Characterization of a supercoil-dependent S1 sensitive site 5\u27 to the Drosophila melanogaster hsp 26 gene

We have analyzed the prominent supercoil-dependent S1 nuclease cleavage site 5\u27 to hsp 26 in the plasmid 88B13, which contains 11.7 kilobases from the Drosophila locus 67B1. The double stranded cleavage product is generated by initial nicking on the purine strand, six preferred sites occurring between positions -96 and -90 (relative to the start of transcription) with weaker ones extending to position -84, followed by cleavage on the pyrimidine strand at positions -86 and -84. A derivative of 88B13, 88B13-X, was generated by insertion of an Xho I linker at position -84; this does not affect the positions or strand specificity of the S1 cleavage in that region. A small deletion, delta 41.1, removes the homopurine/homopyrimidine stretch from positions -86 to -132 and is no longer sensitive to cleavage by S1 nuclease 5\u27 to hsp 26. Mung bean and P1 nucleases recognize the same site 5\u27 to hsp 26 and give the same general pattern of cleavage. All three nucleases show an initial cleavage of 88B13 DNA at this site at pH 5.5 but not at pH 6.5, indicating that the DNA structure there may be pH dependent in vitro

Extra cardiac findings by 64-multidetector computed tomography in patients with symptomatic atrial fibrillation prior to pulmonal vein isolation

The aim of this study was to investigate the prevalence of extracardiac findings diagnosed by 64-multidetector computed tomography (MDCT) examinations prior to circumferential pulmonary vein (PV) ablation of atrial fibrillation (AF). A total of 158 patients (median age, 60.5 years; male 68%) underwent 64-MDCT of the chest and upper abdomen to characterize left atrial and PV anatomy prior to AF ablation. MDCT images were evaluated by a thoracic radiologist and a cardiologist. For additional scan interpretation, bone, lung, and soft tissue window settings were used. CT scans with extra-cardiac abnormalities categorized for the anatomic distribution and divided into two groups: Group 1—exhibiting clinically significant or potentially significant findings, and Group 2—patients with clinically non-significant findings. Extracardiac findings (n = 198) were observed in 113/158 (72%) patients. At least one significant finding was noted in 49/158 patients (31%). Group 1 abnormalities, such as malignancies or pneumonias, were found in 85/198 findings (43%). Group 2 findings, for example mild degenerative spine disease or pleural thickening, were observed in 113/198 findings (72%). 74/198 Extracardiac findings were located in the lung (37%), 35/198 in the mediastinum (18%), 8/198 into the liver (4%) and 81/198 were in other organs (41). There is an appreciable prevalence of prior undiagnosed extracardiac findings detected in patients with AF prior to PV-Isolation by MDCT. Clinically significant or potentially significant findings can be expected in ~40% of patients who undergo cardiac MDCT. Interdisciplinary trained personnel is required to identify and interpret both cardiac and extra cardiac findings

Factive Scientific Understanding Without Accurate Representation

This paper analyzes two ways idealized biological models produce factive scientific understanding. I then argue that models can provide factive scientific understanding of a phenomenon without providing an accurate representation of the (difference-making) features of their real-world target system(s). My analysis of these cases also suggests that the debate over scientific realism needs to investigate the factive scientific understanding produced by scientists’ use of idealized models rather than the accuracy of scientific models themselves

Psychoneural Isomorphism: From Metaphysics to Robustness

At the beginning of the 20th century, Gestalt psychologists put forward the concept of psychoneural isomorphism, which was meant to replace Fechner’s obscure notion of psychophysical parallelism and provide a heuristics that may facilitate the search for the neural correlates of the mind. However, the concept has generated much confusion in the debate, and today its role is still unclear. In this contribution, I will attempt a little conceptual spadework in clarifying the concept of psychoneural isomorphism, focusing exclusively on conscious visual perceptual experience and its neural correlates. Firstly, I will outline the history of our concept, and its alleged metaphysical and epistemic roles. Then, I will clarify the nature of isomorphism and rule out its metaphysical role. Finally, I will review some epistemic roles of our concept, zooming in on the work of Jean Petitot, and suggest that it does not play a relevant heuristic role. I conclude suggesting that psychoneural isomorphism might be an indicator of robustness for certain mathematical descriptions of perceptual content

Effects of eight neuropsychiatric copy number variants on human brain structure

peer reviewedMany copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. © 2021, The Author(s)