Expectancy-based strategic processes are influenced by spatial working memory load and individual differences in working memory capacity

The present research examined whether imposing a high (or low) working memory (WM) load in different types of nonverbal WM task could affect the implementation of expectancy-based strategic processes in a sequential verbal Stroop task. Participants had to identify a colored target (a red vs. green patch) that was preceded by a prime word (RED or GREEN), which was incongruent with the target color on 80% of the trials, and congruent on 20% of trials. Previous findings have shown that participants can strategically use this information to predict the upcoming target color, and avoid the standard Stroop interference effect. The Stroop task was combined with different types of nonverbal WM task. In Experiment 1, participants had to retain sets of four arrows that pointed either in the same direction (low load) or in different directions (high load). In Experiment 2, they had to remember the spatial locations of four dots which either formed a straight line (low load) or were randomly scattered in a square grid (high load).In addition, participants in the two experiments performed a change localization task to obtain a measure of their WM capacity (WMC). The results in both experiments showed a reliable interaction between prime-target congruency and WM load. When participants performed the Stroop task under high WM load, they were unable to efficiently ignore the incongruence of the prime, as they consistently showed a standard Stroop effect, regardless of their WMC. Under a low WM load, however, a strategy-dependent (reversed Stroop) effect was observed. This ability to ignore the incongruence of the prime was modulated by WMC, such that the reversed Stroop effect was mainly found in higher WMC participants. The findings that expectancy-based strategies on a verbal Stroop task are modulated by load on different types of spatial WM tasks point at a domain-general effect of WM on strategic processing. The present results also suggest that the impact of loading WM on expectancy-based strategies can be modulated by individual differences in WMC

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Epidemiological and genomic investigation of chikungunya virus in Rio de Janeiro state, Brazil, between 2015 and 2018

Since 2014, Brazil has experienced an unprecedented epidemic caused by chikungunya virus (CHIKV), with several waves of East-Central-South-African (ECSA) lineage transmission reported across the country. In 2018, Rio de Janeiro state, the third most populous state in Brazil, reported 41% of all chikungunya cases in the country. Here we use evolutionary and epidemiological analysis to estimate the timescale of CHIKV-ECSA-American lineage and its epidemiological patterns in Rio de Janeiro. We show that the CHIKV-ECSA outbreak in Rio de Janeiro derived from two distinct clades introduced from the Northeast region in mid-2015 (clade RJ1, n = 63/67 genomes from Rio de Janeiro) and mid-2017 (clade RJ2, n = 4/67). We detected evidence for positive selection in non-structural proteins linked with viral replication in the RJ1 clade (clade-defining: nsP4-A481D) and the RJ2 clade (nsP1-D531G). Finally, we estimate the CHIKV-ECSA's basic reproduction number (R0) to be between 1.2 to 1.6 and show that its instantaneous reproduction number (Rt) displays a strong seasonal pattern with peaks in transmission coinciding with periods of high Aedes aegypti transmission potential. Our results highlight the need for continued genomic and epidemiological surveillance of CHIKV in Brazil, particularly during periods of high ecological suitability, and show that selective pressures underline the emergence and evolution of the large urban CHIKV-ECSA outbreak in Rio de Janeiro

The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal, South Africa: A Postmortem Study

A postmortem study by Ted Cohen and colleagues reveals a huge toll of tuberculosis among patients dying in hospitals in KwaZulu-Natal, South Africa

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Growth Arrest of BCR-ABL Positive Cells with a Sequence-Specific Polyamide-Chlorambucil Conjugate

Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model

Immigration, work and health in Spain: the influence of legal status and employment contract on reported health indicators

Objective To analyze the relationship of legal status and employment conditions with health indicators in foreign-born and Spanish-born workers in Spain. Methods Cross-sectional study of 1,849 foreign-born and 509 Spanish-born workers (2008–2009, ITSAL Project). Considered employment conditions: permanent, temporary and no contract (foreign-born and Spanish-born); considered legal statuses: documented and undocumented (foreign-born). Joint relationships with self-rated health (SRH) and mental health (MH) were analyzed via logistical regression. Results When compared with male permanently contracted Spanish-born workers, worse health is seen in undocumented foreign-born, time in Spain ≤3 years (SRH aOR 2.68, 95% CI 1.09–6.56; MH aOR 2.26, 95% CI 1.15–4.42); in Spanish-born, temporary contracts (SRH aOR 2.40, 95% CI 1.04–5.53); and in foreign-born, temporary contracts, time in Spain >3 years (MH: aOR 1.96, 95% CI 1.13–3.38). In females, highest self-rated health risks are in foreign-born, temporary contracts (aOR 2.36, 95% CI 1.13–4.91) and without contracts, time in Spain >3 years (aOR 4.63, 95% CI 1.95–10.97). Conclusions Contract type is a health determinant in both foreign-born and Spanish-born workers. This study offers an uncommon exploration of undocumented migration and raises methodological issues to consider in future research.The study was funded partially by Fondo de Investigaciones Sanitarias [Spanish Fund for Health Research] grant numbers FIS PI050497, PI052334, PI061701

DNA Damage Triggers Genetic Exchange in Helicobacter pylori

Many organisms respond to DNA damage by inducing expression of DNA repair genes. We find that the human stomach pathogen Helicobacter pylori instead induces transcription and translation of natural competence genes, thus increasing transformation frequency. Transcription of a lysozyme-like protein that promotes DNA donation from intact cells is also induced. Exogenous DNA modulates the DNA damage response, as both recA and the ability to take up DNA are required for full induction of the response. This feedback loop is active during stomach colonization, indicating a role in the pathogenesis of the bacterium. As patients can be infected with multiple genetically distinct clones of H. pylori, DNA damage induced genetic exchange may facilitate spread of antibiotic resistance and selection of fitter variants through re-assortment of preexisting alleles in this important human pathogen