Frequency-dependent sexual selection with respect to offspring fitness returns is consistent with predictions from rock-paper-scissors dynamics in the European common lizard

Genetic polymorphism can be maintained over time by negative frequency-dependent (FD) selection induced by Rock-paper-scissors (RPS) social systems. RPS games produce cyclic dynamics, and have been suggested to exist in lizards, insects, isopods, plants, and bacteria. Sexual selection is predicted to accentuate the survival of the future progeny during negative FD survival selection. More specifically, females are predicted to select mates that produce progeny genotypes that exhibit highest survival during survival selection imposed by adult males. However, no empirical evidence demonstrates the existence of FD sexual selection with respect to fitness payoffs of genetic polymorphisms. Here we tested this prediction using the common lizard Zootoca vivipara, a species with three male color morphs (orange, white, yellow) that exhibit morph frequency cycles. In a first step we tested the congruence of the morph frequency change with the predicted change in three independent populations, differing in male color morph frequency and state of the FD morph cycle. Thereafter we ran standardized sexual selection assays in which we excluded alternative mechanisms that potentially induce negative FD selection, and we quantified inter-sexual behavior. The patterns of sexual selection and the observed behavior were in line with context-dependent female mate choice and male behavior played a minor role. Moreover, the strength of the sexual selection was within the magnitude of selection required to produce the observed 3-4-year and 6-8 year morph frequency cycles at low and high altitudes, respectively. In summary, the study provides the first experimental evidence that underpins the crucial assumption of the RPS games suggested to exist in lizards, insects, isopods, and plants; namely, that sexual selection produces negative-FD selection. This indicates that sexual selection, in our study exert by females, might be a crucial driver of the maintenance of genetic polymorphisms.

Octacalcium Phosphate (OCP) Crystals Induce Synovial Inflammation and Cartilage

Introduction: The presence of intra-articular basic calcium phosphate (BCP) crystals, including OCP, carbonated-apatite, hydroxyapatite and tricalcium phosphate crystals, is associated with severe osteoarthritis and destructive arthropathies such as Milwaukee shoulder. Although BCP crystals displayed, in vitro, mitogenic, anabolic and catabolic responses, their intra-articular effect was never assessed.Objective: To determine the effects of OCP crystals in joints in vivo.Methods: OCP crystals (200 ug in 20 ml PBS) were injected into the right knee joint (the contra-lateral knee joint injected with 20 ul of PBS serving as a control) of wild-type mice treated or not by the IL1R antagonist Anakinra or mice deficient for the inflammasome proteins ASC and NALP3. 4 days and 17 days after crystal injection, mice were sacrificed and knee joints dissected. Histological scoring for synovial inflammation and characterisation of macrophages, neutrophils and T cells were performed. Technetium (Tc) uptake was measured at 6h, 1 and 4 days after OCP injection. Cartilage degradation was evaluated by Safranin O staining and VDIPEN immunohistochemistry. Intra-articular localisation of injected OCP crystals was evidenced by Von Kossa staining.Results: The intra-articular localisation of injected OCP crystals was evidenced by Von Kossa staining performed on non-decalcified samples embedded in methyl-metacrylate. Injection of OCP crystals into knee joints led at day 4 to an inflammatory response with intense macrophage staining and also some neutrophil recruitment in the synovial membrane. This synovitis was not accompanied by increased Tc uptake into the knee joint, Tc uptake being similar in OCP crystal injected knee or control knee at all time points investigated (6h, 1 day, 4 days). The histological modifications persisted over 17 days, with an additional fibrosis evidenced at this later time-point. The OCP crystal-induced synovitis was totally IL-1a and IL-1 independent as shown by the absence of inhibitory effects of anakinra injected into wild-type mice. Accordingly, OCP crystal-induced synovitis was similar in ASC-/- and NALP3-/- mice as no alterations of inflammation were demonstrated between these mice groups. Concerning cartilage matrix degradation, OCP crystals induced a strong breakdown of proteoglycans 4 and 17 days after injection, as measured by loss of red staining from Safranin O-stained sections of cartilage surfaces. In addition, we also measured advanced cartilage matrix destruction mediated by MMPs, as evidenced by VDIPEN staining of cartilage. OCP-mediated cartilage degradation was similar in all experimental conditions tested (WT+Anakinra, or ASC or NALP3 deficient mice).Conclusion: These data indicate in vivo that the intra-articular presence of OCP crystals is associated with cartilage destruction along with synovial inflammation. This is an interesting and new model of destructive arthropathy related to BCP crystals which will allow to assess new therapies in this disease.

