HLA-DP/DR interaction in early onset pauciarticular juvenile chronic arthritis

We investigated the polymorphic second exon of the HLA-DPB1 and HLA-DRB1 genes, using in vitro DNA amplification by polymerase chain reaction (PCR) and oligonucleotide hybridization in 136 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) and 199 healthy controls. The analysis of the HLA-DRB1 system revealed that most of the DRB1 alleles are not indifferent with respect to susceptibility to EOPA-JCA. There is a hierarchy of susceptible (DRB1*08, DR5), permissive (DRB1*01), moderately protective (DR2, DRB1*04), and protective (DRB1*07) alleles. In contrast, no hierarchy could be shown for the HLA-DPB1 system. DPB1*0201 was found to be susceptible. The relatively frequent alleles DPB1*0402 and DPB1*0401 seem to be indifferent. The associations with DPB1*0201, DR5, and DRB1*08 are independent of each other: that is to say they, are not brought about by linkage disequilibrium. The susceptible alleles DPB1*0201 and DR5 show evidence for interaction in the pathogenesis of EOPA-JCA. Interaction seems likely between DPB1*0201 and DRB1*08, DR5 and DRB1*08, or between DR6 and DRB1*08. The strongest interaction exists between DPB1*0201 and a common DQ factor associated with both DR5 and DRB1*08. Finally, we observed a hierarchy among the various marker combinations, where the risk of developing EOPA-JCA increases with the number of associated markers present in an individual.This work was supported by SFB217.The data presented here are part of the doctoral thesis of C. Paul.     

Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP,DQA1, DQB1 haplotypes in systemic lupus erythematosus

We have investigated the DNA polymorphism for the DQA1 promoter region (QAP) and HLA-class II DRB1, DQA1, and DQB1 genes in 178 central European patients with Systemic lupus erythematosus (SLE) using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides. Increased frequencies of DRB1*02 and *03 are confirmed by DNA typing. In addition, the frequencies of DQA1*0501, *0102 and DQB1*0201, *0602 alleles are increased in the patients as compared to controls. The strongest association to SLE is found with DRB1*03 and DQB1*0201 alleles (p<10^–7, p corr. <10^–5 and p<10^–6, p corr. <10^–4, respectively). By investigating the DQA1 promoter region in the SLE patients we have detected nine different QAP variants. Increased frequencies of QAP1.2 and QAP4.1 are observed in patients as compared to controls (p <0.05, p corr. = n. s.). Analysis of linkage disquilibria demonstrates a very strong association between QAP variants and DQA1, DRB1 alleles. Certain QAP variants are completely associated with DQA1 and DRB1 alleles, whereas others can combine with different DQA1 and DRB1 alleles. All DRB1*02-positive patients and controls carry QAP1.2, and all DRB1*03-positive patients and controls carry QAP4.1. Conversely, the QAP1.2 variant appears only in DRB1*02 haplotypes, while the QAP4.1 variant can be observed in DRB1*03, *11, and *1303 haplotypes. Based on the strong linkage disequilibria between DRB1-DQA1-DQB1 genes and between DRB1-QAP-DQA1, we have deduced the four-point haplotypes for DRB1-QAP-DQA1-DQB1 in patients and controls. Two haplotypes DRB1*02-QAP1.2-DQA1*0102-DQB1*0602-and DRB1*03-QAP4.1-DQA1*0501-DQB1*0201 are significantly increased in patient as compared to controls (p<0.01, p corr. = n.s., RR = 1.8 and p <10^–7, p corr. <10^–5, RR = 3.1, respectively). The analysis of relative risks attributed to the various alleles of QAP, DQA1, and DQB1 as well as the investigation of the deduced DRB1-QAP-DQA1-DQB1 haplotypes leads to the conclusion that QAP4.1 and DQA1*0501 on the DR3 haplotypes are probably not involved in SLE susceptibility. There is no evidence for the involvement of DQ2 / dimers coded in transposition. Thus, susceptibility to SLE is on the DR3 haplotype most probably localized at DRB1 or telomeric of DRB1, while for the DR2 haplotype such orientation cannot be given. SLE study group members: M. Baur, A. Corvetta, H. Ehrfeld, J. Frey, J. R. Kalden, F. Krapf, B. Lang, G. G. Lange, K. Pirner, C. Rittner, E. Röther, P. Schneider, H. P. Seelig, S. Seuchter, W. Stangel, C. Specker, P. Späth, H. Deicher. Correspondence to: Z. Yao.     

