Experimentelle Studien an Amphibienlarven

Ohne Zusammenfassung     

Repeat or not repeat?—Statistical validation of tandem repeat prediction in genomic sequences

Tandem repeats (TRs) represent one of the most prevalent features of genomic sequences. Due to their abundance and functional significance, a plethora of detection tools has been devised over the last two decades. Despite the longstanding interest, TR detection is still not resolved. Our large-scale tests reveal that current detectors produce different, often nonoverlapping inferences, reflecting characteristics of the underlying algorithms rather than the true distribution of TRs in genomic data. Our simulations show that the power of detecting TRs depends on the degree of their divergence, and repeat characteristics such as the length of the minimal repeat unit and their number in tandem. To reconcile the diverse predictions of current algorithms, we propose and evaluate several statistical criteria for measuring the quality of predicted repeat units. In particular, we propose a model-based phylogenetic classifier, entailing a maximum-likelihood estimation of the repeat divergence. Applied in conjunction with the state of the art detectors, our statistical classification scheme for inferred repeats allows to filter out false-positive predictions. Since different algorithms appear to specialize at predicting TRs with certain properties, we advise applying multiple detectors with subsequent filtering to obtain the most complete set of genuine repeats.     

Referate

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Collateral vessel growth induced by femoral artery ligature is impaired by denervation

Innervation plays an important role in development and remodeling of blood vessels. However, very little is known whether innervation is involved in arteriogenesis. In the present study, we tested the hypothesis that innervation may contribute to the process of arteriogenesis induced by ligature of femoral artery in rat/rabbit hind limb with or without denervation. We found that: (1) angiography showed more collateral vessels in the ligature side than that in ligature plus denervation side; (2) collateral vessels in denervation side was characterized by an inward remodeling; (3) in both collateral vessels (CVs) from only femoral ligature side as well as the ligature plus denervation side, ICAM-1 and VCAM-1 expression was up-regulated but increased VCAM-1 was more evident in the adventitia of collateral vessels of only femoral ligature side; (4) 7 days after surgery, in CVs from the femoral ligature side only, numerous macrophages (RAM11 positive cells) and high cell proliferation ratio (ki67 positive cells) were detected, but they were less in the denervation side. In conclusion, our data demonstrate for the first time that neural regulation is one of the factors that contributes to collateral vessel growth in rat/rabbit hind limb ischemic model by showing collateral vessel growth induced by femoral artery ligature is impaired by denervation.     

Recent Developments in the Role of High-Mobility Group Box 1 in Systemic Lupus Erythematosus

High-mobility group box 1 (HMGB1) is an important molecule for several nuclear processes. Recently, HMGB1 has gained much attention as a damage-associated molecular pattern (DAMP) and has been implicated in the pathogenesis of several (auto)-immune diseases, in particular, systemic lupus erythematosus (SLE). A main pathogenic feature in SLE is the accumulation of apoptotic cells. Since HMGB1 is released from apoptotic cells it has been hypothesized that HMGB1 might fuel the inflammatory processes, as seen in this disease, and play a fundamental role in the pathogenesis. In this review, we discuss evidence in support of the theory that HMGB1 is an important mediator in SLE and may be considered a new autoantigen.     

Heritability of gonad size varies across season in a wild songbird

Many organisms advance their seasonal reproduction in response to global warming. In birds, which regress their gonads to a nonfunctional state each winter, these shifts are ultimately constrained by the time required for gonadal development in spring. Gonadal development is photoperiodically controlled and shows limited phenotypic plasticity in relation to environmental factors, such as temperature. Heritable variation in the time required for full gonadal maturation to be completed, based on both onset and speed of development and resulting in seasonally different gonad sizes among individuals, is thus a crucial prerequisite for an adaptive advancement of seasonal reproduction in response to changing temperatures. We measured seasonal gonadal development in climate‐controlled aviaries for 144 great tit (Parus major) pairs, which consisted of siblings obtained as whole broods from the wild. We show that the extent of ovarian follicle development (follicle size) in early spring is highly heritable (h² = 0.73) in females, but found no heritability of the extent of testis development in males. However, heritability in females decreased as spring advanced, caused by an increase in environmental variance and a decrease in additive genetic variation. This low heritability of the variation in a physiological mechanism underlying reproductive timing at the time of selection may hamper genetic adaptation to climate change, a key insight as this great tit population is currently under directional selection for advanced egg‐laying.     

Linkage disequilibrium under recurrent bottlenecks

To model deviations from selectively neutral genetic variation caused by different forms of selection, it is necessary to first understand patterns of neutral variation. Best understood is neutral genetic variation at a single locus. But, as is well known, additional insights can be gained by investigating multiple loci. The resulting patterns reflect the degree of association (linkage) between loci and provide information about the underlying multilocus gene genealogies. The statistical properties of two-locus gene genealogies have been intensively studied for populations of constant size, as well as for simple demographic histories such as exponential population growth and single bottlenecks. By contrast, the combined effect of recombination and sustained demographic fluctuations is poorly understood. Addressing this issue, we study a two-locus Wright-Fisher model of a population subject to recurrent bottlenecks. We derive coalescent approximations for the covariance of the times to the most recent common ancestor at two loci in samples of two chromosomes. This covariance reflects the degree of association and thus linkage disequilibrium between these loci. We find, first, that an effective population-size approximation describes the numerically observed association between two loci provided that recombination occurs either much faster or much more slowly than the population-size fluctuations. Second, when recombination occurs frequently between but rarely within bottlenecks, we observe that the association of gene histories becomes independent of physical distance over a certain range of distances. Third, we show that in this case, a commonly used measure of linkage disequilibrium, σ(2)(d) (closely related to r(2)), fails to capture the long-range association between two loci. The reason is that constituent terms, each reflecting the long-range association, cancel. Fourth, we analyze a limiting case in which the long-range association can be described in terms of a Xi coalescent allowing for simultaneous multiple mergers of ancestral lines.