Summary Purpose The aim of this “Year in Review” article is to summarize and discuss the implications of biochemical marker related articles published between the Osteoarthritis Research Society ...International (OARSI) 2015 Congress in Seattle and the OARSI 2016 Congress in Amsterdam. Methods The PubMed/MEDLINE bibliographic database was searched using the combined keywords: ‘biomarker’ and ‘osteoarthritis’. The PubMed/MEDLINE literature search was conducted using the Advanced Search Builder function ( http://www.ncbi.nlm.nih.gov/pubmed/advanced ). Results Over two hundred new biomarker-related papers were published during the literature search period. Some papers identified new biomarkers whereas others explored the biological properties and clinical utility of existing markers. There were specific references to several adipocytokines including leptin and adiponectin. ADAM Metallopeptidase with Thrombospondin Type 1 motif 4 (ADAMTS-4) and aggrecan ARGS neo-epitope fragment (ARGS) in synovial fluid (SF) and plasma chemokine (CeC motif) ligand 3 (CCL3) were reported as potential new knee biomarkers. New and refined proteomic technologies and novel assays including a fluoro-microbead guiding chip (FMGC) for measuring C-telopeptide of type II collagen (CTX-II) in serum and urine and a novel magnetic nanoparticle-based technology (termed magnetic capture) for collecting and concentrating CTX-II, were described this past year. Conclusion There has been steady progress in osteoarthritis (OA) biomarker research in 2016. Several novel biomarkers were identified and new technologies have been developed for measuring existing biomarkers. However, there has been no “quantum leap” this past year and identification of novel early OA biomarkers remains challenging. During the past year, OARSI published a set of recommendations for the use of soluble biomarkers in clinical trials, which is a major step forward in the clinical use of OA biomarkers and bodes well for future OA biomarker development.
Mechanisms of reef coral resistance to future climate change Palumbi, Stephen R.; Barshis, Daniel J.; Traylor-Knowles, Nikki ...
Science (American Association for the Advancement of Science),
05/2014, Letnik:
344, Številka:
6186
Journal Article
Recenzirano
Reef corals are highly sensitive to heat, yet populations resistant to climate change have recently been identified. To determine the mechanisms of temperature tolerance, we reciprocally transplanted ...corals between reef sites experiencing distinct temperature regimes and tested subsequent physiological and gene expression profiles. Local acclimatization and fixed effects, such as adaptation, contributed about equally to heat tolerance and are reflected in patterns of gene expression. In less than 2 years, acclimatization achieves the same heat tolerance that we would expect from strong natural selection over many generations for these long-lived organisms. Our results show both short-term acclimatory and longer-term adaptive acquisition of climate resistance. Adding these adaptive abilities to ecosystem models is likely to slow predictions of demise for coral reef ecosystems.
The evolution of tolerance to future climate change depends on the standing stock of genetic variation for resistance to climate-related impacts 1, 2, but genes contributing to climate tolerance in ...wild populations are poorly described in number and effect. Physiology and gene expression patterns have shown that corals living in naturally high-temperature microclimates are more resistant to bleaching because of both acclimation and fixed effects, including adaptation 3. To search for potential genetic correlates of these fixed effects, we genotyped 15,399 single nucleotide polymorphisms (SNPs) in 23 individual tabletop corals, Acropora hyacinthus, within a natural temperature mosaic in backreef lagoons on Ofu Island, American Samoa. Despite overall lack of population substructure, we identified 114 highly divergent SNPs as candidates for environmental selection, via multiple stringent outlier tests, and correlations with temperature. Corals from the warmest reef location had higher minor allele frequencies across these candidate SNPs, a pattern not seen for noncandidate loci. Furthermore, within backreef pools, colonies in the warmest microclimates had a higher number and frequency of alternative alleles at candidate loci. These data suggest mild selection for alternate alleles at many loci in these corals during high heat episodes and possible maintenance of extensive polymorphism through multilocus balancing selection in a heterogeneous environment. In this case, a natural population harbors a reservoir of alleles preadapted to high temperatures, suggesting potential for future evolutionary response to climate change.
•Over 100 loci seem to confer heat resistance in colonies of a tabletop coral species•Across a single reef, colonies in warm microclimates have more heat-associated alleles•Heat-associated alleles are often present but rare in cooler environments•Variation at loci adapted to warming is maintained in a heterogeneous environment
Coral reefs are threatened by rising ocean temperatures, but in warm microclimates, some corals thrive. Bay and Palumbi show genetic differences at over 100 loci in heat-tolerant colonies of a tabletop coral. The results suggest that some coral populations might evolve higher heat tolerance as global temperatures increase.
