Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4 T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction. Furthermore, Vpr also amplifies innate sensing of HIV-1 infection in Vpx-treated dendritic cells. Our results identify cGAS as mediator of an IFN-I response to HIV-1 infection in CD4 T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cells of HIV-1.

Reproductive life span and fertility have been shown to depend on successful early folliculogenesis, which involves cell-to-cell communication and the concerted regulation of gene expression at both the oocyte and granulosa cell levels. Recently, micro RNAs (miRNAs) were identified as fine-tuners of gene expression. Here, we report that miRNAs can readily be detected within membrane-enclosed vesicles of human follicular fluid. MiRNA expression profiling of the follicular fluid of younger (<31 years) and older (>38 years) women revealed a set of four differentially expressed miRNAs. The predicted targets of these miRNAs are clearly enriched in genes involved in heparan-sulfate biosynthesis, extracellular matrix-receptor interaction, carbohydrate digestion and absorption, p53 signaling, and cytokine-cytokine-receptor interaction. Several of these pathways have been reported to be determinants of fertility, suggesting that this set of miRNAs and their respective targets should be evaluated in relation to reproductive aging and assisted reproduction.

a b s t r a c tTheoretical values of two correction factors a s = 5/6 and a t = 7/10 are established for the respective transverse shear stress resultants and stress couples within the general, dynamically and kinematically exact, six-field theory of elastic shells. These values do not depend on the shell material symmetry, geometry of the base surface, the shell thickness, or any kind of kinematic and/or dynamic constraints. The analysis is based on the complementary energy density following from the transverse shear stresses acting only on the shell cross section. The appropriate quadratic and cubic distributions of the stresses across the thickness allow one to derive the consistent constitutive equations for the transverse shear stress resultants and stress couples with a s and a t as the respective correction factors. Four numerical examples of highly non-linear shell structures illustrate the influence of different values of a s and a t on the results. In particular, some influence of a t is noticed on the placement of bifurcation points. In dynamic problem of flight of three intersecting plates analysed with Newmark-type temporal algorithm, the value of a t influences the moment at which the relative error of total energy of the system begins to grow indefinitely leading to the solution failure.

SUMMARYWe propose a new four-node C 0 finite element for shell structures undergoing unlimited translations and rotations. The considerations concern the general six-field theory of shells with asymmetric strain measures in geometrically nonlinear static problems. The shell kinematics is of the two-dimensional Cosserat continuum type and is described by two independent fields: the vector field for translations and the proper orthogonal tensor field for rotations. All three rotational parameters are treated here as independent. Hence, as a consequence of the shell theory, the proposed element has naturally six engineering degrees of freedom at each node, with the so-called drilling rotation. This property makes the element suitable for analysis of shell structures containing folds, branches or intersections. To avoid locking phenomena we use the enhanced assumed strain (EAS) concept. We derive and linearize the modified Hu-Washizu principle for six-field theory of shells. What makes the present approach original is the combination of EAS method with asymmetric membrane strain measures. Based on literature, we propose new enhancing field and specify the transformation matrix that accounts for the lack of symmetry. To gain knowledge about the suitability of this field for asymmetric strain measures and to assess the performance of the element, we solve typical benchmark examples with smooth geometry and examples involving orthogonal intersections of shell branches.

Clonal expansion of HIV-infected cells contributes to the long-term persistence of the HIV reservoir in ART-suppressed individuals. However, the contribution from cell clones that harbor inducible proviruses to plasma viremia is poorly understood. Here, we describe a single-cell approach to simultaneously sequence the TCR, integration sites and proviral genomes from translation-competent reservoir cells, called STIP-Seq. By applying this approach to blood samples from eight participants, we show that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5’-end of the genome, often involving the major splice donor site. TCR and integration site sequencing reveal that cell clones with predicted pathogen-specificity can harbor inducible proviruses integrated into cancer-related genes. Furthermore, we find several matches between proviruses retrieved with STIP-Seq and plasma viruses obtained during ART and upon treatment interruption, suggesting that STIP-Seq can capture clones that are responsible for low-level viremia or viral rebound.