Two-stage conversion of syngas and pyrolysis aqueous condensate into L-malate.

Hybrid thermochemical-biological processes have the potential to enhance the carbon and energy recovery from organic waste. This work aimed to assess the carbon and energy recovery potential of multifunctional processes to simultaneously sequestrate syngas and detoxify pyrolysis aqueous condensate (PAC) for short-chain carboxylates production. To evaluate relevant process parameters for mixed culture co-fermentation of syngas and PAC, two identical reactors were run under mesophilic (37 °C) and thermophilic (55 °C) conditions at increasing PAC loading rates. Both the mesophilic and the thermophilic process recovered at least 50% of the energy in syngas and PAC into short-chain carboxylates. During the mesophilic syngas and PAC co-fermentation, methanogenesis was completely inhibited while acetate, ethanol and butyrate were the primary metabolites. Over 90% of the amplicon sequencing variants based on 16S rRNA were assigned to Clostridium sensu stricto 12. During the thermophilic process, on the other hand, Symbiobacteriales, Syntrophaceticus, Thermoanaerobacterium, Methanothermobacter and Methanosarcina likely played crucial roles in aromatics degradation and methanogenesis, respectively, while Moorella thermoacetica and Methanothermobacter marburgensis were the predominant carboxydotrophs in the thermophilic process. High biomass concentrations were necessary to maintain stable process operations at high PAC loads. In a second-stage reactor, Aspergillus oryzae converted acetate, propionate and butyrate from the first stage into L-malate, confirming the successful detoxification of PAC below inhibitory levels. The highest L-malate yield was 0.26 ± 2.2 molL-malate/molcarboxylates recorded for effluent from the mesophilic process at a PAC load of 4% v/v. The results highlight the potential of multifunctional reactors where anaerobic mixed cultures perform simultaneously diverse process roles, such as carbon fixation, wastewater detoxification and carboxylates intermediate production. The recovered energy in the form of intermediate carboxylates allows for their use as substrates in subsequent fermentative stages.

The effects of synthesis gas feedstocks and oxygen perturbation on hydrogen production by Parageobacillus thermoglucosidasius.

BACKGROUND: The facultatively anaerobic thermophile Parageobacillus thermoglucosidasius is able to produce hydrogen gas (H2) through the water-gas shift (WGS) reaction. To date this process has been evaluated under controlled conditions, with gas feedstocks comprising carbon monoxide and variable proportions of air, nitrogen and hydrogen. Ultimately, an economically viable hydrogenogenic system would make use of industrial waste/synthesis gases that contain high levels of carbon monoxide, but which may also contain contaminants such as H2, oxygen (O2) and other impurities, which may be toxic to P. thermoglucosidasius. RESULTS: We evaluated the effects of synthesis gas (syngas) mimetic feedstocks on WGS reaction-driven H2 gas production by P. thermoglucosidasius DSM 6285 in small-scale fermentations. Improved H2 gas production yields and faster onset towards hydrogen production were observed when anaerobic synthetic syngas feedstocks were used, at the expense of biomass accumulation. Furthermore, as the WGS reaction is an anoxygenic process, we evaluated the influence of O2 perturbation on P. thermoglucosidasius hydrogenogenesis. O2 supplementation improved biomass accumulation, but reduced hydrogen yields in accordance with the level of oxygen supplied. However, H2 gas production was observed at low O2 levels. Supplementation also induced rapid acetate consumption, likely to sustain growth. CONCLUSION: The utilisation of anaerobic syngas mimetic gas feedstocks to produce H2 and the relative flexibility of the P. thermoglucosidasius WGS reaction system following O2 perturbation further supports its applicability towards more robust and continuous hydrogenogenic operation.

Prolonged use of nomegestrol acetate and risk of intracranial meningioma: a population-based cohort study.

