Surface ozone in the Colorado northern Front Range and the influence of oil and gas development during FRAPPE/DISCOVER-AQ in summer 2014

High mixing ratios of ozone (O3) in the northern Front Range (NFR) of Colorado are not limited to the urban Denver area but were also observed in rural areas where oil and gas activity is the primary source of O3 precursors. On individual days, oil and gas O3 precursors can contribute in excess of 30 ppb to O3 growth and can lead to exceedances of the EPA O3 National Ambient Air Quality Standard. Data used in this study were gathered from continuous surface O3 monitors for June–August 2013–2015 as well as additional flask measurements and mobile laboratories that were part of the FRAPPE/DISCOVER-AQ field campaign of July–August 2014. Overall observed O3 levels during the summer of 2014 were lower than in 2013, likely due to cooler and damper weather than an average summer. This study determined the median hourly surface O3 mixing ratio in the NFR on summer days with limited photochemical production to be approximately 45–55 ppb. Mobile laboratory and flask data collected on three days provide representative case studies of different O3 formation environments in and around Greeley, Colorado. Observations of several gases (including methane, ethane, CO, nitrous oxide) along with O3 are used to identify sources of O3 precursor emissions. A July 23 survey demonstrated low O3 (45–60 ppb) while August 3 and August 13 surveys recorded O3 levels of 75–80 ppb or more. August 3 exemplifies influence of moderate urban and high oil and gas O3 precursor emissions. August 13 demonstrates high oil and gas emissions, low agricultural emissions, and CO measurements that were well correlated with ethane from oil and gas, suggesting an oil and gas related activity as a NOx and O3 precursor source. Low isoprene levels indicated that they were not a significant contributor to O3 precursors measured during the case studies

Climate Change and invasibility of the Antarctic benthos

Benthic communities living in shallow-shelf habitats in Antarctica (<100-m depth) are archaic in their structure and function. Modern predators, including fast-moving, durophagous (skeleton-crushing) bony fish, sharks, and crabs, are rare or absent; slow-moving invertebrates are the top predators; and epifaunal suspension feeders dominate many soft substratum communities. Cooling temperatures beginning in the late Eocene excluded durophagous predators, ultimately resulting in the endemic living fauna and its unique food-web structure. Although the Southern Ocean is oceanographically isolated, the barriers to biological invasion are primarily physiological rather than geographic. Cold temperatures impose limits to performance that exclude modern predators. Global warming is now removing those physiological barriers, and crabs are reinvading Antarctica. As sea temperatures continue to rise, the invasion of durophagous predators will modernize the shelf benthos and erode the indigenous character of marine life in Antarctica

Intrinsic activity in the fly brain gates visual information during behavioral choices

The small insect brain is often described as an input/output system that executes reflex-like behaviors. It can also initiate neural activity and behaviors intrinsically, seen as spontaneous behaviors, different arousal states and sleep. However, less is known about how intrinsic activity in neural circuits affects sensory information processing in the insect brain and variability in behavior. Here, by simultaneously monitoring Drosophila's behavioral choices and brain activity in a flight simulator system, we identify intrinsic activity that is associated with the act of selecting between visual stimuli. We recorded neural output (multiunit action potentials and local field potentials) in the left and right optic lobes of a tethered flying Drosophila, while its attempts to follow visual motion (yaw torque) were measured by a torque meter. We show that when facing competing motion stimuli on its left and right, Drosophila typically generate large torque responses that flip from side to side. The delayed onset (0.1-1 s) and spontaneous switch-like dynamics of these responses, and the fact that the flies sometimes oppose the stimuli by flying straight, make this behavior different from the classic steering reflexes. Drosophila, thus, seem to choose one stimulus at a time and attempt to rotate toward its direction. With this behavior, the neural output of the optic lobes alternates; being augmented on the side chosen for body rotation and suppressed on the opposite side, even though the visual input to the fly eyes stays the same. Thus, the flow of information from the fly eyes is gated intrinsically. Such modulation can be noise-induced or intentional; with one possibility being that the fly brain highlights chosen information while ignoring the irrelevant, similar to what we know to occur in higher animals

