A novel estimate of ocean oxygen utilisation points to a reduced rate of respiration in the ocean interior

The Apparent Oxygen Utilisation (AOU) is a classical measure of the amount of oxygen respired in the ocean's interior. We show that AOU systematically overestimates True Oxygen Utilisation (TOU) in 6 coupled circulation-biogeochemical ocean models. This is due to atmosphere–ocean oxygen disequilibria in the subduction regions, consistent with previous work. We develop a simple, new, observationally-based approach which we call Evaluated Oxygen Utilisation (EOU). In this approach, we take into account the impact of the upper ocean oxygen disequilibria into the interior, considering that transport takes place predominantly along isopycnal surfaces. The EOU approximates the TOU with less than half of the bias of AOU in all 6 models despite large differences in the physical and biological components of the models. Applying the EOU approach to a global observational dataset yields an oxygen consumption rate 25% lower than that derived from AOU-based estimates, for a given ventilation rate

Preformed and regenerated phosphate in ocean general circulation models: can right total concentrations be wrong?

Phosphate distributions simulated by seven state-of-the-art biogeochemical ocean circulation models are evaluated against observations of global ocean nutrient distributions. The biogeochemical models exhibit different structural complexities, ranging from simple nutrient-restoring to multi-nutrient NPZD type models. We evaluate the simulations using the observed volume distribution of phosphate. The errors in these simulated volume class distributions are significantly larger when preformed phosphate (or regenerated phosphate) rather than total phosphate is considered. Our analysis reveals that models can achieve similarly good fits to observed total phosphate distributions for a very different partitioning into preformed and regenerated nutrient components. This has implications for the strength and potential climate sensitivity of the simulated biological carbon pump. We suggest complementing the use of total nutrient distributions for assessing model skill by an evaluation of the respective preformed and regenerated nutrient components

The histone code reader Spin1 controls skeletal muscle development

While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1(M5) mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1(M5) mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1(M5) mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle (SkM) functional networks. Determination of genome-wide chromatin occupancy in primary myoblast revealed direct Spin1 target genes and suggested that deregulated basic helix-loop-helix transcription factor networks account for developmental defects in Spin1(M5) fetuses. Furthermore, correlating histological and transcriptome analyses, we show that aberrant expression of titin-associated proteins, abnormal glycogen metabolism, and neuromuscular junction defects contribute to SkM pathology in Spin1(M5) mice. Together, we describe the first example of a histone code reader controlling SkM development in mice, which hints at Spin1 as a potential player in human SkM disease

Continuous pulse advances in the negative ion source NIO1

Consorzio RFX and INFN-LNL have designed, built and operated the compact radiofrequency negative ion source NIO1 (Negative Ion Optimization phase 1) with the aim of studying the production and acceleration of H- ions. In particular, NIO1 was designed to keep plasma generation and beam extraction continuously active for several hours. Since 2020 the production of negative ions at the plasma grid (the first grid of the acceleration system) has been enhanced by a Cs layer, deposited though active Cs evaporation in the source volume. For the negative ion sources applied to fusion neutral beam injectors, it is essential to keep the beam current and the fraction of co-extracted electrons stable for at least 1 h, against the consequences of Cs sputtering and redistribution operated by the plasma. The paper presents the latest results of the NIO1 source, in terms of caesiation process and beam performances during continuous (6{\div}7 h) plasma pulses. Due to the small dimensions of the NIO1 source (20 x (diam.)10 cm), the Cs density in the volume is high (10^15 \div 10^16 m^-3) and dominated by plasma-wall interaction. The maximum beam current density and minimum fraction of co-extracted electrons were respectively about 30 A/m^2 and 2. Similarly to what done in other negative ion sources, the plasma grid temperature in NIO1 was raised for the first time, up to 80 {\deg}C, although this led to a minimal improvement of the beam current and to an increase of the co-extracted electron current.Comment: 11 pages, 7 figures. Contributed paper for the 8th International symposium on Negative Ions, Beams and Sources - NIBS'22. Revision 1 of the preprint under evaluation at Journal of Instrumentation (JINST

Oral dosing of rodents using a palatable tablet

Rationale: Delivering orally bioavailable drugs to rodents is an important component to investigating that route of administration in novel treatments for humans. However, the traditional method of oral gavage requires training, is stressful, and can induce oesophageal damage in rodents. Objectives: To demonstrate a novel administrative technique – palatable gelatine tablets – as a stress-free route of oral delivery. Methods: 24 male Lister hooded rats were sacrificed for brain tissue analysis at varying time-points after jelly administration of 30 mg/kg of the wake-promoting drug modafinil. A second group of 22 female rats were tested on locomotor activity after 30 mg/kg modafinil, or after vehicle jellies, with the locomotor data compared to the brain tissue concentrations at the corresponding times. Results: Modafinil was present in the brain tissue at all time-points, reducing in concentration over time. The pattern of brain tissue modafinil concentration is comparable to previously reported results following oral gavage. Modafinil-treated rats were more active than control rats, with greater activity during the later time-periods – similar to that previously reported following intraperitoneal injection of 40 mg/kg modafinil. Conclusions: Palatable jelly tablets are an effective route of administration of thermally-stable orally-bioavailable compounds, eliminating the stress/discomfort and health risk of oral gavage and presenting as an alternative to previously reported palatable routes of administration where high protein and fat levels may adversely affect appetite for food reward, and uptake rate in the gastrointestinal tract.Publisher PDFPeer reviewe

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

Near-future CO2 levels impair the olfactory system of a marine fish

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordData availability: All raw sequence data are accessible at the NCBI Sequence Read Archive through accession number SRP097118. Water chemistry, behaviour and electrophysiology data are available through Pangaea (https://doi.pangaea.de/10.1594/PANGAEA.884674).Survival of marine fishes that are exposed to elevated near-future CO2levels is threatened by their altered responses to sensory cues. Here we demonstrate a physiological and molecular mechanism in the olfactory system that helps to explain altered behaviour under elevated CO2. We combine electrophysiology measurements and transcriptomics with behavioural experiments to investigate how elevated CO2affects the olfactory system of European sea bass (Dicentrarchus labrax). When exposed to elevated CO2(approximately 1,000 µatm), fish must be up to 42% closer to an odour source for detection, compared with current CO2levels (around 400 µatm), decreasing their chances of detecting food or predators. Compromised olfaction correlated with the suppression of the transcription of genes involved in synaptic strength, cell excitability and wiring of the olfactory system in response to sustained exposure to elevated CO2levels. Our findings complement the previously proposed impairment of γ-aminobutyric acid receptors, and indicate that both the olfactory system and central brain function are compromised by elevated CO2levels.This study was supported by grants from Association of European Marine Biology Laboratories (227799), the Natural Environment Research Council (R.W.W.; NE/H017402/1), the Biotechnology and Biological Sciences Research Council (R.W.W.; BB/D005108/1), Fundação para a Ciência e Tecnologia (Portuguese Science Ministry) (UID/Multi/04326/2013) and a Royal Society Newton International Fellowship to C.S.P. C.S.P. is also a beneficiary of a Starting Grant from AXA