Minimization of biosynthetic costs in adaptive gene expression responses of yeast to environmental changes

Yeast successfully adapts to an environmental stress by altering physiology and fine-tuning metabolism. This fine-tuning is achieved through regulation of both gene expression and protein activity, and it is shaped by various physiological requirements. Such requirements impose a sustained evolutionary pressure that ultimately selects a specific gene expression profile, generating a suitable adaptive response to each environmental change. Although some of the requirements are stress specific, it is likely that others are common to various situations. We hypothesize that an evolutionary pressure for minimizing biosynthetic costs might have left signatures in the physicochemical properties of proteins whose gene expression is fine-tuned during adaptive responses. To test this hypothesis we analyze existing yeast transcriptomic data for such responses and investigate how several properties of proteins correlate to changes in gene expression. Our results reveal signatures that are consistent with a selective pressure for economy in protein synthesis during adaptive response of yeast to various types of stress. These signatures differentiate two groups of adaptive responses with respect to how cells manage expenditure in protein biosynthesis. In one group, significant trends towards downregulation of large proteins and upregulation of small ones are observed. In the other group we find no such trends. These results are consistent with resource limitation being important in the evolution of the first group of stress responses.

Isolation and characterization of Saccharomyces cerevisiae mutants resistant to aculeacin A

Aculeacin A is a lipopeptide that inhibits ,B-glucan synthesis in yeasts. A number of Saccharomyces cerevisiae mutants resistant to this antibiotic were isolated, and four loci (ACRI, ACR2, ACR3, and ACR4) whose products are involved in the sensitivity to aculeacin A of yeast ceils were defined. Mutants containing mutations in the four loci were also resistant to echinocandin B, another member of this lipopeptide family of antibiotics. In contrast, acri, acr3, and acr4 mutants were resistant to papulacandin B (an antibiotic containing a disaccharide linked to two fatty acid chains that also inhibits P-glucan synthesis), but acr2 mutants were susceptible'to this antibiotic. This result defines common and specific steps in the entry and action of aculeacin A and papulacandin B. The analysis of double mutants revealed an epistatic effect of the acr2 mutation on the other three mutations. Cell walls of the four different mutants did not show significant alterations in composition with respect to the parental strain, and in vitro glucan synthase activity was also unaffected. However, cell surface hydrophobicity in three of the mutants was considerably decreased with respect to the parental strain.

Health-related quality of life in patients with dual diagnosis: clinical correlates

Background: Although the studies published so far have found an affectation in the Health Related Quality of Life (HRQOL) in both psychiatric and substance use dependence disorders, very few studies have applied HRQOL as an assessment measure in patients suffering both comorbid conditions, or Dual Diagnosis. The aim of the current study was to assess HRQOL in a group of patients with Dual Diagnosis compared to two other non-comorbid groups and to determine what clinical factors are related to HRQOL. Methods: Cross-sectional assessment of three experimental groups was made through the Short Form 36 Item Health Survey (SF-36). The sample consisted of a group with Dual Diagnosis (DD; N=35), one with Severe Mental Illness alone (SMI; N=35) and another one with Substance Use Dependence alone (SUD; N=35). The sample was composed only by males. To assess the clinical correlates of SF-36 HRQOL, lineal regression analyses were carried out. Results: The DD group showed lower scores in most of the subscales, and in the mental health domain. The group with SUD showed in general a better state in the HRQOL while the group with SMI held an intermediate position with respect to the other two groups. Daily medication, suicidal attempts and daily number of coffees were significantly associated to HRQOL, especially in the DD group. Conclusions: The DD group showed lower self-reported mental health quality of life. Assessment of HRQOL in dual patients allows to identify specific needs in this population, and may help to establish therapeutic goals to improve interventions.

The proportional distribution in a cooperative model with external opportunities

[cat] En aquest article es considera un problema de cooperació entre agents on cada agent realitza una contribució (diners, capital, treball, esforç) per tal d'obtenir un benefici comú a repartir. El repartiment proporcional respecte a les contribucions és una distribució que pertany al nucli del joc cooperatiu associat. A partir d'aquest model bàsic s'introdueix un agent extern que pot realitzar una determinada aportació que serveix per avaluar el potencial benefici de cada subcoalició d'agents si aquest nou agent finalment entrés. Aquesta anàlisi pot produir que el poder relatiu dels agents hagi variat. en concret s'avalua si la distribució proporcional és encara robusta des del punt de vista de la seva pertinença al conjunt de negociació. Amb aquest objectiu, analitzem el problema utilitzant el model de joc cooperatius amb estructura de coalició. Donat que, en general, la distribució proporcional, no pertany al conjunt de negociació, s'estudia una condició suficient per a que així sigui. També enunciem una condició necessària, i finalment es proposa una condició suficient que garanteix que el repartiment proporcional és la única distribució existent dins del conjunt de negociació.

The proportional distribution in a cooperative model with external opportunities

[cat] En aquest article es considera un problema de cooperació entre agents on cada agent realitza una contribució (diners, capital, treball, esforç) per tal d'obtenir un benefici comú a repartir. El repartiment proporcional respecte a les contribucions és una distribució que pertany al nucli del joc cooperatiu associat. A partir d'aquest model bàsic s'introdueix un agent extern que pot realitzar una determinada aportació que serveix per avaluar el potencial benefici de cada subcoalició d'agents si aquest nou agent finalment entrés. Aquesta anàlisi pot produir que el poder relatiu dels agents hagi variat. en concret s'avalua si la distribució proporcional és encara robusta des del punt de vista de la seva pertinença al conjunt de negociació. Amb aquest objectiu, analitzem el problema utilitzant el model de joc cooperatius amb estructura de coalició. Donat que, en general, la distribució proporcional, no pertany al conjunt de negociació, s'estudia una condició suficient per a que així sigui. També enunciem una condició necessària, i finalment es proposa una condició suficient que garanteix que el repartiment proporcional és la única distribució existent dins del conjunt de negociació.

Snail blocks the cell cycle and confers resistance to cell death

The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the expression of mesenchymal markers. Here, we show that in addition to inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and confers resistance to cell death induced by the withdrawal of survival factors and by pro-apoptotic signals. Hence, Snail favors changes in cell shape versus cell division, indicating that with respect to oncogenesis, although a deregulation/increase in proliferation is crucial for tumor formation and growth, this may not be so for tumor malignization. Finally, the resistance to cell death conferred by Snail provides a selective advantage to embryonic cells to migrate and colonize distant territories, and to malignant cells to separate from the primary tumor, invade, and form metastasis.

A Cartan-Eilenberg approach to Homotopical Algebra

In this paper we propose an approach to homotopical algebra where the basic ingredient is a category with two classes of distinguished morphisms: strong and weak equivalences. These data determine the cofibrant objects by an extension property analogous to the classical lifting property of projective modules. We define a Cartan-Eilenberg category as a category with strong and weak equivalences such that there is an equivalence of categories between its localisation with respect to weak equivalences and the relative localisation of the subcategory of cofibrant objects with respect to strong equivalences. This equivalence of categories allows us to extend the classical theory of derived additive functors to this non additive setting. The main examples include Quillen model categories and categories of functors defined on a category endowed with a cotriple (comonad) and taking values on a category of complexes of an abelian category. In the latter case there are examples in which the class of strong equivalences is not determined by a homotopy relation. Among other applications of our theory, we establish a very general acyclic models theorem.