Search

Uranium (U) is an important global energy resource and a redox sensitive trace element that reflects changing environmental conditions and geochemical cycling. The redox evolution of U mineral chemistry can be interrogated to understand the formation and distribution of U deposits and the redox processes involved in U geochemistry throughout Earth history. In this study, geochemical modeling using thermodynamic data, and mineral chemistry network analysis are used to investigate U geochemistry and deposition through time. The number of U6+ mineral localities surpasses the number of U4+ mineral localities in the Paleoproterozoic. Moreover, the number of sedimentary U6+ mineral localities increases earlier in the Phanerozoic than the number of U4+ sedimentary mineral localities, likely due to the necessity of sufficient sedimentary organic matter to reduce U6+–U4+. Indeed, modeling calculations indicate that increased oxidative weathering due to surface oxygenation limited U4+ uraninite (UO2) formation from weathered granite and basalt. Louvain network community detection shows that U6+ forms minerals with many more shared elements and redox states than U4+. The range of weighted Mineral Element Electronegativity Coefficient of Variation (wMEECV) values of U6+ minerals increases through time, particularly during the Phanerozoic. Conversely, the range of wMEECV values of U4+ minerals is consistent through time due to the relative abundance of uraninite, coffinite, and brannerite. The late oxidation and formation of U6+ minerals compared to S6+ minerals illustrates the importance of the development of land plants, organic matter deposition, and redox‐controlled U deposition from ground water in continental sediments during this time‐period. Plain Language Summary: Uranium (U) is the most widely used fuel in nuclear fission power plants, and nuclear power results in lower greenhouse gas emissions than fossil fuel energy. The different types of U deposits and minerals have evolved throughout the Earth history with changing environmental conditions and formation processes. In this study, we use modeling calculations and network analysis to understand how the transforming Earth system impacted the global U cycle, evolving U mineral chemistry, and deposit formation through time. Modeling calculations show that the abundant U mineral uraninite (UO2) formed in much greater quantities in the anoxic conditions of the Archean eon than present day oxic conditions. We also find that U minerals are increasingly oxidized through time, in agreement with modeling calculations, resulting in new minerals with diversifying chemical element associations and expanding distribution of U in the environment. The earlier increase in the number of oxidized U minerals in sedimentary localities than unoxidized U minerals in sedimentary localities 350–250 million years ago reflects the importance of land plants and organic matter in the formation of unoxidized U minerals in sedimentary settings. Key Points: Model calculations indicate Earth surface oxidation limited U4+ uraninite formation, in agreement with increased observed U6+ mineralsU oxidation increases the diversity of mineral chemical element associations and distribution in the environmentThe later formation of U6+ minerals compared to S6+ minerals represents differential Earth surface oxidation [ABSTRACT FROM AUTHOR]

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome characterized by the progressive and initially isolated or predominant onset of difficulties in the planning/programming of movements necessary for speech production and can be accompanied by dysarthria. To date, no study has used an evidence-based treatment to address phonation control in patients with PPAOS. The aim of this study was to evaluate the feasibility and efficacy of LSVT LOUD® as a treatment for phonatory control in speakers with PPAOS. Three speakers with PPAOS received LSVT LOUD® therapy, and changes in phonatory control, voice quality and prosody were measured immediately, and one, four and eight weeks after the end of the treatment. Overall, the results suggest that the treatment is feasible and could improve voice quality, intensity, and control in some patients with PPAOS. The generalization of the results is also discussed.

