Biology subjects

Baker, K.

Publications and source records attributed to Baker, K..

43 records · Page 3Linked to original sources

bioRxiv2020

RLP/K enrichment sequencing; a novel method to identify receptor-like protein (RLP) and receptor-like kinase (RLK) genes

O_LIThe identification of immune receptors in crop plants is time-consuming but important for disease control. Previously, resistance gene enrichment sequencing (RenSeq) was developed to accelerate mapping of nucleotide-binding domain and leucine-rich repeat containing (NLR) genes. However, resistances mediated by pattern recognition receptors (PRRs) remain less utilised. C_LIO_LIHere, our pipeline shows accelerated mapping of PRRs. Effectoromics leads to precise identification of plants with target PRRs, and subsequent RLP/K enrichment sequencing (RLP/KSeq) leads to detection of informative SNPs that are linked to the trait. C_LIO_LIUsing Phytophthora infestans as a model, we identified Solanum microdontum plants that recognize the apoplastic effectors INF1 or SCR74. RLP/KSeq in a segregating Solanum population confirmed the localization of the INF1 receptor on chromosome 12, and lead to the rapid mapping of the response to SCR74 to chromosome 9. By using markers obtained from RLP/KSeq in conjunction with additional markers, we fine-mapped the SCR74 receptor to a 43-kbp G-LecRK locus. C_LIO_LIOur findings show that RLP/KSeq enables rapid mapping of PRRs and is especially beneficial for crop plants with large and complex genomes. This work will enable the elucidation and characterisation of the non-NLR plant immune receptors and ultimately facilitate informed resistance breeding. C_LI

plant biology↗

bioRxiv2020

Toward an integrated classification of neuronal cell types: morphoelectric and transcriptomic characterization of individual GABAergic cortical neurons

Neurons are frequently classified into distinct groups or cell types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 3,700 GABAergic mouse visual cortical neurons and reconstructed the local morphologies of 350 of those neurons. We found that most transcriptomic types (t-types) occupy specific laminar positions within mouse visual cortex, and many of those t-types exhibit consistent electrophysiological and morphological features. We observed that these properties could vary continuously between t-types, which limited the ability to predict specific t-types from other data modalities. Despite that, the data support the presence of at least 20 interneuron met-types that have congruent morphological, electrophysiological, and transcriptomic properties. HighlightsO_LIPatch-seq data obtained from >3,700 GABAergic cortical interneurons C_LIO_LIComprehensive characterization of morpho-electric features of transcriptomic types C_LIO_LI20 interneuron met-types that have congruent properties across data modalities C_LIO_LIDifferent Sst met-types preferentially innervate different cortical layers C_LI

neuroscience↗

bioRxiv2019

Maternal antibodies provide partial protection from postnatal Zika viremia in nonhuman primates

Zika virus (ZIKV) will remain a public health threat until effective vaccines and therapeutics are made available in the hardest hit areas of the world. Recent data in a nonhuman primate model showed that infants postnatally infected with ZIKV were acutely susceptible to high viremia and neurological damage, suggesting the window of vulnerability extends beyond gestation. We addressed the susceptibility of two infant rhesus macaques born healthy to dams infected with Zika virus during pregnancy. Passively acquired neutralizing antibody titers dropped below detection limits between 2 and 3 months of age, while binding, possibly non-neutralizing antibodies remained detectable until viral infection at 5 months of age. Post-infection acute serum viremia was substantially reduced relative to adults infected with the same dose of the same stock of a Brazilian isolate of ZIKV (n=11 pregnant females) and another stock of the same isolate (n=4 males and 4 non-pregnant females). Virus was never detected in cerebrospinal fluid nor in neural tissues at necropsy two weeks after infection, suggesting reduced viral burden relative to adults and published data from infants. However, viral RNA was detected in lymph nodes, confirming some tissue dissemination. Though protection was not absolute, our data suggest infants born healthy to infected mothers may harbor a modest but important level of protection from postnatally acquired ZIKV for several months after birth, an encouraging result given the potentially severe infection outcomes of this population.

microbiology↗

bioRxiv2018

Enteric Pathogen Diversity in Infant Foods in Low-income Neighborhoods Of Kisumu, Kenya

Pediatric diarrheal disease remains the 2nd most common cause of preventable illness and death among children under the age of five, especially in Low and Middle-Income Countries (LMICs). However, there is limited information regarding the role of food in pathogen transmission due to measuring infant food contaminations in LMICs. For this study, we examined the frequency of enteric pathogen occurrence and co-occurrence in 127 weaning infant foods in Kisumu, Kenya using a multi-pathogen rt-PCR diagnostic tool, and assessed household food hygiene risk factors for contamination. Bacterial, viral, and protozoa enteric pathogen DNA and RNA were detected in 62% of the infant weaning food samples collected, with 37% of foods containing more than one pathogen type. Multivariable generalized linear mixed model analysis indicated type of infant food best explained the presence and diversity of enteric pathogens in infant food, while most household food hygiene risk factors considered in this study were not significantly associated with pathogen contamination. Specifically, cows milk was significantly more likely to contain a pathogen (adjusted Risk Ratio=14.4; 95% Confidence Interval (CI) 1.78-116.1) and contained 2.35 more types of pathogens (adjusted Risk Ratio=2.35; 95% CI 1.67-3.29) than porridge. Our study demonstrates that infants in this low-income urban setting are frequently exposed to diarrhoeagenic pathogens in food and suggests that interventions are needed to prevent foodborne transmission of pathogens to infants.\n\nImportanceFood is acknowledged as an important pathway for enteric pathogen infection in young children. Yet, information on enteric pathogen contamination in food in low-and-middle income settings is lacking, especially with respect to weaning foods given to young infants. This study assessed which food-related risk factors were associated with increased presence of and diversity in twenty-seven types of enteric pathogens in a variety of foods provided to infants between three and nine months of age in a low-income neighborhood of Kisumu, Kenya. Feeding infants cow milk emerged as the most important risk factor for food contamination by one or more enteric pathogens. The results indicate public health interventions should focus on improving cow milk safety to prevent foodborne pathogen transmission to infants. However, more research is needed to determine whether infant milk contamination was caused by caregiver hygiene practices versus food contamination passed from upstream sources.

