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BackgroundJoubert syndrome (JS) is a recessive neurodevelopmental disorder characterised by hypotonia, ataxia, cognitive impairment, abnormal eye movements, respiratory control disturbances and a distinctive mid-hindbrain malformation. JS demonstrates substantial phenotypic variability and genetic heterogeneity. This study provides a comprehensive view of the current genetic basis, phenotypic range and gene–phenotype associations in JS.MethodsWe sequenced 27 JS-associated genes in 440 affected individuals (375 families) from a cohort of 532 individuals (440 families) with JS, using molecular inversion probe-based targeted capture and next-generation sequencing. Variant pathogenicity was defined using the Combined Annotation Dependent Depletion algorithm with an optimised score cut-off.ResultsWe identified presumed causal variants in 62% of pedigrees, including the first B9D2 mutations associated with JS. 253 different mutations in 23 genes highlight the extreme genetic heterogeneity of JS. Phenotypic analysis revealed that only 34% of individuals have a ‘pure JS’ phenotype. Retinal disease is present in 30% of individuals, renal disease in 25%, coloboma in 17%, polydactyly in 15%, liver fibrosis in 14% and encephalocele in 8%. Loss of CEP290 function is associated with retinal dystrophy, while loss of TMEM67 function is associated with liver fibrosis and coloboma, but we observe no clear-cut distinction between JS subtypes.ConclusionsThis work illustrates how combining advanced sequencing techniques with phenotypic data addresses extreme genetic heterogeneity to provide diagnostic and carrier testing, guide medical monitoring for progressive complications, facilitate interpretation of genome-wide sequencing results in individuals with a variety of phenotypes and enable gene-specific treatments in the future.

The influence of plant traits on forest fire behaviour has evolutionary, ecological and management implications, but is poorly understood and frequently discounted. We use a process model to quantify that influence and provide validation in a diverse range of eucalypt forests burnt under varying conditions. Measured height of consumption was compared to heights predicted using a surface fuel fire behaviour model, then key aspects of our model were sequentially added to this with and without species-specific information. Our fully specified model had a mean absolute error 3.8 times smaller than the otherwise identical surface fuel model (p < 0.01), and correctly predicted the height of larger (≥1 m) flames 12 times more often (p < 0.001). We conclude that the primary endogenous drivers of fire severity are the species of plants present rather than the surface fuel load, and demonstrate the accuracy and versatility of the model for quantifying this.

Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an elusive target for homogeneous catalysis. In this report, reversible acceptorless dehydrogenation of secondary alcohols and diols on iron pincer complexes and reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes with separate transfer of protons and electrons on iridium complexes are shown. This reactivity suggests a strategy for the development of reversible fuel cell electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing fuels. Significance Catalytic hydrogenation and dehydrogenation reactions are extremely important in organic chemistry and recently for energy storage in the form of chemical bonds. Although catalysts are known which catalyze both reactions, the rates and conditions required for the two are frequently very different due to the differences associated with the bonds to be activated (C–H/O–H/N–H and C = O/C = N/H–H). The use of a bifunctional catalyst would substantially simplify the design of processes related to energy storage. In this work, organometallic complexes of iron and iridium are shown to act as catalysts for reversible dehydrogenation of alcohols to carbonyl compounds. This finding opens a pathway to the development of catalysts for direct reversible electrochemical dehydrogenation of organic fuels in energy generation and storage reactions.

[This corrects the article DOI: 10.1371/journal.pone.0312849.].

Aims/hypothesis The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells. Methods We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells. Results The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro. Conclusions/interpretation The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.

Understanding species distribution across habitats and environmental variables is important to inform area-based management. However, observational data are often lacking, particularly from developing countries, hindering effective conservation design. One such data-poor area is the Gulf of Guinea, an understudied and biodiverse region where coastal waters play a critical role in coastal livelihoods. Here, we describe the results of the largest national-scale Baited Remote Underwater Video Systems (BRUVS) survey in the region, aiming to understand the effects of several environmental variables on fish community composition and diversity. From 2018 to 2020, we successfully deployed 417 benthic BRUVS in the coastal waters of the São Tomé and Príncipe (STP) archipelago. Species richness and relative abundance were higher in deeper waters, on steeper slopes, and in rocky reef habitats. Nevertheless, maerl and sand habitats also hosted unique, and economically important species. Our results potentially indicate historical impacts of fishing in the archipelago, especially in São Tomé Island, where observed fishing effort is higher. Indeed, abundance of large predatory fish was low in both islands and abundance of species targeted by artisanal fisheries was lower in São Tomé than in Príncipe. Our results provide crucial information supporting the designation and future monitoring of marine protected areas in STP.