Quantifying the proportion of different cell types in the human cortex using DNA methylation profiles

This is the final version. Available from BMC via the DOI in this record. Availability of data and materials: All data generated or analysed during this study are included in this published article, its supplementary information files and publicly available repositories. Data generated for this project are available at NCBI Gene Express Omnibus (GEO) under accession number GSE234520 [64]. We also reanalysed data previously made available via GEO (via accession numbers GSE74193 [65], GSE59685 [66], GSE80970 [67], GSE88890 [68], GSE43414 [69]) and the synapse platform (syn7072866 [70], syn8263588 [71]). Code for the analyses presented here can be found on GitHub and Zenodo https://github.com/ejh243/BrainFANS/tree/master/array/DNAm/preprocessing (https://doi.org/https://doi.org/10.5281/zenodo.10402167). Specifically, code for the quality control of the DNAm data can be found at https://github.com/ejh243/BrainFANS/tree/master/array/DNAm/preprocessing and the code for the statistical analyses can be found at https://github.com/ejh243/BrainFANS/tree/master/array/DNAm/analysis/neuralCellComposition. Our new trained deconvolution models for brain are made available to the wider research community via our R package CETYGO available on GitHub (https://github.com/ds420/CETYGO; https://doi.org/10.5281/zenodo.10418430).Background: Due to interindividual variation in the cellular composition of the human cortex, it is essential that covariates that capture these differences are included in epigenome-wide association studies using bulk tissue. As experimentally derived cell counts are often unavailable, computational solutions have been adopted to estimate the proportion of different cell types using DNA methylation data. Here, we validate and profile the use of an expanded reference DNA methylation dataset incorporating two neuronal and three glial cell subtypes for quantifying the cellular composition of the human cortex. Results: We tested eight reference panels containing different combinations of neuronal- and glial cell types and characterised their performance in deconvoluting cell proportions from computationally reconstructed or empirically derived human cortex DNA methylation data. Our analyses demonstrate that while these novel brain deconvolution models produce accurate estimates of cellular proportions from profiles generated on postnatal human cortex samples, they are not appropriate for the use in prenatal cortex or cerebellum tissue samples. Applying our models to an extensive collection of empirical datasets, we show that glial cells are twice as abundant as neuronal cells in the human cortex and identify significant associations between increased Alzheimer’s disease neuropathology and the proportion of specific cell types including a decrease in NeuNNeg/SOX10Neg nuclei and an increase of NeuNNeg/SOX10Pos nuclei. Conclusions: Our novel deconvolution models produce accurate estimates for cell proportions in the human cortex. These models are available as a resource to the community enabling the control of cellular heterogeneity in epigenetic studies of brain disorders performed on bulk cortex tissue.Engineering and Physical Sciences Research CouncilMedical Research CouncilAlzheimer's Research UKMedical Research Counci

Graphene Photonics and Optoelectronics

The richness of optical and electronic properties of graphene attracts enormous interest. Graphene has high mobility and optical transparency, in addition to flexibility, robustness and environmental stability. So far, the main focus has been on fundamental physics and electronic devices. However, we believe its true potential to be in photonics and optoelectronics, where the combination of its unique optical and electronic properties can be fully exploited, even in the absence of a bandgap, and the linear dispersion of the Dirac electrons enables ultra-wide-band tunability. The rise of graphene in photonics and optoelectronics is shown by several recent results, ranging from solar cells and light emitting devices, to touch screens, photodetectors and ultrafast lasers. Here we review the state of the art in this emerging field.Comment: Review Nature Photonics, in pres

