Biology subjects

Cook, S.

Publications and source records attributed to Cook, S..

25 records · Page 2Linked to original sources

bioRxiv2019

Lower dormancy with rapid germination is an important strategy for seeds in an arid zone with unpredictable rainfall

Seed germination traits are key drivers of population dynamics, yet they are under-represented in community ecology studies, which have predominately focussed on adult plant and seed morphological traits. We studied the seed traits and germination strategy of eight woody plant species to investigate regeneration strategies in the arid zone of eastern Australia. To cope with stochastic and minimal rainfall, we predict that arid seeds will either have rapid germination across a wide range of temperatures, improved germination under cooler temperatures, or dormancy and/or longevity traits to delay or stagger germination across time. To understand how temperature affects germination responses, seeds of eight keystone arid species were germinated under laboratory conditions, and under three diurnal temperatures (30/20{degrees}C, 25/15{degrees}C and 17/7{degrees}C) for 30 days. Seeds of species in this study are currently stored for minesite restoration projects, hence we tested for decline in seed viability across 24 months in dry storage at similar storage conditions ({approx}20{degrees}C). Six of the eight arid species studied had non-dormant, rapidly germinating seeds, and only two species had physiological dormancy traits. Seed longevity differed widely between species, from one recalcitrant species surviving only months in storage (P50 = <3 months) and one serotinous species surviving for many years (P50 = 84 months). Our results highlight the importance of understanding the reproductive strategies of plant species in arid environments. Rapid germination, the dominant seed trait of species included in this study, allows arid species to capitalise on sporadic rainfall. However, some species also exhibit dormancy and delayed germination; this an alternative strategy which spreads the risk of germination failure over time. We highlight important seed traits and germination strategies of plants from an arid zone with stochastic rainfall and discuss the implications for their restoration.

plant biology↗

bioRxiv2019

Cardiac structure and function in patients with schizophrenia taking antipsychotic drugs: an MRI study

Cardiovascular disease (CVD) is a major cause of excess mortality in schizophrenia. Preclinical evidence shows antipsychotics can cause myocardial fibrosis and myocardial inflammation in murine models, but it is not known if this is the case in patients. We therefore set out to determine if there is evidence of cardiac fibrosis and/or inflammation using cardiac MRI in medicated patients with schizophrenia compared with matched healthy controls. 31 participants (14 patients and 17 controls) underwent cardiac MRI assessing myocardial markers of fibrosis/inflammation, indexed by native myocardial T1 time, and cardiac structure (left ventricular (LV) mass) and function (left/right ventricular end-diastolic and end-systolic volumes, stroke volumes, and ejection fractions). Participants were physically fit, and matched for age, gender, smoking, blood pressure, BMI, HbA1c, ethnicity, and physical activity. Compared with controls, native myocardial T1 was significantly longer in patients with schizophrenia (effect size, d=0.89; p=0.02). Patients had significantly lower LV mass, and lower left/right ventricular end-diastolic and stroke volumes (effect sizes, d=0.86-1.08; all p-values <0.05). There were no significant differences in left/right end-systolic volumes and ejection fractions between groups (p>0.05). These results suggest an early diffuse fibro-inflammatory myocardial process in patients that is independent of established CVD-risk factors and could contribute to the excess cardiovascular mortality associated with schizophrenia. Future studies are required to determine if this is due to antipsychotic treatment or is intrinsic to schizophrenia.

physiology↗

bioRxiv2019

Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging

Despite growing adoption of consumer wearables, the potential for sleep metrics from these devices to contribute to sleep-related biomedical research remains largely uncharacterized. Here we analyze sleep tracking data, along with questionnaire responses and multi-modal phenotypic data, generated from 482 normal volunteers. First, we provide a detailed comparison of wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived sleep duration. We also analyzed our multi-modal phenotypic data and showed that wearable-derived TST and SE are associated with various cardiovascular disease risk markers, whereas self-reported measures were not. Using whole-genome sequencing data, we estimated leukocyte telomere length and showed that volunteers with insufficient sleep also exhibit premature telomere attrition. Our study highlights the potential for sleep metrics generated by consumer wearables to provide novel insights into data generated from population cohort studies.

epidemiology↗

bioRxiv2018

In vivo generation of post-infarct mouse cardiac muscle by cardiomyocyte progenitors produced with a reproducible laminin-promoted human stem cell differentiation system

