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Peters, G.

Publications and source records attributed to Peters, G..

7 recordsLinked to original sources

THE ROLE OF LIQUID CRYSTAL ORDERING IN THE STRUCTURAL ORGANIZATION OF DNA IN BACTERIA.

This paper presents and critically reviews the results of original and some literature based experimental studies conducted by the authors last years on the structural organization of DNA in dormant (starvation stress), anabiotic dormant (4 HR treatment) E. coli cells, as well as the K12 {Delta}dps strain, which lacks the Dps protein (Dps null E. coli). The experimental data includes small-angle synchrotron radiation diffraction (SAXS) and transmission electron microscopy (TEM) data. Synchrotron radiation diffraction experiments on K12{Delta}dps cells allowed us to conclude that peaks at 44.3, 22.1, and 14.8 angstrom resolutions are associated exclusively with ordered DNA organization. Peaks at 44.3, 22.1, and 14.8 angstrom resolutions are also observed for samples of dormant (starvation stress) cells and anabiotically dormant cells. Therefore, this ordered DNA organization also applies to samples of dormant and anabiotically dormant cells. A model is proposed that considers the ordered DNA organization in the cell as a cholesteric liquid crystal. The powder diffraction pattern calculated based on this model is compared with experimental small angle X ray scattering (SAXS) data obtained on Dps-null cell samples. The model completely reproduces the key features of the experimental diffraction pattern from Dps-null cell samples. Accordingly, the cholesteric liquid crystal model corresponds to DNA packaging in dormant and anabiotically dormant cells. Cholesteric liquid crystal ordering should be further considered in all models of cellular DNA packaging. To address the question of which structural organization of DNA predominates in the cell: the cholesteric liquid crystal or nanocrystalline or whether they coexist and fully manifest themselves under different external conditions, it is necessary to utilize the latest methodological advances in structural analysis.

biophysics↗

Measles Whole Genome Sequencing by an Illumina Tiled Amplification Method

Measles virus remains a significant global health threat, and despite the availability of an effective vaccine, measles cases continue to increase worldwide in recent years. Genomic surveillance has become an essential tool for monitoring virus circulation and investigating outbreaks. Here, we describe a wet-laboratory method for whole-genome sequencing of measles virus using a tiled amplicon approach and Illumina sequencing technology. A previously published Oxford Nanopore-based tiled primer scheme was adapted to include both circulating measles genotypes and for use on the Illumina platform. Two Illumina library preparation kits, Illumina DNA Prep (IDP) and Nextera XT (XT), were evaluated for performance. The IDP kit demonstrated more complete genomes and consistent genome coverage compared with XT. Using quantified reference genomes, the limit of detection was determined to be 10,000 genome copies for genotype B3 and D8. Sequence accuracy was evaluated using previously characterized clinical samples and showed high concordance. This method provides a reliable and sensitive approach for measles virus whole-genome sequencing using Illumina platforms and is suitable for genomic surveillance applications.

genomics↗

Curcumin Alleviates Systemic Inflammation and Gut Dysbiosis Induced by Circadian Rhythm Disruption in a Rodent Model of Jet Lag

Circadian rhythm disruption is increasingly recognized as a systemic stressor that promotes immune dysregulation and gut microbial imbalance, processes implicated in a wide range of inflammatory and neurodegenerative diseases. However, therapeutic strategies targeting the gut-immune interface under conditions of circadian misalignment remain limited. Here, we investigated whether curcumin, a plant-derived polyphenol with known anti-inflammatory properties, mitigates inflammation and gut dysbiosis induced by severe circadian disruption in a rodent model of chronic jet lag Rats were subjected to repeated 12-hour inversions of the light-dark cycle and treated daily with curcumin (40 mg/kg/day) or vehicle delivered orally in almond butter. Circadian disruption significantly increased circulating proinflammatory cytokines and altered gut microbial composition. Curcumin treatment markedly reduced plasma levels of IFN-{gamma}, TNF-, IL-6, and CXCL1, decreased Peyers patch size, and partially restored circadian-regulated activity patterns. Shotgun metagenomic analysis revealed that curcumin shifted the gut microbiome toward a more eubiotic profile, characterized by increased species richness, reduced dominance of inflammatory taxa, decreased relative abundance of Proteobacteria, and increased Firmicutes, with a trend toward enrichment of Actinobacteria. Collectively, these findings demonstrate that curcumin attenuates systemic and intestinal inflammation associated with circadian rhythm disruption, likely through combined suppression of proinflammatory signaling and modulation of the gut microbiome. Despite its limited systemic bioavailability, curcumin exerted robust effects at the gut-immune interface, highlighting the microbiome as a critical therapeutic target for chronobiology-associated inflammatory disorders. These results support curcumin as a potentially promising chronoprotective intervention for conditions characterized by circadian misalignment, including shift work and jet lag.

animal behavior and cognition↗

Preparation and Characterization of Inactivated Tick-Borne Encephalitis Virus Samples for Single Particle Imaging at European XFEL

X-ray imaging of virus particles at European XFEL could eventually allow solving their complete structure, potentially approaching resolution of other structural virology methods. To achieve this ambitious goal with todays technologies, several mL of purified virus suspension containing at least 1012 particles per mL are required. Such large amounts of concentrated suspension have never before been obtained for enveloped viruses. Tick-borne encephalitis virus (TBEV) represents an attractive model system for the development of enveloped virus purification and concentration protocols, given the availability of large amounts of inactivated virus material provided by vaccine manufacturing facilities. Here we present the development of a TBEV vaccine purification and concentration scheme combined with a quality control protocol allowing substantial amounts of highly concentrated non-aggregated suspension to be obtained. Preliminary single particle imaging experiments were performed for this sample at European XFEL, showing distinct diffraction patterns.

biophysics↗

Identification of pre-existing microbiome and metabolic vulnerabilities to escalation of oxycodone self-administration and identification of a causal role of short-chain fatty acids in addiction-like behaviors.