Negative human-wildlife interactions (HWI) pose a growing global conservation challenge, yet marine contexts remain underexplored relative to terrestrial systems. Sharks, as an ecologically critical but socially polarising group, exemplify these challenges and current monitoring frameworks often overlook the dynamic and complex nature of human–shark interactions (HSI). Here, we adopt a multi-method approach to characterise HSI at Ascension Island; a remote oceanic island surrounded by one of the world’s largest marine protected areas. By synthesising data from social media ( n  = 135 posts), semi-structured interviews ( n  = 26 interviewees), an online survey ( n  = 14 responses), archival records ( n  = 59 accounts), and remote camera footage ( n  = 325 days monitored), we (1) quantify spatiotemporal variation in HSI, (2) examine how the nature of HSI has changed, and (3) assess changes in local sentiment. Findings reveal fluctuations in the frequency of HSI across multiple temporal scales, from intra- and inter-annual variation to broader decadal oscillations. Collectively, the results suggest a decline in sightings of sharks during the late 20th century, followed by a recent resurgence preceding two shark bites in 2017. Temporal variation in HSI was associated with periods of heightened inshore shark presence and rapid behavioural shifts (e.g. increased aggression), whilst sentiment analysis highlights diverse and shifting views toward sharks, suggesting possible resilience or evolving acceptance within the community. This study highlights the value of a multi-method approach to better understand spatiotemporal dynamics of HSI and support adaptive management to foster coexistence. We underscore the need for monitoring approaches that account for both social and ecological dimensions of HSI and call for further research into the environmental drivers of observed variation in HSI.

Background:Natural killer (NK) cells may be impaired in patients with persistent hepatitis C virus (HCV) infection, but studies to date have yielded inconsistent findings due to patient and virus heterogeneity and difficulties obtaining appropriate controls.Aims:To overcome these variables, we have examined numbers, phenotypes, cytotoxic activities and cytokine profiles of circulating NK cells from Irish women who acquired infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source and matched controls.Results:Comparing 29 women who developed persistent infection with 21 who spontaneously resolved infection and 26 controls, we found that NK cell numbers were consistently lower in the persistently infected group (p = 0.02 and 0.002). This decrease was due to depletions of NK cells expressing low levels of CD56 (CD56dim NK cells; p = 0.004 and 0.0001), whilst CD56bright NK cells were expanded (p = 0.004 and 0.0001). Compared to HCV resolvers, CD56dim NK cells from persistently infected patients less frequently expressed CD16 and more frequently expressed NKG2A/C/E. These phenotypic changes did not significantly affect natural or interleukin-2-induced cytotoxicity by peripheral blood mononuclear cells against K562 and Daudi targets. Greater frequencies of CD56bright NK cells from chronic HCV patients produced interferon-γ compared with HCV responders (p = 0.05) and controls (p = 0.0001) after phorbol ester stimulation in vitro.Conclusions:Alterations in NK subset distributions in chronic HCV infection may explain why previous reports of impaired NK cell functions were difficult to confirm. Altered NK cell functions may contribute to impaired cellular immune responses and chronicity of disease following HCV infection.

The N = Z = 36 nucleus 72 Kr has been studied by inelastic scattering at intermediate energies. Two targets, 9 Be and 197 Au, were used to extract the nuclear deformation length, δ N , and the reduced E 2 transition probability, B ( E 2). The previously unknown non-yrast 2 + and 4 + states as well as a new candidate for the octupole 3 - state have been observed in the scattering on the Be target and placed in the level scheme based on γ - γ coincidences. The second 2 + state was also observed in the scattering on the Au target and the B ( E 2 ; 2 2 + → 0 1 + ) value could be determined for the first time. Analyzing the results in terms of a two-band mixing model shows clear evidence for a oblate-prolate shape coexistence and can be explained by a shape change from an oblate ground state to prolate deformed yrast band from the first 2 + state. This interpretation is corroborated by beyond mean field calculations using the Gogny D1S interaction.

We present a detailed comparison of shell model calculations with inverse kinematic transfer reaction data, obtained using a radioactive beam. Experimentally extracted spectroscopic factors from the 26 Al ( d , p ) 27 Al reaction for both even and odd parity states are found to be exceptionally well reproduced by the shell model and a high level of consistency is observed between bound isobaric analog states in 27 Al and 27 Si , populated via ( d ,  p ) and ( d ,  n ) transfer, respectively. Furthermore, an evaluation of key resonances in the astrophysical 26 Al ( p , γ ) 27 Si reaction indicates that shell model calculations provide relatively accurate predictions for the existence of strong resonances and mirror nucleus comparisons appear to hold exceptionally well for proton-unbound levels. Consequently, we expect that the utilization of both techniques will likely be a very effective tool in the investigation of stellar processes outside the current reach of experiment.