Biology subjects

Neumann, A.

Publications and source records attributed to Neumann, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

A Multi-task Platform for Profiling Cognitive and Motivational Constructs in Humans and Nonhuman Primates

BackgroundUnderstanding the neurobiological substrates of psychiatric disorders requires comprehensive evaluations of cognitive and motivational functions in preclinical research settings. The translational validity of such evaluations will be supported by (1) tasks with high construct validity that are engaging and easy to teach to human and nonhuman participants, (2) software that enables efficient switching between multiple tasks in single sessions, (3) software that supports tasks across a broad range of physical experimental setups, and (4) by platform architectures that are easily extendable and customizable to encourage future optimization and development. New MethodWe describe the Multi-task Universal Suite for Experiments (M-USE), a software platform designed to meet these requirements. It leverages the Unity video game engine and C# programming language to (1) support immersive and engaging tasks for humans and nonhuman primates, (2) allow experimenters or participants to switch between multiple tasks within-session, (3) generate builds that function across computers, tablets, and websites, and (4) is freely available online with documentation and tutorials for users and developers. M-USE includes a task library with seven pre-existing tasks assessing cognitive and motivational constructs of perception, attention, working memory, cognitive flexibility, motivational and affective self-control, relational long-term memory, and visuo-spatial problem solving. ResultsM-USE was used to test NHPs on up to six tasks per session, all available as part of the Task Library, and to extract performance metrics for all major cognitive and motivational constructs spanning the Research Domain Criteria (RDoC) of the National Institutes of Mental Health. Comparison with Existing MethodsOther experiment design and control systems exist, but do not provide the full range of features available in M-USE, including a pre-existing task library for cross-species assessments; the ability to switch seamlessly between tasks in individual sessions; cross-platform build capabilities; license-free availability; and its leveraging of video-engine capabilities used to gamify tasks. ConclusionsThe new multi-task platform facilitates cross-species translational research for understanding the neurobiological substrates of higher cognitive and motivational functions.

animal behavior and cognition↗

bioRxiv2023

From microbial communities to regional biogeography: Unraveling patterns, determinants and the influence of bottom trawling in benthic microbiota

Microbial composition and diversity in marine sediments are shaped by environmental, biological, and anthropogenic processes that operate on different scales. However, our understanding of benthic microbial biogeography remains limited. Here, we study how benthic microbiota vary at a regional scale in the North Sea with sediment characteristics, temperature, organic matter content, shear bed stress and bottom trawling intensity, a prevalent industrial fishing practice which heavily impacts benthic ecosystems. Using 16S rDNA amplicon sequencing, we characterized benthic microbiota from the top centimeter of 349 sediment samples and used uni-and multivariate statistical models, accounting for spatial autocorrelation, to disentangle the effects of the different predictors. Fitted models demonstrate how the geographic interplay of different environmental anthropogenic drivers shapes the structure and functioning of benthic microbial communities. Sediment properties were the primary determinants, with diversity increasing with sediment permeability but at the same time increasing with mud content, highlighting different underlying processes. Alpha diversity also increased nonlinearly with total organic matter content and temperature and showed a more complex relationship with bottom shear stress but decreased with bottom trawling intensity. These trawling associated diversity changes were accompanied by shifts in functional groups related to energy metabolism. Specifically, with increasing trawling intensity, we observed a transition toward more aerobic heterotrophic and less denitrifying metabolism. Our findings provide first insights of benthic microbial biogeographic patterns on a large spatial scale and illustrate how anthropogenic activity such as bottom trawling may influence the distribution and abundances of microbes and overall benthic metabolism at macroecological scales.

ecology↗

bioRxiv2022

ASO targeting temperature-controlled RBM3 poison exon splicing prevents neurodegeneration in vivo

