Phylogeny of Leavenworthia S-alleles suggests unidirectional mating system evolution and enhanced positive selection following an ancient population bottleneck

The adoption of self-fertilization from an ancestral outcrossing state is one of the most common evolutionary transitions in the flowering plants. In the mustard family, outcrossing is typically enforced by sporophytic self-incompatibility (SI), but there are also many self-compatible species. The genus Leavenworthia contains taxa that either possess or lack SI. Here, we present data showing that SI is associated with strict outcrossing and that there is widespread trans-specific sequence polymorphism at the locus involved in the recognition of self-pollen (the S-locus). This ancestral polymorphism is consistent with the presence of an outcrossing mating system in the common ancestor of Leavenworthia species, and suggests that there have been several independent losses of SI in the group. When compared with other mustard species, the bulk of Leavenworthia S-allele sequences are highly diverged from those found in other Brassicaceae and show relatively low levels of nucleotide diversity, a pattern that suggests the common ancestor of the genus likely underwent a strong population bottleneck. The hypothesis of postbottleneck S-locus rediversification is supported by tests showing stronger positive selection acting on S-alleles from Leavenworthia than those found in other Brassicaceae.     

Genome Sequence of a Neisseria meningitidis Capsule Null Locus Strain from the Clonal Complex of Sequence Type 198

Neisseria meningitidis is a commensal and accidental pathogen exclusively of humans. Although the production of polysaccharide capsules is considered to be essential for meningococcal virulence, there have been reports of constitutively unencapsulated strains causing invasive meningococcal disease (IMD). Here we report the genome sequence of a capsule null locus (cnl) strain of sequence type 198 (ST-198), which is found in half of the reported cases of IMD caused by cnl meningococcal strains.     

A colorimetric assay for determination of residual detergent levels in reconstituted membrane protein preparations

Simple and robust methods for the quantification of residual detergent in purified membrane proteins are not readily available. In this article, solubilization of precipitated dye by detergent is shown to be a facile method for the quantification of residual levels of octaethylene-glycol-mono(n-dodecyl)ether in virosomal influenza vaccine. Dye solubilization starts in the critical micellar concentration range. The method is more sensitive than an existing assay and is highly accurate and precise. The method is applicable to other detergents as well. This method of residual detergent quantification is simple and straightforward and is a useful tool for quality control of subunit vaccines.     

Migration rates, frequency-dependent selection and the self-incompatibility locus in Leavenworthia (brassicaceae)

Loci subject to negative frequency-dependent selection are expected to exhibit higher effective migration rates compared to reference loci. Although the number of gene copies transferred between populations by migration is the same for all genes, those subject to negative frequency-dependent selection are more likely to be retained in the immigrant population because rare alleles are selectively favored. So far, evidence for this prediction has been indirect, based on summary statistics rather than on migration rate estimates. Here, we introduce an approximate Bayesian procedure to jointly estimate migration rates at two predefined sets of loci between two populations. We applied the procedure to compare migration rate estimates at the self-incompatibility locus (S-locus) with that at 10 reference loci in two plant species, Leavenworthia alabamica and L. crassa (Brassicaceae). The maximum likelihood estimate for the proportion of migrants (m) was four times higher at the S-locus than at reference loci, but the difference was not statistically significant. Lack of significance might be due to insufficient data, but perhaps also to the recent divergence of the two species (311 ka), because we also show using simulations that the effective migration rate at the S-locus is expected to increase with increasing divergence time. These findings aid in understanding the evolutionary dynamics of negative frequency-dependent selection and they suggest that divergence time should be accounted for when employing migration rates to help detect negative frequency-dependent selection.     

Trends in intensive management of Alaska's grizzly bears, 1980–2010

Hunting regulations for grizzly bears (Ursus arctos) in much of Alaska since 1980 increasingly were designed to reduce bear abundance in the expectation such regulations would lead to increased harvests by hunters of moose (Alces alces) and caribou (Rangifer tarandus). Regulations were liberalized during 1980–2010 primarily in the area we termed the Liberal Grizzly Bear Hunting Area (hereafter Liberal Hunt Area) which encompassed 76.2% of Alaska. By 2010, these changes resulted in longer hunting seasons (100% of Liberal Hunt Area had seasons > 100 days, 99.7% > 200 days, and 67.8% > 300 days), more liberal bag limits (99.1% of the Liberal Hunt Area with a bag limit ≥ 1/yr and 10.1% with a bag limit ≥ 2/yr), and widespread waiver of resident tag fees (waived in 95.7% of the Liberal Hunt Area). During 1995–2010, there were 124 changes that made grizzly bear hunting regulations more liberal and two making them more conservative. The 4-year mean for grizzly bear kills by hunters increased 213% between 1976–1980 (387 grizzly bears) and 2005–2008 (823 grizzly bears). Since 2000, long-term research studies on grizzly populations in the Liberal Hunt Area have been terminated without replacement. Management of large predators by the State of Alaska is constrained by a 1994 state statute mandating “intensive management” in areas classified as important for human consumptive use of ungulates. Current grizzly bear management in the Liberal Hunt Area is inconsistent with the recommendations of the National Research Council's 1997 report on predator management in Alaska. Current attitudes, policies and absence of science-based management of grizzly bears in Alaska are increasingly similar to those that resulted in the near extirpation of grizzly bears south of Canada in the 19th and 20th centuries. If current trends continue, they increase risks to portions of the largest and most intact population of grizzly bears in North America. © 2011 The Wildlife Society.     