Background: Nomegestrol acetate (NOMAC) is a synthetic potent progestogen. This study aimed to assess the risk of intracranial meningioma associated with the prolonged use of NOMAC. Methods: Observational cohort study using SNDS data (France). Women included had ≥ one dispensing of NOMAC between 2007 and 2017 (no dispensing in 2006). Exposure was defined as a cumulative dose >150 mg NOMAC within six months after first dispensing. A control group of women (cumulative dose ≤150 mg) was assembled. The outcome was surgery (resection or decompression) or radiotherapy for one or more intracranial meningioma(s). Poisson models assessed the relative risk (RR) of meningioma. Findings: In total, 1,060,779 women were included in the cohort (535,115 in the exposed group and 525,664 in the control group). The incidence of meningioma in the two groups was 19.3 and 7.0 per 100,000 person-years, respectively (age-adjusted RRa = 2.9 [2.4-3.7]). The RRa for a cumulative dose of more than 6 g NOMAC was 12.0 [9.9-16.0]. In the event of treatment discontinuation for at least one year, the risk of meningioma was identical to that in the control group (RRa = 1.0 [0.8-1.3]). The location of meningiomas in the anterior and middle part of the skull base was more frequent with exposure to NOMAC. Interpretation: We observed a strong dose-dependent association between prolonged use of NOMAC and the risk of intracranial meningiomas. These results are comparable to those obtained for cyproterone acetate, although the magnitude of the risk is lower. It is now recommended to stop using NOMAC if a meningioma is diagnosed. Funding: The French National Health Insurance Fund (Cnam) and the French National Agency for Medicines and Health Products Safety (ANSM) via the Health Product Epidemiology Scientific Interest Group EPI-PHARE.

Antimicrobial resistance in rural rivers: Comparative study of the Coquet (Northumberland) and Eden (Cumbria) River catchments.

Many studies have characterised resistomes in river microbial communities. However, few have compared resistomes in parallel rural catchments that have few point-source inputs of antimicrobial genes (ARGs) and organisms (i.e., AMR) - catchments where one can contrast more nebulous drivers of AMR in rural rivers. Here, we used quantitative microbial profiling (QMP) to compare resistomes and microbiomes in two rural river catchments in Northern England, the Coquet and Eden in Northumberland and Cumbria, respectively, with different hydrological and geographical conditions. The Eden has higher flow rates, higher annual surface runoff, and longer periods of soil saturation, whereas the Coquet is drier and has lower flowrates. QMP analysis showed the Eden contained significantly more abundant microbes associated with soil sources, animal faeces, and wastewater than the Coquet, which had microbiomes like less polluted rivers (Wilcoxon test, p < 0.01). The Eden also had greater ARG abundances and resistome diversity (Kruskal Wallis, p < 0.05), and higher levels of potentially clinically relevant ARGs. The Eden catchment had greater and flashier runoff and more extensive agricultural land use in its middle reach, which explains higher levels of AMR in the river. Hydrological and geographic factors drive AMR in rural rivers, which must be considered in environmental monitoring programmes.

Use of progestogens and the risk of intracranial meningioma: national case-control study.

OBJECTIVE: To assess the risk of intracranial meningioma associated with the use of selected progestogens. DESIGN: National case-control study. SETTING: French National Health Data System (ie, Système National des Données de Santé). PARTICIPANTS: Of 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls). MAIN OUTCOME MEASURES: Selected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma association. RESULTS: Mean age was 57.6 years (standard deviation 12.8). Analyses showed excess risk of meningioma with use of medrogestone (42 exposed cases/18 061 cases (0.2%) v 79 exposed controls/90 305 controls (0.1%), odds ratio 3.49 (95% confidence interval 2.38 to 5.10)), medroxyprogesterone acetate (injectable, 9/18 061 (0.05%) v 11/90 305 (0.01%), 5.55 (2.27 to 13.56)), and promegestone (83/18 061 (0.5%) v 225/90 305 (0.2 %), 2.39 (1.85 to 3.09)). This excess risk was driven by prolonged use (≥one year). Results showed no excess risk of intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. No conclusions could be drawn concerning dienogest or hydroxyprogesterone because of the small number of individuals who received these drugs. A highly increased risk of meningioma was observed for cyproterone acetate (891/18 061 (4.9%) v 256/90 305 (0.3%), odds ratio 19.21 (95% confidence interval 16.61 to 22.22)), nomegestrol acetate (925/18 061 (5.1%) v 1121/90 305 (1.2%), 4.93 (4.50 to 5.41)), and chlormadinone acetate (628/18 061 (3.5%) v 946/90 305 (1.0%), 3.87 (3.48 to 4.30)), which were used as positive controls for use. CONCLUSIONS: Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to increase the risk of intracranial meningioma. The increased risk associated with the use of injectable medroxyprogesterone acetate, a widely used contraceptive, and the safety of levonorgestrel intrauterine systems are important new findings.

