RESUMEN

The approach to ensure food safety (FS) has evolved, including the concept of FS culture, which has been shaped by both the legislation and the scientific literature. In this study, two companies that produce foods associated with potential risks of cross-contamination (gluten-free foods and frozen pastry, respectively) and are certified according to international voluntary FS standards, such as the British Retail Council Global Standard (BRC) and the International Featured Standards Food Version (IFS), were investigated to assess: (a) if the assessment of FS culture's pillars can uncover unexpected critical areas; (b) if the scores of the FS culture's pillars are related to personal traits, namely, age, seniority in the company and locus of control orientation, i.e., the beliefs that an event is the result of external factors (luck, destiny or superior beings), or the result of internal factors (human behavior). Questionnaires for the survey and the scoring system applied were selected from the literature. Results showed that all food handlers had an optimistic bias, which paradoxically could be the consequence of the rigorous application of hygienic procedures. The younger food handlers had significantly (p < 0.05) lower commitment than the older ones. Moreover, the segment of food handlers having an external locus orientation demonstrated weaker normative beliefs than those having an internal locus of control orientation. Results showed that the FS culture survey, which is related to the shared FS culture, could disclose unknown weakness in third-party certified companies, even if the well implemented principles of voluntary FS standards are aligned with the FS-culture pillars. Moreover, the segmentation of food handlers according to their age and the locus of control assessment could provide additional information on the individual orientation toward FS behavior. Hence these tools could assist the leaders in the management of the dynamic nature of human capital.

RESUMEN

Eukaryotic chromosomes compact during mitosis into elongated cylinders-and not the spherical globules expected of self-attracting long flexible polymers. This process is mainly driven by condensin-like proteins. Here, we present Brownian-dynamic simulations involving two types of such proteins with different activities. One, which we refer to as looping condensins, anchors long-lived chromatin loops to create bottlebrush structures. The second, referred to as bridging condensins, forms multivalent bridges between distant parts of these loops. We show that binding of bridging condensins leads to the formation of shorter and stiffer mitotic-like cylinders without requiring any additional energy input. These cylinders have several features matching experimental observations. For instance, the axial condensin backbone breaks up into clusters as found by microscopy, and cylinder elasticity qualitatively matches that seen in chromosome pulling experiments. Additionally, simulating global condensin depletion or local faulty condensin loading gives phenotypes seen experimentally and points to a mechanistic basis for the structure of common fragile sites in mitotic chromosomes.

Asunto(s)

Adenosina Trifosfatasas , Cromosomas , Proteínas de Unión al ADN , Complejos Multiproteicos , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Cromatina/genética , Cromosomas/genética , Cromosomas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Mitosis , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo

RESUMEN

In living cells, the 3D structure of gene loci is dynamic, but this is not revealed by 3C and FISH experiments in fixed samples, leaving a notable gap in our understanding. To overcome these limitations, we applied the highly predictive heteromorphic polymer (HiP-HoP) model to determine chromatin fiber mobility at the Pax6 locus in three mouse cell lines with different transcription states. While transcriptional activity minimally affects movement of 40-kbp regions, we observed that motion of smaller 1-kbp regions depends strongly on local disruption to chromatin fiber structure marked by H3K27 acetylation. This also substantially influenced locus configuration dynamics by modulating protein-mediated promoter-enhancer loops. Importantly, these simulations indicate that chromatin dynamics are sufficiently fast to sample all possible locus conformations within minutes, generating wide dynamic variability within single cells. This combination of simulation and experimental validation provides insight into how transcriptional activity influences chromatin structure and gene dynamics.

Asunto(s)

Cromatina , Cromosomas , Ratones , Animales , Secuencias Reguladoras de Ácidos Nucleicos , Regiones Promotoras Genéticas , Conformación Molecular

RESUMEN

Polymer simulations and predictive mechanistic modelling are increasingly used in conjunction with experiments to study the organization of eukaryotic chromosomes. Here we review some of the most prevalent models for mechanisms which drive different aspects of chromosome organization, as well as a recent simulation scheme which combines several of these mechanisms into a single predictive model. We give some practical details of the modelling approach, as well as review some of the key results obtained by these and similar models in the last few years.

Asunto(s)

Cromosomas , Cromosomas/genética , Simulación por Computador , Eucariontes , Polímeros

RESUMEN

Mammalian chromosomes are three-dimensional entities shaped by converging and opposing forces. Mitotic cell division induces marked chromosome condensation, but following reentry into the G1 phase of the cell cycle, chromosomes reestablish their interphase organization. Here, we tested the role of RNA polymerase II (RNAPII) in this transition using a cell line that allows its auxin-mediated degradation. In situ Hi-C showed that RNAPII is required for both compartment and loop establishment following mitosis. RNAPs often counteract loop extrusion, and in their absence, longer and more prominent loops arose. Evidence from chromatin binding, super-resolution imaging, and in silico modeling allude to these effects being a result of RNAPII-mediated cohesin loading upon G1 reentry. Our findings reconcile the role of RNAPII in gene expression with that in chromatin architecture.

RESUMEN

Braids composed of two interwoven polymer chains exhibit a "buckling" transition whose origin has been explained through the onset of plectonemic structures. Here we study, by a combination of simulation and analytics, the dynamics of plectoneme formation and their statistics in steady state. The introduction of an order parameter-the plectonemic fraction-allows us to map out the phase boundary between the straight-braid phase and the plectonemic one. We then monitor the formation and the growth of plectonemes, observing events typical of phase separation kinetics for liquid-gas systems (fusion, fission, and one-dimensional Ostwald ripening) but also of DNA supercoiling dynamics (plectonemic hopping). Finally, we propose a stochastic field theory for the coupled dynamics of twist and local writhe which explains the phenomenology found with Brownian dynamics simulations as well as the power laws underlying the coarsening of plectonemes.