Shprintzen - Goldberg syndrome without intellectual disability: A clinical report and review of literature.

Shprintzen-Goldberg syndrome is a rare systemic connective tissue disorder caused by heterozygous mutations in the Sloan-Kettering Institute (SKI) gene. The clinical presentation is reminiscent of Marfan and Loeys-Dietz syndromes, making differential diagnosis challenging. Shprintzen-Goldberg syndrome's distinctive features are craniosynostosis and learning disabilities.

Leveraging large-scale multi-omics evidences to identify therapeutic targets from genome-wide association studies.

Background: Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes.

Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.

While significant advances have been made in understanding renal pathophysiology, less is known about the role of glycosphingolipid (GSL) metabolism in driving organ dysfunction. Here, we used a small molecule inhibitor of glucosylceramide synthase to modulate GSL levels in three mouse models of distinct renal pathologies: Alport syndrome (Col4a3 KO), polycystic kidney disease (Nek8), and steroid-resistant nephrotic syndrome (Nphs2 cKO). At the tissue level, we identified a core immune-enriched transcriptional signature that was shared across models and enriched in human polycystic kidney disease.

Interplay between oncolytic measles virus, macrophages and cancer cells induces a proinflammatory tumor microenvironment.

Attenuated measles virus (MV) exerts its oncolytic activity in malignant pleural mesothelioma (MPM) cells that lack type-I interferon (IFN-I) production or responsiveness. However, other cells in the tumor microenvironment (TME), such as myeloid cells, possess functional antiviral pathways. In this study, we aimed to characterize the interplay between MV and the myeloid cells in human MPM.

Using science communication research to practice iterative engagement in collaborative nutrient management.

Thoughtful science communication is essential for the success of collaborative, transdisciplinary environmental research. We present an innovative evaluation of a four-year pilot project that took a highly engaged and collaborative approach to managing excess nutrients in the Cape Cod region of Massachusetts, USA. The evaluation approach included mid- and end-of-project interviews with researchers and project partners and a reflection from the lead science communication researcher.

Genetic analyses of inflammatory polyneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy identified candidate genes.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, immune-mediated disorder in which an aberrant immune response causes demyelination and axonal damage of the peripheral nerves. Genetic contribution to CIDP is unclear and no genome-wide association study (GWAS) has been reported so far. In this study, we aimed to identify CIDP-related risk loci, genes, and pathways.

Lessons learned and recommendations in conducting solutions-driven environmental and public health research.

Solutions-driven research is a transdisciplinary approach that incorporates diverse forms of expertise to identify solutions to stakeholder-identified environmental problems. This qualitative evaluation of early solutions-driven research projects provides transferable recommendations to improve researcher and stakeholder experiences and outcomes in transdisciplinary environmental research projects. Researchers with the U.

Genome-wide association study analysis of disease severity in Acne reveals novel biological insights.

Acne vulgaris is a common skin disease that affects >85% of teenage young adults among which >8% develop severe lesions that leaves permanent scars. Genetic heritability studies of acne in twin cohorts have estimated that the heritability for acne is 80%. Previous genome-wide association studies (GWAS) have identified 50 genetic associated with increased risk of developing acne when compared to healthy individuals.

Numerical evidence of a universal critical behavior of two-dimensional and three-dimensional random quantum clock and Potts models.

The random quantum q-state clock and Potts models are studied in two and three dimensions. The existence of Griffiths phases is tested in the two-dimensional case with q=6 by sampling the integrated probability distribution of local susceptibilities of the equivalent McCoy-Wu three-dimensional classical models with Monte Carlo simulations. For the random Potts model, numerical evidence of the existence of Griffiths phases is given and the finite-size effects are analyzed.

Oncolytic attenuated measles virus encoding NY-ESO-1 induces HLA I and II presentation of this tumor antigen by melanoma and dendritic cells.

Antitumor virotherapy stimulates the antitumor immune response during tumor cell lysis induced by oncolytic viruses (OVs). OV can be modified to express additional transgenes that enhance their therapeutic potential. In this study, we armed the spontaneously oncolytic Schwarz strain of measles viruses (MVs) with the gene encoding the cancer/testis antigen NY-ESO-1 to obtain MVny.

DAN: A Segmentation-Free Document Attention Network for Handwritten Document Recognition.

Unconstrained handwritten text recognition is a challenging computer vision task. It is traditionally handled by a two-step approach, combining line segmentation followed by text line recognition. For the first time, we propose an end-to-end segmentation-free architecture for the task of handwritten document recognition: the Document Attention Network.

Advancing the scholarship and practice of stakeholder engagement in working landscapes: a co-produced research agenda.

