Publications by authors named "Allison Miller"

129 Publications

Slippery when wet: cross-species transmission of divergent coronaviruses in bony and jawless fish and the evolutionary history of the .

Virus Evol 2021 31;7(2):veab050. Epub 2021 May 31.

Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand.

The comprise a genetically diverse group of positive-sense single-stranded RNA virus families that infect a range of invertebrate and vertebrate hosts. Recent metagenomic studies have identified nido-like virus sequences, particularly those related to the , in a range of aquatic hosts including fish, amphibians, and reptiles. We sought to identify additional members of the in both bony and jawless fish through a combination of total RNA sequencing (meta-transcriptomics) and data mining of published RNA sequencing data and from this reveal more of the long-term patterns and processes of coronavirus evolution. Accordingly, we identified a number of divergent viruses that fell within the subfamily of the , including those in a jawless fish-the pouched lamprey. By mining fish transcriptome data, we identified additional virus transcripts matching these viruses in bony fish from both marine and freshwater environments. These new viruses retained sequence conservation in the RNA-dependant RNA polymerase across the but formed a distinct and diverse phylogenetic group. Although there are broad-scale topological similarities between the phylogenies of the major groups of coronaviruses and their vertebrate hosts, the evolutionary relationship of viruses within the does not mirror that of their hosts. For example, the coronavirus found in the pouched lamprey fell within the phylogenetic diversity of bony fish letoviruses, indicative of past host switching events. Hence, despite possessing a phylogenetic history that likely spans the entire history of the vertebrates, coronavirus evolution has been characterised by relatively frequent cross-species transmission, particularly in hosts that reside in aquatic habitats.
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http://dx.doi.org/10.1093/ve/veab050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244743PMC
May 2021

Crop genetic erosion: understanding and responding to loss of crop diversity.

New Phytol 2021 Sep 13. Epub 2021 Sep 13.

Federal Office for Agriculture and Food (BLE), Information and Coordination Centre for Biological Diversity (IBV), Deichmanns Aue 29, 53179, Bonn, Germany.

Crop diversity underpins the productivity, resilience, and adaptive capacity of agriculture. Loss of this diversity, termed crop genetic erosion, is therefore concerning. While alarms regarding evident declines in crop diversity have been raised for over a century, the magnitude, trajectory, drivers, and significance of these losses remain insufficiently understood. We outline the various definitions, measurements, scales, and sources of information on crop genetic erosion. We then provide a synthesis of evidence regarding changes in the diversity of traditional crop landraces on farms, modern crop cultivars in agriculture, crop wild relatives in their natural habitats, and crop genetic resources held in conservation repositories. This evidence indicates that marked losses, but also maintenance and increases in diversity, have occurred in all these contexts, the extent depending on species, taxonomic and geographic scale, and region, as well as analytical approach. We discuss steps needed to further advance knowledge around the agricultural and societal significance, as well as conservation implications, of crop genetic erosion. Finally, we propose actions to mitigate, stem, and reverse further losses of crop diversity.
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http://dx.doi.org/10.1111/nph.17733DOI Listing
September 2021

Socializing the evidence for diabetes control to develop "mindlines": a qualitative pilot study.

BMC Fam Pract 2021 09 7;22(1):177. Epub 2021 Sep 7.

Department of Family & Community Medicine, Virginia Tech Carilion School of Medicine and The Carilion Clinic, 1 Riverside Circle, Suite 102, Roanoke, VA, 24016, USA.

Background: Evidence on specific interventions to improve diabetes control in primary care is available, but this evidence is not always well-implemented. The concept of "mindlines" has been proposed to explain how clinicians integrate evidence using specifics of their practices and patients to produce knowledge-in-practice-in-context. The goal of this pilot study was to operationalize this concept by creating a venue for clinician-staff interaction concerning evidence. The research team attempted to hold "mindlines"-producing conversations in primary care practices about evidence to improve diabetes control.

Methods: Each of four primary care practices in a single health system held practice-wide conversations about a simple diabetes intervention model over a provided lunch. The conversations were relatively informal and encouraged participation from all. The research team recorded the conversations and took field notes. The team analyzed the data using a framework adapted from the "mindlines" research and noted additional emergent themes.

Results: While most of the conversation concerned barriers to implementation of the simple diabetes intervention model, there were examples of practices adopting and adapting the evidence to suit their own needs and context. Performance metrics regarding diabetes control for the four practices improved after the intervention.

