Biology subjects

Ward, J. E.

Publications and source records attributed to Ward, J. E..

6 recordsLinked to original sources

bioRxiv2022

Classic and dissociative psychedelics induce similar hyper-synchronous states in the cognitive-limbic cortex-basal ganglia system

The neurophysiological mechanisms behind the profound changes in perception and cognition induced by psychedelic drugs are not well understood. To identify neuronal activity specific to the psychedelic state, we here investigated the effects of classic psychedelics (LSD, DOI) and dissociative psychedelics (ketamine, PCP) on neuronal firing rates and local field potentials in several brain structures involved in cognitive processing in freely moving rats. The classic psychedelics had a net inhibitory effect on firing rates of putative interneurons and principal cells in all recorded regions. The dissociative psychedelics had a similar inhibitory effect on principal cells, but an opposite excitatory effect on interneurons in most regions. However, the inhibitory effect on principal cells was not specific to the psychedelic state, as similar inhibition occurred with a non-psychedelic psychotropic control (amphetamine). In contrast, both types of psychedelics dramatically increased the prevalence of high-frequency oscillations (HFOs) in local field potentials, while the non-psychedelic control did not. Further analysis revealed strong HFO phase locking between structures and very small phase differences corresponding to <1 ms delays. Such standing-wave behavior suggests local generation of HFOs in multiple regions and weak, fast coupling between structures. The observed HFO hypersynchrony is likely to have major effects on processes that rely on integration of information across neuronal systems, and it might be an important mechanism behind the changes in perception and cognition during psychedelic drug use. Potentially, similar mechanisms could induce hallucinations and delusions in psychotic disorders and would constitute promising targets for new antipsychotic treatments.

neuroscience↗

bioRxiv2021

Pili Expression in Geobacter sulfurreducens Lacking the Putative Gene for the PilB Pilus Assembly Motor

Multiple lines of evidence suggest that electrically conductive pili (e-pili) are an important conduit for long-range electron transport in Geobacter sulfurreducens, a common model microbe for the study of extracellular electron transport mechanisms. One strategy to study the function of e-pili has been to delete the gene for PilB, the pilus assembly motor protein, in order to prevent e-pili expression. However, we found that e-pili are still expressed after the gene for PilB is deleted. Conducting probe atomic force microscopy revealed filaments with the same diameter and similar current-voltage response as e-pili harvested from wild-type G. sulfurreducens or when e-pili are heterologously expressed from the G. sulfurreducens pilin gene in E. coli. Immunogold labeling demonstrated that a G. sulfurreducens strain expressing e-pili with a His-tag continued to express His-tag labelled e-pili when the PilB gene was deleted. Strains with the PilB gene deleted produced maximum current densities comparable to wild-type controls. These results demonstrate that deleting the gene for PilB is not an appropriate strategy for constructing strains of G. sulfurreducens without e-pili, necessitating a reinterpretation of the results of previous studies that have employed this approach. ImportanceGeobacter sulfurreducens is a model microbe for the study of biogeochemically and technologically significant processes such as the reduction of Fe(III) oxides in soils and sediments; bioelectrochemical applications that produce electric current from waste organic matter or drive useful processes with the consumption of renewable electricity; direct interspecies electron transfer in anaerobic digestors and methanogenic soils and sediments; and metal corrosion. The phenotypes associated with gene deletions are an important strategy for determining the mechanisms for extracellular electron transfer in G. sulfurreducens. The results reported here demonstrate that a gene deletion previously thought to prevent the expression of electrically conductive pili in G. sulfurreducens does not have the intended result. Conductive pili continue to be expressed. This finding is important for interpreting the results of several previous studies on conductive pili function.

