Spatial patterns and links between microbial community composition and function in cyanobacterial mats

We imaged reflectance and variable fluorescence in 25 cyanobacterial mats from four distant sites around the globe to assess, at different scales of resolution, spatial variabilities in the physiological parameters characterizing their photosynthetic capacity, including the absorptivity by chlorophyll a (Achl), maximum quantum yield of photosynthesis (Ymax), and light acclimation irradiance (Ik). Generally, these parameters significantly varied within individual mats on a sub-millimeter scale, with about 2-fold higher variability in the vertical than in the horizontal direction. The average vertical profiles of Ymax and Ik decreased with depth in the mat, while Achl exhibited a sub-surface maximum. The within-mat variability was comparable to, but often larger than, the between-sites variability, whereas the within-site variabilities (i.e., between samples from the same site) were generally lowest. When compared based on averaged values of their photosynthetic parameters, mats clustered according to their site of origin. Similar clustering was found when the community composition of the mats' cyanobacterial layers were compared by automated ribosomal intergenic spacer analysis (ARISA), indicating a significant link between the microbial community composition and function. Although this link is likely the result of community adaptation to the prevailing site-specific environmental conditions, our present data is insufficient to identify the main factors determining these patterns. Nevertheless, this study demonstrates that the spatial variability in the photosynthetic capacity and light acclimation of benthic phototrophic microbial communities is at least as large on a sub-millimeter scale as it is on a global scale, and suggests that this pattern of variability scaling is similar for the microbial community composition. © 2014 Al-Najjar, Ramette, Kühl, Hamza, Klatt and Polerecky

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

Where the Wild Things Are: Pathogenesis of SIV Infection in African Nonhuman Primate Hosts

African nonhuman primates that are natural hosts of simian immunodeficiency virus (SIV) are generally spared from disease progression. Pathogenic and nonpathogenic SIV infections share some major features: high viral replication, massive acute depletion of mucosal CD4+ T cells, and partial control of the virus by both adaptive and innate immune responses. A key distinction of natural SIV infections is rapid and active control of immune activation and apoptosis of T cells that contributes to the integrity of mucosal barrier and lack of microbial translocation. This allows partial recovery of CD4+ T cells and preservation of the function of other immune cell subsets. A better understanding of the mechanisms underlying the lack of disease in natural hosts for SIV infection will likely provide important clues as to the therapy of HIV-1 infection

Internet-based medical education: a realist review of what works, for whom and in what circumstances

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A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections

The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication

A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy

BACKGROUND: Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1(ADA)-infected NOD.Cg-Prkdc (scid) Il2rg (tm1Wjl)/SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency. At 6 weeks of infection animals were divided into four groups. One received long-acting (LA) cabotegravir (CAB) and rilpivirine (RVP) (2ART), a second received LA CAB, lamivudine, abacavir and RVP (4ART), a third were left untreated and a fourth served as an uninfected control. After 4 weeks of LA ART treatment, blood, spleen and bone marrow (BM) cells were collected then phenotypically characterized. CD4+ T cell subsets, macrophages and hematopoietic progenitor cells were analyzed for HIV-1 nucleic acids by droplet digital PCR. RESULTS: Plasma viral loads were reduced by two log(10) or to undetectable levels in the 2 and 4ART regimens, respectively. Numbers and distributions of CD4+ memory and regulatory T cells, macrophages and hematopoietic progenitor cells were significantly altered by HIV-1 infection and by both ART regimens. ART reduced viral DNA and RNA in all cell and tissue compartments. While memory cells were the dominant T cell reservoir, integrated HIV-1 DNA was also detected in the BM and spleen macrophages in both regimen-treated mice. CONCLUSION: Despite vigorous ART regimens, HIV-1 DNA and RNA were easily detected in mature macrophages supporting their potential role as an infectious viral reservoir. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-017-0344-7) contains supplementary material, which is available to authorized users

Disulfide relays and phosphorylative cascades: Partners in redox-mediated signaling pathways

Modifications of specific amino-acid residues of proteins are fundamental in order to modulate different signaling processes among which the cascade of phosphorylation represents the most effective example. Recently, also, the modification of the redox state of cysteine residues of certain proteins, which is a widespread mechanism in the regulation of protein function, has been proposed to be involved in signaling pathways. Growing evidence shows that some transcription factors could be modulated by both oxidation and phosphorylation. In particular, the pathways regulated by the mitogen activated protein (MAP) kinases represent well-established examples of the cross talk between redox-mediated signaling and phosphorylative cascades. This review will compare the two modes of signal transduction and propose an evolutionary model of a partnership of the two mechanisms in the eukaryotic cell, with redox-mediated signals being more specific and ancestral and phosphorylative signals being more diffuse but predominant in signal propagation. © 2005 Nature Publishing Group All rights reserved

Enhanced Syllable Discrimination Thresholds in Musicians

Speech processing inherently relies on the perception of specific, rapidly changing spectral and temporal acoustic features. Advanced acoustic perception is also integral to musical expertise, and accordingly several studies have demonstrated a significant relationship between musical training and superior processing of various aspects of speech. Speech and music appear to overlap in spectral and temporal features; however, it remains unclear which of these acoustic features, crucial for speech processing, are most closely associated with musical training. The present study examined the perceptual acuity of musicians to the acoustic components of speech necessary for intra-phonemic discrimination of synthetic syllables. We compared musicians and non-musicians on discrimination thresholds of three synthetic speech syllable continua that varied in their spectral and temporal discrimination demands, specifically voice onset time (VOT) and amplitude envelope cues in the temporal domain. Musicians demonstrated superior discrimination only for syllables that required resolution of temporal cues. Furthermore, performance on the temporal syllable continua positively correlated with the length and intensity of musical training. These findings support one potential mechanism by which musical training may selectively enhance speech perception, namely by reinforcing temporal acuity and/or perception of amplitude rise time, and implications for the translation of musical training to long-term linguistic abilities.Grammy FoundationWilliam F. Milton Fun

A randomised trial of intrapericardial bleomycin for malignant pericardial effusion with lung cancer (JCOG9811)

Safety and efficacy of intrapericardial (ipc) instillation of bleomycin (BLM) following pericardial drainage in patients with malignant pericardial effusion (MPE) remain unclear. Patients with pathologically documented lung cancer, who had undergone pericardial drainage for MPE within 72 h of enrolment, were randomised to either arm A (observation alone after drainage) or arm B (ipc BLM at 15 mg, followed by additional ipc BLM 10 mg every 48 h). The drainage tube was removed when daily drainage was 20 ml or less. The primary end point was survival with MPE control (effusion failure-free survival, EFFS) at 2 months. Eighty patients were enrolled, and 79 were eligible. Effusion failure-free survival at 2 months was 29% in arm A and 46% in arm B (one-sided P=0.086 by Fisher's exact test). Arm B tended to favour EFFS, with a hazard ratio of 0.64 (95% confidence interval: 0.40–1.03, one-sided P=0.030 by log-rank test). No significant differences in the acute toxicities or complications were observed. The median survival was 79 days and 119 days in arm A and arm B, respectively. This medium-sized trial failed to show statistical significance in the primary end point. Although ipc BLM appeared safe and effective in the management of MPE, the therapeutic advantage seems modest