Comparative effects of some medicinal plants on blood glucose concentration and lipid levels in alloxaninduced diabetic rats

The comparative effects of the chloroform extracts of the leaves of Psidium guajava (Myrtaceae), Anacardium occidentale (Anacardiaceae) and Eucalyptus globulus (Myrtaceae) and fruits of Xylopia aethiopica  (Annonaceae) on blood glucose concentration and lipid levels of diabetic rats were investigated using standard methods. The results show 74, 82 and 83% reductions in the blood glucose concentrations upon the  administration of A. occidentale (100 mg/kg body weight), E. globulus (100mg/kg body weight) and X. aethiopica (250 mg/kg body weight) extracts respectively as from the 10th hour of treatments in relation to the 74 and 69% reductions in glibenclamide and diabetic untreated groups respectively while the synergic treatment group [A. occidentale + E. globulus (100 mg/kg body weight)] showed 83% decrease in the blood glucose  concentration as from the 10th hour upon the administration of the combined extracts when compared with the values obtained for the glibenclamide and diabetic untreated groups. P. guajava extract had the greatest significant (p<0.05) reduction in the total cholesterol concentration of the treated rats. P. guajava + X. aethiopica treatment group in a similar manner showed the most significant (p<0.05) decrease in the triglyceride concentration of the treated rats. Hence, the individual  performances of these extracts on blood glucose concentration and blood lipids confirm their ability to reduce blood glucose and diabetic  complications.Key words: Chloroform extract, Psidium guajava (Myrtaceae), Anacardium occidentale (Anacardiaceae), Eucalyptus globulus (Myrtaceae), Xylopia aethiopica (Annonaceae)

Treg and Oligoclonal Expansion of Terminal Effector CD8+ T Cell as Key Players in Multiple Myeloma

The classical paradigm of host-tumor interaction, i.e. elimination, equilibrium, and escape (EEE), is reflected in the clinical behavior of myeloma which progresses from the premalignant condition, Monoclonal Gammopathy of Unknown Significance (MGUS). Despite the role of other immune cells, CD4+ regulatory T cells (Treg) and cytotoxic CD8+ T cells have emerged as the dominant effectors of host control of the myeloma clone. Progression from MGUS to myeloma is associated with alterations in Tregs and terminal effector CD8+ T cells (TTE). These changes involve CD39 and CD69 expression, affecting the adenosine pathway and residency in the bone marrow (BM) microenvironment, together with oligoclonal expansion within CD8+ TTE cells. In this mini-review article, in the context of earlier data, we summarize our recent understanding of Treg involvement in the adenosine pathway, the significance of oligoclonal expansion within CD8+ TTE cells and BM-residency of CD8+ TTE cells in MGUS and newly diagnosed multiple myeloma patients

Role of orexin A signaling in dietary palmitic acid-activated microglial cells

AbstractExcess dietary saturated fatty acids such as palmitic acid (PA) induce peripheral and hypothalamic inflammation. Hypothalamic inflammation, mediated in part by microglial activation, contributes to metabolic dysregulation. In rodents, high fat diet-induced microglial activation results in nuclear translocation of nuclear factor-kappa B (NFκB), and increased central pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). The hypothalamic neuropeptide orexin A (OXA, hypocretin 1) is neuroprotective in brain. In cortex, OXA can also reduce inflammation and neurodegeneration through a microglial-mediated pathway. Whether hypothalamic orexin neuroprotection mechanisms depend upon microglia is unknown. To address this issue, we evaluated effects of OXA and PA on inflammatory response in immortalized murine microglial and hypothalamic neuronal cell lines. We demonstrate for the first time in microglial cells that exposure to PA increases gene expression of orexin-1 receptor but not orexin-2 receptor. Pro-inflammatory markers IL-6, TNF-α, and inducible nitric oxide synthase in microglial cells are increased following PA exposure, but are reduced by pretreatment with OXA. The anti-inflammatory marker arginase-1 is increased by OXA. Finally, we show hypothalamic neurons exposed to conditioned media from PA-challenged microglia have increased cell survival only when microglia were pretreated with OXA. These data support the concept that OXA may act as an immunomodulatory regulator of microglia, reducing pro-inflammatory cytokines and increasing anti-inflammatory factors to promote a favorable neuronal microenvironment

Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B <em>Streptococcus</em>

ABSTRACT: Several bacterial pathogens decorate their surfaces with sialic acid (Sia) residues within cell wall components or capsular exopolysaccharides. Sialic acid expression can promote bacterial virulence by blocking complement activation or by engagement of inhibitory sialic acid-binding immunoglobulin-like lectins (Siglecs) on host leukocytes. Expressed at high levels on splenic and lymph node macrophages, sialoadhesin (Sn) is a unique Siglec with an elongated structure that lacks intracellular signaling motifs. Sialoadhesin allows macrophage to engage certain sialylated pathogens and stimulate inflammatory responses, but the in vivo significance of sialoadhesin in infection has not been shown. We demonstrate that macrophages phagocytose the sialylated pathogen group B Streptococcus (GBS) and increase bactericidal activity via sialoadhesin-sialic-acid-mediated recognition. Sialoadhesin expression on marginal zone metallophillic macrophages in the spleen trapped circulating GBS and restricted the spread of the GBS to distant organs, reducing mortality. Specific IgM antibody responses to GBS challenge were also impaired in sialoadhesin-deficient mice. Thus, sialoadhesin represents a key bridge to orchestrate innate and adaptive immune defenses against invasive sialylated bacterial pathogens. KEY MESSAGE: Sialoadhesin is critical for macrophages to phagocytose and clear GBS. Increased GBS organ dissemination in the sialoadhesin-deficient mice. Reduced anti-GBS IgM production in the sialoadhesin-deficient mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-014-1157-y) contains supplementary material, which is available to authorized users

Bayesian Methods for Exoplanet Science

Exoplanet research is carried out at the limits of the capabilities of current telescopes and instruments. The studied signals are weak, and often embedded in complex systematics from instrumental, telluric, and astrophysical sources. Combining repeated observations of periodic events, simultaneous observations with multiple telescopes, different observation techniques, and existing information from theory and prior research can help to disentangle the systematics from the planetary signals, and offers synergistic advantages over analysing observations separately. Bayesian inference provides a self-consistent statistical framework that addresses both the necessity for complex systematics models, and the need to combine prior information and heterogeneous observations. This chapter offers a brief introduction to Bayesian inference in the context of exoplanet research, with focus on time series analysis, and finishes with an overview of a set of freely available programming libraries.Comment: Invited revie

Robust estimation of microbial diversity in theory and in practice

Quantifying diversity is of central importance for the study of structure, function and evolution of microbial communities. The estimation of microbial diversity has received renewed attention with the advent of large-scale metagenomic studies. Here, we consider what the diversity observed in a sample tells us about the diversity of the community being sampled. First, we argue that one cannot reliably estimate the absolute and relative number of microbial species present in a community without making unsupported assumptions about species abundance distributions. The reason for this is that sample data do not contain information about the number of rare species in the tail of species abundance distributions. We illustrate the difficulty in comparing species richness estimates by applying Chao's estimator of species richness to a set of in silico communities: they are ranked incorrectly in the presence of large numbers of rare species. Next, we extend our analysis to a general family of diversity metrics ("Hill diversities"), and construct lower and upper estimates of diversity values consistent with the sample data. The theory generalizes Chao's estimator, which we retrieve as the lower estimate of species richness. We show that Shannon and Simpson diversity can be robustly estimated for the in silico communities. We analyze nine metagenomic data sets from a wide range of environments, and show that our findings are relevant for empirically-sampled communities. Hence, we recommend the use of Shannon and Simpson diversity rather than species richness in efforts to quantify and compare microbial diversity.Comment: To be published in The ISME Journal. Main text: 16 pages, 5 figures. Supplement: 16 pages, 4 figure

