Uterine Epithelial Cells Specifically Induce Interferon-Stimulated Genes in Response to Polyinosinic-Polycytidylic Acid Independently of Estradiol

Interferon β (IFNβ) is an antiviral cytokine secreted in response to pathogenic exposure that creates a restrictive intracellular environment through the action of downstream interferon-stimulated genes (ISG). The objective of this study was to examine the expression of IFNβ and ISG in both human uterine epithelial cells (UEC) and the ECC-1 uterine epithelial cell line and determine if expression changes with TLR stimulation and hormone exposure. Stimulation of primary uterine epithelial cells and ECC-1 cells with the TLR3 agonist poly (I∶C) induced the mRNA expression of IFNβ, MxA, OAS2 and PKR. Other TLR agonists including imiquimod and CpG had no effect on either IFNβ or ISG expression. In contrast to ECC-1 cell responses which were slower, maximal IFNβ upregulation in UEC occurred 3 hours post-stimulation and preceded the ISG response which peaked approximately 12 hours after poly (I∶C) exposure. Unexpectedly, estradiol, either alone or prior to treatment with poly (I∶C), had no effect on IFNβ or ISG expression. Blockade of the IFN receptor abrogated the upregulation of MxA, OAS2 and PKR. Furthermore, neutralizing antibodies against IFNβ partially inhibited the upregulation of all three ISG. Estradiol, directly and in the presence of poly (I∶C) had no effect on IFNβ and ISG expression. These results indicate that uterine epithelial cells are important sentinels of the innate immune system and demonstrate that uterine epithelial cells are capable of mounting a rapid IFN-mediated antiviral response that is independent of estradiol and is therefore potentially sustained throughout the menstrual cycle to aid in the defense of the uterus against potential pathogens

In-situ measurements of total reactive nitrogen, total water vapor, and aerosols in polar stratospheric clouds in the Antarctic stratosphere

Measurements of total reactive nitrogen, NOy, total water vapor, and aerosols were made as part of the Airborne Antarctic Ozone Experiment. The measurements were made using instruments located onboard the NASA ER-2 aircrafts which conducted twelve flights over the Antarctic continent reaching altitudes of 18 km at 72 S latitude. Each instrument utilized an ambient air sample and provided a measurement up to 1 Hz or every 200 m of flight path. The data presented focus on the flights of Aug. 17th and 18th during which Polar Stratospheric Clouds (PSCs) were encountered containing concentrations of 0.5 to 1.0 micron diameter aerosols greater than 1 cm/cu. The temperature pressure during these events ranged as low as 184 K near 75 mb pressure, with water values near 3.5 ppm by volume (ppmv). With the exception of two short periods, the PSC activity was observed at temperatures above the frost point of water over ice. The data gathered during these flights are analyzed and presented

Extinction and backscatter measurements of Antarctic PSC's, 1987: Implications for particle and vapor removal

The temperature dependence is examined of optical properties measured in the Antarctic during 1987 at the 70 mb level (near 18 km), a level chosen to correlate the results with in situ measurements made from the NASA-Ames ER-2 aircraft during the 1987 Airborne Antarctic Ozone Experiment (AAOE). The data set consists of extinction measurements by Sam 2 inside the Antarctic polar vortex from May to October 1987; and backscatter measurements by the UV-DIAL (Ultraviolet Differential Absorption Lidar) system aboard the Ames DC-8 aircraft during selected AAOE flights. Observed trends are compared with results from a revised version of Pole and McCormick's model to classify the PSC observations by Type (1 or 2) and infer the temporal behavior of the ambient aerosol and ambient vapor mixing ratios. The sample figures show monthly ensembles of the 70-mb Sam 2 extinction ratio (the ratio of aerosol or PSC extinction to molecule extinction) as a function of NMC temperature at the beginning (June) and (October) of the 1987 Antarctic winter. Both ensembles show two rather distinct clusters of points: one oriented in the near vertical direction which depicts the change with temperature of the ambient aerosol extinction ratio; and a second cluster oriented in the near horizontal direction whose position on the vertical scale marks a change in particle phase (i.e., PSC formation) and whose length (the extinction enhancement related to that of the ambient aerosol) is an indicator of PSC type

