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Alternative Splicing Regulates the Physiological Adaptation of the Mouse Hind Limb Postural and Phasic Muscles to Microgravity

Muscle atrophy and fiber type alterations are well-characterized physiological adaptations to microgravity with both understood to be primarily regulated by differential gene expression (DGE). While microgravity-induced DGE has been extensively investigated, adaptations to microgravity due to alternative splicing (AS) have not been studied in a mammalian model. We sought to comprehensively elucidate the transcriptomic underpinnings of microgravity-induced muscle phenotypes in mice by evaluating both DGE and changes in AS due to extended spaceflight. Tissue sections and total RNA were isolated from the gastrocnemius and quadriceps, postural and phasic muscles of the hind limb, respectively, of 32-week-old female BALB/c mice exposed to microgravity or ground control conditions for nine weeks. Immunohistochemistry disclosed muscle type-specific physiological adaptations to microgravity that included i) a pronounced reduction in muscle fiber cross-sectional area in both muscles and ii) a prominent slow-to-fast fiber type transition in the gastrocnemius. RNA sequencing revealed that DGE and AS varied across postural and phasic muscle types with preferential employment of DGE in the gastrocnemius and AS in the quadriceps. Gene ontology analysis indicated that DGE and AS regulate distinct molecular processes. Various non-differentially expressed transcripts encoding musculoskeletal proteins (Tnnt3, Tnnt1, Neb, Ryr1, and Ttn) and muscle-specific RNA binding splicing regulators (Mbnl1 and Rbfox1) were found to have significant changes in AS that altered critical functional domains of their protein products. In striking contrast, microgravity-induced differentially expressed genes were associated with lipid metabolism and mitochondrial function. Our work serves as the first comprehensive investigation of coordinate changes in DGE and AS in large limb muscles across spaceflight. We propose that substantial remodeling of pre-mRNA by AS is a major component of transcriptomic adaptation of skeletal muscle to microgravity. The alternatively spliced genes identified here could be targeted by small molecule splicing regulator therapies to address microgravity-induced changes in muscle during spaceflight.

genomics↗

Symbiosis increases population size and buffers environmental fluctuations in a physiologically-structured model parameterized for thyasirid bivalves

Symbioses whereby one partner provisions a nutritional resource to the other may alter energy allocation towards reproduction and survival in the recipient partner, potentially impacting population dynamics. Asymbiotic thyasirid bivalves feed predominantly on free-living bacteria, which fluctuate in abundance due to seasonality-driven temperature variations. Symbiotic thyasirids are mixotrophs, gaining nutrients from free-living bacteria and symbiotic bacteria that they host on their enlarged gills. Symbiotic bacteria may function as an additional energy reserve for thyasirids, allowing the hosts to allocate more energy to reproduction. We hypothesize that, for symbiotic thyasirids, the symbionts are a nutritional source that mitigates resource limitation. Using Dynamic Energy Budget theory, we built a physiologically-structured population model assuming equal mortality rates in both species. We find that without seasonal fluctuations, symbiotic thyasirids have higher abundances than asymbiotic thyasirids since the symbionts increase reproduction. Both species have similar population sizes in fluctuating environments, suggesting different adaptations to seasonality: asymbiotic thyasirids have adapted their physiology, while symbiotic thyasirids have adapted through mixotrophy. Our results highlight the significance of linking individual energetics and life-history traits to population dynamics and are the first step to-wards understanding the role of symbioses in population and community dynamics.

ecology↗

Dynamic autonomic nervous system patterns differentiate human emotions and manifest in resting physiology

Whether activity in the autonomic nervous system differs during distinct emotions remains controversial. We obtained continuous multichannel recordings of autonomic nervous system activity in healthy adults during a video-based emotional reactivity task. Dimensionality reduction revealed five principal components in the autonomic time series data, and these modes of covariation differentiated periods of baseline from those of video-viewing. Unsupervised clustering of the principal component time series data uncovered separable autonomic states that distinguished among the five emotion-inducing trials. These autonomic states were also detected in baseline physiology but were intermittent and of smaller magnitude. Our results suggest the autonomic nervous system assembles dynamic activity patterns during emotions that are similar across people and are present even during undirected moments of rest. One Sentence SummaryDynamic autonomic patterns distinguish among emotions and are evident in resting physiology.

