ObjectivesRecent investigations in humans and mouse models with lupus have revealed evidence of mitochondrial dysfunction and production of mitochondrial reactive oxygen species (mROS) in T cells and ...neutrophils. This can provoke numerous cellular changes including oxidation of nucleic acids, proteins, lipids and even induction of cell death. We have previously observed that in T cells from patients with lupus, the increased mROS is capable of provoking oligomerisation of mitochondrial antiviral stimulator (MAVS) and production of type I interferon (IFN-I). mROS in SLE neutrophils also promotes the formation of neutrophil extracellular traps (NETs), which are increased in lupus and implicated in renal damage. As a result, in addition to traditional immunosuppression, more comprehensive treatments for lupus may also include non-immune therapy, such as antioxidants.MethodsLupus-prone MRL-lpr mice were treated from weaning for 11 weeks with the mitochondria-targeted antioxidant, MitoQ (200 µM) in drinking water. Mice were then assessed for ROS production in neutrophils, NET formation, MAVS oligomerisation, serum IFN-I, autoantibody production and renal function.ResultsMitoQ-treated mice manifested reduced neutrophil ROS and NET formation, decreased MAVS oligomerisation and serum IFN-I, and reduced immune complex formation in kidneys, despite no change in serum autoantibody .ConclusionsThese findings reveal the potential utility of targeting mROS in addition to traditional immunosuppressive therapy for lupus.
High-resolution velocity map imaged photoelectron spectra of the nitrite anion NO2 – are measured over a range of photodetachment wavelengths between 355 and 550 nm, resolving the vibrational and ...rotational structure of the NO2(X̃ 2 A 1) + e – ← NO2 –(X̃ 1 A 1) + hν transition. A full rotational band model is constructed to define the spectroscopic constants of both the neutral and the lesser studied anion ground states. The corresponding photoelectron angular distributions are characterized by a large positive anisotropy parameter, with β ≈ 1.5 gradually increasing to β ≈ 1.7 upon approaching the threshold. However, at very low kinetic energies, within 0.1 eV of the threshold, β dramatically drops to 0. This behavior is a consequence of the Wigner near-threshold selectivity of the electron partial-wave cross sections, whereby an atomic p-like orbital character adjacent to the threshold is favored. The full kinetic energy dependence of β is reproduced by a new mixed spd orbital model, yielding a NO2 –(X̃ 1 A 1) molecular-orbital decomposition of 2% p, 44% s, and 54% d character.
Multidomain proteins predominate in eukaryotic proteomes. Individual functions assigned to different sequence segments combine to create a complex function for the whole protein. While on-line ...resources are available for revealing globular domains in sequences, there has hitherto been no comprehensive collection of small functional sites/motifs comparable to the globular domain resources, yet these are as important for the function of multidomain proteins. Short linear peptide motifs are used for cell compartment targeting, protein–protein interaction, regulation by phosphorylation, acetylation, glycosylation and a host of other post-translational modifications. ELM, the Eukaryotic Linear Motif server at http://elm.eu.org/, is a new bioinformatics resource for investigating candidate short non-globular functional motifs in eukaryotic proteins, aiming to fill the void in bioinformatics tools. Sequence comparisons with short motifs are difficult to evaluate because the usual significance assessments are inappropriate. Therefore the server is implemented with several logical filters to eliminate false positives. Current filters are for cell compartment, globular domain clash and taxonomic range. In favourable cases, the filters can reduce the number of retained matches by an order of magnitude or more.
The machining of 3D microstructures in single‐crystal artificial diamond is demonstrated with a focused ion beam (FIB)‐assisted lift‐off technique. A sacrificial buried layer is created with MeV ion ...implantation, followed by patterning of selected regions with the FIB technique; the sacrificial layer is then selectively etched, leaving 3D free‐standing microstructures in the bulk (see Figure). Using this fabrication technique, light waveguiding through a microstructure in single‐crystal diamond is demonstrated for the first time.
The super(14)N/ super(15)N ratio for N sub(2) in the atmosphere of Titan was recently measured to be a factor of 2 higher than the corresponding ratio for HCN. Using a one-dimensional photochemical ...model with transport, we incorporate new isotopic photoabsorptlon and photodissociation cross sections of N sub(2), computed quantum-mechanlcally, and show that the difference in the ratio of super(14)N/ super(15)N between N sub(2) and HCN can be explained primarily by the photolytic fractionation of super(14)N super(14)N and super(14)N super(15)N. The HC super(14)N/HC super(15)N ratio produced by N sub(2) photolysis alone is 23. This value, together with the observed ratio, constrains the flux of atomic nitrogen input from the top of the atmosphere to be in the range (1 2) x 10 super(6) atoms cm-2 s-1.
Mycoplasma bovis can be a bacterial inhabitant of the upper respiratory tract of healthy bovines. In body regions other that the upper respiratory tract however, M. bovis is associated with a number ...of clinical syndromes such as bovine respiratory disease (BRD). This study used two enzyme-linked immunosorbent assays to assess the sero-status of M. bovis-specific antibodies in Australian feeder cattle at the time of feedlot induction and at approximately 42 days on feed (follow-up). The apparent sero-prevalence of M. bovis-specific antibody at induction was estimated to be 3.5% (95% confidence interval CI 2.0–5.0%, 47/1354) and 25.3% (95% CI 21.9–28.8%, 343/1354) at follow-up. Exposure to M. bovis between induction and follow-up as demonstrated by an increase in serum antibodies was estimated to be 19.4% (95% CI 16.2–22.6%, 261/1349).
Risk factors associated with sero-positivity at feedlot induction included the region where animals were 28 days prior to induction and saleyard exposure at least 27 days prior to induction. Risk factors associated with a sero-increase between induction and follow-up included breed, source region and access to water shared with an adjoining pen of animals. Of these, shared pen water was considered the most important (odds ratio OR 3.3, 95% CI 1.5–7.4, p = 0.003). Animals exposed to M. bovis between induction and follow-up were at a substantially increased risk of BRD (OR 2.2, 95% CI 1.4–3.4, p = 0.001).
This is the first Australian study that has identified risk factors for M. bovis sero-positivity and sero-increase and shown an association between sero-increase and the risk of BRD in the feeder cattle population. These findings suggest that M. bovis is a significant pathogen in the Australian feeder cattle population. In addition, identification of defined risk factors associated with an increased risk of exposure to M. bovis can assist in the development of targeted control measures to reduce the economic impact of M. bovis associated disease and BRD in feeder cattle.
Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long ...COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.
RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.
RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.
Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.
Positive affect denotes a state of pleasurable engagement with the environment eliciting positive emotion such as contentment, enthusiasm or happiness. Positive affect is associated with favorable ...psychological, physical and economic outcomes in many longitudinal studies. With a heritability of ⩽64%, positive affect is substantially influenced by genetic factors; however, our understanding of genetic pathways underlying individual differences in positive affect is still limited. Here, through a genome-wide association study of positive affect in African-American participants, we identify a single-nucleotide polymorphism, rs322931, significantly associated with positive affect at P<5 × 10
, and replicate this association in another cohort. Furthermore, we show that the minor allele of rs322931 predicts expression of microRNAs miR-181a and miR-181b in human brain and blood, greater nucleus accumbens reactivity to positive emotional stimuli and enhanced fear inhibition. Prior studies have suggested that miR-181a is part of the reward neurocircuitry. Taken together, we identify a novel genetic variant for further elucidation of genetic underpinning of positive affect that mediates positive emotionality potentially via the nucleus accumbens and miR-181.
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