Weak Iron Oxidation by Sulfobacillus thermosulfidooxidans Maintains a Favorable Redox Potential for Chalcopyrite Bioleaching

Bioleaching is an emerging technology, describing the microbially assisted dissolution of sulfidic ores that provides a more environmentally friendly alternative to many traditional metal extraction methods, such as roasting or smelting. Industrial interest is steadily increasing and today, circa 15–20% of the world’s copper production can be traced back to this method. However, bioleaching of the world’s most abundant copper mineral chalcopyrite suffers from low dissolution rates, often attributed to passivating layers, which need to be overcome to use this technology to its full potential. To prevent these passivating layers from forming, leaching needs to occur at a low oxidation/reduction potential (ORP), but chemical redox control in bioleaching heaps is difficult and costly. As an alternative, selected weak iron-oxidizers could be employed that are incapable of scavenging exceedingly low concentrations of iron and therefore, raise the ORP just above the onset of bioleaching, but not high enough to allow for the occurrence of passivation. In this study, we report that microbial iron oxidation by Sulfobacillus thermosulfidooxidans meets these specifications. Chalcopyrite concentrate bioleaching experiments with S. thermosulfidooxidans as the sole iron oxidizer exhibited significantly lower redox potentials and higher release of copper compared to communities containing the strong iron oxidizer Leptospirillum ferriphilum. Transcriptomic response to single and co-culture of these two iron oxidizers was studied and revealed a greatly decreased number of mRNA transcripts ascribed to iron oxidation in S. thermosulfidooxidans when cultured in the presence of L. ferriphilum. This allowed for the identification of genes potentially responsible for S. thermosulfidooxidans’ weaker iron oxidation to be studied in the future, as well as underlined the need for new mechanisms to control the microbial population in bioleaching heaps

Multi-omics Reveals the Lifestyle of the Acidophilic, Mineral-Oxidizing Model Species Leptospirillum ferriphilum \u3csup\u3eT\u3c/sup\u3e

Leptospirillum ferriphilum plays a major role in acidic, metal-rich environments, where it represents one of the most prevalent iron oxidizers. These milieus include acid rock and mine drainage as well as biomining operations. Despite its perceived importance, no complete genome sequence of the type strain of this model species is available, limiting the possibilities to investigate the strategies and adaptations that Leptospirillum ferriphilum DSM 14647T (here referred to as Leptospirillum ferriphilumT) applies to survive and compete in its niche. This study presents a complete, circular genome of Leptospirillum ferriphilumT obtained by PacBio single-molecule real-time (SMRT) long-read sequencing for use as a high-quality reference. Analysis of the functionally annotated genome, mRNA transcripts, and protein concentrations revealed a previously undiscovered nitrogenase cluster for atmospheric nitrogen fixation and elucidated metabolic systems taking part in energy conservation, carbon fixation, pH homeostasis, heavy metal tolerance, the oxidative stress response, chemotaxis and motility, quorum sensing, and biofilm formation. Additionally, mRNA transcript counts and protein concentrations were compared between cells grown in continuous culture using ferrous iron as the substrate and those grown in bioleaching cultures containing chalcopyrite (CuFeS2). Adaptations of Leptospirillum ferriphilumT to growth on chalcopyrite included the possibly enhanced production of reducing power, reduced carbon dioxide fixation, as well as elevated levels of RNA transcripts and proteins involved in heavy metal resistance, with special emphasis on copper efflux systems. Finally, the expression and translation of genes responsible for chemotaxis and motility were enhanced. IMPORTANCE Leptospirillum ferriphilum is one of the most important iron oxidizers in the context of acidic and metal-rich environments during moderately thermophilic biomining. A high-quality circular genome of Leptospirillum ferriphilumT coupled with functional omics data provides new insights into its metabolic properties, such as the novel identification of genes for atmospheric nitrogen fixation, and represents an essential step for further accurate proteomic and transcriptomic investigation of this acidophile model species in the future. Additionally, light is shed on adaptation strategies of Leptospirillum ferriphilumT for growth on the copper mineral chalcopyrite. These data can be applied to deepen our understanding and optimization of bioleaching and biooxidation, techniques that present sustainable and environmentally friendly alternatives to many traditional methods for metal extraction

Bioleaching of Pyrite by Iron-Oxidizing Acidophiles under the Influence of Reactive Oxygen Species

