2,153 research outputs found
PPARÎł and LXR Signaling Inhibit Dendritic Cell-Mediated HIV-1 Capture and trans-Infection
Dendritic cells (DCs) contribute to human immunodeficiency virus type 1 (HIV-1) transmission and dissemination by capturing and transporting infectious virus from the mucosa to draining lymph nodes, and transferring these virus particles to CD4+ T cells with high efficiency. Toll-like receptor (TLR)-induced maturation of DCs enhances their ability to mediate trans-infection of T cells and their ability to migrate from the site of infection. Because TLR-induced maturation can be inhibited by nuclear receptor (NR) signaling, we hypothesized that ligand-activated NRs could repress DC-mediated HIV-1 transmission and dissemination. Here, we show that ligands for peroxisome proliferator-activated receptor gamma (PPARÎł) and liver X receptor (LXR) prevented proinflammatory cytokine production by DCs and inhibited DC migration in response to the chemokine CCL21 by preventing the TLR-induced upregulation of CCR7. Importantly, PPARÎł and LXR signaling inhibited both immature and mature DC-mediated trans-infection by preventing the capture of HIV-1 by DCs independent of the viral envelope glycoprotein. PPARÎł and LXR signaling induced cholesterol efflux from DCs and led to a decrease in DC-associated cholesterol, which has previously been shown to be required for DC capture of HIV-1. Finally, both cholesterol repletion and the targeted knockdown of the cholesterol transport protein ATP-binding cassette A1 (ABCA1) restored the ability of NR ligand treated cells to capture HIV-1 and transfer it to T cells. Our results suggest that PPARÎł and LXR signaling up-regulate ABCA1-mediated cholesterol efflux from DCs and that this accounts for the decreased ability of DCs to capture HIV-1. The ability of NR ligands to repress DC mediated trans-infection, inflammation, and DC migration underscores their potential therapeutic value in inhibiting HIV-1 mucosal transmission. Author SummaryHeterosexual transmission is the primary mode of HIV transmission worldwide. In the absence of an effective vaccine, there is an increasing demand for the development of effective microbicides that block HIV sexual transmission. Dendritic cells (DCs) play a critical role in HIV transmission by efficiently binding virus particles, migrating to lymph nodes, and transmitting them to CD4+ T cells, a process called trans-infection. In addition, DCs secrete proinflammatory cytokines that create a favorable environment for virus replication. DC maturation by pathogen-encoded TLR ligands or proinflammatory cytokines dramatically increases their capacity to capture HIV, migrate to lymphoid tissue, and trans-infect T cells. Here, we report that signaling through the nuclear receptors PPARÎł and LXR prevents DC maturation and proinflammatory cytokine production, as well as migration. In addition, PPARÎł and LXR signaling prevents efficient DC capture and transfer of infectious HIV by increasing ABCA1-mediated cholesterol efflux. Our studies suggest that PPARÎł and LXR may be targets for drugs that can inhibit specific aspects of HIV mucosal transmission, namely inflammation, migration, and virus capture and transfer. These findings provide a rationale for considering PPARÎł and LXR agonists as potential combination therapies with conventional anti-viral microbicides that target other aspects of mucosal HIV transmission.National Institutes of Health (AI073149, AI064099, T32-AI07309, T32-AI0764206, F32-AI084558
MorfometrĂa en dos poblaciones californianas de Gumaga nigricula(McLachlan 1871) (Trichoptera: Sericostomatidae)
Eighty Gumaga nigricula larvae from Hopland Spring and Big Sulphur Creek, northern California, USA, were studied to quantify possible dissimilarities among them. The populations are statistically different in two meristic characters: number of setae on the anterior margin of the pronotum and number of pleural sclerites on abdominal segment VIII. They also appear to be different in a continuous character, head width/length ratio. In all cases, specimens from Big Sulphur Creek have statistically significant higher values. These data are congruent with the hypothesis that there is biologically significant genetic isolation between these populations.Ochenta larvas de Gumaga nigricula provenientes del Hopland Spring y del Big Sulphur Creek en el norte de California, Estados Unidos, se estudiaron para cuantificar las posibles diferencias entre ellas. Estas poblaciones son estadĂsticamente diferentes en dos caracterĂsticas merĂsticas: el nĂșmero de cerdas en el margen anterior del pronoto y el nĂșmero de escleritos pleurales en el segmento abdominal VIH. Estas poblaciones tambiĂ©n parecen ser diferentes en la caracterĂstica continua, cociente ancho/largo de la cabeza. En todos los casos, los ejemplares del Big Sulphur Creek tienen valores significativamente mayores. Estos datos son congruentes con la hipĂłtesis de que existe aislamiento reproductivo significativo entre estas dos poblaciones