Conclusion: It appears that the type of conversations that "mindlines" research describes can be generated with facilitation around evidence, but further research is required to better understand the limitations and impact of this intervention.
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http://dx.doi.org/10.1186/s12875-021-01521-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422605PMC
September 2021

Demographic and Clinical Factors Associated With Death Among Persons <21 Years Old With Multisystem Inflammatory Syndrome in Children-United States, February 2020-March 2021.

Open Forum Infect Dis 2021 Aug 19;8(8):ofab388. Epub 2021 Jul 19.

CDC COVID-19 Response Team, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Multisystem inflammatory syndrome in children (MIS-C) occurs among persons aged <21 years following severe acute respiratory syndrome coronavirus 2 infection. Among 2818 MIS-C cases, 35 (1.2%) deaths were reported, primarily affecting racial/ethnic minority persons. Being 16-20 years old or having comorbidities was associated with death. Targeting coronavirus disease 2019 prevention among these groups and their caregivers might prevent MIS-C-related deaths.
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http://dx.doi.org/10.1093/ofid/ofab388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364981PMC
August 2021

Genetic association study of childhood aggression across raters, instruments, and age.

Transl Psychiatry 2021 07 30;11(1):413. Epub 2021 Jul 30.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (r) among rater-specific assessment of AGG ranged from r = 0.46 between self- and teacher-assessment to r = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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http://dx.doi.org/10.1038/s41398-021-01480-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324785PMC
July 2021

Moderate-intensity exercise versus high-intensity interval training to recover walking post-stroke: protocol for a randomized controlled trial.

Trials 2021 Jul 16;22(1):457. Epub 2021 Jul 16.

Department of Rehabilitation, Exercise and Nutrition Sciences, University of Cincinnati, 3225 Eden Avenue, Cincinnati, OH, USA.

Background: Stroke results in neurologic impairments and aerobic deconditioning that contribute to limited walking capacity which is a major barrier post-stroke. Current exercise recommendations and stroke rehabilitation guidelines recommend moderate-intensity aerobic training post-stroke. Locomotor high-intensity interval training is a promising new strategy that has shown significantly greater improvements in aerobic fitness and motor performance than moderate-intensity aerobic training in other populations. However, the relative benefits and risks of high-intensity interval training and moderate-intensity aerobic training remain poorly understood following stroke. In this study, we hypothesize that locomotor high-intensity interval training will result in greater improvements in walking capacity than moderate-intensity aerobic training.

Methods: Using a single-blind, 3-site randomized controlled trial, 50 chronic (> 6 months) stroke survivors are randomly assigned to complete 36 locomotor training sessions of either high-intensity interval training or moderate-intensity aerobic training. Main eligibility criteria are age 40-80 years, single stroke for which the participant received treatment (experienced 6 months to 5 years prior to consent), walking speed ≤ 1.0 m/s, able to walk at least 3 min on the treadmill at ≥ 0.13 m/s (0.3 mph), stable cardiovascular condition (American Heart Association class B), and the ability to walk 10 m overground without continuous physical assistance. The primary outcome (walking capacity) and secondary outcomes (self-selected and fast gait speed, aerobic fitness, and fatigue) are assessed prior to initiating training and after 4 weeks, 8 weeks, and 12 weeks of training.

Discussion: This study will provide fundamental new knowledge to inform the selection of intensity and duration dosing parameters for gait recovery and optimization of aerobic training interventions in chronic stroke. Data needed to justify and design a subsequent definitive trial will also be obtained. Thus, the results of this study will inform future stroke rehabilitation guidelines on how to optimally improve walking capacity following stroke.

Trial Registration: ClinicalTrials.gov NCT03760016 . Registered on November 30, 2018.
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http://dx.doi.org/10.1186/s13063-021-05419-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284012PMC
July 2021

Outbreaks Associated with Treated Recreational Water - United States, 2015-2019.

MMWR Morb Mortal Wkly Rep 2021 May 21;70(20):733-738. Epub 2021 May 21.

