Biology subjects

Foster, J.

Publications and source records attributed to Foster, J..

27 records · Page 2Linked to original sources

bioRxiv2021

Circulating miRNAs associated with bone mineral density in healthy adult baboons.

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and circulate in the blood, making them attractive biomarkers of disease state for tissues like bone that are challenging to interrogate directly. Here we report on five miRNAs - miR-197-3p, miR-320a, miR-320b, miR-331-5p, and miR-423-5p - that are associated with bone mineral density (BMD) in 147 healthy adult baboons. These baboons range in age from 15 to 25 years (45 to 75 human equivalent years) and were 65% female with a broad range of BMDs including a minority of osteopenic individuals. miRNAs were generated via RNA sequencing from buffy coats collected at necropsy and areal BMD evaluated via DXA of the lumbar vertebrae post-mortem. Differential expression analysis controlled for the underlying pedigree structure of these animals to account for genetic variation which may be driving miRNA abundance and BMD values. While many of these miRNAs have been associated with risk of human osteoporosis, this finding is of interest because the cohort represent a model of normal aging and bone metabolism rather than a disease cohort. The replication of miRNA associations with osteoporosis or other bone metabolic disorders in animals with healthy BMD suggests an overlap in normal variation and disease states. We suggest that these miRNAs are involved in the regulation of cellular proliferation, apoptosis, and protein composition in the extracellular matrix throughout life. However, age-related dysregulation of these systems may lead to disease causing associations of the miRNAs among individuals with clinically defined disease.

genomics↗

bioRxiv2021

Examining the effect of chronic intranasal oxytocin administration on the neuroanatomy and behavior of three autism-related mouse models

1Although initially showing great potential, oxytocin treatment has encountered a translational hurdle in its promise of treating the social deficits of autism. Some debate surrounds the ability of oxytocin to successfully enter the brain, and therefore modify neuroanatomy. Moreover, given the heterogeneous nature of autism, treatment will only amerliorate symptoms in a subset of patients. Therefore, to determine whether oxytocin changes brain circuitry, and whether it does so variably, depending on genotype, we implemented a large randomized, blinded, placebo-controlled, preclinical study on chronic intranasal oxytocin treatment in three different mouse models related to autism with a focus on using neuroanatomical phenotypes to assess and subset treatment response. Intranasal oxytocin (0.6IU) was administered daily, for 28 days, starting at 5 weeks of age to the 16p11.2 deletion, Shank3 (exon 4-9) knockout, and Fmr1 knockout mouse models. Given the sensitivity of structural magnetic resonance imaging (MRI) to the neurological effects of interventions like drugs, along with many other advantages, the mice underwent in vivo longitudinal and high-resolution ex vivo imaging with MRI. The scans included three in vivo T1-weighted, 90um isotropic resolution scans and a T2-weighted, 3D fast spin echo with 40um isotropic resolution ex vivo scan to assess the changes in neuroanatomy using established automated image registration and deformation based morphometry approaches in response to oxytocin treatment. The behavior of the mice was assessed in multiple domains, including social behaviours and repetitive behaviours, among others. Treatment effect on the neuroanatomy did not reach significance, although the pattern of trending effects was promising. No significant effect of treatment was found on social behavior in any of the strains, although a significant effect of treatment was found in the Fmr1 mouse, with treatment normalizing a grooming deficit. No other treatment effect on behavior was observed that survived multiple comparisons correction. Overall, chronic treatment with oxytocin had limited effects on the three mouse models related to autism, and no promising pattern of response susceptibility emerged.

developmental biology↗

bioRxiv2020

Lipid-associated PML domains regulate CCTα, Lipin1 and lipid homeostasis

Nuclear LDs (nLDs) originate at the inner nuclear membrane by a mechanism that involves the promyelocytic leukemia (PML) protein. Here we demonstrate that nLDs in oleate-treated U2OS cells are associated with Lipid-Associated PML (LAP) domains that differ from canonical PML nuclear bodies by the relative absence of SUMO1, SP100 and DAXX. nLDs were also enriched in CTP:phosphocholine cytidylyltransferase (CCT), the phosphatidic acid phosphatase Lipin1 and diacylglycerol (DAG). High resolution imaging revealed that LAP domains and CCT occupy distinct polarized regions on nLDs, and that loss of LAP domains in PML knockout U2OS cells reduced the recruitment of CCT onto nLDs by its amphipathic -helical M-domain. The association of Lipin1 and DAG with nLDs was also LAP domain-dependent. The disruption of CCT and Lipin1 localization on nLDs in PML knockout cells resulted in the inhibition of phosphatidylcholine and triacylglycerol synthesis indicating that LAP domains are a unique PML subdomain involved in nLD assembly and regulation of lipid metabolism.

