Biology subjects

McLean, D.

Publications and source records attributed to McLean, D..

3 recordsLinked to original sources

bioRxiv2021

Crossbill: an open access single objective light-sheet microscopy platform

We present an open access scanned oblique plane microscopy platform Crossbill. It combines a new optical configuration, open hardware assembly, a systematic alignment protocol, and dedicated control software to provide a compact, versatile, high resolution single objective light-sheet microscopy platform. The demonstrated configuration yields the most affordable sub-micron resolution oblique plane microscopy system to date. We add galvanometer enabled tilt-invariant lateral scan for multi-plane, multi-Hz volumetric imaging capability. A precision translation stage extends stitched field of view to centimeter scale. The accompanying open software is optimized for Crossbill and can be easily extended to include alternative configurations. Using Crossbill, we demonstrate large volume structural fluorescence imaging with sub-micron lateral resolution in zebrafish and mouse brain sections. Crossbill is also capable of multiplane functional imaging, and time-lapse imaging. We suggest multiple alternative configurations to extend Crossbill to diverse microscopy applications.

neuroscience↗

bioRxiv2021

Expectation-Based Gist Facilitation: Rapid Scene Understanding and the Role of Top-Down Information

Scene meaning is processed rapidly, with gist extracted even when presentation duration spans a few dozen milliseconds. This has led some to suggest a primacy of bottom-up information. However, gist research has typically relied on showing successions of unrelated scene images, contrary to our everyday experience in which the world unfolds around us in a predictable manner. Thus, we investigated whether top-down information - in the form of observers predictions of an upcoming scene - facilitates gist processing. Within each trial, participants (N=336) experienced a series of images, organised to represent an approach to a destination (e.g., walking down a sidewalk), followed by a final target scene either congruous or incongruous with the expected destination (e.g., a store interior or a bedroom). Over a series of behavioural experiments, we found that: appropriate expectations facilitated gist processing; inappropriate expectations interfered with gist processing; the effect of congruency was driven by provision of contextual information rather than the thematic coherence of approach images, and; expectation-based facilitation was most apparent when destination duration was most curtailed. We then investigated the neural correlates of predictability on scene processing using ERP (N=26). Congruency-related differences were found in a putative scene-selective ERP component, related to integrating visual properties (P2), and in later components related to contextual integration including semantic and syntactic coherence (N400 and P600, respectively). Taken together, these results suggest that in real-world situations, top-down predictions of an upcoming scene influence even the earliest stages of its processing, affecting both the integration of visual properties and meaning.

neuroscience↗

bioRxiv2019

A conserved protein, BcmA, mediates motility, biofilm formation, and host colonisation in Adherent Invasive Escherichia coli

Adherent Invasive Escherichia coli (AIEC) is a non-diarrhoeagenic intestinal E. coli pathotype associated with Crohns Disease. AIEC pathogenesis is characterised by biofilm formation, adhesion to and invasion of intestinal epithelial cells, and intracellular replication within epithelial cells and macrophages. Here, we identify and characterise a protein in the prototypical AIEC strain LF82 which is required for efficient biofilm formation and dispersal - LF82_p314. LF82 {Delta}LF82_314 have defective swimming and swarming motility, indicating LF82_p314 is important for flagellar-mediated motility, and thus surface colonisation and biofilm dispersal. Flagellar morphology and chemotaxis in liquid appear unaffected by deletion of LF82_314, suggesting LF82_p314 does not elicit an effect on flagella biogenesis or environmental sensing. Flagellar motility has been implicated in AIEC virulence, therefore we assessed the role of LF82_p314 in host colonisation using a Caenorhabditis elegans model. We found that LF82 {Delta}LF82_314 have an impaired ability to colonise the C. elegans compared to wild-type LF82. Phylogenetic analysis showed that LF82_314 is conserved in several major enterobacterial pathogens, and suggests the gene may have been acquired horizontally in several genera. Our data suggests LF82_p314 may be a novel component in the flagellar motility pathway and is a novel determinant of AIEC colonisation. Our findings have potential implications not only for the pathogenesis of Crohns Disease, but also for the course of infection in several major bacterial pathogens. We propose a new designation for LF82_314, biofilm coupled to motility A, or bcmA.\n\nAuthor summaryAdherent Invasive Escherichia coli (AIEC) are a group of bacteria implicated in the pathogenesis of Crohns Disease, a chronic inflammatory bowel disease with no cure. Critical to the process of many bacterial infections is the ability of bacteria to swim towards and colonise the host surface using specialised, propeller-like appendages called flagella. In this paper, we describe a novel protein - LF82_p314 (BcmA) - which is required for efficient flagella-mediated motility and surface colonisation in AIEC. Using a nematode worm (Caenorhabditis elegans) infection model, we show that LF82_p314 enables effective colonisation of the C. elegans gut, suggesting a role for the protein during human infection. These findings indicate BcmA is significant for initial colonisation of the human gut by AIEC, and therefore the onset of Crohns Disease.

microbiology↗