Neurodegenerative diseases are increasingly prevalent in the aging population, yet currently no disease-modifying treatments are available. Increasing the expression of the cold-shock protein, RBM3, through therapeutic hypothermia is remarkably neuroprotective, but cooling poses a health risk itself, strongly limiting its clinical application. Selective upregulation of RBM3 at normothermia thus holds immense therapeutic potential. Here we identify a poison exon within the RBM3 gene that is solely responsible for cold-induced RBM3 expression. Genetic removal or ASO-mediated manipulation of this exon yields high RBM3 levels independent of cooling. Notably, a single administration of ASO to exclude the poison exon, using FDA-approved chemistry, results in long-lasting increase of RBM3 expression in mouse brains. In prion-diseased mice, this treatment leads to remarkable neuroprotection, with prevention of neuronal loss and spongiosis despite high levels of prion protein. RBM3-inducing ASOs could thus broadly deliver protection in humans in conditions ranging from acute brain injury to Alzheimers disease. One sentence summaryInducing cold shock protein RBM3 by modulating its alternative splicing at normothermia is neuroprotective in vivo

molecular biology↗

bioRxiv2022

M1 selective muscarinic allosteric modulation enhances cognitive flexibility and effective salience in nonhuman primates

Acetylcholine (ACh) in cortical neural circuits mediates how selective attention is sustained in the presence of distractors and how flexible cognition adjusts to changing task demands. The cognitive domains of attention and cognitive flexibility might be differentially supported by the M1 muscarinic cholinergic sub-receptor. Understanding how M1 mechanisms support these cognitive subdomains is of highest importance for advancing novel drug treatments for conditions with altered attention and reduced cognitive control including Alzheimers disease or schizophrenia. Here, we tested this question by assessing how the subtype selective M1-receptor specific positive allosteric modulator (M1 PAM VU0453595) affects visual search and flexible reward-learning in nonhuman primates. We found that allosteric potentiation of the M1 receptor enhanced flexible learning performance by improving extra-dimensional set shifting, by reducing latent inhibition of previously experienced distractors, and by reducing response perseveration in the absence of adverse side effects. These pro-cognitive effects occurred in the absence of apparent changes of attentional performance during visual search. In contrast, non-selective ACh modulation using the acetylcholinesterase inhibitor donepezil improved attention during visual search at doses that did not alter cognitive flexibility and that already triggered gastrointestinal cholinergic side effects. These findings illustrate that M1 positive allosteric modulation enhances cognitive flexibility without affecting attentional filtering of distraction, consistent with M1 activity boosting the effective salience of relevant over irrelevant objects. These results suggest that M1 PAMs are versatile compounds for enhancing cognitive flexibility in disorders spanning schizophrenia and Alzheimers diseases. Statement of significanceMuscarinic receptors mediate the pro-cognitive effects of acetylcholine, but it has remained unclear whether they differentially affect the cognitive subfunctions of attentional filtering, set shifting, and learning. To clarify the functional specificity of M1 receptors, we assessed these diverse functions using a recently developed, highly selective M1 PAM. This M1 PAM caused domain-specific cognitive improvement of flexible learning and extra-dimensional set shifting, reduced perseverations and enhanced target recognition during learning without altering attentional filtering functions. These domain-specific improvement contrasted to effects of a non-selective acetylcholinesterase inhibitor that primarily enhanced attention and caused dose limiting adverse side effects. These results demonstrate domain-specific improvements of cognitive flexibility suggesting M1 PAMs are versatile compounds for treating cognitive deficits in schizophrenia and Alzheimers disease.

neuroscience↗

bioRxiv2022

Branch point evolution controls species-specific alternative splicing and regulates long term potentiation

Regulation and functionality of species-specific alternative splicing has remained enigmatic to the present date. Calcium/calmodulin-dependent protein kinase II{beta} (CaMKII{beta}) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific Camk2{beta} alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strengths during evolution globally renders constitutive exons alternative, thus providing a paradigm for cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9 we introduced a weaker human branch point into the mouse genome, resulting in human-like CAMK2B splicing in the brain of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point-controlled, species-specific alternative splicing with a fundamental function in learning and memory.

