A temperate super-Jupiter imaged with JWST in the mid-infrared.

Of the approximately 25 directly imaged planets to date, all are younger than 500 Myr, and all but six are younger than 100 Myr (ref. 1). Eps Ind A (HD209100, HIP108870) is a K5V star of roughly solar age (recently derived as 3.7-5.7 Gyr (ref. 2) and 3.5 - 1.3 + 0.8 Gyr (ref. 3)). A long-term radial-velocity trend4,5 and an astrometric acceleration6,7 led to claims of a giant planet2,8,9 orbiting the nearby star (3.6384 ± 0.0013 pc; ref. 10). Here we report JWST coronagraphic images which reveal a giant exoplanet that is consistent with these radial and astrometric measurements but inconsistent with the previously claimed planet properties. The new planet has a temperature of approximately 275 K and is remarkably bright at 10.65 and 15.50 µm. Non-detections between 3.5 and 5.0 µm indicate an unknown opacity source in the atmosphere, possibly suggesting a high-metallicity, high carbon-to-oxygen ratio planet. The best-fitting temperature of the planet is consistent with theoretical thermal evolution models, which were previously untested at this temperature range. The data indicate that this is probably the only giant planet in the system, and therefore we refer to it as b, despite it having significantly different orbital properties than the previously claimed planet b.

A qualitative analysis of online misinformation and conspiracy theories in psoriasis.

Psoriasis is a chronic, hereditary disease with a complex immunopathogenesis, rendering it susceptible to misinformation. Misinformation related to psoriasis can have negative effects both on the public perception of psoriasis and on patients' knowledge of psoriasis. To characterize misinformation related to psoriasis available online, we performed a formal literature review via PubMed and a thematic review via Google. Key themes of misinformation included 'victim-blaming' (hygiene), 'vector' (contagion), 'vaccination', 'vilification' of conventional therapy, 'validation' of natural treatment and diet, 'veneration' of cures and 'vocalization' from celebrities. Misinformation related to psoriasis is pervasive on social media and other websites. Dermatologists, as patient advocates, should be aware of the content of misinformation available online and combat misleading health information to optimize health outcomes for patients with psoriasis.

Non-Invasive Prenatal Testing (NIPT) - We Need a National Programme.

Aims The provision of non-invasive prenatal testing (NIPT), a blood test screening for aneuploidy during pregnancy, varies widely internationally. In Ireland, NIPT is available privately, costing over €400. Gobal research on the patient perspective on NIPT shows a strong desire for the test to be provided for free. Attitudes towards NIPT amongst pregnant women in Ireland have not previously been studied. We assessed this in women attending maternity services in our unit. Methods This was a cross-sectional observational study involving a telephone survey. Women were asked about their prior knowledge of NIPT. Women with no prior knowledge were given information about NIPT and asked about their opinion of the test. Results One hundred and twelve (n=112) women participated. Of these, 60% (n=67) had not heard of NIPT, 86% (n=96) believe it should be freely available, and 80% (n=90) said they would avail of the test if it were free. Cost was the main prohibitive factor for those choosing not to have the test. All women wished to be more informed about NIPT. Conclusion Awareness of NIPT amongst women attending maternity services in Ireland may be low, but there is a desire for more information and a more equitable provision of the test.

Synthesis of sp(3)-rich scaffolds for molecular libraries through complexity-generating cascade reactions.

An efficient strategy for the synthesis of complex small molecules from simple building blocks is presented. Key steps of the strategy include tandem Petasis and Diels-Alder reactions, and divergent complexity-generating cyclization cascades from a key dialdehyde intermediate. The methodology is validated through the synthesis of a representative compound set, which has been used in the production of 1617 molecules for the European Lead Factory.

Regional and global left ventricular function following a simulated 5 km race in sports-trained adolescents.

