Evolution of self-compatibility in Arabidopsis by a mutation in the male specificity gene

Ever since Darwin's pioneering research, the evolution of self-fertilisation (selfing) has been regarded as one of the most prevalent evolutionary transitions in flowering plants. A major mechanism to prevent selfing is the self-incompatibility (SI) recognition system, which consists of male and female specificity genes at the S-locus and SI modifier genes. Under conditions that favour selfing, mutations disabling the male recognition component are predicted to enjoy a relative advantage over those disabling the female component, because male mutations would increase through both pollen and seeds whereas female mutations would increase only through seeds. Despite many studies on the genetic basis of loss of SI in the predominantly selfing plant Arabidopsis thaliana, it remains unknown whether selfing arose through mutations in the female specificity gene (S-receptor kinase, SRK), male specificity gene (S-locus cysteine-rich protein, SCR; also known as S-locus protein 11, SP11) or modifier genes, and whether any of them rose to high frequency across large geographic regions. Here we report that a disruptive 213-base-pair (bp) inversion in the SCR gene (or its derivative haplotypes with deletions encompassing the entire SCR-A and a large portion of SRK-A) is found in 95% of European accessions, which contrasts with the genome-wide pattern of polymorphism in European A. thaliana. Importantly, interspecific crossings using Arabidopsis halleri as a pollen donor reveal that some A. thaliana accessions, including Wei-1, retain the female SI reaction, suggesting that all female components including SRK are still functional. Moreover, when the 213-bp inversion in SCR was inverted and expressed in transgenic Wei-1 plants, the functional SCR restored the SI reaction. The inversion within SCR is the first mutation disrupting SI shown to be nearly fixed in geographically wide samples, and its prevalence is consistent with theoretical predictions regarding the evolutionary advantage of mutations in male components

IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth infection.

Type 2 immune responses are essential in protection against intestinal helminth infections. In this study we show that IL-22, a cytokine important in defence against bacterial infections in the intestinal tract, is also a critical mediator of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite normal levels of type 2 cytokine production. The impaired worm expulsion correlated with reduced goblet cell hyperplasia and reduced expression of goblet cell markers. We further confirmed our findings in a second nematode model, the murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a similar phenotype to that seen in N.brasiliensis infection, with impaired worm expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis demonstrated that IL-22 is able to directly induce the expression of several goblet cell markers, including mucins. Taken together, our findings reveal that IL-22 plays an important role in goblet cell activation, and thus, a key role in anti-helminth immunity

The numerical renormalization group method for quantum impurity systems

In the beginning of the 1970's, Wilson developed the concept of a fully non-perturbative renormalization group transformation. Applied to the Kondo problem, this numerical renormalization group method (NRG) gave for the first time the full crossover from the high-temperature phase of a free spin to the low-temperature phase of a completely screened spin. The NRG has been later generalized to a variety of quantum impurity problems. The purpose of this review is to give a brief introduction to the NRG method including some guidelines of how to calculate physical quantities, and to survey the development of the NRG method and its various applications over the last 30 years. These applications include variants of the original Kondo problem such as the non-Fermi liquid behavior in the two-channel Kondo model, dissipative quantum systems such as the spin-boson model, and lattice systems in the framework of the dynamical mean field theory.Comment: 55 pages, 27 figures, submitted to Rev. Mod. Phy

Metamorphosis of plasma turbulence-shear flow dynamics through a transcritical bifurcation

The structural properties of an economical model for a confined plasma turbulence governor are investigated through bifurcation and stability analyses. A close relationship is demonstrated between the underlying bifurcation framework of the model and typical behavior associated with low- to high-confinement transitions such as shear flow stabilization of turbulence and oscillatory collective action. In particular, the analysis evinces two types of discontinuous transition that are qualitatively distinct. One involves classical hysteresis, governed by viscous dissipation. The other is intrinsically oscillatory and non-hysteretic, and thus provides a model for the so-called dithering transitions that are frequently observed. This metamorphosis, or transformation, of the system dynamics is an important late side-effect of symmetry-breaking, which manifests as an unusual non-symmetric transcritical bifurcation induced by a significant shear flow drive.Comment: 17 pages, revtex text, 9 figures comprised of 16 postscript files. Submitted to Phys. Rev.