The Gram staining method differentiates bacteria based on their cell envelope structure, with the monoderm and diderm cell envelope types traditionally being synonymous with Gram-positive and Gram-negative stain results, respectively. Monoderms have a single phospholipid membrane surrounded by a thick layer of peptidoglycan, while diderms have a lipopolysaccharide outer membrane exterior to a thin peptidoglycan layer. The Bacillota (formerly Firmicutes ) phylum has members with both cell wall types, and recent phylogenetic analyses have shown that monoderm Bacillota evolved from diderm ancestors on multiple occasions. Here, we compiled Gram staining and ultrastructural data for Bacillota species with complete genomes to further investigate the evolution of Gram-positive and Gram-negative cell wall types. The results indicate that many deeply branching lineages at the root of Bacillota phylum stain Gram-negative but do not harbor genes for outer membrane protein or lipopolysaccharide biosynthesis. Phylogenetic reconstructions suggest that several deeply branching Bacillota species have retained a thin peptidoglycan layer in their cell walls, which was inherited from a diderm ancestor. Taxa with this atypical Gram-negative-staining cell wall structure include the thermophilic anaerobe Symbiobacterium thermophilum and members of the Desulfotomaculia, Syntrophamonadia, Desulfitobacteriia, Thermosediminibacteria, and Thermoanaerobacteria . Using Gram-staining results as a proxy for cell wall thickness, our analysis indicates that several independent peptidoglycan thickening events may have occurred in the evolution of the Gram-positive cell envelope., Importance: In this study, we examined the evolution of bacterial cell envelopes, specifically focusing on Gram-positive and Gram-negative cell wall types in the Bacillota phylum. Our results indicate that certain bacteria can stain Gram-negative despite having a monoderm cell wall structure, thus challenging the conventional interpretation of Gram-staining results. Our observations also question the assumption that Gram-negative staining is always indicative of a diderm structure. These findings have broader implications for understanding how and when cell walls thicken during the evolution of bacterial cell envelopes., Competing Interests: The authors declare no conflict of interest.