neuroscience↗

Physiologically distinct neurons within the ventrolateral periaqueductal gray are not defined by mu-opioid receptor expression but are differentially activated by persistent inflammation

The ventrolateral periaqueductal gray (vlPAG) is a key structure within the descending pain modulatory pathway and an important target for opioid-induced analgesia. This area contains heterogeneous neurons with respect to neurotransmitter and receptor expression so it is difficult to define vlPAG neurons that contribute to pain and analgesia. Characterization of intrinsic membrane properties of 371 vlPAG neurons from female and male Long-Evans rats identified 4 neuron types with distinct intrinsic firing patterns: Phasic, Tonic, Onset, and Random. Phasic and Tonic neurons comprise the majority of the neurons sampled. Mu-opioid receptor (MOR) expression was determined by the ability of the selective MOR agonist DAMGO to activate G protein-coupled inwardly-rectifying potassium channel (GIRK) currents. Opioid-sensitive and -insensitive neurons were observed within each neuron type in naive rats and in rats pretreated with Complete Freunds adjuvant in a hindpaw to produce persistent inflammation. The presence of low threshold spikes (LTS) did not correlate with MOR-mediated GIRK currents indicating that MOR expression alone does not define a physiologically distinct neuron type in the vlPAG. MOR activation inhibited firing in nearly all spontaneously active neurons, both in naive and persistent inflammation conditions. CFA-induced inflammation increased Fos expression at both acute (2 h) and persistent inflammation (5-7 d) time points. However, persistent, but not acute, inflammation selectively enhanced spontaneous firing and lowered firing thresholds of Phasic neurons which was maintained in the absence of synaptic inputs. Taken together, persistent inflammation selectively activates Phasic neurons, of which only a subset was opioid-sensitive. Significance statementIntrinsic membrane properties define separate vlPAG neurons types that are functionally important. Persistent, and not acute, inflammation selectively activates Phasic firing vlPAG neurons that are not defined by MOR expression. Although the vlPAG is known to contribute to the descending inhibition of pain, the activation of a single physiologically-defined neuron type in the presence of inflammation may represent a mechanism by which the vlPAG participates in descending facilitation of pain.

neuroscience↗

Separate physiological roles of specific and non-specific DNA binding of HU protein in Escherichia coli

Conserved in bacteria, the histone-like protein HU is crucial for genome organization and expression of many genes. It binds DNA regardless of the sequence and exhibits two binding affinities in vitro, low-affinity to any B-DNA (non-specific) and high-affinity to DNA with distortions like kinks and cruciforms (structure-specific), but the physiological relevance of the two binding modes needed further investigation. We validated and defined the three conserved lysine residues, K3, K18, and K83, in Escherichia coli HU as critical amino acid residues for both non-specific and structure-specific binding and the conserved proline residue P63 additionally for only the structure-specific binding. By mutating these residues in vivo, we showed that two DNA binding modes of HU play separate physiological roles. The DNA structure-specific binding, occurring at specific sites in the E. coli genome, promotes higher-order DNA structure formation, regulating the expression of many genes, including those involved in chromosome maintenance and segregation. The non-specific binding participates in numerous associations of HU with the chromosomal DNA, dictating chromosome structure and organization. Our findings underscore the importance of DNA structure in transcription regulation and promiscuous DNA-protein interactions in a dynamic organization of a bacterial genome.

molecular biology↗

Arabidopsis Topless-related 1 mitigates physiological damage and growth penalties of induced immunity

Transcriptional corepressors of the Topless family are important regulators of plant hormone and immunity signaling. The lack of a genome-wide profile of their chromatin associations limits understanding of transcriptional regulation in plant immune responses. Chromatin immunoprecipitation with sequencing (ChIP-seq) was performed on GFP-tagged Topless-related 1 (TPR1) expressed in Arabidopsis thaliana lines with and without constitutive immunity dependent on Enhanced Disease Susceptibility 1 (EDS1). RNA-seq profiling of pathogen-infected tpl/tpr mutants and assessments of growth and physiological parameters were employed to determine TPL/TPR roles in transcriptional immunity and defense homeostasis. TPR1 bound to promoter regions of ~1,400 genes and ~10% of the detected binding required EDS1 immunity signaling. A tpr1 tpl tpr4 (t3) mutant displayed mildly enhanced defense-related transcriptional reprogramming upon bacterial infection but not increased bacterial resistance. Bacteria or pep1 phytocytokine-challenged t3 plants exhibited, respectively, photosystem II dysfunction and exacerbated root growth inhibition. Transgenic expression of TPR1 restored the t3 physiological defects. We propose that TPR1 and TPL-family proteins function in Arabidopsis to reduce detrimental effects associated with activated transcriptional immunity.

