Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

Publisher Correction: A dynamically cold disk galaxy in the early Universe.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A dynamically cold disk galaxy in the early Universe.

The extreme astrophysical processes and conditions that characterize the early Universe are expected to result in young galaxies that are dynamically different from those observed today1-5. This is because the strong effects associated with galaxy mergers and supernova explosions would lead to most young star-forming galaxies being dynamically hot, chaotic and strongly unstable1,2. Here we report the presence of a dynamically cold, but highly star-forming, rotating disk in a galaxy at redshift6 z = 4.2, when the Universe was just 1.4 billion years old. Galaxy SPT-S J041839-4751.9 is strongly gravitationally lensed by a foreground galaxy at z = 0.263, and it is a typical dusty starburst, with global star-forming7 and dust properties8 that are in agreement with current numerical simulations9 and observations10. Interferometric imaging at a spatial resolution of about 60 parsecs reveals a ratio of rotational to random motions of 9.7 ± 0.4, which is at least four times larger than that expected from any galaxy evolution model at this epoch1-5 but similar to the ratios of spiral galaxies in the local Universe11. We derive a rotation curve with the typical shape of nearby massive spiral galaxies, which demonstrates that at least some young galaxies are dynamically akin to those observed in the local Universe, and only weakly affected by extreme physical processes.

Evaluating the genetic consequences of population subdivision as it unfolds and how to best mitigate them: A rare story about koalas.

The genetic consequences of the subdivision of populations are regarded as significant to long-term evolution, and research has shown that the scale and speed at which this is now occurring is critically reducing the adaptive potential of most species which inhabit human-impacted landscapes. Here, we provide a rare and, to our knowledge, the first analysis of this process while it is happening and demonstrate a method of evaluating the effect of mitigation measures such as fauna crossings. We did this by using an extensive genetic data set collected from a koala population which was intensely monitored during the construction of linear transport infrastructure which resulted in the subdivision of their population. First, we found that both allelic richness and effective population size decreased through the process of population subdivision. Second, we predicted the extent to which genetic drift could impact genetic diversity over time and showed that after only 10 generations the resulting two subdivided populations could experience between 12% and 69% loss in genetic diversity. Lastly, using forward simulations we estimated that a minimum of eight koalas would need to disperse from each side of the subdivision per generation to maintain genetic connectivity close to zero but that 16 koalas would ensure that both genetic connectivity and diversity remained unchanged. These results have important consequences for the genetic management of species in human-impacted landscapes by showing which genetic metrics are best to identify immediate loss in genetic diversity and how to evaluate the effectiveness of any mitigation measures.

We are what we (think we) eat: The effect of expected satiety on subsequent calorie consumption.

Varying expected satiety (ES) for equi-calorie portions of different foods can affect subsequent feelings of hunger and fullness and alter consumption. To our knowledge, no study has manipulated ES for an equal portion of the same solid food, subsequent appetite has not been measured >3 h and studies have not consistently measured later consumption. Further, it is not clear whether any changes in hunger, fullness or later consumption that stem from differing ES are the result of a psychological or physiological response. The aims of this study were to manipulate ES for the same solid food on two occasions in order to compare participants' appetitive responses over a 4-h inter-meal period, to measure later consumption, and to assess whether any effect of ES on these measures was related to a physiological (i.e. total ghrelin) response. Using a within-subjects design, 26 healthy participants had their ES for omelettes manipulated experimentally, believing that a 3-egg omelette contained either 2 (small condition) or 4 (large condition) eggs. When ES was higher (large condition) participants ate significantly fewer calories at a lunchtime test meal (mean difference = 69 kcal [± 95% CI 4-136]) and consumed significantly fewer calories throughout the day (mean difference = 167 kcal [± 95% CI 26-309]). The results show that there was a significant main effect of time on hunger and fullness, but no main effect of 'portion size' (p > .05). There was also a significant interaction between time and portion size for hunger. There was no evidence for any significant differences in appetite or consumtpion resulting from changes in total ghrelin. Overall, the data suggest that ES for a solid food can be manipulated and that, when given at breakfast, having a higher ES for a meal significantly reduces lunchtime and whole day caloric consumption.

A preliminary study of cerebral blood flow, aging and dementia in people with Down syndrome.

