A genetic variant in osteoprotegerin is associated with progression of joint destruction in rheumatoid arthritis

Introduction

Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA.

Methods

1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied.

Results

We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P = 2.35x10⁻⁴). This variant was also significant after Bonferroni correction.

Conclusions

These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA.     

Trophic level asynchrony in rates of phenological change for marine,freshwater and terrestrial environments

Recent changes in the seasonal timing (phenology) of familiar biological events have been one of the most conspicuous signs of climate change. However, the lack of a standardized approach to analysing change has hampered assessment of consistency in such changes among different taxa and trophic levels and across freshwater, terrestrial and marine environments. We present a standardized assessment of 25 532 rates of phenological change for 726 UK terrestrial, freshwater and marine taxa. The majority of spring and summer events have advanced, and more rapidly than previously documented. Such consistency is indicative of shared large scale drivers. Furthermore, average rates of change have accelerated in a way that is consistent with observed warming trends. Less coherent patterns in some groups of organisms point to the agency of more local scale processes and multiple drivers. For the first time we show a broad scale signal of differential phenological change among trophic levels; across environments advances in timing were slowest for secondary consumers, thus heightening the potential risk of temporal mismatch in key trophic interactions. If current patterns and rates of phenological change are indicative of future trends, future climate warming may exacerbate trophic mismatching, further disrupting the functioning, persistence and resilience of many ecosystems and having a major impact on ecosystem services.     

ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.     

Tidal geomorphology affects phytoplankton at the transition from forested streams to tidal rivers

1. Coastal rivers can have long tidally influenced reaches that are affected by tides but do not contain saline water. These tidal freshwater reaches have steep geomorphic gradients where the river transitions from narrow, heavily shaded streams to wide, unshaded channels. The influence of these gradients on river ecosystem production is poorly understood. 2. We characterised gradients in irradiance, geomorphology, water clarity and chlorophyll a along 9‐ to 16‐km tidal freshwater reaches of the Newport and White Oak Rivers in North Carolina, USA, and examined the effect of nutrient enrichment on phytoplankton growth in the Newport River. Underwater irradiance was modelled at 2–4 week intervals along both rivers using measurements of the above‐canopy irradiance, canopy cover, water column light attenuation (K_d) and water depth. Suspended material (TSS), dissolved organic carbon (DOC) and chlorophyll a were sampled at 2‐week interval at five sites on the Newport River and on four dates at four sites on the White Oak River over the course of one year. 3. Phytoplankton nutrient limitation was assessed at three locations along the tidal gradient. River water was collected during March, April, June and October, and incubated in 10‐L plastic outdoor containers under ambient water temperature and sunlight. Additions of inorganic nitrogen and phosphorus served as treatments; growth rate during the 4 days of incubation was calculated from the change in chlorophyll a concentration over time. 4. Canopy cover decreased from more than 90% to <10% over the length of both tidal freshwater rivers. Water column irradiance and phytoplankton biomass increased as tree canopy cover decreased and channel width increased. Channel width exceeded predictions for non‐tidal rivers by threefold because of tidal influence. TSS and DOC decreased significantly along the length of the Newport River, but no significant gradients were observed in the White Oak River. K_d did not vary along the tidal gradient of either river. 5. Mesocosm experiments indicated that inorganic nitrogen and phosphorus enhanced the growth of phytoplankton advected from the non‐tidal river into the tidal freshwater river during spring and summer. Phytoplankton in the tidal freshwater reach were generally not nutrient limited. 6. Tidal hydrology (in the absence of saltwater) directly affected the morphology of the channel and indirectly affected biological growth and production. The significant increase in river width, irradiance and phytoplankton biomass distinguished these tidal freshwater ecosystems from their upstream (non‐tidal fluvial) counterparts, while the strong influence of riparian shading distinguished them from the saline estuaries downstream. Future development of ecosystem and biogeochemical models for tidal freshwater rivers will benefit from the linkages between geomorphology and biological processes identified here.     