plant biology↗

Natural variation in copper tolerance in Drosophila melanogaster is shaped by transcriptional and physiological changes in the gut

Increases in industrialization and anthropogenic activity have resulted in an increase of pollutants released into the environment. Of these pollutants, heavy metals such as copper are particularly concerning due to their bio-accumulative nature. Due to its highly heterogeneous distribution and its dual nature as an essential micronutrient and toxic element, the genetic basis of copper tolerance is likely shaped by a complex interplay of genetic and environmental factors. In this study, we utilized the natural variation present in multiple populations of Drosophila melanogaster collected across Europe to screen for variation in copper tolerance. We found that latitude and the degree of urbanization at the collection sites, rather than any other combination of environmental factors, were linked to copper tolerance. While previously identified copper-related genes were not differentially expressed in tolerant vs. sensitive strains, genes involved in metabolism, reproduction, and protease induction contributed to the differential stress response. Additionally, the greatest transcriptomic and physiological responses to copper toxicity were seen in the midgut; where we found that preservation of gut acidity is strongly linked to greater tolerance. Finally, we identified transposable element insertions likely to play a role in copper stress response. Overall, by combining genome-wide approaches with environmental association analysis, and functional analysis of candidate genes, our study provides a unique perspective on the genetic and environmental factors that shape copper tolerance in natural D. melanogaster populations, and identifies new genes, transposable elements and physiological traits involved in this complex phenotype.

evolutionary biology↗

PROGRAMMED AXON DEATH EXECUTOR SARM1 IS A MULTI-FUNCTIONAL NAD(P)ASE WITH PROMINENT BASE EXCHANGE ACTIVITY, ALL REGULATED BY PHYSIOLOGICAL LEVELS OF NMN, NAD, NADP AND OTHER METABOLITES

SARM1 is an NAD glycohydrolase and TLR adapter with an essential, prodegenerative role in programmed axon death (Wallerian degeneration). It has low basal NADase activity that becomes strongly activated by NAD precursor NMN. Very high levels of NAD oppose this activation, competing for the same allosteric site on SARM1s regulatory ARM domain. Injury or diseases that deplete axons of NMNAT2, an essential enzyme converting NMN to NAD, cause SARM1 activation. The resulting NAD degradation by SARM1, combined with loss of NAD synthesis by NMNAT2, causes rapid depletion of axonal NAD. This NAD loss is widely assumed to mediate axon death and is consequently a key focus for therapeutic strategies for axonopathies. However, like other NAD(P) glycohydrolases, SARM1 has additional enzyme activities whose contributions, consequences and regulation need to be fully understood. Here, we compare the multiple actions and regulation of recombinant human SARM1 with those of two other NAD(P) glycohydrolases, human CD38 and Aplysia californica ADP ribosyl cyclase. We find that SARM1 has the highest transglycosidation (base exchange) activity of these enzymes at neutral pH and with some bases this dominates NAD(P) hydrolysis and cyclisation. Moreover, like its NADase and NADPase reactions, SARM1-mediated base exchange at neutral pH is activated by increases in the NMN:NAD ratio, which we show for the first time can act in the presence of physiological levels of both metabolites. We establish that SARM1 base exchange is the most likely physiological source of calcium mobilizing agent NaADP, and potentially of other NAD(P) analogues, which could contribute to axon and cell death. We also identify regulatory effects of free pyridine bases, of NADP and of nicotinic acid riboside (NaR) on SARM1 that represent further therapeutic opportunities. These data will help to pinpoint which of the multiple functions of SARM1 is responsible for axon degeneration and how it can be optimally targeted to block axon degeneration in disease.

biochemistry↗

The most comprehensive annotation of the Krill transcriptome provides new insights for the study of physiological processes and environmental adaptation

