Functionalized Upconversion Nanoparticles for Targeted Labelling of Bladder Cancer Cells.

Bladder cancer is the ninth most common cancer worldwide. Due to a high risk of recurrence and progression of bladder cancer, every patient needs long-term surveillance, which includes regular cystoscopy, sometimes followed by a biopsy of suspicious lesions or resections of recurring tumours. This study addresses the development of novel biohybrid nanocomplexes representing upconversion nanoparticles (UCNP) coupled to antibodies for photoluminescent (PL) detection of bladder cancer cells. Carrying specific antibodies, these nanoconjugates selectively bind to urothelial carcinoma cells and make them visible by emitting visible PL upon excitation with deeply penetrating near-infrared light. UCNP were coated with a silica layer and linked to anti-Glypican-1 antibody MIL38 via silica-specific solid-binding peptide. Conjugates have been shown to specifically attach to urothelial carcinoma cells with high expression of Glypican-1. This result highlights the potential of produced conjugates and conjugation technology for further studies of their application in the tumour detection and fluorescence-guided resection

breakpointR:an R/Bioconductor package to localize strand state changes in Strand-seq data

MOTIVATION: Strand-seq is a specialized single-cell DNA sequencing technique centered around the directionality of single-stranded DNA. Computational tools for Strand-seq analyses must capture the strand-specific information embedded in these data. RESULTS: Here we introduce breakpointR, an R/Bioconductor package specifically tailored to process and interpret single-cell strand-specific sequencing data obtained from Strand-seq. We developed breakpointR to detect local changes in strand directionality of aligned Strand-seq data, to enable fine-mapping of sister chromatid exchanges, germline inversion and to support global haplotype assembly. Given the broad spectrum of Strand-seq applications we expect breakpointR to be an important addition to currently available tools and extend the accessibility of this novel sequencing technique. AVAILABILITY: R/Bioconductor package https://bioconductor.org/packages/breakpointR

Status report of a systematic investigation on low-dose ionizing radiation effects in mammalian cells

In the last 15 years a growing interest in the biological effects induced by low doses of ionizing radiation has arisen in the scientific community, due to an increasing number of experimental evidences showing a plethora of non-linear effects occurring after low-dose irradiations. In particular, hyper-radiosensitivity and induced radioresistance (HRS/IRR) have been reported after exposure to low- and high-LET radiation, in human (normal and tumoural) and other mammalian cells in vitro. In this framework, Chinese hamster V79 cells, human primary fibroblasts (HFFF2) and murine embryonic fibroblasts (MEFs) were irradiated with broadbeams of protons in the dose range 0.1–5.0Gy and at 1 Gy/min dose-rate. Cellular response has been evaluated in terms of cell survival, micronuclei induction, chromosomal aberrations and telomere length alterations. For comparison purpose, the same end-points were studied after X/γ-rays irradiation

AGER expression and alternative splicing in bronchial biopsies of smokers and never smokers

Abstract Cigarette smoking is one of the major risk factors for the development of chronic obstructive pulmonary disease (COPD). Evidence is accumulating that Receptor for Advanced Glycation-End products (RAGE)-signaling is a key pathway in the pathophysiology of COPD. To date, it is unknown how smoking affects RAGE expression. In the current study, we investigated the effect of smoking on AGER, the gene encoding RAGE, expression and on alternative splicing of AGER. To this end, we conducted RNA-Seq on bronchial biopsies for asymptomatic smokers (n = 36) and never smokers (n = 40). Total AGER gene expression was accessed using DESeq2, while alternative splicing was investigated by measuring the number of specific split reads spanning exon-exon junctions and the total split reads. One of the major isoforms of RAGE is endogenous soluble (es) RAGE, an anti-inflammatory decoy receptor, making up for approximately 10% of the total amount of soluble (s)RAGE. We found that smokers show decreased total gene expression of AGER in bronchial biopsies, while the relative abundance of the esRAGE isoform is increased. Furthermore, no difference in the serum levels of total sRAGE were observed between smokers and non-smokers. Our data indicates that smoking initiates a protective anti-inflammatory mechanism with decreased expression of the pro-inflammatory gene AGER and increased relative abundance of the anti-inflammatory isoform esRAGE

Compression of volume-surface integral equation matrices via Tucker decomposition for magnetic resonance applications