The Law of Facebook: Borders, Regulation and Global Social Media

This paper provides an outline of the talks presented at the webinar event “The Law of Facebook: Borders, Regulation and Global Social Media” on 15 May 2020, jointly hosted by the City Law School Jean Monnet Chair of Law & Transatlantic Relations, the Institute for the study of European Law (ISEL) and the International Law and Affairs Group (ILAG)

Can Physician Champions Improve Kangaroo Care? Trends over 5 Years in Rural Western India

Introduction: In 2013, approximately 2.8 million children worldwide died within the neonatal period. India is at the epicenter of this tragedy, accounting for one-third of all neonatal mortalities. Prematurity and/or with low birth weight are the leading cause of neonatal mortality and India has the highest number of neonates born preterm and weighing less than 2,500 grams worldwide. It is estimated that Kangaroo Care can avert up to 48% of all neonatal deaths among premature babies by 2025. However, the promise of Kangaroo Care as a low-cost, safe, and efficacious intervention to reduce neonatal mortality in India has not been realized due to suboptimal implementation. Physician champions can improve Kangaroo Care implementation, but the magnitude of their impact is unknown. Methods: A retrospective cohort study of 648 infants identified using clinical data from a NICU located in rural western India. Physicians who led Kangaroo Care training sessions with neonates and coached peer healthcare professionals were considered champions. Two Kangaroo Care champions were on staff full-time from January 2010 through June 2011, part-time from July 2011 through June 2012, and absent thereafter. We examined the effect of the withdrawal of physician champions on overall use using logistic regression, time to initiation using competing risk cox regression, and intensity using linear regression models of the two main components of Kangaroo Care, skin-to-skin care and breastfeeding, separately. Findings: In comparison to when Kangaroo Care champions were present, their absence was associated with a 45% decrease in the odds of receiving skin-to-skin care (95% CI): 64% to 17%), 38% decrease in the rate of initiation of skin-to-skin care (95% CI: 53% to 82%), and on average, 1.47 less hours of skin-to-skin care (95% CI: -2.07 to -0.86). Breastfeeding practices were similar across different champion environments. Interpretation: Withdrawal of Kangaroo Care champions from neonatal intensive care unit in rural western India is associated with diminished administration, delayed initiation, and shorter duration of skin-to-skin care, but did not impact breastfeeding practices. Training healthcare workers and community stakeholders to become champions could help in scaling up and maintaining Kangaroo Care practices. Funding: This research was supported by TL1-TR001454 (to A.S.) from National Center for Advancing Translational Sciences, and P60-MD006912-05 (to J.A.) from National Institute on Minority Health and Disparities. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH

Sex Hormones Regulate Tenofovir-Diphosphate in Female Reproductive Tract Cells in Culture

The conflicting results of recent pre-exposure prophylaxis (PrEP) trials utilizing tenofovir (TFV) to prevent HIV infection in women led us to evaluate the accumulation of intracellular TFV-diphosphate (TFV-DP) in cells from the female reproductive tract (FRT) and whether sex hormones influence the presence of TFV-DP in these cells. Following incubation with TFV, isolated epithelial cells, fibroblasts, CD4+ T cells and CD14+ cells from the FRT as well as blood CD4+ T cells and monocyte-derived macrophages convert TFV to TFV-DP. Unexpectedly, we found that TFV-DP concentrations (fmol/million cells) vary significantly with the cell type analyzed and the site within the FRT. Epithelial cells had 5-fold higher TFV-DP concentrations than fibroblasts; endometrial epithelial cells had higher TFV-DP concentrations than cells from the ectocervix. Epithelial cells had 125-fold higher TFV-DP concentrations than FRT CD4+ T cells, which were comparable to that measured in peripheral blood CD4+ T cells. These findings suggest the existence of a TFV-DP gradient in the FRT where epithelial cells \u3e fibroblasts \u3e CD4+ T cells and macrophages. In other studies, estradiol increased TFV-DP concentrations in endometrial and endocervical/ectocervical epithelial cells, but had no effect on fibroblasts or CD4+ T cells from FRT tissues. In contrast, progesterone alone and in combination with estradiol decreased TFV-DP concentrations in FRT CD4+ T cells. Our results suggest that epithelial cells and fibroblasts are a repository of TFV-DP that is under hormonal control. These cells might act either as a sink to decrease TFV availability to CD4+ T cells and macrophages in the FRT, or upon conversion of TFV-DP to TFV increase TFV availability to HIV-target cells. In summary, these results indicate that intracellular TFV-DP varies with cell type and location in the FRT and demonstrate that estradiol and/or progesterone regulate the intracellular concentrations of TFV-DP in FRT epithelial cells and CD4+ T cells