The effects of a short, high-intensity bout of exercise on cardiac systolic and diastolic function are not well understood in adolescent athletes. Consequently, the aims of the study were to evaluate global left ventricular (LV) systolic and diastolic function, as well as segmental wall motion responses (cardiac strain), prior to as well as 45 and 225 min following a simulated 5 km cross-country race. Twenty trained, adolescent males (age: 15.2 ± 0.7 years) volunteered for exercise testing. LV fractional shortening and the ratio of early (E) and late (A) peak flow velocities reflected global systolic and diastolic function, respectively. Peak longitudinal mitral annular septal tissue velocities were also determined during systole and diastole. Longitudinal strain (ε) and strain rates were determined across the LV. LV fractional shortening was significantly (P < 0.05) higher at 225 min post-race (37.6 ± 5.8%) compared to pre-race (34.5 ± 4.7%) and 45 min post-race (34.9 ± 5.4 %). This difference was abolished after adjusting for post-race heart rates. There was a significant (P < 0.05) decrease in the E:A ratio at both 45 min (2.04 ± 0.57) and 225 min post-race (2.20 ± 0.66) compared to the pre-race value (2.80 ± 0.68). When these data were adjusted for post-race heart rates, these pre-post-race differences in E:A ratio were abolished. There were no significant alterations in either tissue Doppler velocities or longitudinal ε. The evidence suggests that a 5 km race does not lead to any significant post-exercise attenuation in global or regional LV systolic and diastolic function in trained adolescents.

Unsteady flow affects swimming energetics in a labriform fish (Cymatogaster aggregata).

Unsteady water flows are common in nature, yet the swimming performance of fishes is typically evaluated at constant, steady speeds in the laboratory. We examined how cyclic changes in water flow velocity affect the swimming performance and energetics of a labriform swimmer, the shiner surfperch, Cymatogaster aggregata, during station holding. Using intermittent-flow respirometry, we measured critical swimming speed (Ucrit), oxygen consumption rates (O2) and pectoral fin use in steady flow versus unsteady flows with either low- [0.5 body lengths (BL) s(-1)] or high-amplitude (1.0 BL s(-1)) velocity fluctuations, with a 5 s period. Individuals in low-amplitude unsteady flow performed as well as fish in steady flow. However, swimming costs in high-amplitude unsteady flow were on average 25.3% higher than in steady flow and 14.2% higher than estimated values obtained from simulations based on the non-linear relationship between swimming speed and oxygen consumption rate in steady flow. Time-averaged pectoral fin use (fin-beat frequency measured over 300 s) was similar among treatments. However, measures of instantaneous fin use (fin-beat period) and body movement in high-amplitude unsteady flow indicate that individuals with greater variation in the duration of their fin beats were better at holding station and consumed less oxygen than fish with low variation in fin-beat period. These results suggest that the costs of swimming in unsteady flows are context dependent in labriform swimmers, and may be influenced by individual differences in the ability of fishes to adjust their fin beats to the flow environment.

Conversational artificial intelligence: the interface with the patient concerns inventory.

The patient concerns inventory (PCI) allows patients to highlight the issues they would like to discuss at their outpatient consultation. It improves patient-clinician communication and has proven benefits. While the PCI is effective, patient experiences could be improved with better access to it and the ability to more easily and frequently express their concerns. This, of course, is in the context of ever-increasing healthcare challenges and limited resources. Use of conversational artificial intelligence (CAI) represents an opportunity to improve information flow between patients and professionals remote from the consultation. This paper highlights the potential for CAI to provide an 'always-on' platform, using natural language interface technology and based on the PCI, which patients can access via their mobile devices. We also discuss potential pitfalls and concerns, along with outlining a current clinical trial assessing, in the first instance, usability of this technology.

Bifidobacterium animalis subsp. lactis BLa80 regulates the intestinal habit in adults with chronic constipation: a multicentre, randomised, double-blind, placebo-controlled study.

