Organization of mammary epithelial cells into 3D acinar structures requires glucocorticoid and JNK signaling

Mammary epithelial cells cultured on a concentrated laminin-rich extracellular matrix formed 3D acinar structures that matured to polarized monolayers surrounding a lumen. In the absence of glucocorticoids mature acinus formation failed and the expression of an acinus-associated, activator protein 1 (AP1) and nuclear factor κB transcription factor DNA-binding profile was lost. Treatment with the JNK inhibitor, SP600125, caused similar effects, whereas normal organization of the mammary epithelial cells as acini caused JNK activation in a glucocorticoid-dependent manner. The forming acini expressed BRCA1, GADD45β, MEKK4, and the JNK activating complex GADD 45β−MEKK4 in a glucocorticoid-dependent fashion. JNK catalyzed phosphorylation of c-Jun was also detected in the acini. In addition, expression of β4 integrin and in situ occupation of its promoter by AP1 components, c-Jun and Fos, was glucocorticoid dependent. These results suggest that glucocortocoid signaling regulates acinar integrity through a pathway involving JNK regulation of AP1 transcription factors and β4 integrin expression

Retrieval of daytime mesospheric ozone using OSIRIS observations of O2 (a1Δg) emission

This work is distributed under the Creative Commons Attribution 4.0 License. Improving knowledge of the ozone global distributions in the mesosphere-lower thermosphere (MLT) is a crucial step in understanding the behaviour of the middle atmosphere. However, the concentration of ozone under sunlit conditions in the MLT is often so low that its measurement requires instruments with very high sensitivity. Fortunately, the bright oxygen airglow can serve as a proxy to retrieve the daytime ozone density indirectly, due to the strong connection to ozone photolysis in the Hartley band. The OSIRIS IR imager (hereafter, IRI), one of the instruments on the Odin satellite, routinely measures the oxygen infrared atmospheric band (IRA band) at 1.27 μm. In this paper, we will primarily focus on the detailed description of the steps done for retrieving the calibrated IRA band limb radiance (with <10 % random error), the volume emission rate of O2 (a1i"g) (with <25 % random error) and finally the ozone number density (with <20 % random error). This retrieval technique is applied to a 1-year sample from the IRI dataset. The resulting product is a new ozone dataset with very tight along-track sampling distance (<20 km). The feasibility of the retrieval technique is demonstrated by a comparison of coincident ozone measurements from other instruments aboard the same spacecraft, as well as zonal mean and monthly average comparisons between Odin-OSIRIS (both spectrograph and IRI), Odin-SMR and Envisat-MIPAS. We find that IRI appears to have a positive bias of up to 25 % below 75 km, and up to 50 % in some regions above. We attribute these differences to uncertainty in the IRI calibration as well as uncertainties in the photochemical constants. However, the IRI ozone dataset is consistent with the compared dataset in terms of the overall atmospheric distribution of ozone between 50 and 100 km. If the origin of the bias can be identified before processing the entire dataset, this will be corrected and noted in the dataset description. The retrieval technique described in this paper can be further applied to all the measurements made throughout the 19 year mission, leading to a new, long-term high-resolution ozone dataset in the middle atmosphere

The OH (3-1) nightglow volume emission rate retrieved from OSIRIS measurements: 2001 to 2015

The OH airglow has been used to investigate the chemistry and dynamics of the mesosphere and the lower thermosphere (MLT) for a long time. The infrared imager (IRI) aboard the Odin satellite has been recording the night-time 1.53 mu m OH (3-1) emission for more than 15 years (2001-2015), and we have recently processed the complete data set. The newly derived data products contain the volume emission rate profiles and the Gaussian-approximated layer height, thickness, peak intensity and zenith intensity, and their corresponding error estimates. In this study, we describe the retrieval steps for these data products. We also provide data screening recommendations. The monthly zonal averages depict the well-known annual oscillation and semi-annual oscillation signatures, which demonstrate the fidelity of the data set (https://doi.org/10.5281/zenodo.4746506, Li et al., 2021). The uniqueness of this Odin IRI OH long-term data set makes it valuable for studying various topics, for instance, the sudden stratospheric warming events in the polar regions and solar cycle influences on the MLT