Do Proton Pump Inhibitors Reduce Upper Gastrointestinal Bleeding in Older Patients with Atrial Fibrillation Treated with Oral Anticoagulants? A Nationwide Cohort Study in France.

BACKGROUND: Proton pump inhibitors (PPIs) are largely used in older adults and data are needed in off-label indications, such as the prevention of upper gastrointestinal bleeding (UGIB) in patients receiving oral anticoagulants (OACs). This study aimed to assess whether PPIs reduce the risk of UGIB in patients initiating oral anticoagulation. METHODS: We conducted a longitudinal study based on the French national health database. The study population included 109,693 patients aged 75-110 years with a diagnosis of atrial fibrillation who initiated OACs [vitamin K antagonist (VKA) or direct OAC (DOAC)] between 2012 and 2016. We used multivariable Cox models weighted by inverse of probability of treatment to estimate the adjusted hazard ratio (aHR) of UGIB between PPI users and nonusers over a 6- and 12-month follow-up. RESULTS: PPI users represented 23% of the study population (28% among VKA initiators and 17% among DOAC initiators). The mean age (83 ± 5.3 years) and proportion of women (near 60%) were similar between groups. The risk of UGIB in the first 6 months after initiation of OAC decreased by 20% in PPI users compared with PPI nonusers [aHR6 months = 0.80, 95% confidence interval (CI) 0.65-0.98], but was not significantly modified when the follow-up was extended to 12 months (aHR12 months = 0.90, 95% CI 0.76-1.07), with a stronger effect among patients treated with vitamin K antagonists (aHR6 months = 0.73, 95% CI 0.58-0.93; aHR12 months = 0.81, 95% CI 0.67-0.99). CONCLUSIONS: This study suggests that PPIs were associated with reduced risk of gastrointestinal bleeding after initiation of oral anticoagulation in older patients with atrial fibrillation, particularly within 6 months after initiation of an antivitamin K antagonist.

Caproate production from Enset fiber in one-pot two-step fermentation using anaerobic fungi (Neocallimastix cameroonii strain G341) and Clostridium kluyveri DSM 555.

BACKGROUND: Lignocellulosic biomass plays a crucial role in creating a circular bioeconomy and minimizing environmental impact. Enset biomass is a byproduct of traditional Ethiopian Enset food processing that is thrown away in huge quantities. This study aimed to produce caproate from Enset fiber using Neocallimastix cameroonii strain G341 and Clostridium kluyveri DSM 555 in one-pot two-step fermentation. RESULTS: The process started by growing N. cameroonii on Enset fiber as a carbon source for 7 days. Subsequently, the fungal culture was inoculated with active C. kluyveri preculture and further incubated. The results showed that N. cameroonii grew on 0.25 g untreated Enset fiber as the sole carbon source and produced 1.16 mmol acetate, 0.51 mmol hydrogen, and 1.34 mmol formate. In addition, lactate, succinate, and ethanol were detected in small amounts, 0.17 mmol, 0.08 mmol, and 0.7 mmol, respectively. After inoculating with C. kluyveri, 0.3 mmol of caproate and 0.48 mmol of butyrate were produced, and hydrogen production also increased to 0.95 mmol compared to sole N. cameroonii fermentation. Moreover, after the culture was supplemented with 2.18 mmol of ethanol during C. kluyveri inoculation, caproate, and hydrogen production was further increased to 1.2 and 1.36 mmol, respectively, and the consumption of acetate also increased. CONCLUSION: A novel microbial cell factory was developed to convert untreated lignocellulosic Enset fiber into the medium chain carboxylic acid caproate and H2 by a co-culture of the anaerobic fungi N. cameroonii and C. kluyveri. This opens a new value chain for Enset farmers, as the process requires only locally available raw materials and low-price fermenters. As the caproate production was mainly limited by the available ethanol, the addition of locally produced ethanol-containing fermentation broth ("beer") would further increase the titer.

