Tracing nerve fibers with volume electron microscopy to quantitatively analyze brain connectivity.

The highly complex structure of the brain requires an approach that can unravel its connectivity. Using volume electron microscopy and a dedicated software we can trace and measure all nerve fibers present within different samples of brain tissue. With this software tool, individual dendrites and axons are traced, obtaining a simplified "skeleton" of each fiber, which is linked to its corresponding synaptic contacts. The result is an intricate meshwork of axons and dendrites interconnected by a cloud of synaptic junctions. To test this methodology, we apply it to the stratum radiatum of the hippocampus and layers 1 and 3 of the somatosensory cortex of the mouse. We find that nerve fibers are densely packed in the neuropil, reaching up to 9 kilometers per cubic mm. We obtain the number of synapses, the number and lengths of dendrites and axons, the linear densities of synapses established by dendrites and axons, and their location on dendritic spines and shafts. The quantitative data obtained through this method enable us to identify subtle traits and differences in the synaptic organization of the samples, which might have been overlooked in a qualitative analysis.

Evidence for widespread translation of 5' untranslated regions.

Ribosome profiling experiments support the translation of a range of novel human open reading frames. By contrast, most peptides from large-scale proteomics experiments derive from just one source, 5' untranslated regions. Across the human genome we find evidence for 192 translated upstream regions, most of which would produce protein isoforms with extended N-terminal ends. Almost all of these N-terminal extensions are from highly abundant genes, which suggests that the novel regions we detect are just the tip of the iceberg. These upstream regions have characteristics that are not typical of coding exons. Their GC-content is remarkably high, even higher than 5' regions in other genes, and a large majority have non-canonical start codons. Although some novel upstream regions have cross-species conservation - five have orthologues in invertebrates for example - the reading frames of two thirds are not conserved beyond simians. These non-conserved regions also have no evidence of purifying selection, which suggests that much of this translation is not functional. In addition, non-conserved upstream regions have significantly more peptides in cancer cell lines than would be expected, a strong indication that an aberrant or noisy translation initiation process may play an important role in translation from upstream regions.

Chemical Composition, Antioxidant Activities, Antidepressant Effect, and Lipid Peroxidation of Peruvian Blueberry: Molecular Docking Studies on Targets Involved in Oxidative Stress and Depression.

Blueberries (Vaccinium corymbosum L.) are cultivated worldwide and are among the best dietary sources of bioactive compounds with beneficial health effects. This study aimed to investigate the components of Peruvian blueberry using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS/MS), identifying 11 compounds. Furthermore, we assessed in vitro the antioxidant activity and in vivo the antidepressant effect using a rat model and protective effect on lipid peroxidation (in the serum, brain, liver, and stomach). We also conducted molecular docking simulations with proteins involved in oxidative stress and depression for the identified compounds. Antioxidant activity was assessed by measuring total phenolic and flavonoid contents, as well as using 1,1-diphenyl-2-picrylhydrazin (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+), and ferric-reducing antioxidant power (FRAP) assays. Peruvian blueberries demonstrated higher antioxidant activity than Vaccinium corymbosum fruits from Chile, Brazil, the United States, Turkey, Portugal, and China. The results showed that oral administration of Peruvian blueberries (10 and 20 mg/kg) for 28 days significantly (p < 0.001) increased swimming and reduced immobility in the forced swimming test (FST). Additionally, at doses of 40 and 80 mg/kg, oxidative stress was reduced in vivo (p < 0.001) by decreasing lipid peroxidation in brain, liver, stomach, and serum. Molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed. In the molecular docking studies, quercitrin and 3,5-di-O-caffeoylquinic acid showed the best docking scores for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, and xanthine oxidase; while 3,5-dicaffeoylquinic acid methyl ester and caffeoyl coumaroylquinic acid had the best docking scores for monoamine oxidase and serotonin receptor 5-HT2. In summary, our results suggest that the antidepressant and protective effects against lipid peroxidation might be related to the antioxidant activity of Peruvian Vaccinium corymbosum L.

