IL-21 induces IL-22 production in CD4+ T-cells

IL-22 produced by innate lymphoid cells (ILCs) and CD4+ T cells plays an important role in host defense and mucosal homeostasis, thus it is important to investigate the mechanisms that regulate IL-22 production. We investigated the regulation IL-22 production by CD4+ T cells. Here we show that IL-21 triggers IL-22, but not IL-17 production by CD4+ T cells. STAT3, activated by IL-21, controls the epigenetic status of the il22 promoter and its interaction with the aryl hydrocarbon receptor (AhR). Moreover, IL-21 and AhR signaling in T cells control IL-22 production and the development of dextran sodium sulfate-induced colitis in ILC-deficient mice. Thus, we have identified IL-21 as an inducer of IL-22 production in CD4+ T cells in vitro and in vivo

Reservoir architecture and heterogeneity distribution in floodplain sandstones: Key features in outcrop, core and wireline logs

Exploration and production from formations deposited in low-gradient fluvial systems is typically associated with a high degree of uncertainty; a reflection of the inherent characteristics of these environments, notably the dominance of non-reservoir floodplain fines, rapid lateral facies variations and associated heterogeneities at different scales. However, for a field development to be successful it becomes crucial to know the location, geometry, dimensions and connectivity of the most permeable facies, related to the main channel and the associated proximal overbank deposits (crevasse-splay complexes). With the aim of addressing this problem, a multi-disciplinary study is presented, combining outcrop data, high-resolution sedimentological descriptions and advanced visualization techniques based on Digital Outcrop Models. This is compared with subsurface data from behind the outcrop (core, gamma ray and borehole image logs). The Mudstone–Sandstone Unit of the Triassic Red Beds of Iberian Meseta formation in south-central Spain was selected for the present study. The unit is characterized by the lateral and vertical stacking of four architectural elements: (i) channelized sandstone bodies; (ii) asymmetrical sigmoidal-shaped sandstone bodies; (iii) lobe-shaped to sheet-like sandstone bodies; and (iv) sheet-like mudstones. These elements represent meandering channel, crevasse-channel-splay and floodplain sub-environments, comprising a distal, low-gradient meandering fluvial system. Together with well-documented outcrop and core facies, calibrated log responses are also presented for the channel bodies (bell-shape Gamma Ray profile, random azimuths and low to high dip angles), the crevasse-splay bodies (funnel-shape Gamma Ray profile, unidirectional azimuths and low dip angles) and the floodplain deposits (serrated Gamma Ray profile, unidirectional azimuths and very low dip angles). The full integration of outcrop and subsurface datasets has enabled generation of a robust conceptual model with predictive potential when establishing the three-dimensional stacking of facies, distribution of heterogeneities, and the connectivity between reservoir rock geobodies of primary (channel) and secondary (crevasse complex) interest in this type of fluvial reservoir.Fil: Yeste, Luis Miguel. Universidad de Granada. Facultad de Ciencias. Departamento de Estratigrafía y Paleontología.; EspañaFil: Varela, Augusto Nicolás. YPF - Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Viseras, César. Universidad de Granada. Facultad de Ciencias. Departamento de Estratigrafía y Paleontología.; EspañaFil: Mcdougall, Neil D.. No especifíca;Fil: García García, Fernando. Universidad de Granada. Facultad de Ciencias. Departamento de Estratigrafía y Paleontología.; Españ

ILC3 function as a double-edged sword in inflammatory bowel diseases

Inflammatory bowel diseases (IBD), composed mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function and the bias of NCR+ ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cells’ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Monte Carlo-based sensitivity analysis of the RIM2D hydrodynamic model for the 2021 flood event in western Germany

Hydrodynamic models are crucial for flood forecasts and early warnings, particularly in response to events such as the devastating floods in Germany's Ahr region in July 2021. However, several uncertainties can be present in these models stemming from various sources, such as model structure, parameters, and boundary conditions. In this study, we aim to address these uncertainties and enhance the existing hydrodynamic model set up using RIM2D (Rapid Inundation Model 2D), introduced by Apel et al. (2022) for the Ahr region. The goal is to fortify its robustness and reliability for inundation simulations in the area. For this, we employ a large number of Monte Carlo simulations, assessing the effects of various model elements such as floodplain and channel roughness coefficients, as well as terrain resolution, on river dynamics and inundation. Our findings emphasize the critical role of proper parameter assignment in attaining optimal simulation results. The results show that sensitivity to input factors varies depending on the performance metrics used and the output predicted. We demonstrate that to simulate flow formation and water level in the river channel, the roughness parameter of the river channel and the model's resolution are paramount. On the other hand, to simulate flood extent and the distribution of water depth across the domain, even coarser resolutions prove adequate and, due to their reduced computation time, might be better suited for early-warning systems. Furthermore, our findings suggest that the differences observed between finer- and coarser-resolution models may stem from the varying representations of the river channel and buildings within the model. Ultimately, this work provides a guideline for the parameterization of RIM2D and similar physically based fluvial models tailored to the Ahr region, offering valuable insights for future hydrodynamic modeling endeavors in the area.</p

