Interaction of Ebola Virus with the Innate Immune System

Ebola viruses (EBOV) are zoonotic pathogens that cause severe diseases in humans and have been responsible for several disease outbreaks over the past 40 years. Ebola virus disease (EVD) leads to death on an average of 45–50% of cases, but in some outbreaks, the figures have been higher. The largest EVD outbreak in West Africa in 2014–2015 lead to more than 28,000 cases and 11,300 fatalities. Host innate immune responses are vital in restricting the spread of viral infections including that of Ebola virus. EBOV and some other filoviruses are known to trigger uncontrolled virus replication by suppressing host innate immune responses, mainly by targeting the antiviral response through virus proteins. At least EBOV VP24 and VP35 proteins have been shown to inhibit the expression of type I and III interferon (IFN) genes as well as to inhibit IFN signaling leading to downregulated IFN-induced antiviral responses. In this review we concentrate on describing the mechanisms by which EBOV contributes to the pathogenesis of severe disease and on how the virus interacts with the host innate immune system

Effectiveness of the Close Collaboration with Parents intervention on parent-infant closeness in NICU

BackgroundParent-infant closeness during hospital care of newborns has many benefits for both infants and parents. We developed an educational intervention for neonatal staff, Close Collaboration with Parents, to increase parent-infant closeness during hospital care. The aim of this study was to evaluate the effectiveness of the intervention on parent-infant closeness in nine hospitals in Finland.MethodsParents of hospitalized infants were recruited in the hospitals during 3-month periods before and after the Close Collaboration with Parents intervention. The data were collected using daily Closeness diaries. Mothers and fathers separately filled in the time they spent in the hospital and the time of skin-to-skin contact with their infant during each hospital care day until discharge. Statistical analyses were done using a linear model with covariates.ResultsDiaries were kept before and after the intervention by a total of 170 and 129 mothers and 126 and 84 fathers, respectively. Either parent was present on average 453min per day before the intervention and 620min after the intervention in the neonatal unit. In the adjusted model, the increase was 99min per day (p=0.0007). The infants were in skin-to-skin contact on average 76min per day before the intervention and 114min after the intervention. In the adjusted model, skin-to-skin contact increased by 24min per day (p=0.0405).ConclusionThe Close Collaboration with Parents intervention increased parents' presence and skin-to-skin contact in nine hospitals. This study suggests that parent-infant closeness may be one mediating factor explaining benefits of parenting interventions.Trial registrationClinicalTrials.govNCT04635150. Retrospectively registered

HyperCP: A high-rate spectrometer for the study of charged hyperon and kaon decays

The HyperCP experiment (Fermilab E871) was designed to search for rare phenomena in the decays of charged strange particles, in particular CP violation in $\Xi$ and $\Lambda$ hyperon decays with a sensitivity of $10^{-4}$. Intense charged secondary beams were produced by 800 GeV/c protons and momentum-selected by a magnetic channel. Decay products were detected in a large-acceptance, high-rate magnetic spectrometer using multiwire proportional chambers, trigger hodoscopes, a hadronic calorimeter, and a muon-detection system. Nearly identical acceptances and efficiencies for hyperons and antihyperons decaying within an evacuated volume were achieved by reversing the polarities of the channel and spectrometer magnets. A high-rate data-acquisition system enabled 231 billion events to be recorded in twelve months of data-taking.Comment: 107 pages, 45 Postscript figures, 14 tables, Elsevier LaTeX, submitted to Nucl. Instrum. Meth.

Filovirus VP24 Proteins Differentially Regulate RIG-I and MDA5-Dependent Type I and III Interferon Promoter Activation

Filovirus family consists of highly pathogenic viruses that have caused fatal outbreaks especially in many African countries. Previously, research focus has been on Ebola, Sudan and Marburg viruses leaving other filoviruses less well studied. Filoviruses, in general, pose a significant global threat since they are highly virulent and potentially transmissible between humans causing sporadic infections and local or widespread epidemics. Filoviruses have the ability to downregulate innate immunity, and especially viral protein 24 (VP24), VP35 and VP40 have variably been shown to interfere with interferon (IFN) gene expression and signaling. Here we systematically analyzed the ability of VP24 proteins of nine filovirus family members to interfere with retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated antigen 5 (MDA5) induced IFN-beta and IFN-lambda 1 promoter activation. All VP24 proteins were localized both in the cell cytoplasm and nucleus in variable amounts. VP24 proteins of Zaire and Sudan ebolaviruses, Lloviu, Tai Forest, Reston, Marburg and Bundibugyo viruses (EBOV, SUDV, LLOV, TAFV, RESTV, MARV and BDBV, respectively) were found to inhibit both RIG-I and MDA5 stimulated IFN-beta and IFN-lambda 1 promoter activation. The inhibition takes place downstream of interferon regulatory factor 3 phosphorylation suggesting the inhibition to occur in the nucleus. VP24 proteins of Mengla (MLAV) or Bombali viruses (BOMV) did not inhibit IFN-beta or IFN-lambda 1 promoter activation. Six ebolavirus VP24s and Lloviu VP24 bound tightly, whereas MARV and MLAV VP24s bound weakly, to importin alpha 5, the subtype that regulates the nuclear import of STAT complexes. MARV and MLAV VP24 binding to importin alpha 5 was very weak. Our data provides new information on the innate immune inhibitory mechanisms of filovirus VP24 proteins, which may contribute to the pathogenesis of filovirus infections

