4 results on '"Konkel J"'
Search Results
2. Alternating high-fat diet enhances atherosclerosis by neutrophil reprogramming.
- Author
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Lavillegrand JR, Al-Rifai R, Thietart S, Guyon T, Vandestienne M, Cohen R, Duval V, Zhong X, Yen D, Ozturk M, Negishi Y, Konkel J, Pinteaux E, Lenoir O, Vilar J, Laurans L, Esposito B, Bredon M, Sokol H, Diedisheim M, Saliba AE, Zernecke A, Cochain C, Haub J, Tedgui A, Speck NA, Taleb S, Mhlanga MM, Schlitzer A, Riksen NP, and Ait-Oufella H
- Subjects
- Animals, Female, Male, Mice, Apolipoproteins E deficiency, Apolipoproteins E genetics, Bone Marrow Cells cytology, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, Extracellular Traps, Inflammation pathology, Interleukin-1beta metabolism, Mice, Inbred C57BL, Myelopoiesis, Plaque, Atherosclerotic metabolism, Plaque, Atherosclerotic pathology, Receptors, LDL deficiency, Receptors, LDL genetics, Signal Transduction, Atherosclerosis metabolism, Atherosclerosis pathology, Cellular Reprogramming, Diet, High-Fat adverse effects, Neutrophils metabolism, Neutrophils pathology
- Abstract
Systemic immune responses caused by chronic hypercholesterolaemia contribute to atherosclerosis initiation, progression and complications
1 . However, individuals often change their dietary habits over time2 , and the effects of an alternating high-fat diet (HFD) on atherosclerosis remain unclear. Here, to address this relevant issue, we developed a protocol using atherosclerosis-prone mice to compare an alternating versus continuous HFD while maintaining similar overall exposure periods. We found that an alternating HFD accelerated atherosclerosis in Ldlr-/- and Apoe-/- mice compared with a continuous HFD. This pro-atherogenic effect of the alternating HFD was also observed in Apoe-/- Rag2-/- mice lacking T, B and natural killer T cells, ruling out the role of the adaptive immune system in the observed phenotype. Discontinuing the HFD in the alternating HFD group downregulated RUNX13 , promoting inflammatory signalling in bone marrow myeloid progenitors. After re-exposure to an HFD, these cells produced IL-1β, leading to emergency myelopoiesis and increased neutrophil levels in blood. Neutrophils infiltrated plaques and released neutrophil extracellular traps, exacerbating atherosclerosis. Specific depletion of neutrophils or inhibition of IL-1β pathways abolished emergency myelopoiesis and reversed the pro-atherogenic effects of the alternating HFD. This study highlights the role of IL-1β-dependent neutrophil progenitor reprogramming in accelerated atherosclerosis induced by alternating HFD., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
- Full Text
- View/download PDF
3. From Rangelands to Cropland, Land-Use Change and Its Impact on Soil Organic Carbon Variables in a Peruvian Andean Highlands: A Machine Learning Modeling Approach.
- Author
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Carbajal M, Ramírez DA, Turin C, Schaeffer SM, Konkel J, Ninanya J, Rinza J, De Mendiburu F, Zorogastua P, Villaorduña L, and Quiroz R
- Abstract
Andean highland soils contain significant quantities of soil organic carbon (SOC); however, more efforts still need to be made to understand the processes behind the accumulation and persistence of SOC and its fractions. This study modeled SOC variables-SOC, refractory SOC (RSOC), and the
13 C isotope composition of SOC (δ13 CSOC )-using machine learning (ML) algorithms in the Central Andean Highlands of Peru, where grasslands and wetlands ("bofedales") dominate the landscape surrounded by Junin National Reserve. A total of 198 soil samples (0.3 m depth) were collected to assess SOC variables. Four ML algorithms-random forest (RF), support vector machine (SVM), artificial neural networks (ANNs), and eXtreme gradient boosting (XGB)-were used to model SOC variables using remote sensing data, land-use and land-cover (LULC, nine categories), climate topography, and sampled physical-chemical soil variables. RF was the best algorithm for SOC and δ13 CSOC prediction, whereas ANN was the best to model RSOC. "Bofedales" showed 2-3 times greater SOC (11.2 ± 1.60%) and RSOC (1.10 ± 0.23%) and more depleted δ13 CSOC (- 27.0 ± 0.44 ‰) than other LULC, which reflects high C persistent, turnover rates, and plant productivity. This highlights the importance of "bofedales" as SOC reservoirs. LULC and vegetation indices close to the near-infrared bands were the most critical environmental predictors to model C variables SOC and δ13 CSOC . In contrast, climatic indices were more important environmental predictors for RSOC. This study's outcomes suggest the potential of ML methods, with a particular emphasis on RF, for mapping SOC and its fractions in the Andean highlands., Supplementary Information: The online version contains supplementary material available at 10.1007/s10021-024-00928-7., (© The Author(s) 2024.)- Published
- 2024
- Full Text
- View/download PDF
4. Granulocyte transfusion during cord blood transplant for relapsed, refractory AML is associated with massive CD8 + T-cell expansion, significant cytokine release syndrome and induction of disease remission.
- Author
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Borrill R, Poulton K, Kusyk L, Routledge A, Bonney D, Hanasoge-Nataraj R, Powys M, Mustafa O, Campbell H, Senthil S, Dillon R, Jovanovic J, Morton S, James B, Rao K, Stanworth S, Konkel J, and Wynn R
- Subjects
- Child, Humans, CD8-Positive T-Lymphocytes pathology, Cytokine Release Syndrome etiology, Granulocytes pathology, Interferon-gamma, Neoplasm Recurrence, Local etiology, Remission Induction, Cord Blood Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
In high-risk myeloid malignancy, relapse is reduced using cord blood transplant (CBT) but remains the principal cause of treatment failure. We previously described T-cell expansion in CBT recipients receiving granulocyte transfusions. We now report the safety and tolerability of such transfusions, T-cell expansion data, immunophenotype, cytokine profiles and clinical response in children with post-transplant relapsed acute leukaemia who received T-replete, HLA-mismatched CBT and pooled granulocytes within a phase I/II trial (ClinicalTrials.Gov NCT05425043). All patients received the transfusion schedule without significant clinical toxicity. Nine of ten patients treated had detectable measurable residual disease (MRD) pre-transplant. Nine patients achieved haematological remission, and eight became MRD negative. There were five deaths: transplant complications (n = 2), disease (n = 3), including two late relapses. Five patients are alive and in remission with 12.7 months median follow up. Significant T-cell expansion occurred in nine patients with a greater median lymphocyte count than a historical cohort between days 7-13 (median 1.73 × 10
9 /L vs. 0.1 × 109 /L; p < 0.0001). Expanded T-cells were predominantly CD8+ and effector memory or TEMRA phenotype. They exhibited markers of activation and cytotoxicity with interferon-gamma production. All patients developed grade 1-3 cytokine release syndrome (CRS) with elevated serum IL-6 and interferon-gamma., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2023
- Full Text
- View/download PDF
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