Isolation and characterization of microsatellite loci from mother‐of‐millions,Bryophyllum delagoense (Crassulaceae), and its hybrid with Bryophyllum daigremontianum, ‘Houghton's hybrid’

Nine microsatellite loci were developed, and are transferable, across the Madagascan succulents Bryophyllum daigremontianum, Bryophyllum delagoense (mother‐of‐millions) and their horticultural hybrid (Houghton's), from enriched libraries of the later two species. For B. delagoense, a tetraploid, three to 13 alleles per locus were found for native Madagascan (H_O = 0.4–1.0), and one to nine in invasive Australian (H_O = 0.0–1.0) samples. In addition for 91 Australian samples, only five multilocus genotypes were found (95% of individuals were of two genotypes), suggesting extensive clonality in its introduced range. These loci will be used to examine genetic diversity, hybrid origin and mating system in natural and introduced populations.     

Variation in social rank acquisition influences lifetime reproductive success in black-capped chickadees

Dominance relationships structure many animal societies, yet the process of rank attainment is poorly understood. We investigated acquisition of social dominance in winter flocks and its fitness consequences in male black-capped chickadees (Poecile atricapillus) over a 10-year period. Age was the best predictor of rank, and paired comparisons showed high-ranked males to be older than their low-ranked flock-mates. When controlling for age, morphological variables did not predict male social rank, but high-ranked males were heavier, had lower fat scores and were in leaner condition than low-ranked males. Males that survived between years tended to increase in rank over time; however, the rate of rank advancement varied individually. Rank reversals between familiar contestants were rare, and changes in male social rank were associated with changes in flock membership. Average lifetime reproductive success (LRS) of males and females was variable and best predicted by lifespan. Male rank history also influenced realized reproductive success. Birds with higher average rank over their lifespan were more likely to reproduce successfully. However, among successful birds, average rank did not significantly predict LRS. Thus, birds that lived longer and attained high social rank earlier had higher fitness, but this effect was not manifested as fine-scale differences among successful individuals. Taken together, these findings demonstrate the importance of social factors influencing individual fitness.  © 2007 The Linnean Society of London, Biological Journal of the Linnean Society , 2007, 90 , 85–95.     

Foraging tactics in alternative heterochronic salamander morphs: trophic quality of ponds matters more than water permanency

1. In lentic freshwater habitats, the composition of animal assemblages shifts along a gradient from temporary to permanent basins. When habitats with different degrees of permanence are at the scale of the home range of species, they constitute alternatives in terms of energy acquisition through feeding. 2. In this context, previous studies showed an advantage of metamorphic over paedomorphic tiger salamanders (Ambystoma tigrinum) in temporary ponds which are only available to metamorphs. The aim of this study was to establish whether salamanders obtain similar benefits in ponds that do not differ in water permanence and whether salamanders shifted from detrimental to advantageous ponds. To this end, we determined the feeding habits, body condition and movement patterns of the two morphs in a complex of four permanent and four temporary ponds. 3. Consistent with previous studies, metamorphs consumed higher‐quality diets than paedomorphs in term of energy intake. However, these differences occurred because metamorphs consumed fairy shrimp in a single temporary pond. Individual movement patterns confirmed that most of the metamorphs used different aquatic habitats both within and between years and that most of them moved from permanent ponds for breeding towards the most profitable temporary pond in terms of foraging. 4. These results indicate that habitat selection by salamanders is optimal in term of energy intake in metamorphs that use high quality ponds independently of hydroperiod. It seems that both spatial and temporal variation can influence the relative foraging success of each morph.     

Dispersal Characteristics of Juvenile Bobcats in South-Central Indiana

ABSTRACT Bobcat (Lynx rufus) populations in the Midwestern United States experienced historic declines due to habitat loss and exploitation but have rebounded in recent decades. We investigated natal dispersal of juvenile bobcats from a population in south-central Indiana, USA, from 1999 to 2006. We radiocollared 16 juvenile bobcats (11 M, 5 F) and monitored them for 237–1,014 days (x̄ = 506). One female (20%) and 11 males (100%) dispersed from natal home ranges that averaged 14.6 km² in size. Most juveniles (70%) initiated dispersal from mid-February through March, late in their first year. Only 5 bobcats (42%) ultimately established a final home range 63 ± 35 km² in size 13–92 km (x̄ = 44) from their natal range 140 ± 45 days after initiating dispersal. Survival did not differ (P = 0.93) between dispersing (S = 0.73) and philopatric (S = 0.75) individuals, although 4 bobcats (3 M, 1 F) were killed in collisions with vehicles. We found dispersal of bobcats in fragmented landscapes is prolonged and often unsuccessful; the ability of dispersers to locate suitable vacant habitat patches may be vital to the continued growth of bobcat populations recolonizing the agricultural Midwest.