Witness Response at Acute Onset of Stroke: A Qualitative Theory-Guided Study

Background: Delay in calling emergency medical services following stroke limits access to early treatment that can reduce disability. Emergency medical services contact is mostly initiated by stroke witnesses (often relatives), rather than stroke patients. This study explored appraisal and behavioural factors that are potentially important in influencing witness behaviour in response to stroke. Methods and Findings: Semi-structured interviews with 26 stroke witnesses were transcribed and theory-guided content analysed was undertaken based on the Common Sense Self-Regulation Model (appraisal processes) and Theory Domains Framework (behavioural determinants). Response behaviours were often influenced by heuristics-guided appraisal (i.e. mental rules of thumb). Some witnesses described their responses to the situation as ‘automatic' and ‘instinctive', rather than products of deliberation. Potential behavioural influences included: environmental context and resources (e.g. time of day), social influence (e.g. prompts from patients) and beliefs about consequences (e.g. 999 accesses rapid help). Findings are based on retrospective accounts and need further verification in prospective studies. Conclusions: Witnesses play a key role in patient access to emergency medical services. Factors that potentially influence witnesses' responses to stroke were identified and could inform behavioural interventions and future research. Interventions might benefit from linking automatic/instinctive threat perceptions with deliberate appraisal of stroke symptoms, prompting action to call emergency medical services

The MATS satellite mission - gravity wave studies by Mesospheric Airglow/Aerosol Tomography and Spectroscopy

Global three-dimensional data are a key to understanding gravity waves in the mesosphere and lower thermosphere. MATS (Mesospheric Airglow/Aerosol Tomography and Spectroscopy) is a new Swedish satellite mission that addresses this need. It applies space-borne limb imaging in combination with tomographic and spectroscopic analysis to obtain gravity wave data on relevant spatial scales. Primary measurement targets are O-2 atmospheric band dayglow and nightglow in the near infrared, and sunlight scattered from noctilucent clouds in the ultraviolet. While tomography provides horizontally and vertically resolved data, spectroscopy allows analysis in terms of mesospheric temperature, composition, and cloud properties. Based on these dynamical tracers, MATS will produce a climatology on wave spectra during a 2-year mission. Major scientific objectives include a characterization of gravity waves and their interaction with larger-scale waves and mean flow in the mesosphere and lower thermosphere, as well as their relationship to dynamical conditions in the lower and upper atmosphere. MATS is currently being prepared to be ready for a launch in 2020. This paper provides an overview of scientific goals, measurement concepts, instruments, and analysis ideas

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

The "ram effect": new insights into neural modulation of the gonadotropic axis by male odors and socio-sexual interactions

Reproduction in mammals is controlled by the hypothalamo-pituitary-gonadal (HPG) axis under the influence of external and internal factors such as photoperiod, stress, nutrition, and social interactions. Sheep are seasonal breeders and stop mating when day length is increasing (anestrus). However, interactions with a sexually active ram during this period can override the steroid negative feedback responsible for the anoestrus state, stimulate LH secretion and eventually reinstate cyclicity. This is known as the ram effect and research into the mechanisms underlying it is shedding new light on HPG axis regulation. The first step in the ram effect is increased LH pulsatile secretion in anestrus ewes exposed to a sexually active male or only to its fleece, the latter finding indicating a pheromone-like effect. Estradiol secretion increases in all ewes and this eventually induces a LH surge and ovulation, just as during the breeding season. An exception is a minority of ewes that exhibit a precocious LH surge (within 4h) with no prior increase in estradiol. The main olfactory system and the cortical nucleus of the amygdala are critical brain structures in mediating the ram effect since it is blocked by their inactivation. Sexual experience is also important since activation (increased c-fos expression) in these and other regions is greatly reduced in sexually naïve ewes. In adult ewes kisspeptin neurons in both arcuate and preoptic regions and some preoptic GnRH neurons are activated 2h after exposure to a ram. Exposure to rams also activates noradrenergic neurons in the locus coeruleus and A1 nucleus and increased noradrenalin release occurs in the posterior preoptic area. Pharmacological modulation of this system modifies LH secretion in response to the male or his odor. Together these results show that the ram effect can be a fruitful model to promote both a better understanding of the neural and hormonal regulation of the HPG axis in general and also the spe

OSIRIS: A Decade of Scattered Light

Into year 11 of a 2-yr mission, OSIRIS is redefining how limb-scattered sunlight can be used to probe the atmosphere, even into the upper troposphere