Implementation of a clinical long-term follow-up database for adult childhood cancer survivors in Germany: a feasibility study at two specialised late effects clinics.

PURPOSE: Childhood cancer survivors (CCS) are at risk for increased morbidity and reduced quality of life associated with treatment-related late effects. In Germany, however, only a few of the more than 40,000 CCS registered in the German Childhood Cancer Registry (GCCR) currently benefit from adequate clinical long-term follow-up (LTFU) structures. To establish a comprehensive knowledge base on CCS' long-term health in Germany, a database was developed in cooperation with the GCCR. Following a first evaluation phase at two German university centres, this database will be implemented more widely within Germany allowing longitudinal documentation of clinical LTFU data. METHODS: The feasibility study cohort comprised 208 CCS aged 18 or older whose medical, mental and psychosocial health data were collected during routine LTFU or first clinic visits in adult care. CCS were enrolled from 04/2021 to 12/2022, and data entry was completed by 03/2023. Descriptive data analysis was conducted. All CCS were stratified into three risk groups (RG) based on their individual risk for developing late effects resulting from their respective diagnoses and treatments. RESULTS: Chronic health conditions of various organ systems associated with late and long-term effects of cancer therapy affected CCS in all RG supporting the clinical relevance of risk-adapted LTFU. Enrolment into the database was feasible and broadly accepted amongst CCS. CONCLUSION: Implementation of a clinical follow-up care infrastructure and database in Germany will pave the way to collect clinically evaluated and regularly updated health data of potentially over 40,000 German CCS and facilitate future national and international cooperation.

Reduction Pathway-Dependent Formation of Reactive Fe(II) Sites in Clay Minerals.

Structural Fe in clay minerals is an important, potentially renewable source of electron equivalents for contaminant reduction, yet our knowledge of how clay mineral Fe reduction pathways and Fe reduction extent affect clay mineral Fe(II) reactivity is limited. Here, we used a nitroaromatic compound (NAC) as a reactive probe molecule to assess the reactivity of chemically reduced (dithionite) and Fe(II)-reduced nontronite across a range of reduction extents. We observed biphasic transformation kinetics for all nontronite reduction extents of ≥5% Fe(II)/Fe(total) regardless of the reduction pathway, indicating that two Fe(II) sites of different reactivities form in nontronite at environmentally relevant reduction extents. At even lower reduction extents, Fe(II)-reduced nontronite completely reduced the NAC whereas dithionite-reduced nontronite could not. Our 57Fe Mössbauer spectroscopy, ultraviolet-visible spectroscopy, and kinetic modeling results suggest that the highly reactive Fe(II) entities likely comprise di/trioctahedral Fe(II) domains in the nontronite structure regardless of the reduction mechanism. However, the second Fe(II) species, of lower reactivity, varies and for Fe(II)-reacted NAu-1 likely comprises Fe(II) associated with an Fe-bearing precipitate formed during electron transfer from aqueous to nontronite Fe. Both our observation of biphasic reduction kinetics and the nonlinear relationship of rate constant and clay mineral reduction potential EH have major implications for contaminant fate and remediation.

Formate-induced CO tolerance and methanogenesis inhibition in fermentation of syngas and plant biomass for carboxylate production.

