Anti-type II collagen antibodies are associated with early radiographic destruction in rheumatoid arthritis

Introduction

We have previously reported that high levels of antibodies specific for native human type II collagen (anti-CII) at the time of RA diagnosis were associated with concurrent but not later signs of inflammation. This was associated with CII/anti-CII immune complex (IC)-induced production of pro-inflammatory cytokines in vitro. In contrast, anti-cyclic citrullinated peptide antibodies (anti-CCP) were associated both with late inflammation and late radiological destruction in the same RA cohort. We therefore hypothesized that anti-CII are also associated with early erosions.

Methods

Two-hundred-and-fifty-six patients from an early RA cohort were included. Baseline levels of anti-CII, anti-CCP and anti-mutated citrullinated vimentin were analyzed with ELISA, and rheumatoid factor levels were determined by nephelometry. Radiographs of hands and feet at baseline, after one and after two years were quantified using the 32-joints Larsen erosion score.

Results

Levels of anti-CII were bimodally distributed in the RA cohort, with a small (3.1%, 8/256) group of very high outliers with a median level 87 times higher than the median for the healthy control group. Using a cut-off discriminating the outlier group that was associated with anti-CII IC-induced production of proinflammatory cytokines in vitro, baseline anti-CII antibodies were significantly (p = 0.0486) associated with increased radiographic damage at the time of diagnosis. Anti-CII-positive patient had also significantly increased HAQ score (p = 0.0303), CRP (p = 0.0026) and ESR (p = 0.0396) at the time of diagnosis but not during follow-up. The median age among anti-CII-positive subjects was 12 years higher than among the anti-CII-negative patients.

Conclusion

In contrary to anti-CCP, anti-CII-positive patients with RA have increased joint destruction and HAQ score at baseline. Anti-CII thus characterizes an early inflammatory/destructive phenotype, in contrast to the late appearance of an inflammatory/destructive phenotype in anti-CCP positive RA patients. The anti-CII phenotype might account for part of the elderly acute onset RA phenotype with rather good prognosis.     

Life cycle inventory modeling of phosphorus substitution,losses and crop uptake after land application of organic waste products

Purpose

Life cycle assessments (LCAs) that attempt to provide advice on treatment options for phosphorus (P) containing organic waste products encounter problems related to the quantification of mineral P fertilizer substitution, P loss and crop P uptake after land application. The purpose of this study was to develop a relatively easy to use life cycle inventory model, known as PLCI, that could be used to estimate these values.

Methods

A life cycle inventory model for P was developed, which estimates the effect of an application of organic waste followed by ordinary fertilizer management in the modeling period. This was compared with a simulation without the initial waste application. The difference in mineral P fertilizer application (substitution), P loss and crop P uptake was then calculated and expressed as a proportion of the amount of waste applied. As an example, the effect of an initial application of mineral fertilizer, sewage sludge and ash on two farm types was simulated. These results were applied in an LCA case study of different sewage sludge treatment options.

Results and discussion

Farm type influenced the P fertilizer substitution, loss and crop uptake factors. The application on an arable farm showed a substitution of 28 to 31%, relatively low P loss and a large spread in crop P uptake for the different P sources, compared with the pig farm. Application on a pig farm showed no mineral P substitution. For substitution, mineral fertilizer outperformed waste product fertilizer with a short modeling period, due to higher immediate P availability, which was not the case with a long period. The LCA case study showed that the P substitution factor had an influence on the environmental impact categories climate change and depletion of reserve-based abiotic resources while the P loss factor influenced freshwater eutrophication. Application of the P loss and substitution factors generated from the PLCI model resulted in higher environmental burdens and lower savings than using conventional factors.

Conclusions

The soil P status mainly affected P substitution and loss, with the fertilizer type only having a small influence when soils had a low P status. The PLCI model can facilitate more coherent and rigorous estimates of P substitution and loss to be used in LCA studies involving application of waste products on agricultural land. This is important since P substitution and loss can have an important influence on impact categories, such as freshwater eutrophication and resource depletion.

     

Nothia ex gr. excelsa (Grzybowski, 1898), ‘flysch-type’ agglutinated foraminifera from the Karpatian (Early-Miocene) of Hungary

Abstract

Nothia ex gr. excelsa (Grzybowski, 1898) branched, agglutinated, tubular foraminifera is documented for the first time from the Karpatian (latest Burdigalian) molasse sediments of the Paratethys. Excellently preserved specimens allowed the study of the macro- and microstructure of the test using reflected and polarized light microscopes, SEM and Raman spectroscopy. The mineralogical components of the agglutinated grains, the appearance of the protruded aperture with a scalloped-edge, the microstructure of the bilamellar wall, the presence of the calcite microgranular cement could all be described in detail. Based on autecology, the test morphology and the associated fauna indicate that Nothia ex gr. excelsa was a surface-dwelling detritivore with a seasonal-phytophagous mode of life.     

The 141-year period for Dr. Beal's seed viability experiment: A hybrid surprise

Premise

In 1879, Dr. William Beal buried 20 glass bottles filled with seeds and sand at a single site at Michigan State University. The goal of the experiment was to understand seed longevity in the soil, a topic of general importance in ecology, restoration, conservation, and agriculture, by periodically assaying germinability of these seeds over 100 years. The interval between germination assays has been extended and the experiment will now end after 221 years, in 2100.

Methods

We dug up the 16th bottle in April 2021 and attempted to germinate the 141-year-old seeds it contained. We grew germinants to maturity and identified these to species by vegetative and reproductive phenotypes. For the first time in the history of this experiment, genomic DNA was sequenced to confirm species identities.