BACKGROUND: People with Down syndrome (DS) develop Alzheimer's disease (AD) at an earlier age of onset than those with sporadic AD. AD neuropathology is typically present in DS by 40 years of age with an onset of dementia approximately 10 years later. This early onset is due to the overexpression of amyloid precursor protein from the third copy of chromosome 21. Cerebrovascular neuropathology is thought to contribute in 40-60% of cases sporadic AD. However, the vascular contribution to dementia in people with DS has been relatively unexplored. We hypothesised that vascular perfusion is compromised in older adults with DS relative to younger individuals and is further exacerbated in those with dementia. METHOD: Cerebral blood flow (CBF) was measured using pulsed arterial spin labelling in 35 cognitively characterised adults with DS (26-65 years). DS participants were also compared with 15 control subjects without DS or dementia (26-65 years). Linear regression evaluated the difference in CBF across groups and diagnosis along with assessing the association between CBF and cognitive measures within the DS cohort. RESULTS: Cerebral blood flow was significantly lower among DS participants with probable AD compared with controls (P = 0.02) and DS participants with no dementia (P = 0.01). Within the DS cohort, CBF was significantly associated with the Severe Impairment Battery (SIB) measure and the Dementia Questionnaire for People with Learning Disabilities (DLD) rating (F3,25  = 5.13; P = 0.007). Both the SIB (ß = 0.74; t = 2.71; P = 0.01) and DLD (ß = -0.96; t = -3.87; P < 0.001) indicated greater impairment as global CBF decreased. Age was significantly associated with CBF among participants with DS. There was a non-linear effect of age, whereby CBF declined more rapidly after 45 years of age. CONCLUSIONS: This preliminary study of CBF in DS indicates that cerebrovascular pathology may be a significant contributor to dementia in DS. CBF was associated with diagnosis, cognition and age. Notably, CBF decreases at a greater rate after age 45 and may represent a significant prodromal event in AD progression.

A qualitative study of the processes by which carers of people with dementia derive meaning from caring.

BACKGROUND: Most individuals with dementia live in the community, receiving care from family or lay carers. Carers' wellbeing, and the quality of the care they provide, partly depends on their ability to derive meaning from caring for someone with dementia. Both carers' previous relationship with their relative and the caregiving process itself contribute to this sense of meaning. However, it remains unclear why some carers derive meaning from these sources, whereas others do not. OBJECTIVE: To further explore the processes by which carers derive a sense of meaning from caring. METHODS: Representative case sampling was used to recruit a purposive sample of 20 carers for individuals living with dementia. In-depth semi-structured interviews were audio-recorded and transcribed, and analysed using pluralist qualitative methodology. RESULTS: A framework of three sources from which carers derived meaning from caring was identified, encompassing: carers' perceptions of how 'right' or 'symmetrical' caring felt in light of their current and previous relationship with the person with dementia; maintenance of a 'protected' sense of self within the care relationship; and carers' perceptions of their 'social connectedness' outside the relationships. CONCLUSION: Holistic assessment based on this framework could help to tailor individualised provision of support, foster resilience and safeguard carers' well-being.

Putative chemosensory receptors are differentially expressed in the sensory organs of male and female crown-of-thorns starfish, Acanthaster planci.

BACKGROUND: Chemosensation is a critical signalling process for all organisms and is achieved through the interaction between chemosensory receptors and their ligands. The Crown-of-thorns starfish, Acanthaster planci species complex (COTS), is a predator of coral polyps and Acanthaster cf. solaris is currently considered to be one of the main drivers of coral loss on the Great Barrier Reef in Queensland, Australia. RESULTS: This study reveals the presence of putative variant Ionotropic Receptors (IRs) which are differentially expressed in the olfactory organs of COTS. Several other types of G protein-coupled receptors such as adrenergic, metabotropic glutamate, cholecystokinin, trace-amine associated, GRL101 and GPCR52 receptors have also been identified. Several receptors display male-biased expression within the sensory tentacles, indicating possible reproductive significance. CONCLUSIONS: Many of the receptors identified in this study may have a role in reproduction and are therefore key targets for further investigation. Based on their differential expression within the olfactory organs and presence in multiple tissues, it is possible that several of these receptor types have expanded within the Echinoderm lineage. Many are likely to be species-specific with novel ligand-binding affinity and a diverse range of functions. This study is the first to describe the presence of variant Ionotropic Glutamate Receptors in any Echinoderm, and is only the second study to investigate chemosensory receptors in any starfish or marine pest. These results represent a significant step forward in understanding the chemosensory abilities of COTS.

The impact of fatigue on the non-technical skills performance of critical care air ambulance clinicians.

