MWD) was significantly larger in permanent raised beds with residue retention compared to permanent raised beds with removal of the residue (average for maize and wheat), while the percentages free microaggregates and silt and clay fraction was lower. Cultivation of maize significantly reduced the large macroaggregates, while wheat reduced the silt and clay fraction (average over all systems). Cultivation of maize reduced the C and N content of the free microaggregates compared to soil cultivated with wheat, while removal of plant residue reduced the C and N content of the silt and clay fraction compared to soil where residue was retained. The C and N content of the coarse particulate organic matter (cPOM) and microaggregates within the macroaggregates was significantly larger in permanent raised beds compared to conventionally tilled raised beds both with full residue retention, while C and N content of the cPOM was significantly lower when residue was removed or partially removed compared to the soil where the residue was retained. The δ ¹³C ‰ signatures of the macroaggregates, microaggregates, the silt and clay fraction, cPOM and microaggregates within the macroaggregates were not affected by tillage or residue management when wheat was the last crop, but removal of residue reduced the δ ¹³C ‰ signatures of the macro-, microaggregates and microaggregates within the macroaggregates significantly compared to soil where the residue was retained. Retaining only 30–50% of the organic residue still improved the soil structure considerably compared to plots where it was removed completely. Permanent raised beds without residue retention, however, is a practice leading to soil degradation. Kelly Lichter and Bram Govaerts contributed equally to this publication.     

不同施肥处理黑土覆膜后秸秆碳氮在团聚体中的固存特征

地膜覆盖是提高作物产量的重要措施,理解覆膜条件下黑土团聚体中外源碳和氮的固存特征,为深刻认识地膜覆盖措施的可持续应用提供理论依据。选取长期定位试验站(29年)不施肥(CK)、单施化肥(NPK)和有机肥配施化肥(MNPK)3个典型施肥处理,表层土壤(0—20 cm)添加¹³C¹⁵N双标记玉米秸秆后设置裸地和覆膜的田间原位微区培养试验,探讨不同施肥处理结合覆膜黑土团聚体中有机碳和全氮对秸秆来源碳和氮的响应。结果表明,与裸地相比,所有处理覆膜后微团聚体(<0.25 mm)中秸秆来源碳和氮的含量平均降低了26.49%和32.05%。覆膜MNPK与裸地处理相比大团聚体(>0.25 mm)中秸秆来源碳和氮的含量显著降低了35.58%和15.97%,但大团聚体中原土壤有机碳的含量提高了9.16%。在CK和NPK处理微团聚体中,秸秆来源碳占该粒级团聚体有机碳的比例表现为覆膜>裸地,而在MNPK处理各粒级团聚体中则表现为裸地>覆膜。无论覆膜与否,秸秆来源碳对团聚体有机碳和秸秆来源氮对团聚体全氮的贡献率受施肥处理的影响表现为CK>N...     

紫色土线虫对长期不同施肥措施的响应

土壤线虫在农田生态系统中数量丰富且对土壤环境变化敏感, 可用于评估不同田间管理条件下的土壤健康。本文探究了紫色土区长期不同施肥措施及土壤团聚体粒径对线虫群落的分布及其生态功能多样性的影响。试验设置了5个施肥处理: 不施肥(对照, CK)、单施化肥(NPK)、生物炭 + 化肥(BCNPK)、商品猪粪 + 化肥(OMNPK)和秸秆 + 化肥(RSDNPK)。团聚体粒径分为: 原状土(BS)、大团聚体(> 2 mm; LA)和小团聚体(0.25-2 mm; SA)。结果表明, 与对照相比, 施肥可促进线虫数量增长, 其中单施化肥处理下增幅最小(66%); 有机物料与化肥配施对线虫数量的提升更为显著, 秸秆 + 化肥处理下增幅达206%。不同施肥处理间线虫类群相对丰度差异显著, 大小均表现为: 食细菌线虫(BA) > 杂食/捕食线虫(OP) > 植食线虫(PP) > 食真菌线虫(FU)。小团聚体较其他土壤团聚体的杂食/捕食线虫丰度更低, 食细菌线虫丰度较高。秸秆与化肥配施处理下线虫群落结构指数和富集指数显著增加, 且各施肥处理下线虫功能足迹呈现明显差异。有机肥与化肥配施(尤其是秸秆 + 化肥)可提高土壤养分供应且有利于形成稳定健康的土壤生态系统, 助推区域农业的可持续发展。     

Identification of new celiac disease autoantigens using proteomic analysis

Celiac disease is an autoimmune disorder in which gluten peptides presented by specific HLA-DQ2- and HLA-DQ8-positive antigen presenting cells elicit immune response in connective tissue of lamina propria. Immunoglobulin A (IgA) antiendomysial antibodies are specific for celiac disease and are used for screening, diagnosis and follow-up of this disease with an almost 100% sensitivity and specificity. The major target antigen of IgA antiendomysial antibodies was identified as tissue transglutaminase; nevertheless, the existence of the additional unique celiac disease-specific autoantigens is anticipated. In this study we have utilized a proteomic approach in order to search out new autoantigens recognized by serum antibodies of patients with active celiac disease. We report the detection of 11 proteins that were immunorecognized with various frequencies by sera of patients with celiac disease. Four autoantigens were identified by mass fingerprinting approach as actin, ATP synthase beta chain and two charge variants of enolase alpha. While production of IgA antibodies against actin molecules were described earlier, the existence of autoantibodies to ATP synthase beta chain and enolase alpha species in sera collected from patients with active celiac disease are described for the first time. These results are suggestive of the existence of additional celiac disease autoantigens with possible diagnostic utility.     

Cell signaling events: a view from the matrix.

Cellular activities are primarily initiated, modulated and sustained by multifunctional molecules (cytokines and growth factors) that are secreted into the extracellular space and that signal through membrane-bound, high-affinity receptors. In contrast to the fairly well understood mechanisms that mediate the specificity of signal transduction within the confined and compartmentalized environment of the cell, significantly less is known about the mechanisms that regulate the availability of signaling molecules in the extracellular milieu. Recent findings have implicated the participation of extracellular protein macroaggregates in signaling events controlling patterning and morphogenesis. The results suggest a functional coupling between the tissue-specific organization of collagenous and elastic macroaggregates and their ability to perform instructive as well as structural functions. These observations open the way to a novel understanding in these poorly understood and critically important areas of cell and developmental biology.