Cytokines Elevated in HIV Elite Controllers Reduce HIV Replication In Vitro and Modulate HIV Restriction Factor Expression

A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4+ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects. Four cytokines were elevated in ECs but not NCs or ART subjects: CCL14, CCL21, CCL27, and XCL1. In addition, median stromal cell-derived factor-1 (SDF-1) levels were 43% higher in ECs than in NCs. The combination of the five cytokines suppressed R5 and X4 virus replication in resting CD4+ T cells, and individually SDF-1β, CCL14, and CCL27 suppressed R5 virus replication, while SDF-1β, CCL21, and CCL14 suppressed X4 virus replication. Functional studies revealed that the combination of the five cytokines upregulated CD69 and CCR5 and downregulated CXCR4 and CCR7 on CD4+ T cells. The CD69 and CXCR4 effects were driven by SDF-1, while CCL21 downregulated CCR7. The combination of the EC-associated cytokines induced expression of the anti-HIV host restriction factors IFITM1 and IFITM2 and suppressed expression of RNase L and SAMHD1. These results identify a set of cytokines that are elevated in ECs and define their effects on cellular activation, HIV coreceptor expression, and innate restriction factor expression. This cytokine pattern may be a signature characteristic of HIV-1 elite control, potentially important for HIV therapeutic and curative strategies.IMPORTANCE Approximately 1% of people infected with HIV control virus replication without taking antiviral medications. These subjects, termed elite controllers (ECs), are known to have stronger immune responses targeting HIV than the typical HIV-infected subject, but the exact mechanisms of how their immune responses control infection are not known. In this study, we identified five soluble immune signaling molecules (cytokines) in the blood that were higher in ECs than in subjects with typical chronic HIV infection. We demonstrated that these cytokines can activate CD4+ T cells, the target cells for HIV infection. Furthermore, these five EC-associated cytokines could change expression levels of intrinsic resistance factors, or molecules inside the target cell that fight HIV infection. This study is significant in that it identified cytokines elevated in subjects with a good immune response against HIV and defined potential mechanisms as to how these cytokines could induce resistance to the virus in target cells

Does urbanization explain differences in interactions between an insect herbivore and its natural enemies and mutualists?

Urbanization can alter the composition of arthropod communities. However, little is known about how urbanization affects ecological interactions. Using experimental colonies of the black bean aphid Aphis fabae Scopoli reared on Vicia faba L, we asked if patterns of predator-prey, host-parasitoid and ant-aphid mutualisms varied along an urbanization gradient across a large town in southern England. We recorded the presence of naturally occurring predators, parasitoid wasps and mutualistic ants together with aphid abundance. We examined how biotic (green areas and plant richness) and abiotic features (impervious surfaces and distance to town center) affected (1) aphid colony size, (2) the likelihood of finding predators, mutualistic ants and aphid mummies (indicating the presence of parasitoids), and (3) how the interplay among these factors affected patterns of parasitoid attack, predator abundance, mutualistic interactions and aphid abundance. The best model to predict aphid abundance was the number of mutualistic ants attending the colonies. Aphid predators responded negatively to both the proportion of impervious surfaces and to the number of mutualistic ants farming the colonies, and positively to aphid population size, whereas parasitized aphids were found in colonies with higher numbers of aphids and ants. The number of mutualistic ants attending was positively associated with aphid colony size and negatively with the number of aphid predators. Our findings suggest that for insect-natural enemy interactions, urbanization may affect some groups, while not influencing others, and that local effects (mutualists, host plant presence) will also be key determinants of how urban ecological communities are formed

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

Mobile DNA elements in T4 and related phages

Mobile genetic elements are common inhabitants of virtually every genome where they can exert profound influences on genome structure and function in addition to promoting their own spread within and between genomes. Phage T4 and related phage have long served as a model system for understanding the molecular mechanisms by which a certain class of mobile DNA, homing endonucleases, promote their spread. Homing endonucleases are site-specific DNA endonucleases that initiate mobility by introducing double-strand breaks at defined positions in genomes lacking the endonuclease gene, stimulating repair and recombination pathways that mobilize the endonuclease coding region. In phage T4, homing endonucleases were first discovered as encoded within the self-splicing td, nrdB and nrdD introns of T4. Genomic data has revealed that homing endonucleases are extremely widespread in T-even-like phage, as evidenced by the astounding fact that ~11% of the T4 genome encodes homing endonuclease genes, with most of them located outside of self-splicing introns. Detailed studies of the mobile td intron and its encoded endonuclease, I-TevI, have laid the foundation for genetic, biochemical and structural aspects that regulate the mobility process, and more recently have provided insights into regulation of homing endonuclease function. Here, we summarize the current state of knowledge regarding T4-encoded homing endonucleases, with particular emphasis on the td/I-TevI model system. We also discuss recent progress in the biology of free-standing endonucleases, and present areas of future research for this fascinating class of mobile genetic elements

