A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly

Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to life-long neurological handicap. Collectively NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n=85 anencephaly and n=5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N=509), we identified 397 rare variants (MAF<1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly

Beyond the Langevin horn: transducer arrays for the acoustic levitation of liquid drops

The acoustic levitation of liquid drops has been a key phenomenon for more than 40 years, driven partly by the ability to mimic a microgravity environment. It has seen more than 700 research articles published in this time and has seen a recent resurgence in the past 5 years, thanks to low cost developments. As well as investigating the basic physics of levitated drops, acoustic levitation has been touted for container free delivery of samples to a variety of measurements systems, most notably in various spectroscopy techniques including Raman and Fourier transform infrared in addition to numerous X-ray techniques. For 30 years, the workhorse of the acoustic levitation apparatus was a stack comprising a piezoelectric transducer coupled to a horn shaped radiative element often referred to as the Langevin horn. Decades of effort have been dedicated to such devices, paired with a matching and opposing device or a reflector, but they have a significant dependence on temperature and require precision alignment. The last decade has seen a significant shift away from these in favor of arrays of digitally driven, inexpensive transducers, giving a new dynamic to the topic which we review herein

Modeling the interactions between river morphodynamics and riparian vegetation

The study of river-riparian vegetation interactions is an important and intriguing research field in geophysics. Vegetation is an active element of the ecological dynamics of a floodplain which interacts with the fluvial processes and affects the flow field, sediment transport, and the morphology of the river. In turn, the river provides water, sediments, nutrients, and seeds to the nearby riparian vegetation, depending on the hydrological, hydraulic, and geomorphological characteristic of the stream. In the past, the study of this complex theme was approached in two different ways. On the one hand, the subject was faced from a mainly qualitative point of view by ecologists and biogeographers. Riparian vegetation dynamics and its spatial patterns have been described and demonstrated in detail, and the key role of several fluvial processes has been shown, but no mathematical models have been proposed. On the other hand, the quantitative approach to fluvial processes, which is typical of engineers, has led to the development of several morphodynamic models. However, the biological aspect has usually been neglected, and vegetation has only been considered as a static element. In recent years, different scientific communities (ranging from ecologists to biogeographers and from geomorphologists to hydrologists and fluvial engineers) have begun to collaborate and have proposed both semiquantitative and quantitative models of river-vegetation interconnections. These models demonstrate the importance of linking fluvial morphodynamics and riparian vegetation dynamics to understand the key processes that regulate a riparian environment in order to foresee the impact of anthropogenic actions and to carefully manage and rehabilitate riparian areas. In the first part of this work, we review the main interactions between rivers and riparian vegetation, and their possible modeling. In the second part, we discuss the semiquantitative and quantitative models which have been proposed to date, considering both multi- and single-thread river

Association of Transcription Factor 4 (TCF4) variants with schizophrenia and intellectual disability

Genome wide association studies (GWAS) have revolutionized the study of complex diseases and have uncovered common genetic variants associated with an increased risk for major psychiatric disorders. A recently published schizophrenia GWAS replicated earlier findings implicating common variants in Transcription factor 4 (TCF4) as susceptibility loci for schizophrenia. By contrast, loss of function TCF4 mutations, although rare, cause Pitt-Hopkins syndrome (PTHS); a disorder characterized by intellectual disability (ID), developmental delay and behavioral abnormalities. TCF4 mutations have also been described in individuals with ID and non-syndromic neurodevelopmental disorders. TCF4 is a member of the basic helix-loop-helix (bHLH) family of transcription factors that regulate gene expression at E-box-containing promoters and enhancers. Accordingly, TCF4 has an important role during brain development and can interact with a wide array of transcriptional regulators including some proneural factors. TCF4 may, therefore, participate in the transcriptional networks that regulate the maintenance and differentiation of distinct cell types during brain development. Here, we review the role of TCF4 variants in the context of several distinct brain disorders associated with impaired cognition