Large-effect flowering time mutations reveal conditionally adaptive paths through fitness landscapes in Arabidopsis thaliana.

Contrary to previous assumptions that most mutations are deleterious, there is increasing evidence for persistence of large-effect mutations in natural populations. A possible explanation for these observations is that mutant phenotypes and fitness may depend upon the specific environmental conditions to which a mutant is exposed. Here, we tested this hypothesis by growing large-effect flowering time mutants of Arabidopsis thaliana in multiple field sites and seasons to quantify their fitness effects in realistic natural conditions. By constructing environment-specific fitness landscapes based on flowering time and branching architecture, we observed that a subset of mutations increased fitness, but only in specific environments. These mutations increased fitness via different paths: through shifting flowering time, branching, or both. Branching was under stronger selection, but flowering time was more genetically variable, pointing to the importance of indirect selection on mutations through their pleiotropic effects on multiple phenotypes. Finally, mutations in hub genes with greater connectedness in their regulatory networks had greater effects on both phenotypes and fitness. Together, these findings indicate that large-effect mutations may persist in populations because they influence traits that are adaptive only under specific environmental conditions. Understanding their evolutionary dynamics therefore requires measuring their effects in multiple natural environments

The OH-F substitution in synthetic pargasite at 1.5 kbar, 850 °C.

Amphiboles were synthesized at 1.5 kbar PH2O and 850 °C along the join pargasite-fluoropargasite. Structural variations in the amphibole as a function of F have been characterized by a combination of SEM-EDS, X-ray powder diffraction, and infrared spectroscopy. SEM-EDS analyses show that, for increasing F in the system, there is a decrease in Altot in the amphibole and a significant decrease of F incorporation in the structure. In agreement with the EDS data, the variation in cell parameters and IR spectra show that incorporation of F in pargasite is restricted to about 1.0 atoms per formula unit (apfu). The OH-stretching spectra show fine structure caused by F replacing OH at the O3 anion site, and are consistent with two-mode behavior typical of A-site-filled amphiboles. The agreement between calculated and observed relative band intensities suggests complete short-range disorder of OH and F at the O3 anion site

Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence.

Rickettsia are obligate intracellular bacteria that evade antimicrobial autophagy in the host cell cytosol by unknown mechanisms. Other cytosolic pathogens block different steps of autophagy targeting, including the initial step of polyubiquitin-coat formation. One mechanism of evasion is to mobilize actin to the bacterial surface. Here, we show that actin mobilization is insufficient to block autophagy recognition of the pathogen Rickettsia parkeri. Instead, R. parkeri employs outer membrane protein B (OmpB) to block ubiquitylation of the bacterial surface proteins, including OmpA, and subsequent recognition by autophagy receptors. OmpB is also required for the formation of a capsule-like layer. Although OmpB is dispensable for bacterial growth in endothelial cells, it is essential for R. parkeri to block autophagy in macrophages and to colonize mice because of its ability to promote autophagy evasion in immune cells. Our results indicate that OmpB acts as a protective shield to obstruct autophagy recognition, thereby revealing a distinctive bacterial mechanism to evade antimicrobial autophagy

Site occupancies in synthetic monoclinic amphiboles: Rietveld structure refinement and infrared spectroscopy of (nickel, magnesium, cobalt)-richterite.

Amphiboles were synthesized at 750 8C, 1 kbar (H2O) on the binary joins (nickel, magnesium)-richterite and (magnesium, cobalt)-richterite. Structural variations and site occupancies were characterized by Rietveld structure refinement, with final RBragg indices in the range 4–9%, and by powder infrared spectroscopy in the principal OH-stretching region. Site-occupancy refinement of Ni-Mg and Mg-Co distributions give the partition coefficients over M1,3 and M2 where KM21 5 (M21/Mg)M1,3/(M21/Mg)M2, and M21 5 Ni21 or Co21, K 5 2.98 6 0.37 and K 5 1.34 6 0.31. Both Kd Ni Co values are greater than 1.0, d d whereas [6]r(Ni21 ) , [6]r(Mg) , [6]r(Co21 ); this indicates that cation size is not the primary factor affecting the ordering of Ni-Mg and Mg-Co over the octahedral sites. The infrared spectra of intermediate binary compositions show fine structure caused by ordering of Ni- Mg or Mg-Co over the M1,3 sites and by ordering of Na and M (vacancy) at the A site; thus intermediate compositions show an eight-band spectrum in the principal OHstretching region. Precise band intensities were derived by nonlinear least-squares fitting of Gaussian band shapes to the observed spectra. The relative observed intensities of the combinations of bands 3IA1 2IB1 IC and IB 1 2IC 1 3ID are in accord with the equations o o o o o o of Burns and Strens (1966), indicating that there is no significant variation in molar absorptivity with frequency (energy) for individual bands within a single sample (spectrum). Combined with the results of Skogby and Rossman (1991) on polarized single-crystal infrared spectra of amphiboles, this result suggests that different local configurations of M1,3 cations in amphiboles couple such that the transition probabilities of the associated OH groups are equal

