Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vivo Activation of Human NK Cells by Treatment with an Interleukin-15 Superagonist Potently Inhibits Acute In Vivo HIV-1 Infection in Humanized Mice

ABSTRACT Natural killer (NK) cells with anti-HIV-1 activity may inhibit HIV-1 replication and dissemination during acute HIV-1 infection. We hypothesized that the capacity of NK cells to suppress acute in vivo HIV-1 infection would be augmented by activating them via treatment with an interleukin-15 (IL-15) superagonist, IL-15 bound to soluble IL-15Rα, an approach that potentiates human NK cell-mediated killing of tumor cells. In vitro stimulation of human NK cells with a recombinant IL-15 superagonist significantly induced their expression of the cytotoxic effector molecules granzyme B and perforin; their degranulation upon exposure to K562 cells, as indicated by cell surface expression of CD107a; and their capacity to lyse K562 cells and HIV-1-infected T cells. The impact of IL-15 superagonist-induced activation of human NK cells on acute in vivo HIV-1 infection was investigated by using hu-spl-PBMC-NSG mice, NOD-SCID-IL2rγ−/− (NSG) mice intrasplenically injected with human peripheral blood mononuclear cells (PBMCs) which develop productive in vivo infection after intrasplenic inoculation with HIV-1. IL-15 superagonist treatment potently inhibited acute HIV-1 infection in hu-spl-PBMC-NSG mice even when delayed until 3 days after intrasplenic HIV-1 inoculation. Removal of NK cells from human PBMCs prior to intrasplenic injection into NSG mice completely abrogated IL-15 superagonist-mediated suppression of in vivo HIV-1 infection. Thus, the in vivo activation of NK cells, integral mediators of the innate immune response, by treatment with an IL-15 superagonist increases their anti-HIV activity and enables them to potently suppress acute in vivo HIV-1 infection. These results indicate that in vivo activation of NK cells may represent a new immunotherapeutic approach to suppress acute HIV-1 infection. IMPORTANCE Epidemiological studies have indicated that NK cells contribute to the control of HIV-1 infection, and in vitro studies have demonstrated that NK cells can selectively kill HIV-1-infected cells. We demonstrated that in vivo activation of NK cells by treatment with an IL-15 superagonist that potently stimulates the antitumor activity of NK cells markedly inhibited acute HIV-1 infection in humanized mice, even when activation of NK cells by IL-15 superagonist treatment is delayed until 3 days after HIV-1 inoculation. NK cell depletion from PBMCs prior to their intrasplenic injection abrogated the suppression of in vivo HIV-1 infection observed in humanized mice treated with the IL-15 superagonist, demonstrating that activated human NK cells were mediating IL-15 superagonist-induced inhibition of acute HIV-1 infection. Thus, in vivo immunostimulation of NK cells, a promising therapeutic approach for cancer therapy, may represent a new treatment modality for HIV-1-infected individuals, particularly in the earliest stages of infection.
Simian Immunodeficiency Virus SIVagm from African Green Monkeys Does Not Antagonize Endogenous Levels of African Green Monkey Tetherin/BST-2

ABSTRACT The Vpu accessory gene that originated in the primate lentiviral lineage leading to human immunodeficiency virus type 1 is an antagonist of human tetherin/BST-2 restriction. Most other primate lentivirus lineages, including the lineage represented by simian immunodeficiency virus SIVagm from African green monkeys (AGMs), do not encode Vpu. While some primate lineages encode gene products other than Vpu that overcome tetherin/BST-2, we find that SIVagm does not antagonize physiologically relevant levels of AGM tetherin/BST-2. AGM tetherin/BST-2 can be induced by low levels of type I interferon and can potently restrict two independent strains of SIVagm. Although SIVagm Nef had an effect at low levels of AGM tetherin/BST-2, simian immunodeficiency virus SIVmus Vpu, from a virus that infects the related monkey Cercopithecuscephus, is able to antagonize even at high levels of AGM tetherin/BST-2 restriction. We propose that since the replication of SIVagm does not induce interferon production in vivo, tetherin/BST-2 is not induced, and therefore, SIVagm does not need Vpu. This suggests that primate lentiviruses evolve tetherin antagonists such as Vpu or Nef only if they encounter tetherin during the typical course of natural infection.
Sperm Morphology and Natural Biomolecules from Marine Snail Telescopium telescopium: a Phylogenetic Perspective

