Phenotypic and functional characteristics of highly differentiated CD57 +NKG2C + NK cells in HIV-1- infected individuals

Natural killer (NK) cells are important anti-viral effector cells. The function and phenotype of the NK cells that constitute an individual’s NK cell repertoire can be influenced by ongoing and/or previous viral infections. Indeed, infection with human cytomegalovirus (HCMV) drives the expansion of a highly differentiated NK cell population characterized by expression of CD57 and the activating NKG2C receptor. This NK cell population has also been noted to occur in HIV-1-infected individuals. We evaluated the NK cells of HIV-1-infected and –uninfected individuals to determine the relative frequency of highly differentiated CD57 +NKG2C + NK cells and characterize these cells for their receptor expression and responsiveness to diverse stimuli. Highly differentiated CD57 +NKG2C + NK cells occurred at higher frequencies in HCMV-infected donors relative to HCMV-uninfected donors and were dramatically expanded in HIV-1/HCMV co-infected donors. The expanded CD57 +NKG2C + NK cell population in HIV-1-infected donors remained stable following antiretroviral therapy. CD57 +NKG2C + NK cells derived from HIV-1-infected individuals were robustly activated by antibody-dependent stimuli that contained anti-HIV-1 antibodies or therapeutic anti-CD20 antibody, and these NK cells mediated cytolysis through NKG2C. Lastly, CD57 +NKG2C + NK cells from HIV-1-infected donors were characterized by reduced expression of the inhibitory NKG2A receptor. The abundance of highly functional CD57 +NKG2C + NK cells in HIV-1-infected individuals raises the possibility that these NK cells could play a role in HIV-1 pathogenesis or serve as effector cells for therapeutic/cure strategies

Non-song vocalizations of pygmy blue whales in Geographe Bay, Western Australia.

Non-song vocalizations of migrating pygmy blue whales (Balaenoptera musculus brevicauda) in Western Australia are described. Simultaneous land-based visual observations and underwater acoustic recordings detected 27 groups in Geographe Bay, WA over 2011 to 2012. Six different vocalizations were recorded that were not repeated in a pattern or in association with song, and thus were identified as non-song vocalizations. Five of these were not previously described for this population. Their acoustic characteristics and context are presented. Given that 56% of groups vocalized, 86% of which produced non-song vocalizations and 14% song units, the inclusion of non-song vocalizations in passive-acoustic monitoring is proposed

Availability of the THERMIT thermal hydraulic reactor computer codes through M.I.T.

Cover titleStatement of responsibility on title reads: D. Kent Parsons, Neil E. Todreas, Mujid S. Kazimi, David D. Lanning"April 1981."Includes bibliographical references (pages 19-21)Three of the THERMIT thermal hydraulic reactor computer codes are available through the Department of Nuclear Engineering at MIT. The three available codes are THERMIT-2, for LWR subchannel analysis, THIOD, for BWR analysis and NATOF-2D, for LMFBR sodium boiling analysis. Descriptive summaries and sample results are given for each code. In addition, a list of THERMIT references is given

An Introduction to the THERMIT thermal hydraulic reactor computer codes at M.I.T.

Cover titleStatement of responsibility on title reads: D. Kent Parsons, Neil E. Todreas, Mujid S. Kazimi, David D. Lanning"April 1981."Includes bibliographical references (pages 29-31)The THERMIT thermal hydraulic reactor computer codes developed at MIT are described. The codes include THERMIT-2, THIOD, NATOF-2D, THERMIT-3, THERMIT-2D-PLENUM, THERFLIBE, THERLIT, THERMIT (sodium) and THERMIT-SIEX. Descriptive code summaries and sample code results from each THERMIT version are given. Finally, a complete THERMIT bibliography is presented

Improving conservation practice with principles and tools from systems thinking and evaluation