Lab-on-a-Chip Analysis Using Benchtop NMR Technology

We present the design and optimization of a benchtop NMR spectrometer for real-time metabolic monitoring of 3D tissue on microfluidic platforms, utilizing hyperpolarization via dynamic nuclear polarisation. We show the modifications made to a commercial benchtop NMR spectrometer, the design and fabrication of a microfluidic platform ensuring consistent injection of hyperpolarized substrates and ongoing cell media renewal, and its integration with a radio frequency (RF) coil for data transmission and reception (Tx/Rx). Additionally, the construction of a sample carrier is presented. Preliminary NMR results from this system are also provided.This work has received funding from: The European Union’s Horizon 2020 research and innovation program (GA-863037); the Spanish grants with reference PID2020- 117859RA-I00 funded by MCIN/AEI/10.13039/501100011033 (NARMYD), RYC2020-029099-I funded by MCIN/AEI10.13039/501100011033 and by “ESF Investing in your future”, PLEC2022-009256 funded by MCIN/AEI/10.13039/501100011033 and by the “European Union NextGenerationEU/PRTR”; The BIST (Barcelona Institute of Science and Technology)-“la Caixa” Banking Foundation Chemical Biology programme

Lab-on-a-Chip Analysis Using Benchtop NMR Technology

We present the design and optimization of a benchtop NMR spectrometer for real-time metabolic monitoring of 3D tissue on microfluidic platforms, utilizing hyperpolarization via dynamic nuclear polarisation. We show the modifications made to a commercial benchtop NMR spectrometer, the design and fabrication of a microfluidic platform ensuring consistent injection of hyperpolarized substrates and ongoing cell media renewal, and its integration with a radio frequency (RF) coil for data transmission and reception (Tx/Rx). Additionally, the construction of a sample carrier is presented. Preliminary NMR results from this system are also provided.This work has received funding from: The European Union’s Horizon 2020 research and innovation program (GA-863037); the Spanish grants with reference PID2020- 117859RA-I00 funded by MCIN/AEI/10.13039/501100011033 (NARMYD), RYC2020-029099-I funded by MCIN/AEI10.13039/501100011033 and by “ESF Investing in your future”, PLEC2022-009256 funded by MCIN/AEI/10.13039/501100011033 and by the “European Union NextGenerationEU/PRTR”; The BIST (Barcelona Institute of Science and Technology)-“la Caixa” Banking Foundation Chemical Biology programme

Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program

CONTEXT: Safety concerns regarding premature mortality, diabetes, neoplasia and cerebrovascular disease in association with growth hormone (GH) therapy have been raised. OBJECTIVE: To assess incidence of key safety outcomes. DESIGN: Prospective, multinational, observational study (1999-2015). SETTING: 22,311 GH-treated children from 827 investigative sites in 30 countries. PATIENTS: Children with growth disorders. INTERVENTIONS: GH treatment. MAIN OUTCOME MEASURES: Standardized mortality (SMR) and incidence (SIR) ratios with 95% confidence intervals (CI) for mortality, diabetes, and primary cancer, using general population registries. RESULTS: Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean±SD follow-up of 4.2±3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with SMR (95% CI) of 0.61 (0.44-0.82); the SMR was elevated for patients with cancer-related organic GH deficiency (5.87 [3.21-9.85]). Based on 18 cases, Type 2 diabetes (T2DM) risk was elevated (SIR 3.77 [2.24-5.96]), but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed (SIR 0.71 [0.39-1.20]). Second neoplasms occurred in 31/622 (5.0%) cancer survivors (10.7 [7.5-15.2] cases/1000 PY), and intracranial tumor recurrences in 67/823 (8.1%) tumor survivors (16.9 [13.3-21.5] cases/1000 PY). All 3 hemorrhagic stroke cases had risk factors. CONCLUSIONS: GeNeSIS data support the favourable safety profile of pediatric GH treatment. Overall risk for death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared to the general population, but most cases had diabetes risk factors

Los equipos de pediatria ante la obesidad infantil: Un estudio cualitativo dentro del proyecto STOP

[spa] Introducción Comprender los factores que influyen en el tratamiento del sobrepeso y la obesidad infantil es crucial para ofrecer el mejor apoyo a las familias y solucionar este grave problema de salud pública. Objetivo Describir las actitudes y sentimientos del personal de pediatría al tratar con los padres el sobrepeso y la obesidad de sus hijos, explorando los facilitadores y las barreras percibidas, a fin de realizar una atención efectiva. Sujetos y método Estudio cualitativo por cuestionarios individuales semiestructurados de personal pediátrico (pediatras y enfermeras pediatras; n=57; 68% mujeres) de centros de atención primaria y hospitales de la isla de Mallorca, sobre los que se aplicó un análisis temático. Resultados Se identificaron 3 temas: «La actitud de los padres en la obesidad infantil» (subtemas «La conciencia de los padres», «Los padres piden ayuda»), «El personal pediátrico y la obesidad infantil» (subtemas «Aproximación al problema: la entrevista con los padres», «Buscando juntos la solución») y «Barreras del sistema» (subtemas «Mejorar el trabajo en equipo y la política de salud», «Participación familiar al abordar y estudiar la obesidad infantil»). Conclusiones El personal pediátrico sabe tratar la obesidad infantil, pero demanda entrenamiento en motivación. La terapia de la obesidad infantil será efectiva cuando los padres/cuidadores reconocen el problema y establecen confianza con los equipos pediátricos. El sistema de salud aún es una barrera a la actividad del personal pediátrico