Initial Experiences with Amyloid-Related Imaging Abnormalities in Patients Receiving Aducanumab Following Accelerated Approval.

Aducanumab is the first FDA-approved amyloid-lowering immunotherapy for Alzheimer's disease. There is little real-world data to guide management of amyloid-related imaging abnormalities (ARIA), a potentially serious side-effect which requires surveillance with magnetic resonance imaging. We report our experiences in managing ARIA in patients receiving aducanumab at the Butler Hospital Memory and Aging Program during the year following FDA approval. We followed the Appropriate Use Recommendations for aducanumab to guide patient selection, detection, and management of ARIA (1). ARIA-E occurred in 6 out of 24 participants treated; all APOE-ε4 carriers. Treatment was discontinued in 4 cases of moderate-severe ARIA-E, temporarily held in 1 moderate case, and dosed through in 1 mild case (mean duration = 3 months, range, 1-6 months). No participants required hospitalization or high dose corticosteroids. Participants on anticoagulation were excluded and no macrohemorrhages occurred. These data support the measured approaches to treatment outlined in the Appropriate Use Recommendations.

Asc-Seurat: analytical single-cell Seurat-based web application.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of transcriptomes, arising as a powerful tool for discovering and characterizing cell types and their developmental trajectories. However, scRNA-seq analysis is complex, requiring a continuous, iterative process to refine the data and uncover relevant biological information. A diversity of tools has been developed to address the multiple aspects of scRNA-seq data analysis. However, an easy-to-use web application capable of conducting all critical steps of scRNA-seq data analysis is still lacking. We present Asc-Seurat, a feature-rich workbench, providing an user-friendly and easy-to-install web application encapsulating tools for an all-encompassing and fluid scRNA-seq data analysis. Asc-Seurat implements functions from the Seurat package for quality control, clustering, and genes differential expression. In addition, Asc-Seurat provides a pseudotime module containing dozens of models for the trajectory inference and a functional annotation module that allows recovering gene annotation and detecting gene ontology enriched terms. We showcase Asc-Seurat's capabilities by analyzing a peripheral blood mononuclear cell dataset. CONCLUSIONS: Asc-Seurat is a comprehensive workbench providing an accessible graphical interface for scRNA-seq analysis by biologists. Asc-Seurat significantly reduces the time and effort required to analyze and interpret the information in scRNA-seq datasets.

Identification and Expression Profile of Two Putative Odorant-Binding Proteins from the Neotropical Brown Stink Bug, Euschistus heros (Fabricius) (Hemiptera: Pentatomidae).

This work presents the first identification of putative odorant-binding proteins (OBPs) from a member of the Pentatomidae, i.e. the brown stink bug Euschistus heros (Fabricius), an important pest of soybean in Brazil. Antennae from both sexes of E. heros adults (12 days old and unmated) were used to construct a cDNA library, from which two transcripts encoding putative E. heros OBPs (EherOBPs) were identified. The expression levels of EherOBP1 and EherOBP2 were found to be higher in male antennae than in female and there was difference in expression in legs, wings, and abdomens of the two sexes. The histolocalization of EherOBP1 and EherOBP2 transcripts in antennae also showed a sexual dimorphism in the chemoreception system, with different expression sites in the antennal segments between males and females, occurring predominantly at the base of the sensillum. The implications of these findings for stink bug chemoreception are discussed.

Identification of genes encoding hypothetical proteins in open-reading frame expressed sequence tags from mammalian stages of Trypanosoma cruzi.

Approximately 50% of the predicted protein-coding genes of the Trypanosoma cruzi CL Brener strain are annotated as hypothetical or conserved hypothetical proteins. To further characterize these genes, we generated 1161 open-reading frame expressed sequence tags (ORESTES) from the mammalian stages of the VL10 human strain. Sequence clustering resulted in 435 clusters, consisting of 339 singletons and 96 contigs. Significant matches to the T. cruzi predicted gene database were found for ~94% contigs and ~69% singletons. These included genes encoding surface proteins, known to be intensely expressed in the parasite mammalian stages and implicated in host cell invasion and/or immune evasion mechanisms. Among 151 contigs and singletons with similarity to predicted hypothetical protein-coding genes and conserved hypothetical protein-coding genes, 83% showed no match with T. cruzi EST and/or proteome databases. These ORESTES are the first experimental evidence that the corresponding genes are in fact transcribed. Sequences with no significant match were searched against several T. cruzi and National Center for Biotechnology Information non-redundant sequence databases. The ORESTES analysis indicated that 124 predicted conserved hypothetical protein-coding genes and 27 predicted hypothetical protein-coding genes annotated in the CL Brener genome are transcribed in the VL10 mammalian stages. Six ORESTES annotated as hypothetical protein-coding genes showing no match to EST and/or proteome databases were confirmed by Northern blot in VL10. The generation of this set of ORESTES complements the T. cruzi genome annotation and suggests new stage-regulated genes encoding hypothetical proteins.