Outbreaks associated with treated recreational water can be caused by pathogens or chemicals in aquatic venues such as pools, hot tubs, water playgrounds, or other artificially constructed structures that are intended for recreational or therapeutic purposes. For the pseriod 2015-2019, public health officials from 36 states and the District of Columbia (DC) voluntarily reported 208 outbreaks associated with treated recreational water. Almost all (199; 96%) of the outbreaks were associated with public (nonbackyard) pools, hot tubs, or water playgrounds. These outbreaks resulted in at least 3,646 cases of illness, 286 hospitalizations, and 13 deaths. Among the 155 (75%) outbreaks with a confirmed infectious etiology, 76 (49%) were caused by Cryptosporidium (which causes cryptosporidiosis, a gastrointestinal illness) and 65 (42%) by Legionella (which causes Legionnaires' disease, a severe pneumonia, and Pontiac fever, a milder illness with flu-like symptoms). Cryptosporidium accounted for 2,492 (84%) of 2,953 cases resulting from the 155 outbreaks with a confirmed etiology. All 13 deaths occurred in persons affected by a Legionnaires' disease outbreak. Among the 208 outbreaks, 71 (34%) were associated with a hotel (i.e., hotel, motel, lodge, or inn) or a resort, and 107 (51%) started during June-August. Implementing recommendations in CDC's Model Aquatic Health Code (MAHC) (1) can help prevent outbreaks associated with treated recreational water in public aquatic venues.
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http://dx.doi.org/10.15585/mmwr.mm7020a1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136425PMC
May 2021

The Eating Disorders Genetics Initiative (EDGI): study protocol.

BMC Psychiatry 2021 05 4;21(1):234. Epub 2021 May 4.

QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Herston, QLD, 4029, Australia.

Background: The Eating Disorders Genetics Initiative (EDGI) is an international investigation exploring the role of genes and environment in anorexia nervosa, bulimia nervosa, and binge-eating disorder.

Methods: A total of 14,500 individuals with eating disorders and 1500 controls will be included from the United States (US), Australia (AU), New Zealand (NZ), and Denmark (DK). In the US, AU, and NZ, participants will complete comprehensive online phenotyping and will submit a saliva sample for genotyping. In DK, individuals with eating disorders will be identified by the National Patient Register, and genotyping will occur using bloodspots archived from birth. A genome-wide association study will be conducted within EDGI and via meta-analysis with other data from the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED).

Discussion: EDGI represents the largest genetic study of eating disorders ever to be conducted and is designed to rapidly advance the study of the genetics of the three major eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder). We will explicate the genetic architecture of eating disorders relative to each other and to other psychiatric and metabolic disorders and traits. Our goal is for EDGI to deliver "actionable" findings that can be transformed into clinically meaningful insights.

Trial Registration: EDGI is a registered clinical trial: clinicaltrials.gov NCT04378101 .
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http://dx.doi.org/10.1186/s12888-021-03212-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097919PMC
May 2021

Beyond Physical Capacity: Factors Associated With Real-world Walking Activity After Stroke.

Arch Phys Med Rehabil 2021 Apr 21. Epub 2021 Apr 21.

Department of Biomechanics and Movement Science Program, University of Delaware, Newark, DE; Department of Physical Therapy, University of Delaware, Newark, DE. Electronic address:

Objective: To identify homogeneous subsets of survivors of chronic stroke who share similar characteristics across several domains and test if these groups differ in real-world walking activity. We hypothesized that variables representing the domains of walking ability, psychosocial, environment, and cognition would be important contributors in differentiating real-world walking activity in survivors of chronic stroke.

Design: Cross-sectional, secondary data analysis.

Setting: University/laboratory.

Participants: A total of 283 individuals with chronic (≥6mo) stroke (N=238).

Interventions: Not applicable.

Main Outcome Measures: Thirteen variables representing 5 domains were included: (1) walking ability: 6-minute walk test (6MWT), self-selected speed (SSS) of gait; (2) psychosocial: Patient Health Questionnaire-9, Activities-specific Balance Confidence (ABC) scale; (3) physical health: low-density lipoprotein cholesterol, body mass index, Charlson Comorbidity Index (CCI); (4) cognition: Montreal Cognitive Assessment (MoCA); and (5) environment: living situation and marital status, work status, Area Deprivation Index (ADI), Walk Score. Mixture modeling was used to identify latent classes of survivors of stroke. After identifying the latent classes, walking activity, measured as steps per day (SPD), was included as a distal outcome to understand if classes were meaningfully different in their real-world walking RESULTS: A model with 3 latent classes was selected. The 6MWT, SSS, ABC scale, and Walk Score were significantly different among all 3 classes. Differences were also seen for the MoCA, ADI, and CCI between 2 of the 3 classes. Importantly, the distal outcome of SPD was significantly different in all classes, indicating that real-world walking activity differs among the groups identified by the mixture model.