molecular biology↗

bioRxiv2022

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

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 co-fed to a fermenter to alleviate this dependence. 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{degrees}C). Co-fermentation of syngas with corn silage increased the overall carboxylate yield per gram of volatile solids (VS) by up to 44% (0.36 {+/-} 0.07 g gVS-1; in comparison to 0.23 {+/-} 0.04 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 86% (electron equivalents) of all products at 49 kPa CO, by favoring lactic acid bacteria and actinobacteria over n-butyrate and n-caproate producers. This happened even when an inoculum pre-acclimatized 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. The concept of co-fermenting syngas and plant biomass shows promise in two aspects: by making anaerobic fermentation a carbon-fixing process and by increasing the production of propionate and acetate. Testing the concept in a continuous process could improve selectivity to n-butyrate and n-caproate by enriching chain-elongating bacteria adapted to CO and complex biomass.

bioengineering↗

bioRxiv2022

Molecular mechanisms of long-term light adaptation of an extremophilic alga Cyanidioschyzon merolae

Oxygenic phototrophs have evolved a remarkable plethora of strategies to react to changes in light intensity and spectral range, which allows them to thrive in a wide range of environmental conditions. Varying light quality and quantity influences the balance between solar energy capture and utilisation in photosynthesis, affecting concomitantly the downstream processes of central carbon and nitrogen metabolism as well as cellular growth and division. Here, we performed a comprehensive analysis of the mechanisms of long-term photoacclimation of an extremophilic red alga Cyanidioschyzon merolae that grows in sulphuric hot springs at high temperatures and low pH. By using spectroscopic, confocal fluorescence microscopy, photosynthetic performance measurements and global transcriptome analyses, we identified several molecular mechanisms underlying the long-term adaptation of this acido-thermophilic red alga to varying light intensity and spectral quality. These include: (1) remodelling of the functional antenna size of both photosystems; (2) rearrangement of the PSB/PSII/PSI microdomains within thylakoids; (3) modulation of the photosynthetic performance parameters, especially at the level of non-photochemical quenching, and (4) transcriptional regulation of photosynthesis and its regulatory components as well as downstream metabolic pathways related to ROS detoxification, cell/organelle division, and central carbon and nitrogen metabolism. Such an intricate network of interplay between light-driven reactions and downstream metabolic pathways provides the necessary basis for maintaining the highest photosynthetic performance under light-limiting conditions.

plant biology↗

bioRxiv2021

Natural variation in gene expression and Zika virus susceptibility revealed by villages of neural progenitor cells

Variation in the human genome contributes to abundant diversity in human traits and vulnerabilities, but the underlying molecular and cellular mechanisms are not yet known, and will need scalable approaches to accelerate their recognition. Here, we advanced and applied an experimental platform that analyzes genetic, molecular, and phenotypic heterogeneity across cells from very many human donors cultured in a single, shared in vitro environment, with algorithms (Dropulation and Census-seq) for assigning phenotypes to individual donors. We used natural genetic variation and synthetic (CRISPR-Cas9) genetic perturbations to analyze the vulnerability of neural progenitor cells to infection with Zika virus. These analyses identified a common variant in the antiviral IFITM3 gene that regulated IFITM3 expression and explained most inter-individual variation in NPCs susceptibility to Zika virus infectivity. These and other approaches could provide scalable ways to recognize the impact of genes and genetic variation on cellular phenotypes. HIGHLIGHTSO_LIMeasuring cellular phenotypes in iPSCs and hPSC-derived NPCs from many donors C_LIO_LIEffects of donor sex, cell source, genetic and other variables on hPSC RNA expression C_LIO_LINatural genetic variation and synthetic perturbation screens both identify IFITM3 in NPC susceptibility to Zika virus C_LIO_LIA common genetic variant in IFITM3 explains most inter-individual variation in NPC susceptibility to Zika virus C_LI

genomics↗

bioRxiv2021

The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia

To study how the 22q11.2 deletion predisposes to psychiatric disease, we generated induced pluripotent stem cells from deletion carriers and controls, as well as utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Upon differentiation into neural progenitor cells, we found the deletion acted in trans to alter the abundance of transcripts associated with risk for neurodevelopmental disorders including Autism Spectrum Disorder. In more differentiated excitatory neurons, altered transcripts encoded presynaptic factors and were associated with genetic risk for schizophrenia, including common (per-SNP heritability p ({tau}c)= 4.2 x 10-6) and rare, loss of function variants (p = 1.29x10-12). These findings suggest a potential relationship between cellular states, developmental windows and susceptibility to psychiatric conditions with different ages of onset. To understand how the deletion contributed to these observed changes in gene expression, we developed and applied PPItools, which identifies the minimal protein-protein interaction network that best explains an observed set of gene expression alterations. We found that many of the genes in the 22q11.2 interval interact in presynaptic, proteasome, and JUN/FOS transcriptional pathways that underlie the broader alterations in psychiatric risk gene expression we identified. Our findings suggest that the 22q11.2 deletion impacts genes and pathways that may converge with risk loci implicated by psychiatric genetic studies to influence disease manifestation in each deletion carrier.