El pop y el rock como productos de gran consumo: Los Beatles como marca

El treball final de carrera El pop i el rock com a productes de gran consum: els Beatles com a marca, té l’objectiu de demostrar la dimensió del màrketing en el cas dels Beatles. Primerament exposa la evolució dels gèneres musicals i dels compositors i grups més influents de la música pop i rock. Seguidament una breu contextualització dels Beatles, per posteriorment abordar l’objectiu principal del projecte, el qual pretén demostrar que el conjunt de Liverpool va ser una gran marca nascuda de la barreja d’estils musicals i del consumisme.

Over-expression of PHO1 in Arabidopsis leaves reveals its role in mediating phosphate efflux.

Inorganic phosphate (Pi) homeostasis in multi-cellular eukaryotes depends not only on Pi influx into cells, but also on Pi efflux. Examples in plants for which Pi efflux is crucial are transfer of Pi into the xylem of roots and release of Pi at the peri-arbuscular interface of mycorrhizal roots. Despite its importance, no protein has been identified that specifically mediates phosphate efflux either in animals or plants. The Arabidopsis thaliana PHO1 gene is expressed in roots, and was previously shown to be involved in long-distance transfer of Pi from the root to the shoot. Here we show that PHO1 over-expression in the shoot of A. thaliana led to a two- to threefold increase in shoot Pi content and a severe reduction in shoot growth. (31) P-NMR in vivo showed a normal initial distribution of intracellular Pi between the cytoplasm and the vacuole in leaves over-expressing PHO1, followed by a large efflux of Pi into the infiltration medium, leading to a rapid reduction of the vacuolar Pi pool. Furthermore, the Pi concentration in leaf xylem exudates from intact plants was more than 100-fold higher in PHO1 over-expressing plants compared to wild-type. Together, these results show that PHO1 over-expression in leaves leads to a dramatic efflux of Pi out of cells and into the xylem vessel, revealing a crucial role for PHO1 in Pi efflux.

Phosphate import at the arbuscule: just a nutrient?

Central to the mutualistic arbuscular mycorrhizal symbiosis is the arbuscule, the site where symbiotic phosphate is delivered. Initial investigations in legumes have led to the exciting observation that symbiotic phosphate uptake not only enhances plant growth but also regulates arbuscule dynamics and is, furthermore, required for maintenance of the symbiosis. This review evaluates the possible role of the phosphate ion, not only as a nutrient but also as a signal that is necessary for reprogramming the host cortex cell for symbiosis.

Analyzing complex rock slope deformation at Stampa, western Norway, by integrating geomorphology, kinematics and numerical modeling

