PPARγ 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 (PPARγ) 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, PPARγ 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. PPARγ 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 PPARγ 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 PPARγ and LXR prevents DC maturation and proinflammatory cytokine production, as well as migration. In addition, PPARγ and LXR signaling prevents efficient DC capture and transfer of infectious HIV by increasing ABCA1-mediated cholesterol efflux. Our studies suggest that PPARγ 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 PPARγ 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

Morfometría 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 estadísticamente diferentes en dos características merísticas: el número de cerdas en el margen anterior del pronoto y el número de escleritos pleurales en el segmento abdominal VIH. Estas poblaciones también parecen ser diferentes en la característica 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 hipótesis 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 (1767–1843) 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 “genetic force, the mother of all living things”. 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 (1767–1843) 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 “genetic force, the mother of all living things”. 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 U–Mo/Al–Si 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 für Bildung und Forschung (BMBF) and the Bayerisches Staatsministerium für Wissenschaft, Forschung und Kunst (StMWFK).U–Mo/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 U–Mo/Al–Si 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 U–Mo 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$\alpha$ 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

EPITRAGUS AURULENTUS (KIRSCH) (COLEOPTERA: TENEBRIONIDAE): A NEW RECORD AND REPORT FOR PUERTO RICO

EPITRAGUS AURULENTUS (KIRSCH) (COLEOPTERA: TENEBRIONIDAE): A NEW RECORD AND REPORT FOR PUERTO RIC