Compressive Inverse Scattering II. SISO Measurements with Born scatterers

Inverse scattering methods capable of compressive imaging are proposed and analyzed. The methods employ randomly and repeatedly (multiple-shot) the single-input-single-output (SISO) measurements in which the probe frequencies, the incident and the sampling directions are related in a precise way and are capable of recovering exactly scatterers of sufficiently low sparsity. For point targets, various sampling techniques are proposed to transform the scattering matrix into the random Fourier matrix. The results for point targets are then extended to the case of localized extended targets by interpolating from grid points. In particular, an explicit error bound is derived for the piece-wise constant interpolation which is shown to be a practical way of discretizing localized extended targets and enabling the compressed sensing techniques. For distributed extended targets, the Littlewood-Paley basis is used in analysis. A specially designed sampling scheme then transforms the scattering matrix into a block-diagonal matrix with each block being the random Fourier matrix corresponding to one of the multiple dyadic scales of the extended target. In other words by the Littlewood-Paley basis and the proposed sampling scheme the different dyadic scales of the target are decoupled and therefore can be reconstructed scale-by-scale by the proposed method. Moreover, with probes of any single frequency \om the coefficients in the Littlewood-Paley expansion for scales up to \om/(2\pi) can be exactly recovered.Comment: Add a new section (Section 3) on localized extended target

A somatosensory circuit for cooling perception in mice

The temperature of an object provides important somatosensory information for animals performing tactile tasks. Humans can perceive skin cooling of less than one degree, but the sensory afferents and central circuits that they engage to enable the perception of surface temperature are poorly understood. To address these questions, we examined the perception of glabrous skin cooling in mice. We found that mice were also capable of perceiving small amplitude skin cooling and that primary somatosensory (S1) cortical neurons were required for cooling perception. Moreover, the absence of the menthol-gated transient receptor potential melastatin 8 ion channel in sensory afferent fibers eliminated the ability to perceive cold and the corresponding activation of S1 neurons. Our results identify parts of a neural circuit underlying cold perception in mice and provide a new model system for the analysis of thermal processing and perception and multimodal integration

Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

In response to cell swelling, volume-regulated anion channels (VRACs) participate in a process known as regulatory volume decrease (RVD). Only recently, first insight into the molecular identity of mammalian VRACs was obtained by the discovery of the leucine-rich repeats containing 8A (LRRC8A) gene. Here, we show that bestrophin 1 (BEST1) but not LRRC8A is crucial for volume regulation in human retinal pigment epithelium (RPE) cells. Whole-cell patch-clamp recordings in RPE derived from human-induced pluripotent stem cells (hiPSC) exhibit an outwardly rectifying chloride current with characteristic functional properties of VRACs. This current is severely reduced in hiPSC-RPE cells derived from macular dystrophy patients with pathologic BEST1 mutations. Disruption of the orthologous mouse gene (Best1−/−) does not result in obvious retinal pathology but leads to a severe subfertility phenotype in agreement with minor endogenous expression of Best1 in murine RPE but highly abundant expression in mouse testis. Sperm from Best1−/− mice showed reduced motility and abnormal sperm morphology, indicating an inability in RVD. Together, our data suggest that the molecular identity of VRACs is more complex—that is, instead of a single ubiquitous channel, VRACs could be formed by cell type- or tissue-specific subunit composition. Our findings provide the basis to further examine VRAC diversity in normal and diseased cell physiology, which is key to exploring novel therapeutic approaches in VRAC-associated pathologies

The Effects of Dietary Polyphenols on Circulating Cardiovascular Disease Biomarkers and Iron Status:A Systematic Review

The prevalence of cardiovascular disease (CVD) is rising worldwide, remaining the major cause of death in developed countries. Polyphenols have been shown to have cardioprotective properties; however, their impact on iron bioavailability and potential impact on other aspects of health is unclear. A systematic review was undertaken to evaluate the current status of the relationship between habitual polyphenol consumption, iron status, and circulating biomarkers of CVD. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 guidelines, searches were performed across 5 electronic databases (PubMed, Cochrane Library, Scopus, Web of Science, and CINAHL) to identify randomized controlled trials which investigated the effects of polyphenol consumption on inflammatory markers, serum lipid profile, and iron absorption and bioavailability. In total, 1174 records were identified, with only 7 studies meeting the inclusion criteria. The selected studies involved 133 participants and used a variety of foods and supplements, including olive oil and cherries, rich in polyphenols including hydroxytyrosol, quercetin, and resveratrol, as well as catechin enriched drinks. The duration of the studies ranged from between 56 and 145 days, with total polyphenolic content of the food items and supplements ranging from 45 to 1015 mg (per 100 g). Polyphenols did not appear to interfere with iron status, and most studies reported improvements in inflammatory markers and lipid profile. While these results are promising, the limited number of studies and considerable heterogeneity across the interventions support the need for more extensive trials assessing the relationship between polyphenol intake, iron bioavailability, and CVD risk

Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase

The biogenesis of mitochondrial intermembrane space proteins depends on specific machinery that transfers disulfide bonds to precursor proteins. The machinery shares features with protein relays for disulfide bond formation in the bacterial periplasm and endoplasmic reticulum. A disulfide-generating enzyme/sulfhydryl oxidase oxidizes a disulfide carrier protein, which in turn transfers a disulfide to the substrate protein. Current views suggest that the disulfide carrier alternates between binding to the oxidase and the substrate. We have analyzed the cooperation of the disulfide relay components during import of precursors into mitochondria and identified a ternary complex of all three components. The ternary complex represents a transient and intermediate step in the oxidation of intermembrane space precursors, where the oxidase Erv1 promotes disulfide transfer to the precursor while both oxidase and precursor are associated with the disulfide carrier Mia40

Bestrophin1: A Gene that Causes Many Diseases

Bestrophinopathies are a group of clinically distinct inherited retinal dystrophies that lead to the gradual loss of vision in and around the macular area. There are no treatments for patients suffering from bestrophinopathies, and no measures can be taken to prevent visual deterioration in those who have inherited disease-causing mutations. Bestrophinopathies are caused by mutations in the Bestrophin1 gene (BEST1), a protein found exclusively in the retinal pigment epithelial (RPE) cells of the eye. Mutations in BEST1 affect the function of the RPE leading to the death of overlying retinal cells and subsequent vision loss. The pathogenic mechanisms arising from BEST1 mutations are still not fully understood, and it is not clear how mutations in BEST1 lead to diseases with distinct clinical features. This chapter discusses BEST1, the use of model systems to investigate the effects of mutations and the potential to investigate individual bestrophinopathies using induced pluripotent stem cells

OEMC D2.1 Report "Stakeholder Committee and Open- Earth-Monitor Design" workshop

This deliverable of the Open-Earth-Monitor project describes the approach taken to compile and categorize the project's stakeholders, and provides recommendations for the future stakeholder interactions based on the results of a survey from the OEMC design workshop, which took place during the project's kick-off meeting in July, 2022

Molecular Analysis of Ring Y Chromosome in a 10-Year-Old Boy with Mixed Gonadal Dysgenesis and Growth Hormone Deficiency

Ring Y chromosome is a very rare chromosomal aberration. The published mixed gonadal dysgenesis (MGD) patients with a ring Y chromosome are short in stature, but are not growth hormone (GH) deficient. We present the molecular cytogenetic and molecular characterization of ring Y chromosome mosaicism in a 10-year-old boy with MGD whose short stature could be explained by the high percentage of cells monosomic for the X-chromosome, but also by the presence of severe GH deficiency. The ring Y chromosome in our patient is a de novo structural aberration. The fathers karyotype was normal

Modeling the Structural Consequences of \u3cem\u3eBEST1\u3c/em\u3e Missense Mutations

Mutations in the bestrophin-1 gene (BEST1) are an important cause of inherited retinal disorders. Hitherto, over 100 unique allelic variants have been linked to the human BEST1 (hBEST1), and associated with disease phenotypes, broadly termed as bestrophinopathies. A spontaneous animal model recapitulating BEST1-related phenotypes, canine multifocal retinopathy (cmr), is caused by mutations in the canine gene ortholog (cBEST1). We have recently characterized molecular consequences of cmr, demonstrating defective protein trafficking as a result of G161D (cmr2) mutation. To further investigate the pathological effects of BEST1 missense mutations, canine and human peptide fragments derived from the protein sequence have been studied in silico as models for early events in the protein folding. The results showed that G161D as well as I201T substitutions cause severe conformational changes in the structure of bestrophin-1, suggesting protein misfolding as an underlying disease mechanism. The comparative modeling studies expand our insights into BEST1 pathogenesis