BACKGROUND: The relationship between fatigue-related risk and impaired clinical performance is not entirely clear. Non-technical factors represent an important component of clinical performance and may be sensitive to the effects of fatigue. The hypothesis was that the sum score of overall non-technical performance is degraded by fatigue. METHODS: Nineteen physicians undertook two different simulated air ambulance missions, once when rested, and once when fatigued (randomised crossover design). Trained assessors blinded to participants' fatigue status performed detailed structured assessments based on expected behaviours in four non-technical skills domains: teamwork, situational awareness, task management, and decision making. Participants also provided self-ratings of their performance. The primary endpoint was the sum score of overall non-technical performance. RESULTS: The main finding, the overall non-technical skills performance rating of the clinicians, was better in rested than fatigued states (mean difference with 95% CI, 2.8 [2.2-3.4]). The findings remained consistent across individual non-technical skills domains; also when controlling for an order effect and examining the impact of a number of possible covariates. There was no difference in self-ratings of clinical performance between rested and fatigued states. CONCLUSION: Non-technical performance of critical care air transfer clinicians is degraded when they are fatigued. Fatigued clinicians may fail to recognise the degree to which their performance is compromised. These findings represent risk to clinical care quality and patient safety in the dynamic and isolated environment of air ambulance transfer.

Mechanisms of extracellular S0 globule production and degradation in Chlorobaculumtepidum via dynamic cell-globule interactions.

The Chlorobiales are anoxygenic phototrophs that produce solid, extracellular elemental sulfur globules as an intermediate step in the oxidation of sulfide to sulfate. These organisms must export sulfur while preventing cell encrustation during S0 globule formation; during globule degradation they must find and mobilize the sulfur for intracellular oxidation to sulfate. To understand how the Chlorobiales address these challenges, we characterized the spatial relationships and physical dynamics of Chlorobaculum tepidum cells and S0 globules by light and electron microscopy. Cba. tepidum commonly formed globules at a distance from cells. Soluble polysulfides detected during globule production may allow for remote nucleation of globules. Polysulfides were also detected during globule degradation, probably produced as an intermediate of sulfur oxidation by attached cells. Polysulfides could feed unattached cells, which made up over 80% of the population and had comparable growth rates to attached cells. Given that S0 is formed remotely from cells, there is a question as to how cells are able to move toward S0 in order to attach. Time-lapse microscopy shows that Cba. tepidum is in fact capable of twitching motility, a finding supported by the presence of genes encoding type IV pili. Our results show how Cba. tepidum is able to avoid mineral encrustation and benefit from globule degradation even when not attached. In the environment, Cba. tepidum may also benefit from soluble sulfur species produced by other sulfur-oxidizing or sulfur-reducing bacteria as these organisms interact with its biogenic S0 globules.

Attitudes towards HIV testing via home-sampling kits ordered online (RUClear pilots 2011-12).

BACKGROUND: The burden of disease relating to undiagnosed HIV infection is significant in the UK. BHIVA (British HIV Association) recommends population screening in high prevalence areas, expanding outside traditional antenatal/GUM settings. METHODS: RUClear 2011-12 piloted expanding HIV testing outside traditional settings using home-sampling kits (dry-blood-spot testing) ordered online. Greater Manchester residents (≥age 16) could request testing via an established, online chlamydia testing service (www.ruclear.co.uk). Participant attitudes towards this new service were assessed. Qualitative methods (thematic analysis) were used to analyse free-text data submitted by participants via hard copy questionnaires issued in all testing kits. RESULTS: 79.9% (2447/3062) participants completed questionnaires, of which 30.9% (756/2447) provided free-text data. Participants overwhelmingly supported the service, valuing particularly accessibility and convenience, allowing individuals to order tests any time of day and self-sample comfortably at home; avoiding the invasive nature of venipuncture and avoiding the need for face-to-face interaction with health services. The pilot was also clinically and cost-effective. CONCLUSION: Testing via home-sampling kits ordered online (dry-blood-spot testing) was felt to be an acceptable and convenient method for accessing a HIV test. Many individuals undertook HIV testing where they would otherwise not have been tested at all. Expansion of similar services may increase the uptake of HIV testing.

Dentin Dysplasia in Notum Knockout Mice.

