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021) and CNVs (9 of 397 vs 24 of 562, p=0.065) compared with individuals who manifested both autism and ID (IQ less then 70). Pathogenic variants disrupting autism-associated genes conferred a 4.85-fold increased risk (p=0.011) for comorbid ID, while de novo variants observed in individuals with high-functioning autism disrupted genes with little functional relevance towards neurodevelopment. CONCLUSIONS Pathogenic de novo variants disrupting autism-associated genes contribute towards autism and ID comorbidity, while other genetic factors are likely to be causal for high-functioning autism. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Identifying environmental risk and protective exposures that have causal effects on health is an important scientific goal. Many environmental exposures are nonrandomly allocated and influenced by dispositional factors including inherited ones. We review family-based designs that can separate the influence of environmental exposures from inherited influences shared between parent and offspring. https://www.selleckchem.com/products/terfenadine.html We focus on prenatal exposures. We highlight that the family-based designs that can separate the prenatal environment from inherited confounds are different to those that are able to pull apart later-life environmental exposures from inherited confounds. We provide a brief review of the literature on maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) and conduct problems; these inconsistencies in the literature make a review useful and this illustrates that results of family-based genetically informed studies are inconsistent with a causal interpretation for this exposure and these two offspring outcomes. Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.Non-Hodgkin lymphomas (NHLs) are a diverse group of entities, both clinically and molecularly. Here, we review the evolution of classification schemes in B-cell lymphoma, noting the now standard WHO classification system that is based on immune cell-of-origin and molecular phenotypes. We review how lymphomas arise throughout the B-cell development process as well as the molecular and clinical features of prominent B-cell lymphomas. We provide an overview of the major progress that has occurred over the past decade in terms of our molecular understanding of these diseases. We discuss treatment options available and focus on a number of the diverse research tools that have been employed to improve our understanding of these diseases. We discuss the problem of heterogeneity in lymphomas and anticipate that the near future will bring significant advances that provide a measurable impact on NHL outcomes. Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.The last decade has witnessed tremendous progress in immunology and vaccinology, owing to several scientific and technological breakthroughs. Systems vaccinology is a field that has emerged at the forefront of vaccine research and development and provides a unique way to probe immune responses to vaccination in humans. The goals of systems vaccinology are to use systems-based approaches to define signatures that can be used to predict vaccine immunogenicity and efficacy and to delineate the molecular mechanisms driving protective immunity. The application of systems biological approaches in influenza vaccination studies has enabled the discovery of early signatures that predict immunogenicity to vaccination and yielded novel mechanistic insights about vaccine-induced immunity. Here we review the contributions of systems vaccinology to influenza vaccine development and critically examine the potential of systems vaccinology toward enabling the development of a universal influenza vaccine that provides robust and durable immunity against diverse influenza viruses. Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired under selective pressure, have been shown to reduce drug binding, thereby affecting the effectiveness of NA inhibitors. Drug resistance and other drawbacks have prompted the search for the next-generation NA-targeting therapeutics. One of the promising approaches is the identification of monoclonal antibodies (mAbs) targeting the conserved NA epitopes. Anti-NA mAbs demonstrate Fab-based antiviral activity supplemented with Fc-mediated immune effector functions. Antiviral Fc-conjugates offer another cutting-edge strategy that is based on a multimodal mechanism of action. These novel antiviral agents are composed of a small-molecule NA inhibitor and an Fc-region that simultaneously engages the immune system. The significant advancements made in recent years further support the value of NA as an attractive target for the antiviral development. Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.Horses are the third major mammalian species, along with humans and swine, long known to be subject to acute upper respiratory disease from influenza A virus infection. The viruses responsible are subtype H7N7, which is believed extinct, and H3N8, which circulates worldwide. The equine influenza lineages are clearly divergent from avian influenza lineages of the same subtypes. Their genetic evolution and potential for interspecies transmission, as well as clinical features and epidemiology, are discussed. Equine influenza is spread internationally and vaccination is central to control efforts. The current mechanism of international surveillance and virus strain recommendations for vaccines is described. Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.