Achieving nature conservation goals require grappling with ‘wicked’ problems. These intractable problems arise from the complexity and dynamism of the social–ecological systems in which they are embedded. To enhance their ability to address these problems, conservation professionals are increasingly looking to the transdisciplines of systems thinking and evaluation, which provide philosophies, theories, methods, tools and approaches that show promise for addressing intractable problems in a variety of other sectors. These transdisciplines come together especially around praxis, i.e., the process by which a theory or idea is enacted, embodied or realized. We present a review and synthesis of the learnings about praxis that have emerged from The Silwood Group, a consortium of conservation professionals, professional evaluators, and complexity and systems thinkers. The Silwood Group believes that for conservation activities to achieve ambitious goals, we should benefit nature without compromising the well-being of people, and that framing a praxis for conservation in the context of social–ecological systems will provide the greatest potential for positive impact. The learnings are presented as four key principles of a ‘praxis for effective conservation’. The four principles are: (1) attend to the whole with humility; (2) engage constructively with the values, cultures, politics, and histories of stakeholders; (3) learn through evaluative, systemic enquiry, and (4) exercise wisdom in judgement and action. We also provide descriptions and references for tools and methods to support such praxis and discuss how the thinking and approaches used by conservation professionals can be transformed to achieve greater effectiveness

Influence of Cytokines on HIV-Specific Antibody-Dependent Cellular Cytotoxicity Activation Profile of Natural Killer Cells

There is growing interest in HIV-specific antibody-dependent cellular cytotoxicity (ADCC) as an effective immune response to prevent or control HIV infection. ADCC relies on innate immune effector cells, particularly NK cells, to mediate control of virus-infected cells. The activation of NK cells (i.e., expression of cytokines and/or degranulation) by ADCC antibodies in serum is likely subject to the influence of other factors that are also present. We observed that the HIV-specific ADCC antibodies, within serum samples from a panel of HIV-infected individuals induced divergent activation profiles of NK cells from the same donor. Some serum samples primarily induced NK cell cytokine expression (i.e., IFNγ), some primarily initiated NK cell expression of a degranulation marker (CD107a) and others initiated a similar magnitude of responses across both effector functions. We therefore evaluated a number of HIV-relevant soluble factors for their influence on the activation of NK cells by HIV-specific ADCC antibodies. Key findings were that the cytokines IL-15 and IL-10 consistently enhanced the ability of NK cells to respond to HIV-specific ADCC antibodies. Furthermore, IL-15 was demonstrated to potently activate “educated” KIR3DL1+ NK cells from individuals carrying its HLA-Bw4 ligand. The cytokine was also demonstrated to activate “uneducated” KIR3DL1+ NK cells from HLA-Bw6 homozygotes, but to a lesser extent. Our results show that cytokines influence the ability of NK cells to respond to ADCC antibodies in vitro. Manipulating the immunological environment to enhance the potency of NK cell-mediated HIV-specific ADCC effector functions could be a promising immunotherapy or vaccine strategy

Use of a Molecular Diagnostic Test in AFB Smear Positive Tuberculosis Suspects Greatly Reduces Time to Detection of Multidrug Resistant Tuberculosis

Background: The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB). There are limited data on the performance and impact of these tests in field settings. Methods: The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST) using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program. Results: Among 500 AFB smear-positive sputum specimens, 458 (91.6%) had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH) resistanc

Network of Cancer Genes: a web resource to analyze duplicability, orthology and network properties of cancer genes

The Network of Cancer Genes (NCG) collects and integrates data on 736 human genes that are mutated in various types of cancer. For each gene, NCG provides information on duplicability, orthology, evolutionary appearance and topological properties of the encoded protein in a comprehensive version of the human protein-protein interaction network. NCG also stores information on all primary interactors of cancer proteins, thus providing a complete overview of 5357 proteins that constitute direct and indirect determinants of human cancer. With the constant delivery of results from the mutational screenings of cancer genomes, NCG represents a versatile resource for retrieving detailed information on particular cancer genes, as well as for identifying common properties of precompiled lists of cancer genes. NCG is freely available at: http://bio.ifom-ieo-campus.it/ncg