Results

Twenty seeds germinated over the 244-day assay. Eight germinated in the first 11 days. All 20 belonged to the Verbascum genus: Nineteen were V. blattaria according to phenotype and ITS2 genotype; and one had a hybrid V. blattaria × V. thapsus phenotype and ITS2 genotype. In total, 20/50 (40%) of the original Verbascum seeds in the bottle germinated in year 141.

Conclusions

While most species in the Beal experiment lost all seed viability in the first 60 years, a high percentage of Verbascum seeds can still germinate after 141 years in the soil. Long-term experiments such as this one are rare and invaluable for studying seed viability in natural soil conditions.     

Turning Up the Heat on a Hotspot: DNA Barcodes Reveal 80% More Species of Geometrid Moths along an Andean Elevational Gradient

We sampled 14,603 geometrid moths along a forested elevational gradient from 1020–3021 m in the southern Ecuadorian Andes, and then employed DNA barcoding to refine decisions on species boundaries initially made by morphology. We compared the results with those from an earlier study on the same but slightly shorter gradient that relied solely on morphological criteria to discriminate species. The present analysis revealed 1857 putative species, an 80% increase in species richness from the earlier study that detected only 1010 species. Measures of species richness and diversity that are less dependent on sample size were more than twice as high as in the earlier study, even when analysis was restricted to an identical elevational range. The estimated total number of geometrid species (new dataset) in the sampled area is 2350. Species richness at single sites was 32–43% higher, and the beta diversity component rose by 43–51%. These impacts of DNA barcoding on measures of richness reflect its capacity to reveal cryptic species that were overlooked in the first study. The overall results confirmed unique diversity patterns reported in the first investigation. Species diversity was uniformly high along the gradient, declining only slightly above 2800 m. Species turnover also showed little variation along the gradient, reinforcing the lack of evidence for discrete faunal zones. By confirming these major biodiversity patterns, the present study establishes that incomplete species delineation does not necessarily conceal trends of biodiversity along ecological gradients, but it impedes determination of the true magnitude of diversity and species turnover.     

Self-assembly of sensory neurons into ganglia-like microtissues

Unraveling intra- and inter-cellular signaling networks managing cell-fate control, coordinating complex differentiation regulatory circuits and shaping tissues and organs in living systems remain major challenges in the post-genomic era. Resting on the laurels of past-century monolayer culture technologies, the cell culture community has only recently begun to appreciate the potential of three-dimensional mammalian cell culture systems to reveal the full scope of mechanisms orchestrating the tissue-like cell quorum in space and time. Capitalizing on gravity-enforced self-assembly of monodispersed primary embryonic mouse cells in hanging drops, we designed and characterized a three-dimensional cell culture model for ganglion-like structures. Within 24h, a mixture of mouse embryonic fibroblasts (MEF) and cells, derived from the dorsal root ganglion (DRG) (sensory neurons and Schwann cells) grown in hanging drops, assembled to coherent spherical microtissues characterized by a MEF feeder core and a peripheral layer of DRG-derived cells. In a time-dependent manner, sensory neurons formed a polar ganglion-like cap structure, which coordinated guided axonal outgrowth and innervation of the distal pole of the MEF feeder spheroid. Schwann cells, present in embryonic DRG isolates, tended to align along axonal structures and myelinate them in an in vivo-like manner. Whenever cultivation exceeded 10 days, DRG:MEF-based microtissues disintegrated due to an as yet unknown mechanism. Using a transgenic MEF feeder spheroid, engineered for gaseous acetaldehyde-inducible interferon-beta (ifn-beta) production by cotransduction of retro-/ lenti-viral particles, a short 6-h ifn-beta induction was sufficient to rescue the integrity of DRG:MEF spheroids and enable long-term cultivation of these microtissues. In hanging drops, such microtissues fused to higher-order macrotissue-like structures, which may pave the way for sophisticated bottom-up tissue engineering strategies. DRG:MEF-based artificial micro- and macrotissue design demonstrated accurate key morphological aspects of ganglions and exemplified the potential of self-assembled scaffold-free multicellular micro-/macrotissues to provide new insight into organogenesis.     

A dynamic mass balance model for phosphorus fluxes and concentrations in coastal areas

This paper presents a general, process-based mass balance model (CoastMab) for total phosphorus (TP) in defined coastal areas (at the ecosystem scale). The model is based on ordinary differential equations and calculates inflow, outflow and internal fluxes on a monthly basis. It consists of four compartments: surface water, deep water, erosion/transportation areas for fine sediments and accumulation areas for fine sediments. The separation between surface water and deep water is not done based on water temperature, but on sedimentological criteria instead (from the theoretical wave base). There are algorithms for all major internal TP fluxes (sedimentation, resuspension, diffusion, mixing and burial). Validations were performed using data from 21 different Baltic coastal areas. The results show that the model predicts monthly TP in water and chlorophyll a very well (generally within the uncertainty bands of the empirical data). The model has also been put through sensitivity tests, which show that the most important factor regulating the predictions of the model is generally the TP concentration in the sea beyond the coast. The model is simple to apply, since all driving variables may be accessed from maps or monitoring programs. The driving variables include coastal area, section area (between the defined coastal area and the adjacent sea), mean and maximum depths, latitude (used to predict water temperatures, stratification and mixing), salinity and TP concentration in the sea. Many of the model structures are general and could be used for areas other than those included in this study, e.g., for open coasts, estuaries or tidal coasts, as well as for other substances than phosphorus.