Genetic network identification using convex programming.

Gene regulatory networks capture interactions between genes and other cell substances, resulting in various models for the fundamental biological process of transcription and translation. The expression levels of the genes are typically measured as mRNA concentration in micro-array experiments. In a so-called genetic perturbation experiment, small perturbations are applied to equilibrium states and the resulting changes in expression activity are measured. One of the most important problems in systems biology is to use these data to identify the interaction pattern between genes in a regulatory network, especially in a large scale network. The authors develop a novel algorithm for identifying the smallest genetic network that explains genetic perturbation experimental data. By construction, our identification algorithm is able to incorporate and respect a priori knowledge known about the network structure. A priori biological knowledge is typically qualitative, encoding whether one gene affects another gene or not, or whether the effect is positive or negative. The method is based on a convex programming relaxation of the combinatorially hard problem of L(0) minimisation. The authors apply the proposed method to the identification of a subnetwork of the SOS pathway in Escherichia coli, the segmentation polarity network in Drosophila melanogaster, and an artificial network for measuring the performance of the method.

Characterization of Aspergillus flavus strains from Brazilian Brazil nuts and cashew by RAPD and ribosomal DNA analysis.

AIMS: The aim of this study was to determine the genetic variability in Aspergillus flavus populations from Brazil nut and cashew and develop a polymerase chain reaction (PCR) detection method. METHODS AND RESULTS: Chomatography analysis of 48 isolates identified 36 as aflatoxigenic (75%). One hundred and forty-one DNA bands were generated with 11 random amplified polymorphic DNA (RAPD) primers and analysed via unweighted pair group analysis, using arithmetic means (UPGMA). Isolates grouped according to host, with differentiation of those from A. occidentale also according to geographical origin. Aspergillus flavus-specific PCR primers ASPITSF2 and ASPITSR3 were designed from ribosomal DNA internal transcribed spacers (ITS 1 and 2), and an internal amplification control was developed, to prevent false negative results. Specificity to only A. flavus was confirmed against DNA from additional aspergilli and other fungi. CONCLUSIONS: RAPD-based characterization differentiated isolates according to plant host. The PCR primer pair developed showed specificity to A. flavus, with a detection limit of 10 fg. SIGNIFICANCE AND IMPACT OF THE STUDY: Genetic variability observed in A. flavus isolates from two Brazilian agroecosystems suggested reproductive isolation. The PCR detection method developed for A. flavus represents progress towards multiplex PCR detection of aflatoxigenic and nonaflatoxigenic strains in Hazard Analysis Critical Control Point systems.

Generation and molecular cytogenetic characterization of a radiation-reduction hybrid panel for human chromosome 6.

A neoR marked chromosome-6 containing hybrid (D113JA) was used to generate a panel of 15 radiation-reduced hybrid cell lines. The panel was constructed by irradiating microcells isolated from D113JA at 800 or 8000 rads, providing different levels of chromosome 6 retention. These hybrids have been systematically analyzed using interspersed repetitive elements, previously assigned markers for chromosome 6, and fluorescent in situ hybridization (FISH). As expected, G418 selection has favored the retention of fragments near the insertion site of the neoR gene (6q16). The panel as constituted provides an important resource for regional assignment of molecular markers, especially to regions on 6q.

Regional assignment by hybrid mapping of 36 expressed sequence tags (ESTs) on human chromosome 6.

We have determined the regional chromosome assignment of 36 cDNAs from infant brain libraries by assessing the concordant segregation of PCR products using a human-rodent hybrid mapping panel that subdivides chromosome 6 into 15 regions. These mapped sequences serve as markers for the physical and expression maps of chromosome 6, as well as candidate genes for various disease loci. Sequence analysis has identified putative functions and motifs for some of these genes.