Purpose
The purpose of the study is to review all peer-reviewed published reports of women receiving ovarian tissue transplantation (OTT) with frozen/thawed tissue (OTC) with respect to age, ...diagnosis, transplantation site, fertility outcome, and potential side effects, including data from all women in the Danish program.
Methods
A systematic review of the literature was performed in PubMed combined with results from all patients who had received OTT in Denmark up to December 2017.
Results
OTT has been reported from 21 different countries comprising a total of 360 OTT procedures in 318 women. In nine women, malignancy was diagnosed after OTT; none were considered to be directly caused by the OTT. Despite a potential under reporting of cancer recurrence, there is currently no evidence to suggest that OTT causes reseeding of the original cancer. Renewed ovarian endocrine function was reported in 95% of the women. Half of all children born following OTT resulted from natural conception, and newborns were reported to be healthy except for one neonate with a chromosome anomaly with a family disposition. Women who conceived after OTT were significantly younger than those who failed.
Conclusion
This study found no indications of sufficient numbers of malignant cells present in the ovarian tissue to cause recurrence of cancer after OTT. Further, it is unlikely that OTC affects the well-being of children born. OTC is now an established method of fertility preservation in Denmark with public reimbursement. The current data encourage that women who require gonadotoxic treatment should be offered an individual evaluation considering fertility preservation.
There is an increasing demand for accurate endotyping of patients according to their pathogenesis to allow more targeted treatment. We explore a combination of blood-based joint tissue metabolites ...(neoepitopes) to enable patient clustering through distinct disease profiles. We analysed data from two RA studies (LITHE (N = 574, follow-up 24 and 52 weeks), OSKIRA-1 (N = 131, follow-up 24 weeks)). Two osteoarthritis (OA) studies (SMC01 (N = 447), SMC02 (N = 81)) were included as non-RA comparators. Specific tissue-derived neoepitopes measured at baseline, included: C2M (cartilage degradation); CTX-I and PINP (bone turnover); C1M and C3M (interstitial matrix degradation); CRPM (CRP metabolite) and VICM (macrophage activity). Clustering was performed to identify putative endotypes. We identified five clusters (A-E). Clusters A and B were characterized by generally higher levels of biomarkers than other clusters, except VICM which was significantly higher in cluster B than in cluster A (p<0.001). Biomarker levels in Cluster C were all close to the median, whilst Cluster D was characterised by low levels of all biomarkers. Cluster E also had low levels of most biomarkers, but with significantly higher levels of CTX-I compared to cluster D. There was a significant difference in ΔSHP score observed at 52 weeks (p<0.05). We describe putative RA endotypes based on biomarkers reflecting joint tissue metabolism. These endotypes differ in their underlining pathogenesis, and may in the future have utility for patient treatment selection.
Abstract The extracellular matrix (ECM) of articular cartilage is comprised of complex networks of proteins and glycoproteins, all of which are expressed by its resident cell, the chondrocyte. ...Cartilage is a unique tissue given its complexity and ability to resist repeated load and deformation. The mechanisms by which articular cartilage maintains its integrity throughout our lifetime is not fully understood, however there are numerous regulatory pathways known to govern ECM turnover in response to mechanical stimuli. To further our understanding of this field, we envision that proteomic analysis of the secretome will provide information on how the chondrocyte remodels the surrounding ECM in response to load, in addition to providing information on the metabolic state of the cell. In this review, we attempt to summarize the recent mass spectrometry-based proteomic discoveries in healthy and diseased cartilage and chondrocytes, to facilitate the discovery of novel biomarkers linked to degenerative pathologies, such as osteoarthritis (OA).
Comparative analysis of the expanding genomic resources for scleractinian corals may provide insights into the evolution of these organisms, with implications for their continued persistence under ...global climate change. Here, we sequenced and annotated the genome of Pocillopora damicornis, one of the most abundant and widespread corals in the world. We compared this genome, based on protein-coding gene orthology, with other publicly available coral genomes (Cnidaria, Anthozoa, Scleractinia), as well as genomes from other anthozoan groups (Actiniaria, Corallimorpharia), and two basal metazoan outgroup phlya (Porifera, Ctenophora). We found that 46.6% of P. damicornis genes had orthologs in all other scleractinians, defining a coral 'core' genome enriched in basic housekeeping functions. Of these core genes, 3.7% were unique to scleractinians and were enriched in immune functionality, suggesting an important role of the immune system in coral evolution. Genes occurring only in P. damicornis were enriched in cellular signaling and stress response pathways, and we found similar immune-related gene family expansions in each coral species, indicating that immune system diversification may be a prominent feature of scleractinian coral evolution at multiple taxonomic levels. Diversification of the immune gene repertoire may underlie scleractinian adaptations to symbiosis, pathogen interactions, and environmental stress.