cell biology↗

bioRxiv2019

Population genomic evidence that human and animal infections in Africa come from the same populations of Dracunculus medinensis

BackgroundGuinea worm - Dracunculus medinensis - was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 30 human cases reported globally last year. Despite the enormous success of eradication efforts to date, one complication has arisen. Over the last few years, hundreds of dogs have been found infected with this previously apparently anthroponotic parasite, almost all in Chad. Moreover, the relative numbers of infections in humans and dogs suggests that dogs may be key in maintaining transmission in that country.\n\nResultsIn an effort to shed light on this peculiar epidemiology of Guinea worm in Chad, we have sequenced and compared the genomes of worms from dog, human and other animal infections. Confirming previous work with other molecular markers, we show that all of these worms are D. medinensis, and that the same population of worms are causing both infections, can confirm the suspected transmission between host species and detect signs of a population bottleneck due to the eradication efforts. The diversity of worms in Chad appears to exclude the possibility that there were no, or very few, worms present in the country during a 10-year absence of reported cases.\n\nConclusionsThis work reinforces the importance of adequate surveillance of both human and dog populations in the Guinea worm eradication campaign and suggests that control programs should stay aware of the possible emergence of unusual epidemiology as they approach elimination.

genomics↗

bioRxiv2019

Computational and experimental analysis of the glycophosphatidylinositol-anchored proteome of the human parasitic nematode Brugia malayi

Further characterization of essential systems in the parasitic filarial nematode Brugia malayi is needed to better understand its biology, its interaction with its hosts, and to identify critical components that can be exploited to develop novel treatments. The production of glycophosphatidylinositol-anchored proteins (GPI-APs) is essential in humans, yeast, and the nematode Caenorhabditis elegans. In addition, GPI-APs perform many important roles for cells. In this study, we characterized the B. malayi GPI-anchored proteome using both computational and experimental approaches. We used bioinformatic strategies to show the presence or absence of B. malayi GPI-AP biosynthetic pathway genes and to compile a putative B. malayi GPI-AP proteome using available prediction programs. We verified these in silico analyses using proteomics to identify GPI-AP candidates prepared from the surface of intact worms and from membrane enriched extracts. Our study represents the first description of the GPI-anchored proteome in B. malayi and lays the groundwork for further exploration of this essential protein modification as a target for novel anthelmintic therapeutic strategies.

molecular biology↗

bioRxiv2018

Priming winter wheat seeds with the bacterial quorum sensing signal N-hexanoyl-L-homoserine lactone (C6-HSL) shows potential to improve plant growth and seed yield

Several model plants are known to respond to bacterial quorum sensing molecules with altered root growth and gene expression patterns and induced resistance to plant pathogens. These compounds may represent novel elicitors that could be applied as seed primers to enhance cereal crop resistance to pathogens and abiotic stress and to improve yields. We investigated whether the acyl-homoserine lactone N-hexanoyl-L-homoserine lactone (C6-HSL) impacted winter wheat (Triticum aestivum L.) seed germination, plant development and productivity, using two Ukrainian varieties, Volodarka and Yatran 60, in both in vitro experiments and field trials. In vitro germination experiments indicated that C6-HSL seed priming had a small but significant positive impact on germination levels (1.2x increase, p < 0.0001), coleoptile and radicle development (1.4x increase, p < 0.0001). Field trials over two growing seasons (2015-16 and 2016-17) also demonstrated significant improvements in biomass at the tillering stage (1.4x increase, p < 0.0001), and crop structure and productivity at maturity including grain yield (1.4 - 1.5x increase, p < 0.0007) and quality (1.3x increase in good grain, p < 0.0001). In some cases variety effects were observed (p [≤] 0.05) suggesting that the effect of C6-HSL seed priming might depend on plant genetics, and some benefits of priming were also evident in F1 plants grown from seeds collected the previous season (p [≤] 0.05). These field-scale findings suggest that bacterial acyl-homoserine lactones such as C6-HSL could be used to improve cereal crop growth and yield and reduce reliance on fungicides and fertilisers to combat pathogens and stress.

plant biology↗

bioRxiv2018

Independent control of slow and fast flight manoeuvres in insects: the roles of vision and antennal mechanoreception

