Spatial focalization of pheromone/MAPK signaling triggers commitment to cell-cell fusion.

Cell fusion is universal in eukaryotes for fertilization and development, but what signals this process is unknown. Here, we show in Schizosaccharomyces pombe that fusion does not require a dedicated signal but is triggered by spatial focalization of the same pheromone-GPCR (G-protein-coupled receptor)-MAPK signaling cascade that drives earlier mating events. Autocrine cells expressing the receptor for their own pheromone trigger fusion attempts independently of cell-cell contact by concentrating pheromone release at the fusion focus, a dynamic actin aster underlying the secretion of cell wall hydrolases. Pheromone receptor and MAPK cascade are similarly enriched at the fusion focus, concomitant with fusion commitment in wild-type mating pairs. This focalization promotes cell fusion by immobilizing the fusion focus, thus driving local cell wall dissolution. We propose that fusion commitment is imposed by a local increase in MAPK concentration at the fusion focus, driven by a positive feedback between fusion focus formation and focalization of pheromone release and perception

Infertility and hypergonadotropic hypogonadism as first evidence of hereditary apolipoprotein A-I amyloidosis

Purpose: We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein. Materials and Methods: Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene. Results: All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels. Conclusions: Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary

Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing during Yeast Mating.

Cell pairing is central for many processes, including immune defense, neuronal connection, hyphal fusion, and sexual reproduction. How does a cell orient toward a partner, especially when faced with multiple choices? Fission yeast Schizosaccharomyces pombe P and M cells, which respectively express P and M factor pheromones [1, 2], pair during the mating process induced by nitrogen starvation. Engagement of pheromone receptors Map3 and Mam2 [3, 4] with their cognate pheromone ligands leads to activation of the Gα protein Gpa1 to signal sexual differentiation [3, 5, 6]. Prior to cell pairing, the Cdc42 GTPase, a central regulator of cell polarization, forms dynamic zones of activity at the cell periphery at distinct locations over time [7]. Here we show that Cdc42-GTP polarization sites contain the M factor transporter Mam1, the general secretion machinery, which underlies P factor secretion, and Gpa1, suggesting that these are sub-cellular zones of pheromone secretion and signaling. Zone lifetimes scale with pheromone concentration. Computational simulations of pair formation through a fluctuating zone show that the combination of local pheromone release and sensing, short pheromone decay length, and pheromone-dependent zone stabilization leads to efficient pair formation. Consistently, pairing efficiency is reduced in the absence of the P factor protease. Similarly, zone stabilization at reduced pheromone levels, which occurs in the absence of the predicted GTPase-activating protein for Ras, leads to reduction in pairing efficiency. We propose that efficient cell pairing relies on fluctuating local signal emission and perception, which become locked into place through stimulation

Conformal invariance studies of the Baxter-Wu model and a related site-colouring problem

The partition function of the Baxter-Wu model is exactly related to the generating function of a site-colouring problem on a hexagonal lattice. We extend the original Bethe ansatz solution of these models in order to obtain the eigenspectra of their transfer matrices in finite geometries and general toroidal boundary conditions. The operator content of these models are studied by solving numerically the Bethe-ansatz equations and by exploring conformal invariance. Since the eigenspectra are calculated for large lattices, the corrections to finite-size scaling are also calculated.Comment: 12 pages, latex, to appear in J. Phys. A: Gen. Mat

Enumeration of simple random walks and tridiagonal matrices

We present some old and new results in the enumeration of random walks in one dimension, mostly developed in works of enumerative combinatorics. The relation between the trace of the $n$-th power of a tridiagonal matrix and the enumeration of weighted paths of $n$ steps allows an easier combinatorial enumeration of the paths. It also seems promising for the theory of tridiagonal random matrices .Comment: several ref.and comments added, misprints correcte

Renal apolipoprotein A-I amyloidosis: a rare and usually ignored cause of hereditary tubulointerstitial nephritis

12openopenGregorini G; Izzi C; Obici L; Tardanico R; Röcken C; Viola BF; Capistrano M; Donadei S; Biasi L; Scalvini T; Merlini G; Scolari F.Gregorini, G; Izzi, C; Obici, L; Tardanico, R; Röcken, C; Viola, Bf; Capistrano, M; Donadei, S; Biasi, L; Scalvini, T; Merlini, G; Scolari, Francesc

A Dynamic, Distributed Hydrologic Model for the Blue Earth River Watershed, Minnesota With Implications Regarding Land Use and Water Quality

The Blue Earth River (BER) watershed covers approximately one million acres of south-central Minnesota and northern Iowa. Modern farming practices have led to the loss of over 90 percent of the watershed\u27s original wetlands. Corresponding changes in runoff and stream flow have led to dramatically reduced water quality in the BER\u27s main stem following most precipitation events. The purpose of this research is to examine the relationships among precipitation, infiltration, base flow, and runoff in the Blue Earth River watershed basin. This study developed a calibrated numerical hydrologic model for BER watershed using the distributed flow model, Vflo™. The model was developed the seven major runoff events for the 2008 monitoring season (March – June). The research showed the importance of soil depth, hydrologic conductivity, and initial saturation in simulating peak flow volume. Where as overland roughness and channel roughness were found to attenuate the timing of the peak flow volume within the channel. The calibrated model is able to simulate flows where flows have not been observed in the field in both temporal v and spatial dimensions. The model is able to accurately depict the onset of the rising limb event and peak discharges to within ten percent of each event. Results of this research provide a better understanding of the hydrologic regime, prediction of flow rate, depth, and flow-weight total contaminant loads, of the BER watershed. These results therefore provide an objective means for improving best management practices within the Blue Earth River watershed

Critical and off-critical studies of the Baxter-Wu model with general toroidal boundary conditions

The operator content of the Baxter-Wu model with general toroidal boundary conditions is calculated analytically and numerically. These calculations were done by relating the partition function of the model with the generating function of a site-colouring problem in a hexagonal lattice. Extending the original Bethe-ansatz solution of the related colouring problem we are able to calculate the eigenspectra of both models by solving the associated Bethe-ansatz equations. We have also calculated, by exploring the conformal invariance at the critical point, the mass ratios of the underlying massive theory governing the Baxter-Wu model in the vicinity of its critical point.Comment: 32 pages latex, to appear in J. Phys. A: Math. Ge

Proteomic and phosphoproteomic analyses reveal that TORC1 is reactivated by pheromone signaling during sexual reproduction in fission yeast.

Starvation, which is associated with inactivation of the growth-promoting TOR complex 1 (TORC1), is a strong environmental signal for cell differentiation. In the fission yeast Schizosaccharomyces pombe, nitrogen starvation has distinct physiological consequences depending on the presence of mating partners. In their absence, cells enter quiescence, and TORC1 inactivation prolongs their life. In presence of compatible mates, TORC1 inactivation is essential for sexual differentiation. Gametes engage in paracrine pheromone signaling, grow towards each other, fuse to form the diploid zygote, and form resistant, haploid spore progenies. To understand the signaling changes in the proteome and phospho-proteome during sexual reproduction, we developed cell synchronization strategies and present (phospho-)proteomic data sets that dissect pheromone from starvation signals over the sexual differentiation and cell-cell fusion processes. Unexpectedly, these data sets reveal phosphorylation of ribosomal protein S6 during sexual development, which we establish requires TORC1 activity. We demonstrate that TORC1 is re-activated by pheromone signaling, in a manner that does not require autophagy. Mutants with low TORC1 re-activation exhibit compromised mating and poorly viable spores. Thus, while inactivated to initiate the mating process, TORC1 is reactivated by pheromone signaling in starved cells to support sexual reproduction