Neoarchaean oxygen-based nitrogen cycle en route to the Great Oxidation Event.

The nitrogen isotopic composition of sedimentary rocks (δN) can trace redox-dependent biological pathways and early Earth oxygenation. However, there is no substantial change in the sedimentary δN record across the Great Oxidation Event about 2.45 billion years ago (Ga), a prominent redox change.

Evaluation of Postoperative Efficacy and Safety of Celecoxib in Children Hospitalized After Adenotonsillectomy.

Objective: The choice of optimal analgesia following an adenotonsillectomy is a clinical issue because of the risk of respiratory depression and bleeding. The objective of this study was to assess the effect of celecoxib on opioid use and pain scores in children hospitalized after adenotonsillectomy and to document its adverse effects.

Methods: This retrospective study was conducted in a tertiary care pediatric hospital.

Vasopressin in newborns with refractory acute pulmonary hypertension.

Background: Acute pulmonary hypertension (aPH) in newborns can be life threatening and challenging to manage. In newborns with refractory aPH, there is currently limited therapeutic agents.

Methods: Retrospective single-center cohort study in newborns less than one month old who were treated with vasopressin for a minimum of one hour in the context of refractory aPH in the neonatal and pediatric intensive care units of a tertiary university center between 2016 and 2022.

Genetic Reduction of IRF5 Expression after Disease Initiation Reduces Disease in a Mouse Lupus Model by Impacting Systemic and End-Organ Pathogenic Pathways.

Gain-of-function polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus. Global homozygous or heterozygous deficiency of IRF5 from birth confers protection in many lupus mouse models. However, less is known about the effects of IRF5 targeting after autoimmunity has already developed.

Prey consumption does not restore hydration state but mitigates the energetic costs of water deprivation in an insectivorous lizard.

To cope with limited availability of drinking water in their environment, terrestrial animals have developed numerous behavioral and physiological strategies including maintaining an optimal hydration state through dietary water intake. Recent studies performed in snakes, which are generalist carnivorous reptiles, suggest that the benefits of dietary water intake are negated by hydric costs of digestion. Most lizards are generalist insectivores that can shift their prey types, but firm experimental demonstration of dietary water intake is currently missing in these organisms.

The "parasite detoxification hypothesis": lead exposure potentially changes the ecological interaction from parasitism to mutualism.

In urban areas, organisms are exposed to high pollutant levels, especially element trace metals that may impact host-parasite interactions. Indeed, parasites have been reported to reduce the negative effects of pollutants on their hosts. The fitness of parasitized organisms in polluted environments may therefore be greater than that of unparasitized organisms.

Iron-mediated anaerobic ammonium oxidation recorded in the early Archean ferruginous ocean.

The nitrogen isotopic composition of organic matter is controlled by metabolic activity and redox speciation and has therefore largely been used to uncover the early evolution of life and ocean oxygenation. Specifically, positive δ N values found in well-preserved sedimentary rocks are often interpreted as reflecting the stability of a nitrate pool sustained by water column partial oxygenation. This study adds much-needed data to the sparse Paleoarchean record, providing carbon and nitrogen concentrations and isotopic compositions for more than fifty samples from the 3.

PD-1 combination therapy with IL-2 modifies CD8 T cell exhaustion program.

Combination therapy with PD-1 blockade and IL-2 is highly effective during chronic lymphocytic choriomeningitis virus infection. Here we examine the underlying basis for this synergy. We show that PD-1 + IL-2 combination therapy, in contrast to PD-1 monotherapy, substantially changes the differentiation program of the PD-1TCF1 stem-like CD8 T cells and results in the generation of transcriptionally and epigenetically distinct effector CD8 T cells that resemble highly functional effector CD8 T cells seen after an acute viral infection.

Methane production controls in a young thermokarst lake formed by abrupt permafrost thaw.

Methane (CH ) release to the atmosphere from thawing permafrost contributes significantly to global CH emissions. However, constraining the effects of thaw that control the production and emission of CH is needed to anticipate future Arctic emissions. Here are presented robust rate measurements of CH production and cycling in a region of rapidly degrading permafrost.

Monoallelic IRF5 deficiency in B cells prevents murine lupus.

Gain-of-function polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus. However, the IRF5-expressing cell type(s) responsible for lupus pathogenesis in vivo is not known. We now show that monoallelic IRF5 deficiency in B cells markedly reduced disease in a murine lupus model.

MOG autoantibodies trigger a tightly-controlled FcR and BTK-driven microglia proliferative response.

Autoantibodies are a hallmark of numerous neurological disorders, including multiple sclerosis, autoimmune encephalitides and neuromyelitis optica. Whilst well understood in peripheral myeloid cells, the pathophysiological significance of autoantibody-induced Fc receptor signalling in microglia remains unknown, in part due to the lack of a robust in vivo model. Moreover, the application of therapeutic antibodies for neurodegenerative disease also highlights the importance of understanding Fc receptor signalling in microglia.

Next-generation Bruton's tyrosine kinase inhibitor BIIB091 selectively and potently inhibits B cell and Fc receptor signaling and downstream functions in B cells and myeloid cells.

Objectives: Bruton's tyrosine kinase (BTK) plays a non-redundant signaling role downstream of the B-cell receptor (BCR) in B cells and the receptors for the Fc region of immunoglobulins (FcR) in myeloid cells. Here, we characterise BIIB091, a novel, potent, selective and reversible small-molecule inhibitor of BTK.

Methods: BIIB091 was evaluated and in preclinical models and in phase 1 clinical trial.

Simultaneously acquired PET and ASL imaging biomarkers may be helpful in differentiating progression from pseudo-progression in treated gliomas.