Conclusions: Survivors of stroke with lower walking ability, lower self-efficacy, lower cognitive abilities, and greater area deprivation had lower SPD. These results demonstrate that the physical and social environment (including socioeconomic factors) and cognitive function should also be considered when developing interventions to improve real-world walking activity after stroke.
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http://dx.doi.org/10.1016/j.apmr.2021.03.023DOI Listing
April 2021

Genome-wide impact of hydrogen peroxide on maintenance DNA methylation in replicating cells.

Epigenetics Chromatin 2021 Mar 24;14(1):17. Epub 2021 Mar 24.

Department of Pathology and Biomedical Science, University of Otago, PO Box 4345, Christchurch, 8140, New Zealand.

Background: Environmental factors, such as oxidative stress, have the potential to modify the epigenetic landscape of cells. We have previously shown that DNA methyltransferase (DNMT) activity can be inhibited by sublethal doses of hydrogen peroxide (HO). However, site-specific changes in DNA methylation and the reversibility of any changes have not been explored. Using bead chip array technology, differential methylation was assessed in Jurkat T-lymphoma cells following exposure to HO.

Results: Sublethal HO exposure was associated with an initial genome-wide decrease in DNA methylation in replicating cells, which was largely corrected 72 h later. However, some alterations were conserved through subsequent cycles of cell division. Significant changes to the variability of DNA methylation were also observed both globally and at the site-specific level.

Conclusions: This research indicates that increased exposure to HO can result in long-term alterations to DNA methylation patterns, providing a mechanism for environmental factors to have prolonged impact on gene expression.
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http://dx.doi.org/10.1186/s13072-021-00388-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992848PMC
March 2021

Transcriptional analysis of sodium valproate in a serotonergic cell line reveals gene regulation through both HDAC inhibition-dependent and independent mechanisms.

Pharmacogenomics J 2021 06 1;21(3):359-375. Epub 2021 Mar 1.

Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.

Sodium valproate (VPA) is a histone deacetylase (HDAC) inhibitor, widely prescribed in the treatment of bipolar disorder, and yet the precise modes of therapeutic action for this drug are not fully understood. After exposure of the rat serotonergic cell line RN46A to VPA, RNA-sequencing (RNA-Seq) analysis showed widespread changes in gene expression. Analysis by four bioinformatic pipelines revealed as many as 230 genes were significantly upregulated and 72 genes were significantly downregulated. A subset of 23 differentially expressed genes was selected for validation using the nCounter® platform, and of these we obtained robust validation for ADAM23, LSP1, MAOB, MMP13, PAK3, SERPINB2, SNAP91, WNT6, and ZCCHC12. We investigated the effect of lithium on this subset and found four genes, CDKN1C, LSP1, SERPINB2, and WNT6 co-regulated by lithium and VPA. We also explored the effects of other HDAC inhibitors and the VPA analogue valpromide on the subset of 23 selected genes. Expression of eight of these genes, CDKN1C, MAOB, MMP13, NGFR, SHANK3, VGF, WNT6 and ZCCHC12, was modified by HDAC inhibition, whereas others did not appear to respond to several HDAC inhibitors tested. These results suggest VPA may regulate genes through both HDAC-dependent and independent mechanisms. Understanding the broader gene regulatory effects of VPA in this serotonergic cell model should provide insights into how this drug works and whether other HDAC inhibitor compounds may have similar gene regulatory effects, as well as highlighting molecular processes that may underlie regulation of mood.
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http://dx.doi.org/10.1038/s41397-021-00215-xDOI Listing
June 2021

Functional Characteristics and Phenotypic Plasticity of CD57PD1 CD4 T Cells and Their Relationship with Transplant Immunosuppression.

J Immunol 2021 04 17;206(7):1668-1676. Epub 2021 Feb 17.

Department of Surgery, Duke University, Durham, NC 27710.