Preovulatory follicular fluid secretome added to in vitro maturation medium influences the metabolism of equine cumulus-oocyte complexes.

BACKGROUND: In vitro embryo production is a highly demanded reproductive technology in horses, which requires the recovery (in vivo or post-mortem) and in vitro maturation (IVM) of oocytes. Oocytes subjected to IVM exhibit poor developmental competence compared to their in vivo counterparts, being this related to a suboptimal composition of commercial maturation media. The objective of this work was to study the effect of different concentrations of secretome obtained from equine preovulatory follicular fluid (FF) on cumulus-oocyte complexes (COCs) during IVM. COCs retrieved in vivo by ovum pick up (OPU) or post-mortem from a slaughterhouse (SLA) were subjected to IVM in the presence or absence of secretome (Control: 0 µg/ml, S20: 20 µg/ml or S40: 40 µg/ml). After IVM, the metabolome of the medium used for oocyte maturation prior (Pre-IVM) and after IVM (Post-IVM), COCs mRNA expression, and oocyte meiotic competence were analysed. RESULTS: IVM leads to lactic acid production and an acetic acid consumption in COCs obtained from OPU and SLA. However, glucose consumption after IVM was higher in COCs from OPU when S40 was added (Control Pre-IVM vs. S40 Post-IVM: 117.24 ± 7.72 vs. 82.69 ± 4.24; Mean µM ± SEM; p < 0.05), while this was not observed in COCs from SLA. Likewise, secretome enhanced uptake of threonine (Control Pre-IVM vs. S20 Post-IVM vs. S40 Post-IVM: 4.93 ± 0.33 vs. 3.04 ± 0.25 vs. 2.84 ± 0.27; Mean µM ± SEM; p < 0.05) in COCs recovered by OPU. Regarding the relative mRNA expression of candidate genes related to metabolism, Lactate dehydrogenase A (LDHA) expression was significantly downregulated when secretome was added during IVM at 20-40 µg/ml in OPU-derived COCs (Control vs. S20 vs. S40: 1.77 ± 0.14 vs. 1 ± 0.25 vs. 1.23 ± 0.14; fold change ± SEM; p < 0.05), but not in SLA COCs. CONCLUSIONS: The addition of secretome during in vitro maturation (IVM) affects the gene expression of LDHA, glucose metabolism, and amino acid turnover in equine cumulus-oocyte complexes (COCs), with diverging outcomes observed between COCs retrieved using ovum pick up (OPU) and slaughterhouse-derived COCs (SLA).

Differences between Patients with Sporadic and Familial Pheochromocytoma-Is It Possible to Avoid Genetic Testing in Certain Patients?

BACKGROUND: Pheochromocytoma (PHEO) is a rare neuroendocrine tumour with a strong genetic link, which therefore may modify its clinical behaviour and prognosis. The aim of the study is to evaluate the epidemiological and clinical differences between patients with sporadic and familial PHEO, as well as the specific differences in the index cases. METHODS: A retrospective analysis of 136 patients in a tertiary hospital (1984-2021). Epidemiological, clinical, and histological variables were analysed. STATISTICS: SPSS 28.0 software was used. Univariate and multivariate logistic regression analyses were performed. p < 0.05 was considered statistically significant. RESULTS: 64.71% of the cases (n = 88) presented a genetic mutation (familial cases). Additionally, 32.39% (n = 23) corresponded to index cases and the rest to screening cases. The main differences between patients with familial and sporadic PHEO were age (OR = 0.93 (0.89-0.97)), blood pressure-related symptoms (OR = 0.22 (0.06-0.89)), bilaterality (OR = 15.49 (3.76-63.84)), and size (OR = 0.70 (0.54-0.92)). Among patients with sporadic PHEO and index cases, only bilaterality was significant (OR = 13.53 (1.24-144.34)). CONCLUSIONS: Patients with familial PHEO diagnosed by screening differ from sporadic cases in terms of age, clinical features, and size. However, patients with sporadic PHEO only differ from index cases by a lower presence of bilaterality, which reaffirms the importance of genetic screening of patients with PHEO and their relatives.

A Sample Preparation Procedure for Isobaric Labeling-Based Single-Cell Proteomics.

Mass spectrometry-based proteomics has traditionally been limited by the amount of input material for analysis. Single-cell proteomics has emerged as a challenging discipline due to the ultra-high sensitivity required. Isobaric labeling-based multiplex strategies with a carrier proteome offer an approach to overcome the sensitivity limitations. Following this as the basic strategy, we show here the general workflow for preparing cells for single-cell mass spectrometry-based proteomics. This protocol can also be applied to manually isolated cells when large cells, such as cardiomyocytes, are difficult to isolate properly with conventional fluorescence-activated cell sorting (FACS) sorter methods.

Impacts of a newly formed lava delta on the marine environment: Lava-induced upwelling and abrupt chlorophyll depletion during the Tajogaite eruption (La Palma, 2021).

The 2021 Tajogaite eruption in La Palma (Canary Islands, Spain) emitted vast volumes of lava during 85 days, which reached the ocean in several occasions at the western flank of the island. Most of these flows merged to create a primary lava delta, covering an area of 48 ha, with an additional 30 ha underwater. Here we characterize the effects of the lava-seawater interaction on the surrounding marine environment. The area was sampled during two multidisciplinary oceanographic cruises: the first one comprised the days before the lava reached the ocean and after the first contact; and the second took place a month later, when the lava delta was already formed but still receiving lava inputs. Physical-chemical anomalies were found in the whole water column at different depths up to 300 m in all measured parameters, such as turbidity (+9 NTU), dissolved oxygen concentration (-17.17 µmol kg-1), pHT25 (-0.1), and chlorophyll-a concentration (-0.33 mg m-3). Surface temperature increased up to +2.3 °C (28.5 °C) and surface salinity showed increases and decreases of -1.01 and +0.70, respectively, in a radius of 4 km around the lava delta. In the water column, the heated waters experimented a lava-induced upwelling, bringing deeper, nutrient-rich waters to shallower depths; however, this feature did not trigger any phytoplankton bloom. In fact, integrated chlorophyll-a showed an abrupt decrease of -41 % in just two days and -69 % a month later, compared to prior conditions. The chlorophyll-a depletion reached a distance larger than 2.5 km (not delimited).

Use of Periodic Mesoporous Organosilica-Benzene Adsorbent for CO2 Capture to Reduce the Greenhouse Effect.

The CO2 adsorption of a phenylene-bridged ordered mesoporous organosilica (PMO-benzene) was analyzed. The maximum capture capacity was 638.2 mg·g-1 (0 °C and 34 atm). Approximately 0.43 g would be enough to reduce the amount of atmospheric CO2 in 1 m3 to pre-industrial levels. The CO2 adsorption data were analyzed using several isotherm models, including Langmuir, Freundlich, Sips, Toth, Dubinin-Radushkevich, and Temkin models. This study confirmed the capability of this material for use in reversible CO2 capture with a minimal loss of capacity (around 1%) after 10 capture cycles. Various techniques were employed to characterize this material. The findings from this study can help mitigate the greenhouse effect caused by CO2.

Performance Projection of Vacuum Gate Dielectric Doping-Free Carbon Nanoribbon/Nanotube Field-Effect Transistors for Radiation-Immune Nanoelectronics.