The unstable rock slope, Stampa, above the village of Flåm, Norway, shows signs of both active and postglacial gravitational deformation over an area of 11 km2. Detailed structural field mapping, annual differential Global Navigation Satellite System (GNSS) surveys, as well as geomorphic analysis of high-resolution digital elevation models based on airborne and terrestrial laser scanning indicate that slope deformation is complex and spatially variable. Numerical modeling was used to investigate the influence of former rockslide activity and to better understand the failure mechanism. Field observations, kinematic analysis and numerical modeling indicate a strong structural control of the unstable area. Based on the integration of the above analyses, we propose that the failure mechanism is dominated by (1) a toppling component, (2) subsiding bilinear wedge failure and (3) planar sliding along the foliation at the toe of the unstable slope. Using differential GNSS, 18 points were measured annually over a period of up to 6 years. Two of these points have an average yearly movement of around 10 mm/year. They are located at the frontal cliff on almost completely detached blocks with volumes smaller than 300,000 m3. Large fractures indicate deep-seated gravitational deformation of volumes reaching several 100 million m3, but the movement rates in these areas are below 2 mm/year. Two different lobes of prehistoric rock slope failures were dated with terrestrial cosmogenic nuclides. While the northern lobe gave an average age of 4,300 years BP, the southern one resulted in two different ages (2,400 and 12,000 years BP), which represent most likely multiple rockfall events. This reflects the currently observable deformation style with unstable blocks in the northern part in between Joasete and Furekamben and no distinct blocks but a high rockfall activity around Ramnanosi in the south. With a relative susceptibility analysis it is concluded that small collapses of blocks along the frontal cliff will be more frequent. Larger collapses of free-standing blocks along the cliff with volumes > 100,000 m3, thus large enough to reach the fjord, cannot be ruled out. A larger collapse involving several million m3 is presently considered of very low likelihood.

Structural characterization of Turtle Mountain anticline (Alberta, Canada) and impact on rock slope failure

his paper proposes a structural investigation of the Turtle Mountain anticline (Alberta, Canada) to better understand the role of the different tectonic features on the development of both local and large scale rock slope instabilities occurring in Turtle Mountain. The study area is investigated by combining remote methods with detailed field surveys. In particular, the benefit of Terrestrial Laser Scanning for ductile and brittle tectonic structure interpretations is illustrated. The proposed tectonic interpretation allows the characterization of the fracturing pattern, the fold geometry and the role of these tectonic features in rock slope instability development. Ten discontinuity sets are identified in the study area, their local variations permitting the differentiation of the study zone into 20 homogenous structural domains. The anticline is described as an eastern verging fold that displays considerable geometry differences along its axis and developed by both flexural slip and tangential longitudinal strain folding mechanisms. Moreover, the origins of the discontinuity sets are determined according to the tectonic phases affecting the region (pre-folding, folding, post-folding). The localization and interpretation of kinematics of the different instabilities revealed the importance of considering the discrete brittle planes of weakness, which largely control the kinematic release of the local instabilities, and also the rock mass damage induced by large tectonic structures (fold hinge, thrust).

A pea plasma membrane protein exhibiting blue light-induced phosphorylation retains photosensitivity following triton solubilization.

Phosphorylation of a polypeptide of approximately 120 kD in pea (Pisum sativum L.) plasma membranes in response to blue light has been shown to be involved in phototropic curvature, but the relationship of this protein to the kinase and photoreceptor acting upon it is uncertain. Using two-phase aqueous partitioning to isolate right-side-out plasma membrane vesicles, we have obtained evidence suggesting that the photoreceptor, kinase, and substrate are localized to the plasma membrane fraction. Latent phosphorylation accessible through Triton X-100 or freeze/thaw treatments of purified plasma membrane vesicles indicates that at least the kinase moiety is present on the internal face of the plasma membrane. Effects of solubilization of vesicles on fluence-response characteristics and on phosphorylation levels provide evidence that the receptor, kinase, and protein substrate are present together in individual mixed detergent micelles, either as a stable complex or as domains of a single polypeptide. In vivo blue-light irradiation results in a small but significant decrease in mobility of the 120-kD phosphorylated protein on sodium dodecylsulfate gel electrophoresis. This mobility shift is evident on Coomassie-stained gels and on western blots probed with polyclonal antibodies raised against the 120-kD protein. Among the plasma membrane proteins bound to the reactive nucleotide analog fluorosulfonylbenzoyladenine (FSBA), a distinct protein band at 120 kD can be detected on blots probed with anti-FSBA antibodies. This band exhibits an in vivo light-dependent mobility shift identical to that observed for the protein band and antibodies specific for the 120-kD protein, implying that the 120-kD protein has an integral nucleotide binding site and consistent with the possibility that the substrate protein is also a kinase.

Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum

In Plasmodium falciparum, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, central intermediates in the biosynthesis of isoprenoids, occurs via the methylerythritol phosphate (MEP) pathway. Fosmidomycin is a specific inhibitor of the second enzyme of the MEP pathway, 1-deoxy-D-xylulose-5-phosphate reductoisomerase. We analyzed the effect of fosmidomycin on the levels of each intermediate and its metabolic requirement for the isoprenoid biosynthesis, such as dolichols and ubiquinones, throughout the intraerythrocytic cycle of P. falciparum. The steady-state RNA levels of the MEP pathway-associated genes were quantified by real-time polymerase chain reaction and correlated with the related metabolite levels. Our results indicate that MEP pathway metabolite peak precede maximum transcript abundance during the intraerythrocytic cycle. Fosmidomycin-treatment resulted in a decrease of the intermediate levels in the MEP pathway as well as in ubiquinone and dolichol biosynthesis. The MEP pathway associated transcripts were modestly altered by the drug, indicating that the parasite is not strongly responsive at the transcriptional level. This is the first study that compares the effect of fosmidomycin on the metabolic and transcript profiles in P. falciparum, which has only the MEP pathway for isoprenoid biosynthesis.

A rice cis-natural antisense RNA acts as a translational enhancer for its cognate mRNA and contributes to phosphate homeostasis and plant fitness.

cis-natural antisense transcripts (cis-NATs) are widespread in plants and are often associated with downregulation of their associated sense genes. We found that a cis-NAT positively regulates the level of a protein critical for phosphate homeostasis in rice (Oryza sativa). PHOSPHATE1;2 (PHO1;2), a gene involved in phosphate loading into the xylem in rice, and its associated cis-NATPHO1;2 are both controlled by promoters active in the vascular cylinder of roots and leaves. While the PHO1;2 promoter is unresponsive to the plant phosphate status, the cis-NATPHO1;2 promoter is strongly upregulated under phosphate deficiency. Expression of both cis-NATPHO1;2 and the PHO1;2 protein increased in phosphate-deficient plants, while the PHO1;2 mRNA level remained stable. Downregulation of cis-NATPHO1;2 expression by RNA interference resulted in a decrease in PHO1;2 protein, impaired the transfer of phosphate from root to shoot, and decreased seed yield. Constitutive overexpression of NATPHO1;2 in trans led to a strong increase of PHO1;2, even under phosphate-sufficient conditions. Under all conditions, no changes occurred in the level of expression, sequence, or nuclear export of PHO1;2 mRNA. However, expression of cis-NATPHO1;2 was associated with a shift of both PHO1;2 and cis-NATPHO1;2 toward the polysomes. These findings reveal an unexpected role for cis-NATPHO1;2 in promoting PHO1;2 translation and affecting phosphate homeostasis and plant fitness.

FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone.

The functional interaction between fibroblast growth factor 23 (FGF-23) and Klotho in the control of vitamin D and phosphate homeostasis is manifested by the largely overlapping phenotypes of Fgf23- and Klotho-deficient mouse models. However, to date, targeted inactivation of FGF receptors (FGFRs) has not provided clear evidence for an analogous function of FGFRs in this process. Here, by means of pharmacologic inhibition of FGFRs, we demonstrate their involvement in renal FGF-23/Klotho signaling and elicit their role in the control of phosphate and vitamin D homeostasis. Specifically, FGFR loss of function counteracts renal FGF-23/Klotho signaling, leading to deregulation of Cyp27b1 and Cyp24a1 and the induction of hypervitaminosis D and hyperphosphatemia. In turn, this initiates a feedback response leading to high serum levels of FGF-23. Further, we show that FGFR inhibition blocks Fgf23 transcription in bone and that this is dominant over vitamin D-induced Fgf23 expression, ultimately impinging on systemic FGF-23 protein levels. Additionally, we identify Fgf23 as a specific target gene of FGF signaling in vitro. Thus, in line with Fgf23- and Klotho-deficient mouse models, our study illustrates the essential function of FGFRs in the regulation of vitamin D and phosphate levels. Further, we reveal FGFR signaling as a novel in vivo control mechanism for Fgf23 expression in bone, suggesting a dual function of FGFRs in the FGF-23/Klotho pathway leading to vitamin D and phosphate homeostasis.

