Rho Guanosine Triphosphatase Mediates the Selective Stabilization of Microtubules Induced by Lysophosphatidic Acid

The asymmetric distribution of stable, posttranslationally modified microtubules (MTs) contributes to the polarization of many cell types, yet the factors controlling the formation of these MTs are not known. We have found that lysophosphatidic acid (LPA) is a major serum factor responsible for rapidly generating stable, detyrosinated (Glu) MTs in serum-starved 3T3 cells. Using C3 toxin and val14 rho we showed that rho was both necessary and sufficient for the induction of Glu MTs by LPA and serum. Unlike previously described factors that induce MT stability, rho induced the stabilization of only a subset of the MTs and, in wound-edge cells, these stable MTs were appropriately oriented toward the leading edge of the cell. LPA had little effect on individual parameters of MT dynamics, but did induce long states of pause in a subset of MTs near the edge of the cell. Rho stimulation of MT stability was independent of actin stress fiber formation. These results identify rho as a novel regulator of the MT cytoskeleton that selectively stabilizes MTs during cell polarization by acting as a switch between dynamic and stable states of MTs rather than as a modulator of MT assembly and disassembly.     

Selfish mothers: reproductive expenditure and resource availability in bighorn ewes

We present a marginal value model explaining intraspecific andinterspecific variation of mating systems in nonterritorialungulates. The model takes into account the simultaneous effectsof spatial and temporal distribution of females, female groupsize, male-male competition, female choice, and the operationalsex ratio (i.e., the proportion of estrous females). The modelpredicts that higher numbers of females per group increasesthe average exploitation time of such groups by males. An increasein female group density, operational sex ratio, and age-specificfighting success of males are predicted to reduce the averageexploitation time of female groups, leading to roving of males(i.e., moving between female groups). In contrast, an increasein die female rejection rate of males and in the time spentby males on nonmating activities (i. e., foraging, lying down,ruminating, migrating) are predicted to increase the averageexploitation time of female groups and to favor staying behaviorof males (i.e., defending a female group over a longer periodof time). Consequently, die model predicts that young maleswill tend to be "stayers," whereas middle-aged and old malesare expected to be "rovers." Model predictions were tested widifield data collected on muskoxen Ovibos moschatus in a naturalpopulation in west Greenland. Observed correlations betweenbull exploitation times of cow groups and the six above-mentionedsocial and environmental parameters were all in die predicteddirection and statistically significant in five of die six cases.Overall, 69% of die observed variation in exploitation timeof cow groups by males was explained by die model predictions.Stepwise regression suggested that, of die six parameters, variationin sex ratio (R² = .56) and time spent on nonmating activities(R² = .35) had the largest effects on male exploitation time.Also, die observed age-specific variation in bull exploitationtime of cow groups was as predicted.     

Soil Methane Sink Capacity Response to a Long-Term Wildfire Chronosequence in Northern Sweden

Boreal forests occupy nearly one fifth of the terrestrial land surface and are recognised as globally important regulators of carbon (C) cycling and greenhouse gas emissions. Carbon sequestration processes in these forests include assimilation of CO₂ into biomass and subsequently into soil organic matter, and soil microbial oxidation of methane (CH₄). In this study we explored how ecosystem retrogression, which drives vegetation change, regulates the important process of soil CH₄ oxidation in boreal forests. We measured soil CH₄ oxidation processes on a group of 30 forested islands in northern Sweden differing greatly in fire history, and collectively representing a retrogressive chronosequence, spanning 5000 years. Across these islands the build-up of soil organic matter was observed to increase with time since fire disturbance, with a significant correlation between greater humus depth and increased net soil CH₄ oxidation rates. We suggest that this increase in net CH₄ oxidation rates, in the absence of disturbance, results as deeper humus stores accumulate and provide niches for methanotrophs to thrive. By using this gradient we have discovered important regulatory controls on the stability of soil CH₄ oxidation processes that could not have not been explored through shorter-term experiments. Our findings indicate that in the absence of human interventions such as fire suppression, and with increased wildfire frequency, the globally important boreal CH₄ sink could be diminished.     