neuroscience↗

bioRxiv2021

Food interactions observed in a pharmacokinetic investigation comparing two marketed cold preparations (BNO1016 and ELOM-080) after administration to male beagle dogs

The cold remedies Sinupret extract (BNO 1016) and Gelomyrtol forte (ELOM-080) represent the two top-selling cold remedies in Germany nowadays. Whereas BNO 1016 is a typical immediate release coated tablet, ELOM-080 is an enteric-coated soft gelatin capsule. The latter formulation, however, is at risk of pharmacokinetic interactions affecting absorption especially in the case of concomitant food intake. In the present pilot study, we investigated the risk of a possible food effect on BNO 1016 in comparison to ELOM-080 in three male beagle dogs. Single doses of BNO 1016 and ELOM-80 at 80 mg/kg and 160 mg/kg, respectively, were administered under fasting and fed conditions according to a 4-period, 4-treatment within-design. Blood sampling took place until up to 30 h p.a. and plasma concentrations of gentiopicroside, verbenalin and from a further marker analyte (BNO 1016 analytes) as well as 1,8-cineole, limonene and perillic acid (ELOM-080 analytes) were determined. Pharmacokinetic parameters focusing on rate and extent of absorption were derived. BNO 1016 analytes demonstrated a homogenous course in all animals in both, the fasted and fed state. Pharmacokinetic characteristics of a typical immediate release drug formulation were observed for all analytes and a food effect could be ruled out. ELOM-080 analytes also showed a homogeneous picture in the fasted state. However, lag-times (tlag) of up to 2 h p.a. with corresponding tmax values of 3 to 4 h were observed, reflecting a longer gastric residence time of the formulation. In the fed state, ELOM-080 showed significant pharmacokinetic characteristics suggesting a clear food effect. A major observation was a double peak phenomenon that could be observed in two out of three dogs. Furthermore, lag-times of some analytes up to 3-4 h and corresponding tmax values of up to 6-8 h occurred. In contrast to BNO 1016, these findings suggest that, as with other enteric-coated formulations, there may be a significant risk for food effects with ELOM-080 also in humans.

pharmacology and toxicology↗

bioRxiv2021

Dose-dependent dissociation of pro-cognitive effects of donepezil on attention and cognitive flexibility in rhesus monkeys

BACKGROUNDDonepezil exerts pro-cognitive effects by non-selectively enhancing acetylcholine (ACh) across multiple brain systems. The brain systems that mediate pro-cognitive effects of attentional control and cognitive flexibility are the prefrontal cortex and the anterior striatum which have different pharmacokinetic sensitivities to ACh modulation. We speculated that these area-specific ACh profiles lead to distinct optimal dose-ranges for donepezil to enhance the cognitive domains of attention and flexible learning. METHODSTo test for dose-specific effects of donepezil on different cognitive domains we devised a multi-task paradigm for nonhuman primates (NHPs) that assessed attention and cognitive flexibility. NHPs received either vehicle or variable doses of donepezil prior to task performance. We measured donepezil intracerebral and how strong it prevented the breakdown of ACh within prefrontal cortex and anterior striatum using solid-phase-microextraction neurochemistry. RESULTSThe highest administered donepezil dose improved attention and made subjects more robust against distractor interference, but it did not improve flexible learning. In contrast, only a lower dose range of donepezil improved flexible learning and reduced perseveration, but without distractor-dependent attentional improvement. Neurochemical measurements confirmed a dose-dependent increase of extracellular donepezil and decreases in choline within the prefrontal cortex and the striatum. CONCLUSIONSThe donepezil dose for maximally improving attention functions differed from the dose range that enhanced cognitive flexibility despite the availability of the drug in the major brain systems supporting these cognitive functions. Thus, the non-selective acetylcholine esterase inhibitor donepezil inherently trades improvement in the attention domain for improvement in the cognitive flexibility domain at a given dose range.