Summary
Background
Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease.
Aim
To determine whether ...serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease.
Methods
Serum biomarkers for type I, III, V and VI collagen formation (P1NP, Pro‐C3, Pro‐C5, Pro‐C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls. Active inflammation was defined as CRP >5 mg/L.
Results
C3M and Pro‐C5 levels were higher in penetrating vs nonpenetrating/nonstricturing and stricturing disease (33.6±5 vs 25.8±2.2 P=.004 and 27.2±2.3 P=.018 nmol/L C3M, 1262.7±259.4 vs 902.9±109.9 P=.005 and 953.0±106.4 P=.015 nmol/L Pro‐C5). C1M (71.2±26.1 vs 46.2±6.2 nmol/L P<.001), C3M (31.6±3.9 vs 26.1±1.6 nmol/L P=.002 and Pro‐C5 levels (1171.7±171.5 vs 909.6±80.4 nmol/L P=.002) were higher in patients with active inflammation vs without active inflammation. Pro‐C3/C3M‐ratios were best to differentiate between penetrating vs nonstricturing/nonpenetrating and stricturing disease with area under the curves of 0.815±0.109 (P<.001) and 0.746±0.114 (P=.002) respectively.
Conclusions
Serological biomarkers show that penetrating Crohn's disease is characterised by increased matrix metalloproteinase‐9 degraded type III collagen and formation of type V collagen. Active inflammation in Crohn's disease is characterised by increased formation of type V collagen and increased matrix metalloproteinase mediated breakdown of type I, III collagen. Pro‐C3/C3M ratios are superior in differentiating between penetrating Crohn's disease vs inflammatory and stricturing Crohn's disease.
Summary Objectives Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis ...and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase-mediated cartilage degradation. Methods Cartilage degradation was induced in bovine articular cartilage explants by oncostatin M (OSM) and tumor necrosis factor (TNF), in the presence or absence of specific inhibitors of the mitogen-activated protein kinases (MAPKs) P38, P44/42 and Src family. Toxicity was followed by the AlamarBlue colorimetric assay. MMP-activity was assessed using a fluorescent substrate assay and MMP-9 and -2 activities by gelatinase zymography. MMP-mediated collagen type II degradation and MMP as well as aggrecanase-mediated aggrecan degradation was investigated with specific ELISA and hydroxyproline release by standard methods. The findings were verified by immunohistochemistry and histology. Results Stimulation of cartilage degradation by OSM + TNF resulted in 100-fold induction of CTX-II release ( P < 0.01). This was dose-dependently inhibited by MAPK P38 inhibitors and by the MAPK P44/42 inhibitors. MMP-activity and expression was significantly decreased, as evaluated by cleavage of fluorescence MMP-substrate and zymography. Immunohistochemistry confirmed these findings. Interestingly, only the P44/42 inhibitors abrogated aggrecanase-mediated aggrecan degradation. Conclusion We found that inhibition of MAPK P38, P44/42 and Src family abrogated proteolytic cartilage degradation by blocking MMP synthesis and activity. However, only MAPK P44/42 was essential for aggrecanase-mediated aggrecan degradation. These data suggest that various aspects of cartilage degradation can be targeted independently by inhibiting specific upstream signaling pathway.
Population response to environmental variation involves adaptation, acclimation, or both. For long-lived organisms, acclimation likely generates a faster response but is only effective if the rates ...and limits of acclimation match the dynamics of local environmental variation. In coral reef habitats, heat stress from extreme ocean warming can occur over several weeks, resulting in symbiont expulsion and widespread coral death. However, transcriptome regulation during short-term acclimation is not well understood. We examined acclimation during a 11-day experiment in the coral Acropora nana. We acclimated colonies to three regimes: ambient temperature (29 °C), increased stable temperature (31 °C), and variable temperature (29-33 °C), mimicking local heat stress conditions. Within 7-11 days, individuals acclimated to increased temperatures had higher tolerance to acute heat stress. Despite physiological changes, no gene expression changes occurred during acclimation before acute heat stress. However, we found strikingly different transcriptional responses to heat stress between acclimation treatments across 893 contigs. Across these contigs, corals acclimated to higher temperatures (31 °C or 29-33 °C) exhibited a muted stress response--the magnitude of expression change before and after heat stress was less than in 29 °C acclimated corals. Our results show that corals have a rapid phase of acclimation that substantially increases their heat resilience within 7 days and that alters their transcriptional response to heat stress. This is in addition to a previously observed longer term response, distinguishable by its shift in baseline expression, under nonstressful conditions. Such rapid acclimation may provide some protection for this species of coral against slow onset of warming ocean temperatures.
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