El analisis bioquimico de la fraccion aislada del citosol desde las glandulas ovotestes/espermateca del molusco marino Telescopium telescopium y su estructura tubular espermatica revelaron biomoleculas relativamente similares como tales como diferentes enzimas, hormonas, minerales y estructuras de los espermatozoides que tambien existen en los seres humanos. Por otra parte, en el antisuero de la fraccion citosolica se encontro una reaccion cruzada con los antigenos del esperma humano indicando la presencia de una superficie espermatica de antigenicidad comun entre estas dos diversificadas especies. Estos hallazgos pueden apoyar y/o hipotetizar sobre el origen y la diversificacion de las moleculas de los vertebrados desde su forma (s) ancestral desde los invertebrados, y funciones basicas fisiologicas de estas biomoleculas ancestrales incluyendo algunas de las estructuras celulares siendo plausiblemente las mismas, independientemente de sus cambios estructurales incluso despues de la evolucion.
Diverging Affinity of Tospovirus RNA Silencing Suppressor Proteins, NSs, for Various RNA Duplex Molecules

ABSTRACT The tospovirus NSs protein was previously shown to suppress the antiviral RNA silencing mechanism in plants. Here the biochemical analysis of NSs proteins from different tospoviruses, using purified NSs or NSs containing cell extracts, is described. The results showed that all tospoviral NSs proteins analyzed exhibited affinity to small double-stranded RNA molecules, i.e., small interfering RNAs (siRNAs) and micro-RNA (miRNA)/miRNA* duplexes. Interestingly, the NSs proteins from tomato spotted wilt virus (TSWV), impatiens necrotic spot virus (INSV), and groundnut ringspot virus (GRSV) also showed affinity to long double-stranded RNA (dsRNA), whereas tomato yellow ring virus (TYRV) NSs did not. The TSWV NSs protein was shown to be capable of inhibiting Dicer-mediated cleavage of long dsRNA in vitro. In addition, it suppressed the accumulation of green fluorescent protein (GFP)-specific siRNAs during coinfiltration with an inverted-repeat-GFP RNA construct in Nicotiana benthamiana. In vivo interference of TSWV NSs in the miRNA pathway was shown by suppression of an enhanced GFP (eGFP) miRNA sensor construct. The ability to stabilize miRNA/miRNA* by different tospovirus NSs proteins in vivo was demonstrated by increased accumulation and detection of both miRNA171c and miRNA171c* in tospovirus-infected N. benthamiana. All together, these data suggest that tospoviruses interfere in the RNA silencing pathway by sequestering siRNA and miRNA/miRNA* molecules before they are uploaded into their respective RNA-induced silencing complexes. The observed affinity to long dsRNA for only a subset of the tospoviruses studied is discussed in light of evolutional divergence and their ancestral relation to the animal-infecting members of the Bunyaviridae.
Evolution of the Global Tobacco Surveillance System (GTSS) 1998–2008

Tobacco use is one of the leading preventable causes of morbidity and mortality worldwide. Given that country-specific international data on tobacco use were limited or nonexistent, in 1998, the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the Canadian Public Health Association (CPHA) initiated the Global Tobacco Surveillance System (GTSS) to assist countries in establishing tobacco control surveillance and monitoring programs. GTSS includes collection of data through three school-based surveys: the Global Youth Tobacco Survey (GYTS) for youth; the Global School Personnel Survey (GSPS), and the Global Health Professions Student Survey (GHPSS) for adults; and one household survey: the Global Adult Tobacco Survey (GATS) for adults. The GTSS provides a globally implemented and consistent framework for conducting surveillance including standard sampling procedures, core questionnaire items, training in field procedures and analysis of data consistent across all GTSS countries. The GTSS also enhances the role of the nongovernmental sector by supporting participation of civil society agencies in surveillance, monitoring, and policy and program development. The synergy between countries passing tobacco control laws, regulations or decrees, ratifying and complying with the WHO Framework Convention on Tobacco Control, and conducting GTSS surveys offers a unique opportunity to develop, implement, and evaluate comprehensive tobacco control policy that can be helpful to each country document the development, growth, and collaboration in sustaining the GTSS. The report highlights countries’ involvement in tobacco control measures and the establishment of comprehensive tobacco control programs worldwide. This report can assist countries in prioritizing and developing tobacco control programs, including surveillance, evaluation, and policy development. (Global Health Promotion, 2009; Supp (2): pp. 04-37)
New constraining method for partitioned block frequency-domain adaptive filters