Implant Optimisation for Primary Hip Replacement in Patients over 60 Years with Osteoarthritis: A Cohort Study of Clinical Outcomes and Implant Costs Using Data from England and Wales

Background

Hip replacement is one of the most commonly performed surgical procedures worldwide; hundreds of implant configurations provide options for femoral head size, joint surface material and fixation method with dramatically varying costs. Robust comparative evidence to inform the choice of implant is needed. This retrospective cohort study uses linked national databases from England and Wales to determine the optimal type of replacement for patients over 60 years undergoing hip replacement for osteoarthritis.

Methods and Findings

Implants included were the commonest brand from each of the four types of replacement (cemented, cementless, hybrid and resurfacing); the reference prosthesis was the cemented hip procedure. Patient reported outcome scores (PROMs), costs and risk of repeat (revision) surgery were examined. Multivariable analyses included analysis of covariance to assess improvement in PROMs (Oxford hip score, OHS, and EQ5D index) (9159 linked episodes) and competing risks modelling of implant survival (79,775 procedures). Cost of implants and ancillary equipment were obtained from National Health Service procurement data.

Results

EQ5D score improvements (at 6 months) were similar for all hip replacement types. In females, revision risk was significantly higher in cementless hip prostheses (hazard ratio, HR = 2.22, p<0.001), when compared to the reference hip. Although improvement in OHS was statistically higher (22.1 versus 20.5, p<0.001) for cementless implants, this small difference is unlikely to be clinically important. In males, revision risk was significantly higher in cementless (HR = 1.95, p = 0.003) and resurfacing implants, HR = 3.46, p<0.001), with no differences in OHS. Material costs were lowest with the reference implant (cemented, range £1103 to £1524) and highest with cementless implants (£1928 to £4285).Limitations include the design of the study, which is intrinsically vulnerable to omitted variables, a paucity of long-term implant survival data (reflecting the duration of data collection), the possibility of revision under-reporting, response bias within PROMs data, and issues associated with current outcome scoring systems, which may not accurately reflect level of improvement in some patients.

Conclusions

Cement fixation, using a polyethylene cup and a standard sized head offers good outcomes, with the lowest risks and at the lowest costs. The most commonly used cementless and resurfacing implants were associated with higher risk of revision and were more costly, while perceptions of improved function and longevity were unsupported.     

Stereochemistry–activity relationship of orally active tetralin S1P agonist prodrugs

Modifying FTY720, an immunosuppressant modulator, led to a new series of well phosphorylated tetralin analogs as potent S1P1 receptor agonists. The stereochemistry effect of tetralin ring was probed, and (?)-(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol was identified as a good SphK2 substrate and potent S1P1 agonist with good oral bioavailability.     

What does it take to be a plant pathogen: genomic insights from <Emphasis Type="Italic">Streptomyces</Emphasis> species

Plant pathogenicity is rare in the genus Streptomyces, with only a dozen or so species possessing this trait out of the more than 900 species described. Nevertheless, such species have had a significant impact on agricultural economies throughout the world due to their ability to cause important crop diseases such as potato common scab, which is characterized by lesions that form on the potato tuber surface. All pathogenic species that cause common scab produce a family of phytotoxins called the thaxtomins, which function as cellulose synthesis inhibitors. In addition, the nec1 and tomA genes are conserved in several pathogenic streptomycetes, the former of which is predicted to function in the suppression of plant defense responses. Streptomyces scabies is the oldest plant pathogen described and has a world-wide distribution, whereas species such as S. turgidiscabies and S. acidiscabies are believed to be newly emergent pathogens found in more limited geographical locations. The genome sequence of S. scabies 87-22 was recently completed, and comparative genomic analyses with other sequenced microbial pathogens have revealed the presence of additional genes that may play a role in plant pathogenicity, an idea that is supported by functional analysis of one such putative virulence locus. In addition, the availability of multiple genome sequences for both pathogenic and nonpathogenic streptomycetes has provided an opportunity for comparative genomic analyses to identify the Streptomyces pathogenome. Such genomic analyses will contribute to the fundamental understanding of the mechanisms and evolution of plant pathogenicity and plant-microbe biology within this genus.