Willpower and Conscious Percept: Volitional Switching in Binocular Rivalry

When dissimilar images are presented to the left and right eyes, awareness switches spontaneously between the two images, such that one of the images is suppressed from awareness while the other is perceptually dominant. For over 170 years, it has been accepted that even though the periods of dominance are subject to attentional processes, we have no inherent control over perceptual switching. Here, we revisit this issue in response to evidence that top-down attention can target perceptually suppressed ‘vision for action’ representations in the dorsal stream. We investigated volitional control over rivalry between apparent motion (AM), drifting (DM) and stationary (ST) grating pairs. Observers demonstrated a remarkable ability to generate intentional switches in the AM and D conditions, but not in the ST condition. Corresponding switches in the pursuit direction of optokinetic nystagmus verified this finding objectively. We showed it is unlikely that intentional perceptual switches were triggered by saccadic eye movements, because their frequency was reduced substantially in the volitional condition and did not change around the time of perceptual switches. Hence, we propose that synergy between dorsal and ventral stream representations provides the missing link in establishing volitional control over rivalrous conscious percepts

Ouabain Stimulates a Na+/K+-ATPase-Mediated SFK-Activated Signalling Pathway That Regulates Tight Junction Function in the Mouse Blastocyst

The Na+/K+-ATPase plays a pivotal role during preimplantation development; it establishes a trans-epithelial ionic gradient that facilitates the formation of the fluid-filled blastocyst cavity, crucial for implantation and successful pregnancy. The Na+/K+-ATPase is also implicated in regulating tight junctions and cardiotonic steroid (CTS)-induced signal transduction via SRC. We investigated the expression of SRC family kinase (SFK) members, Src and Yes, during preimplantation development and determined whether SFK activity is required for blastocyst formation. Embryos were collected following super-ovulation of CD1 or MF1 female mice. RT-PCR was used to detect SFK mRNAs encoding Src and Yes throughout preimplantation development. SRC and YES protein were localized throughout preimplantation development. Treatment of mouse morulae with the SFK inhibitors PP2 and SU6656 for 18 hours resulted in a reversible blockade of progression to the blastocyst stage. Blastocysts treated with 10−3 M ouabain for 2 or 10 minutes and immediately immunostained for phosphorylation at SRC tyr418 displayed reduced phosphorylation while in contrast blastocysts treated with 10−4 M displayed increased tyr418 fluorescence. SFK inhibition increased and SFK activation reduced trophectoderm tight junction permeability in blastocysts. The results demonstrate that SFKs are expressed during preimplantation development and that SFK activity is required for blastocyst formation and is an important mediator of trophectoderm tight junction permeability

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

CGRPα-Expressing Sensory Neurons Respond to Stimuli that Evoke Sensations of Pain and Itch

Calcitonin gene-related peptide (CGRPα, encoded by Calca) is a classic marker of nociceptive dorsal root ganglia (DRG) neurons. Despite years of research, it is unclear what stimuli these neurons detect in vitro or in vivo. To facilitate functional studies of these neurons, we genetically targeted an axonal tracer (farnesylated enhanced green fluorescent protein; GFP) and a LoxP-stopped cell ablation construct (human diphtheria toxin receptor; DTR) to the Calca locus. In culture, 10–50% (depending on ligand) of all CGRPα-GFP-positive (+) neurons responded to capsaicin, mustard oil, menthol, acidic pH, ATP, and pruritogens (histamine and chloroquine), suggesting a role for peptidergic neurons in detecting noxious stimuli and itch. In contrast, few (2.2±1.3%) CGRPα-GFP+ neurons responded to the TRPM8-selective cooling agent icilin. In adult mice, CGRPα-GFP+ cell bodies were located in the DRG, spinal cord (motor neurons and dorsal horn neurons), brain and thyroid—reproducibly marking all cell types known to express Calca. Half of all CGRPα-GFP+ DRG neurons expressed TRPV1, ∼25% expressed neurofilament-200, <10% contained nonpeptidergic markers (IB4 and Prostatic acid phosphatase) and almost none (<1%) expressed TRPM8. CGRPα-GFP+ neurons innervated the dorsal spinal cord and innervated cutaneous and visceral tissues. This included nerve endings in the epidermis and on guard hairs. Our study provides direct evidence that CGRPα+ DRG neurons respond to agonists that evoke pain and itch and constitute a sensory circuit that is largely distinct from nonpeptidergic circuits and TRPM8+/cool temperature circuits. In future studies, it should be possible to conditionally ablate CGRPα-expressing neurons to evaluate sensory and non-sensory functions for these neurons