SNAI1 and SNAI2 Are Asymmetrically Expressed at the 2-Cell Stage and Become Segregated to the TE in the Mouse Blastocyst

SNAI1 and SNAI2 are transcription factors that initiate Epithelial-to-Mesenchymal cell transitions throughout development and in cancer metastasis. Here we show novel expression of SNAI1 and SNAI2 throughout mouse preimplantation development revealing asymmetrical localization of both SNAI1 and SNAI2 in individual blastomeres beginning at the 2-cell stage through to the 8-cell stage where SNAI1 and SNAI2 are then only detected in outer cells and not inner cells of the blastocyst. This study implicates SNAI1 and SNAI2 in the lineage segregation of the trophectoderm and inner cell mass, and provides new insight into these oncogenes

Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model

<p>Abstract</p> <p>Background</p> <p>The binding of peptide fragments of extracellular peptides to class II MHC is a crucial event in the adaptive immune response. Each MHC allotype generally binds a distinct subset of peptides and the enormous number of possible peptide epitopes prevents their complete experimental characterization. Computational methods can utilize the limited experimental data to predict the binding affinities of peptides to class II MHC.</p> <p>Results</p> <p>We have developed the Regularized Thermodynamic Average, or RTA, method for predicting the affinities of peptides binding to class II MHC. RTA accounts for all possible peptide binding conformations using a thermodynamic average and includes a parameter constraint for regularization to improve accuracy on novel data. RTA was shown to achieve higher accuracy, as measured by AUC, than SMM-align on the same data for all 17 MHC allotypes examined. RTA also gave the highest accuracy on all but three allotypes when compared with results from 9 different prediction methods applied to the same data. In addition, the method correctly predicted the peptide binding register of 17 out of 18 peptide-MHC complexes. Finally, we found that suboptimal peptide binding registers, which are often ignored in other prediction methods, made significant contributions of at least 50% of the total binding energy for approximately 20% of the peptides.</p> <p>Conclusions</p> <p>The RTA method accurately predicts peptide binding affinities to class II MHC and accounts for multiple peptide binding registers while reducing overfitting through regularization. The method has potential applications in vaccine design and in understanding autoimmune disorders. A web server implementing the RTA prediction method is available at <url>http://bordnerlab.org/RTA/</url>.</p

Biotic resistance to invasion along an estuarine gradient

Biotic resistance is the ability of native communities to repel the establishment of invasive species. Predation by native species may confer biotic resistance to communities, but the environmental context under which this form of biotic resistance occurs is not well understood. We evaluated several factors that influence the distribution of invasive Asian mussels (Musculista senhousia) in Mission Bay, a southern California estuary containing an extensive eelgrass (Zostera marina) habitat. Asian mussels exhibit a distinct spatial pattern of invasion, with extremely high densities towards the back of Mission Bay (up to 4,000 m−2) in contrast with near-complete absence at sites towards the front of the bay. We established that recruits arrived at sites where adult mussels were absent and found that dense eelgrass does not appear to preclude Asian mussel growth and survival. Mussel survival and growth were high in predator-exclusion plots throughout the bay, but mussel survival was low in the front of the bay when plots were open to predators. Additional experiments revealed that consumption by spiny lobsters (Panulirus interruptus) and a gastropod (Pteropurpura festiva) likely are the primary factors responsible for resistance to Asian mussel invasion. However, biotic resistance was dependent on location within the estuary (for both species) and also on the availability of a hard substratum (for P. festiva). Our findings indicate that biotic resistance in the form of predation may be conferred by higher order predators, but that the strength of resistance may strongly vary across estuarine gradients and depend on the nature of the locally available habitat

Nonzero |Ue3| from charged lepton corrections and the atmospheric neutrino mixing angle

After the successful determination of the reactor neutrino mixing angle \theta_13 ~ 0.16 \neq 0, a new feature suggested by the current neutrino oscillation data is a sizeable deviation of the atmospheric neutrino mixing angle \theta_23 from \pi/4. Using the fact that the neutrino mixing matrix U = U_e^\dagger U_\nu, where U_e and U_\nu result from the diagonalisation of the charged lepton and neutrino mass matrices, and assuming that U_\nu has a i) bimaximal (BM), ii) tri-bimaximal (TBM) form, or else iii) corresponds to the conservation of the lepton charge L' = L_e - L_\mu - L_\tau (LC), we investigate quantitatively what are the minimal forms of U_e, in terms of angles and phases it contains, that can provide the requisite corrections to U_\nu so that \theta_13, \theta_23 and the solar neutrino mixing angle \theta_12 have values compatible with the current data. Two possible orderings of the 12 and the 23 rotations in U_e, "standard" and "inverse", are considered. The results we obtain depend strongly on the type of ordering. In the case of "standard" ordering, in particular, the Dirac CP violation phase \delta, present in U, is predicted to have a value in a narrow interval around i) \delta ~ \pi in the BM (or LC) case, ii) \delta ~ 3\pi/2 or \pi/2 in the TBM case, the CP conserving values \delta = 0, \pi, 2\pi being excluded in the TBM case at more than 4\sigma

Transmission of Fusarium boothii Mycovirus via Protoplast Fusion Causes Hypovirulence in Other Phytopathogenic Fungi

