Biology subjects

Ahrens, C.

Publications and source records attributed to Ahrens, C..

8 recordsLinked to original sources

bioRxiv2026

Shared mechanisms of dopamine and ATP transmission in the nucleus accumbens

Dopamine (DA) neurons of the midbrain project throughout the striatum, including the nucleus accumbens core (NAc) and are thought to co-release ATP with DA from vesicles. The mechanisms of evoked NAc ATP release and clearance and their relationship to exocytotic DA transmission are largely unexplored and the focus of the present work. Using fast scan cyclic voltammetry (FSCV), we measured simultaneous ATP and DA transmission in response to pharmacological manipulations of release and reuptake cellular machinery. ATP transmission is tightly coupled to that of DA, though ATP release concentrations are typically smaller. Manipulations that increase DA transmission (increased release via 4-aminopyridine Kv channel blockade or decreased uptake via cocaine) also increase ATP transmission, though to a smaller extent. Blocking DA vesicular packaging (reserpine) or action potentials (lidocaine), results in attenuated DA and ATP release. Interestingly, reserpine or lidocaine can result in completely abolished DA release, but not a complete prevention in ATP release, suggesting a secondary source for ATP transmission thats not dependent on DA terminals. Both transmitters were reduced to a similar extent following nAChR blockade, demonstrating that nAChR activation regulates ATP in addition to DA. Surprisingly, cocaine inhibition of DATs reduced clearance for both ATP and DA, which correlated with one another when cocaine concentration was highest. There was also a strong relationship between the effect of cocaine on release of ATP and DA. As the first FSCV study to examine evoked NAc ATP release, this paper bridges prior work to confirm the strong association between ATP and DA in the mesolimbic circuit and identifies unexpected overlap in mechanisms regulating their transmission. Our results contribute novel evidence of both vesicular and non-vesicular ATP release in the NAc and demonstrate that extracellular ATP is a modulator of DA terminal function.

neuroscience↗

bioRxiv2026

Low levels of metabolic auxotrophy among environmental Pseudomonas isolates

Auxotrophy, the inability of bacteria to synthesize one or multiple essential metabolites (e.g. amino acids, vitamins, metabolites) is thought to be common among bacteria. However, studies often rely either on bioinformatic tools to predict auxotrophies from genome data or on experiments with low numbers of strains. Here, we combine experimental and bioinformatic approaches to assess amino acid auxotrophy levels among 315 co-isolated natural Pseudomonas strains from pond and soil habitats. Both approaches revealed that Pseudomonas isolates are predominantly prototrophs. We identified one single histidine auxotroph and five non-specific auxotrophs featuring complex growth phenotypes incompatible with single amino acid auxotrophies. While different bioinformatic pipelines vary in the extent to which auxotrophy is over- or underestimated, none of the pipelines could resolve the basis of non-specific auxotrophies. Our analysis further revealed the existence of multiple alternative biosynthesis pathways for methionine, proline, and phenylalanine, with significant enrichments of specific pathways among soil or pond strains. We conclude that combining experiments with bioinformatics is a powerful approach to assess the metabolic potential of environmental bacteria. Moreover, taxa like Pseudomonas can be predominantly prototrophic possibly owing to their generalist lifestyle, thus calling for nuanced ecological concepts predicting auxotrophy levels based on lifestyle and habitat.

microbiology↗

bioRxiv2024

Chronic innate immune impairment and ZIKV persistence in the gastrointestinal tract during SIV infection in pigtail macaques

Mosquito borne flaviviruses, including dengue (DENV) and Zika (ZIKV) viruses, have caused global epidemics in areas with high HIV prevalence due to the expanded geographic range of arthropod vectors. Despite the occurrence of large flavivirus outbreaks in countries with high HIV prevalence, there is little knowledge regarding the effects of flavivirus infection in people living with HIV (PLWH). Here, we use a pigtail macaque model of HIV/AIDS to investigate the impact of simian immunodeficiency virus (SIV)-induced immunosuppression on ZIKV replication and pathogenesis. Early acute SIV infection induced expansion of peripheral ZIKV cellular targets and increased innate immune activation and peripheral blood mononuclear cells (PBMC) from SIV infected macaques were less permissive to ZIKV infection in vitro. In SIV-ZIKV co-infected animals, we found increased persistence of ZIKV in the periphery and tissues corresponding to alterations in innate cellular (monocytes, neutrophils) recruitment to the blood and tissues, decreased anti-ZIKV immunity, and chronic peripheral inflammatory and innate immune gene expression. Collectively, these findings suggest that untreated SIV infection may impair cellular innate responses and create an environment of chronic immune activation that promotes prolonged ZIKV viremia and persistence in the gastrointestinal tract. These results suggest that PLWH or other immunocompromised individuals could be at a higher risk for chronic ZIKV replication, which in turn could increase the timeframe of ZIKV transmission. Thus, PLWH are important populations to target during the deployment of vaccine and treatment strategies against ZIKV. Author SummaryFlaviviruses, including Zika virus (ZIKV), cause global epidemics in areas with high HIV prevalence. Yet questions remain as to whether ZIKV disease is altered during an immunocompromised state and the potential immune mechanisms contributing to enhanced disease. This is essential to our understanding of ZIKV disease in people living with HIV (PLWH). Here, we use a non-human primate (NHP) model of HIV/AIDS to investigate the impact of immune suppression on ZIKV replication and pathogenesis. The use of the NHP model was critical for the assessment of longitudinal specimens across tissues that are active sites of flavivirus replication and host immune responses. This study broadly demonstrates that ZIKV pathogenesis is altered and more persistent in states of immunosuppression. Collectively, this study suggests that in PLWH and immunocompromised individuals, other arboviruses, including dengue and West Nile viruses, could similarly alter pathogenesis and/or viral peristance in tissues. Furthermore, this study highlights the need to prioritize immunocompromised individuals in the design and rollout of vaccines against arboviral diseases.