This paper investigates the performance of vacuum gate dielectric doping-free carbon nanotube/nanoribbon field-effect transistors (VGD-DL CNT/GNRFETs) via computational analysis employing a quantum simulation approach. The methodology integrates the self-consistent solution of the Poisson solver with the mode space non-equilibrium Green's function (NEGF) in the ballistic limit. Adopting the vacuum gate dielectric (VGD) paradigm ensures radiation-hardened functionality while avoiding radiation-induced trapped charge mechanisms, while the doping-free paradigm facilitates fabrication flexibility by avoiding the realization of a sharp doping gradient in the nanoscale regime. Electrostatic doping of the nanodevices is achieved via source and drain doping gates. The simulations encompass MOSFET and tunnel FET (TFET) modes. The numerical investigation comprehensively examines potential distribution, transfer characteristics, subthreshold swing, leakage current, on-state current, current ratio, and scaling capability. Results demonstrate the robustness of vacuum nanodevices for high-performance, radiation-hardened switching applications. Furthermore, a proposal for extrinsic enhancement via doping gate voltage adjustment to optimize band diagrams and improve switching performance at ultra-scaled regimes is successfully presented. These findings underscore the potential of vacuum gate dielectric carbon-based nanotransistors for ultrascaled, high-performance, energy-efficient, and radiation-immune nanoelectronics.

The Surface Chemistry of Methanol on Pd(111) and H-Pd(111) Surfaces: C-O Bond Cleavage and the Effects of Metal Hydride Formation.

Palladium catalysts are frequently employed in processes where methanol is an energy vector or carrier, being useful for the synthesis of methanol from mixtures of carbon dioxide and hydrogen (CO2/H2) or its steam reforming on demand. Results of synchrotron-based ambient pressure X-ray photoelectron spectroscopy for the adsorption of methanol on a Pd(111) model catalyst show a rich surface chemistry and complex phenomena that strongly depend on pressure and temperature. At low pressures (<10-6 Torr) and temperatures (<300 K), CO is the dominant decomposition product. As the pressure increases, cleavage of C-H, O-H, and C-O bonds is observed, and at elevated temperatures (400-600 K) the formation of CO and CHx/C fragments compete on the surface. Thus, existing reaction networks for methanol decomposition must be modified. Furthermore, surface and subsurface hydrogen (coming from PdHx) play a significant role in the stability and removal of CHx and C species.

3D Nanocrystallography and the Imperfect Molecular Lattice.

Crystallographic analysis relies on the scattering of quanta from arrays of atoms that populate a repeating lattice. While large crystals built of lattices that appear ideal are sought after by crystallographers, imperfections are the norm for molecular crystals. Additionally, advanced X-ray and electron diffraction techniques, used for crystallography, have opened the possibility of interrogating micro- and nanoscale crystals, with edges only millions or even thousands of molecules long. These crystals exist in a size regime that approximates the lower bounds for traditional models of crystal nonuniformity and imperfection. Accordingly, data generated by diffraction from both X-rays and electrons show increased complexity and are more challenging to conventionally model. New approaches in serial crystallography and spatially resolved electron diffraction mapping are changing this paradigm by better accounting for variability within and between crystals. The intersection of these methods presents an opportunity for a more comprehensive understanding of the structure and properties of nanocrystalline materials.

Role of Atomicity and Interface on InOx-TiO2 Composites: Thermo-Photo Valorization of CO2.

The synthesis, physicochemical, and functional properties of composite solids resulting from the surface spread of oxidized indium species onto nanoplatelets of anatase were investigated. Both the size and the interaction between the indium- and titanium-containing components control the functional properties. In the reduction of CO2 to CO, the best samples have an indium content between ca. 2 and 5 mol % and showed an excess rate over the photo and thermo-alone processes above 33% and an energy efficiency of 1.3%. Subnanometric (monomeric and dimeric) indium species present relatively weak thermal catalytic response but strong thermo-photo promotion of the activity. A gradual change in functional properties was observed with the growth of the indium content of the solids, leading to a progressive increase of thermal activity but lower thermo-photo promotion. The study provides a well-defined structure-activity relationship rationalizing the dual thermo-photo properties of the catalysts and establishes a guide for the development of highly active and stable composite solids for the elimination and valorization of CO2.

Theoretical Prediction and Experimental Verification of IrOx Supported on Titanium Nitride for Acidic Oxygen Evolution Reaction.