Regeneration of human heart muscle after injury is extremely limited and an unmet clinical need. Despite extensive research, there are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). Here, we identified laminin-221 (LN-221) as the main cardiac laminin, which was produced here as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates genes associated with pluripotency and teratoma development. We developed a chemically defined, xeno-free laminin-based cardiomyocyte differentiation protocol to reproducibly generate CVPs that form human muscle in vivo. We assessed the reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from two different hESC lines. Single-cell RNA sequencing of CVPs derived from two hESC lines further showed high reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology.

cell biology↗

bioRxiv2018

IL-11 is a therapeutic target in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) remains a progressive disease despite best medical management. We previously identified IL-11 as a critical factor for cardiovascular fibrosis and examine here its role in pulmonary fibrosis. IL-11 is consistently upregulated in IPF genomic datasets, which we confirmed by histology. Pulmonary fibroblasts stimulated with IL-11 transform into invasive myofibroblasts whereas fibroblasts from Il11ra deleted mice did not respond to pro-fibrotic stimuli. In the mouse, injection of recombinant Il-11 or fibroblast-specific expression of Il-11 caused pulmonary fibrosis. We then generated a neutralising IL-11 binding antibody that blocks lung fibroblast activation across species. In a mouse model of IPF, anti-IL-11 therapy attenuated lung fibrosis and specifically blocked Erk activation. These data prioritise IL-11 as an accessible drug target in IPF.\n\nOne Sentence SummaryNon-canonical IL-11 signalling is a central hallmark of idiopathic pulmonary fibrosis and represents a novel target for antibody therapies.

molecular biology↗

bioRxiv2017

Reliable detection of translational regulation with Ribo-seq

Ribosome profiling1 (Ribo-Seq) reveals genome-wide translation rates via the quantification of ribosome protected fragments (RPFs) of mRNAs. Significant differences of RPFs between conditions can indicate differential translation if they do not match changes in transcription. Reliably identifying translational differences is complicated by the fact that the mRNA level of the transcript directly affects the ribosome occupancy. Changes in mRNA abundances result in changes in RPFs due to differential transcription and not translation. As such, identification of differentially translated genes (DTGs) requires finding significant changes in RPF read counts that cannot be explained by variation in mRNA read counts.\n\nXiao et al.2 developed Xtail with the purpose of more accurately identifying DTGs in pairwise comparisons. Several other methods were also recently released (Ribodiff3 ...

bioinformatics↗

bioRxiv2017

Using DNase Hi-C techniques to map global and local three-dimensional genome architecture at high resolution

The folding and three-dimensional (3D) organization of chromatin in the nucleus critically impacts genome function. The past decade has witnessed rapid advances in genomic tools for delineating 3D genome architecture. Among them, chromosome conformation capture (3C)-based methods such as Hi-C are the most widely used techniques for mapping chromatin interactions. However, traditional Hi-C protocols rely on restriction enzymes (REs) to fragment chromatin and are therefore limited in resolution. We recently developed DNase Hi-C for mapping 3D genome organization, which uses DNase I for chromatin fragmentation. DNase Hi-C overcomes RE-related limitations associated with traditional Hi-C methods, leading to improved methodological resolution. Furthermore, combining this method with DNA capture technology provides a high-throughput approach (targeted DNase Hi-C) that allows for mapping fine-scale chromatin architecture at exceptionally high resolution. Hence, targeted DNase Hi-C will be valuable for delineating the physical landscapes of cis-regulatory networks that control gene expression and for characterizing phenotype-associated chromatin 3D signatures. Here, we provide a detailed description of method design and step-by-step working protocols for these two methods.\n\nHighlightsO_LIDNase Hi-C, a method for comprehensive mapping of chromatin contacts on a whole-genome scale, is based on random chromatin fragmentation by DNase I digestion instead of sequence-specific restriction enzyme (RE) digestion.\nC_LIO_LITargeted DNase Hi-C, which combines DNase Hi-C with DNA capture technology, is a high-throughput method for mapping fine-scale chromatin architecture of genomic loci of interest at a resolution comparable to that of genomic annotations of functional elements.\nC_LIO_LIDNase Hi-C and targeted DNase Hi-C provide the first high-throughput way to overcome the RE-digestion-associated resolution limit of 3C-based methods.\nC_LIO_LIStep-by-step whole-genome and targeted DNase Hi-C protocols for mapping global and local 3D genome architecture, respectively, are described.\nC_LI

genomics↗