The krill species Euphausia superba plays a critical role in the food chain of the Antarctic ecosystem, as the abundance of its biomass affects trophic levels both below it and above. Major changes in climate conditions observed in the Antarctic Peninsula region in the last decades have already altered the distribution of the krill population and its reproductive dynamics. A deeper understanding of the adaptation capabilities of this species, and of the molecular mechanisms behind it are urgently needed. The availability of a large body of RNA-seq assays gave us the opportunity to extend the current knowledge of the krill transcriptome, considerably reducing errors and redundancies. Our study covered the entire developmental process, from larval stages to adult individuals, providing information of central relevance for ecological studies. Here we describe the KrillDB2 database, a resource combining the latest annotation of the krill transcriptome with a series of analyses specifically targeting genes and molecular processes relevant to krill physiology. KrillDB2 provides in a single resource the most complete collection of experimental data and bioinformatic annotations: it includes an extended catalog of krill genes; an atlas of their expression profiles over all RNA-seq datasets publicly available; a study of differential expression across multiple conditions such as developmental stages, geographical regions, seasons, and sexes. Finally, it provides initial indications about non-coding RNAs, a class of molecules whose contribute to krill physiology has never been reported before.

ecology↗

A toolbox for studying cortical physiology in primates

Lesioning and neurophysiological studies have facilitated the elucidation of cortical functions and mechanisms of functional recovery following injury. Clinical translation of such studies is contingent on their employment in non-human primates (NHPs), yet tools for monitoring and modulating cortical physiology are incompatible with conventional NHP lesioning techniques. To address these challenges, we developed a toolbox demonstrated in seven macaques. We introduce the photothrombotic method to induce focal cortical lesions alongside a quantitative model for the design of lesion profiles based on experimental needs. Large-scale ([~]5 cm2) vascular and neural dynamics can be monitored and lesion induction can be validated in vivo with optical coherence tomography angiography and our electrocorticographic array, the latter of which also enables testing stimulation-based interventions. By combining optical and electrophysiological techniques in NHPs, we can enhance our understanding of cortical functions, investigate functional recovery mechanisms, integrate physiological and behavioral findings, and develop treatments for neurological disorders.

neuroscience↗

Physiological Magnesium Concentrations Increase Fidelity of Diverse Reverse Transcriptases from HIV-1, HIV-2, and Foamy Virus, but not MuLV or AMV

Reverse transcriptases (RTs) are typically assayed in vitro using optimized Mg2+ concentrations ([~]5-10 mM) several-fold higher than physiological cellular free Mg2+ ([~]0.5 mM). Analysis of fidelity using lacZ-based -complementation assays showed that tested HIV RTs, including HIV-1 from subtype B (HXB2-derived), HIV-2, subtype A/E, and several drug-resistant HXB2 derivatives all showed significantly higher fidelity using physiological Mg2+. This also occurred with prototype foamy virus (PFV) RT. In contrast, Moloney murine leukemia virus (MuLV) and avian myeloblastosis virus (AMV) RTs demonstrated equivalent fidelity in both low and high Mg2+. In 0.5 mM Mg2+, all RTs demonstrated {approx} equal fidelity, except for PFV RT which showed higher fidelity. A Next Generation Sequencing (NGS) approach that used barcoding to accurately determine mutation rates and profiles was used to examine the types of mutations made by HIV-1 (subtype B, wild type) in low (0.5 mM) and high (6 mM) Mg2+ with DNA or RNA that coded for lacZ. Unlike the -complementation assay, which is dependent on LacZ activity, the NGS assay scores mutations at all positions and of every type. Consistent with -complementation assays, a [~]4-fold increase in mutations was observed in high Mg2+. These findings help explain why HIV RT displays lower fidelity in vitro (with high Mg2+ concentrations) than other RTs (e.g., MuLV and AMV), yet cellular fidelity for these viruses is comparable. Establishing in vitro conditions that accurately represent RTs activity in cells is pivotal to determining the contribution of RT and other factors to the mutation profile observed with HIV.

biochemistry↗

The eyes have it: The pupillary light response as a physiological index of aphantasia, sensory and phenomenological imagery strength

