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Biology subjects

Clayton, M.

Publications and source records attributed to Clayton, M..

6 recordsLinked to original sources

The female larval fly CNS connectome: first draft

We release an enhanced FIB-SEM volume and associated neuron, mitochondria, synapse and glia automated segmentations for the complete, gap- and artifact-free central nervous system of the first instar female larval Drosophila melanogaster. Segmentation data is largely unproofread besides select neurons in the premotor and proprioceptive system and select subvolumes where synapses have been manually annotated, serving as training and evaluation data. The dataset represents the first complete central nervous system of the larval fly, and now awaits substantial improvement of machine vision approaches that effectively leverage domain knowledge for the automated yet data-guided proofreading, or substantial and costly human proofreading. All the data and methods are publicly available for further improvement and analysis.

neuroscience↗

Olfactory Loss Enhances Visual Learning in Drosophila through Structural and Functional Reorganisation

Loss of a sensory modality can enhance performance in the remaining senses. However, the circuit mechanisms by which such cross-modal compensation can improve cognitive functions, including learning, are unknown. Here, we show that compromising olfaction in both larval and adult Drosophila enhances visual associative learning. Using behavioural analysis, functional imaging, and comparative connectomics, we reveal the circuit mechanisms that underlie this improvement. Animals with improved learning ability have enhanced responses to visual stimuli in the higher-order learning circuit. The complementary circuit mechanisms that can enhance these responses are structural reweighting of inputs in the larva, resulting in an increased fraction of synaptic inputs from visual pathways onto neurons in the learning circuit, and a reduction in cross-modal inhibition in the adult. Together, these findings reveal synaptic and disinhibitory circuit mechanisms that enhance learning in higher-order associative networks following sensory loss.

neuroscience↗

The central complex of the larval fruit fly brain

In holometabolous insects such as the fruit fly Drosophila melanogaster, the brain central complex (CX) develops during metamorphosis and serves the adult stage. Whether a form of the CX exists in the brain of the evolutionarily novel larval stages is not known. Here, we analyzed the connectome of the larval brain and, on the basis of neuronal lineages, synaptic connectivity patterns, and anatomy, identified a putative larval CX, comprising 4 key neuropils: the protocerebral bridge (PB), the ellipsoid body (EB), the fan-shaped body (FB) and the noduli (NO). Consistent with our interpretation, we found in the larval brain synaptic connectivity patterns characteristic of the adult, including (i) visual input into the PB and EB; (ii) modulation of CX neuropil inputs by the mushroom body (MB); (iii) reciprocal connectivity between CX neuropils and select MB compartments; and (iv) strong connectivity between CX neuropils. While some neuronal lineages contributing to the larval CX do not contribute to the adult CX, many others are conserved. The characterization of a larval CX brings structure to largely unexamined larval brain circuits, linking with a vast body of literature, and will inform the design of experiments to probe larval brain function.

neuroscience↗

An outbreak of SARS-CoV-2 with high mortality in mink (Neovison vison) on multiple Utah farms