Characterization of the rice PHO1 gene family reveals a key role for OsPHO1;2 in phosphate homeostasis and the evolution of a distinct clade in dicotyledons.

Phosphate homeostasis was studied in a monocotyledonous model plant through the characterization of the PHO1 gene family in rice (Oryza sativa). Bioinformatics and phylogenetic analysis showed that the rice genome has three PHO1 homologs, which cluster with the Arabidopsis (Arabidopsis thaliana) AtPHO1 and AtPHO1;H1, the only two genes known to be involved in root-to-shoot transfer of phosphate. In contrast to the Arabidopsis PHO1 gene family, all three rice PHO1 genes have a cis-natural antisense transcript located at the 5 ' end of the genes. Strand-specific quantitative reverse transcription-PCR analyses revealed distinct patterns of expression for sense and antisense transcripts for all three genes, both at the level of tissue expression and in response to nutrient stress. The most abundantly expressed gene was OsPHO1;2 in the roots, for both sense and antisense transcripts. However, while the OsPHO1;2 sense transcript was relatively stable under various nutrient deficiencies, the antisense transcript was highly induced by inorganic phosphate (Pi) deficiency. Characterization of Ospho1;1 and Ospho1;2 insertion mutants revealed that only Ospho1;2 mutants had defects in Pi homeostasis, namely strong reduction in Pi transfer from root to shoot, which was accompanied by low-shoot and high-root Pi. Our data identify OsPHO1;2 as playing a key role in the transfer of Pi from roots to shoots in rice, and indicate that this gene could be regulated by its cis-natural antisense transcripts. Furthermore, phylogenetic analysis of PHO1 homologs in monocotyledons and dicotyledons revealed the emergence of a distinct clade of PHO1 genes in dicotyledons, which include members having roles other than long-distance Pi transport.

Analysis of teichoic acid biosynthesis regulation reveals that the extracytoplasmic function sigma factor sigmaM is induced by phosphate depletion in Bacillus subtilis W23.

The expression of the Bacillus subtilis W23 tar genes specifying the biosynthesis of the major wall teichoic acid, the poly(ribitol phosphate), was studied under phosphate limitation using lacZ reporter fusions. Three different regulation patterns can be deduced from these beta-galactosidase activity data: (i) tarD and tarL gene expression is downregulated under phosphate starvation; (ii) tarA and, to a minor extent, tarB expression after an initial decrease unexpectedly increases; and (iii) tarO is not influenced by phosphate concentration. To dissect the tarA regulatory pattern, its two promoters were analysed under phosphate limitation: The P(tarA)-ext promoter is repressed under phosphate starvation by the PhoPR two-component system, whereas, under the same conditions, the P(tarA)-int promoter is upregulated by the action of an extracytoplasmic function (ECF) sigma factor, sigma(M). In contrast to strain 168, sigma(M) is activated in strain W23 in phosphate-depleted conditions, a phenomenon indirectly dependent on PhoPR, the two-component regulatory system responsible for the adaptation to phosphate starvation. These results provide further evidence for the role of sigma(M) in cell-wall stress response, and suggest that impairment of cell-wall structure is the signal activating this ECF sigma factor.