The pupillary light response is an important automatic physiological response that optimises light reaching the retina. Recent work has shown that the pupil also adjusts in response to illusory brightness and a range of cognitive functions, however, it remains unclear what exactly drives these endogenous changes. Here we show that the imagery pupillary light response correlates with objective measures of sensory imagery strength. Further, the trial-by-trial phenomenological vividness of visual imagery is tracked by the imagery pupillary light response. We also demonstrated that there was no evidence for an imagery pupillary light response in a group of individuals without visual imagery (aphantasia), however, they did show perceptual pupil light responses and pupil dilation with larger cognitive load. Our results provide evidence that the pupillary light response indexes the sensory strength of visual imagery and also provides the first physiological validation of aphantasia.

neuroscience↗

High temporal resolution measurements of movement reveal novel early-life physiological decline in C. elegans.

Age-related physiological changes are most notable and best-studied late in life, while the nature of aging in early- or middle-aged individuals has not been explored as thoroughly. In C. elegans, studies of movement vs. age generally delineate three distinct phases: sustained, youthful movement; a discrete onset of rapidly progressing impairment; and gross immobility. We investigated whether this first period of early-life adult movement is simply a sustained "healthy" level of high function followed by a discrete "movement catastrophe" -- or whether there are early-life changes in movement that precede future physiological declines. To determine how movement varies during early adult life, we followed isolated individuals throughout life with a previously unachieved combination of duration and temporal resolution. By tracking individuals across the first six days of adulthood, we observed declines in movement starting as early as the first two days of adult life, as well as high interindividual variability in total daily movement. These findings suggest that movement is a highly dynamic behavior early in life, and that factors driving movement decline may begin acting as early as the first day of adulthood. Using simulation studies based on acquired data, we suggest that too infrequent sampling in common movement assays limits observation of early-adult changes in motility, and we propose feasible alternate strategies and a framework for designing assays with increased sensitivity for early movement declines.

animal behavior and cognition↗

Simultaneous Triple-Parametric Optical Mapping of Transmembrane Potential, Intracellular Calcium and NADH for Cardiac Physiology Assessment

Investigation of the complex relationships and dependencies of multiple cellular processes that govern cardiac physiology and pathophysiology requires simultaneous dynamic assessment of multiple parameters. In this study, we introduce triple-parametric optical mapping to simultaneously image metabolism, electrical excitation, and calcium signaling from the same field of view and demonstrate its application in the field of drug testing and cardiovascular research. We applied this metabolism-excitation-contraction coupling (MECC) methodology to test the effects of blebbistatin, 4-aminopyridine and verapamil on cardiac physiology. While blebbistatin and 4-aminopyridine alter multiple aspects of cardiac function suggesting off-target effects, the effects of verapamil were on-target and it altered only one of ten tested parameters. Triple-parametric optical mapping was also applied during ischemia and reperfusion; and we identified that metabolic changes precede the effects of ischemia on cardiac electrophysiology.

bioengineering↗

Reversing the miRNA -5p/-3p stoichiometry reveals physiological roles and targets of miR-140 miRNAs

The chondrocyte specific miR-140 miRNAs are necessary for normal endochondral bone growth in mice. miR-140 deficiency causes dwarfism and craniofacial deformity. However, the physiologically important targets of miR-140 miRNAs are still unclear. The miR-140 gene (Mir140) encodes three chondrocyte-specific microRNAs, miR-140-5p, derived from the 5 strand of primary miR-140, and miR140-3p.1 and -3p.2, derived from the 3 strand of primary miR-140. miR-140-3p miRNAs are ten times more abundant than miR-140-5p likely due to the non-preferential loading of miR-140-5p to Argonaute proteins. To differentiate the role of miR-140-5p and -3p miRNAs in endochondral bone development, two distinct mouse models, miR140-C>T, in which the first nucleotide of miR-140-5p was altered from cytosine to uridine, and miR140-CG, where the first two nucleotides of miR-140-3p were changed to cytosine and guanine, were created. These changes are expected to alter Argonaute protein loading preference of -5p and -3p to increase -5p loading and decrease -3p loading without changing the function of miR140-5p. These models presented a mild delay in epiphyseal development with delayed chondrocyte maturation. Using RNA-sequencing analysis of the two models, direct targets of miR140-5p, including Wnt11, were identified. Disruption of the predicted miR140-5p binding site in the 3 untranslated region of Wnt11 was shown to increase Wnt11 mRNA expression and caused a modest acceleration of epiphyseal development. These results show that the relative abundance of miRNA-5p and -3p can be altered by changing the first nucleotide of miRNAs in vivo, and this method can be useful to identify physiologically important miRNA targets.

