Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring.

Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker for allograft injury detection. This study aimed to evaluate a new, decentralized dd-cfDNA testing kit against a centralized dd-cfDNA testing service broadly utilized in the United States. Kidney transplant recipients with decentralized and centralized dd-cfDNA measurements and concomitant kidney allograft biopsies were included in the study.

Multi-centre analytical performance verification of an IVD assay to quantify donor-derived cell-free DNA in solid organ transplant recipients.

Donor-derived cell-free DNA (dd-cfDNA) has been widely studied as biomarker for non-invasive allograft rejection monitoring. Earlier rejection detection enables more prompt diagnosis and intervention, ultimately improving patient treatment and outcomes. This multi-centre study aims to verify analytical performance of a next-generation sequencing-based dd-cfDNA assay at end-user environments.

Anti-interleukin-6 Antibody Clazakizumab in Antibody-mediated Kidney Transplant Rejection: Effect on Donor-derived Cell-free DNA and C-X-C Motif Chemokine Ligand 10.

Unlabelled: Targeting interleukin-6 (IL-6) was shown to counteract donor-specific antibody production and antibody-mediated rejection (AMR) activity. It is not known whether, or to what extent, IL-6 antagonism modulates biomarkers indicative of tissue damage (donor-derived cell-free DNA [dd-cfDNA]) and parenchymal inflammation (C-X-C motif chemokine ligand [CXCL] 10).

Methods: We report a secondary endpoint analysis of a phase 2 trial of anti-IL-6 antibody clazakizumab in late AMR (ClinicalTrials.

Levels of donor-derived cell-free DNA and chemokines in BK polyomavirus-associated nephropathy.

Background: BK polyomavirus-associated nephropathy (BKPyVAN) carries a risk of irreversible allograft injury. While detection of BK viremia and biopsy assessment are the current diagnostic gold standard, the diagnostic value of biomarkers reflecting tissue injury (donor-derived cell-free DNA [dd-cfDNA]) or immune activation (C-X-C motif chemokine ligand [CXCL]9 and CXCL10) remains poorly defined.

Methods: For this retrospective study, 19 cases of BKPyVAN were selected from the Vienna transplant cohort (biopsies performed between 2012 and 2019).

Freeform hyperspectral imager design in a CubeSat format.

A freeform pushbroom hyperspectral imager design was investigated as a combination of a freeform reflective triplet imager and a freeform reflective triplet spectrometer used in double-pass. The design operates at about F/2 with a 15-degree cross-track field-of-view and a 30 mm entrance pupil diameter. The design process led to achieving a small volume of less than 2 liters that fits comfortably within a 3U CubeSat geometry, exemplifying the compactness of this hyperspectral imager.

Diagnostic value of donor-derived cell-free DNA to predict antibody-mediated rejection in donor-specific antibody-positive renal allograft recipients.

Circulating donor-specific antibodies (DSA) do not necessarily indicate antibody-mediated rejection (ABMR). Here, we evaluated the diagnostic value of donor-derived cell-free DNA (dd-cfDNA) as an add-on to DSA detection. The study included two independent cohorts of DSA kidney allograft recipients, 45 subclinical cases identified by cross-sectional antibody screening (cohort 1), and 30 recipients subjected to indication biopsies (cohort 2).

Type IA topoisomerases: a simple puzzle?

Type IA topoisomerases are enzymes that can modify DNA topology. They form a distinct family of proteins present in all domains of life, from bacteria to archaea and higher eukaryotes. They are composed of two domains: a core domain containing all the conserved motifs involved in the trans-esterification reactions, and a carboxyl-terminal domain that is highly variable in size and sequence.

Giant proteins that move DNA: bullies of the genomic playground.

As genetic material DNA is wonderful, but as a macromolecule it is unruly, voluminous and fragile. Without the action of DNA replicases, topoisomerases, helicases, translocases and recombinases, the genome would collapse into a topologically entangled random coil that would be useless to the cell. We discuss the organization, movement and energetics of these proteins that are crucial to the preservation of a molecule that has such beautiful biological but challenging physical properties.

Proteolytic cleavage of the hyperthermophilic topoisomerase I from Thermotoga maritima does not impair its enzymatic properties.

Using limited proteolysis, we show that the hyperthermophilic topoisomerase I from Thermotoga maritima exhibits a unique hot spot susceptible to proteolytic attack with a variety of proteases. The remaining of the protein is resistant to further proteolysis, which suggests a compact folding of the thermophilic topoisomerase, when compared to its mesophilic Escherichia coli homologue. We further show that a truncated version of the T.

Thermotoga maritima-Escherichia coli chimeric topoisomerases. Answers about involvement of the carboxyl-terminal domain in DNA topoisomerase I-mediated catalysis.

Bacterial topoisomerases I are generally composed of two domains as follows: a core domain, which contains all the conserved motifs involved in the trans-esterification reactions, and a carboxyl-terminal domain, highly variable in size and sequence. In the present work, we have addressed the question of the respective roles of the two domains in the different steps of the topoisomerization cycle. For this purpose, we prepared various recombinant topoisomerases from two model enzymes: topoisomerase I from the hyperthermophilic bacterium Thermotoga maritima and topoisomerase I from Escherichia coli.