Decoupling property of the supersymmetric Higgs sector with four doublets

In supersymmetric standard models with multi Higgs doublet fields, selfcoupling constants in the Higgs potential come only from the D-terms at the tree level. We investigate the decoupling property of additional two heavier Higgs doublet fields in the supersymmetric standard model with four Higgs doublets. In particular, we study how they can modify the predictions on the quantities well predicted in the minimal supersymmetric standard model (MSSM), when the extra doublet fields are rather heavy to be measured at collider experiments. The B-term mixing between these extra heavy Higgs bosons and the relatively light MSSM-like Higgs bosons can significantly change the predictions in the MSSM such as on the masses of MSSM-like Higgs bosons as well as the mixing angle for the two light CP-even scalar states. We first give formulae for deviations in the observables of the MSSM in the decoupling region for the extra two doublet fields. We then examine possible deviations in the Higgs sector numerically, and discuss their phenomenological implications.Comment: 26 pages, 24 figures, text sligtly modified,version to appear in Journal of High Energy Physic

The Spin Structure of the Nucleon

We present an overview of recent experimental and theoretical advances in our understanding of the spin structure of protons and neutrons.Comment: 84 pages, 29 figure

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Genetic variation in the Solanaceae fruit bearing species lulo and tree tomato revealed by Conserved Ortholog (COSII) markers

The Lulo or naranjilla (Solanum quitoense Lam.) and the tree tomato or tamarillo (Solanum betaceum Cav. Sendt.) are both Andean tropical fruit species with high nutritional value and the potential for becoming premium products in local and export markets. Herein, we present a report on the genetic characterization of 62 accessions of lulos (n = 32) and tree tomatoes (n = 30) through the use of PCR-based markers developed from single-copy conserved orthologous genes (COSII) in other Solanaceae (Asterid) species. We successfully PCR amplified a set of these markers for lulos (34 out of 46 initially tested) and tree tomatoes (26 out of 41) for molecular studies. Six polymorphic COSII markers were found in lulo with a total of 47 alleles and five polymorphic markers in tree tomato with a total of 39 alleles in the two populations. Further genetic analyses indicated a high population structure (with FST > 0.90), which may be a result of low migration between populations, adaptation to various niches and the number of markers evaluated. We propose COSII markers as sound tools for molecular studies, conservation and the breeding of these two fruit species

Modulation of defense signal transduction by flagellin-induced WRKY41 transcription factor in Arabidopsis thaliana

Flagellin, a component of the flagellar filament of Pseudomonas syringae pv. tabaci 6605 (Pta), induces hypersensitive reaction in its non-host Arabidopsis thaliana. We identified the WRKY41 gene, which belongs to a multigene family encoding WRKY plant-specific transcription factors, as one of the flagellin-inducible genes in A. thaliana. Expression of WRKY41 is induced by inoculation with the incompatible pathogen P. syringae pv. tomato DC3000 (Pto) possessing AvrRpt2 and the non-host pathogens Pta within 6-h after inoculation, but not by inoculation with the compatible Pto. Expression of WRKY41 was also induced by inoculation of A. thaliana with an hrp-type three secretion system (T3SS)-defective mutant of Pto, indicating that effectors produced by T3SS in the Pto wild-type suppress the activation of WRKY41. Arabidopsis overexpressing WRKY41 showed enhanced resistance to the Pto wild-type but increased susceptibility to Erwinia carotovora EC1. WRKY41-overexpressing Arabidopsis constitutively expresses the PR5 gene, but suppresses the methyl jasmonate-induced PDF1.2 gene expression. These results demonstrate that WRKY41 may be a key regulator in the cross talk of salicylic acid and jasmonic acid pathways.</p