Determination of the Weak Axial Vector Coupling λ=g_{A}/g_{V} from a Measurement of the β-Asymmetry Parameter A in Neutron Beta Decay

We report on a new measurement of the neutron beta-asymmetry parameter A with the instrument \perkeo. Main advancements are the high neutron polarization of P=99.7(1) from a novel arrangement of super mirror polarizers and reduced background from improvements in beam line and shielding. Leading corrections were thus reduced by a factor of 4, pushing them below the level of statistical error and resulting in a significant reduction of systematic uncertainty compared to our previous experiments. From the result A0=−0.11996(58), we derive the ratio of the axial-vector to the vector coupling constant λ=gA/gV=−1.2767(16)

{\it Hox\/} genes and specification of regional identity in the axial skeleton: Analysis of the individual and combined mutant phenotypes of the paralogous group 4 murine {\it Hox\/} genes; {\it hoxa\/}-4, {\it hoxb\/}-4 and {\it hoxd\/}-4

The Hox gene products are transcription factors involved in specifying regional identity along the anteroposterior body axis. In Drosophila, where these genes are known as HOM-C (Homeotic-complex) genes and where they have been most extensively studied, they are expressed in restricted domains along the anteroposterior axis with different anterior limits. Genetic analysis of a large number of gain- and loss-of-function alleles of these genes has revealed that these genes are important in specifying segmental identity at their anterior limits of expression. Furthermore, there is a functional dominance of posterior genes over anterior genes, such that posterior genes can dominantly specify their developmental programs in spite of the expression of more anterior genes in the same segment. In the mouse, there are four clusters of HOM-C genes, called Hox genes. Thus, there may be up to four genes, called paralogs, that are more highly homologous to each other and to their Drosophila homolog than they are to the other mouse Hox genes. The single mutants for two paralogous genes, hoxa-4 and hoxd-4, presented in this dissertation, are similar to several other mouse Hox mutants in that they show partial, incompletely penetrant homeotic transformations of vertebrae at their anterior limit of expression. These mutants were then bred with hoxb-4 mutants (Ramirez-Solis, et al. 1993) to generate the three possible double mutant combinations as well as the triple mutant. The skeletal phenotypes of these group 4 Hox compound mutants displayed clear alterations in regional identity, such that a nearly complete transformation towards the morphology of the first cervical vertebra occurs. These results suggest a certain degree of functional redundancy among paralogous genes in specifying regional identity. Furthermore, there was a remarkable dose-dependent increase in the number of vertebrae transformed to a first cervical vertebra identity, including the second through the fifth cervical vertebrae in the triple mutant. Thus, these genes are required in a larger anteroposterior domain than is revealed by the single mutant phenotypes alone, such that multiple mutations in these genes result in transformations of vertebrae that are not at their anterior limit of expression. ^

Atlanto-axial rotatory subluxations in postmortem CT: radiologists be aware of a common pitfall

The aim of the present study was to determine the frequency of atlanto-axial rotatory subluxations (AARS) in multi detector computed tomography (MDCT) performed on human corpses for forensic purposes and to investigate whether these are a physiological postmortem finding or indicate a trauma to the neck region. 80 forensic cases examined with MDCT from November 2003 to March 2007 were included in the study. The study was approved by the regional ethics committee. For each case volumes were rendered and investigated with reference to suspected AARS and any other anomalies of the head and neck region. The rotation of the head as well as in the atlanto-axial joint were measured and occurring AARS were judged according Fielding's classification. The finding of AARS was correlated to case criteria such as postmortem head rotation, sex, age, cause of death, time since death and further autopsy results. Statistical analysis was performed using Fisher's exact test, Wilcoxon's rank sums test and Chi-square test with Pearson approximation. 70% (n=56) of the cases included in the study presented with an AARS. A strong correlation (P<.0001) between suspected AARS and postmortem head rotation was found. Two cases presented with an atlanto-axial rotation greater than the head rotation. One showed an undiscovered lateral dislocation of the atlas, and one an unfused atlas-ring. There was no correlation to any further investigated case criteria. Ipsilateral AARS with head rotation alone does not indicate trauma to the neck. PmCT can substantially support forensic examinations of the skeleton, especially in body regions, which are elaborate to access at autopsy, such as the cervical spine. Isolated AARS (Fielding type I) on pmCT is usually a normal finding associated with ipsilateral head rotation.

