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Author |
Peris, J.B.; Davis, P.; Cuevas, J.M.; Nebot, M.; Sanjuan, R. |
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Title |
Distribution of Fitness Effects Caused by Single-Nucleotide Substitutions in Bacteriophage f1 |
Type |
Journal Article |
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Year |
2010 |
Publication |
Genetics |
Abbreviated Journal |
Genetics |
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Volume |
185 |
Issue |
2 |
Pages |
603-U308 |
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Keywords |
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Abstract |
Empirical knowledge of the fitness effects of mutations is important for understanding many evolutionary processes, yet this knowledge is often hampered by several sources of measurement error and bias. Most of these problems can be solved using site-directed mutagenesis to engineer single mutations, an approach particularly suited for viruses due to their small genomes. Here, we used this technique to measure the fitness effect of 100 single-nucleotide substitutions in the bacteriophage f1, a filamentous single-strand DNA virus. We found that approximately one-fifth of all mutations are lethal. Viable ones reduced fitness by 11% on average and were accurately described by a log-normal distribution. More than 90% of synonymous substitutions were selectively neutral, while those affecting intergenic regions reduced fitness by 14% on average. Mutations leading to amino acid substitutions had an overall mean deleterious effect of 37%, which increased to 45% for those changing the amino acid polarity. Interestingly, mutations affecting early steps of the infection cycle tended to be more deleterious than those affecting late steps. Finally, we observed at least two beneficial mutations. Our results confirm that high mutational sensitivity is a general property of viruses with small genomes, including RNA and single-strand DNA viruses infecting animals, plants, and bacteria. |
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Address |
[Peris, Joan B.; Davis, Paulina; Cuevas, Jose M.; Sanjuan, Rafael] Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolut, Valencia 46980, Spain, Email: rafael.sanjuan@uv.es |
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Publisher |
Genetics Soc Am |
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Language |
English |
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ISSN |
0016-6731 |
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Conference |
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Notes |
ISI:000281905200017 |
Approved |
no |
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Is ISI |
yes |
International Collaboration  |
no |
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Call Number |
IFIC @ elepoucu @ |
Serial |
383 |
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Author |
Sanjuan, R.; Nebot, M.; Peris, J.B.; Alcami, J. |
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Title |
Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1 |
Type |
Journal Article |
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Year |
2013 |
Publication |
Plos Biology |
Abbreviated Journal |
PLoS. Biol. |
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Volume |
11 |
Issue |
4 |
Pages |
e1001523 - 10pp |
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Keywords |
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Abstract |
The immune system should constitute a strong selective pressure promoting viral genetic diversity and evolution. However, HIV shows lower sequence variability at T-cell epitopes than elsewhere in the genome, in contrast with other human RNA viruses. Here, we propose that epitope conservation is a consequence of the particular interactions established between HIV and the immune system. On one hand, epitope recognition triggers an anti-HIV response mediated by cytotoxic T-lymphocytes (CTLs), but on the other hand, activation of CD4(+) helper T lymphocytes (T-H cells) promotes HIV replication. Mathematical modeling of these opposite selective forces revealed that selection at the intrapatient level can promote either T-cell epitope conservation or escape. We predict greater conservation for epitopes contributing significantly to total immune activation levels (immunodominance), and when T-H cell infection is concomitant to epitope recognition (transinfection). We suggest that HIV-driven immune activation in the lymph nodes during the chronic stage of the disease may offer a favorable scenario for epitope conservation. Our results also support the view that some pathogens draw benefits from the immune response and suggest that vaccination strategies based on conserved T-H epitopes may be counterproductive. |
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Address |
Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolut, Valencia, Spain, Email: rafael.sanjuan@uv.es |
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Publisher |
Public Library Science |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
1545-7885 |
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Area |
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Conference |
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Notes |
WOS:000318687800003 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
no |
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Call Number |
IFIC @ pastor @ |
Serial |
1446 |
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Author |
Bernabeu, J.; Botella, F.J.; Nebot, M. |
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Title |
Novel T-Violation observable open to any pair of decay channels at meson factories |
Type |
Journal Article |
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Year |
2014 |
Publication |
Physics Letters B |
Abbreviated Journal |
Phys. Lett. B |
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Volume |
728 |
Issue |
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Pages |
95-98 |
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Keywords |
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Abstract |