For adaptive filters with many taps, a short processing delay, and relative low computational complexity, the partitioned block frequency-domain adaptive filter (PBFDAF) is a good choice. The computational complexity of this algorithm is significantly reduced by using the alternated constrained PBFDAF. This particular algorithm applies gradient constraints in an alternating manner. In this paper, a serious problem in performance of the alternated constrained PBFDAF is described. Furthermore, a modification is proposed that effectively alleviates this problem. By using this modification together with a gradient constraint approximation, a new efficient alternated constrained PBFDAF is developed. Compared with the fully constrained PBFDAF, this new constraining method does not show any significant performance loss and still has a much smaller computational complexity.
Using System Dynamics tools to gain insight into intervention options related to the interaction between tobacco and tuberculosis

Tobacco exposure is an important risk factor for tuberculosis (TB) when considering its effects on population-level disease outcomes. If we hope to gain control over TB globally, we must begin to think ‘outside of the box’ to identify an extended and multi-faceted intervention strategy that is grounded in an understanding of the particular ways in which key risk factors worsen TB. In light of the role of tobacco exposure as an important, identifiable, modifiable, and preventable risk factor for TB, efforts aiming at reducing tobacco use merit inclusion in such a comprehensive TB control program. The goal of this paper is to share the conceptual framework we have developed using System Dynamics methodology, which diagrams the likely effects of tobacco exposure on TB dynamics in a typical low-income country setting. Using this framework as a guide, we leverage an understanding of the likely mechanisms by which tobacco exposure affects TB risk to systematically explore TB control intervention options. We hope that this paper will help inspire new approaches to extend and enhance traditional TB control efforts. We also hope that the conceptual framework will spark further discussion and research on this important and potentially explosive combination of global public health crises.
Sec24C-Dependent Transport of Claudin-1 Regulates Hepatitis C Virus Entry

ABSTRACT Claudin-1 is a hepatitis C virus (HCV) coreceptor required for viral entry. Although extensive studies have focused on claudin-1 as an anti-HCV target, little is known about how the level of claudin-1 at the cell surface is regulated by host vesicular transport. Here, we identified an interaction between claudin-1 and Sec24C, a cargo-sorting component of the coat protein complex II (COPII) vesicular transport system. By interacting with Sec24C through its C-terminal YV, claudin-1 is transported from the endoplasmic reticulum (ER) and is eventually targeted to the cell surface. Blocking COPII transport inhibits HCV entry by reducing the level of claudin-1 at the cell surface. These findings provide mechanistic insight into the role of COPII vesicular transport in HCV entry. IMPORTANCE Tight junction protein claudin-1 is one of the cellular receptors for hepatitis C virus, which infects 185 million people globally. Its cellular distribution plays important role in HCV entry; however, it is unclear how the localization of claudin-1 to the cell surface is controlled by host transport pathways. In this paper, we not only identified Sec24C as a key host factor for HCV entry but also uncovered a novel mechanism by which the COPII machinery transports claudin-1 to the cell surface. This mechanism might be extended to other claudins that contain a C-terminal YV or V motif.
Becoming a health promoting school: key components of planning