BACKGROUND: Production of monocarboxylates using microbial communities is highly dependent on local and degradable biomass feedstocks. Syngas or different mixtures of H2, CO, and CO2 can be sourced from biomass gasification, excess renewable electricity, industrial off-gases, and carbon capture plants and co-fed to a fermenter to alleviate dependence on local biomass. To understand the effects of adding these gases during anaerobic fermentation of plant biomass, a series of batch experiments was carried out with different syngas compositions and corn silage (pH 6.0, 32 °C). RESULTS: Co-fermentation of syngas with corn silage increased the overall carboxylate yield per gram of volatile solids (VS) by up to 29% (0.47 ± 0.07 g gVS-1; in comparison to 0.37 ± 0.02 g gVS-1 with a N2/CO2 headspace), despite slowing down biomass degradation. Ethylene and CO exerted a synergistic effect in preventing methanogenesis, leading to net carbon fixation. Less than 12% of the electrons were misrouted to CH4 when either 15 kPa CO or 5 kPa CO + 1.5 kPa ethylene was used. CO increased the selectivity to acetate and propionate, which accounted for 85% (electron equivalents) of all products at 49 kPa CO, by favoring lactic acid bacteria and actinobacteria over n-butyrate and n-caproate producers. Inhibition of n-butyrate and n-caproate production by CO happened even when an inoculum preacclimatized to syngas and lactate was used. Intriguingly, the effect of CO on n-butyrate and n-caproate production was reversed when formate was present in the broth. CONCLUSIONS: The concept of co-fermenting syngas and plant biomass shows promise in three aspects: by making anaerobic fermentation a carbon-fixing process, by increasing the yields of short-chain carboxylates (propionate and acetate), and by minimizing electron losses to CH4. Moreover, a model was proposed for how formate can alleviate CO inhibition in certain acidogenic bacteria. Testing the fermentation of syngas and plant biomass in a continuous process could potentially improve selectivity to n-butyrate and n-caproate by enriching chain-elongating bacteria adapted to CO and complex biomass.

Mixotrophic chain elongation with syngas and lactate as electron donors.

Feeding microbial communities with both organic and inorganic substrates can improve sustainability and feasibility of chain elongation processes. Sustainably produced H2 , CO2 , and CO can be co-fed to microorganisms as a source for acetyl-CoA, while a small amount of an ATP-generating organic substrate helps overcome the kinetic hindrances associated with autotrophic carboxylate production. Here, we operated two semi-continuous bioreactor systems with continuous recirculation of H2 , CO2 , and CO while co-feeding an organic model feedstock (lactate and acetate) to understand how a mixotrophic community is shaped during carboxylate production. Contrary to the assumption that H2 , CO2 , and CO support chain elongation via ethanol production in open cultures, significant correlations (p < 0.01) indicated that relatives of Clostridium luticellarii and Eubacterium aggregans produced carboxylates (acetate to n-caproate) while consuming H2 , CO2 , CO, and lactate themselves. After 100 days, the enriched community was dominated by these two bacteria coexisting in cyclic dynamics shaped by the CO partial pressure. Homoacetogenesis was strongest when the acetate concentration was low (3.2 g L-1 ), while heterotrophs had the following roles: Pseudoramibacter, Oscillibacter, and Colidextribacter contributed to n-caproate production and Clostridium tyrobutyricum and Acidipropionibacterium spp. grew opportunistically producing n-butyrate and propionate, respectively. The mixotrophic chain elongation community was more efficient in carboxylate production compared with the heterotrophic one and maintained average carbon fixation rates between 0.088 and 1.4 g CO2 equivalents L-1  days-1 . The extra H2 and CO consumed routed 82% more electrons to carboxylates and 50% more electrons to carboxylates longer than acetate. This study shows for the first time long-term, stable production of short- and medium-chain carboxylates with a mixotrophic community.

Benefits and Risks Associated With Continuation of Anti-Tumor Necrosis Factor After 24 Weeks of Pregnancy in Women With Inflammatory Bowel Disease : A Nationwide Emulation Trial.

