Confirmation of co-denitrification in grazed grassland

peer-reviewedPasture-based livestock systems are often associated with losses of reactive forms of nitrogen (N) to the environment. Research has focused on losses to air and water due to the health, economic and environmental impacts of reactive N. Di-nitrogen (N2) emissions are still poorly characterized, both in terms of the processes involved and their magnitude, due to financial and methodological constraints. Relatively few studies have focused on quantifying N2 losses in vivo and fewer still have examined the relative contribution of the different N2 emission processes, particularly in grazed pastures. We used a combination of a high 15N isotopic enrichment of applied N with a high precision of determination of 15N isotopic enrichment by isotope-ratio mass spectrometry to measure N2 emissions in the field. We report that 55.8 g N m−2 (95%, CI 38 to 77 g m−2) was emitted as N2 by the process of co-denitrification in pastoral soils over 123 days following urine deposition (100 g N m−2), compared to only 1.1 g N m−2 (0.4 to 2.8 g m−2) from denitrification. This study provides strong evidence for co-denitrification as a major N2 production pathway, which has significant implications for understanding the N budgets of pastoral ecosystems.The authors are grateful for the funding that was provided through the Research Stimulus Fund Program administered by the Department of Agriculture & Food under the National Development Plan 2007–2013 RSF 07536. The first author is grateful for the funding provided by Teagasc through the Walsh Fellowship Scheme

IGLV3-21*01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling

The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementarity-determining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21-derived heavy chains (HCs) with IGLV3-21-derived light chains (LCs), and is associated with an unfavorable prognosis. Importantly, the subset 2 LC carries a single-point mutation, termed R110, at the junction between the variable and constant LC regions. By analyzing 4 independent clinical cohorts through BCR sequencing and by immunophenotyping with antibodies specifically recognizing wild-type IGLV3-21 and R110-mutated IGLV3-21 (IGLV3-21R110), we show that IGLV3-21R110-expressing CLL represents a distinct subset with poor prognosis independent of IGHV mutations. Compared with other alleles, only IGLV3-21*01 facilitates effective homotypic BCR-BCR interaction that results in autonomous, oncogenic BCR signaling after acquiring R110 as a single-point mutation. Presumably, this mutation acts as a standalone driver that transforms IGLV3-21*01-expressing B cells to develop CLL. Thus, we propose to expand the conventional definition of CLL subset 2 to subset 2L by including all IGLV3-21R110-expressing CLL cases regardless of IGHV mutational status. Moreover, the generation of monoclonal antibodies recognizing IGLV3-21 or mutated IGLV3-21R110 facilitates the recognition of B cells carrying this mutation in CLL patients or healthy donors

Regional cerebral blood flow alterations in obstructive sleep apnea

Obstructive sleep apnea (OSA) is a condition characterized by upper airway muscle atonia with continued diaphragmatic efforts, resulting in repeated airway obstructions, periods of intermittent hypoxia, large thoracic pressure changes, and substantial shifts in arterial pressure with breathing cessation and resumption. The hypoxic exposure and hemodynamic changes likely induce the structural and functional deficits found in multiple brain areas, as shown by magnetic resonance imaging (MRI) procedures. Altered cerebral blood flow (CBF) may contribute to these localized deficits; thus, we examined regional CBF, using arterial spin labeling procedures, in 11 OSA (age, 49.1±12.2 years; 7 male) and 16 control subjects (42.3±10.2 years; 6 male) with a 3.0-Tesla MRI scanner. CBF maps were calculated, normalized to a common space, and regional CBF values across the brain quantified. Lowered CBF values emerged near multiple bilateral brain sites in OSA, including the corticospinal tracts, superior cerebellar peduncles, and pontocerebellar fibers. Lateralized, decreased CBF appeared near the left inferior cerebellar peduncles, left tapetum, left dorsal fornix/stria terminalis, right medial lemniscus, right red nucleus, right midbrain, and midline pons. Regional CBF values in OSA are significantly reduced in major sensory and motor fiber systems and motor regulatory sites, especially in structures mediating motor coordination; those reductions are often lateralized. The asymmetric CBF declines in motor regulatory areas may contribute to loss of coordination between upper airway and diaphragmatic musculature, and lead to further damage in the syndrome