This article looks at the practicalities of implementing the health promoting school (HPS) framework, including conducting a whole school audit, to enable a primary school to successfully adopt the HPS principles. A partnership agreement was signed, between EACH Social and Community Health which is a local Community Health Centre and a primary school in the Eastern suburbs of Melbourne, in Australia. An audit was conducted of the school community with four follow up focus groups of students from grades 3 to 6. Qualitative data was gathered from 20 teachers at the school at a professional development day facilitated by the health promotion staff of the Community Health Centre. The results of the school audit identified that students in grades 3 to 6 and parents valued the outside environment of the school most highly. The staff valued staff attributes most highly. Suggestions from students to improve the school included improving the canteen and outside environment. Staff were most concerned about fitness of both the staff and the students. Parents also identified lack of healthy eating as a concern. The school community sees the value of adopting the HPS framework, however on-going structured support is required if the school is to successfully adopt the HPS approach. The school community needs to understand that the move toward cultural and environmental change is slow. Successful adoption of the HPS model requires time and collaboration. The emphasis needs to be on supporting teachers to change their school from within. Relationships are important.
An Endogenous Foamy Virus in the Aye-Aye (Daubentonia madagascariensis)

ABSTRACT We report the discovery and analysis of an endogenous foamy virus (PSFVaye) within the genome of the aye-aye (Daubentonia madagascariensis), a strepsirrhine primate from Madagascar. Phylogenetic analyses indicate that PSFVaye is divergent from all known simian foamy viruses, suggesting an association between foamy viruses and primates since the haplorrhine-strepsirrhine split. The discovery of PSFVaye indicates that primate foamy virus might be more broadly distributed than previously thought.
The Polycomb Group Protein Bmi1 Binds to the Herpes Simplex Virus 1 Latent Genome and Maintains Repressive Histone Marks during Latency

ABSTRACT The mechanism by which herpes simplex virus 1 (HSV-1) establishes latency in sensory neurons is largely unknown. Recent studies indicate that epigenetic modifications of the chromatin associated with the latent genome may play a key role in the transcriptional control of lytic genes during latency. In this study, we found both constitutive and facultative types of heterochromatin to be present on the latent HSV-1 genome. Deposition of the facultative marks trimethyl H3K27 and histone variant macroH2A varied at different sites on the genome, whereas the constitutive marker trimethyl H3K9 did not. In addition, we show that in the absence of the latency-associated transcript (LAT), the latent genome shows a dramatic increase in trimethyl H3K27, suggesting that expression of the LAT during latency may act to promote an appropriate heterochromatic state that represses lytic genes but is still poised for reactivation. Due to the presence of the mark trimethyl H3K27, we examined whether Polycomb group proteins, which methylate H3K27, were present on the HSV-1 genome during latency. Our data indicate that Bmi1, a member of the Polycomb repressive complex 1 (PRC1) maintenance complex, associates with specific sites in the genome, with the highest level of enrichment at the LAT enhancer. To our knowledge, these are the first data demonstrating that a virus can repress its gene transcription to enter latency by exploiting the mechanism of Polycomb-mediated repression.
Exploring health promotion practitioners’ experiences of moral distress in Canada and Australia

This article introduces moral distress – the experience of painful feelings due to institutional constraints on personal moral action – as a significant issue for the international health promotion workforce. Our exploratory study of practitioners’ experiences of health promotion in Australia and Canada during 2009–2010 indicated that practitioners who work in upstream policy- and systems-level health promotion are affected by experiences of moral distress. Health promotion practitioners at all levels of the health promotion continuum also described themselves as being engaged in a minority practice within a larger dominant system that does not always value health promotion. We argue that health promotion practitioners are vulnerable to moral distress due to the values-driven and political nature of the practice, the emphasis on systems change and the inherent complexity and diversity of the practice. This vulnerability to moral distress poses significant challenges to both workers and organisations and the communities they seek to benefit. We propose that further research should be undertaken to fully identify the causes and symptoms of moral distress in health promotion. Extensive existing research on moral distress in nursing provides ample resources to conduct such research.
Antiangiogenic Arming of an Oncolytic Vaccinia Virus Enhances Antitumor Efficacy in Renal Cell Cancer Models