Axial suspension test to assess pre-operative spinal flexibility in patients with adolescent idiopathic scoliosis.

INTRODUCTION An accurate description of the biomechanical behavior of the spine is crucial for the planning of scoliotic surgical correction as well as for the understanding of degenerative spine disorders. The current clinical assessments of spinal mechanics such as side-bending or fulcrum-bending tests rely on the displacement of the spine observed during motion of the patient. Since these tests focused solely on the spinal kinematics without considering mechanical loads, no quantification of the mechanical flexibility of the spine can be provided. METHODS A spinal suspension test (SST) has been developed to simultaneously monitor the force applied on the spine and the induced vertebral displacements. The system relies on cervical elevation of the patient and orthogonal radiographic images are used to measure the position of the vertebras. The system has been used to quantify the spinal flexibility on five AIS patients. RESULTS Based on the SST, the overall spinal flexibility varied between 0.3 °/Nm for the patient with the stiffer curve and 2 °/Nm for the less rigid curve. A linear correlation was observed between the overall spinal flexibility and the change in Cobb angle. In addition, the segmental flexibility calculated for five segments around the apex was 0.13 ± 0.07 °/Nm, which is similar to intra-operative stiffness measurements previously published. CONCLUSIONS In summary, the SST seems suitable to provide pre-operative information on the complex functional behavior and stiffness of spinal segments under physiological loading conditions. Such tools will become increasingly important in the future due to the ever-increasing complexity of the surgical instrumentation and procedures.

Retinal Laser Lesion Visibility in Simultaneous Ultra-High Axial Resolution Optical Coherence Tomography

Ex vivo porcine retina laser lesions applied with varying laser power (20 mW–2 W, 10 ms pulse, 196 lesions) are manually evaluated by microscopic and optical coherence tomography (OCT) visibility, as well as in histological sections immediately after the deposition of the laser energy. An optical coherence tomography system with 1.78 um axial resolution specifically developed to image thin retinal layers simultaneously to laser therapy is presented, and visibility thresholds of the laser lesions in OCT data and fundus imaging are compared. Optical coherence tomography scans are compared with histological sections to estimate the resolving power for small optical changes in the retinal layers, and real-time time-lapse scans during laser application are shown and analyzed quantitatively. Ultrahigh-resolution OCT inspection features a lesion visibility threshold 40–50 mW (17 reduction) lower than for visual inspection. With the new measurement system, 42 of the lesions that were invisible using state-of-the-art ophthalmoscopic methods could be detected.

Treatment with tumor necrosis factor inhibitors in axial spondyloarthritis: comparison between private rheumatology practices and academic centers in a large observational cohort

OBJECTIVE To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers. METHODS We compared newly initiated TNF inhibition for axSpA in 363 patients enrolled in private practices with 100 patients recruited in 6 university hospitals within the Swiss Clinical Quality Management (SCQM) cohort. RESULTS All patients had been treated with ≥ 1 nonsteroidal antiinflammatory drug and > 70% of patients had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 before anti-TNF agent initiation. The proportion of patients with nonradiographic axSpA (nr-axSpA) treated with TNF inhibitors was higher in hospitals versus private practices (30.4% vs 18.7%, p = 0.02). The burden of disease as assessed by patient-reported outcomes at baseline was slightly higher in the hospital setting. Mean levels (± SD) of the Ankylosing Spondylitis Disease Activity Score were, however, virtually identical in private practices and academic centers (3.4 ± 1.0 vs 3.4 ± 0.9, p = 0.68). An Assessment of SpondyloArthritis international Society (ASAS40) response at 1 year was reached for ankylosing spondylitis in 51.7% in private practices and 52.9% in university hospitals (p = 1.0) and for nr-axSpA in 27.5% versus 25.0%, respectively (p = 1.0). CONCLUSION With the exception of a lower proportion of patients with nr-axSpA newly treated with anti-TNF agents in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings.