genetics↗

Intestinal Transgene Delivery with Native E. coli Chassis Allows Persistent Physiological Changes

Live bacterial therapeutics (LBT) could reverse disease by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally-raised (CR) hosts have been unsuccessful, because engineered microbial organisms (i.e., chassis) cannot colonize the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli isolated from stool cultures of CR mice were modified to express functional bacterial (bile salt hydrolase) and eukaryotic (Interleukin-10) genes. Reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect host physiology and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to "knock-in" specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts, and enables LBT with curative intent.

synthetic biology↗

Impact of pre-anthesis drought stress on physiology, yield-related traits and drought responsive genes in green super rice

Optimum soil water availability is vital for maximum yield production in rice which is challenged by increasing spells of drought. The reproductive stage drought is among the main limiting factors leading to the drastic reduction in grain yield. Objective of this study was to investigate the molecular and morpho-physiological responses of pre-anthesis stage drought stress in green super rice. The study assessed the performance of 26 rice lines under irrigated and drought conditions. Irrigated treatment was allowed to grow normally while drought stress was imposed for 30 days at pre-anthesis stage. Three important physiological traits including pollen fertility percentage (PFP), cell membrane stability (CMS) and normalized difference vegetative index (NDVI) were recorded at anthesis stage during the last week of drought stress. Agronomic traits of economic importance including grain yield were recorded at maturity stage. The analysis of variance demonstrated significant variation among the genotypes for most of the studied traits. Correlation and principal component analyses demonstrated highly significant associations of particular agronomic traits with grain yield, and genetic diversity among genotypes, respectively. Our study demonstrated a higher drought tolerance potential of GSR lines compared to local cultivars, mainly by higher pollen viability, plant biomass, CMS, and harvest index under drought. In addition, the molecular basis of drought tolerance in GSR lines was related to upregulation of certain drought responsive genes including OsSADRI, OsDSM1, and OsDT11. Our study identified novel drought tolerance related genes (OsDRG-1, OsDRG-2, OsDRG-3 and OsDRG-4) that could be further characterized using reverse genetics to be utilized in molecular breeding for drought tolerance.

plant biology↗

Physiological roles of short-chain and long-chain menaquinones (vitamin K2) in Lactococcus cremoris

Lactococcus cremoris and L. lactis are well-known for their occurrence and applications in dairy fermentations, but their niche extends to a range of natural and food production environments. L. cremoris and L. lactis produce MKs (vitamin K2), mainly as the long-chain forms represented by MK-9 and MK-8, and a detectable amount of short-chain forms represented by MK-3. The physiological significance of the different MK forms in the lifestyle of these bacterial species has not been investigated extensively. In this study, we used L. cremoris MG1363 to construct mutants producing different MK profiles by deletion of genes encoding (i) a menaquinone-specific isochorismate synthase, (ii) a geranyltranstransferase and (iii) a prenyl diphosphate synthase. These gene deletions resulted in (i) a non-MK producer ({Delta}menF), (ii) a presumed MK-1 producer ({Delta}ispA) and (iii) a MK-3 producer ({Delta}llmg_0196), respectively. By examining the phenotypes of the MG1363 wildtype strain and respective mutants, including biomass accumulation, stationary phase survival, oxygen consumption, primary metabolites, azo dye/copper reduction, and proteomes, under aerobic, anaerobic and respiration-permissive conditions, we could infer that short-chain MKs like MK-1 and MK-3 are preferred to mediate extracellular electron transfer and reaction with extracellular oxygen, while the long-chain MKs like MK-9 and MK-8 are more efficient in aerobic respiratory electron transport chain. The different electron transfer routes mediated by short-chain and long-chain MKs likely support growth and survival of L. cremoris in a range of (transiently) anaerobic and aerobic niches including food fermentations, highlighting the physiological significance of diverse MKs in L. cremoris.

microbiology↗