Preliminary mechanical characterization of the small bowel for in vivo robotic mobility

In this work we present test methods, devices, and preliminary results for the mechanical characterization of the small bowel for intra luminal robotic mobility. Both active and passive forces that affect mobility are investigated. Four investigative devices and testing methods to characterize the active and passive forces are presented in this work: (1) a novel manometer and a force sensor array that measure force per cm of axial length generated by the migrating motor complex, (2) a biaxial test apparatus and method for characterizing the biomechanical properties of the duodenum, jejunum, and ileum, (3) a novel in vitro device and protocol designed to measure the energy required to overcome the self-adhesivity of the mucosa, and (4) a novel tribometer that measures the in vivo coefficient of friction between the mucus membrane and the robot surface. The four devices are tested on a single porcine model to validate the approach and protocols. Mean force readings per cm of axial length of intestine that occurred over a 15?min interval in vivo were 1.34?±?0.14 and 1.18?±?0.22?N cm(-1) in the middle and distal regions, respectively. Based on the biaxial stress/stretch tests, the tissue behaves anisotropically with the circumferential direction being more compliant than the axial direction. The mean work per unit area for mucoseparation of the small bowel is 0.08?±?0.03 mJ cm(-2). The total energy to overcome mucoadhesion over the entire length of the porcine small bowel is approximately 0.55?J. The mean in vivo coefficient of friction (COF) of a curved 6.97 cm(2) polycarbonate sled on live mucosa traveling at 1?mm s(-1) is 0.016?±?0.002. This is slightly lower than the COF on excised tissue, given the same input parameters. We have initiated a comprehensive program and suite of test devices and protocols for mechanically characterizing the small bowel for in vivo mobility. Results show that each of the four protocols and associated test devices has successfully gathered preliminary data to confirm the validity of our test approach.     

Demographic signatures accompanying the evolution of selfing in Leavenworthia alabamica

The evolution of selfing from outcrossing is a common transition, yet little is known about the mutations and selective factors that promote this shift. In the mustard family, single-locus self-incompatibility (SI) enforces outcrossing. In this study, we test whether mutations causing self-compatibility (SC) are linked to the self-incompatibility locus (S-locus) in Leavenworthia alabamica, a species where two selfing races (a2 and a4) co-occur with outcrossing populations. We also infer the ecological circumstances associated with origins of selfing using molecular sequence data. Genealogical reconstruction of the Lal2 locus, the putative ortholog of the SRK locus, showed that both selfing races are fixed for one of two different S-linked Lal2 sequences, whereas outcrossing populations harbor many S-alleles. Hybrid crosses demonstrated that S-linked mutations cause SC in each selfing race. These results strongly suggest two origins of selfing in this species, a result supported by population admixture analysis of 16 microsatellite loci and by a population tree built from eight nuclear loci. One selfing race (a4) shows signs of a severe population bottleneck, suggesting that reproductive assurance might have caused the evolution of selfing in this case. In contrast, the population size of race a2 cannot be distinguished from that of outcrossing populations after correcting for differences in selfing rates. Coalescent-based analyses suggest a relatively old origin of selfing in the a4 race (～150 ka ago), whereas selfing evolved recently in the a2 race (～12-48 ka ago). These results imply that S-locus mutations have triggered two recent shifts to selfing in L. alabamica, but that these transitions are not always associated with a severe population bottleneck, suggesting that factors other than reproductive assurance may play a role in its evolution.     

Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies

Intact synaptic homeostasis is a fundamental prerequisite for a healthy brain. Thus, it is not surprising that altered synaptic morphology and function are involved in the molecular pathogenesis of so-called synaptopathies including autism, schizophrenia (SCZ) and Alzheimer's disease (AD). Intriguingly, various recent studies revealed a crucial role of postsynaptic ProSAP/Shank scaffold proteins in all of the aforementioned disorders. Considering these findings, we follow the hypothesis that ProSAP/Shank proteins are key regulators of synaptic development and plasticity with clear-cut isoform-specific roles. We thus propose a model where ProSAP/Shank proteins are in the center of a postsynaptic signaling pathway that is disrupted in several neuropsychiatric disorders.     

Spared Piriform Cortical Single-Unit Odor Processing and Odor Discrimination in the Tg2576 Mouse Model of Alzheimer's Disease

Alzheimer''s disease is a neurodegenerative disorder that is the most common cause of dementia in the elderly today. One of the earliest reported signs of Alzheimer''s disease is olfactory dysfunction, which may manifest in a variety of ways. The present study sought to address this issue by investigating odor coding in the anterior piriform cortex, the primary cortical region involved in higher order olfactory function, and how it relates to performance on olfactory behavioral tasks. An olfactory habituation task was performed on cohorts of transgenic and age-matched wild-type mice at 3, 6 and 12 months of age. These animals were then anesthetized and acute, single-unit electrophysiology was performed in the anterior piriform cortex. In addition, in a separate group of animals, a longitudinal odor discrimination task was conducted from 3–12 months of age. Results showed that while odor habituation was impaired at all ages, Tg2576 performed comparably to age-matched wild-type mice on the olfactory discrimination task. The behavioral data mirrored intact anterior piriform cortex single-unit odor responses and receptive fields in Tg2576, which were comparable to wild-type at all age groups. The present results suggest that odor processing in the olfactory cortex and basic odor discrimination is especially robust in the face of amyloid β precursor protein (AβPP) over-expression and advancing amyloid β (Aβ) pathology. Odor identification deficits known to emerge early in Alzheimer''s disease progression, therefore, may reflect impairments in linking the odor percept to associated labels in cortical regions upstream of the primary olfactory pathway, rather than in the basic odor processing itself.