Mechanisms of Zika virus infection and neuropathogenesis

A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain–Barré syndrome associated with infection. In this review, we discuss the recent literature on ZIKV-host interactions, including new mechanistic insight concerning the basis of ZIKV-induced neuropathogenesis

The opposites task: Using general rules to test cognitive flexibility in preschoolers

A brief narrative description of the journal article, document, or resource. Executive functions play an important role in cognitive development, and during the preschool years especially, children's performance is limited in tasks that demand flexibility in their behavior. We asked whether preschoolers would exhibit limitations when they are required to apply a general rule in the context of novel stimuli on every trial (the "opposites" task). Two types of inhibitory processing were measured: response interference (resistance to interference from a competing response) and proactive interference (resistance to interference from a previously relevant rule). Group data show 3-year-olds have difficulty inhibiting prepotent tendencies under these conditions, whereas 5-year-olds' accuracy is near ceiling in the task. (Contains 4 footnotes and 1 table.

SARS-CoV-2 and interferon blockade

© 2020, The Author(s). The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications

The ALTO project at IPN Orsay

In order to probe neutron rich radioactive noble gases produced by photo-fission, a PARRNe1 experiment (Production d'Atomes Radioactifs Riches en Neutrons) has been carried out at CERN. The incident electron beam of 50 MeV was delivered by the LIL machine: LEP Injector Linac. The experiment allowed to compare under the same conditions two production methods of radioactive noble gases: fission induced by fast neutrons and photo-fission. The obtained results show that the use of the electrons is a promising mode to get intense neutron rich ion beams. Thereafter, the success of this photo-fission experiment, a conceptual design for the installation at IPN Orsay of a 50 MeV electron accelerator close to the PARRNe-2 device has been worked out: ALTO Project. This work has started within a collaboration between IPNO, LAL and CERN groups.Comment: 14 pages, pdf file, International School-Seminar on Heavy-Ion Physics 7 (2002

The interferon-induced exonuclease ISG20 exerts antiviral activity through upregulation of type I interferon response proteins

The host immune responses to infection lead to the production of type I interferon (IFN), and the upregulation of interferon-stimulated genes (ISGs) reduces virus replication and virus dissemination within a host. Ectopic expression of the interferon-induced 20-kDa exonuclease ISG20 suppressed replication of chikungunya virus and Venezuelan equine encephalitis virus, two mosquito-vectored RNA alphaviruses. Since the replication of alphavirus genomes occurs exclusively in the cytoplasm, the mechanism of nucleus-localized ISG20 inhibition of replication is unclear. In this study, we determined that ISG20 acts as a master regulator of over 100 genes, many of which are ISGs. Specifically, ISG20 upregulated IFIT1 genes and inhibited translation of the alphavirus genome. Furthermore, IFIT1-sensitive alphavirus replication was increased in Isg20−/− mice compared to the replication of wild-type viruses but not in cells ectopically expressing ISG20. We propose that ISG20 acts as an indirect regulator of RNA virus replication in the cytoplasm through the upregulation of many other ISGs.Type I interferon (IFN)-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20-kDa ISG ISG20 is a nuclear 3′–5′ exonuclease with preference for single-stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Although the exonuclease activity of ISG20 has been shown to degrade viral RNA in vitro, evidence has yet to be presented that virus inhibition in cells requires this activity. Here, we utilized a combination of an inducible, ectopic expression system and newly generated Isg20−/− mice to investigate mechanisms and consequences of ISG20-mediated restriction. Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus and restricted replication of chikungunya and Venezuelan equine encephalitis viruses. Although restriction by ISG20 was associated with inhibition of translation of infecting genomic RNA, degradation of viral RNAs was not observed. Instead, translation inhibition of viral RNA was associated with ISG20-induced upregulation of over 100 other genes, many of which encode known antiviral effectors. ISG20 modulated the production of IFIT1, an ISG that suppresses translation of alphavirus RNAs. Consistent with this observation, the pathogenicity of IFIT1-sensitive alphaviruses was increased in Isg20−/− mice compared to that of wild-type viruses but not in cells ectopically expressing ISG20. Our findings establish an indirect role for ISG20 in the early restriction of RNA virus replication by regulating expression of other ISGs that inhibit translation and possibly other activities in the replication cycle

Attachment-based family therapy for adolescents with suicidal ideation: a randomized controlled trial.

OBJECTIVE: To evaluate whether Attachment-Based Family Therapy (ABFT) is more effective than Enhanced Usual Care (EUC) for reducing suicidal ideation and depressive symptoms in adolescents. METHOD: This was a randomized controlled trial of suicidal adolescents between the ages of 12 and 17, identified in primary care and emergency departments. Of 341 adolescents screened, 66 (70% African American) entered the study for 3 months of treatment. Assessment occurred at baseline, 6 weeks, 12 weeks, and 24 weeks. ABFT consisted of individual and family meetings, and EUC consisted of a facilitated referral to other providers. All participants received weekly monitoring and access to a 24-hour crisis phone. Trajectory of change and clinical recovery were measured for suicidal ideation and depressive symptoms. RESULTS: Using intent to treat, patients in ABFT demonstrated significantly greater rates of change on self-reported suicidal ideation at post-treatment evaluation, and benefits were maintained at follow-up, with a strong overall effect size (ES = 0.97). Between-group differences were similar on clinician ratings. Significantly more patients in ABFT met criteria for clinical recovery on suicidal ideation post-treatment (87%; 95% confidence interval [CI] = 74.6-99.6) than patients in EUC (51.7%; 95% CI = 32.4-54.32). Benefits were maintained at follow-up (ABFT, 70%; 95% CI = 52.6-87.4; EUC 34.6%; 95% CI = 15.6-54.2; odds ratio = 4.41). Patterns of depressive symptoms over time were similar, as were results for a subsample of adolescents with diagnosed depression. Retention in ABFT was higher than in EUC (mean = 9.7 versus 2.9). CONCLUSIONS: ABFT is more efficacious than EUC in reducing suicidal ideation and depressive symptoms in adolescents. Additional research is warranted to confirm treatment efficacy and to test the proposed mechanism of change (the Family Safety Net Study).Clinical Trial Registry Information: Preventing Youth Suicide in Primary Care: A Family Model, URL: http://www.clinicaltrials.gov, unique identifier: NCT00604097

Transport control by coherent zonal flows in the core/edge transitional regime

3D Braginskii turbulence simulations show that the energy flux in the core/edge transition region of a tokamak is strongly modulated - locally and on average - by radially propagating, nearly coherent sinusoidal or solitary zonal flows. The flows are geodesic acoustic modes (GAM), which are primarily driven by the Stringer-Winsor term. The flow amplitude together with the average anomalous transport sensitively depend on the GAM frequency and on the magnetic curvature acting on the flows, which could be influenced in a real tokamak, e.g., by shaping the plasma cross section. The local modulation of the turbulence by the flows and the excitation of the flows are due to wave-kinetic effects, which have been studied for the first time in a turbulence simulation.Comment: 5 pages, 5 figures, submitted to PR

Interferon lambda protects the female reproductive tract against Zika virus infection

Zika virus infections can cause devastating congenital birth defects but the underlying interactions with the host immune system are not well understood. Here, the authors examine the immune basis of vaginal protection and susceptibility to Zika viral infection, and identify a hormonal dependent role for interferon-lambda-mediated protection against disease