Land use change alters malaria transmission parameters by modifying temperature in a highland area of Uganda

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73403/1/j.1365-3156.2000.00551.x.pd

Early Emergence of Ethnic Differences in Type 2 Diabetes Precursors in the UK: The Child Heart and Health Study in England (CHASE Study)

Peter Whincup and colleagues carry out a cross-sectional study examining ethnic differences in precursors of of type 2 diabetes among children aged 9–10 living in three UK cities

Tai Chi on psychological well-being: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Physical activity and exercise appear to improve psychological health. However, the quantitative effects of Tai Chi on psychological well-being have rarely been examined. We systematically reviewed the effects of Tai Chi on stress, anxiety, depression and mood disturbance in eastern and western populations.</p> <p>Methods</p> <p>Eight English and 3 Chinese databases were searched through March 2009. Randomized controlled trials, non-randomized controlled studies and observational studies reporting at least 1 psychological health outcome were examined. Data were extracted and verified by 2 reviewers. The randomized trials in each subcategory of health outcomes were meta-analyzed using a random-effects model. The quality of each study was assessed.</p> <p>Results</p> <p>Forty studies totaling 3817 subjects were identified. Approximately 29 psychological measurements were assessed. Twenty-one of 33 randomized and nonrandomized trials reported that 1 hour to 1 year of regular Tai Chi significantly increased psychological well-being including reduction of stress (effect size [ES], 0.66; 95% confidence interval [CI], 0.23 to 1.09), anxiety (ES, 0.66; 95% CI, 0.29 to 1.03), and depression (ES, 0.56; 95% CI, 0.31 to 0.80), and enhanced mood (ES, 0.45; 95% CI, 0.20 to 0.69) in community-dwelling healthy participants and in patients with chronic conditions. Seven observational studies with relatively large sample sizes reinforced the beneficial association between Tai Chi practice and psychological health.</p> <p>Conclusions</p> <p>Tai Chi appears to be associated with improvements in psychological well-being including reduced stress, anxiety, depression and mood disturbance, and increased self-esteem. Definitive conclusions were limited due to variation in designs, comparisons, heterogeneous outcomes and inadequate controls. High-quality, well-controlled, longer randomized trials are needed to better inform clinical decisions.</p

The non-coding transcriptome as a dynamic regulator of cancer metastasis.

Since the discovery of microRNAs, non-coding RNAs (NC-RNAs) have increasingly attracted the attention of cancer investigators. Two classes of NC-RNAs are emerging as putative metastasis-related genes: long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs). LncRNAs orchestrate metastatic progression through several mechanisms, including the interaction with epigenetic effectors, splicing control and generation of microRNA-like molecules. In contrast, snoRNAs have been long considered "housekeeping" genes with no relevant function in cancer. However, recent evidence challenges this assumption, indicating that some snoRNAs are deregulated in cancer cells and may play a specific role in metastasis. Interestingly, snoRNAs and lncRNAs share several mechanisms of action, and might synergize with protein-coding genes to generate a specific cellular phenotype. This evidence suggests that the current paradigm of metastatic progression is incomplete. We propose that NC-RNAs are organized in complex interactive networks which orchestrate cellular phenotypic plasticity. Since plasticity is critical for cancer cell metastasis, we suggest that a molecular interactome composed by both NC-RNAs and proteins orchestrates cancer metastasis. Interestingly, expression of lncRNAs and snoRNAs can be detected in biological fluids, making them potentially useful biomarkers. NC-RNA expression profiles in human neoplasms have been associated with patients' prognosis. SnoRNA and lncRNA silencing in pre-clinical models leads to cancer cell death and/or metastasis prevention, suggesting they can be investigated as novel therapeutic targets. Based on the literature to date, we critically discuss how the NC-RNA interactome can be explored and manipulated to generate more effective diagnostic, prognostic, and therapeutic strategies for metastatic neoplasms