pharmacology and toxicology↗

bioRxiv2021

A Kiosk Station for the Assessment of Multiple Cognitive Domains and Enrichment of Monkeys

BackgroundNonhuman primates (NHPs) are self-motivated to perform cognitive tasks on touchscreens in their animal housing setting. To leverage this ability, fully integrated hardware and software solutions are needed, that work within housing and husbandry routines while also spanning cognitive task constructs of the Research Domain Criteria (RDoC). New MethodWe describe a Kiosk Station (KS-1) that provides robust hardware and software solutions for running cognitive tasks in cage-housed NHPs. KS-1 consists of a frame for mounting flexibly on housing cages, a touchscreen animal interface with mounts for receptables, reward pumps and cameras, and a compact computer cabinet with an interface for controlling behavior. Behavioral control is achieved with a unity3D program that is virtual-reality capable, allowing semi-naturalistic visual tasks to assess multiple cognitive domains. ResultsKS-1 is fully integrated into the regular housing routines of monkeys. A single person can operate multiple KS-1s. Monkeys engage with KS-1 at high motivation and cognitive performance levels at high intra-individual consistency. Comparison with Existing MethodsKS-1 is optimized for flexible mounting onto standard apartment cage systems. KS-1 has a robust animal interface with options for gaze/reach monitoring. It has an integrated user interface for controlling multiple cognitive task using a common naturalistic object space designed to enhance task engagement. All custom KS-1 components are open-sourced. ConclusionsKS-1 is a versatile tool for cognitive profiling and enrichment of cage-housed monkeys. It reliably measures multiple cognitive domains which promises to advance our understanding of animal cognition, inter-individual differences and underlying neurobiology in refined, ethologically meaningful behavioral foraging contexts.

animal behavior and cognition↗

bioRxiv2020

Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills.

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts (N=2196-3798) within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall, verbal and non-verbal cognitive scores. The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that cord blood DNA methylation at single CpGs can predict cognitive skills and further studies are needed to confirm regional differences.

developmental biology↗

bioRxiv2020

Gender, race and parenthood impact academic productivity during the COVID-19 pandemic: from survey to action.

While the Coronavirus disease 2019 (COVID-19) pandemic is altering academia dynamics, those juggling remote work and domestic demands - including childcare - have already felt the impacts on productivity. Female authors are facing a decrease in papers submission rates since the beginning of the pandemic period. The reasons for this decline in women productivity need to be further investigated. Here we show the influence of gender, parenthood and race in academics productivity during the pandemic period, based on a survey answered by 3,345 Brazilian academics from various knowledge areas and research institutions. Findings revealed that male academics - especially childless ones - were the least affected group, whereas female academics, especially Black women and mothers, were the most impacted group. This scenario will leave long-term effects on the career progression of the most affected groups. The results presented here are crucial for the development of actions and policies that aim to avoid further deepening the gender gap in science. This particular situation we are facing during the pandemic demands institutional flexibility and academia should foster the discussion about actions to benefit Black scientists and academics with families in the post-pandemic scenario.

scientific communication and education↗

bioRxiv2020

Mapping genetic effects on cellular phenotypes with "cell villages"