Costimulation blockade (CoB)-based immunosuppression offers the promise of improved transplantation outcomes with reduced drug toxicity. However, it is hampered by early acute rejections, mediated at least in part by differentiated, CoB-resistant T cells, such as CD57PD1 CD4 T cells. In this study, we characterize these cells pretransplant, determine their fate posttransplant, and examine their proliferative capacity in vitro in humans. Our studies show that CD57PD1 CD4 T cells are correlated with increasing age and CMV infection pretransplant, and persist for up to 1 y posttransplant. These cells are replication incompetent alone but proliferated in the presence of unsorted PBMCs in a contact-independent manner. When stimulated, cells sorted by CD57/PD1 status upregulate markers of activation with proliferation. Up to 85% of CD57PD1 cells change expression of CD57/PD1 with stimulation, typically, upregulating PD1 and downregulating CD57. PD1 upregulation is accentuated in the presence of rapamycin but prevented by tacrolimus. These data support a general theory of CoB-resistant cells as Ag-experienced, costimulation-independent cells and suggest a mechanism for the synergy of belatacept and rapamycin, with increased expression of the activation marker PD1 potentiating exhaustion of CoB-resistant cells.
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http://dx.doi.org/10.4049/jimmunol.2000736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987798PMC
April 2021

Grapevine Microbiota Reflect Diversity among Compartments and Complex Interactions within and among Root and Shoot Systems.

Microorganisms 2021 Jan 2;9(1). Epub 2021 Jan 2.

Department of Biology, Saint Louis University, 3507 Laclede Ave, St. Louis, MO 63103, USA.

Grafting connects root and shoot systems of distinct individuals, bringing microbial communities of different genotypes together in a single plant. How do root system and shoot system genotypes influence plant microbiota in grafted grapevines? To address this, we utilized clonal replicates of the grapevine 'Chambourcin', growing ungrafted and grafted to three different rootstocks in three irrigation treatments. Our objectives were to (1) characterize the microbiota (bacteria and fungi) of below-ground compartments (roots, adjacent soil) and above-ground compartments (leaves, berries), (2) determine how rootstock genotype, irrigation, and their interaction influences grapevine microbiota in different compartments, and (3) investigate abundance of microorganisms implicated in the late-season grapevine disease sour rot ( and ). We found that plant compartment had the largest influence on microbial diversity. Neither rootstock genotype nor irrigation significantly influenced microbial diversity or composition. However, differential abundance of bacterial and fungal taxa varied as a function of rootstock and irrigation treatment; in particular, and displayed higher relative abundance in berries of grapevines grafted to '1103P' and 'SO4' rootstocks and varied across irrigation treatments. This study demonstrates that grapevine compartments retain distinct microbiota and identifies associations between rootstock genotypes, irrigation treatment, and the relative abundance of agriculturally relevant microorganisms in the berries.
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http://dx.doi.org/10.3390/microorganisms9010092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823683PMC
January 2021

Readiness to Change is Related to Real-World Walking and Depressive Symptoms in Chronic Stroke.

J Neurol Phys Ther 2021 01;45(1):28-35

Departments of Biomechanics and Movement Science Program (A.M., D.S.R.), Physical Therapy (T.W., H.W., E.T., D.S.R.), and Biostatistics Core Facility (R.T.P.), University of Delaware, Newark.

Background And Purpose: The transtheoretical model is a health behavior model used to understand an individual's readiness to change their behavior. This study aims to apply the transtheoretical model in understanding a person with stroke's readiness to change their activity level, as it relates to physical capacity, physical health, depressive symptoms, self-efficacy, and daily stepping activity.

Methods: This was a cross-sectional analysis of baseline data from a clinical trial. Participants' readiness to change their activity levels was measured via self-report and daily stepping activity was measured using a step activity monitor. Robust regression (M-estimation with robust standard errors) was used to test the relationship between readiness to change and measures of physical capacity (6-minute walk test, self-selected walking speed), physical health (body mass index, age-adjusted Charlson Comorbidity Index), depressive symptoms (Patient Health Questionnaire-9), self-efficacy (Activities-Specific Balance Confidence Scale), and daily stepping (steps per day).

Results: A total of 274 individuals were included in the analysis. Adjusted for age, readiness to change was positively related to daily stepping (β = 0.29, P < 0.001) and negatively related to depressive symptoms (β = -0.13, P = 0.01). Readiness to change was not significantly associated with measures of physical capacity, physical health, or self-efficacy.

Discussion: These results suggest that individuals with stroke in the later stages of change may demonstrate greater daily stepping activity and lower depressive symptoms compared with those in earlier stages.

