Hasil untuk "Genetics"

M. Benarie

C. Fiore, R. Nuti, S. Ortolani

L. Silver

G. Barsh, I. Farooqi, S. O’Rahilly

F. Salamini, H. Özkan, A. Brandolini et al.

S. Page, R. Hawley

K. Clément

Urmzd Mukhammadnaim

Linear Genetic Programming (LGP) is a powerful technique that allows for a variety of problems to be solved using a linear representation of programs. However, there still exists some limitations to the technique, such as the need for humans to explicitly map registers to actions. This thesis proposes a novel approach that uses Q-Learning on top of LGP, Reinforced Linear Genetic Programming (RLGP) to learn the optimal register-action assignments. In doing so, we introduce a new framework "linear-gp" written in memory-safe Rust that allows for extensive experimentation for future works.

A. Zhernakova, C. V. Diemen, C. Wijmenga

M. Handel, J. Schimenti

D. Wallace, W. Fan

Frédéric Marin, Camille Beluffi-Marin, Frédéric Fischer

In the first paper of this series, we included the effects of population genetics in the agent-based Monte Carlo code HERITAGE under the hypothesis of neutral phenotypic effects. It implied that mutations (genetic changes) had only neutral physical manifestations. We now relax this assumption by including genetic effects of mutation and neo-mutations (from radiations) onto the population's life expectancy, fertility, pregnancy chances and miscarriage rates. When applied to a population aboard a generation ship that travels at sub-light speed towards a distant exoplanet, we demonstrate that natural selection indirectly affects the genetic structure of a population via the contribution of phenotypes, in agreement with past studies in conservation biology. For large starting crews (about 500 individuals), the effect aligns with the neutral hypothesis and the frequency of alleles (for non-sexual chromosomes) is stable over centuries. Results are completely different if the spacecraft shielding, integrated into hull design, fails to efficiently protect the crew from high-energy cosmic rays and showers of secondary particles. We tested different scenarios, in which the level of radiation is either fixed at normal or extreme levels, or changing over time due to, e.g., shield degradation, on-board nuclear incident or the outburst of a supernova situated 50 light-years away.

Camila Queraltó, Iván L. Calderón, Isidora Flores et al.

<i>Clostridioides difficile</i> is a Gram-positive bacterium recognized for its ability to produce toxins and form spores. It is mainly accountable for the majority of instances of antibiotic-related diarrhea. <b>Background.</b> Bacterial persister represent a minor fraction of the population that shows temporary tolerance to bactericidal agents, and they pose considerable medical issues because of their link to the rise of antibiotic resistance and challenging chronic or recurrent infections. Our previous research has shown a persister-like phenotype associated with treatments that include pefloxacin. Nonetheless, the mechanism is still mostly unclear, mainly because of the difficulty in isolating this small group of cells. <b>Objectives.</b> To enhance the understanding of <i>C. difficile</i> persister cells, we made an enrichment and characterization of these cells from bacterial cultures during the exponential phase under pefloxacin treatment and lysis treatment. <b>Results.</b> We demonstrate the appearance of cells with lower metabolism and DNA damage. Furthermore, we noted the participation of toxin–antitoxin systems and Clp proteases in the generation of persister cells. <b>Conclusions.</b> This work demonstrates the formation of <i>C. difficile</i> persister cells triggered by a lethal concentration of pefloxacin.

I. Hoppenbrouwers, R. Hintzen

Renato Tinós, Liang Zhao, Francisco Chicano et al.

The NK hybrid genetic algorithm for clustering is proposed in this paper. In order to evaluate the solutions, the hybrid algorithm uses the NK clustering validation criterion 2 (NKCV2). NKCV2 uses information about the disposition of $N$ small groups of objects. Each group is composed of $K+1$ objects of the dataset. Experimental results show that density-based regions can be identified by using NKCV2 with fixed small $K$. In NKCV2, the relationship between decision variables is known, which in turn allows us to apply gray box optimization. Mutation operators, a partition crossover, and a local search strategy are proposed, all using information about the relationship between decision variables. In partition crossover, the evaluation function is decomposed into $q$ independent components; partition crossover then deterministically returns the best among $2^q$ possible offspring with computational complexity $O(N)$. The NK hybrid genetic algorithm allows the detection of clusters with arbitrary shapes and the automatic estimation of the number of clusters. In the experiments, the NK hybrid genetic algorithm produced very good results when compared to another genetic algorithm approach and to state-of-art clustering algorithms.

Marco Gnugnoli, Carlo Rinaldi, Erika Casari et al.

Summary: Homologous recombination is initiated by the nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection is a two-step process. In the short-range step, the MRX (Mre11-Rad50-Xrs2) complex, together with Sae2, incises the 5′-terminated strand at the DSB end and resects back toward the DNA end. Then, the long-range resection nucleases Exo1 and Dna2 further elongate the resected DNA tracts. We found that mutations lowering proteasome functionality bypass the need for Sae2 in DSB resection. In particular, the dysfunction of the proteasome subunit Rpn11 leads to hyper-resection and increases the levels of both Exo1 and Dna2 to such an extent that it allows the bypass of the requirement for either Exo1 or Dna2, but not for both. These observations, along with the finding that Exo1 and Dna2 are ubiquitylated, indicate a role of the proteasome in restraining DSB resection by negatively controlling the abundance of the long-range resection nucleases.

María Domínguez-Ruiz, Silvia Murillo-Cuesta, Julio Contreras et al.

Abstract Inherited hearing impairment is a remarkably heterogeneous monogenic condition, involving hundreds of genes, most of them with very small (< 1%) epidemiological contributions. The exception is GJB2, the gene encoding connexin-26 and underlying DFNB1, which is the most frequent type of autosomal recessive non-syndromic hearing impairment (ARNSHI) in most populations (up to 40% of ARNSHI cases). DFNB1 is caused by different types of pathogenic variants in GJB2, but also by large deletions that keep the gene intact but remove an upstream regulatory element that is essential for its expression. Such large deletions, found in most populations, behave as complete loss-of-function variants, usually associated with a profound hearing impairment. By using CRISPR-Cas9 genetic edition, we have generated a murine model (Dfnb1 em274 ) that reproduces the most frequent of those deletions, del(GJB6-D13S1830). Dfnb1 em274 homozygous mice are viable, bypassing the embryonic lethality of the Gjb2 knockout, and present a phenotype of profound hearing loss (> 90 dB SPL) that correlates with specific structural abnormalities in the cochlea. We show that Gjb2 expression is nearly abolished and its protein product, Cx26, is nearly absent all throughout the cochlea, unlike previous conditional knockouts in which Gjb2 ablation was not obtained in all cell types. The Dfnb1 em274 model recapitulates the clinical presentation of patients harbouring the del(GJB6-D13S1830) variant and thus it is a valuable tool to study the pathological mechanisms of DFNB1 and to assay therapies for this most frequent type of human ARNSHI.

I. Martin, V. Dawson, T. Dawson