There is increasing concern regarding the use of fungicides to control plant diseases, whereby interest has increased in the biological control of phytopathogenic fungi by the application of hypovirulent mycoviruses as a possible alternative to fungicides. Transmission of hypovirulence-associated double-stranded RNA (dsRNA) viruses between mycelia, however, is prevented by the vegetative incompatibility barrier that often exists between different species or strains of filamentous fungi. We determined whether protoplast fusion could be used to transmit FgV1-DK21 virus, which is associated with hypovirulence on F. boothii (formerly F. graminearum strain DK21), to F. graminearum, F. asiaticum, F. oxysporum f. sp. lycopersici, and Cryphonectria parasitica. Relative to virus-free strains, the FgV1-DK21 recipient strains had reduced growth rates, altered pigmentation, and reduced virulence. These results indicate that protoplast fusion can be used to introduce FgV1-DK21 dsRNA into other Fusarium species and into C. parasitica and that FgV1-DK21 can be used as a hypovirulence factor and thus as a biological control agent

Predictions for the Leptonic Dirac CP Violation Phase: a Systematic Phenomenological Analysis

We derive predictions for the Dirac phase $\delta$ present in the $3\times 3$ unitary neutrino mixing matrix $U = U_e^{\dagger} \, U_{\nu}$, where $U_e$ and $U_{\nu}$ are $3\times 3$ unitary matrices which arise from the diagonalisation respectively of the charged lepton and the neutrino mass matrices. We consider forms of $U_e$ and $U_{\nu}$ allowing us to express $\delta$ as a function of three neutrino mixing angles, present in $U$, and the angles contained in $U_{\nu}$. We consider several forms of $U_{\nu}$ determined by, or associated with, symmetries, tri-bimaximal, bimaximal, etc., for which the angles in $U_{\nu}$ are fixed. For each of these forms and forms of $U_e$ allowing to reproduce the measured values of the neutrino mixing angles, we construct the likelihood function for $\cos \delta$, using i) the latest results of the global fit analysis of neutrino oscillation data, and ii) the prospective sensitivities on the neutrino mixing angles. Our results, in particular, confirm the conclusion reached in earlier similar studies that the measurement of the Dirac phase in the neutrino mixing matrix, together with an improvement of the precision on the mixing angles, can provide unique information about the possible existence of symmetry in the lepton sector

Sizeable \theta_13 from the Charged Lepton Sector in SU(5), (Tri-)Bimaximal Neutrino Mixing and Dirac CP Violation

The recent results from T2K and MINOS experiments point towards a relatively large value of the reactor angle \theta_13 in the lepton sector. In this paper we show how a large \theta_13 can arise from the charged lepton sector alone in the context of an SU(5) GUT. In such a scenario (tri-)bimaximal mixing in the neutrino sector is still a viable possibility. We also analyse the general implications of the considered scenario for the searches of CP violation in neutrino oscillations.Comment: 19 pages, 3 figures; version to be published in JHE

Proteomics-Based Systems Biology Modeling of Bovine Germinal Vesicle Stage Oocyte and Cumulus Cell Interaction

BACKGROUND: Oocytes are the female gametes which establish the program of life after fertilization. Interactions between oocyte and the surrounding cumulus cells at germinal vesicle (GV) stage are considered essential for proper maturation or 'programming' of oocytes, which is crucial for normal fertilization and embryonic development. However, despite its importance, little is known about the molecular events and pathways involved in this bidirectional communication. METHODOLOGY/PRINCIPAL FINDINGS: We used differential detergent fractionation multidimensional protein identification technology (DDF-Mud PIT) on bovine GV oocyte and cumulus cells and identified 811 and 1247 proteins in GV oocyte and cumulus cells, respectively; 371 proteins were significantly differentially expressed between each cell type. Systems biology modeling, which included Gene Ontology (GO) and canonical genetic pathway analysis, showed that cumulus cells have higher expression of proteins involved in cell communication, generation of precursor metabolites and energy, as well as transport than GV oocytes. Our data also suggests a hypothesis that oocytes may depend on the presence of cumulus cells to generate specific cellular signals to coordinate their growth and maturation. CONCLUSIONS/SIGNIFICANCE: Systems biology modeling of bovine oocytes and cumulus cells in the context of GO and protein interaction networks identified the signaling pathways associated with the proteins involved in cell-to-cell signaling biological process that may have implications in oocyte competence and maturation. This first comprehensive systems biology modeling of bovine oocytes and cumulus cell proteomes not only provides a foundation for signaling and cell physiology at the GV stage of oocyte development, but are also valuable for comparative studies of other stages of oocyte development at the molecular level

Generalised geometrical CP violation in a T' lepton flavour model

We analyse the interplay of generalised CP transformations and the non-Abelian discrete group T \u2032 and use the semi-direct product G f = T \u2032 caH CP, as family symmetry acting in the lepton sector. The family symmetry is shown to be spontaneously broken in a geometrical manner. In the resulting flavour model, naturally small Majorana neutrino masses for the light active neutrinos are obtained through the type I see-saw mechanism. The known masses of the charged leptons, lepton mixing angles and the two neutrino mass squared differences are reproduced by the model with a good accuracy. The model allows for two neutrino mass spectra with normal ordering (NO) and one with inverted ordering (IO). For each of the three spectra the absolute scale of neutrino masses is predicted with relatively small uncertainty. The value of the Dirac CP violation (CPV) phase \u3b4 in the lepton mixing matrix is predicted to be \u3b4 = \u3c0/2 or 3\u3c0/2. Thus, the CP violating effects in neutrino oscillations are predicted to be maximal (given the values of the neutrino mixing angles) and experimentally observable. We present also predictions for the sum of the neutrino masses, for the Majorana CPV phases and for the effective Majorana mass in neutrinoless double beta decay. The predictions of the model can be tested in a variety of ongoing and future planned neutrino experiments