Two Sides of a Coin: Case Report of Unilateral Synangiosis and Contralateral Stroke Highlighting Consequences of Disease Progression and Efficacy of Revascularization in Sickle Cell Disease Associated Moyamoya Syndrome

Moyamoya syndrome increases the risk of stroke in sickle cell disease, but revascularization surgery can modify this risk. Collaborative management between hematology and neurosurgery offers effective strategies to reduce stroke risk in these patients. We describe a challenging case where a patient with sickle cell disease undergoing standard of care management as prescribed by the Stroke Prevention Trial in Sickle Cell Anemia (STOP) and revascularization with pial synangiosis subsequently developed rapidly progressive disease in other cerebral vessels and suffered ischemic hemispheric stroke. This case demonstrates the success of management in accordance with American Heart Association (AHA) and American Stroke Association (ASA) guidelines, but also demonstrates critical areas where we lack understanding of disease progression.

Discovering differential genome sequence activity with interpretable and efficient deep learning

Discovering sequence features that differentially direct cells to alternate fates is key to understanding both cellular development and the consequences of disease related mutations. We introduce Expected Pattern Effect and Differential Expected Pattern Effect, two black-box methods that can interpret genome regulatory sequences for cell type-specific or condition specific patterns. We show that these methods identify relevant transcription factor motifs and spacings that are predictive of cell state-specific chromatin accessibility. Finally, we integrate these methods into framework that is readily accessible to non-experts and available for download as a binary or installed via PyPI or bioconda at https://cgs.csail.mit.edu/deepaccess-package/.

A Perspective on COVID-19 Management

A novel coronavirus—Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2)—outbreak correlated with the global coronavirus disease 2019 (COVID-19) pandemic was declared by the WHO in March 2020, resulting in numerous counted cases attributed to SARS-CoV-2 worldwide. Herein, we discuss current knowledge on the available therapy options for patients diagnosed with COVID-19. Based on available scientific data, we present an overview of solutions in COVID-19 management by use of drugs, vaccines and antibodies. Many questions with non-conclusive answers on the measures for the management of the COVID-19 pandemic and its impact on health still exist—i.e., the actual infection percentage of the population, updated precise mortality data, variability in response to infection by the population, the nature of immunity and its duration, vaccine development issues, a fear that science might end up with excessive promises in response to COVID-19—and were raised among scientists. Indeed, science may or may not deliver results in real time. In the presented paper we discuss some consequences of disease, its detection and serological tests, some solutions to disease prevention and management, pitfalls and obstacles, including vaccination. The presented ideas and data herein are meant to contribute to the ongoing debate on COVID-19 without pre-selection of available information.

Global network analysis in Schizosaccharomyces pombe reveals three distinct consequences of the common 1-kb deletion causing juvenile CLN3 disease

Juvenile CLN3 disease is a recessively inherited paediatric neurodegenerative disorder, with most patients homozygous for a 1-kb intragenic deletion in CLN3. The btn1 gene is the Schizosaccharomyces pombe orthologue of CLN3. Here, we have extended the use of synthetic genetic array (SGA) analyses to delineate functional signatures for two different disease-causing mutations in addition to complete deletion of btn1. We show that genetic-interaction signatures can differ for mutations in the same gene, which helps to dissect their distinct functional effects. The mutation equivalent to the minor transcript arising from the 1-kb deletion (btn1102–208del) shows a distinct interaction pattern. Taken together, our results imply that the minor 1-kb deletion transcript has three consequences for CLN3: to both lose and retain some inherent functions and to acquire abnormal characteristics. This has particular implications for the therapeutic development of juvenile CLN3 disease. In addition, this proof of concept could be applied to conserved genes for other mendelian disorders or any gene of interest, aiding in the dissection of their functional domains, unpacking the global consequences of disease pathogenesis, and clarifying genotype–phenotype correlations. In doing so, this detail will enhance the goals of personalised medicine to improve treatment outcomes and reduce adverse events.

Discovering differential genome sequence activity with interpretable and efficient deep learning

Discovering sequence features that differentially direct cells to alternate fates is key to understanding both cellular development and the consequences of disease related mutations. Here we present a new method that efficiently learns sequence features that can predict cell state-specific chromatin accessibility in a framework that is readily accessible to non-experts.

Conspiracy Theories about Infectious Diseases: An Introduction

Understanding why people believe conspiracy theories related to disease outbreaks and the consequences of such beliefs is critical for combating both the COVID-19 pandemic and its corresponding “infodemic.” In the introduction to this special issue on conspiracy theories about infectious diseases, the authors first provide a brief overview of the narratives of conspiracy theories related to COVID-19, followed by a review of extant theoretical frameworks regarding the psychology of conspiracy beliefs. Specifically, they discuss how epistemic, existential, and social needs contribute to the holding of conspiracy beliefs. Then, the authors summarize the major findings from the nine empirical articles featured in this issue, particularly how they shed light on the antecedents and consequences of disease-related conspiracy beliefs. They conclude by discussing future directions for the study of disease-related conspiracy beliefs.

High-resolution ex vivo NMR spectroscopy of human Z α1-antitrypsin

Genetic mutations predispose the serine protease inhibitor α1-antitrypsin to misfolding and polymerisation within hepatocytes, causing liver disease and chronic obstructive pulmonary disease. This misfolding occurs via a transiently populated intermediate state, but our structural understanding of this process is limited by the instability of recombinant α1-antitrypsin variants in solution. Here we apply NMR spectroscopy to patient-derived samples of α1-antitrypsin at natural isotopic abundance to investigate the consequences of disease-causing mutations, and observe widespread chemical shift perturbations for methyl groups in Z AAT (E342K). By comparison with perturbations induced by binding of a small-molecule inhibitor of misfolding we conclude that they arise from rapid exchange between the native conformation and a well-populated intermediate state. The observation that this intermediate is stabilised by inhibitor binding suggests a paradoxical approach to the targeted treatment of protein misfolding disorders, wherein the stabilisation of disease-associated states provides selectivity while inhibiting further transitions along misfolding pathways.