immunology↗

bioRxiv2024

The Effects of Acute Coordinative vs. Acute Endurance Exercise on the Cortisol Concentration

BackgroundPhysical exercise interventions can cause neuroendocrine activation, which in turn increases salivary cortisol concentrations. Until now there have been no studies comparing endurance and coordinative exercise. ObjectiveThe purpose of this study was to examine the effects of these different interventions with an intraindividual comparison. Methods61 students between 18 and 30 years of age were included and first completed a coordinative exercise and one week later an endurance exercise of the same intensity and length which was self-set on the first day, with a maximum heart rate of 64 - 76% (HRmax) over a period of 15 min. To measure changes in the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, saliva samples were collected before (t1) and after exercise (t2 and t3). ResultsBaseline values of cortisol (t0) did not differ significantly between coordinative and endurance exercise, t(55) = .233, p = .816. Post hoc tests revealed that the cortisol values of the second coordinative vs. endurance time point, t(55) = 2.097, p = .040, d = .741, and third coordinative vs. endurance time point, t(55) = 3.004, p = .004, d = .735, differed significantly with large effect sizes. ConclusionThe results show for the first time that coordinative exercise produced a higher cortisol release than endurance exercise of the same intensity and duration. Interventions such as coordinative exercise require higher cognitive components resulting in stronger cortisol release than endurance exercise. Thus, the type of acute exercise is a psychophysiological factor in determining the neuroendocrine stress response. Key pointsCortisol is an important catabolic hormone when it comes to overtraining or burnout in an athlete. Our results show for the first time that acute coordinative exercise produces a higher cortisol release than endurance exercise of the same intensity and duration.

physiology↗

bioRxiv2023

Bacterial tolerance to host-exuded specialized metabolites structures the maize root microbiome

Plants exude specialized metabolites from their roots and these compounds are known to structure the root microbiome. However, the underlying mechanisms are poorly understood. We established a representative collection of maize root bacteria and tested their tolerance against benzoxazinoids, the dominant specialized and bioactive metabolites in the root exudates of maize plants. In vitro experiments revealed that benzoxazinoids inhibited bacterial growth in a strain- and compound-dependent manner. Tolerance against these selective antimicrobial compounds depended on bacterial cell wall structure. Further, we found that native root bacteria isolated from maize tolerated the benzoxazinoids better compared to non-host Arabidopsis bacteria. This finding suggests the adaptation of the root bacteria to the specialized metabolites of their host plant. Bacterial tolerance to 6-methoxy-benzoxazolin-2-one (MBOA), the most abundant and selective antimicrobial metabolite in the maize rhizosphere, correlated significantly with the abundance of these bacteria on benzoxazinoid-exuding maize roots. Thus, strain-dependent tolerance to benzoxazinoids largely explained the abundance pattern of bacteria on maize roots. Abundant bacteria generally tolerated MBOA, while low abundant root microbiome members were sensitive to this compound. Our findings reveal that tolerance to plant specialized metabolites is an important competence determinant for root colonization. We propose that bacterial tolerance to plant-secreted antimicrobial compounds is an underlying mechanism determining the structure of host-specific microbial communities. Significance StatementDiverse microbial communities colonize plant roots. They feed on carbon rich root exudates which contain a diverse mix of chemicals including primary and specialized metabolites. Here we show that specialized metabolites act as selective antibiotics to shape the root bacterial communities. By growing single isolates of maize root bacteria in the presence of benzoxazinoids in vitro, we find that the strains differ greatly in their tolerance to benzoxazinoids. Their different levels of tolerance largely explained their abundance on benzoxazinoid-exuding roots. Our work shows how plant specialized metabolites act to shape the maize root microbial community and thus deepened our mechanistic understanding of how plants shape their microbiome.