Unlabelled: Participatory approaches to science and decision making, including stakeholder engagement, are increasingly common for managing complex socio-ecological challenges in working landscapes. However, critical questions about stakeholder engagement in this space remain. These include normative, political, and ethical questions concerning who participates, who benefits and loses, what good can be accomplished, and for what, whom, and by who.

Using researcher and stakeholder perspectives to develop promising practices to improve stakeholder engagement in the solutions-driven research process.

Unlabelled: Translational approaches to science have the potential to produce research that better meets the needs of community stakeholders and advances scientific understanding. Researchers involved in translational research make committed efforts to increased engagement and communication with stakeholders throughout the research process, from planning through implementation and evaluation. Referred to as solutions-driven research within the U.

A systematic analysis of gene-gene interaction in multiple sclerosis.

Background: For the most part, genome-wide association studies (GWAS) have only partially explained the heritability of complex diseases. One of their limitations is to assume independent contributions of individual variants to the phenotype. Many tools have therefore been developed to investigate the interactions between distant loci, or epistasis.

CRISPR-Cas9 Engineering in Hypobetalipoproteinemia: A Promising Tool for Functional Studies of Novel Variants.

Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in the gene, a condition associated with fatty liver and steatohepatitis. Nevertheless, many families with a FHBL phenotype carry missense variants of uncertain significance (VUS).

[Medulloblastoma : management of a usually pediatric tumour in a young adult].

Medulloblastoma is a cerebellar grade IV tumour according to the WHO classification, mainly seen in children under the age of 15. This cancer can nevertheless occur in adults. We report the case of a 22-year-old patient with a medulloblastoma disseminated in the spine.

Apoptosis during ZIKA Virus Infection: Too Soon or Too Late?

Cell death by apoptosis is a major cellular response in the control of tissue homeostasis and as a defense mechanism in the case of cellular aggression such as an infection. Cell self-destruction is part of antiviral responses, aimed at limiting the spread of a virus. Although it may contribute to the deleterious effects in infectious pathology, apoptosis remains a key mechanism for viral clearance and the resolution of infection.

End-to-End Handwritten Paragraph Text Recognition Using a Vertical Attention Network.

Unconstrained handwritten text recognition remains challenging for computer vision systems. Paragraph text recognition is traditionally achieved by two models: the first one for line segmentation and the second one for text line recognition. We propose a unified end-to-end model using hybrid attention to tackle this task.

Nonlinear post-selection inference for genome-wide association studies.

To address the lack of statistical power and interpretability of genome-wide association studies (GWAS), gene-level analyses combine the p-values of individual single nucleotide polymorphisms (SNPs) into gene statistics. However, using all SNPs mapped to a gene, including those with low association scores, can mask the association signal of a gene.We therefore propose a new two-step strategy, consisting in first selecting the SNPs most associated with the phenotype within a given gene, before testing their joint effect on the phenotype.

Homozygous Co-Deletion of Type I Interferons and Genes in Thoracic Cancers: Potential Consequences for Therapy.

Homozygous deletion (HD) of the tumor suppressor gene is the most frequent genetic alteration in malignant pleural mesothelioma and is also frequent in non-small cell lung cancers. This HD is often accompanied by the HD of the type I interferons (IFN I) genes that are located closed to the gene on the p21.3 region of chromosome 9.

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network.

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs).

Novel methods for epistasis detection in genome-wide association studies.

More and more genome-wide association studies are being designed to uncover the full genetic basis of common diseases. Nonetheless, the resulting loci are often insufficient to fully recover the observed heritability. Epistasis, or gene-gene interaction, is one of many hypotheses put forward to explain this missing heritability.

The distribution of biodiversity richness in the tropics.

We compare the numbers of vascular plant species in the three major tropical areas. The Afrotropical Region (Africa south of the Sahara Desert plus Madagascar), roughly equal in size to the Latin American Region (Mexico southward), has only 56,451 recorded species (about 170 being added annually), as compared with 118,308 recorded species (about 750 being added annually) in Latin America. Southeast Asia, only a quarter the size of the other two tropical areas, has approximately 50,000 recorded species, with an average of 364 being added annually.

Frequent Homozygous Deletions of Type I Interferon Genes in Pleural Mesothelioma Confer Sensitivity to Oncolytic Measles Virus.

Introduction: Oncolytic immunotherapy is based on the use of nonpathogenic replicative oncolytic viruses that infect and kill tumor cells exclusively. Recently, we found that the spontaneous oncolytic activity of the Schwarz strain of measles virus (MV) against human malignant pleural mesothelioma (MPM) depends on defects in the antiviral type I interferon (IFN-I) response in tumor cells.

Methods: In this study, we studied three independent human MPM bio-collections to identify the defects in the IFN-I responses in tumor cells.