BACKGROUND: Continuation of biologics for inflammatory disorders during pregnancy is still a difficult decision. Many women with inflammatory bowel diseases (IBDs) stop anti-tumor necrosis factor (anti-TNF) treatment after 24 weeks. OBJECTIVE: To evaluate the benefits and risks of anti-TNF continuation after 24 weeks of pregnancy for mothers with IBD and their offspring. DESIGN: Target trial emulation between 2010 and 2020. SETTING: Nationwide population-based study using the Système National des Données de Santé. PATIENTS: All pregnancies with birth exposed to anti-TNF between conception and 24 weeks of pregnancy in women with IBD. INTERVENTION: Continuation of anti-TNF after 24 weeks of pregnancy. MEASUREMENTS: Occurrence of maternal IBD relapse up to 6 months after pregnancy, adverse pregnancy outcomes, and serious infections in the offspring during the first 5 years of life was compared according to anti-TNF continuation after 24 weeks of pregnancy using inverse probability-weighted marginal models. RESULTS: A total of 5293 pregnancies were included; among them, anti-TNF treatment was discontinued before 24 weeks for 2890 and continued beyond 24 weeks for 2403. Continuation of anti-TNF was associated with decreased frequencies of maternal IBD relapse (35.8% vs. 39.0%; adjusted risk ratio [aRR], 0.93 [95% CI, 0.86 to 0.99]) and prematurity (7.6% vs. 8.9%; aRR, 0.82 [CI, 0.68 to 0.99]). No difference according to anti-TNF continuation was found regarding stillbirths (0.4% vs. 0.2%; aRR, 2.16 [CI, 0.64 to 7.81]), small weight for gestational age births (13.1% vs. 12.9%; aRR, 1.01 [CI, 0.88 to 1.17]), and serious infections in the offspring (54.2 vs. 50.2 per 1000 person-years; adjusted hazard ratio, 1.08 [CI, 0.94 to 1.25]). LIMITATION: Algorithms rather than clinical data were used to identify patients with IBD, pregnancies, and serious infections. CONCLUSION: Continuation of anti-TNF after 24 weeks of pregnancy appears beneficial regarding IBD activity and prematurity, while not affecting neonatal outcomes and serious infections in the offspring. PRIMARY FUNDING SOURCE: None.

Investigating the Processing Potential of Ethiopian Agricultural Residue Enset/Ensete ventricosum for Biobutanol Production.

The Enset plant is a potential food source for about 20 million Ethiopians. A massive amount of residual byproduct is discarded from traditional Ethiopian Enset food processing. This study shows a compositional analysis of Enset biomass and its use for biobutanol production. The Enset biomass was pretreated with 2% (w/v) NaOH or 2% (v/v) H2SO4 and subjected to enzymatic hydrolysis. The enzymatic hydrolysates were then fermented anaerobically by C. saccharoperbutylacetonicum DSM 14923. The majority of Enset biomass waste samples contained 36-67% cellulose, 16-20% hemicelluloses, and less than 6.8% lignin. In all alkali-pretreated Enset biomass samples, the enzyme converted 80-90% of the biomass to glucose within 24 h, while it took 60 h to convert 48-80% of the acid-pretreated Enset biomass. In addition, the alkali pretreatment method released more glucose than the acid pretreatment in all Enset biomass samples. After 72 h of ABE fermentation, 2.8 g/L acetone, 9.9 g/L butanol, and 1.6 g/L ethanol were produced from mixed Enset waste hydrolysate pretreated with alkali, achieving an ABE yield of 0.32 g/g and productivity of 0.2 g × L-1 × h-1, showing the first value of butanol produced from Enset biomass in the literature.

Fe(II) Induced Reduction of Incorporated U(VI) to U(V) in Goethite.

