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1.
New Phytol ; 226(3): 666-671, 2020 05.
Article in English | MEDLINE | ID: mdl-31912507

ABSTRACT

The emergence of critical zone (CZ) science has provided an integrative platform for investigating plant ecophysiology in the context of landscape evolution, weathering and hydrology. The CZ lies between the top of the vegetation canopy and fresh, chemically unaltered bedrock and plays a pivotal role in sustaining life. We consider what the CZ perspective has recently brought to the study of plant ecophysiology. We specifically highlight novel research demonstrating the importance of the deeper subsurface for plant water and nutrient relations. We also point to knowledge gaps and research opportunities, emphasising, in particular, greater focus on the roles of deep, nonsoil resources and how those resources influence and coevolve with plants as a frontier of plant ecophysiological research.


Subject(s)
Plants , Soil , Ecosystem , Hydrology , Water , Weather
2.
BMJ Case Rep ; 12(10)2019 Oct 17.
Article in English | MEDLINE | ID: mdl-31628092

ABSTRACT

We report a case of prolonged survival in a patient with known cervical intramedullary H3K27M-mutant diffuse midline glioma. A 39-year-old man presented for evaluation with several months of progressive upper extremity pain and weakness. MRI of the cervical spine revealed an intramedullary ring-enhancing lesion centred at C3-C4. Following subtotal surgical resection, a diagnosis of glioblastoma (GBM) was confirmed. Subsequent testing at a later date revealed an H3K27M mutation. He was initially treated with radiation and concomitant and adjuvant temozolomide. He had multiply recurrent disease and was treated with various regimens, including the histone deacetylase inhibitor valproic acid. The patient passed away 31 months (~2.5 years) after diagnosis. Our case is one of few reported adult spinal cord GBMs possessing the H3K27M mutation, and one with the longest reported overall survival in the literature to date.


Subject(s)
Cervical Cord/pathology , Glioblastoma/genetics , Glioblastoma/therapy , Spinal Cord Neoplasms/genetics , Spinal Cord Neoplasms/therapy , Adult , Cervical Cord/diagnostic imaging , Combined Modality Therapy , Fatal Outcome , Glioblastoma/diagnostic imaging , Histones/genetics , Humans , Laminectomy , Magnetic Resonance Imaging , Male , Radiotherapy , Spinal Cord Neoplasms/diagnostic imaging
3.
Forensic Sci Int Genet ; 31: 160-170, 2017 11.
Article in English | MEDLINE | ID: mdl-28950155

ABSTRACT

Samples containing low-copy numbers of DNA are routinely encountered in casework. The signal acquired from these sample types can be difficult to interpret as they do not always contain all of the genotypic information from each contributor, where the loss of genetic information is associated with sampling and detection effects. The present work focuses on developing a validation scheme to aid in mitigating the effects of the latter. We establish a scheme designed to simultaneously improve signal resolution and detection rates without costly large-scale experimental validation studies by applying a combined simulation and experimental based approach. Specifically, we parameterize an in silico DNA pipeline with experimental data acquired from the laboratory and use this to evaluate multifarious scenarios in a cost-effective manner. Metrics such as signal1copy-to-noise resolution, false positive and false negative signal detection rates are used to select tenable laboratory parameters that result in high-fidelity signal in the single-copy regime. We demonstrate that the metrics acquired from simulation are consistent with experimental data obtained from two capillary electrophoresis platforms and various injection parameters. Once good resolution is obtained, analytical thresholds can be determined using detection error tradeoff analysis, if necessary. Decreasing the limit of detection of the forensic process to one copy of DNA is a powerful mechanism by which to increase the information content on minor components of a mixture, which is particularly important for probabilistic system inference. If the forensic pipeline is engineered such that high-fidelity electropherogram signal is obtained, then the likelihood ratio (LR) of a true contributor increases and the probability that the LR of a randomly chosen person is greater than one decreases. This is, potentially, the first step towards standardization of the analytical pipeline across operational laboratories.


Subject(s)
DNA Fingerprinting/standards , Electrophoresis, Capillary , Humans , Likelihood Functions , Limit of Detection , Microsatellite Repeats , Monte Carlo Method , Reproducibility of Results
4.
Electrophoresis ; 38(6): 855-868, 2017 03.
Article in English | MEDLINE | ID: mdl-27981603

ABSTRACT

Short tandem repeat (STR) profiling from DNA samples has long been the bedrock of human identification. The laboratory process is composed of multiple procedures that include quantification, sample dilution, PCR, electrophoresis, and fragment analysis. The end product is a short tandem repeat electropherogram comprised of signal from allele, artifacts, and instrument noise. In order to optimize or alter laboratory protocols, a large number of validation samples must be created at significant expense. As a tool to support that process and to enable the exploration of complex scenarios without costly sample creation, a mechanistic stochastic model that incorporates each of the aforementioned processing features is described herein. The model allows rapid in silico simulation of electropherograms from multicontributor samples and enables detailed investigations of involved scenarios. An implementation of the model that is parameterized by extensive laboratory data is publically available. To illustrate its utility, the model was employed in order to evaluate the effects of sample dilutions, injection time, and cycle number on peak height, and the nature of stutter ratios at low template. We verify the model's findings by comparison with experimentally generated data.


Subject(s)
Computer Simulation , DNA Copy Number Variations , DNA/analysis , Electrophoresis, Capillary/methods , Polymerase Chain Reaction/methods , Alleles , DNA Fingerprinting , Humans , Microsatellite Repeats , Sensitivity and Specificity
5.
Brain Behav Immun ; 51: 176-195, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26296565

ABSTRACT

Spinal cord injury (SCI) leads to increased anxiety and depression in as many as 60% of patients. Yet, despite extensive clinical research focused on understanding the variables influencing psychological well-being following SCI, risk factors that decrease it remain unclear. We hypothesized that excitation of the immune system, inherent to SCI, may contribute to the decrease in psychological well-being. To test this hypothesis, we used a battery of established behavioral tests to assess depression and anxiety in spinally contused rats. The behavioral tests, and subsequent statistical analyses, revealed three cohorts of subjects that displayed behavioral characteristics of (1) depression, (2) depression and anxiety, or (3) no signs of decreased psychological well-being. Subsequent molecular analyses demonstrated that the psychological cohorts differed not only in behavioral symptoms, but also in peripheral (serum) and central (hippocampi and spinal cord) levels of pro-inflammatory cytokines. Subjects exhibiting a purely depression-like profile showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects exhibiting a depression- and anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord). These changes in inflammation were not associated with injury severity; suggesting that the association between inflammation and the expression of behaviors characteristic of decreased psychological well-being was not confounded by differential impairments in motor ability. These data support the hypothesis that inflammatory changes are associated with decreased psychological well-being following SCI.


Subject(s)
Anxiety/immunology , Depression/immunology , Encephalitis/metabolism , Inflammation/metabolism , Spinal Cord Injuries/immunology , Animals , Anxiety/etiology , Cytokines/blood , Cytokines/metabolism , Depression/etiology , Disease Models, Animal , Encephalitis/etiology , Hippocampus/metabolism , Inflammation/etiology , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Locomotion , Male , Organ Size , Pain/etiology , Pain/immunology , Pain Threshold , Rats , Rats, Sprague-Dawley , Recovery of Function , Spinal Cord/metabolism , Spinal Cord Injuries/complications , Thymus Gland/pathology , alpha-Macroglobulins/metabolism
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