microbiology↗

bioRxiv2019

Decorating Microbially Produced Protein Nanowires with Peptide Ligands

The potential applications of electrically conductive protein nanowires (e-PNs) harvested from Geobacter sulfurreducens might be greatly expanded if the outer surface of the wires could be modified to confer novel sensing capabilities or to enhance binding to other materials. We developed a simple strategy for functionalizing e-PNs with surface-exposed peptide ligands. The G. sulfurreducens gene for the monomer that assembles into e-PNs was modified to add known peptide ligands at the carboxyl terminus of the monomer. Strains of G. sulfurreducens were constructed that fabricated synthetic e-PNs with a six-histidine His-tag or both the His-tag and a nine-peptide HA-tag exposed on the outer surface. Addition of the peptide ligands did not diminish e-PN conductivity. The abundance of HA-tag in e-PNs was controlled by placing expression of the gene for the synthetic monomer with the HA-tag under transcriptional regulation. These studies suggest broad possibilities for tailoring e-PN properties for diverse applications.

synthetic biology↗

bioRxiv2018

Structure of a cytochrome-based bacterial nanowire

Electrically conductive pili from Geobacter species, termed bacterial \"nanowires\", are intensely studied for their biological significance and potential in the development of new materials. We have characterized a unique nanowire from conductive G. sulfurreducens pili preparations by cryo-electron microscopy composed solely of the c-type cytochrome OmcS. We present here, at 3.4 [A] resolution, a novel structure of a cytochrome-based filament and discuss its possible role in long-range biological electron transport.\n\nSummary sentenceCryo-electron microscopy reveals the remarkable assembly of a c-type cytochrome into filaments comprising a heme-based bacterial nanowire.

biophysics↗

bioRxiv2018

Syntrophus Conductive Pili Demonstrate that Common Hydrogen-Donating Syntrophs can have a Direct Electron Transfer Option

Syntrophic interspecies electron exchange is essential for the stable functioning of diverse anaerobic microbial communities. Hydrogen/formate interspecies electron transfer (HFIT), in which H2 and/or formate function as diffusible electron carriers, has been considered to be the primary mechanism for electron sharing because most common syntrophs were thought to lack biochemical components, such as electrically conductive pili (e-pili), necessary for direct interspecies electron transfer (DIET). Here we report that Syntrophus aciditrophicus, one of the most intensively studied microbial models for HFIT, produces e-pili and can grow via DIET. Pilin genes likely to yield e-pili were found in other genera of hydrogen/formate-producing syntrophs. The finding that DIET is a likely option for diverse syntrophs that are abundant in many anaerobic environments necessitates a reexamination of the paradigm that HFIT is the predominant mechanism for syntrophic electron exchange within anaerobic microbial communities of biogeochemical and practical significance.

microbiology↗

bioRxiv2017

Electrically Conductive Pili from Pilin Genes of Phylogenetically Diverse Microorganisms

The possibility that bacteria other than Geobacter species might contain genes for electrically conductive pili (e-pili) was investigated by heterologously expressing pilin genes of interest in Geobacter sulfurreducens. Strains of G. sulfurreducens producing high current densities, which are only possible with e-pili, were obtained with pilin genes from Flexistipes sinusarabici, Calditerrivibrio nitroreducens, and Desulfurivibrio alkaliphilus. The conductance of pili from these strains was comparable to native G. sulfurreducens e-pili. The e-pili derived from C. nitroreducens, and D. alkaliphilus pilin genes are the first examples of relatively long (> 100 amino acids) pilin monomers assembling into e-pili. The pilin gene from Desulfofervidus auxilii did not yield e-pili, suggesting that the hypothesis that this sulfate reducer wires itself to ANME-1 microbes with e-pili to promote anaerobic methane oxidation should be reevaluated. A high density of aromatic amino acids and a lack of substantial aromatic-free gaps along the length of long pilins may be important characteristics leading to e-pili. This study demonstrates a simple method to screen pilin genes from difficult-to-culture microorganisms for their potential to yield e-pili; reveals new potential sources for biologically based electronic materials; and suggests that a wide phylogenetic diversity of microorganisms may employ e-pili for extracellular electron exchange.

microbiology↗