The Cytomegalovirus Tegument Protein UL35 Antagonizes Pattern Recognition Receptor-Mediated Type I IFN Transcription.

The rapid activation of pattern recognition receptor (PRR)-mediated type I interferon (IFN) signaling is crucial for the host response to infection. In turn, human cytomegalovirus (HCMV) must evade this potent response to establish life-long infection. Here, we reveal that the HCMV tegument protein UL35 antagonizes the activation of type I IFN transcription downstream of the DNA and RNA sensors cGAS and RIG-I, respectively. We show that ectopic expression of UL35 diminishes the type I IFN response, while infection with a recombinant HCMV lacking UL35 induces an elevated type I IFN response compared to wildtype HCMV. With a series of luciferase reporter assays and the analysis of signaling kinetics upon HCMV infection, we observed that UL35 downmodulates PRR signaling at the level of the key signaling factor TANK-binding kinase 1 (TBK1). Finally, we demonstrate that UL35 and TBK1 co-immunoprecipitate when co-expressed in HEK293T cells. In addition, we show that a previously reported cellular binding partner of UL35, O-GlcNAc transferase (OGT), post-translationally GlcNAcylates UL35, but that this modification is not required for the antagonizing effect of UL35 on PRR signaling. In summary, we have identified UL35 as the first HCMV protein to antagonize the type I IFN response at the level of TBK1, thereby enriching our understanding of how this important herpesvirus escapes host immune responses.

Towards Non-invasive Labour Detection: A Free-Living Evaluation.

In this paper we show early evidence of the feasibility of detecting labour during pregnancy, non-invasively and in free-living. In particular, we present machine learning models aiming at dealing with the challenges of unsupervised, free-living data collection, such as identifying periods of high quality data and detecting physiological changes as labour approaches. During a first phase, physiological data including electrohysterography (EHG, the electrical activity of the uterus), heart rate (HR) and gestational age (GA) were collected in laboratory conditions for model development. In particular, data were collected 1) during simulated activities of daily living, aiming at eliciting artifacts and developing diagnostic models for free-living data 2) during pregnancy, including labour, aiming at developing labour probability models from clean, supervised physiological recordings. Machine learning models using datasets 1) and 2) were deployed in free-living, longitudinally, in 142 pregnant women, between week 22 of pregnancy and delivery. A total of 1014 hours of data and an average of 7 hours per person were collected. Output of the developed models was analyzed to determine the feasibility of detecting labour non-invasively using physiological data, acquired with a single sensor placed on the abdomen. Results showed that the probability of being in labour for recordings collected during the last 24 hours of pregnancy was consistently higher than the probability during any other pregnancy week. Thus, non-invasive labour detection from physiological data seems promising.

Obese women's barriers to mammography and pap smear: the possible role of personality.

Obese women are at increased risk of developing and dying from cancer, but are less likely than nonobese women to receive cancer screening examinations. Our qualitative study explores obese women's barriers to Pap smears and mammograms in greater depth than previous research. We also seek to understand why some obese women undergo screening whereas others do not. A purposive sample of moderately to severely obese women over age 40 was recruited from community-based organizations, health clinics, and retail establishments. Semi-structured in-depth interviews (N = 33) informed by the Theory of Care-Seeking Behavior and three prior focus groups of obese women (N = 18) were recorded and transcribed. Qualitative analysis was iterative, using a grounded theory approach involving a series of immersion/crystallization cycles. Participants verified many barriers to cervical and breast cancer screening previously identified in the general population, including fear, modesty, competing demands, and low perceived risk. Participants also highlighted several weight-related barriers, including insensitive comments about weight and equipment and gowns that could not accommodate them. Comparison of participants who were up-to-date with both Pap smears and mammograms with those not up-to-date with either screening showed no discernable differences in these barriers, however. Instead, we found that the participants who followed through on their cancer screenings may share certain personality traits, such as conscientiousness or self-regulatory ability, that allow them to complete difficult or feared tasks. Our research therefore suggests that personality may act as an important mediator in health behavior, and should be taken into account in future theoretical models and health behavior interventions, particularly for obese women.