Enhancing the structural diversity between forest patches—A concept and real-world experiment to study biodiversity,multifunctionality and forest resilience across spatial scales

Intensification of land use by humans has led to a homogenization of landscapes and decreasing resilience of ecosystems globally due to a loss of biodiversity, including the majority of forests. Biodiversity–ecosystem functioning (BEF) research has provided compelling evidence for a positive effect of biodiversity on ecosystem functions and services at the local (α-diversity) scale, but we largely lack empirical evidence on how the loss of between-patch β-diversity affects biodiversity and multifunctionality at the landscape scale (γ-diversity). Here, we present a novel concept and experimental framework for elucidating BEF patterns at α-, β-, and γ-scales in real landscapes at a forest management-relevant scale. We examine this framework using 22 temperate broadleaf production forests, dominated by Fagus sylvatica. In 11 of these forests, we manipulated the structure between forest patches by increasing variation in canopy cover and deadwood. We hypothesized that an increase in landscape heterogeneity would enhance the β-diversity of different trophic levels, as well as the β-functionality of various ecosystem functions. We will develop a new statistical framework for BEF studies extending across scales and incorporating biodiversity measures from taxonomic to functional to phylogenetic diversity using Hill numbers. We will further expand the Hill number concept to multifunctionality allowing the decomposition of γ-multifunctionality into α- and β-components. Combining this analytic framework with our experimental data will allow us to test how an increase in between patch heterogeneity affects biodiversity and multifunctionality across spatial scales and trophic levels to help inform and improve forest resilience under climate change. Such an integrative concept for biodiversity and functionality, including spatial scales and multiple aspects of diversity and multifunctionality as well as physical and environmental structure in forests, will go far beyond the current widely applied approach in forestry to increase resilience of future forests through the manipulation of tree species composition.     

Geographic differences in Blainville's beaked whale (Mesoplodon densirostris) echolocation clicks

Aim

Understanding cetacean species' distributions and population structure over space and time is necessary for effective conservation and management. Geographic differences in acoustic signals may provide a line of evidence for population-level discrimination in some cetacean species. We use acoustic recordings collected over broad spatial and temporal scales to investigate whether global variability in echolocation click peak frequency could elucidate population structure in Blainville's beaked whale (Mesoplodon densirostris), a cryptic species well-studied acoustically.

Location

North Pacific, Western North Atlantic and Gulf of Mexico.

Time period

2004–2021.

Major taxa studied

Blainville's beaked whale.

Methods

Passive acoustic data were collected at 76 sites and 150 cumulative years of data were analysed to extract beaked whale echolocation clicks. Using an automated detector and subsequent weighted network clustering on spectral content and interclick interval of clicks, we determined the properties of a primary cluster of clicks with similar characteristics per site. These were compared within regions and across ocean basins and evaluated for suitability as population-level indicators.

Results

Spectral averages obtained from primary clusters of echolocation clicks identified at each site were similar in overall shape but varied in peak frequency by up to 8 kHz. We identified a latitudinal cline, with higher peak frequencies occurring in lower latitudes.

Main conclusions

It may be possible to acoustically delineate populations of Blainville's beaked whales. The documented negative correlation between signal peak frequency and latitude could relate to body size. Body size has been shown to influence signal frequency, with lower frequencies produced by larger animals, which are subsequently more common in higher latitudes for some species, although data are lacking to adequately investigate this for beaked whales. Prey size and depth may shape frequency content of echolocation signals, and larger prey items may occur in higher latitudes, resulting in lower signal frequencies of their predators.     

Nitrogen fertilizer enhances vegetation establishment of a high-altitude machine-graded ski slope

Machine grading is frequently required to prepare the terrain when building high-altitude ski slopes in the Alps. However, this kind of disturbance alters the natural environment, destroying the vegetation and hampering its reestablishment. Thus, specific restoration plans are necessary to encourage the recovery of vegetation, which is already affected by different natural constraints in this harsh environment. One of the main critical factors affecting plant growth in high-altitude areas is the lack of available nitrogen (N) in the soil. In this context, the addition of a slow-release N fertilizer was carried out in an experimental revegetated ski slope between 2,800 and 2,900 m above sea level in the western Italian Alps. Both vegetation and soil were monitored during a 5-year period in order to test the effectiveness of N addition on the restoration process. Even if effects on soil carbon and N contents were negligible, vegetation was remarkably affected by the fertilization, since the total vegetation cover and the species richness significantly increased. Against the expectations, there was a remarkable increase in spontaneous forbs, rather than in most of the sown graminoids, which slightly varied during the experimental period. Actually, graminoids responded in different ways, mostly increasing (likewise forbs), but the slight decrease of the dominant Festuca nigrescens (Chewing's Fescue) masked their spread. This study confirms the noteworthy role of N in high-altitude alpine soils and consequently its importance to improve the restoration process of degraded ecosystems.     