Chip Off the Old Block : Generation, Development, and Ancestral Concepts of Heredity
Heredity is such a fundamental concept that it is hard to imagine a world where the connection between parents and offspring is not understood. Three hundred years ago thinking of the phenomenon of heredity bore on a cluster of distinct philosophical questions inherited from antiquity concerning the nature and origin of substances or beings that lacked biological meaning. We are reminded of this philosophical heritage by the fact that in the 18th century the study of reproduction, embryology and development was referred to as "the science of generation". It is now clear that reproduction, the biological process by which parents produce offspring, is a fundamental feature of all life on Earth. Heredity, the transmission of traits from parents to offspring via sexual or asexual reproduction, allows differences between individuals to accumulate and evolve through natural selection. Genetics is the study of heredity, and in particular, variation of fundamental units responsible for heredity. Ideas underlying this theory evolved in considerably different and unrelated ways across a number of knowledge domains, including philosophy, medicine, natural history, and breeding. The fusion of these different domains into a single comprehensive theory in 19th century biology was a historically and culturally interdependent process, thus examining genetic prehistory should unravel these entanglements. The major goal of our review is tracing the various threads of thought that gradually converged into our contemporary understanding of heredity.Peer reviewe
Themes of Biological Inheritance in Early Nineteenth Century Sheep Breeding as Revealed by J. M. Ehrenfels
Among the so-called sheep breeders interested in biological inheritance in the late eighteenth and early nineteenth centuries and well before Gregor Johann Mendel, J. M. Ehrenfels (1767â1843) produced some of the most cogent writings on the subject. Although earlier in his career Ehrenfels was a strong advocate of environmental factors as influencers on the appearance of organisms, as a result of his discussions with Imre Festetics, he became convinced that whatever is passed from parents to progeny is more important and it is dependent on a âgenetic force, the mother of all living thingsâ. The sheep breeders kept issues of inheritance at the forefront of the Central European cultural context late into the nineteenth century
Themes of Biological Inheritance in Early Nineteenth Century Sheep Breeding as Revealed by J. M. Ehrenfels
Among the so-called sheep breeders interested in biological inheritance in the late eighteenth and early nineteenth centuries and well before Gregor Johann Mendel, J. M. Ehrenfels (1767â1843) produced some of the most cogent writings on the subject. Although earlier in his career Ehrenfels was a strong advocate of environmental factors as influencers on the appearance of organisms, as a result of his discussions with Imre Festetics, he became convinced that whatever is passed from parents to progeny is more important and it is dependent on a âgenetic force, the mother of all living thingsâ. The sheep breeders kept issues of inheritance at the forefront of the Central European cultural context late into the nineteenth century
Annealing tests of in-pile irradiated oxide coated UâMo/AlâSi dispersed nuclear fuel