Reducing iridium (Ir) catalyst loading for acidic oxygen evolution reaction (OER) is a critical strategy for large-scale hydrogen production via proton exchange membrane (PEM) water electrolysis. However, simultaneously achieving high activity, long-term stability, and reduced material cost remains challenging. To address this challenge, we develop a framework by combining density functional theory (DFT) prediction using model surfaces and proof-of-concept experimental verification using thin films and nanoparticles. DFT results predict that oxidized Ir monolayers over titanium nitride (IrOx/TiN) should display higher OER activity than IrOx while reducing Ir loading. This prediction is verified by depositing Ir monolayers over TiN thin films via physical vapor deposition. The promising thin film results are then extended to commercially viable powder IrOx/TiN catalysts, which demonstrate a lower overpotential and higher mass activity than commercial IrO2 and long-term stability of 250 h to maintain a current density of 10 mA cm-2. The superior OER performance of IrOx/TiN is further confirmed using a proton exchange membrane water electrolyzer (PEMWE), which shows a lower cell voltage than commercial IrO2 to achieve a current density of 1 A cm-2. Both DFT and in situ X-ray absorption spectroscopy reveal that the high OER performance of IrOx/TiN strongly depends on the IrOx-TiN interaction via direct Ir-Ti bonding. This study highlights the importance of close interaction between theoretical prediction based on mechanistic understanding and experimental verification based on thin film model catalysts to facilitate the development of more practical powder IrOx/TiN catalysts with high activity and stability for acidic OER.

A Video Mosaicing-Based Sensing Method for Chicken Behavior Recognition on Edge Computing Devices.

Chicken behavior recognition is crucial for a number of reasons, including promoting animal welfare, ensuring the early detection of health issues, optimizing farm management practices, and contributing to more sustainable and ethical poultry farming. In this paper, we introduce a technique for recognizing chicken behavior on edge computing devices based on video sensing mosaicing. Our method combines video sensing mosaicing with deep learning to accurately identify specific chicken behaviors from videos. It attains remarkable accuracy, achieving 79.61% with MobileNetV2 for chickens demonstrating three types of behavior. These findings underscore the efficacy and promise of our approach in chicken behavior recognition on edge computing devices, making it adaptable for diverse applications. The ongoing exploration and identification of various behavioral patterns will contribute to a more comprehensive understanding of chicken behavior, enhancing the scope and accuracy of behavior analysis within diverse contexts.

Histological and scanning electron microscope observations on the developing retina of the cuttlefish (Sepia officinalis Linnaeus, 1758).

In this work we present a detailed study of the major events during retinal histogenesis of the cuttlefish Sepia officinalis from early embryos to newly hatched animals and juveniles. For this purpose, we carried out morphometric and histological analyses using light and scanning electron microscopy. From St19, the first embryonic stage analysed, to St23/24 the embryonic retina is composed of a pseudostratified epithelium showing abundant mitotic figures in the more internal surface. At St24 the first photoreceptor nuclei appear in the presumptive inner segment layer, while an incipient layer of apical processes of the future rhabdomeric layer become visible at St25. From this stage onwards, both the rhabdomeric layer and the inner segment layer increase in size until postnatal ages. In contrast, the width of the supporting cell layer progressively decreases from St25/26 until postnatal ages. S. officinalis embryos hatched in a morphologically advanced state, showing a differentiated retina even in the last stages of the embryonic period. However, features of immaturity are still observable in the retinal tissue during the first postnatal weeks of life, such as the existence of mitotic figures in the apical region of the supporting cell layer and migrating nuclei of differentiating photoreceptors crossing the basal membrane to reach their final location in the inner segment layer. Therefore, postnatal retinal neurogenesis is present in juvenile specimens of S. officinalis.

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.

BACKGROUND: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. METHODS: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. FINDINGS: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10-8; OR 1·19 [95% CI 1·12-1·26]) and VTN (rs704; p=2·75 × 10-9; OR 0·84 [0·79-0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10-8; OR 1·18 [1·12-1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15-3·82]; p=1·73 × 10-13). INTERPRETATION: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis. FUNDING: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Research.