Secreted WNT proteins control cell differentiation and proliferation in many tissues, and NOTUM is a secreted enzyme that modulates WNT morphogens by removing a palmitoleoylate moiety that is essential for their activity. To better understand the role this enzyme in development, the authors produced NOTUM-deficient mice by targeted insertional disruption of the Notum gene. The authors discovered a critical role for NOTUM in dentin morphogenesis suggesting that increased WNT activity can disrupt odontoblast differentiation and orientation in both incisor and molar teeth. Although molars in Notum(-/-) mice had normal-shaped crowns and normal mantle dentin, the defective crown dentin resulted in enamel prone to fracture during mastication and made teeth more susceptible to endodontal inflammation and necrosis. The dentin dysplasia and short roots contributed to tooth hypermobility and to the spread of periodontal inflammation, which often progressed to periapical abscess formation. The additional incidental finding of renal agenesis in some Notum (-/-) mice indicated that NOTUM also has a role in kidney development, with undiagnosed bilateral renal agenesis most likely responsible for the observed decreased perinatal viability of Notum(-/-) mice. The findings support a significant role for NOTUM in modulating WNT signaling pathways that have pleiotropic effects on tooth and kidney development.

Diffusion-weighted signal patterns of intracranial haemorrhage.

The signal pattern of intracranial haemorrhage on diffusion-weighted imaging (DWI) as it evolves over time is rarely discussed due to the sensitivity of T2*-weighted sequences and the specificity of classic signal patterns on T1 and T2-weighted sequences. The DWI signal is strongly affected by the magnetic susceptibility of paramagnetic blood products and, therefore, is markedly hypointense in the same phases that demonstrate hypointensity on T2*-weighted sequences; however, hyperacute haemorrhage (oxyhaemoglobin-predominant clot) and late subacute haemorrhage (extracellular methaemoglobin) do not demonstrate T2* hypointensity. Moreover, T2*-weighted sequences are less sensitive to the presence of extra-axial haemorrhage than to intraparenchymal haemorrhage. At these stages of evolution, haemorrhage demonstrates high DWI signal in association with low ADC values, which may be more pronounced than even its corresponding fluid-attenuated inversion recovery (FLAIR) signal. DWI is useful for identifying hyperacute subarachnoid haemorrhage and as a problem-solving tool in challenging cases.

Nephronophthisis and retinal degeneration in tmem218-/- mice: a novel mouse model for Senior-Løken syndrome?

Mice deficient in TMEM218 (Tmem218(-/-) ) were generated as part of an effort to identify and validate pharmaceutically tractable targets for drug development through large-scale phenotypic screening of knockout mice. Routine diagnostics, expression analysis, histopathology, and electroretinogram analyses completed on Tmem218(-/-) mice identified a previously unknown role for TMEM218 in the development and function of the kidney and eye. The major observed phenotypes in Tmem218(-/-) mice were progressive cystic kidney disease and retinal degeneration. The renal lesions were characterized by diffuse renal cyst development with tubulointerstitial nephropathy and disruption of tubular basement membranes in essentially normal-sized kidneys. The retinal lesions were characterized by slow-onset loss of photoreceptors, which resulted in reduced electroretinogram responses. These renal and retinal lesions are most similar to those associated with nephronophthisis (NPHP) and retinitis pigmentosa in humans. At least 10% of NPHP cases present with extrarenal conditions, which most often include retinal degeneration. Senior-Løken syndrome is characterized by the concurrent development of autosomal recessive NPHP and retinitis pigmentosa. Since mutations in the known NPHP genes collectively account for only about 30% of NPHP cases, it is possible that TMEM218 could be involved in the development of similar ciliopathies in humans. In reviewing all other reported mouse models of NPHP, we suggest that Tmem218(-/-) mice could provide a useful model for elucidating the pathogenesis of cilia-associated disease in both the kidney and the retina, as well as in developing and testing novel therapeutic strategies for Senior-Løken syndrome.

Mesenchymal cells of the intestinal lamina propria.

The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone marrow-derived stromal stem cells, smooth muscle of the muscularis mucosae, and smooth muscle surrounding the lymphatic lacteals. These cells share similar marker molecules, origins, and coordinated biological functions previously ascribed solely to subepithelial myofibroblasts. We review the functional anatomy of intestinal mesenchymal cells and describe what is known about their origin in the embryo and their replacement in adults. As part of their putative role in intestinal mucosal morphogenesis, we consider the intestinal stem cell niche. Lastly, we review emerging information about myofibroblasts as nonprofessional immune cells that may be important as an alarm system for the gut and as a participant in peripheral immune tolerance.

Establishing a Telephone Medication Order Policy and Protocol for a Small Private Hospital in Jamaica.