Authors do acknowledge the MERARG team for their experimental work (CEA) and F. Charollais, J. Noirot and finally B. Kapusta for their advices and comments. This study was supported by a combined Grant (FRM0911) of the Bundesministerium fĂŒr Bildung und Forschung (BMBF) and the Bayerisches Staatsministerium fĂŒr Wissenschaft, Forschung und Kunst (StMWFK).UâMo/Al based nuclear fuels have been worldwide considered as a promising high density fuel for the conversion of high flux research reactors from highly enriched uranium to lower enrichment. In this paper, we present the annealing test up to 1800°C of in-pile irradiated UâMo/AlâSi fuel plate samples. More than 70% of the fission gases (FGs) are released during two major FG release peaks around 500°C and 670°C. Additional characterisations of the samples by XRD, EPMA and SEM suggest that up to 500°C FGs are released from IDL/matrix interfaces. The second peak at 670°C representing the main release of FGs originates from the interaction between UâMo and matrix in the vicinity of the cladding
Performance based grouping of adapted and exotic drought tolerant maize (Zea mays L) inbred lines under stressed and nonstressed conditions
Knowledge of the heterotic responses of elite adapted and exotic maize inbred lines can facilitate their utilization for population improvement and hybrid development. In the present study, a line x tester mating design was used to determine the combining ability of 20 elite drought-tolerant maize inbred lines developed at CIMMYT and IITA and to classify them into heterotic groups under diverse growing conditions. The 20 lines were crossed each with two inbred line testers representing the tropical and temperate heterotic pattern established in West and Cental Africa (WCA), to generate 40 testcrosses. A trial comprising the 40 testcrosses along with the cross between the two testers and three hybrid checks were evaluated at two environments in the dry season and at six environments in the rainy season. GCA effects were more important than SCA effects in controlling grain yield in both seasons. Two exotic lines in the dry season and four exotic lines in the rainy season had significantly positive GCA effects. Only EXL22 was identified as a superior line in the two seasons. Only two adapted lines had significantly positive GCA effects in either or both seasons while three adapted lines consistently had significantly negative GCA effects in both seasons. Hybrid between EXL22 and tester 9071 showed broad adaptation to all test environments. The two testers separated some of the lines into two main heterotic groups. the lines in each heterotic group and the good combiners will be utilized for developing populations for extracting new improved inbred lines
EXO 2030+375 Restarts in Reverse
The Be X-ray binary pulsar EXO 2030+375, first detected in 1985, has shown a
significant detected X-ray outburst at nearly every periastron passage of its
46-day orbit for the past ~25 years, with one low state accompanied by a torque
reversal in the 1990s. In early 2015 the outbursts progressively became fainter
and less regular while the monotonic spin-up flattened. At the same time a
decrease in the H line equivalent width was reported, indicating a
change in the disk surrounding the mass donor.
In order to explore the source behaviour in the poorly explored low-flux
state with a possible transition to a state of centrifugal inhibition of
accretion we have undertaken an observing campaign with Swift/XRT, NuSTAR and
the Nordic Optical Telescope (NOT). This conference contribution reports the
preliminary results obtained from our campaign.Comment: 11th INTEGRAL Conference Gamma-Ray Astrophysics in Multi-Wavelength
Perspective, 10-14 October 2016, Amsterdam, The Netherlands. 7 page
Trabectedin and its potential in the treatment of soft tissue sarcoma
Trabectedin is a new marine-derived compound that binds the DNA minor groove and interacts with proteins of the DNA repair machinery. Phase I trials have established the standard regimen as 1500 ÎŒg/m2 24-hour continuous infusion repeated every 3 weeks. Several phase II trials have shown response in 5%â10% of unselected patients with soft tissue sarcoma failing prior chemotherapy and disease stabilisation in 30%â40%. Furthermore, prolonged disease control has been described in 15%â20% of patients. Toxicities are mainly haematological and hepatic with grade 3â4 neutropenia and thrombocytopenia observed in approximately 50% and 20% of patients respectively, and grade 3â4 elevation of liver enzymes observed in 35%â50% of patients treated with trabectedin. Current research focuses on the identification of predictive factors for patients with soft tissue sarcoma treated with trabectedin
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