Liquid Polymorphism and Double Criticality in a Lattice Gas Model

We analyze the possible phase diagrams of a simple model for an associating liquid proposed previously. Our two-dimensional lattice model combines oreintati onal ice-like interactions and \"{}Van der Waals\"{} interactions which may be repulsive, and in this case represent a penalty for distortion of hydrogen bonds in the presence of extra molecules. These interactions can be interpreted in terms of two competing distances, but not necessarily soft-core. We present mean -field calculations and an exhaustive simulation study for different parameters which represent relative strength of the bonding interaction to the energy penalty for its distortion. As this ratio decreases, a smooth disappearance of the doubl e criticality occurs. Possible connections to liquid-liquid transitions of molecul ar liquids are suggested

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Modeling the interaction of computer errors by four-valued contaminating logics

Logics based on weak Kleene algebra (WKA) and related structures have been recently proposed as a tool for reasoning about flaws in computer programs. The key element of this proposal is the presence, in WKA and related structures, of a non-classical truth-value that is “contaminating” in the sense that whenever the value is assigned to a formula ϕ, any complex formula in which ϕ appears is assigned that value as well. Under such interpretations, the contaminating states represent occurrences of a flaw. However, since different programs and machines can interact with (or be nested into) one another, we need to account for different kind of errors, and this calls for an evaluation of systems with multiple contaminating values. In this paper, we make steps toward these evaluation systems by considering two logics, HYB1 and HYB2, whose semantic interpretations account for two contaminating values beside classical values 0 and 1. In particular, we provide two main formal contributions. First, we give a characterization of their relations of (multiple-conclusion) logical consequence—that is, necessary and sufficient conditions for a set Δ of formulas to logically follow from a set Γ of formulas in HYB1 or HYB2 . Second, we provide sound and complete sequent calculi for the two logics

Karyotype differentiation in three species of Tripogandra Raf. (Commelinaceae) with different ploidy levels

Most species of the genus Tripogandra (Commelinaceae) are taxonomically poorly circumscribed, in spite of having a relatively stable basic number x = 8. Aiming to estimate the cytological variation among Tripogandra species carrying this base number, several structural karyotypic characters were investigated in the diploid T. glandulosa, the hexaploid T. serrulata, and the octoploid T. diuretica. A careful evaluation of chromosome size and morphology did not reveal clear chromosome homeologies among karyotypes. The mean chromosome size was strongly reduced in the octoploid species, but not in the hexaploid species. They also differed largely in the CMA+ banding pattern and in the number of 5S and 45S rDNA sites per monoploid chromosome complement. All three species showed proximal DAPI + heterochromatin, although in T. serrulata this kind of heterochromatin was only visible after FISH. Further, the meiosis in T. serrulata was highly irregular, suggesting that this species has a hybrid origin. The data indicate that, in spite of the conservation of the base number, these species are karyologically quite different from each other

Minor psychiatric disorders among Brazilian ragpickers: a cross-sectional study

BACKGROUND: Ragpickers are informal workers who collect recyclable materials to earn a small wage. Their life and working conditions are extremely difficult. We examined minor psychiatric disorders (MPD) among a cohort of ragpickers in Pelotas, a city in southern Brazil. METHODS: Ragpickers were matched by sex, age, and years of schooling with a sample of non-ragpickers from the same poor neighborhoods. The cross-sectional study gathered data by interview on 990 individuals in 2004. MPD were assessed using a standard self-reporting questionnaire, the SRQ-20. RESULTS: The prevalence of MPD among ragpickers was 44.7%, higher than reported by neighborhood controls (33.6%; p < 0.001). MPD were more common among females, those of lower economic level, smokers and alcoholics. Among occupational characteristics, MPD prevalence was associated with frequent static postures, low job satisfaction and recent work accidents. CONCLUSION: Ragpickers more frequently report MPD than other poor workers living in the same neighborhoods, with many of the same life conditions. Improving the work lives of these precarious workers should address not only the physical hazards of their jobs but their mental and emotional health as well

HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

BACKGROUND: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naive HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. CONCLUSIONS: Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate

Alkylation of the Tumor Suppressor PTEN Activates Akt and β-Catenin Signaling: A Mechanism Linking Inflammation and Oxidative Stress with Cancer

PTEN, a phosphoinositide-3-phosphatase, serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism. Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation, especially reactive carbonyl species, which are commonly occurring by-products of arachidonic acid peroxidation. Using MCF7 and HEK-293 cells, we report that several reactive aldehydes and ketones, e.g. electrophilic α,β-enals (acrolein, 4-hydroxy-2-nonenal) and α,β-enones (prostaglandin A2, Δ12-prostaglandin J2 and 15-deoxy-Δ-12,14-prostaglandin J2) covalently modify and inactivate cellular PTEN, with ensuing activation of PKB/Akt kinase; phosphorylation of Akt substrates; increased cell proliferation; and increased nuclear β-catenin signaling. Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation, oxidative stress, or aging