After 24h of exposure to acidic media, pyrite generates reactive oxygen species (ROS). Freshly-crushed pyrite with grain sizes between 50-100 μm at a 5 % (w/v), pulp density generated 0.17 ± 0.01 mM H2O2, while 10% pyrite generated 0.29 ± 0.01 mM and 30 % pyrite generated approximately 0.83 ± 0.06 mM. These levels of H2O2 inhibit iron oxidation in iron-grown cells of AcidithiobacillusferrooxidansT but not in pyrite-grown cells. ROS originating from pyrite, which was incubated for 24 h in acidic medium, prohibited pyrite dissolution by iron-grown cells, while pyrite-grown cells were adapted to these concentrations of ROS. Periodical addition of 100 μM H2O2 to pyrite cultures inoculated with pyrite-grown cells did not lower iron dissolution as it was observed with iron-grown cells. By high throughput proteomics analysis, an increased expression of proteins related to oxidative stress management, iron-and sulfur oxidation systems, carbon fixation and biofilm formation was observed in biofilm cells grown on pyrite compared to iron-grown cells.</jats:p

Weak Iron Oxidation by Sulfobacillus thermosulfidooxidans Maintains a Favorable Redox Potential for Chalcopyrite Bioleaching

Bioleaching is an emerging technology, describing the microbially assisted dissolution of sulfidic ores that provides a more environmentally friendly alternative to many traditional metal extraction methods, such as roasting or smelting. Industrial interest is steadily increasing and today, circa 15–20% of the world’s copper production can be traced back to this method. However, bioleaching of the world’s most abundant copper mineral chalcopyrite suffers from low dissolution rates, often attributed to passivating layers, which need to be overcome to use this technology to its full potential. To prevent these passivating layers from forming, leaching needs to occur at a low oxidation/reduction potential (ORP), but chemical redox control in bioleaching heaps is difficult and costly. As an alternative, selected weak iron-oxidizers could be employed that are incapable of scavenging exceedingly low concentrations of iron and therefore, raise the ORP just above the onset of bioleaching, but not high enough to allow for the occurrence of passivation. In this study, we report that microbial iron oxidation by Sulfobacillus thermosulfidooxidans meets these specifications. Chalcopyrite concentrate bioleaching experiments with S. thermosulfidooxidans as the sole iron oxidizer exhibited significantly lower redox potentials and higher release of copper compared to communities containing the strong iron oxidizer Leptospirillum ferriphilum. Transcriptomic response to single and co-culture of these two iron oxidizers was studied and revealed a greatly decreased number of mRNA transcripts ascribed to iron oxidation in S. thermosulfidooxidans when cultured in the presence of L. ferriphilum. This allowed for the identification of genes potentially responsible for S. thermosulfidooxidans’ weaker iron oxidation to be studied in the future, as well as underlined the need for new mechanisms to control the microbial population in bioleaching heaps

Altered grey matter networks in young patients with MS at genetic risk for Alzheimer's disease [Abstract]

Background: The Apolipoprotein E (APOE) ε4 is the major susceptibility factor for cognitive impairment and Alzheimer’s disease. Cognitive decline is also a concern in patients with multiple sclerosis (MS). Whether APOE ε4 exerts an effect on brain structure and grey matter (GM) networks in MS patients that could potentiate the long-term cognitive disabilities is unclear. Moreover the description of the exact link between genetic markers and MR driven measures of brain integrity are of essential importance to study cognition in patients with MS and for interventions to prevent longitudinal deterioration. Methods: MS Patients with no immunomodulatory treatment were enrolled in the “Krankheitsbezogene Kompetenznetz Multiple Sclerosis (KKNMS)”. From this multicenter dataset 37 heterozygous APOE ε4 carriers (i.e. having the genotype ε3/ε4) and 37 non-carriers (ε3/ε3) were matched for demographics (mean age: 38.4±9.2 yrs, mean EDSS 1.23±0.99) from one site. A replication study was performed in a cohort (n=46) from a second site. Cortical thickness (CT) was derived from 3T MRI using FreeSurfer. GM connectivity networks were reconstructed from the CT correlation between the 68 regions of the Desikan-Killiany atlas. Cortical integrity and network connectivity -derived from graph theoretical approaches- were compared between the groups in both cohorts. Results corrected for multiple comparisons were considered (p< 0.05 FDR). Results: No regional or global cortical atrophy differences were attested between the two groups in both cohorts. In the network connectivity analysis a decreased local connectivity pattern (reduced transitivity, t=-3.24 p=0.008) was evident in APOE ε4 carriers. Regions with decreased connectivity were consistently seen in the medial part of the left temporal lobe. APOE ε4 status was further associated with raised whole brain connectivity, reflected by increased global efficiency (t=4.34 p=0.005) and reduced modularity (t=-2.84 p=0.02). This network pattern was shown in the frontal, parietal and lateral temporal associative cortices. The results were entirely replicated in the second cohort. Conclusion: We found that MS patients at genetic risk for cognitive decline have significant abnormalities of local GM networks and possibly compensatory increased long-range connectivity patterns. Chronic or focal neuroinflammation could lead to behaviourally relevant memory impairments in these patients through a specific break-down of the long-range paths

Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap

BACKGROUND AND OBJECTIVES: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS. METHODS: In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS). RESULTS: We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00-0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51-0.59], p < 0.001). DD gap significantly explained EDSS changes (B = 0.060 [0.038-0.082], p < 0.001), adding to BAG (ΔR2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change (r = 0.50 [0.39-0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (ΔR2 = 0.064, p < 0.001). DISCUSSION: The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression

Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis

Objective: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing–remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease. Methods: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy. For significant results (p &lt; 0.05), volumes of atrophic areas are reported. Results: We studied 135 MOGAD patients, 135 AQP4+NMOSD, 175 RRMS, and 144 healthy controls (HC). Compared with HC, MOGAD showed lower GM volumes in the temporal lobes, deep GM, insula, and cingulate cortex (75.79 cm3); AQP4+NMOSD in the occipital cortex (32.83 cm3); and RRMS diffusely in the GM (260.61 cm3). MOGAD showed more pronounced temporal cortex atrophy than RRMS (6.71 cm3), whereas AQP4+NMOSD displayed greater occipital cortex atrophy than RRMS (19.82 cm3). RRMS demonstrated more pronounced deep GM atrophy in comparison with MOGAD (27.90 cm3) and AQP4+NMOSD (47.04 cm3). In MOGAD, higher periventricular and cortical/juxtacortical lesions were linked to reduced temporal cortex, deep GM, and insula volumes. In RRMS, the diffuse GM atrophy was associated with lesions in all locations. AQP4+NMOSD showed no lesion/GM volume correlation. Interpretation: GM atrophy is more widespread in RRMS compared with the other two conditions. MOGAD primarily affects the temporal cortex, whereas AQP4+NMOSD mainly involves the occipital cortex. In MOGAD and RRMS, lesion-related tract degeneration is associated with atrophy, but this link is absent in AQP4+NMOSD. ANN NEUROL 2024;96:276–288

Young FSU Migrants in Germany: Educational Attainment and Early Labor Market Outcomes

This study analyzes the educational attainment and early labor market outcomes of young migrants from the Former Soviet Union (FSU) who arrived in Germany between 1989 and 1994. The results reveal that migrants have lower educational attainments than natives, and that within the group of migrants, Jewish migrants perform better than ethnic German migrants. A decomposition analysis reveals that this competitive edge can, for the most part, be explained by a higher socioeconomic background. In the labor market, migrants cannot compensate for their educational disadvantage and have poorer labor market outcomes than natives. The results of this study stress the importance of an early educational integration of migrants for a successful labor market integration in the long run.Diese Studie analysiert den Bildungserfolg und die Arbeitsmarktintegration von jungen Migranten aus der ehemaligen Sowjetunion, die zwischen 1989 und 1994 nach Deutschland eingewandert sind. Die Ergebnisse zeigen, dass Migranten einen geringeren Bildungserfolg als Einheimische haben. Innerhalb der Gruppe der Migranten aus der ehemaligen Sowjetunion sind jüdische Migranten erfolgreicher als (Spät-)Aussiedler. Eine Dekompositionsanalyse zeigt, dass dieser Vorsprung größtenteils durch den soziökonomischen Hintergrund erklärt werden kann. Auf dem Arbeitsmarkt können Migranten ihren Bildungsnachteil nicht ausgleichen und haben größere Probleme bei der Arbeitsmarktintegration als Einheimische

80 Improving Documentation of DNAR Decisions on the Acute Medical Take

Abstract Introduction The BMA, Resuscitation Council and Royal College of Nursing have set out clear guidelines on documentation of Resuscitation discussions and decisions.1 On the acute medical take documentation of these discussions and decisions can be unclear despite use of an electronic patient record (EPR). The aim of this audit was to improve documentation of Do Not Attempt Resuscitation (DNAR) decisions in EPR. Methods We listed patients admitted on the medical take over 1-week, looking at resuscitation status and the documentation of the DNAR decision. We then implemented a change to the format of the EPR treatment escalation plan (TEP) form. Prior to the change the DNAR form was behind the TEP form which had to be clicked on separately and was not mandatory to complete. After the intervention the DNAR decision was placed in a box on the front page of the TEP form to ensure that it was clear and accessible. Results Pre-intervention we reviewed 114 patients notes of which 94 were DNAR. Of these 94 only 17 (18%) had correctly documented DNAR decisions in EPR. Following the intervention we again looked at all admissions to the medical take over a 1-week period, out of 151 patients 75 were DNAR and of these 75 patients 29 had correctly documented DNAR forms. This shows an increase in the percentage of the DNAR decisions filled in from 18% to 39%. Conclusion The results show that although there has been an improvement in the number of DNAR decisions being documented there are still a large percentage of patients who do not have this correctly documented. We are designing further interventions to ensure that the DNAR documentation is marked as a mandatory part of the TEP form as well as educating around the importance of this documentation. </jats:sec