Lifespan extension by caloric restriction is determined by type and level of food reduction and by reproductive mode in Brachionus manjavacas (Rotifera)

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in The Journals of Gerontology, Series A: Biological Sciences 68 (2013): 349-358, doi:10.1093/gerona/gls170.We measured lifespan and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased lifespan 50 – 70% for all three modes, while CCR increased lifespan of asexual females derived from sexually- or asexually-produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum lifespan; in contrast CR in sexual females greatly increased the lifespan of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, while differences in lifespan allocations suggest that multiple genetic mechanisms mediate lifespan extension.This work was supported by the National Institute on Aging Division of Aging Biology (R01 AG037960-01).2013-08-1

Duplex assessment of venous reflux and chronic venous insufficiency: The significance of deep venous reflux

AbstractPurpose: This study was undertaken to examine the role of superficial and deep venous reflux, as defined by duplex-derived valve closure times (VCTs), in the pathogenesis of chronic venous insufficiency.Methods: Between January 1992 and November 1995, 320 patients and 500 legs were evaluated with clinical examinations and duplex scans for potential venous reflux. VCTs were obtained with the cuff deflation technique with the patient in the upright position. Imaging was performed at the saphenofemoral junction, the middle segment of the greater saphenous vein, the lesser saphenous vein, the superficial femoral vein, the profunda femoris vein, and the popliteal vein. Not all patients had all segments examined because tests early in the series did not examine the profunda femoris or lesser saphenous vein and because some patients had previous ligation and stripping or venous thrombosis. VCTs were examined for individual segment reflux, grouped into superficial and deep systems, and then correlated with the clinical stage as defined by the SVS/ISCVS original reporting standards in venous disease. Segment reflux was considered present if the VCT was greater than 0.5 seconds, and system reflux was considered present if the sum of the segments was greater than 1.5 seconds. Between-group differences were analyzed with analysis of variance and post hoc tests where appropriate.Results: Sixty-nine limbs studied were in class 0, 149 limbs were in class 1, 168 limbs were in class 2, and 114 limbs were in class 3. VCTs in the superficial veins were significantly lower in class 0 than in the other clinical classes. There was no difference in superficial reflux in the symptomatic limbs (classes 1 to 3). Reflux VCTs in the superficial femoral and popliteal veins increased as the clinical symptoms progressed, with a significant increase in class 3 ulcerated limbs when compared with nonulcerated limbs. The incidence of deep venous reflux was 60% in class 3 limbs, compared with 29% in class 2 limbs, whereas the incidence of superficial venous reflux did not differ among the symptomatic limbs. Isolated superficial femoral and popliteal vein reflux was uncommon, even in class 3 limbs, but combined superficial femoral and popliteal vein reflux was found in 53% of class 3 limbs, compared with 18.5% of class 2 limbs.Conclusions: Reflux in the deep venous system plays a significant role in the progression of chronic venous insufficiency. Deep system reflux increases as clinical changes become more severe, with significant axial reflux contributing to ulcer formation. (J Vasc Surg 1996;24:755-62.

Subsidizing Religious Participation through Groups: A Model of the “Megachurch” Strategy for Growth

Either despite or because of their non-traditional approach, megachurches have grown significantly in the United States since 1980. This paper models religious participation as an imperfect public good which, absent intervention, yields suboptimal participation by members from the church’s perspective. Megachurches address this problem in part by employing secular-based group activities to subsidize religious participation that then translates into an increase in the attendees’ religious investment. This strategy not only allows megachurches to attract and retain new members when many traditional churches are losing members but also results in higher levels of an individual’s religious capital. As a result, the megachurch may raise expectations of members’ levels of commitment and faith practices. Data from the FACT2000 survey provide evidence that megachurches employ groups more extensively than other churches, and this approach is consistent with a strategy to use groups to help subsidize individuals’ religious investment. Religious capital rises among members of megachurches relative to members of non-megachurches as a result of this strategy

How to find an attractive solution to the liar paradox

The general thesis of this paper is that metasemantic theories can play a central role in determining the correct solution to the liar paradox. I argue for the thesis by providing a specific example. I show how Lewis’s reference-magnetic metasemantic theory may decide between two of the most influential solutions to the liar paradox: Kripke’s minimal fixed point theory of truth and Gupta and Belnap’s revision theory of truth. In particular, I suggest that Lewis’s metasemantic theory favours Kripke’s solution to the paradox over Gupta and Belnap’s. I then sketch how other standard criteria for assessing solutions to the liar paradox, such as whether a solution faces a so-called revenge paradox, fit into this picture. While the discussion of the specific example is itself important, the underlying lesson is that we have an unused strategy for resolving one of the hardest problems in philosophy