Over 60 years of nuclear activities have resulted in a global legacy of radioactive wastes, with uranium considered a key radionuclide in both disposal and contaminated land scenarios. With the understanding that U has been incorporated into a range of iron (oxyhydr)oxides, these minerals may be considered a secondary barrier to the migration of radionuclides in the environment. However, the long-term stability of U-incorporated iron (oxyhydr)oxides is largely unknown, with the end-fate of incorporated species potentially impacted by biogeochemical processes. In particular, studies show that significant electron transfer may occur between stable iron (oxyhydr)oxides such as goethite and adsorbed Fe(II). These interactions can also induce varying degrees of iron (oxyhydr)oxide recrystallization (<4% to >90%). Here, the fate of U(VI)-incorporated goethite during exposure to Fe(II) was investigated using geochemical analysis and X-ray absorption spectroscopy (XAS). Analysis of XAS spectra revealed that incorporated U(VI) was reduced to U(V) as the reaction with Fe(II) progressed, with minimal recrystallization (approximately 2%) of the goethite phase. These results therefore indicate that U may remain incorporated within goethite as U(V) even under iron-reducing conditions. This develops the concept of iron (oxyhydr)oxides acting as a secondary barrier to radionuclide migration in the environment.

Not All That Glitters Is Gold: The Paradox of CO-dependent Hydrogenogenesis in Parageobacillus thermoglucosidasius.

The thermophilic bacterium Parageobacillus thermoglucosidasius has recently gained interest due to its ability to catalyze the water gas shift reaction, where the oxidation of carbon monoxide (CO) is linked to the evolution of hydrogen (H2) gas. This phenotype is largely predictable based on the presence of a genomic region coding for a carbon monoxide dehydrogenase (CODH-Coo) and hydrogen evolving hydrogenase (Phc). In this work, seven previously uncharacterized strains were cultivated under 50% CO and 50% air atmosphere. Despite the presence of the coo-phc genes in all seven strains, only one strain, Kp1013, oxidizes CO and yields H2. The genomes of the H2 producing strains contain unique genomic regions that code for proteins involved in nickel transport and the detoxification of catechol, a by-product of a siderophore-mediated iron acquisition system. Combined, the presence of these genomic regions could potentially drive biological water gas shift (WGS) reaction in P. thermoglucosidasius.

Global Transcriptome Profile of the Oleaginous Yeast Saitozyma podzolica DSM 27192 Cultivated in Glucose and Xylose.

Unlike conventional yeasts, several oleaginous yeasts, including Saitozyma podzolica DSM 27192, possess the innate ability to grow and produce biochemicals from plant-derived lignocellulosic components such as hexose and pentose sugars. To elucidate the genetic basis of S. podzolica growth and lipid production on glucose and xylose, we performed comparative temporal transcriptome analysis using RNA-seq method. Approximately 3.4 and 22.2% of the 10,670 expressed genes were differentially (FDR < 0.05, and log2FC > 1.5) expressed under batch and fed batch modes, respectively. Our analysis revealed that a higher number of sugar transporter genes were significantly overrepresented in xylose relative to glucose-grown cultures. Given the low homology between proteins encoded by most of these genes and those of the well-characterised transporters, it is plausible to conclude that S. podzolica possesses a cache of putatively novel sugar transporters. The analysis also suggests that S. podzolica potentially channels carbon flux from xylose via both the non-oxidative pentose phosphate and potentially via the first steps of the Weimberg pathways to yield xylonic acid. However, only the ATP citrate lyase (ACL) gene showed significant upregulation among the essential oleaginous pathway genes under nitrogen limitation in xylose compared to glucose cultivation. Combined, these findings pave the way toward the design of strategies or the engineering of efficient biomass hydrolysate utilization in S. podzolica for the production of various biochemicals.

Carbon Monoxide Induced Metabolic Shift in the Carboxydotrophic Parageobacillus thermoglucosidasius DSM 6285.

