Biology subjects

Manning, C.

Publications and source records attributed to Manning, C..

5 recordsLinked to original sources

bioRxiv2026

Topographical differences during motion processing in autistic and dyslexic children

Atypical motion processing has been reported in multiple developmental conditions, including autism and dyslexia, and taken as support for a general developmental vulnerability in the dorsal stream. Yet by uncovering dynamically unfolding processes, electroencephalography can determine the extent to which motion processing signatures are shared or distinct across different developmental conditions. Here we used pre-registered topographical analyses across the whole high-density electrode array to determine, for the first time, whether autistic and dyslexic children activate the same or distinct brain pathways as typically developing children, when completing two motion processing tasks. Participants were 29 autistic, 44 dyslexic and 57 typically developing children aged 6 to 14 years. Group differences in overall brain response strength were found in both tasks. Topographical activity differed in both autistic and dyslexic children compared to typically developing children (but not between autistic and dyslexic children) in a motion coherence task between 456 - 560 ms. However, group differences in a direction integration task (with no incoherent motion) depended on stimulus difficulty and time window (434 - 500 ms and 538 - 638 ms), with different patterns of divergence from typical development in autism and dyslexia. These results suggest that there are differences in the brain networks used to accomplish motion processing tasks in both autistic and dyslexic children, and demonstrate the utility of a topographical approach for detecting group differences in neural mechanisms, which can be missed by univariate approaches. Key pointsO_LIWe use an electrical neuroimaging approach to provide new insights into the neural mechanisms of motion processing in autism and dyslexia C_LIO_LIAutistic and dyslexic children both differed from typically developing children in the strength and topography of their brain responses. C_LIO_LIMotion processing activates atypical brain networks in both autistic and dyslexic children. C_LI

neuroscience↗

bioRxiv2025

The dietary emulsifier polysorbate-80 induces lipid accumulation and cell death in intestinal epithelial cells via ferroptosis

Chronic inflammatory and metabolic diseases are major global health issues increasingly linked to dietary factors. Consumption of dietary emulsifiers like polysorbate-80 (p80), common in ultra-processed foods and pharmaceuticals, has raised concerns about gut health. RNA sequencing on intestinal epithelial cells (IECs) exposed to p80 revealed increased expression of ferroptosis-associated genes and disruption of lipid metabolism pathways further demonstrated by mitochondrial dysfunction, including altered membrane potential and architecture, and accumulation of reactive oxygen species, iron, lipid peroxidation, and lipid droplet formation. Lipidomic profiling identified significant alterations in triglyceride species and elevated pro-ferroptotic polyunsaturated fatty acids. These data indicate that p80 disrupts lipid homeostasis in IECs and triggers ferroptotic cell death, mechanisms potentially contributing to the increased incidence of chronic conditions like inflammatory bowel disease and metabolic syndrome. The study highlights critical implications for public health, emphasizing the need for reassessment of emulsifier safety standards while balancing needs with consumer safety.

cell biology↗

bioRxiv2024

Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis

In the developing mouse ventral spinal cord, HES5, a transcription factor downstream of Notch signalling, is expressed as evenly spaced clusters of high HES5-expressing neural progenitor cells along the dorsoventral axis. While Notch signalling requires direct membrane contact for its activation, we have previously shown mathematically that contact needs to extend beyond neighbouring cells for the HES5 pattern to emerge. However, the presence of cellular structures that could enable such long-distance signalling was unclear. Here, we report that cellular protrusions are present all along the apicobasal axis of individual neural progenitor cells. Through live imaging, we show that these protrusions dynamically extend and retract reaching lengths of up to [~]20m, enough to extend membrane contact beyond adjacent cells. The Notch ligand DLL1 was found to colocalise with protrusions, further supporting the idea that Notch signalling can be transduced at a distance. The effect of protrusions on the HES5 pattern was tested by reducing the density of protrusions using the CDC42 inhibitor ML141, leading to a tendency to decrease the distance between high HES5 cell clusters. However, this tendency was not significant and leaves an open question about their role in the fine-grained organisation of neurogenesis.

developmental biology↗

bioRxiv2020

Identification, Mapping and Relative Quantitation of SARS-Cov2 Spike Glycopeptides by Mass-Retention Time Fingerprinting

We describe a novel analytical method for rapid and robust identification, mapping and relative quantitation of glycopeptides from SARS-CoV-2 Spike protein. The method may be executed using any LC-TOF mass spectrometer, requires no specialised knowledge of glycan analysis and makes use of the differential resolving power of reversed phase HPLC. While this separation technique resolves peptides with high efficiency, glycans are resolved poorly, if at all. Consequently, glycopeptides consisting of the same peptide bearing different glycan structures will all possess very similar retention times and co-elute. While this has previously been viewed as a disadvantage, we show that shared retention time can be used to map multiple glycan species to the same peptide and location. In combination with MSMS and pseudo MS3, we have constructed a detailed mass-retention time database for Spike. This database allows any ESI-TOF equipped lab to reliably identify and quantify spike glycans from a single overnight elastase protein digest in less than 90 minutes.

biochemistry↗

bioRxiv2018

A toolbox of IgG subclass-switched recombinant monoclonal antibodies for enhanced multiplex immunolabeling of brain

Generating recombinant monoclonal antibodies (R-mAbs) from mAb-producing hybridomas offers numerous advantages that increase the effectiveness, reproducibility, and transparent reporting of research. We report here the generation of a novel resource in the form of a library of recombinant R-mAbs validated for neuroscience research. We cloned immunoglobulin G (IgG) variable domains from cryopreserved hybridoma cells and input them into an integrated pipeline for expression and validation of functional R-mAbs. To improve efficiency over standard protocols, we eliminated aberrant Sp2/0-Ag14 hybridoma-derived variable light transcripts using restriction enzyme treaent. Further, we engineered a plasmid backbone that allows for switching of the IgG subclasses without altering target binding specificity to generate R-mAbs useful in simultaneous multiplex labeling experiments not previously possible. The method was also employed to rescue IgG variable sequences and generate functional R-mAbs from a non-viable cryopreserved hybridoma. All R-mAb sequences and plasmids will be archived and disseminated from open source suppliers.

neuroscience↗