Conclusions: Understanding the relationship between readiness to change, daily stepping, and depressive symptoms will help clinicians implement appropriate stage-specific intervention strategies and facilitate greater improvement in activity levels.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A333).
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http://dx.doi.org/10.1097/NPT.0000000000000345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739270PMC
January 2021

RAD-sequencing reveals patterns of diversification and hybridization, and the accumulation of reproductive isolation in a clade of partially sympatric, tropical island trees.

Mol Ecol 2021 Sep 2;30(18):4520-4537. Epub 2020 Dec 2.

Center for Conservation and Sustainable Development, Missouri Botanical Garden, St. Louis, MO, USA.

A common pattern observed in temperate tree clades is that species are often morphologically distinct and partially interfertile but maintain species cohesion despite ongoing hybridization where ranges overlap. Although closely related species commonly occur in sympatry in tropical ecosystems, little is known about patterns of hybridization within a clade over time, and the implications of this hybridization for the maintenance of species boundaries. In this study, we focused on a clade of sympatric trees in the genus Diospyros in the Mascarene islands and investigated whether species are genetically distinct, whether they hybridize, and how patterns of hybridization are related to the time since divergence among species. We sampled multiple populations from each of 12 Mascarene Diospyros species, generated genome-wide single nucleotide polymorphism data using 2bRADseq, and conducted population genomic and phylogenomic analyses. We found that Mascarene Diospyros species diverged millions of years ago and are today largely genetically distinct from one another. Although hybridization was observed between closely related species belonging to the same subclade, more distantly related species showed little evidence of interspecific hybridization. Phylogenomic analyses also suggested that introgression has occurred during the evolutionary history of the clade. This suggests that, as diversification progressed, interspecific hybridization occurred among species, but became infrequent as lineages diverged from one another and evolved reproductive barriers. Species now coexist in partial sympatry, and experience limited hybridization between close relatives. Additional research is needed to better understand the role that introgression may have played in adaptation and diversification of Mascarene Diospyros, and its relevance for conservation.
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http://dx.doi.org/10.1111/mec.15736DOI Listing
September 2021

SARS-CoV-2-Associated Deaths Among Persons Aged <21 Years - United States, February 12-July 31, 2020.

MMWR Morb Mortal Wkly Rep 2020 Sep 18;69(37):1324-1329. Epub 2020 Sep 18.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED). These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.
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http://dx.doi.org/10.15585/mmwr.mm6937e4DOI Listing
September 2020

Social and physical environmental factors in daily stepping activity in those with chronic stroke.

Top Stroke Rehabil 2021 04 10;28(3):161-169. Epub 2020 Aug 10.

Department of Biomechanics and Movement Science Program, University of Delaware, Newark, DE, USA.

Background, Purpose/objective: Walking behavior in the chronic stroke population is multi-factorial. Previous work focused on the role of physical and biopsychosocial factors in understanding daily stepping post stroke. However, qualitative evidence suggests that social and physical environmental factors also affect daily stepping in those with stroke. The purpose of this study was to understand the role of social and physical environmental factors in daily stepping after stroke.

Methods: A total of 249 individuals ≥6 months post stroke were included in this cross-sectional analysis (129 females, mean age 62.98 years, SD 11.94). The social environment included living situation, work status, and marital status. The physical environment included the Area Deprivation Index (ADI) and Walk Score. At least 3 days of stepping was collected using an accelerometry-based device. Predictors were entered sequentially into a regression model: demographic characteristics, social environmental factors, and physical environmental factors.

Results: After adjusting for demographic factors, social environmental factors explained 6.2% ( =.017) of the variance in post stroke daily stepping. The addition of physical environmental factors improved the model (ΔR =.029, =.024). The final model explained 9.2% ( =.003) of the variance in daily stepping. Lower area deprivation (ADI β = -0.178, =.015) and working (working vs. retired β = -0.187, = .029 and working vs. unemployed β = -0.227, =.008) were associated with greater daily stepping.

Discussion/conclusion: Social and physical environmental factors predicted daily stepping and should be considered when setting expectations relative to the effects of rehabilitation on daily stepping in individuals poststroke.
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http://dx.doi.org/10.1080/10749357.2020.1803571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873161PMC
April 2021

Outbreaks Associated with Untreated Recreational Water - California, Maine, and Minnesota, 2018-2019.