Leptogenesis from R parity nonconservation

It is known that realistic neutrino masses for neutrino oscillations may be obtained from R parity nonconserving supersymmetry. It is also known that such interactions would erase any preexisting lepton or baryon asymmetry of the Universe because of the inevitable intervention of the electroweak sphalerons. We now show how a crucial subset of these R parity nonconserving terms may in fact create its own successful leptogenesis.Comment: 4 pages latex file with one postscript figur

Composite quasiparticle formation and the low-energy effective Hamiltonians of the one- and two-dimensional Hubbard Model

We investigate the effect of hole doping on the strong-coupling Hubbard model at half-filling in spatial dimensions $D\ge 1$. We start with an antiferromagnetic mean-field description of the insulating state, and show that doping creates solitons in the antiferromagnetic background. In one dimension, the soliton is topological, spinless, and decoupled from the background antiferromagnetic fluctuations at low energies. In two dimensions and above, the soliton is non-topological, has spin quantum number 1/2, and is strongly coupled to the antiferromagnetic fluctuations. We derive the effective action governing the quasiparticle motion, study the properties of a single carrier, and comment on a possible description at finite concentration.Comment: REVTEX 3.0, 22 pages with 14 figures in the PostScript format compressed using uufile. Submitted to Phys. Rev. B. The complete PostScript file including figures can be obtained via ftp at ftp://serval.berkeley.edu/hubbard.ps . It is also available via www at http://roemer.fys.ku.dk/recent.ht

Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering

<p>Abstract</p> <p>Background</p> <p>Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments.</p> <p>Results</p> <p>We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification.</p> <p>Conclusion</p> <p>We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability analysis. Moreover, the availability of fully automated microfluidic platforms explicitly developed for the task of biochemical model identification will hopefully reduce the effects of the 'data rich-data poor' paradox in Systems Biology.</p

Interleukin 6 increases production of cytokines by colonic innate lymphoid cells in mice and patients with chronic intestinal inflammation

Background & Aims: Innate lymphoid cells (ILCs) are a heterogeneous group of mucosal inflammatory cells that participate in chronic intestinal inflammation. We investigated the role of interleukin 6 (IL6) in inducing activation of ILCs in mice and in human beings with chronic intestinal inflammation. Methods: ILCs were isolated from colons of Tbx21-/- × Rag2-/- mice (TRUC), which develop colitis; patients with inflammatory bowel disease (IBD); and patients without colon inflammation (controls). ILCs were characterized by flow cytometry; cytokine production was measured by enzyme-linked immunosorbent assay and cytokine bead arrays. Mice were given intraperitoneal injections of depleting (CD4, CD90), neutralizing (IL6), or control antibodies. Isolated colon tissues were analyzed by histology, explant organ culture, and cell culture. Bacterial DNA was extracted from mouse fecal samples to assess the intestinal microbiota. Results: IL17A- and IL22-producing, natural cytotoxicity receptor-negative, ILC3 were the major subset of ILCs detected in colons of TRUC mice. Combinations of IL23 and IL1α induced production of cytokines by these cells, which increased further after administration of IL6. Antibodies against IL6 reduced colitis in TRUC mice without significantly affecting the structure of their intestinal microbiota. Addition of IL6 increased production of IL17A, IL22, and interferon-γ by human intestinal CD3-negative, IL7-receptor-positive cells, in a dose-dependent manner. Conclusions: IL6 contributes to activation of colonic natural cytotoxicity receptor-negative, CD4-negative, ILC3s in mice with chronic intestinal inflammation (TRUC mice) by increasing IL23- and IL1α-induced production of IL17A and IL22. This pathway might be targeted to treat patients with IBD because IL6, which is highly produced in colonic tissue by some IBD patients, also increased the production of IL17A, IL22, and interferon-γ by cultured human colon CD3-negative, IL7-receptor-positive cells