Performing group-level functional image analyses based on homologous functional regions mapped in individuals

Functional MRI (fMRI) studies have traditionally relied on intersubject normalization based on global brain morphology, which cannot establish proper functional correspondence between subjects due to substantial intersubject variability in functional organization. Here, we reliably identified a set of discrete, homologous functional regions in individuals to improve intersubject alignment of fMRI data. These functional regions demonstrated marked intersubject variability in size, position, and connectivity. We found that previously reported intersubject variability in functional connectivity maps could be partially explained by variability in size and position of the functional regions. Importantly, individual differences in network topography are associated with individual differences in task-evoked activations, suggesting that these individually specified regions may serve as the localizer to improve the alignment of task-fMRI data. We demonstrated that aligning task-fMRI data using the regions derived from resting state fMRI may lead to increased statistical power of task-fMRI analyses. In addition, resting state functional connectivity among these homologous regions is able to capture the idiosyncrasies of subjects and better predict fluid intelligence (gF) than connectivity measures derived from group-level brain atlases. Critically, we showed that not only the connectivity but also the size and position of functional regions are related to human behavior. Collectively, these findings suggest that identifying homologous functional regions across individuals can benefit a wide range of studies in the investigation of connectivity, task activation, and brain-behavior associations. Author summary No two individuals are alike. The size, shape, position, and connectivity patterns of brain functional regions can vary drastically between individuals. While interindividual differences in functional organization are well recognized, to date, standard procedures for functional neuroimaging research still rely on aligning different subjects' data to a nominal average brain based on global brain morphology. We developed an approach to reliably identify homologous functional regions in each individual and demonstrated that aligning data based on these homologous functional regions can significantly improve the study of resting state functional connectivity, task-fMRI activations, and brain-behavior associations. Moreover, we showed that individual differences in size, position, and connectivity of brain functional regions are dissociable, and each can provide nonredundant information in explaining human behavior

Kinetic Characterisation of a Single Chain Antibody against the Hormone Abscisic Acid: Comparison with Its Parental Monoclonal

A single-chain Fv fragment antibody (scFv) specific for the plant hormone abscisic acid (ABA) has been expressed in the bacterium Escherichia coli as a fusion protein. The kinetics of ABA binding have been measured using surface plasmon resonance spectrometry (BIAcore 2000) using surface and solution assays. Care was taken to calculate the concentration of active protein in each sample using initial rate measurements under conditions of partial mass transport limitation. The fusion product, parental monoclonal antibody and the free scFv all have low nanomolar affinity constants, but there is a lower dissociation rate constant for the parental monoclonal resulting in a three-fold greater affinity. Analogue specificity was tested and structure-activity binding preferences measured. The biologically-active (+)-ABA enantiomer is recognised with an affinity three orders of magnitude higher than the inactive (-)-ABA. Metabolites of ABA including phaseic acid, dihydrophaseic acid and deoxy-ABA have affinities over 100-fold lower than that for (+)-ABA. These properties of the scFv make it suitable as a sensor domain in bioreporters specific for the naturally occurring form of ABA

Automatic covariance pattern analysis outperforms visual reading of 18 F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) in variant progressive supranuclear palsy

Background: To date, studies on positron emission tomography (PET) with F-18-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS). Objectives: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice. Methods: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern. Results: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample. Conclusions: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. (C) 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Genomic deletion and promoter methylation status of Hypermethylated in Cancer 1 (HIC1) in mantle cell lymphoma

Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity

Polysomal mRNA Association and Gene Expression in <i>Trypanosoma brucei</i>

Background: The contrasting physiological environments of Trypanosoma brucei procyclic (insect vector) and bloodstream (mammalian host) forms necessitates deployment of different molecular processes and, therefore, changes in protein expression. Transcriptional regulation is unusual in T. brucei because the arrangement of genes is polycistronic; however, genes which are transcribed together are subsequently cleaved into separate mRNAs by trans-splicing. Following pre-mRNA processing, the regulation of mature mRNA stability is a tightly controlled cellular process. While many stage-specific transcripts have been identified, previous studies using RNA-seq suggest that changes in overall transcript level do not necessarily reflect the abundance of the corresponding protein. Methods: To better understand the regulation of gene expression in T. brucei, we performed a bioinformatic analysis of RNA-seq on total, sub-polysomal, and polysomal mRNA samples. We further cross-referenced our dataset with a previously published proteomics dataset to identify new protein coding sequences. Results: Our analyses showed that several long non-coding RNAs are more abundant in the sub-polysome samples, which possibly implicates them in regulating cellular differentiation in T. brucei. We also improved the annotation of the T.brucei genome by identifying new putative protein coding transcripts that were confirmed by mass spectrometry data. Conclusions: Several long non-coding RNAs are more abundant in the sub-polysome cellular fractions and might pay a role in the regulation of gene expression. We hope that these data will be of wide general interest, as well as being of specific value to researchers studying gene regulation expression and life stage transitions in T. brucei

FLOW INJECTION IMMUNOANALYSIS (FIIA) FOR THE DETERMINATION OF PESTICIDES IN WATER

The principle of a heterogeneous competitive enzyme immunoassay was applied to a flow injection system. This flow injection immunoassay (FIIA) can be run automatically. Antibodies to the triazine herbicide atrazin were immobilized on membranes. Antibody containing membranes were mounted in a cross-flow reactor and changed after each assay. In the assay atrazin competed with an atrazin-peroxidase conjugate for the antibody binding sites. The product of the enzyme reaction was measured fluorimetrically. One assay is completed within 15 minutes. Sensitivities of the FIIA proved similar to the ELISA and depended mainly on the properties of the antibodies and conjugation strategies. The potential and limitations of the FIIA system will be discussed