Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV

Dutch and German 3-year-olds’ representations of voicing alternations

The voicing contrast is neutralised syllable and word finally in Dutch and German, leading to alternations within the morphological paradigm (e.g. Dutch ‘bed(s)’, be[t] be[d]en, German ‘dog(s)’, Hun[t]-Hun[d]e). Despite structural similarity, language-specific morphological, phonological and lexical properties impact on the distribution of this alternation in the two languages. Previous acquisition research has focused on one language only, predominantly focusing on children’s production accuracy, concluding that alternations are not acquired until late in the acquisition process in either language. This paper adapts a perceptual method to investigate how voicing alternations are represented in the mental lexicon of Dutch and German 3-year-olds. Sensitivity to mispronunciations of voicing word-medially in plural forms was measured using a visual fixation procedure. Dutch children exhibited evidence of overgeneralising the voicing alternation, whereas German children consistently preferred the correct pronunciation to mispronunciations. Results indicate that the acquisition of voicing alternations is influenced by language-specific factors beyond the alternation itself

The effect of a preoperative subconjuntival injection of dexamethasone on blood–retinal barrier breakdown following scleral buckling retinal detachment surgery: a prospective randomized placebo-controlled double blind clinical trial

textabstractBackground: Blood-retinal barrier breakdown secondary to retinal detachment and retinal detachment repair is a factor in the pathogenesis of proliferative vitreoretinopathy (PVR). We wished to investigate whether an estimated 700 to 1000 ng/ml subretinal dexamethasone concentration at the time of surgery would decrease the blood-retinal barrier breakdown postoperatively. Methods: Prospective, placebo-controlled, double blind clinical trial. In 34 patients with rhegmatogenous retinal detachment scheduled for conventional scleral buckling retinal detachment surgery, a subconjunctival injection of 0.5 ml dexamethasone diphosphate (10 mg) or 0.5 ml placebo was given 5-6 hours before surgery. Differences in laser flare photometry (KOWA) measurements taken 1, 3 and 6 weeks after randomisation between dexamethasone and placebo were analysed using mixed model ANOVA, while correcting for the preoperative flare measurement. Results: Six patients did not complete the study, one because of recurrent detachment within 1 week, and five because they missed their postoperative laser flare visits. The use of dexamethasone resulted in a statistically significant decrease in laser flare measurements at the 1-week postoperative visit. Conclusion: The use of a preoperative subconjunctival injection of dexamethasone decreased 1-week postoperative blood-retina barrier breakdown in patients undergoing conventional scleral buckling retinal detachment surgery. This steroid priming could be useful as a part of a peri-operative regime that would aim at decreasing the incidence of PVR

ManyBabies 5: A large-scale investigation of the proposed shift from familiarity preference to novelty preference in infant looking time

Much of our basic understanding of cognitive and social processes in infancy relies on measures of looking time, and specifically on infants’ visual preference for a novel or familiar stimulus. However, despite being the foundation of many behavioral tasks in infant research, the determinants of infants’ visual preferences are poorly understood, and differences in the expression of preferences can be difficult to interpret. In this large-scale study, we test predictions from the Hunter and Ames model of infants' visual preferences. We investigate the effects of three factors predicted by this model to determine infants’ preference for novel versus familiar stimuli: age, stimulus familiarity, and stimulus complexity. Drawing from a large and diverse sample of infant participants (N = XX), this study will provide crucial empirical evidence for a robust and generalizable model of infant visual preferences, leading to a more solid theoretical foundation for understanding the mechanisms that underlie infants’ responses in common behavioral paradigms. Moreover, our findings will guide future studies that rely on infants' visual preferences to measure cognitive and social processes

What infant-directed speech tells us about the development of compensation for assimilation

In speech addressed to adults, words are seldom realized in their canonical, or citation, form. For example, the word ‘green’ in the phrase ‘green beans’ can often be realized as ‘greem’ due to English place assimilation, where word-final coronals take on the place of articulation of neighboring velars. In such a situation, adult listeners readily ‘undo’ the assimilatory process and perceive the underlying intended lexical form of ‘greem’ (i.e. they access the lexical representation ‘green’). An interesting developmental question is how children, with their limited lexical knowledge, come to cope with phonologically conditioned connected speech processes such as place assimilation. Here, we begin to address this issue by examining the occurrence of place assimilation in the input to English-learning 18-month-olds. Perceptual and acoustic analyses of elicited speech, as well as analysis of a corpus of spontaneous speech, all converge on the finding that caregivers do not spoon-feed their children canonical tokens of words. Rather, infant-directed speech contains just as many non-canonical realizations of words in place assimilation contexts as adult-directed speech. Implications for models of developmental speech perception are discussed

Virus-induced congenital malformations in cattle

Diagnosing the cause of bovine congenital malformations (BCMs) is challenging for bovine veterinary practitioners and laboratory diagnosticians as many known as well as a large number of not-yet reported syndromes exist. Foetal infection with certain viruses, including bovine virus diarrhea virus (BVDV), Schmallenberg virus (SBV), blue tongue virus (BTV), Akabane virus (AKAV), or Aino virus (AV), is associated with a range of congenital malformations. It is tempting for veterinary practitioners to diagnose such infections based only on the morphology of the defective offspring. However, diagnosing a virus as a cause of BCMs usually requires laboratory examination and even in such cases, interpretation of findings may be challenging due to lack of experience regarding genetic defects causing similar lesions, even in cases where virus or congenital antibodies are present. Intrauterine infection of the foetus during the susceptible periods of development, i.e. around gestation days 60–180, by BVDV, SBV, BTV, AKAV and AV may cause malformations in the central nervous system, especially in the brain. Brain lesions typically consist of hydranencephaly, porencephaly, hydrocephalus and cerebellar hypoplasia, which in case of SBV, AKAV and AV infections may be associated by malformation of the axial and appendicular skeleton, e.g. arthrogryposis multiplex congenita. Doming of the calvarium is present in some, but not all, cases. None of these lesions are pathognomonic so diagnosing a viral cause based on gross lesions is uncertain. Several genetic defects share morphology with virus induced congenital malformations, so expert advice should be sought when BCMs are encountered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-015-0145-8) contains supplementary material, which is available to authorized users