Search

New regulations from the International Maritime Organization (IMO) limiting sulfur emissions from the shipping industry are expected to have large benefits in terms of public health but come with an undesired side effect: an acceleration of global warming as the climate-cooling effects of ship pollution on marine clouds is diminished. Previous work has found a substantial decrease in the detection of ship tracks in clouds after the IMO 2020 regulations went into effect but changes in large-scale cloud properties have been more equivocal. Using a statistical technique that estimates counterfactual fields of what large-scale cloud and radiative properties within an isolated shipping corridor in the southeastern Atlantic would have been in the absence of shipping, we confidently detect a reduction in the magnitude of cloud droplet effective radius decreases within the shipping corridor and find evidence for a reduction in the magnitude of cloud brightening as well. The instantaneous radiative forcing due to aerosol–cloud interactions from the IMO 2020 regulations is estimated as O (1 W m-2) within the shipping corridor, lending credence to global estimates of O (0.1 W m-2). In addition to their geophysical significance, our results also provide independent evidence for general compliance with the IMO 2020 regulations. [ABSTRACT FROM AUTHOR]

New regulations from the International Maritime Organization (IMO) limiting sulfur emissions from the shipping industry are expected to have large benefits in terms of public health but come with an undesired side effect: an acceleration of global warming as the climate-cooling effects of ship pollution on marine clouds is diminished. Previous work has found a substantial decrease in the detection of ship tracks in clouds after the IMO 2020 regulations went into effect but changes in large-scale cloud properties have been more equivocal. Using a statistical technique that estimates counterfactual fields of what large-scale cloud and radiative properties within an isolated shipping corridor in the southeastern Atlantic would have been in the absence of shipping, we confidently detect a reduction in the magnitude of cloud droplet effective radius decreases within the shipping corridor and find evidence for a reduction in the magnitude of cloud brightening as well. The instantaneous radiative forcing due to aerosol–cloud interactions from the IMO 2020 regulations is estimated as O(1 W m-2 ) within the shipping corridor, lending credence to global estimates of O(0.1 W m-2 ). In addition to their geophysical significance, our results also provide independent evidence for general compliance with the IMO 2020 regulations. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether using progesterone as a trigger of a gonadotropin surge will induce ovulation and a competent corpus luteum. Methods: Patients were administered 5 or 10 mg of progesterone intramuscularly when the leading follicle reached preovulatory size. Results: We demonstrate that progesterone injections result in classical ultrasonographic hallmarks of ovulation about 48 h later and the formation of a corpus luteum competent to support pregnancy. Conclusion: Our results support further exploration of using progesterone to trigger a gonadotropin surge in assisted human reproduction. [ABSTRACT FROM AUTHOR]

The determinants of severe disease caused by West Nile virus (WNV) and why only ~1% of individuals progress to encephalitis remain poorly understood. Here, we use human and mouse enteroids, and a mouse model of pathogenesis, to explore the capacity of WNV to directly infect gastrointestinal (GI) tract cells and contribute to disease severity. At baseline, WNV poorly infects human and mouse enteroid cultures and enterocytes in mice. However, when STAT1 or type I interferon (IFN) responses are absent, GI tract cells become infected, and this is associated with augmented GI tract and blood-brain barrier (BBB) permeability, accumulation of gut-derived molecules in the brain, and more severe WNV disease. The increased gut permeability requires TNF-α signaling, and is absent in WNV-infected IFN-deficient germ-free mice. To link these findings to human disease, we measured auto-antibodies against type I IFNs in serum from WNV-infected human cohorts. A greater frequency of auto- and neutralizing antibodies against IFN-α2 or IFN-ω is present in patients with severe WNV infection, whereas virtually no asymptomatic WNV-infected subjects have such antibodies (odds ratio 24 [95% confidence interval: 3.0 − 192.5; P = 0.003]). Overall, our experiments establish that blockade of type I IFN signaling extends WNV tropism to enterocytes, which correlates with increased gut and BBB permeability, and more severe disease.In this study, Lin and Zhao et al. show that type I IFN autoantibodies promote West Nile virus infection in enterocytes, which correlates with encephalitis disease risk in humans; while in mice, type I IFN signaling defects associate with gastrointestinal tract and blood-brain barrier permeability and disease severity. [ABSTRACT FROM AUTHOR]

Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available (1,2). We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern., We performed a genome-wide inhibition of West Nile virus (WNV)-induced cell death screen using the CRISPR/Cas9 system (3-7) and lentiviruses targeting 19,050 genes (Extended Data Fig. 1a). Whereas in the [...]

The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer leaflet of their membranes, enabling TAM receptor activation and downregulation of antiviral responses. Accordingly, we hypothesized that a deficiency of TAM receptors would enhance antiviral responses and protect against viral infection. Unexpectedly, mice lacking Mertk and/or Axl, but not Tyro3, exhibited greater vulnerability to infection with neuroinvasive West Nile and La Crosse encephalitis viruses. This phenotype was associated with increased blood-brain barrier permeability, which enhanced virus entry into and infection of the brain. Activation of Mertk synergized with interferon-β to tighten cell junctions and prevent virus transit across brain microvascular endothelial cells. Because TAM receptors restrict pathogenesis of neuroinvasive viruses, these findings have implications for TAM antagonists that are currently in clinical development., The TAM receptors Tyro3, Axl, and Mertk have pleiotropic functions in cancer metastasis, angiogenesis, thrombus stabilization and innate immune regulation (1, 2). Axl and/or Mertk are expressed on cells that [...]