Parageobacillus thermoglucosidasius is known to catalyse the biological water gas shift (WGS) reaction, a pathway that serves as a source of alternative energy and carbon to a wide variety of bacteria. Despite increasing interest in this bacterium due to its ability to produce biological hydrogen through carbon monoxide (CO) oxidation, there are no data on the effect of toxic CO gas on its physiology. Due to its general requirement of O2, the organism is often grown aerobically to generate biomass. Here, we show that carbon monoxide (CO) induces metabolic changes linked to distortion of redox balance, evidenced by increased accumulation of organic acids such as acetate and lactate. This suggests that P. thermoglucosidasius survives by expressing several alternative pathways, including conversion of pyruvate to lactate, which balances reducing equivalents (oxidation of NADH to NAD+), and acetyl-CoA to acetate, which directly generates energy, while CO is binding terminal oxidases. The data also revealed clearly that P. thermoglucosidasius gained energy and grew during the WGS reaction. Combined, the data provide critical information essential for further development of the biotechnological potential of P. thermoglucosidasius.

Oral anticoagulants and risk of acute liver injury in patients with nonvalvular atrial fibrillation: a propensity-weighted nationwide cohort study.

Insufficient real-world data on acute liver injury (ALI) risk associated with oral anticoagulants (OACs) exist in patients with nonvalvular atrial fibrillation (NVAF). Using the French national healthcare databases, a propensity-weighted nationwide cohort study was performed in NVAF patients initiating OACs from 2011 to 2016, considering separately those (1) with no prior liver disease (PLD) as main population, (2) with PLD, (3) with a history of chronic alcoholism. A Cox proportional hazards model was used to estimate the hazard ratio with 95% confidence interval (HR [95% CI]) of serious ALI (hospitalised ALI or liver transplantation) during the first year of treatment, for each non-vitamin K antagonist (VKA) oral anticoagulant (NOAC: dabigatran, rivaroxaban, apixaban) versus VKA. In patients with no PLD (N = 434,015), only rivaroxaban new users were at increased risk of serious ALI compared to VKA initiation (adjusted HR: 1.41 [1.05-1.91]). In patients with chronic alcoholism history (N = 13,173), only those initiating dabigatran were at increased risk of serious ALI compared to VKA (2.88 [1.74-4.76]) but an ancillary outcome suggested that differential clinical follow-up between groups might partly explain this association. In conclusion, this study does not suggest an increase of the 1-year risk of ALI in NOAC versus VKA patients with AF.

Time-Course Transcriptome of Parageobacillus thermoglucosidasius DSM 6285 Grown in the Presence of Carbon Monoxide and Air.

Parageobacillus thermoglucosidasius is a metabolically versatile, facultatively anaerobic thermophile belonging to the family Bacillaceae. Previous studies have shown that this bacterium harbours co-localised genes coding for a carbon monoxide (CO) dehydrogenase (CODH) and Ni-Fe hydrogenase (Phc) complex and oxidises CO and produces hydrogen (H2) gas via the water-gas shift (WGS) reaction. To elucidate the genetic events culminating in the WGS reaction, P. thermoglucosidasius DSM 6285 was cultivated under an initial gas atmosphere of 50% CO and 50% air and total RNA was extracted at ~8 (aerobic phase), 20 (anaerobic phase), 27 and 44 (early and late hydrogenogenic phases) hours post inoculation. The rRNA-depleted fraction was sequenced using Illumina NextSeq, v2.5, 1x75bp chemistry. Differential expression revealed that at 8 vs 20, 20 vs 27 and 27 vs 44 hours post inoculation, 2190, 2118 and 231 transcripts were differentially (FDR < 0.05) expressed. Cluster analysis revealed 26 distinct gene expression trajectories across the four time points. Of these, two similar clusters, showing overexpression at 20 relative to 8 hours and depletion at 27 and 44 hours, harboured the CODH and Phc transcripts, suggesting possible regulation by O2. The transition between aerobic respiration and anaerobic growth was marked by initial metabolic deterioration, as reflected by up-regulation of transcripts linked to sporulation and down-regulation of transcripts linked to flagellar assembly and metabolism. However, the transcriptome and growth profiles revealed the reversal of this trend during the hydrogenogenic phase.