Low-dose arsenic compromises the immune response to influenza A infection in vivo

This paper is not subject to U.S. copyright. The definitive version was published in Environmental Health Perspectives 117 (2009): 1441–1447, doi:10.1289/ehp.0900911.Arsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week exposure to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components of the innate immune response in mouse lung, which we hypothesize is an important contributor to the increased risk of lung disease in exposed human populations. We investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease. In this study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks, followed by intranasal inoculation with a sublethal dose of influenza A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection. Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 postinfection. We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection. Our data indicate that chronic As exposure significantly compromises the immune response to infection. Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.This work was supported by grant P42 ES007373 from the National Institute of Environmental Health Sciences [J.W.H.; Superfund Basic Research Program (SBRP) Project 2]. C.D.K. was supported by a graduate fellowship from P42 ES007373 (SBRP, Training Core) and by National Institutes of Health predoctoral fellowship T32-DF007301

Signatures of immune selection in intact and defective proviruses distinguish HIV-1 elite controllers

Increasing evidence suggests that durable drug-free control of HIV-1 replication is enabled by effective cellular immune responses that may induce an attenuated viral reservoir configuration with a weaker ability to drive viral rebound. Here, we comprehensively tracked effects of antiviral immune responses on intact and defective proviral sequences from elite controllers (ECs), analyzing both classical escape mutations and HIV-1 chromosomal integration sites as biomarkers of antiviral immune selection pressure. We observed that, within ECs, defective proviruses were commonly located in permissive genic euchromatin positions, which represented an apparent contrast to autologous intact proviruses that were frequently located in heterochromatin regions; this suggests differential immune selection pressure on intact versus defective proviruses in ECs. In comparison to individuals receiving antiretroviral therapy, intact and defective proviruses from ECs showed reduced frequencies of escape mutations in cytotoxic T cell epitopes and antibody contact regions, possibly due to the small and poorly inducible reservoir that may be insufficient to drive effective viral escape in ECs. About 15% of ECs harbored nef deletions in intact proviruses, consistent with increased viral vulnerability to host immunity in the setting of nef dysfunction. Together, these results suggest a distinct signature of immune footprints in proviral sequences from ECs.This work is supported by NIH grants HL134539 (to X.G.Y.), AI155171 (to X.G.Y.), AI116228 (to X.G.Y.), AI078799 (to X.G.Y.), DA047034 (to X.G.Y.), AI150396 (to X.G.Y.), the Bill and Melinda Gates Foundation (INV-002703) (to X.G.Y.), AI114235 (to M.L.), AI117841 (to M.L.), AI120008 (to M.L.), AI130005 (to M.L.), DK120387 (to M.L.), AI152979 (to M.L.), AI135940 (to M.L.), AI155233 (to M.L.), and the American Foundation for AIDS Research (amfAR#110181) (to M.L.). X.G.Y. and M.L. are members of the DARE Collaboratory (UM1AI126611) and the BEAT-HIV Martin Delaney Collaboratory (UM1 AI126620). E.R.-M. was supported by Consejo Superior de Investigaciones Científicas (CSIC) and by grant PI19/01127, Instituto de Salud Carlos III, Fondos FEDER, and Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades Junta de Andalucia (P20_01276). Support was also provided by the Harvard University and University of California at San Francisco (UCSF)/Gladstone Institute for HIV Cure Research Centers for AIDS Research (P30 AI060354 and P30 AI027763, respectively), which are supported by the following institutes and centers co-funded by and participating with the U.S. National Institutes of Health: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR. Additional support for the SCOPE cohort was provided by the Delaney AIDS Research Enterprise (DARE; AI096109 and A127966) and the amfAR Institute for HIV Cure Research (amfAR 109301). The International HIV Controller Cohort is supported by the Bill and Melinda Gates Foundation (OPP1066973), the Ragon Institute of MGH, MIT and Harvard, the NIH (R37 AI067073 to B.D.W.), and the Mark and Lisa Schwartz Family Foundation. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. This research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research