microbiology↗

bioRxiv2018

Horizontal gene transfer as an indispensible driver for Neocallimastigomycota evolution into a distinct gut-dwelling fungal lineage

Survival and growth of the anaerobic gut fungi (AGF, Neocallimastigomycota) in the herbivorous gut necessitate the possession of multiple abilities absent in other fungal lineages. We hypothesized that horizontal gene transfer (HGT) was instrumental in forging the evolution of AGF into a phylogenetically distinct gut-dwelling fungal lineage. Patterns of HGT were evaluated in the transcriptomes of 27 AGF strains, 22 of which were isolated and sequenced in this study, and 4 AGF genomes broadly covering the breadth of AGF diversity. We identified 283 distinct incidents of HGT in AGF transcriptomes, with subsequent gene duplication resulting in an HGT frequency of 2.1-3.6% in AGF genomes. The majority of HGT events were AGF specific (91.5%) and wide (70.7%), indicating their occurrence at early stages of AGF evolution. The acquired genes allowed AGF to expand their substrate utilization range, provided new venues for electron disposal, augmented their biosynthetic capabilities, and facilitated their adaptation to anaerobiosis. The majority of donors were anaerobic fermentative bacteria prevalent in the herbivorous gut. This work strongly indicates that HGT indispensably forged the evolution of AGF as a distinct fungal phylum and provides a unique example of the role of HGT in shaping the evolution of a high rank taxonomic eukaryotic lineage. ImportanceThe anaerobic gut fungi (AGF) represent a distinct basal phylum lineage (Neocallimastigomycota) commonly encountered in the rumen and alimentary tracts of herbivores. Survival and growth of anaerobic gut fungi in these anaerobic, eutrophic, and prokaryotes dominated habitats necessitates the acquisition of several traits absent in other fungal lineages. This manuscript assesses the role of horizontal gene transfer as a relatively fast mechanism for trait acquisition by the Neocallimastigomycota post sequestration in the herbivorous gut. Analysis of twenty-seven transcriptomes that represent the broad Neocallimastigomycota diversity identified 283 distinct HGT events, with subsequent gene duplication resulting in an HGT frequency of 2.1-3.6% in AGF genomes. These HGT events have allowed AGF to survive in the herbivorous gut by expanding their substrate utilization range, augmenting their biosynthetic pathway, providing new routes for electron disposal by expanding fermentative capacities, and facilitating their adaptation to anaerobiosis. HGT in the AGF is also shown to be mainly a cross-kingdom affair, with the majority of donors belonging to the bacteria. This work represents a unique example of the role of HGT in shaping the evolution of a high rank taxonomic eukaryotic lineage.

microbiology↗

bioRxiv2018

Functional network dynamics in a neurodevelopmental disorder of known genetic origin

Cognitive processing depends on the temporal co-ordination of functional brain networks. This fundamental aspect of neurophysiology potentially bridges the genetic regulation of neuronal activity and developmental cognitive impairments. We investigated brain network dynamics in a neurodevelopmental disorder of known genetic origin, by comparing individuals with ZDHHC9-associated intellectual disability to individuals with no known impairment. We used Hidden Markov Modelling on magnetoencephalography (MEG) data, at rest and during auditory oddball stimulation, to characterise transient network dynamics. At rest, network dynamics distinguished the groups, with ZDHHC9 participants showing longer state activation. Crucially, ZDHHC9 gene expression levels predicted the group differences across networks, supporting an association between molecular pathology and neurophysiology. In contrast, network dynamics during auditory oddball stimulation did not show this association. We demonstrate a link between brain network dynamics and regional gene expression, and present a valuable method for understanding the real-time neural mechanisms linking genetic variation to cognitive difficulties.

neuroscience↗

bioRxiv2018

Characterizing Genetic Circuit Components in E. coli towards a Campylobacter jejuni Biosensor.

Campylobacter jejuni is responsible for most cases of bacterial gastroenteritis (food poisoning) in the United Kingdom. The most common routes of transmission are by contact with raw poultry. Current detection systems for the pathogen are time-consuming, expensive or inaccessible for everyday users. In this article we propose a cheaper and faster system for detection of C. jejuni using a synthetic biology approach. We aimed to detect C. jejuni by the presence of xylulose, an uncommon bacterial capsular saccharide. We characterized two sugar-based regulatory systems that displayed potential to act as tools for detection of xylulose. Using a two-plasmid reporter system in Escherichia coli, we investigated the regulatory protein component (MtlR) of the mannitol operon from Pseudomonas fluorescens. Our findings suggest that the promoter of mtlE is activated by MtlR in the presence of a variety of sugar inducer molecules, and may exhibit cross-activity with a native regulator of E. coli. Additionally, we engineered the L-arabinose transcriptional activator (AraC) of E. coli for altered ligand specificity. We performed site-specific saturation mutagenesis to generate AraC variants with altered effector specificity, with an aim to generate a mutant activated by xylulose. We characterized several mutant AraC variants which have lost the ability to respond specifically to the native L-arabinose effector. We promote this technique as a powerful tool for future iGEM teams to create regulatory circuits activated by novel small molecule ligands.

synthetic biology↗