The Use of Aspirin for Venous Thromboembolism Prophylaxis in Patients Who Have Morbid Obesity Undergoing Primary and Revision Total Joint Arthroplasty.

BACKGROUND: Venous thromboembolism (VTE) poses a major clinical concern due to its life-threatening nature, and obese and morbidly obese patients are thought to be at an increased risk for VTE. The aims of this study were twofold; first, to explore VTE rates in patients who have a body mass index (BMI) > 40 undergoing primary and revision total joint arthroplasty, and second, to investigate aspirin (ASA) efficacy and safety. METHODS: We identified all patients (n = 4,672) who had a BMI > 40 who underwent primary and revision total joint arthroplasty from 2016 to 2022 at a single academic tertiary care center. Patients were stratified by BMI groups: 40 to 44.9 (n = 3,462), 45 to 49.9 (n = 935), and 50+ (n = 275). The primary outcome was any VTE event within 90 days postoperatively. The secondary outcome consisted of wound complications within 90 days postoperatively. RESULTS: The total VTE rate was 0.4% (n = 21) and did not differ statistically between the BMI groups (0.4 versus 0.4 versus 0.7%, P = .669). The VTEs consisted of 6 deep venous thromboses (DVTs), 14 pulmonary embolisms, and one concomitant deep venous thrombosis and pulmonary embolism. The VTE rates were not statistically different between patients who received aspirin 325 mg 0.5% (n = 9), aspirin 81 mg 0.2% (n = 1), aspirin + anticoagulant (AC) 0.5% (n = 6), and AC alone 0.4% (n = 5) (P = .954). In addition, wound complications did not differ significantly between patients who received ASA 325 mg, ASA 81mg, ASA + AC, or AC alone (1.6 versus 1.0 versus 1.8 versus 1.1%, P = .351). CONCLUSIONS: The use of aspirin 325 and 81 mg was found to have similar VTE rates as aspirin + ACs and ACs alone, with no significant increase in wound complications. In patients who have a BMI > 40, the use of aspirin is a safe option for VTE prophylaxis and should be prescribed in the context of the patient who has other risk factors for VTE.

Decoding CD4+ T cell transcriptome in giant cell arteritis: Novel pathways and altered cross-talk with monocytes.

BACKGROUND: Giant cell arteritis (GCA) is an immune-mediated large-vessels vasculitis with complex etiology. Although the pathogenic mechanisms remain poorly understood, a central role for CD4+ T cells has been demonstrated. In this context, understanding the transcriptome dysregulation in GCA CD4+ T cells will yield new insights into its pathogenesis. METHODS: Transcriptome analysis was conducted on CD4+ T cells from 70 patients with GCA with different disease activity and treatment status (active patients before treatment and patients in remission with and without glucocorticoid treatment), and 28 healthy controls. The study also evaluated potential impacts of DNA methylation on gene expression alterations and assessed cross-talk with CD14+ monocytes. RESULTS: This study has uncovered a substantial number of genes and pathways potentially contributing to the pathogenicity of CD4+ T cells in GCA. Specifically, CD4+ T cells from GCA patients with active disease exhibited altered expression levels of genes involved in multiple immune-related processes, including various interleukins (IL) signaling pathways. Notably, IL-2, a decisive interleukin for regulatory T cells homeostasis, was among the most significant. Additionally, impaired apoptotic pathways appear crucial in GCA development. Our findings also suggest that histone-related epigenetic pathways may be implicated in promoting an inflammatory phenotype in GCA active patients. Finally, our study observed altered signaling communication, such as the Jagged-Notch signaling, between CD4+ T cells and monocytes that could have pathogenic relevance in GCA. CONCLUSIONS: Our study suggests the participation of novel cytokines and pathways and the occurrence of a disruption of monocyte-T cell crosstalk driving GCA pathogenesis.