In this work, we propose a method for the compression of the coupling matrix in volume\hyp surface integral equation (VSIE) formulations. VSIE methods are used for electromagnetic analysis in magnetic resonance imaging (MRI) applications, for which the coupling matrix models the interactions between the coil and the body. We showed that these effects can be represented as independent interactions between remote elements in 3D tensor formats, and subsequently decomposed with the Tucker model. Our method can work in tandem with the adaptive cross approximation technique to provide fast solutions of VSIE problems. We demonstrated that our compression approaches can enable the use of VSIE matrices of prohibitive memory requirements, by allowing the effective use of modern graphical processing units (GPUs) to accelerate the arising matrix\hyp vector products. This is critical to enable numerical MRI simulations at clinical voxel resolutions in a feasible computation time. In this paper, we demonstrate that the VSIE matrix\hyp vector products needed to calculate the electromagnetic field produced by an MRI coil inside a numerical body model with $1$ mm$^3$ voxel resolution, could be performed in $\sim 33$ seconds in a GPU, after compressing the associated coupling matrix from $\sim 80$ TB to $\sim 43$ MB.Comment: 13 pages, 11 figure

Smoking increases expression of the SARS-CoV-2 spike protein-binding long ACE2 isoform in bronchial epithelium

After more than two years the COVID-19 pandemic, that is caused by infection with the respiratory SARS-CoV-2 virus, is still ongoing. The risk to develop severe COVID-19 upon SARS-CoV-2 infection is increased in individuals with a high age, high body mass index, and who are smoking. The SARS-CoV-2 virus infects cells of the upper respiratory tract by entering these cells upon binding to the Angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is expressed in various cell types in the lung but the expression is especially high in goblet and ciliated cells. Recently, it was shown that next to its full-length isoform, ACE2 also has a short isoform. The short isoform is unable to bind SARS-CoV-2 and does not facilitate viral entry. In the current study we investigated whether active cigarette smoking increases the expression of the long or the short ACE2 isoform. We showed that in active smokers the expression of the long, active isoform, but not the short isoform of ACE2 is higher compared to never smokers. Additionally, it was shown that the expression of especially the long, active isoform of ACE2 was associated with secretory, club and goblet epithelial cells. This study increases our understanding of why current smokers are more susceptible to SARS-CoV-2 infection, in addition to the already established increased risk to develop severe COVID-19.</p

TAVISCORE: a computer program for risk stratification of complications after aortic valve interventions in patients with reduced ejection fraction

Aim. To demonstrate the TAVISCORE program designed to stratify the risk of complications after aortic valve (AV) interventions in patients with reduced ejection fraction.Material and methods. For the period from 2015-2022 at the Almazov Federal North-West Medical Research Center, 128 interventions on AV were performed for aortic stenosis in patients with reduced ejection fraction as follows: 61 — surgical AV replacement (SAVR), 67 — transcatheter aortic valve implantation (TAVI). To create an interactive calculator TAVISCORE (link for free download: https://drive.google.com/file/d/1a3s2MK6Tpk0cIQ_aMB7xe63upEwJsJOh/view?usp=sharing) all patients were combined into one group. For each factor present in the patient, the prognostic coefficient, its contribution to the likelihood of an event in the long-term follow-up period (death, myocardial infarction, stroke), was calculated. The next step, based on the calculations obtained and using the Python 3.10.6 language, was the creation of the TAVISCORE program.Results. The TAVISCORE was created for the personalized choice of tactics for the treatment of patients with aortic stenosis. It contains 54 risk factors and makes it possible to determine probability of cardiac or non-cardiac events in the long-term follow-up period after SAVR and TAVI. Thus, a tactic with lower probability of a complication can be chosen as optimal in this particular case. Retrospective use of the TAVISCORE after surgery can identify patients at high risk of complications, which will allow them to be selected for more thorough management and more frequent screening.Conclusion. The TAVISCORE can be used by a multidisciplinary consensus to select the treatment tactics and stratify the risk of complications after different AV replacement variants in patients with a reduced ejection fraction. Further prospective testing of this program is required

Spectral characteristics of side face excited microstructured fibers for photonic integrated circuits formations

We propose a new method for mass production of the photonic crystal devices on the basis of widely-known and well-developed technology such as microstructured optical fibers. In this paper, we investigate the optical properties of side-excited microstructured optical fiber and discuss the conditions for utilization such a structure as a planar photonic crystal device, namely, the high-quality resonance filter.Comment: 7 pages, 7 figure

Dense and accurate whole-chromosome haplotyping of individual genomes

The diploid nature of the human genome is neglected in many analyses done today, where a genome is perceived as a set of unphased variants with respect to a reference genome. This lack of haplotype-level analyses can be explained by a lack of methods that can produce dense and accurate chromosome-length haplotypes at reasonable costs. Here we introduce an integrative phasing strategy that combines global, but sparse haplotypes obtained from strand-specific single-cell sequencing (Strand-seq) with dense, yet local, haplotype information available through long-read or linked-read sequencing. We provide comprehensive guidance on the required sequencing depths and reliably assign more than 95% of alleles (NA12878) to their parental haplotypes using as few as 10 Strand-seq libraries in combination with 10-fold coverage PacBio data or, alternatively, 10X Genomics linked-read sequencing data. We conclude that the combination of Strand-seq with different technologies represents an attractive solution to chart the genetic variation of diploid genomes

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript