Tissue-resident Lymphocytes Are Released During Hypothermic and Normothermic Machine Perfusion of Human Donor Kidneys

BACKGROUND: Machine perfusion is the preferred preservation method for deceased donor kidneys. Perfusate fluid, which contains a complex mixture of components, offers potential insight into the organ's viability and function. This study explored immune cell release, particularly tissue-resident lymphocytes (TRLs), during donor kidney machine perfusion and its correlation with injury markers.METHODS: Perfusate samples from hypothermic machine perfusion (HMP; n = 26) and normothermic machine perfusion (NMP; n = 16) of human donor kidneys were analyzed for TRLs using flow cytometry. Residency was defined by expressions of CD69, CD103, and CD49as. TRL release was quantified exclusively in NMP. Additionally, levels of cell-free DNA, neutrophil gelatinase-associated lipocalin, and soluble E-cadherin (sE-cadherin) were measured in NMP supernatants with quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.RESULTS: Both HMP and NMP samples contained a heterogeneous population of TRLs, including CD4+ tissue-resident memory T cells, CD8+ tissue-resident memory T cells, tissue-resident natural killer cells, tissue-resident natural killer T cells, and helper-like innate lymphoid cells. Median TRL proportions among total CD45+ lymphocytes were 0.89% (NMP) and 0.84% (HMP). TRL quantities in NMP did not correlate with donor characteristics, perfusion parameters, posttransplant outcomes, or cell-free DNA and neutrophil gelatinase-associated lipocalin concentrations. However, CD103+ TRL release positively correlated with the release of sE-cadherin, the ligand for the CD103 integrin.CONCLUSIONS: Human donor kidneys release TRLs during both HMP and NMP. The release of CD103+ TRLs was associated with the loss of their ligand sE-cadherin but not with general transplant injury biomarkers.</p

The Science and Practice of Carcinogen Identification and Evaluation

Several national and international health agencies have established programs with the aim of identifying agents and exposures that cause cancer in humans. Carcinogen identification is an activity grounded in the scientific evaluation of the results of human epidemiologic studies, long-term bioassays in experimental animals, and other data relevant to an evaluation of carcinogenicity and its mechanisms. In this commentary, after a brief discussion of the science basis common to the evaluation of carcinogens across different programs, we discuss in more detail the principles and procedures currently used by the IARC Monographs program

Mildly relativistic motion in the radio-quiet quasar PG 1351+640

Measuring the proper motion of the emission component in radio-quiet quasars (RQQs) could help to distinguish between the origins of the radio emission and to understand whether the jet production mechanism is the same in radio-loud quasars and RQQs. PG 1351+640 is one of the few RQQs suitable for proper motion studies: it has two compact components on milli-arcsec scales, a flat-spectrum core and a steep-spectrum jet; both components are ≳2 mJy at 5 GHz and are well suited for Very Long Baseline Array (VLBA) observations. We compare recent VLBA observations with that made seventeen years ago and find no significant change in the core-jet separation between 2005 and 2015 (a proper motion of 0.003 mas yr-1). However, the core-jet separation increased significantly between 2015 and 2022, inferring a jet proper motion velocity of 0.063 mas yr-1, which corresponds to an apparent transverse velocity of. The result suggests that the jet of the RQQ PG 1351+640 is mildly relativistic and oriented at a relatively small viewing angle

Radio Astronomy

Contains reports on twelve research projects.National Science Foundation (Grant AST77-06052)Joint Services Electronics Program (Contract DAAB07-76-C-1400)National Aeronautics and Space Administration (Contract NAS5-21980)U.S. Air Force - Electronic Systems Division (Contract F19628-75-C-0122)U.S. Department of Commerce - National Oceanic Atmospheric Administration (Grant 04-8-M01-1)National Aeronautics and Space Administration (Contract NAS5-22929)National Aeronautics and Space Administration (Contract NAS5-23677)National Science Foundation (Grant AST73-05042-A03)National Science Foundation (Grant AST76-20376

The PARADIGM project I: a multiscale radio morphological analysis of local U/LIRGS

Disentangling the radio flux contribution from star formation (SF) and active-galactic-nuclei (AGNs) activity is a long-standing problem in extragalactic astronomy, since at frequencies of ≲ 10 GHz, both processes emit synchrotron radiation. We present in this work the general objectives of the PARADIGM (PAnchromatic high-Resolution Analysis of DIstant Galaxy Mergers) project, a multi-instrument concept to explore SF and mass assembly of galaxies. We introduce two novel general approaches for a detailed multiscale study of the radio emission in local (ultra) luminous infrared galaxies (U/LIRGs). In this work, we use archival interferometric data from the Very Large Array (VLA) centred at ∼ 6 GHz (C band) and present new observations from the e-Multi-Element Radio-Linked Interferometer Network (e-MERLIN) for UGC 5101, VV 705, VV 250, and UGC 8696. Using our image decomposition methods, we robustly disentangle the radio emission into distinct components by combining information from the two interferometric arrays. We use e-MERLIN as a probe of the core-compact radio emission (AGN or starburst) at ∼ 20 pc scales, and as a probe of nuclear diffuse emission, at scales ∼100–200 pc. With VLA, we characterize the source morphology and the flux density on scales from ∼200 pc up to and above 1 kpc. As a result, we find deconvolved and convolved sizes for nuclear regions from ∼10 to ∼200 pc. At larger scales, we find sizes of 1.5–2 kpc for diffuse structures (with effective sizes of ∼ 300–400 pc). We demonstrate that the radio emission from nuclear extended structures (∼ 100 pc) can dominate over core-compact components, providing a significant fraction of the total multiscale SF output. We establish a multiscale radio tracer for SF by combining information from different instruments. Consequently, this work sets a starting point to potentially correct for overestimations of AGN fractions and underestimates of SF activity

Meeting Report: Summary of IARC Monographs on Formaldehyde, 2-Butoxyethanol, and 1-tert-Butoxy-2-Propanol

An international, interdisciplinary working group of expert scientists met in June 2004 to develop IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans (IARC Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. Each IARC Monograph includes a critical review of the pertinent scientific literature and an evaluation of an agent’s potential to cause cancer in humans. After a thorough discussion of the epidemiologic, experimental, and other relevant data, the working group concluded that formaldehyde is carcinogenic to humans, based on sufficient evidence in humans and in experimental animals. In the epidemiologic studies, there was sufficient evidence that formaldehyde causes nasopharyngeal cancer, “strong but not sufficient” evidence of leukemia, and limited evidence of sinonasal cancer. The working group also concluded that 2-butoxyethanol and 1-tert-butoxy-2-propanol are not classifiable as to their carcinogenicity to humans, each having limited evidence in experimental animals and inadequate evidence in humans. These three evaluations and the supporting data will be-published as Volume 88 of the IARC Monographs

Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass

Kidney transplant (KTx) biopsies showing transplant glomerulopathy (TG) (glomerular basement membrane double contours (cg) &gt; 0) and microvascular inflammation (MVI) in the absence of C4d staining and donor-specific antibodies (DSAs) do not fulfill the criteria for chronic active antibody–mediated rejection (CA-AMR) diagnosis and do not fit into any other Banff category. To investigate this, we initiated a multicenter intercontinental study encompassing 36 cases, comparing the immunomic and transcriptomic profiles of 14 KTx biopsies classified as cg+MVI DSA-/C4d- with 22 classified as CA-AMR DSA+/C4d+ through novel transcriptomic analysis using the NanoString Banff-Human Organ Transplant (B-HOT) panel and subsequent orthogonal subset analysis using two innovative 5-marker multiplex immunofluorescent panels. Nineteen genes were differentially expressed between the two study groups. Samples diagnosed with CA-AMR DSA+/C4d+ showed a higher glomerular abundance of natural killer cells and higher transcriptomic cell type scores for macrophages in an environment characterized by increased expression of complement-related genes (i.e., C5AR1) and higher activity of angiogenesis, interstitial fibrosis tubular atrophy, CA-AMR, and DSA-related pathways when compared to samples diagnosed with cg+MVI DSA-/C4d-. Samples diagnosed with cg+MVI DSA-/C4d- displayed a higher glomerular abundance and activity of T cells (CD3+, CD3+CD8+, and CD3+CD8-). Thus, we show that using novel multiomic techniques, KTx biopsies with cg+MVI DSA-/C4d- have a prominent T-cell presence and activity, putting forward the possibility that these represent a more T-cell dominant phenotype.</p

Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass

Kidney transplant (KTx) biopsies showing transplant glomerulopathy (TG) (glomerular basement membrane double contours (cg) &gt; 0) and microvascular inflammation (MVI) in the absence of C4d staining and donor-specific antibodies (DSAs) do not fulfill the criteria for chronic active antibody–mediated rejection (CA-AMR) diagnosis and do not fit into any other Banff category. To investigate this, we initiated a multicenter intercontinental study encompassing 36 cases, comparing the immunomic and transcriptomic profiles of 14 KTx biopsies classified as cg+MVI DSA-/C4d- with 22 classified as CA-AMR DSA+/C4d+ through novel transcriptomic analysis using the NanoString Banff-Human Organ Transplant (B-HOT) panel and subsequent orthogonal subset analysis using two innovative 5-marker multiplex immunofluorescent panels. Nineteen genes were differentially expressed between the two study groups. Samples diagnosed with CA-AMR DSA+/C4d+ showed a higher glomerular abundance of natural killer cells and higher transcriptomic cell type scores for macrophages in an environment characterized by increased expression of complement-related genes (i.e., C5AR1) and higher activity of angiogenesis, interstitial fibrosis tubular atrophy, CA-AMR, and DSA-related pathways when compared to samples diagnosed with cg+MVI DSA-/C4d-. Samples diagnosed with cg+MVI DSA-/C4d- displayed a higher glomerular abundance and activity of T cells (CD3+, CD3+CD8+, and CD3+CD8-). Thus, we show that using novel multiomic techniques, KTx biopsies with cg+MVI DSA-/C4d- have a prominent T-cell presence and activity, putting forward the possibility that these represent a more T-cell dominant phenotype.</p

Virus-specific T_RM cells of both donor and recipient origin reside in human kidney transplants

Tissue-resident lymphocytes (TRLs) are critical for local protection against viral pathogens in peripheral tissue. However, it is unclear if TRLs perform a similar role in transplanted organs under chronic immunosuppressed conditions. In this study, we aimed to characterize the TRL compartment in human kidney transplant nephrectomies and examine its potential role in antiviral immunity. The TRL compartment of kidney transplants contained diverse innate, innate-like, and adaptive TRL populations expressing the canonical residency markers CD69, CD103, and CD49a. Chimerism of donor and recipient cells was present in 43% of kidney transplants and occurred in all TRL subpopulations. Paired single-cell transcriptome and T cell receptor (TCR) sequencing showed that donor and recipient tissue–resident memory T (TRM) cells exhibit striking similarities in their transcriptomic profiles and share numerous TCR clonotypes predicted to target viral pathogens. Virus dextramer staining further confirmed that CD8 TRM cells of both donor and recipient origin express TCRs with specificities against common viruses, including CMV, EBV, BK polyomavirus, and influenza A. Overall, the study results demonstrate that a diverse population of TRLs resides in kidney transplants and offer compelling evidence that TRM cells of both donor and recipient origin reside within this TRL population and may contribute to local protection against viral pathogens.</p

Radio Astronomy

Contains research objectives and summary of research on seven research projects.M.I.T. Sloan Fund for Basic ResearchNational Aeronautics and Space Administration (Contract NAS5-21980)National Aeronautics and Space Administration (Contract NAS5-22485)National Aeronautics and Space Administration (Contract NAS5-23677)National Aeronautics and Space Administration (Contract NAS5-22929)U. S. Air Force - Electronic Systems Division (Contract F19628-75-C-0122)National Science Foundation (Grant AST73-05043-A02)National Science Foundation (Grant AST73-05042-A03