Flying animals need constant sensory feedback about their body position and orientation for flight control. The visual system provides essential but slow feedback. In contrast, mechanosensory channels can provide feedback at much shorter timescales. How the contributions from these two senses are integrated remains an open question in most insect groups. In Diptera, fast mechanosensory feedback is provided by organs called halteres, and is crucial for the control of rapid flight manoeuvres, while vision controls manoeuvres in lower temporal frequency bands. Here we have investigated the visual-mechanosensory integration in an insect which lacks halteres: the hawkmoth Macroglossum stellatarum. They represent a large group of insects that use Johnstons organs in their antennae to provide mechanosensory feedback on perturbations in body position. High-speed videos of freely-flying hawkmoths hovering at stationary or oscillating artificial flowers showed that positional fidelity during flight was reduced in flagella ablated animals, but was recovered after flagella re-attachment. Our experiments show that antennal mechanosensory feedback specifically mediates fast flight manoeuvres, but not slow ones. Differences in the latency of visual feedback (in different light intensities) affected all antennal conditions equally, suggesting there was no compensatory interaction between antennal and visual feedback under the tested conditions. These results establish the importance of antennal mechanosensors in providing rapid mechanosensory feedback for finer control of flight manoeuvres, acting in parallel to visual feedback.

neuroscience↗

bioRxiv2018

Targeted enrichment outperforms other enrichment techniques and enables more multi-species RNA-Seq analyses

Enrichment methodologies enable analysis of minor members in multi-species transcriptomic analyses. We compared standard enrichment of bacterial and eukaryotic mRNA to targeted enrichment with Agilent SureSelect (AgSS) capture for Brugia malayi, Aspergillus fumigatus, and the Wolbachia endosymbiont of B. malayi (wBm). Without introducing significant systematic bias, the AgSS quantitatively enriched samples, resulting in more reads mapping to the target organism. The AgSS-enriched libraries consistently had a positive linear correlation with its unenriched counterpart (r2=0.559-0.867). Up to a 2,242-fold enrichment of RNA from the target organism was obtained following a power law (r2=0.90), with the greatest fold enrichment achieved in samples with the largest ratio difference between the major and minor members. While using a single total library for prokaryote and eukaryote in a single sample could be beneficial for samples where RNA is limiting, we observed a decrease in reads mapping to protein coding genes and an increase of multi-mapping reads to rRNAs in AgSS enrichments from eukaryotic total RNA libraries as opposed to eukaryotic poly(A)-enriched libraries. Our results support a recommendation of using Agilent SureSelect targeted enrichment on poly(A)-enriched libraries for eukaryotic captures and total RNA libraries for prokaryotic captures to increase the robustness of multi-species transcriptomic studies.

genomics↗

bioRxiv2017

Working memory implements distinct maintenance mechanisms depending on task goals

Working memory is the function by which we temporarily maintain information to achieve current task goals. Models of working memory typically debate where this information is stored, rather than how it is stored. Here we ask instead what neural mechanisms are involved in storage, and how these mechanisms change as a function of task goals. Participants either had to reproduce the orientation of a memorized bar (continuous recall task), or identify the memorized bar in a search array (visual search task). The sensory input and retention interval were identical in both tasks. Next, we used decoding and forward modeling on multivariate electroencephalogram (EEG) and time-frequency decomposed EEG to investigate which neural signals carry more informational content during the retention interval. In the continuous recall task, working memory content was preferentially carried by induced oscillatory alpha-band power, while in the visual search task it was more strongly carried by the distribution of evoked (consistently elevated and non-oscillatory) EEG activity. To show the independence of these two signals, we were able to remove informational content from one signal without affecting informational content in the other. Finally, we show that the tuning characteristics of both signals change in opposite directions depending on the current task goal. We propose that these signals reflect oscillatory and elevated firing-rate mechanisms that respectively support location-based and object-based maintenance. Together, these data challenge current models of working memory that place storage in particular regions, but rather emphasize the importance of different distributed maintenance signals depending on task goals.\n\nSignificance statement (120 words)Without realizing, we are constantly moving things in and out of our minds eye, an ability also referred to as working memory. Where did I put my screwdriver? Do we still have milk in the fridge? A central question in working memory research is how the brain maintains this information temporarily. Here we show that different neural mechanisms are involved in working memory depending on what the memory is used for. For example, remembering what a bottle of milk looks like invokes a different neural mechanism from remembering how much milk it contains: the first one primarily involved in being able to find the object, and the other one involving spatial position, such as the milk level in the bottle.

neuroscience↗