CD32-RNA Co-localizes with HIV-RNA in CD3+ Cells Found within Gut Tissues from Viremic and ART-Suppressed Individuals.

BackgroundIdentifying biomarkers for cells harboring replication-competent HIV is a major research priority. Recently, there have been mixed reports addressing the possibility that CD32-expressing T cells are enriched for HIV. There is growing evidence that CD32 expression increases with cellular activation that may be related to, but not necessarily specific for, infection with HIV. However, the relationship of CD32 expression to HIV-infection in subtypes of tissue-resident leukocytes is unclear.MethodsFirst, we used duplex chromogenic in situ hybridization to identify cells actively transcribing RNA for both CD32 and HIV on human gut tissues. Then we performed multiplexed immunofluorescence and in situ hybridization (mIFISH) on sections from the same tissues to determine the phenotype of individual cells co-expressing HIV-RNA and CD32-RNA.ResultsHIV-RNA+ cells were more abundant in tissues from viremic individuals than in those receiving suppressive anti-retroviral therapy (ART). However, staining by both methods indicated that a higher proportion of HIV-RNA+ cells co-expressed CD32-RNA in ART-suppressed individuals than in those with viremia. The majority of HIV-RNA+ cells were CD3+.ConclusionsOur data suggest that the transcription of CD32-RNA is correlated with HIV transcriptional activity in CD3+ cells found within human gut tissue. Whether or not up-regulation of CD32-RNA is a direct result of HIV transcription or more global T-cell activation remains unclear

TFAP2C regulates transcription in human naive pluripotency by opening enhancers.

Naive and primed pluripotent human embryonic stem cells bear transcriptional similarity to pre- and post-implantation epiblast and thus constitute a developmental model for understanding the pluripotent stages in human embryo development. To identify new transcription factors that differentially regulate the unique pluripotent stages, we mapped open chromatin using ATAC-seq and found enrichment of the activator protein-2 (AP2) transcription factor binding motif at naive-specific open chromatin. We determined that the AP2 family member TFAP2C is upregulated during primed to naive reversion and becomes widespread at naive-specific enhancers. TFAP2C functions to maintain pluripotency and repress neuroectodermal differentiation during the transition from primed to naive by facilitating the opening of enhancers proximal to pluripotency factors. Additionally, we identify a previously undiscovered naive-specific POU5F1 (OCT4) enhancer enriched for TFAP2C binding. Taken together, TFAP2C establishes and maintains naive human pluripotency and regulates OCT4 expression by mechanisms that are distinct from mouse

Diabetes, Abdominal Adiposity, and Atherogenic Dyslipoproteinemia in Women Compared With Men

OBJECTIVE—To understand why atherogenic risk differs more between diabetic and nondiabetic women than between diabetic and nondiabetic men

Localization of IFN-γ-Activated Stat1 and IFN Regulatory Factors 1 and 2 in Breast Cancer Cells

The aim of the present work was to evaluate the induction and localization of Stat1, interferon (IFN) regulatory factor-1 (IRF-1), and IRF-2 after IFN-γ exposure of human breast cancer cell lines, SKBR3, MDA468, MCF7, and BT20. Results from growth assays, Western staining, electrophoretic mobility shift assay (EMSA), and immunohistochemical staining were collated to test our hypothesis that immunohistochemical analysis of Stat1, IRF-1, and IRF-2 would provide additional information about the functionality of the IFN-γ signaling pathway in human tumor lines. EMSA results showed that in each of four cell lines, Stat1 expression was increased and demonstrated functional activity after IFN-γ stimulation. Western and EMSA analysis showed upregulation of IRF-1 but not IRF-2 in each cell line. Confocal microscopy of cells stained for Stat1, IRF-1, and IRF-2 confirmed the results and also provided novel information about the intracellular localization of proteins and intercellular variations in responses. The proportion of cells with IRF-1 stimulation and translocation was positively correlated with the IFN-γ growth suppression in vitro. In conclusion, using four independent assays, we have demonstrated that heterogeneity in IFN-γ-mediated upregulation of signal transduction proteins can be detected in vitro and that these differences can explain distinct cellular growth effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63148/1/107999003322558755.pd

Diabetes, Abdominal Adiposity, and Atherogenic Dyslipoproteinemia in Women Compared With Men

OBJECTIVE—To understand why atherogenic risk differs more between diabetic and nondiabetic women than between diabetic and nondiabetic men

AD Leonis: Radial Velocity Signal of Stellar Rotation or Spin–Orbit Resonance?

AD Leonis is a nearby magnetically active M dwarf. We find Doppler variability with a period of 2.23 days, as well as photometric signals: (1) a short-period signal, which is similar to the radial velocity signal, albeit with considerable variability; and (2) a long-term activity cycle of 4070 ± 120 days. We examine the short-term photometric signal in the available All-Sky Automated Survey and Microvariability and Oscillations of STars (MOST) photometry and find that the signal is not consistently present and varies considerably as a function of time. This signal undergoes a phase change of roughly 0.8 rad when considering the first and second halves of the MOST data set, which are separated in median time by 3.38 days. In contrast, the Doppler signal is stable in the combined High-Accuracy Radial velocity Planet Searcher and High Resolution Echelle Spectrometer radial velocities for over 4700 days and does not appear to vary in time in amplitude, phase, period, or as a function of extracted wavelength. We consider a variety of starspot scenarios and find it challenging to simultaneously explain the rapidly varying photometric signal and the stable radial velocity signal as being caused by starspots corotating on the stellar surface. This suggests that the origin of the Doppler periodicity might be the gravitational tug of a planet orbiting the star in spin–orbit resonance. For such a scenario and no spin–orbit misalignment, the measured v sin i indicates an inclination angle of 15°̣5 ± 2°̣5 and a planetary companion mass of 0.237 ± 0.047 M Jup

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

Topological doping and the stability of stripe phases

We analyze the properties of a general Ginzburg-Landau free energy with competing order parameters, long-range interactions, and global constraints (e.g., a fixed value of a total ``charge'') to address the physics of stripe phases in underdoped high-Tc and related materials. For a local free energy limited to quadratic terms of the gradient expansion, only uniform or phase-separated configurations are thermodynamically stable. ``Stripe'' or other non-uniform phases can be stabilized by long-range forces, but can only have non-topological (in-phase) domain walls where the components of the antiferromagnetic order parameter never change sign, and the periods of charge and spin density waves coincide. The antiphase domain walls observed experimentally require physics on an intermediate lengthscale, and they are absent from a model that involves only long-distance physics. Dense stripe phases can be stable even in the absence of long-range forces, but domain walls always attract at large distances, i.e., there is a ubiquitous tendency to phase separation at small doping. The implications for the phase diagram of underdoped cuprates are discussed.Comment: 18 two-column pages, 2 figures, revtex+eps