Genomics of Divergence along a Continuum of Parapatric Population Differentiation

The patterns of genomic divergence during ecological speciation are shaped by a combination of evolutionary forces. Processes such as genetic drift, local reduction of gene flow around genes causing reproductive isolation, hitchhiking around selected variants, variation in recombination and mutation rates are all factors that can contribute to the heterogeneity of genomic divergence. On the basis of 60 fully sequenced three-spined stickleback genomes, we explore these different mechanisms explaining the heterogeneity of genomic divergence across five parapatric lake and river population pairs varying in their degree of genetic differentiation. We find that divergent regions of the genome are mostly specific for each population pair, while their size and abundance are not correlated with the extent of genome-wide population differentiation. In each pair-wise comparison, an analysis of allele frequency spectra reveals that 25–55% of the divergent regions are consistent with a local restriction of gene flow. Another large proportion of divergent regions (38–75%) appears to be mainly shaped by hitchhiking effects around positively selected variants. We provide empirical evidence that alternative mechanisms determining the evolution of genomic patterns of divergence are not mutually exclusive, but rather act in concert to shape the genome during population differentiation, a first necessary step towards ecological speciation.

Contemporary ecotypic divergence during a recent range expansion was facilitated by adaptive introgression

Although rapid phenotypic evolution during range expansion associated with colonization of contrasting habitats has been documented in several taxa, the evolutionary mechanisms that underlie such phenotypic divergence have less often been investigated. A strong candidate for rapid ecotype formation within an invaded range is the three-spine stickleback in the Lake Geneva region of central Europe. Since its introduction only about 140 years ago, it has undergone a significant expansion of its range and its niche, now forming phenotypically differentiated parapatric ecotypes that occupy either the pelagic zone of the large lake or small inlet streams, respectively. By comparing museum collections from different times with contemporary population samples, we here reconstruct the evolution of parapatric phenotypic divergence through time. Using genetic data from modern samples, we infer the underlying invasion history. We find that parapatric habitat-dependent phenotypic divergence between the lake and stream was already present in the first half of the twentieth century, but the magnitude of differentiation increased through time, particularly in antipredator defence traits. This suggests that divergent selection between the habitats occurred and was stable through much of the time since colonization. Recently, increased phenotypic differentiation in antipredator defence traits likely results from habitat-dependent selection on alleles that arrived through introgression from a distantly related lineage from outside the Lake Geneva region. This illustrates how hybridization can quickly promote phenotypic divergence in a system where adaptation from standing genetic variation was constrained.

Quick divergence but slow convergence during ecotype formation in lake and stream stickleback pairs of variable age

When genetic constraints restrict phenotypic evolution, diversification can be predicted to evolve along so-called lines of least resistance. To address the importance of such constraints and their resolution, studies of parallel phenotypic divergence that differ in their age are valuable. Here, we investigate the parapatric evolution of six lake and stream threespine stickleback systems from Iceland and Switzerland, ranging in age from a few decades to several millennia. Using phenotypic data, we test for parallelism in ecotypic divergence between parapatric lake and stream populations and compare the observed patterns to an ancestral-like marine population. We find strong and consistent phenotypic divergence, both among lake and stream populations and between our freshwater populations and the marine population. Interestingly, ecotypic divergence in low-dimensional phenotype space (i.e. single traits) is rapid and seems to be often completed within 100 years. Yet, the dimensionality of ecotypic divergence was highest in our oldest systems and only there parallel evolution of unrelated ecotypes was strong enough to overwrite phylogenetic contingency. Moreover, the dimensionality of divergence in different systems varies between trait complexes, suggesting different constraints and evolutionary pathways to their resolution among freshwater systems.

Disentangling the role of phenotypic plasticity and genetic divergence in contemporary ecotype formation during a biological invasion

The occurrence of contemporary ecotype formation through adaptive divergence of populations within the range of an invasive species typically requires standing genetic variation but can be facilitated by phenotypic plasticity. The relative contributions of both of these to adaptive trait differentiation have rarely been simultaneously quantified in recently diverging vertebrate populations. Here we study a case of intraspecific divergence into distinct lake and stream ecotypes of threespine stickleback that evolved in the past 140 years within the invasive range in Switzerland. Using a controlled laboratory experiment with full-sib crosses and treatments mimicking a key feature of ecotypic niche divergence, we test if the phenotypic divergence that we observe in the wild results from phenotypic plasticity or divergent genetic predisposition. Our experimental groups show qualitatively similar phenotypic divergence as those observed among wild adults. The relative contribution of plasticity and divergent genetic predisposition differs among the traits studied, with traits related to the biomechanics of feeding showing a stronger genetic predisposition, whereas traits related to locomotion are mainly plastic. These results implicate that phenotypic plasticity and standing genetic variation interacted during contemporary ecotype formation in this case.

