Human and murine IFIT1 proteins do not restrict infection of negative-sense RNA viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae families

UNLABELLED: Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5\u27-triphosphates (5\u27-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5\u27-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1(-/-) and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1(-/-) and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5\u27 ends of IAV gene segments. The affinity for 5\u27-ppp RNA was approximately 10-fold lower than that for non-2\u27-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. IMPORTANCE: Negative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this study, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis both in vitro and in vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses

Valley splitting of Si/SiGe heterostructures in tilted magnetic fields

We have investigated the valley splitting of two-dimensional electrons in high quality Si/Si$_{1-x}$Ge$_x$ heterostructures under tilted magnetic fields. For all the samples in our study, the valley splitting at filling factor $\nu=3$ ($\Delta_3$) is significantly different before and after the coincidence angle, at which energy levels cross at the Fermi level. On both sides of the coincidence, a linear density dependence of $\Delta_3$ on the electron density was observed, while the slope of these two configurations differs by more than a factor of two. We argue that screening of the Coulomb interaction from the low-lying filled levels, which also explains the observed spin-dependent resistivity, is responsible for the large difference of $\Delta_3$ before and after the coincidence.Comment: REVTEX 4 pages, 4 figure

Social conditioning and extinction paradigm: A translational study in virtual reality

In human beings, experiments investigating fear conditioning with social stimuli are rare. The current study aims at translating an animal model for social fear conditioning (SFC) to a human sample using an operant SFC paradigm in virtual reality (VR). Forty participants actively (using a joystick) approached virtual male agents that served as conditioned stimuli (CS). During the acquisition phase, unconditioned stimuli (US), a combination of an air blast (5 bar, 10 ms) and a female scream (95 dB, 40 ms), were presented when participants reached a defined proximity to the agent with a contingency of 75% for CS+ agents and never for CS- agents. During the extinction and the test phases, no US was delivered. Outcome variables were pleasantness ratings and physiological reactions in heart rate and fear-potentiated startle. Additionally, the influence of social anxiety, which was measured with the Social Phobia Inventory scale, was evaluated. As expected after the acquisition phase the CS+ was rated clearly less pleasant than the CS-. This difference vanished during extinction. Furthermore, the HR remained high for the CS+, while the HR for the CS- was clearly lower after than before the acquisition. Furthermore, a clear difference between CS+ and CS- after the acquisition indicated successful conditioning on this translational measure. Contrariwise extinction was not observed on the physiological variables. Importantly, at the generalization test, higher socially fearful participants rated pleasantness of all agents as low whereas the lower socially fearful participants rated pleasantness as low only for the CS+. SFC was successfully induced and extinguished confirming operant conditioning in this SFC paradigm. These findings suggest that the paradigm is suitable to expand the knowledge about the learning and unlearning of social fears. Further studies should investigate the operant mechanisms of development and treatment of social anxiety disorder

An annotated bird checklist for Gam island, Raja Ampat, including field notes on species monitoring and conservation

Species checklists are a fundamental component of biodiversity research. They foster understanding of species distributions and habitat preferences, thus reducing gaps of knowledge in geographical occurrences of species. Especially in light of the limited availability of data on species distributions for Tanah Papua, an increasing scientific focus on the region is crucial to foster and refine the knowledge of species occurrences and to inform potential conservation planning. Despite a strong focus on conservation of Raja Ampat´s marine areas, surprisingly few studies have focused on the terrestrial biodiversity of the archipelago. As a consequence, detailed species checklists are largely missing. Here, we provide a preliminary bird species checklist for the island of Gam and its surrounding islands, located in the central Raja Ampat archipelago. During nine sampling periods between 2013 and 2019, we recorded 132 bird species in six distinct habitat types. Of the detected species, six are considered threatened by IUCN Red List criteria. We further recorded three new species for Gam Island, thereby expanding their known extent of occurrence

Elucidation of the Cellular Interactome of Ebola Virus Nucleoprotein and Identification of Therapeutic Targets

Ebola virus (EBOV) infection results in severe disease and in some cases lethal haemorrhagic fever. The infection is directed by seven viral genes that encode nine viral proteins. By definition viruses are obligate intracellular parasites and require aspects of host cell biology in order to replicate their genetic material, assemble new virus particles and subvert host cell anti-viral responses. Currently licenced antivirals are targeted against viral proteins to inhibit their function. However, experience with treating HIV and influenza virus demonstrates that resistant viruses are soon selected. An emerging area in virology is to transiently target host cell proteins that play critical proviral roles in virus biology, especially for acute infections. This has the advantage that the protein being targeted is evolutionary removed from the genome of the virus. Proteomics can aid in discovery biology and identify cellular proteins that may be utilised by the virus to facilitate infection. This work focused on defining the interactome of the EBOV nucleoprotein and identified that cellular chaperones, including HSP70, associate with this protein to promote stability. Utilisation of a mini-genome replication system based on a recent Makona isolate demonstrated that disrupting the stability of NP had an adverse effect on viral RNA synthesis

Psychotherapy in Europe

Psychotherapy was an invention of European modernity, but as the 20th century unfolded, and we trace how it crossed national and continental borders, its goals and the particular techniques by which it operated become harder to pin down. This introduction briefly draws together the historical literature on psychotherapy in Europe, asking comparative questions about the role of location and culture, and networks of transmission and transformation. It introduces the six articles in this special issue on Greece, Hungary, Yugoslavia, Russia, Britain and Sweden as well as its parallel special issue of History of Psychology on ‘Psychotherapy in the Americas’. It traces what these articles tell us about how therapeutic developments were entangled with the dramatic, and often traumatic, political events across the continent: in the wake of the Second World War, the emergence of Communist and authoritarian regimes, the establishment of welfare states and the advance of neoliberalism

Nonprimate hepaciviruses in domestic horses, United kingdom

Although the origin of hepatitis C virus infections in humans remains undetermined, a close homolog of this virus, termed canine hepacivirus (CHV) and found in respiratory secretions of dogs, provides evidence for a wider distribution of hepaciviruses in mammals. We determined frequencies of active infection among dogs and other mammals in the United Kingdom. Samples from dogs (46 respiratory, 99 plasma, 45 autopsy samples) were CHV negative by PCR. Screening of 362 samples from cats, horses, donkeys, rodents, and pigs identified 3 (2%) positive samples from 142 horses. These samples were genetically divergent from CHV and nonprimate hepaciviruses that horses were infected with during 2012 in New York state, USA. Investigation of infected horses demonstrated nonprimate hepacivirus persistence, high viral loads in plasma (105–107 RNA copies/mL), and liver function test results usually within reference ranges, although several values ranged from high normal to mildly elevated. Disease associations and host range of nonprimate hepaciviruses warrant further investigation