The breadth of animal hosts that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may serve as reservoirs for continued viral transmission are not known entirely. In August 2020, an outbreak of SARS-CoV-2 occurred in multiple mink farms in Utah and was associated with high mink mortality and rapid viral transmission between animals. The outbreaks epidemiology, pathology, molecular characterization, and tissue distribution of virus within infected mink is provided. Infection of mink was likely by reverse zoonosis. Once established, infection spread rapidly between independently housed animals and farms, and caused severe respiratory disease and death. Clinical signs were most notably sudden death, anorexia, and increased respiratory effort. Gross pathology examination revealed severe pulmonary congestion and edema. Microscopically there was pulmonary edema with moderate vasculitis, perivasculitis, and fibrinous interstitial pneumonia. Reverse transcriptase polymerase chain reaction (RT-PCR) of tissues collected at necropsy demonstrated the presence of SARS-CoV-2 viral RNA in multiple organs including nasal turbinates, lung, tracheobronchial lymph node, epithelial surfaces, and others. Whole genome sequencing from multiple mink was consistent with published SARS-CoV-2 genomes with few polymorphisms. The Utah mink SARS-CoV-2 strain fell into Clade GH, which is unique among mink and other animal strains sequenced to date and did not share other spike RBD mutations Y453F and F486L found in mink. Localization of viral RNA by in situ hybridization revealed a more localized infection, particularly of the upper respiratory tract. Mink in the outbreak reported herein had high levels of virus in the upper respiratory tract associated with mink-to-mink transmission in a confined housing environment and were particularly susceptible to disease and death due to SARS-CoV-2 infection. Author SummaryThe recent emergence and worldwide spread of the novel coronavirus has resulted in worldwide disease and economic hardship. The virus, known as SARS-CoV-2 is believed to have originated in bats and has spread worldwide through human-to-human virus transmission. It remains unclear which animal species, other than humans, may also be susceptible to viral infection and could naturally transmit the virus to susceptible hosts. In this study, we describe an outbreak of disease and death due to SARS-CoV-2 infection in farmed mink in Utah, United States. The investigation reveals that mink can spread the virus rapidly between animals and that the disease in mink is due to the viral infection and damage to tissues of the upper and lower respiratory system. The determination that mink are susceptible to SARS-CoV-2 indicates the need for strict biosecurity measures on mink farms to remediate mink-to-mink and human-to-mink transmission for the protection of mink, as well as prevent potential transmission from mink to humans.

microbiology↗

Increased and ectopic expression of Triticum polonicum VRT-A2 underlies elongated glumes and grains in hexaploid wheat in a dosage-dependent manner

Flower development is a major determinant of yield in crops. In wheat, natural variation for the size of spikelet and floral organs is particularly evident in Triticum polonicum, a tetraploid subspecies of wheat with long glumes, lemmas, and grains. Using map-based cloning, we identified VRT2, a MADS-box transcription factor belonging to the SVP family, as the gene underlying the T. polonicum long-glume (P1) locus. The causal P1 mutation is a sequence re-arrangement in intron-1 that results in both increased and ectopic expression of the T. polonicum VRT-A2 allele. Based on allelic variation studies, we propose that the intron-1 mutation in VRT-A2 is the unique T. polonicum species defining polymorphism, which was later introduced into hexaploid wheat via natural hybridizations. Near-isogenic lines differing for the P1 locus revealed a gradient effect of P1 across florets. Transgenic lines of hexaploid wheat carrying the T. polonicum VRT-A2 allele show that expression levels of VRT-A2 are highly correlated with spike, glume, grain, and floral organ length. These results highlight how changes in expression profiles, through variation in cis-regulation, can impact on agronomic traits in a dosage-dependent manner in polyploid crops. One-sentence summaryAn intron-1 rearrangement in the MADS-box transcription factor VRT-A2 leads to its misexpression and defines the long-glume phenotype of Polish wheat (T. polonicum).

plant biology↗

Comparing genome-wide association study results from different measurements of an underlying phenotype

Increasing popularity of high-throughput phenotyping technologies, such as image-based phenotyping, offer novel ways for quantifying plant growth and morphology. These new methods can be more or less accurate and precise than traditional, manual measurements. Many large-scale phenotyping efforts are conducted to enable genome-wide association studies (GWAS), but it is unclear exactly how alternative methods of phenotyping will affect GWAS results. In this study we simulate phenotypes that are controlled by the same set of causal loci but have differing heritability, similar to two different measurements of the same morphological character. We then perform GWAS with the simulated traits and create receiver operating characteristic (ROC) curves from the results. The areas under the ROC curves (AUCs) provide a metric that allows direct comparisons of GWAS results from different simulated traits. We use this framework to evaluate the effects of heritability and the number of causative loci on the AUCs of simulated traits; we also test the differences between AUCs of traits with differing heritability. We find that both increasing the number of causative loci and decreasing the heritability reduce a traits AUC. We also find that when two traits are controlled by a greater number of causative loci, they are more likely to have significantly different AUCs as the difference between their heritabilities increases. These results provide a framework for deciding between competing phenotyping strategies when the ultimate goal is to generate and use phenotype-genotype associations from GWAS.

genomics↗