Ignoring heterozygous sites biases phylogenomic estimates of divergence times: implications for the evolutionary history of Microtus voles

Phylogenetic reconstruction of the evolutionary history of closely related organisms may be difficult because of the presence of unsorted lineages and of a relatively high proportion of heterozygous sites that are usually not handled well by phylogenetic programs. Genomic data may provide enough fixed polymorphisms to resolve phylogenetic trees, but the diploid nature of sequence data remains analytically challenging. Here, we performed a phylogenomic reconstruction of the evolutionary history of the common vole (Microtus arvalis) with a focus on the influence of heterozygosity on the estimation of intraspecific divergence times. We used genome-wide sequence information from 15 voles distributed across the European range. We provide a novel approach to integrate heterozygous information in existing phylogenetic programs by repeated random haplotype sampling from sequences with multiple unphased heterozygous sites. We evaluated the impact of the use of full, partial, or no heterozygous information for tree reconstructions on divergence time estimates. All results consistently showed four deep and strongly supported evolutionary lineages in the vole data. These lineages undergoing divergence processes split only at the end or after the last glacial maximum based on calibration with radiocarbon-dated paleontological material. However, the incorporation of information from heterozygous sites had a significant impact on absolute and relative branch length estimations. Ignoring heterozygous information led to an overestimation of divergence times between the evolutionary lineages of M. arvalis. We conclude that the exclusion of heterozygous sites from evolutionary analyses may cause biased and misleading divergence time estimates in closely related taxa.

Hybrid ‘superswarm’ leads to rapid divergence and establishment of populations during a biological invasion

Understanding the genetic background of invading species can be crucial information clarifying why they become invasive. Intraspecific genetic admixture among lineages separated in the native ranges may promote the rate and extent of an invasion by substantially increasing standing genetic variation. Here we examine the genetic relationships among threespine stickleback that recently colonized Switzerland. This invasion results from several distinct genetic lineages that colonized multiple locations and have since undergone range expansions, where they coexist and admix in parts of their range. Using 17 microsatellites genotyped for 634 individuals collected from 17 Swiss and two non-Swiss European sites, we reconstruct the invasion of stickleback and investigate the potential and extent of admixture and hybridization among the colonizing lineages from a population genetic perspective. Specifically we test for an increase in standing genetic variation in populations where multiple lineages coexist. We find strong evidence of massive hybridization early on, followed by what appears to be recent increased genetic isolation and the formation of several new genetically distinguishable populations, consistent with a hybrid ‘superswarm’. This massive hybridization and population formation event(s) occurred over approximately 140 years and likely fuelled the successful invasion of a diverse range of habitats. The implications are that multiple colonizations coupled with hybridization can lead to the formation of new stable genetic populations potentially kick-starting speciation and adaptive radiation over a very short time.

Experimental Evidence of an Eco-evolutionary Feedback during Adaptive Divergence

Differences in how organisms modify their environment can evolve rapidly and might influence adaptive population divergence [1, 2]. In a common garden experiment in aquatic mesocosms, we found that adult stickleback from a recently diverged pair of lake and stream populations had contrasting effects on ecosystem metrics. These modifications were caused by both genetic and plastic differences between populations and were sometimes comparable in magnitude to those caused by the presence/ absence of stickleback. Lake and streamfish differentially affected the biomass of zooplankton and phytoplankton, the concentration of phosphorus, and the abundance of several prey (e.g., copepods) and non-prey (e.g., cyanobacteria) species. The adult mediated effects on mesocosm ecosystems influenced the survival and growth of a subsequent generation of juvenile stickleback reared in the same mesocosms. The prior presence of adults decreased the overall growth rate of juveniles, and the prior presence of stream adults lowered overall juvenile survival. Among the survivors, lake juveniles grew faster than co-occurring stream juveniles, except in mesocosm ecosystems previously modified by adult lake fish that were reared on plankton. Overall, our results provide evidence for reciprocal interactions between ecosystem dynamics and evolutionary change (i.e., eco-evolutionary feedbacks) in the early stages of adaptive population divergence.