Treatment with probiotics can help manage chronic constipation by softening the stools and possibly acting synergistically with front-line treatments. We assessed the efficacy of Bifidobacterium animalis subsp. lactis BLa80 in maltodextrin as a food supplement in regulating the intestinal habit of subjects with chronic constipation with type 1 or 2 stools on the Bristol scale index and/or less than three stools per week. A multicentre, randomised, double-blind, placebo-controlled clinical trial was carried out in subjects aged 18 and over with chronic constipation. The study enrolled forty-six subjects who were randomised one-to-one to receive the potential probiotic in maltodextrin (n = 23) or a placebo (n = 23). Investigators assessed changes in intestinal habits by analysing the mean number of weekly stools and the stool types according to the Bristol Scale. Patients reported constipation symptoms with PAC-SYM (patient assessment of constipation - symptoms), and the impact on quality of life with PAC-QoL (patient assessment of constipation - quality of life) and GI-QLI (gastrointestinal quality of life index). Patients on the intervention group showed a greater tendency to normalise the type of stools than those in the placebo group. This difference towards regular stool types (type 3 and 4) was statistically significant at weeks 8 and 12 relative to week 4 (P-values = 0.006 and 0.027, respectively). The proportion of constipated patients in the experimental group dropped over time, while the rate slightly increased in the placebo group in a statistically significant manner at week 12 relative to week 4 ( P = 0.037). Overall, the present study shows oral intake of B. animalis subsp. lactis BLa80 in maltodextrin for 12 weeks improves intestinal habits in subjects with chronic constipation. Our study provides evidence to the efficacy and safety use of this formulation as an effective tool for improving stool consistency in constipated patients. The trial was registered at ClinicalTrials.gov: NCT05980988.

Reversible disruption of pericentric heterochromatin and centromere function by inhibiting deacetylases.

Histone modifications might act to mark and maintain functional chromatin domains during both interphase and mitosis. Here we show that pericentric heterochromatin in mammalian cells is specifically responsive to prolonged treatment with deacetylase inhibitors. These defined regions relocate at the nuclear periphery and lose their properties of retaining HP1 (heterochromatin protein 1) proteins. Subsequent defects in chromosome segregation arise in mitosis. All these changes can reverse rapidly after drug removal. Our data point to a crucial role of histone underacetylation within pericentric heterochromatin regions for their association with HP1 proteins, their nuclear compartmentalization and their contribution to centromere function.

Constraints on the duration and freshwater release of Heinrich event 4 through isotope modelling.

Heinrich events--abrupt climate cooling events due to ice-sheet instability that occurred during the last glacial period--are recorded in sediment cores throughout the North Atlantic Ocean. Modelling studies have described likely physical mechanisms for these events, but the quantitative characteristics of Heinrich events are less well known. Here we use a climate model of intermediate complexity that explicitly calculates the distribution of oxygen isotopes in the oceans to simulate Heinrich event 4 at about 40,000 yr ago. We compare an ensemble of scenarios for this Heinrich event with oxygen isotope data measured in foraminiferal calcite of a comprehensive set of sediment cores. From this comparison, we obtain a duration of 250 +/- 150 yr and an ice release of 2 +/- 1 m sea-level equivalent for Heinrich event 4, significantly reducing the uncertainties in both values compared to earlier estimates of up to 2,000 yr and 15 m of sea-level equivalent ice release, respectively. Our results indicate that the consequences of Heinrich events may have been less severe than previously assumed, at least with respect to Greenland climate and sea level.

Cluster of Legionnaires' disease associated with a public whirlpool spa, France, April-May 2010.

In May 2010, a cluster of three cases of Legionnaires' disease was identified in France. The results of the epidemiological, environmental and microbiological investigations allowed the rapid identification of a public whirlpool spa as the most probable source of contamination and the implementation of appropriate control measures. This investigation has stressed the need for good cooperation between partners and the importance of the molecular analysis of Legionella strains.

Recruitment of phosphorylated chromatin assembly factor 1 to chromatin after UV irradiation of human cells.