Objectives: The aim of this work was investigating the methods based on coupling cerebral perfusion (ASL) and amino acid metabolism ([F]DOPA-PET) measurements to evaluate the diagnostic performance of PET/MRI in glioma follow-up.

Methods: Images were acquired using a 3-T PET/MR system, on a prospective cohort of patients addressed for possible glioma progression. Data were preprocessed with statistical parametric mapping (SPM), including registration on T1-weighted images, spatial and intensity normalization, and tumor segmentation.

The effect of temperature on sulfur and oxygen isotope fractionation by sulfate reducing bacteria (Desulfococcus multivorans).

Temperature influences microbiological growth and catabolic rates. Between 15 and 35 °C the growth rate and cell specific sulfate reduction rate of the sulfate reducing bacterium Desulfococcus multivorans increased with temperature. Sulfur isotope fractionation during sulfate reduction decreased with increasing temperature from 27.

Thiomicrorhabdus streamers and sulfur cycling in perennial hypersaline cold springs in the Canadian high Arctic.

The Gypsum Hill (GH) springs on Axel Heiberg Island in the Canadian high Arctic are host to chemolithoautotrophic, sulfur-oxidizing streamers that flourish in the high Arctic winter in water temperatures from -1.3 to 7°C with ~8% salinity in a high Arctic winter environment with air temperatures commonly less than -40°C and an average annual air temperature of -15°C. Metagenome sequencing and binning of streamer samples produced a 96% complete Thiomicrorhabdus sp.

Large sulfur isotope fractionation by bacterial sulfide oxidation.

A sulfide-oxidizing microorganism, (DA), generates a consistent enrichment of sulfur-34 ( ) in the produced sulfate of +12.5 per mil or greater. This observation challenges the general consensus that the microbial oxidation of sulfide does not result in large enrichments and suggests that sedimentary sulfides and sulfates may be influenced by metabolic activity associated with sulfide oxidation.

The Biogeochemical Sulfur Cycle of Marine Sediments.

Microbial dissimilatory sulfate reduction to sulfide is a predominant terminal pathway of organic matter mineralization in the anoxic seabed. Chemical or microbial oxidation of the produced sulfide establishes a complex network of pathways in the sulfur cycle, leading to intermediate sulfur species and partly back to sulfate. The intermediates include elemental sulfur, polysulfides, thiosulfate, and sulfite, which are all substrates for further microbial oxidation, reduction or disproportionation.

Effect of Hydroxychloroquine and Anti-BDCA2 mAb Treatment on pDC IFNα Production From Patients Affected With Cutaneous Lupus Erythematosus.

Plasmacytoid dendritic cells (pDCs) are a major source of Type-I Interferon (IFN-I), a key driver in cutaneous lupus erythematosus (CLE). Currently evaluated in Phase II clinical trial, 24F4A (BIIB059) is an antibody targeting BDCA2, an inhibitory receptor expressed on pDCs. Given that Hydroxychloroquine (HCQ), a widely-used CLE therapy, and 24F4A are both able to inhibit pDC-derived IFN-I production; this study aimed to determine whether 24F4A would show an additional inhibitory effect on pDC response after or treatment with HCQ.

Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus.

Background: Plasmacytoid DCs (pDC) produce large amounts of type I IFN (IFN-I), cytokines convincingly linked to systemic lupus erythematosus (SLE) pathogenesis. BIIB059 is a humanized mAb that binds blood DC antigen 2 (BDCA2), a pDC-specific receptor that inhibits the production of IFN-I and other inflammatory mediators when ligated. A first-in-human study was conducted to assess safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) effects of single BIIB059 doses in healthy volunteers (HV) and patients with SLE with active cutaneous disease as well as proof of biological activity and preliminary clinical response in the SLE cohort.

Deconstructing the Dissimilatory Sulfate Reduction Pathway: Isotope Fractionation of a Mutant Unable of Growth on Sulfate.

The sulfur isotope record provides key insight into the history of Earth's redox conditions. A detailed understanding of the metabolisms driving this cycle, and specifically microbial sulfate reduction (MSR), is crucial for accurate paleoenvironmental reconstructions. This includes a precise knowledge of the step-specific sulfur isotope effects during MSR.

Inhaled Epoprostenol for Pulmonary Hypertension Treatment in Neonates: A 12-Year Experience.

Background: Persistent pulmonary hypertension of the newborn (PPHN) occurs in 10% of neonatal respiratory insufficiency. To selectively reduce pulmonary vascular resistance, several treatments have been tried. Inhaled epoprostenol (iPGI) has been used for 12 years in our institution for the management of refractory PPHN despite the gaps in the literature to support this use.

A pre-clinical quantitative model predicts the pharmacokinetics/pharmacodynamics of an anti-BDCA2 monoclonal antibody in humans.

BIIB059 is a novel humanized monoclonal antibody (mAb) that is currently under development for the treatment of Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus. BIIB059 is targeted against the blood dendritic cell antigen 2 (BDCA2), a receptor exclusively expressed on the surface of plasmacytoid dendritic cells (pDCs). Herein, we utilized pre-clinical pharmacokinetic (PK) and pharmacodynamic (PD) data to develop a non-human primate (NHP) model and to address whether the NHP model can be successfully scaled to predict the human PK/PD.

A quantitative and semi-automatic measurement of transverse sinus stenosis improves idiopathic intracranial hypertension diagnostic accuracy.

We propose a new reliable transverse sinus stenosis (TSS) index based on magnetic resonance venography (MRV) for the diagnosis of idiopathic intracranial hypertension (IIH). Our quantitative semi-automatic measurement analysis based on segmentation and cross-sectional TS diameter from 48 IIH patients and controls matched for age and sex, had a good inter-observer agreement (κ=0.729) compared to a visual examination (κ=0.