Tens of thousands of genetic variants shape human phenotypes, mostly by unknown cellular mechanisms. Here we describe Census-seq, a way to measure cellular phenotypes in cells from many people simultaneously. Analogous to pooled CRISPR screens but for natural variation, Census-seq associates cellular phenotypes to donors genotypes by quantifying the presence of each donors DNA in cell "villages" before and after sorting or selection for cellular traits of interest. Census-seq enables population-scale cell-biological phenotyping with low cost and high internal control. We demonstrate Census-seq through investigation of genetic effects on the SMN protein whose deficiency underlies spinal muscular atrophy (SMA). Census-seq quantified and mapped effects of many common alleles on SMN protein levels and response to SMN-targeted therapeutics, including a common, cryptic non-responder allele. We provide tools enabling population-scale cell experiments and explain how Census-seq can be used to map genetic effects on diverse cell phenotypes. O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/174383v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@169bf4borg.highwire.dtl.DTLVardef@18dd9c0org.highwire.dtl.DTLVardef@1d30ca5org.highwire.dtl.DTLVardef@e35bf0_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LICensus-seq reveals how inherited genetic variation affects cell phenotypes C_LIO_LIGenetic analysis of cellular traits in cell villages of >100 donors C_LIO_LICharacterizing human alleles that shape SMN protein expression and drug responses C_LIO_LIDevelopment of protocols and software to enable cellular population genetics C_LI

genetics↗

bioRxiv2020

Simplicity in numbers: Implications of diversity for the community Bioturbation Potential (BPc)

The mobility of particles and solutes within aquatic sediment is substantially impacted by faunal bioturbation activities such as bioirrigation and sediment reworking. The non-quantitative community bioturbation potential (BPc) aims to estimate the potential of a given benthic community for bioturbation activities, based on the functional traits of the species within that community. We argue that in sufficiently diverse communities, the characteristics of individual species, expressed as traits scores, average each other out, and approach a universal constant. This enables to derive a simpler community bioturbation potential (BPs), which may be applied in cases when taxonomic expertise or trait data are not available. As a proof of concept, we evaluated a dataset of 84 benthos assemblages, and found a high degree of agreement of full BPc and simplified BPs.

ecology↗

bioRxiv2020

Alternative splicing coupled nonsense-mediated decay shapes the temperature-dependent transcriptome

Mammalian body temperature oscillates with the time of the day and is altered in diverse pathological conditions. We recently identified a body temperature-sensitive thermometer-like kinase, which alters SR protein phosphorylation and thereby globally controls alternative splicing (AS). AS can generate mRNA variants containing premature termination codons, which are degraded by nonsense-mediated decay (NMD). Here we show extensive coupling of body temperature-controlled AS to NMD, leading to global control of temperature-dependent gene expression (GE). Temperature-controlled NMD-inducing splicing events are evolutionarily conserved and pervasively found within RNA-binding proteins, including most SR proteins. NMD-inducing exons are essential for rhythmic GE of SR proteins and have a global role in establishing temperature-dependent rhythmic GE profiles, both, in mammals under circadian body temperature cycles and in plants in response to ambient temperature changes. Together, these data identify body temperature-driven AS-NMD as an evolutionary ancient, core clock-independent mechanism to generate rhythmic GE.

molecular biology↗

bioRxiv2020

Effect of Cysteine, Yeast Extract, pH Regulation and Gas Flow on Acetate and Ethanol Formation and Growth Profiles of Clostridium ljungdahlii Syngas Fermentation

The fermentation of synthesis gas, or syngas, which consists mainly of CO, CO2 and H2 by acetogenic bacteria has the potential to help in transitioning from a fossil-fuel-based to a renewable bio-economy. Clostridium ljungdahlii, one of such microorganisms, has as main fermentation products acetate and ethanol. Multiple research efforts have been directed towards understanding how the metabolism and the product formation of this, and other acetogenic bacteria, can be directed towards increasing productivities and yields; nonetheless, transferring those findings to a particular set-up can prove challenging. This study used a well-established and robust fed-batch fermentation system with C. ljungdahlii to look into the effects of different fermentation pH profiles, gas flow, and the supplementation with additional yeast extract or cysteine on growth, product formation ratios, yields, and productivities, as well as gas consumption. Neither yeast extract nor cysteine supplementation had a noticeable impact on cell growth, product formation or overall gas consumption. The lowering of the pH proved mainly detrimental, with decreased productivities and no improvement in ethanol ratios. The most notable shift towards ethanol was achieved by the combination of lowering both the pH and the gas flow after 24 h, but with the caveat of lower productivity. The obtained results, unexpected to some extent, highlight the necessity for a better understanding of the physiology and the metabolic regulation of acetogenic bacteria in order for this process to become more industrially relevant.

bioengineering↗