Identification of an urinary metabolite profile associated with osteoarthritis

OBJECTIVE: Osteoarthritis (OA) is one of the most common diseases among the elderly. The main characteristic is the progressive destruction of articular cartilage. We lack quantitative and sensitive biomarkers for OA to detect changes in the joints in an early stage of the disease. In this study, we investigated whether a urinary metabolite profile could be found that could serve as a diagnostic biomarker for OA in humans. We also compared the profile we obtained previously in the guinea pig spontaneous OA model. METHODS: Urine samples of 92 participants (47 non-OA controls and 45 individuals with radiographic OA of the knees or hips) were selected from the Johnston County Osteoarthritis Project (North Carolina, USA). Participants ranged in age from 60 to 84 years. Samples were measured by 1H nuclear magnetic resonance spectroscopy (NMR) with subsequent principal component discriminant analysis and partial least squares regression analysis. RESULTS: Differences were observed between urine NMR spectra of OA cases and controls (P<0.001 for both male and female subjects). A metabolite profile could be determined which was strongly associated with OA. This profile largely resembled the profile previously identified for guinea pigs with OA (approximately 40 out of the approximately 125 signals of the human profile were present in the guinea pig profile as well). A correlation was found between the metabolite profile and radiographic OA severity (R2 = 0.82 (male); R2 = 0.93 (female)). CONCLUSION: This study showed that a urine metabolite profile may serve as a novel discriminating biomarker of OA

Maternal diabetes causes developmental delay and death in early-somite mouse embryos

Maternal diabetes causes congenital malformations and delays embryonic growth in the offspring. We investigated effects of maternal diabetes on mouse embryos during gastrulation and early organogenesis (ED7.5-11.5). Female mice were made diabetic with streptozotocin, treated with controlled-release insulin implants, and mated. Maternal blood glucose concentrations increased up to embryonic day (ED) 8.5. Maternal hyperglycemia induced severe growth retardation (approx.1 day) in 53% of the embryos on ED8.5, death in most of these embryos on ED9.5, and the termination of pregnancy on ED10.5 in litters with >20% dead embryos. Due to this selection, developmental delays and reduction in litter size were no longer observed thereafter in diabetic pregnancies. Male and female embryos were equally sensitive. High-throughput mRNA sequencing and pathway analysis of differentially expressed genes showed that retarded embryos failed to mount the adaptive suppression of gene expression that characterized non-retarded embryos (cell proliferation, cytoskeletal remodeling, oxidative phosphorylation). We conclude that failure of perigastrulation embryos of diabetic mothers to grow and survive is associated with their failure to shut down pathways that are strongly down-regulated in otherwise similar non-retarded embryos. Embryos that survive the early and generalized adverse effect of maternal diabetes, therefore, appear the subset in which malformations become manifest

Growth forms and life-history strategies predict the occurrence of aquatic macrophytes in relation to environmental factors in a shallow peat lake complex

Aquatic ecosystems provide vital services, and macrophytes play a critical role in their functioning. Conceptual models indicate that in shallow lakes, plants with different growth strategies are expected to inhabit contrasting habitats. For shallow peat lakes, characterized by incohesive sediments, roles of growth forms, life-history strategies and environmental factors in determining the occurrence of aquatic vegetation remain unknown. In a field survey, we sampled 64 points in a peat lake complex and related macrophyte occurrence to growth forms (floating-leaved rooted and submerged), life-history strategies for overwintering (turions, seeds, rhizomes) and environmental factors (water depth, fetch, and porewater nutrients). Our survey showed that macrophyte occurrence relates to water depth, wind-fetch, and nutrients, and depends on growth form and life-history strategies. Specifically, rooted floating-leaved macrophytes occur at lower wind-fetch/shallower waters. Submerged macrophytes occur from low to greater wind-fetch/water depth, depending on life-history strategies; macrophytes with rhizomes occur at greater wind-fetch/depth relative to species that overwinter with seeds or turions. We conclude that growth form and life-history strategies for overwintering predict macrophytes occurrence regarding environmental factors in peat lakes. Therefore, we propose an adapted model for macrophyte occurrence for such lakes. Altogether, these results may aid in species-selection to revegetate peat lakes depending on its environment

Life cycle informed restoration:Engineering settlement substrate material characteristics and structural complexity for reef formation

Ecosystems are degrading world-wide, with severe ecological and economic consequences. Restoration is becoming an important tool to regain ecosystem services and preserve biodiversity. However, in harsh ecosystems dominated by habitat-modifying organisms, restoration is often expensive and failure prone. Establishment of such habitat modifiers often hinges on self-facilitation feedbacks generated by traits that emerge when individuals aggregate, causing density- or patch size-dependent establishment thresholds. To overcome these thresholds, adult or juvenile habitat-forming species are often transplanted in clumped designs, or stress-mitigating structures are deployed. However, current restoration approaches focus on introducing or facilitating a single life stage, while many habitat modifiers experience multiple bottlenecks throughout their life as they transition through sequential life stages. Here, we define and experimentally test ‘life cycle informed restoration’, a restoration concept that focuses on overcoming multiple bottlenecks throughout the target species’ lifetime. To provide proof of concept, and show its general applicability, we carried out complementary experiments in intertidal soft-sediment systems in Florida and the Netherlands where oysters and mussels act as reef-building habitat modifiers. We used biodegradable structures designed to facilitate bivalve reef recovery by both stimulating settlement with hard and fibrous substrates and post-settlement survival by reducing predation. Our trans-Atlantic experiments demonstrate that these structures enabled bivalve reef formation by: (a) facilitating larval recruitment via species-specific settlement substrates, and (b) enhancing post-settlement survival by lowering predation. In the Netherlands, structures with coir rope most strongly facilitated mussels by providing fibrous settlement substrate, and predation-lowering spatially complex hard attachment substrate. In Florida, oysters were greatly facilitated by hard substrates, while coir rope proved unbeneficial. Synthesis and applications. Our findings demonstrate that artificial biodegradable reefs can enhance bivalve reef restoration across the Atlantic by mimicking emergent traits that ameliorate multiple bottlenecks over the reef-forming organism’ life cycle. This highlights the potential of our approach as a cost-effective and practical tool for nature managers to restore systems dominated by habitat modifiers whose natural recovery is hampered by multiple life stage-dependent bottlenecks. Therefore, investment in understanding how to achieve life cycle informed restoration on larger scales and whether the method it is applicable to restore other ecosystems is now required

Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts.

Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings

Microbial Transformations of Nitrogen, Sulfur, and Iron Dictate Vegetation Composition in Wetlands: A Review

The majority of studies on rhizospheric interactions focus on pathogens, mycorrhizal symbiosis, or carbon transformations. Although the biogeochemical transformations of N, S, and Fe have profound effects on vegetation, these effects have received far less attention. This review, meant for microbiologists, biogeochemists, and plant scientists includes a call for interdisciplinary research by providing a number of challenging topics for future ecosystem research. Firstly, all three elements are plant nutrients, and microbial activity significantly changes their availability. Secondly, microbial oxidation with oxygen supplied by radial oxygen loss from roots in wetlands causes acidification, while reduction using alternative electron acceptors leads to generation of alkalinity, affecting pH in the rhizosphere, and hence plant composition. Thirdly, reduced species of all three elements may become phytotoxic. In addition, Fe cycling is tightly linked to that of S and P. As water level fluctuations are very common in wetlands, rapid changes in the availability of oxygen and alternative terminal electron acceptors will result in strong changes in the prevalent microbial redox reactions, with significant effects on plant growth. Depending on geological and hydrological settings, these interacting microbial transformations change the conditions and resource availability for plants, which are both strong drivers of vegetation development and composition by changing relative competitive strengths. Conversely, microbial composition is strongly driven by vegetation composition. Therefore, the combination of microbiological and plant ecological knowledge is essential to understand the biogeochemical and biological key factors driving heterogeneity and total (i.e., microorganisms and vegetation) community composition at different spatial and temporal scales

Initiating and upscaling mussel reef establishment with life cycle informed restoration:Successes and future challenges

Worldwide, coastal ecosystems are rapidly degrading in quality and extent. While novel restoration designs include facilitation to enhance restoration success in stressful environments, they typically focus on a single life-stage, even though many organisms go through multiple life-stages accompanied by different bottlenecks. A new approach – life cycle informed restoration – was designed to ameliorate multiple bottlenecks throughout an organism's life cycle. It has successfully been tested on a small scale to facilitate intertidal bivalve reef formation in the Netherlands and Florida. Yet, it remains unknown whether this approach can be scaled to ecosystem-relevant scales. To test whether life cycle informed restoration is upscalable, we conducted a large-scale restoration experiment using blue mussel reefs as a model system. In our experiment, we used biodegradable structures to temporarily facilitate mussel reef formation by providing early-life settlement substrates, and subsequently, reduce post-settlement predation on an intertidal flat in the Wadden Sea, the Netherlands. The structures were placed in 10 × 20 m plots, mimicking bands found in natural mussel beds, spread out across 650 m, and were followed for two years. Our results show that the structures enhance mussel biomass (0.7 ± 0.2 kg DW m−2), as mussels were absent in bare plots. However, biomass varied within plots; in intact structures it was 60 times higher (1.2 ± 0.2 kg DW m−2) than in those that became buried (0.02 ± 0.009 kg DW m−2). Next to burial, 18–46% of the structures were lost due to technical failure, especially during winters at this exposed site. We show that the life cycle informed restoration principle works, but we encountered technical challenges due to larger scale processes (e.g. sedimentation). Furthermore, environmental information is essential for site selection, and for restoration, the functioning of such structures should be tested under extreme conditions before upscaling

Onderzoek ten behoeve van het herstel en beheer van Nederlandse laagveenwateren; eindrapportage 2003-2006

Dit rapport presenteert de resultaten en conclusies van het onderzoek aan laagveenwateren binnen het kader van het Overlevingsplan Bos en Natuur in de eerste fase (obn, 2003-2006). In Hoofdstuk 3 wordt een overzicht gegeven van de onderzoekslocaties. Vervolgens worden in Hoofdstuk 4 de belangrijkste bevindingen van het correlatieve onderzoek naar de samenhang tusen biodiversiteit en milieukwaliteit gepresenteerd, met in Hoofdstuk 5 de rol van hydrologie in het laagveenlandschap. In de daaropvolgende hoofdstukken 6 tot en met 10 staan de onderzoeksvragen, methoden, resultaten en conclusies van de verschillende deelonderzoeken weergegeven met betrekking tot visstandsbeheer (Hoofdstuk 6), water- en veenkwaliteit (Hoofdstuk 7), verlanding en veenvorming (Hoofdstuk 8), voedselwebrelaties (Hoofdstuk 9) en fauna (Hoofdstuk 10). Ten slotte worden in Hoofdstuk 11 de belangrijkste conclusies van het onderzoek in de eerste fase samengebracht en bediscussieerd, in relatie tot de directe betekenis voor het laagveenbeheer. Dit zal uitgewerkt worden aan de hand van de nieuw gegenereerde kennis en bestaande literatuur over de betreffende milieuproblemen (‘ver’-thema’s), en de voor- en nadelen van beschikbare OBN-maatregelen. Als afsluiting wordt aan de hand van de resultaten in fase 1 aangegeven welke onderzoeksvragen geprioriteerd zijn voor de tweede fas