OBJECTIVE: To institutionalize an evidence-based policy/protocol adapted from the Agency for Healthcare Research and Quality (AHRQ) national medication standards for managing telephone medication orders (TMO) and to determine the impact of the policy/protocol on the number of telephone medication errors (TME) on two medical units of a small private hospital in Jamaica. METHODS: Kotter's Eight-step Change Model was used to facilitate organizational change among nurses and physicians by teaching and implementing the TMO policy/protocol adapted from AHRQ standards and collecting pre-policy and post-policy frequency of TMEs. A convenience sample of 80 nurses and physicians participated in training about the policy/protocol, took post-instructional tests and participated in the implementation of the policy/protocol. Chart audits over six weeks monitored adherence to the policy/protocol. The annual monthly mean of TMEs for the prior year was compared with the number of TMEs just prior to implementation of policy/protocol and at the end of the first six weeks of implementation. RESULTS: One hundred per cent of the convenience sample of 80 nurses and doctors passed the post-instructional test; the workforce adhered fully to the protocol during six weeks of implementation, and there was a 100% reduction in TMEs between the prior year and six weeks after policy/protocol implementation. CONCLUSIONS: Kotter's eight-step framework of organizational change was a successful strategy in institutionalizing and sustaining adherence to the TMO policy/protocol, reducing the number of TMEs and positively influencing the organizational culture.

Development and characterization of microsatellite loci for Ocotea species (Lauraceae) threatened with extinction.

The Atlantic rainforest species Ocotea catharinensis, Ocotea odorifera, and Ocotea porosa have been extensively harvested in the past for timber and oil extraction and are currently listed as threatened due to overexploitation. To investigate the genetic diversity and population structure of these species, we developed 8 polymorphic microsatellite markers for O. odorifera from an enriched microsatellite library by using 2 dinucleotide repeats. The microsatellite markers were tested for cross-amplification in O. catharinensis and O. porosa. The average number of alleles per locus was 10.2, considering all loci over 2 populations of O. odorifera. Observed and expected heterozygosities for O. odorifera ranged from 0.39 to 0.93 and 0.41 to 0.92 across populations, respectively. Cross-amplification of all loci was successfully observed in O. catharinensis and O. porosa except 1 locus that was found to lack polymorphism in O. porosa. Combined probabilities of identity in the studied Ocotea species were very low ranging from 1.0 x 10-24 to 7.7 x 10-24. The probability of exclusion over all loci estimated for O. odorifera indicated a 99.9% chance of correctly excluding a random nonparent individual. The microsatellite markers described in this study have high information content and will be useful for further investigations on genetic diversity within these species and for subsequent conservation purposes.

The effect of nutritional status and muscle fiber type on myogenic satellite cell fate and apoptosis.

Satellite cells (SC) are multipotential stem cells that can be induced by nutrition to alter their cellular developmental fate, which may vary depending on their fiber type origin. The objective of the current study was to determine the effect of restricting protein synthesis on inducing adipogenic transdifferentiation and apoptosis of SC originating from fibers of the fast glycolytic pectoralis major (p. major) and fast oxidative and glycolytic biceps femoris (b. femoris) muscles of the chicken. The availability of the essential sulfur amino acids Met and Cys was restricted to regulate protein synthesis during SC proliferation and differentiation. The SC were cultured and treated with 1 of 6 Met/Cys concentrations: 60/192, 30/96 (control), 7.5/24, 3/9.6, 1/3.2, or 0/0 mg/L. Reductions in Met/Cys concentrations from the control level resulted in increased lipid staining and expression of the adipogenic marker genes peroxisome proliferator-activated receptor gamma and stearoyl-CoA desaturase during differentiation in the p. major SC. Although b. femoris SC had increased lipid staining at lower Met/Cys concentrations, there was no increase in expression of either adipogenic gene. For both muscle types, SC Met/Cys, concentration above the control increased the expression of peroxisome proliferator-activated receptor gamma and stearoyl-CoA desaturase during differentiation. As Met/Cys concentration was decreased during proliferation, a dose-dependent decline in all apoptotic cells occurred except for early apoptotic cells in the p. major, which had no treatment effect (P < 0.05). During differentiation, decreasing Met/Cys concentration caused an increase in early apoptotic cells in both fiber types and no effect on late apoptotic cells except for an increase in the p. major 7.5/24 mg/L of Met/Cys treatment. In general, the viability of the SC was unaffected by the Met/Cys concentration except during proliferation in the p. major 0/0 mg/L of Met/Cys treatment, which increased SC viability. These data demonstrate the effect of nutrition on SC transdifferentiation to an adipogenic lineage and apoptosis, and the effect of fiber type on this response in an in vitro context.