MMWR Morb Mortal Wkly Rep 2020 Jun 26;69(25):781-783. Epub 2020 Jun 26.

Outbreaks associated with fresh or marine (i.e., untreated) recreational water can be caused by pathogens or chemicals, including toxins. Voluntary reporting of these outbreaks to CDC's National Outbreak Reporting System (NORS) began in 2009. NORS data for 2009-2017 are finalized, and data for 2018-2019 are provisional. During 2009-2019 (as of May 13, 2020), public health officials from 31 states voluntarily reported 119 untreated recreational water-associated outbreaks, resulting at least 5,240 cases; 103 of the outbreaks (87%) started during June-August. Among the 119 outbreaks, 88 (74%) had confirmed etiologies. The leading etiologies were enteric pathogens: norovirus (19 [22%] outbreaks; 1,858 cases); Shiga toxin-producing Escherichia coli (STEC) (19 [22%]; 240), Cryptosporidium (17 [19%]; 237), and Shigella (14 [16%]; 713). This report highlights three examples of outbreaks that occurred during 2018-2019, were caused by leading etiologies (Shigella, norovirus, or STEC), and demonstrate the wide geographic distribution of such outbreaks across the United States. Detection and investigation of untreated recreational water-associated outbreaks are challenging, and the sources of these outbreaks often are not identified. Tools for controlling and preventing transmission of enteric pathogens through untreated recreational water include epidemiologic investigations, regular monitoring of water quality (i.e., testing for fecal indicator bacteria), microbial source tracking, and health policy and communications (e.g., observing beach closure signs and not swimming while ill with diarrhea).
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http://dx.doi.org/10.15585/mmwr.mm6925a3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316318PMC
June 2020

MinION Sequencing of colorectal cancer tumour microbiomes-A comparison with amplicon-based and RNA-Sequencing.

PLoS One 2020 20;15(5):e0233170. Epub 2020 May 20.

Department of Surgery, University of Otago, Christchurch, New Zealand.

Background: Recent evidence suggests a role for the gut microbiome in the development and progression of many diseases and many studies have been carried out to analyse the microbiome using a variety of methods. In this study, we compare MinION sequencing with meta-transcriptomics and amplicon-based sequencing for microbiome analysis of colorectal tumour tissue samples.

Methods: DNA and RNA were extracted from 11 colorectal tumour samples. 16S rRNA amplicon sequencing and MinION sequencing was carried out using genomic DNA, and RNA-Sequencing for meta-transcriptomic analysis. Non-human MinION and RNA-Sequencing reads, and 16S rRNA amplicon sequencing reads were taxonomically classified using a database built from available RefSeq bacterial and archaeal genomes and a k-mer based algorithm in Kraken2. Concordance between the three platforms at different taxonomic levels was tested on a per-sample basis using Spearman's rank correlation.

Results: The average number of reads per sample using RNA-Sequencing was greater than 129 times that generated using MinION sequencing. However, the average read length of MinION sequences was more than 13 times that of RNA or 16S rRNA amplicon sequencing. Taxonomic assignment using 16S sequencing was less reliable beyond the genus level, and both RNA-Sequencing and MinION sequencing could detect greater numbers of phyla and genera in the same samples, compared to 16S sequencing. Bacterial species associated with colorectal cancer, Fusobacterium nucleatum, Parvimonas micra, Bacteroides fragilis and Porphyromonas gingivalis, were detectable using MinION, RNA-Sequencing and 16S rRNA amplicon sequencing data.

Conclusions: Long-read sequences generated using MinION sequencing can compensate for low numbers of reads for bacterial classification. MinION sequencing can discriminate between bacterial strains and plasmids and shows potential as a cost-effective tool for rapid microbiome sequencing in a clinical setting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233170PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239435PMC
August 2020

Current technologies to endotoxin detection and removal for biopharmaceutical purification.

Biotechnol Bioeng 2020 08 16;117(8):2588-2609. Epub 2020 May 16.

Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri.