Background: Oncogenic 'hotspot' mutations of KRAS and GNAS are two major driver alterations in intraductal papillary mucinous neoplasms (IPMNs), which are bona fide precursors to pancreatic ductal adenocarcinoma. We previously reported that pancreas-specific Kras G12D and Gnas R201C co-expression in p48 Cre ; Kras LSL-G12D ; Rosa26 LSL-rtTA ; Tg (TetO-Gnas R201C ) mice ( 'Kras;Gnas ' mice) caused development of cystic lesions recapitulating IPMNs., Objective: We aim to unveil the consequences of mutant Gnas R201C expression on phenotype, transcriptomic profile and genomic dependencies., Design: We performed multimodal transcriptional profiling (bulk RNA sequencing, single-cell RNA sequencing and spatial transcriptomics) in the 'Kras;Gnas ' autochthonous model and tumour-derived cell lines ( Kras;Gnas cells), where Gnas R201C expression is inducible. A genome-wide CRISPR/ Cas 9 screen was conducted to identify potential vulnerabilities in Kras G12D ;Gnas R201C co-expressing cells., Results: Induction of Gnas R201C -and resulting G (s) alpha signalling-leads to the emergence of a gene signature of gastric (pyloric type) metaplasia in pancreatic neoplastic epithelial cells. CRISPR screening identified the synthetic essentiality of glycolysis-related genes Gpi1 and Slc2a1 in Kras G12D ; Gnas R201C co-expressing cells. Real-time metabolic analyses in Kras;Gnas cells and autochthonous Kras;Gnas model confirmed enhanced glycolysis on Gnas R201C induction. Induction of Gnas R201C made Kras G12D expressing cells more dependent on glycolysis for their survival. Protein kinase A-dependent phosphorylation of the glycolytic intermediate enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) was a driver of increased glycolysis on Gnas R201C induction., Conclusion: Multiple orthogonal approaches demonstrate that Kras G12D and Gnas R201C co-expression results in a gene signature of gastric pyloric metaplasia and glycolytic dependency during IPMN pathogenesis. The observed metabolic reprogramming may provide a potential target for therapeutics and interception of IPMNs., Competing Interests: Competing interests: AM is listed as an inventor on a patent that has been licensed by Johns Hopkins University to Thrive Earlier Detection. AM serves as a consultant for Tezcat Biosciences., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The higher rate of mental illness, including severe psychotic disorders, among people in prisons compared to the general community is well-established. However, there have been no reviews or attempts to pool data on the reported prevalence of mental illness across prisons in Australia and New Zealand., Methods: A systematic search of electronic databases from 1966 to the end of 2020 was conducted to identify studies reporting rates of 'any' mental illness, and separately rates of psychotic illness, among adult men and women in Australian and New Zealand prisons. A meta-analysis was performed according to PRISMA guidelines (PROSPERO ID: CRD42021241946), with separate analyses conducted for lifetime and current prevalence rates., Results: Seventeen studies, with a total of 10,209 people in prison, met inclusion criteria. The pooled lifetime prevalence of 'any' mental illness was 69.0% (95% confidence interval = [0.56, 0.79]), and the pooled lifetime prevalence for psychosis was 9.1% (95% confidence interval = [0.07, 0.12]). Meanwhile, the pooled prevalence for 'any' current mental illness was 54.0% (95% confidence interval = [0.39, 0.68]) and for any current psychosis was 6.4% (95% confidence interval = [0.04, 0.10]). There was substantial heterogeneity between studies, with evidence that lifetime rates of psychosis have increased over time, with true prevalence estimates in 95% of all comparable populations falling between 2.7% and 26.4%., Conclusion: The prevalence of mental illness, including severe psychotic illness, is high in Australian and New Zealand prisons. Furthermore, there is evidence that the prevalence of psychosis may be increasing over time, indicating more effort is needed to ensure diversion of people with mental illness away from the criminal justice system and into healthcare pathways., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Purpose: Despite the high rates of psychotic disorders amongst people in prison, current prison mental health screening approaches have not included assessment of the full psychosis spectrum to capture those at-risk of an emerging psychosis as well as those with established illness nor assessed the concurrent validity of psychosis symptom screening., Methods: Using a clinical staging approach to establish the prevalence of Ultra High Risk (UHR), first episode of psychosis (FEP) and established psychosis (EP) groups, 291 adults entering custody in two prison reception centres in NSW completed a two-stage (screening and validation) interview process. The Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to determine the clinical stages of psychosis and concurrent validity of symptom screening in identifying individuals on the psychosis spectrum was formally assessed., Results: Amongst men and women entering prison, almost one quarter (24.1%) met UHR criteria, 5.1% met the FEP threshold and 10.6% had an established psychosis. Those on the psychosis spectrum reported greater disadvantage across sociodemographic and justice factors. The presence of perceptual disturbance and paranoid beliefs emerged as the two best screening items for identifying those with an underlying psychosis spectrum illness., Conclusion: The prevalence of psychosis spectrum illness, including the UHR state, amongst those entering prison is high. Current prison mental health approaches should include screening for the presence of perceptual disturbances and paranoid beliefs to improve the detection of psychosis spectrum illness., (© 2024. The Author(s).)

Microbial reduction of organic disulfides affects the macromolecular structure and chemical reactivity of natural organic matter. Currently, the enzymatic pathways that mediate disulfide bond reduction in soil and sedimentary organic matter are poorly understood. In this study, we examined the extracellular reduction of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) by Shewanella oneidensis strain MR-1. A transposon mutagenesis screen performed with S. oneidensis resulted in the isolation of a mutant that lost ~90% of its DTNB reduction activity. Genome sequencing of the mutant strain revealed that the transposon was inserted into the dsbD gene, which encodes for an oxidoreductase involved in cytochrome c maturation. Complementation of the mutant strain with the wild-type dsbD partially restored DTNB reduction activity. Because DsbD catalyzes a critical step in the assembly of multi-heme c -type cytochromes, we further investigated the role of extracellular electron transfer cytochromes in organic disulfide reduction. The results indicated that mutants lacking proteins in the Mtr system were severely impaired in their ability to reduce DTNB. These findings provide new insights into extracellular organic disulfide reduction and the enzymatic pathways of organic sulfur redox cycling. IMPORTANCE Organic sulfur compounds in soils and sediments are held together by disulfide bonds. This study investigates how Shewanella oneidensis breaks apart extracellular organic sulfur compounds. The results show that an enzyme involved in the assembly of c -type cytochromes as well as proteins in the Mtr respiratory pathway is needed for S. oneidensis to transfer electrons from the cell surface to extracellular organic disulfides. These findings have important implications for understanding how organic sulfur decomposes in terrestrial ecosystems., Competing Interests: The authors declare no conflict of interest.