Quantum entanglement between the two neutral mesons produced in meson factories has allowed the first indisputable direct observation of Time Reversal Violation in the time evolution of the neutral meson between the two decays. The exceptional meson transitions are directly connected to semileptonic and CP eigenstate decay channels. The possibility of extending the observable asymmetries to more decay channels confronts the problem of the “orthogonality condition”, which can be stated with this tonguetwister: Given a decay channel f, which is the decay channel f' such that the meson state not decaying to f is orthogonal to the meson state not decaying to f? In this Letter we propose an alternative T-Violation asymmetry at meson factories which allows its opening to any pair of decay channels. Instead of searching which is the pair of decay channels associated to the T-reverse meson transition, we build an asymmetry which tags the initial states of both the Reference and the T-reverse meson transitions. This observable filters the appropriate final states by means of two measurable survival probabilities. We discuss the methodology to be followed in the analysis of the new observable and the results expected in specific examples. |
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Address |
[Nebot, Miguel] Univ Valencia, Dept Fis Teor, CSIC, E-46100 Burjassot, Spain, Email: Jose.Bernabeu@uv.es; |
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Publisher |
Elsevier Science Bv |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
0370-2693 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
WOS:000330556000017 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
no |
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Call Number |
IFIC @ pastor @ |
Serial |
1705 |
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Author |
Bernabeu, J.; Botella, F.J.; Nebot, M. |
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Title |
Genuine T, CP, CPT asymmetry parameters for the entangled B-d system |
Type |
Journal Article |
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Year |
2016 |
Publication |
Journal of High Energy Physics |
Abbreviated Journal |
J. High Energy Phys. |
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Volume |
06 |
Issue |
6 |
Pages |
100 - 24pp |
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Keywords |
Discrete Symmetries; Space-Time Symmetries |
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Abstract |
The precise connection between the theoretical T, CP, CPT asymmetries, in terms of transition probabilities between the filtered neutral meson B-d states, and the experimental asymmetries, in terms of the double decay rate intensities for Flavour-CP eigenstate decay products in a B-d-factory of entangled states, is established. This allows the identification of genuine Asymmetry Parameters in the time distribution of the asymmetries and their measurability by disentangling genuine and possible fake terms. We express the nine asymmetry parameters three different observables for each one of the three symmetries in terms of the ingredients of the Weisskopf-Wigner dynamical description of the entangled B-d-meson states and we obtain a global fit to their values from the BaBar collaboration experimental results. The possible fake terms are all compatible with zero and the information content of the nine asymmetry parameters is indeed different. The non -vanishing Delta l(c)(T) = 0.687 +/- 0.020 and Delta l(c)(CP) = 0.680 +/- 0.021 are impressive separate direct evidence of Time -Reversal -violation and CP-violation in these transitions and compatible with Standard Model expectations. An intriguing 2 sigma effect for the Re(theta) parameter responsible of CPT -violation appears which, interpreted as an upper limit, leads to vertical bar M (B) over baro (B) over baro vertical bar MBoBo < 4.0 x 10(-5) eV at 95% C.L. for the diagonal flavour terms of the mass matrix. It contributes to the CP-violating Delta l(c)(CP) asymmetry parameter in an unorthodox manner – in its cos(Delta M t) time dependence-, and it is accessible in facilities with non-entangled B-d's, like the LHCb experiment. |
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Address |
[Bernabeu, Jose] Univ Valencia, Dept Fis Teor, E-46100 Valencia, Spain, Email: Jose.Bernabeu@uv.es; |
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Corporate Author |
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Thesis |
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Publisher |
Springer |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
1029-8479 |
ISBN |
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Conference |
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Notes |
WOS:000379028400001 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
no |
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Call Number |
IFIC @ pastor @ |
Serial |
2752 |
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Author |
Bernabeu, J.; Botella, F.J.; Nebot, M.; Segarra, A. |
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Title |
B-0 – (B)over-bar(0) entanglement for an ideal experiment for the direct CP violation phi(3)/gamma phase |
Type |
Journal Article |
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Year |
2022 |
Publication |
Physical Review D |
Abbreviated Journal |
Phys. Rev. D |
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Volume |
106 |
Issue |
5 |
Pages |
054026 - 7pp |
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Keywords |
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Abstract |
B-0-(B) over bar0 entanglement offers a conceptual alternative to the single charged B-decay asymmetry for the measurement of the direct CP-violating gamma/phi(3) phase. With f = J/Psi(L); J/Psi K-S and g = (pi pi)(0); (rho(L)rho(L))(0), the 16 time-ordered double-decay rate intensities to (f, g) depend on the relative phase between the f- and g-decay amplitudes given by gamma at tree level. Several constraining consistencies appear. An intrinsic accuracy of the method at the level of +/- 1 degrees could be achievable at Belle-II with an improved determination of the penguin amplitude to g channels from existing facilities. |
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Address |
[Bernabeu, Jose; Botella, Francisco J.; Nebot, Miguel] Univ Valencia, Dept Theoret Phys, Valencia 46100, Spain |
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Corporate Author |
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Thesis |
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Publisher |
Amer Physical Soc |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
2470-0010 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
WOS:000882839300002 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
no |
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Call Number |
IFIC @ pastor @ |
Serial |
5406 |
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