Estradiol Reduces Susceptibility of CD4+ T Cells and Macrophages to HIV-Infection

The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described to influence HIV infection in epidemiological studies and regulate different immune responses that may affect HIV infection, the direct role that female sex hormones play in altering the susceptibility of target cells to HIV-infection is largely unknown. Here we evaluated the direct effect of 17-b-estradiol (E2) and ethinyl estradiol (EE) in HIV-infection of CD4+ T-cells and macrophages. Purified CD4+ T-cells and monocyte-derived macrophages were generated in vitro from peripheral blood and infected with R5 and X4 viruses. Treatment of CD4+ T-cells and macrophages with E2 prior to viral challenge reduced their susceptibility to HIV infection in a dose-dependent manner. Addition of E2 2h after viral challenge however did not result in reduced infection. In contrast, EE reduced infection in macrophages to a lesser extent than E2 and had no effect on CD4+ T-cell infection. Reduction of HIV-infection induced by E2 in CD4+ T-cells was not due to CCR5 down-regulation, but was an entry-mediated mechanism since infection with VSV-G pseudotyped HIV was not modified by E2. In macrophages, despite the lack of an effect of on CCR5 expression, E2 –treatment reduced viral entry 2 h after challenge and increased MIP-1 b secretion. These results demonstrate the direct effect of E2 on susceptibility of HIV-target cells to infection and indicate that inhibition of target cell infection involves cell-entry related mechanisms

Deficits in temporal order memory induced by interferon-alpha (IFN-α) treatment are rescued by aerobic exercise

Patients receiving cytokine immunotherapy with IFN-α frequently present with neuropsychiatric consequences and cognitive impairments, including a profound depressive-like symptomatology. While the neurobiological substrates of the dysfunction that leads to adverse events in IFN-α-treated patients remains ill-defined, dysfunctions of the hippocampus and prefrontal cortex (PFC) are strong possibilities. To date, hippocampal deficits have been well-characterised; there does however remain a lack of insight into the nature of prefrontal participation. Here, we used a PFC-supported temporal order memory paradigm to examine if IFN-α treatment induced deficits in performance; additionally, we used an object recognition task to assess the integrity of the perirhinal cortex (PRH). Finally, the utility of exercise as an ameliorative strategy to recover temporal order deficits in rats was also explored. We found that IFN-α-treatment impaired temporal order memory discriminations, whereas recognition memory remained intact, reflecting a possible dissociation between recognition and temporal order memory processing. Further characterisation of temporal order memory impairments using a longitudinal design revealed that deficits persisted for 10 weeks following cessation of IFN-α-treatment. Finally, a 6 week forced exercise regime reversed IFN-α-induced deficits in temporal order memory. These data provide further insight into the circuitry involved in cognitive impairments arising from IFN-α-treatment. Here we suggest that PFC (or the hippocampo-prefrontal pathway) may be compromised whilst the function of the PRH is preserved. Deficits may persist after cessation of IFN-α-treatment which suggests that extended patient monitoring is required. Aerobic exercise may be restorative and could prove beneficial for patients treated with IFN-α