ABSTRACT Oncolytic vaccinia viruses have shown compelling results in preclinical cancer models and promising preliminary safety and antitumor activity in early clinical trials. However, to facilitate systemic application it would be useful to improve tumor targeting and antitumor efficacy further. Here we report the generation of vvdd-VEGFR-1-Ig, a targeted and armed oncolytic vaccinia virus. Tumor targeting was achieved by deletion of genes for thymidine kinase and vaccinia virus growth factor, which are necessary for replication in normal but not in cancer cells. Given the high vascularization typical of kidney cancers, we armed the virus with the soluble vascular endothelial growth factor (VEGF) receptor 1 protein for an antiangiogenic effect. Systemic application of high doses of vvdd-VEGFR-1-Ig resulted in cytokine induction in an immunocompromised mouse model. Upon histopathological analysis, splenic extramedullary hematopoiesis was seen in all virus-injected mice and was more pronounced in the vvdd-VEGFR-1-Ig group. Analysis of the innate immune response after intravenous virus injection revealed high transient and dose-dependent cytokine elevations. When medium and low doses were used for intratumoral or intravenous injection, vvdd-VEGFR-1-Ig exhibited a stronger antitumor effect than the unarmed control. Furthermore, expression of VEGFR-1-Ig was confirmed, and a concurrent antiangiogenic effect was seen. In an immunocompetent model, systemic vvdd-VEGFR-1-Ig exhibited superior antitumor efficacy compared to the unarmed control virus. In conclusion, the targeted and armed vvdd-VEGFR-1-Ig has promising anticancer activity in renal cell cancer models. Extramedullary hematopoiesis may be a sensitive indicator of vaccinia virus effects in mice.
Exploring Creole women’s health using ethnography and Photovoice in Bluefields, Nicaragua

Bluefields, Nicaragua is the largest city in the Southern Atlantic Autonomous Region (RAAS), and home to communities of Nicaragua’s six ethnic groups. Photovoice research techniques were used in this ethnographic study to explore the health experiences of Creole women. After participating in focus groups to discuss women’s health, 12 Creole women took photographs to describe their health experiences. The researcher then interviewed them about what each picture meant, and participants selected photos for a community-wide exhibition in Bluefields. Photos and narratives were analyzed to construct a description of the cultural context in which Creole women experienced health. One of the greatest women’s health concerns reported was that participants believed the younger generation was losing touch with Creole culture, putting them at risk of disease and illness. For participants, photos were a way to document Creole traditions of healing, traditions in the Creole home, and environmental health concerns.
HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV

ABSTRACT Studying HIV-infected individuals who control HIV replication (elite controllers [ECs]) enables exploration of effective anti-HIV immunity. HIV Env-specific and non-Env-specific antibody-dependent cellular cytotoxicity (ADCC) may contribute to protection from progressive HIV infection, but the evidence is limited. We recruited 22 ECs and matched them with 44 viremic subjects. HIV Env- and Vpu-specific ADCC responses in sera were studied using a novel enzyme-linked immunosorbent assay (ELISA)-based dimeric recombinant soluble FcγRIIIa (rsFcγRIIIa)-binding assay, surface plasmon resonance, antibody-dependent natural killer (NK) cell activation assays, and ADCC-mediated killing assays. ECs had higher levels of HIV Env-specific antibodies capable of binding FcγRIIIa, activating NK cells, and mediating granzyme B activity (all P < 0.01) than viremic subjects. ECs also had higher levels of antibodies against a C-terminal 13-mer Vpu peptide capable of mediating FcγRIIIa binding and NK cell activation than viremic subjects (both P < 0.05). Our data associate Env-specific and Vpu epitope-specific ADCC in effective immune responses against HIV among ECs. Our findings have implications for understanding the role of ADCC in HIV control. IMPORTANCE Understanding immune responses associated with elite control of HIV may aid the development of immunotherapeutic and vaccine strategies for controlling HIV infection. Env is a major HIV protein target of functional antibody responses that are heightened in ECs. Interestingly, EC antibodies also target Vpu, an accessory protein crucial to HIV, which degrades CD4 and antagonizes tetherin. Antibodies specific to Vpu are a common feature of the immune response of ECs that may prove to be of functional importance to the design of improved ADCC-based immunotherapy and preventative HIV vaccines.