The subcellular distribution and posttranslational modification of human chromatin assembly factor 1 (CAF-1) have been investigated after UV irradiation of HeLa cells. In an asynchronous cell population only a subfraction of the two large CAF-1 subunits, p150 and p60, were found to exist in a chromatin-associated fraction. This fraction is most abundant during S phase in nonirradiated cells and is much reduced in G2 cells. After UV irradiation, the chromatin-associated form of CAF-1 dramatically increased in all cells irrespective of their position in the cell cycle. Such chromatin recruitment resembles that seen for PCNA, a DNA replication and repair factor. The chromatin-associated fraction of p60 was predominantly hypophosphorylated in nonirradiated G2 cells. UV irradiation resulted in the rapid recruitment to chromatin of phosphorylated forms of the p60 subunit. Furthermore, the amount of the p60 and p150 subunits of CAF-1 associated with chromatin was a function of the dose of UV irradiation. Consistent with these in vivo observations, we found that the amount of CAF-1 required to stimulate nucleosome assembly during the repair of UV photoproducts in vitro depended upon both the number of lesions and the phosphorylation state of CAF-1. The recruitment of CAF-1 to chromatin in response to UV irradiation of human cells described here supports a physiological role for CAF-1 in linking chromatin assembly to DNA repair.

Duplication and maintenance of heterochromatin domains.

To investigate the mechanisms that assure the maintenance of heterochromatin regions, we took advantage of the fact that clusters of heterochromatin DNA replicate late in S phase and are processed in discrete foci with a characteristic nuclear distribution. At the light microscopy level, within these entities, we followed DNA synthesis, histone H4 acetylation, heterochromatin protein 1 (Hp1alpha and -beta), and chromatin assembly factor 1 (CAF-1). During replication, Hp1alpha and -beta domains of concentration are stably maintained, whereas heterochromatin regions are enriched in both CAF-1 and replication-specific acetylated isoforms of histone H4 (H4Ac 5 and 12). We defined a time window of 20 min for the maintenance of this state. Furthermore, treatment with Trichostatin A (TSA), during and after replication, sustains the H4Ac 5 and 12 state in heterochromatin excluding H4Ac 8 and 16. In comparison, early replication foci, at the same level, did not display any specific enrichment in H4Ac 5 and 12. These data emphasize the specific importance for heterochromatin of the replication-associated H4 isoforms. We propose that perpetuation of heterochromatin involves self-maintenance factors, including local concentration of Hp1alpha and -beta, and that a degree of plasticity is provided by the cycle of H4 acetylation/deacetylation assisted by CAF-1.

Spindle microtubule differentiation and deployment during micronuclear mitosis in Paramecium.

Spindles underwent a 12-fold elongation before anaphase B was completed during the closed mitoses of micronuclei in Paramecium tetraurelia. Two main classes of spindle microtubules have been identified. A peripheral sheath of microtubules with diameters of 27-32 nm was found to be associated with the nuclear envelope and confined to the midportion of each spindle. Most of the other microtubules had diameters of approximately 24 nm and were present along the entire lengths of spindles. Nearly all of the 24-nm microtubules were eliminated from spindle midportions (largely because of microtubule disassembly) at a relatively early stage of spindle elongation. Disassembly of some of these microtubules also occurred at the ends of spindles. About 60% of the total microtubule content of spindles was lost at this stage. Most, perhaps all, peripheral sheath microtubules remained intact. Many of them detached from the nuclear envelope and regrouped to form a compact microtubule bundle in the spindle midportion. There was little, if any, further polymerization of 24-nm microtubules after the disassembly phase. Polymerization of microtubules with diameters of 27-32 nm continued as spindle elongation progressed. Most microtubules in the midportions of well-elongated spindles were constructed from 14-16 protofilaments. A few 24-nm microtubules with 13 protofilaments were also present. The implications of these findings for spatial control of microtubule assembly, disassembly, positioning, and membrane association, that apparently discriminate between microtubules with different protofilament numbers have been explored. The possibility that microtubule sliding occurs during spindle elongation has also been considered.

Structure of the RNA polymerase domain of E. coli primase.

All cellular organisms use specialized RNA polymerases called "primases" to synthesize RNA primers for the initiation of DNA replication. The high-resolution crystal structure of a primase, comprising the catalytic core of the Escherichia coli DnaG protein, was determined. The core structure contains an active-site architecture that is unrelated to other DNA or RNA polymerase palm folds, but is instead related to the "toprim" fold. On the basis of the structure, it is likely that DnaG binds nucleic acid in a groove clustered with invariant residues and that DnaG is positioned within the replisome to accept single-stranded DNA directly from the replicative helicase.