Copper (Cu) is a cofactor in numerous key proteins and, thus, an essential element for life. In biological systems, Cu isotope abundances shift with metabolic and homeostatic state. However, the mechanisms underpinning these isotopic shifts remain poorly understood, hampering use of Cu isotopes as biomarkers. Computational predictions suggest that isotope fractionation occurs when proteins bind Cu, with the magnitude of this effect dependent on the identity and arrangement of the coordinating amino acids. This study sought to constrain equilibrium isotope fractionation values for Cu bound by common amino acids at protein metal-binding sites. Free and bound metal ions were separated via Donnan dialysis using a cation-permeable membrane. Isotope ratios of pre- and post-dialysis solutions were measured by MC-ICP-MS following purification. Sulfur ligands (cysteine) preferentially bound the light isotope ( 63 Cu) relative to water (Δ 65 Cu complex-free  = - 0.48 ± 0.18‰) while oxygen ligands favored the heavy isotope ( 65 Cu; + 0.26 ± 0.04‰ for glutamate and + 0.16 ± 0.10‰ for aspartate). Binding by nitrogen ligands (histidine) imparted no isotope effect (- 0.01 ± 0.04‰). This experimental work unequivocally demonstrates that amino acids differentially fractionate Cu isotopes and supports the hypothesis that metalloprotein biosynthesis affects the distribution of transition metal isotopes in biological systems., (© 2024. The Author(s).)

Introduction: Pulmonary infections, such as tuberculosis, can result in numerous pleural complications including empyemas, pneumothoraces with broncho-pleural fistulas, and persistent air leak (PAL). While definitive surgical interventions are often initially considered, management of these complications can be particularly challenging if a patient has an active infection and is not a surgical candidate., Case Presentation: Autologous blood patch pleurodesis and endobronchial valve placement have both been described in remedying PALs effectively and safely. PALs due to broncho-pleural fistulas in active pulmonary disease are rare, and we present two such cases that were managed with autologous blood patch pleurodesis and endobronchial valves., Conclusion: The two cases presented illustrate the complexities of PAL management and discuss the treatment options that can be applied to individual patients., (© 2024 S. Karger AG, Basel.)

Rates of both violent victimization and violence perpetration are known to be elevated among individuals with mental illness compared with those in the general population, though the relative risk of each outcome is less well established. In this systematic review, PubMed, Embase, Web of Science, PsycINFO, and Criminal Justice Abstracts were searched for articles published any time before October 2021 that reported the prevalence or incidence of both violent victimization and perpetration. We performed two searches to identify studies using samples or cohorts of (1) persons with mental illnesses and (2) persons in the general population. A total of 25 studies (9 examining persons with mental illnesses, 13 examining persons in the general population, and 3 examining both sample/cohort types) were identified and data was extracted to describe the type and size of cohort or sample, definitions and terminology (i.e., mental illness, violence victimization, violence perpetration), data source(s), observation period, prevalence/incidence of victimization, and prevalence/incidence of perpetration. The Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data was used to conduct a quality assessment of all included studies. Due to marked study heterogeneity, results were presented using a narrative synthesis approach. Across studies, findings were mixed, and the methodological approaches varied greatly. Broadly, the review provides evidence for (1) higher rates of victimization than perpetration for both individuals with mental illness and those in the general population and (2) higher rates of both victimization and perpetration for those with mental illness compared to those in the general population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.