microbiology↗

bioRxiv2022

A replicon RNA vaccine induces durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned

The global SARS-CoV-2 pandemic prompted rapid development of COVID-19 vaccines. Although several vaccines have received emergency approval through various public health agencies, the SARS-CoV-2 pandemic continues. Emergent variants of concern, waning immunity in the vaccinated, evidence that vaccines may not prevent transmission and inequity in vaccine distribution have driven continued development of vaccines against SARS-CoV-2 to address these public health needs. In this report, we evaluated a novel self-amplifying replicon RNA vaccine against SARS-CoV-2 in a pigtail macaque model of COVID-19 disease. We found that this vaccine elicited strong binding and neutralizing antibody responses. While binding antibody responses were sustained, neutralizing antibody waned to undetectable levels after six months but were rapidly recalled and conferred protection from disease when the animals were challenged 7 months after vaccination as evident by reduced viral replication and pathology in the lower respiratory tract, reduced viral shedding in the nasal cavity and lower concentrations of pro-inflammatory cytokines in the lung. Cumulatively, our data demonstrate in pigtail macaques that a self-amplifying replicon RNA vaccine can elicit durable and protective immunity to SARS-CoV-2 infection. Furthermore, these data provide evidence that this vaccine can provide durable protective efficacy and reduce viral shedding even after neutralizing antibody responses have waned to undetectable levels.

immunology↗

bioRxiv2019

Posttranscriptional regulation of ribosomal and multiresistance genes by the bacterial leader peptide peTrpL

The ribosome-dependent attenuator located upstream of bacterial tryptophan biosynthesis genes harbors a small ORF trpL containing tryptophan codons. When tryptophan is available, efficient trpL translation causes transcription termination and release of the attenuator RNA rnTrpL. In Sinorhizobium meliloti, rnTrpL is a trans-acting sRNA. Here, we identified an evolutionary conserved function for the trpL-encoded 14-aa leader peptide peTrpL. Upon exposure to tetracycline, the cellular peTrpL levels were increased and rnTrpL was generated independently of tryptophan availability. Both peTrpL and rnTrpL were found to be involved in tetracycline-dependent destabilization of rplUrpmA mRNA encoding ribosomal proteins L21 and L27. We provide evidence for redirection of the sRNA rnTrpL from its antibiotic-independent target trpDC to rplUrpmA by formation of an antibiotic-dependent ribonucleoprotein complex (ARNP). ARNPs comprising peTrpL, rnTrpL, rplUrpmA and antisense RNA were also observed for other translation-inhibiting antibiotics, suggesting that bacteria evolved mechanisms to utilize antibiotics for mRNA destabilization.

microbiology↗

bioRxiv2019

The polyploid genome of the mitotic parthenogenetic root knot nematode Meloidogyne enterolobii

Root-knot nematodes (genus Meloidogyne) are plant parasitic species that cause huge economic loss in the agricultural industry and affect the prosperity of communities in developing countries. Control methods against these plant pests are sparse and the current preferred method is deployment of plant cultivars bearing resistance genes against Meloidogyne species. However, some species such as M. enterolobii are not controlled by the resistance genes deployed in the most important crop plants cultivated in Europe. The recent identification of this species in Europe is thus a major concern. Like the other most damaging Meloidogyne species (e.g. M. incognita, M. arenaria and M. javanica), M. enterolobii reproduces by obligatory mitotic parthenogenesis. Genomic singularities such as a duplicated genome structure and a relatively high proportion of transposable elements have previously been described in the above mentioned mitotic parthenogenetic Meloidogyne.\n\nTo gain a better understanding of the genomic and evolutionary background we sequenced the genome of M. enterolobii using high coverage short and long read technologies. The information contained in the long reads helped produce a highly contiguous genome assembly of M. enterolobii, thus enabling us to perform high quality annotations of coding and non-coding genes, and transposable elements.\n\nThe genome assembly and annotation reveals a genome structure similar to the ones described in the other mitotic parthenogenetic Meloidogyne, described as recent hybrids. Most of the genome is present in 3 different copies that show high divergence. Because most of the genes belong to these duplicated regions only few gene losses took place, which suggest a recent polyploidization. The most likely hypothesis to reconcile high divergence between genome copies despite few gene losses and translocations is also a recent hybrid origin. Consistent with this hypothesis, we found an abundance of transposable elements at least as high as the one observed in the mitotic parthenogenetic nematodes M. incognita and M. javanica.

genomics↗