Neutral gravitaxis of gliding Loxodes exposed to normal and raised gravity

Summary In the statocystoid-bearing, flat ciliate Loxodes, the peculiar steady locomotion on submersed substrates (called gliding) was investigated between 1 g and 5.4 g under controlled environmental conditions in a centrifuge microscope. Videorecordings of the movements of large cell populations were processed with an automated analysis procedure. At 1 g, possible sedimentation was fully compensated, and vertical shifts of the population were neutralized because upward and downward orientations of the cells occurred at equal proportions (neutral gravitaxis). With rising gravity the resultant velocity of upward-gliding cells remained unchanged, whereas the velocity of downward-gliding cells increased continuously. Long-term exposure to hypergravity did not generate detectable signs of adaptation. The bipolar orientation of Loxodes persisted even under fivefold normal gravity, but the axis of orientation rotated from the gravity axis in the counterclockwise direction. The data suggest that both gravikinesis and graviorientation of gliding Loxodes are instrumental in perfect neutralization of sedimentation at terrestrial conditions.     

Distribution,causal agents,and infection dynamic of emerging ink disease of sweet chestnut in Southern Switzerland

Emerging diseases caused by both native and exotic pathogens represent a main threat to forest ecosystems worldwide. The two invasive soilborne pathogens Phytophthora cinnamomi and Phytophthora × cambivora are the causal agents of ink disease, which has been threatening Castanea sativa in Europe for several centuries and seems to be re-emerging in recent years. Here, we investigated the distribution, causal agents, and infection dynamics of ink disease in southern Switzerland. A total of 25 outbreaks were identified, 19 with only P. cinnamomi, 5 with only P. × cambivora, and 1 with both species. Dendrochronological analyses showed that the disease emerged in the last 20–30 years. Infected trees either died rapidly within 5–15 years post-infection or showed a prolonged state of general decline until death. Based on a generalized linear model, the local risk of occurrence of ink disease was increased by an S-SE aspect of the chestnut stand, the presence of a pure chestnut stand, management activities, the proximity of roads and buildings, and increasing annual mean temperature and precipitation. The genetic structure of the local P. cinnamomi population suggests independent introductions and local spread of the pathogen.     

Antiproliferative effects of heparin on normal and transformed NIH/3T3 fibroblasts.

We studied the effect of heparin on proliferation and signalling in normal NIH/3T3 fibroblasts, and in cells transformed by different oncogenes. Heparin inhibited the proliferation of normal as well as of v-sis and v-erbB transformed fibroblasts in the presence of serum, but failed to inhibit v-erbB-driven proliferation in serum-starved cultures; under these conditions, heparin inhibited by approximately 50% the proliferation of normal and v-sis- transformed cells. Heparin also inhibited PDGF-induced cell proliferation and inositol lipid turnover in v-sis transformants, but it did not affect PDGF mitogenic signalling in NIH/3T3 fibroblasts.     

Circadian rhythms and glial cells of the central nervous system

Glial cells are the most abundant cells in the central nervous system and play crucial roles in neural development, homeostasis, immunity, and conductivity. Over the past few decades, glial cell activity in mammals has been linked to circadian rhythms, the 24-h chronobiological clocks that regulate many physiological processes. Indeed, glial cells rhythmically express clock genes that cell-autonomously regulate glial function. In addition, recent findings in rodents have revealed that disruption of the glial molecular clock could impact the entire organism. In this review, we discuss the impact of circadian rhythms on the function of the three major glial cell types – astrocytes, microglia, and oligodendrocytes – across different locations within the central nervous system. We also review recent evidence uncovering the impact of glial cells on the body's circadian rhythm. Together, this sheds new light on the involvement of glial clock machinery in various diseases.