The gut brain axis is thought to play a role in behavior and physiological responses through chemical, immunological, and metabolite signaling. Antibiotics, diet, and drugs can alter the transit time of gut contents as well as the makeup of the microbiome. Heterogeneity in genetics and environment are also well-known factors involved in the initiation and perpetuation of substance use disorders. Few viable genetic or biological markers are available to identify individuals who are at risk of escalating opioid intake. Primarily, the addiction field has focused on the nervous system, limiting the discovery of peripheral factors that contribute to addiction. To address this gap, we characterized the microbiome before and after drug exposure, and after antibiotics depletion in male and female heterogenous stock rats to determine if microbiome constituents are protective of escalation. We hypothesized that individuals that are prone to escalation of opioid self-administration will have distinct microbial and metabolic profiles. The fecal microbiome and behavioral responses were measured over several weeks of oxycodone self-administration and after antibiotic treatment. Antibiotic treatment reduces circulating short-chain fatty acids (SCFA) by depleting microbes that ferment fiber into these essential signaling molecules for the gut-brain axis. Depletion of the microbiome increased oxycodone self-administration in a subpopulation of animals (Responders). Supplementation of SCFAs in antibiotic depleted animals decreased elevated oxycodone self-administration. Phylogenetic functional analysis reveals distinct metabolic differences in the subpopulations of animals that are sensitive to antibiotic depletion and animals rescued by SCFA supplementation. In conclusion, this study identifies pre-existing microbiome and metabolic vulnerabilities to escalation of oxycodone self-administration, demonstrates that escalation of oxycodone self-administration dysregulates the microbiome and metabolic landscape, and identifies a causal role of short-chain fatty acids in addiction-like behaviors.

neuroscience↗

Dynamics of Human Serum Transferrin in Varying Physicochemical Conditions Explored by Using Molecular Dynamics Simulations

Conformational stability of human serum transferrin (Tf) at varying pH, salt, and excipient concentrations were investigated using molecular dynamics (MD) simulations and the results are compared with previously published small angle X-ray scattering (SAXS) experiments. SAXS study showed that at pH 5, Tf is predominantly present in partially open (PO) form, and the factions of PO differ based on the physicochemical condition and drifts towards closed form (HO) as the pH increases. Tf is a bilobal glycoprotein that is composed of homologous halves termed as N-lobe and C-lobe. The current study shows that the protonation of Y188 and K206 at pH 5 is the primary conformational drive into PO, which shifts towards the closed (HO) conformer as the pH increases. Furthermore, at pH 6.5, PO is unfavorable due to negative charge-charge repulsion at the N/C-lobe interface linker region causing increased hinge distance when compared to HO, which has favorable attractive electrostatics. Subsequently, the effect of salt concentration at 70 and 140 mM NaCl was studied. At 70 mM NaCl and pH 5, chloride ions bind strongly in the N-lobe iron-binding site, whereas these interactions are weak at pH 6.5. With increasing salt concentration at pH 5, regions surrounding the N-lobe iron-binding site are saturated and as a consequence sodium and chloride ions accumulate into the bulk. Additionally, protein-excipient interactions were investigated. At pH 5, excipients interact in similar loop regions, E89-T93, D416-D420, located in the C-lobe and N-lobe of the HO conformer, respectively. It is anticipated that interactions of additives in these two loop regions cause conformational changes that lead to iron coordinating residues in the N-lobe to drift away from iron and thus drive HO to PO conversion. Furthermore, at pH 6.5 and 140 mM histidine or phosphate, these interactions are negligible leading to the stabilization of HO.

biophysics↗

Individual differences in members of Actinobacteria, Bacteroidetes, and Firmicutes is associated with resistance or vulnerability to addiction-like behaviors in heterogeneous stock rats

An emerging element in psychiatry is the gut-brain-axis, the bi-directional communication pathways between the gut microbiome and the brain. A prominent hypothesis, mostly based on preclinical studies, is that individual differences in the gut microbiome composition and drug-induced dysbiosis may be associated with vulnerability to psychiatric disorders including substance use disorder. However, most studies used small sample size, ignored individual differences, or used animal models with limited relevance to addiction. Here, we test the hypothesis that pre-existing microbiome composition and drug-induced changes in microbiome composition can predict addiction-like behaviors using an advanced animal model of extended access to cocaine self-administration in a large cohort of heterogenous stock (HS) rats. Adult male and female HS rats were allowed to self-administer cocaine under short (2h/day) and long access (6h/day) for ~7 weeks under various schedule of reinforcement to identify individuals that are resistant or vulnerable to addiction-like behaviors and fecal samples were collected before the first session and after the last session to assess differences in the microbiome composition. Linear discriminant analysis (LDA) identified sex-dependent and sex-independent differences at the phylum, order, and species level that are differentially abundant in resistant vs. vulnerable individuals, including high level of actinobacteria both before the first exposure to cocaine and after 7 weeks of cocaine self-administration in resistant animals. Predictions of functional gene content using PICRUSt revealed differential regulation of short-chain fatty acid processing in the vulnerable group after self-administration. These results identify microbiome constituents as well as metabolic pathways that are associated with resistance or vulnerability to addiction-like behaviors in rats. Identification of microbes and tangential metabolic pathways involved in cocaine resilience/vulnerability may represent an innovative strategy for the development of novel biomarkers and medication for the treatment of cocaine use disorder.

animal behavior and cognition↗