Endotoxins are the major contributors to the pyrogenic response caused by contaminated pharmaceutical products, formulation ingredients, and medical devices. Recombinant biopharmaceutical products are manufactured using living organisms, including Gram-negative bacteria. Upon the death of a Gram-negative bacterium, endotoxins (also known as lipopolysaccharides) in the outer cell membrane are released into the lysate where they can interact with and form bonds with biomolecules, including target therapeutic compounds. Endotoxin contamination of biologic products may also occur through water, raw materials such as excipients, media, additives, sera, equipment, containers closure systems, and expression systems used in manufacturing. The manufacturing process is, therefore, in critical need of methods to reduce and remove endotoxins by monitoring raw materials and in-process intermediates at critical steps, in addition to final drug product release testing. This review paper highlights a discussion on three major topics about endotoxin detection techniques, upstream processes for the production of therapeutic molecules, and downstream processes to eliminate endotoxins during product purification. Finally, we have evaluated the effectiveness of endotoxin removal processes from a perspective of high purity and low cost.
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http://dx.doi.org/10.1002/bit.27362DOI Listing
August 2020

Comparative Analysis of Early Life Stage Traits in Annual and Perennial Crops and Their Wild Relatives.

Front Plant Sci 2020 10;11:34. Epub 2020 Mar 10.

Department of Biology, Saint Louis University, St. Louis, MO, United States.

Herbaceous perennial species are receiving increased attention for their potential to provide both edible products and ecosystem services in agricultural systems. Many legumes (Fabaceae Lindl.) are of special interest due to nitrogen fixation carried out by bacteria in their roots and their production of protein-rich, edible seeds. However, herbaceous perennial legumes have yet to enter widespread use as pulse crops, and the response of wild, herbaceous perennial species to artificial selection for increased seed yield remains under investigation. Here we compare cultivated and wild accessions of congeneric annual and herbaceous perennial legume species to investigate associations of lifespan and cultivation with early life stage traits including seed size, germination, and first year vegetative growth patterns, and to assess variation and covariation in these traits. We use "cultivated" to describe accessions with a history of human planting and use, which encompasses a continuum of domestication. Analyses focused on three annual and four perennial species of the economically important genus . We found a significant association of both lifespan and cultivation status with seed size (weight, two-dimensional lateral area, length), node number, and most biomass traits (with cultivation alone showing additional significant associations). Wild annual and perennial accessions primarily showed only slight differences in trait values. Relative to wild forms, both cultivated annual and cultivated perennial accessions exhibited greater seed size and larger overall vegetative size, with cultivated perennials showing greater mean trait differences relative to wild accessions than cultivated annuals. Germination proportion was significantly lower in cultivated relative to wild annual accessions, while no significant difference was observed between cultivated and wild perennial germination. Regardless of lifespan and cultivation status, seed size traits were positively correlated with most vegetative traits, and all biomass traits examined here were positively correlated. This study highlights some fundamental similarities and differences between annual and herbaceous perennial legumes and provides insights into how perennial legumes might respond to artificial selection compared to annual species.
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http://dx.doi.org/10.3389/fpls.2020.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076113PMC
March 2020

Common CYP2D6, CYP2C9, and CYP2C19 Gene Variants, Health Anxiety, and Neuroticism Are Not Associated With Self-Reported Antidepressant Side Effects.

Front Genet 2019 26;10:1199. Epub 2019 Nov 26.

Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.

Many patients prescribed an antidepressant stop taking it because of side effects. Genetic factors and psychological factors including state or trait anxiety, may explain variation in side effect outcomes. Our aim was to examine the relative contribution of genetic and psychological factors in people with self-reported antidepressant side effects. We undertook a case control study (n = 194) of people who took a selective serotonin reuptake inhibitor (SSRI) or serotonin/noradrenaline reuptake inhibitor (SNRI) in the past 2 years, recruited social media advertising. Cases had previously not tolerated at least one trial of an SSRI or SNRI, evidenced by stopping the drug or reducing the dose by at least 50% because of a side effect. Control participants had taken an SSRI or SNRI but did not meet case criteria. Variation in the genes , , and was analyzed by Sanger sequencing on DNA extracted from blood or saliva. Participants completed the Short Health Anxiety Inventory-18, K10, and NEO-FFI-3 personality questionnaire. Participants were 87.1% female. 70.8% had a current K10 score of 22 or more. There was no consistent evidence that cases had higher psychological distress, health anxiety, or neuroticism. There was low correspondence between participants' CYP2D6, CYP2C19, and CYP2C9 phenotypes and their history of antidepressant tolerability. For this cohort of patients a history of not tolerating SSRI or SNRI therapy was not associated with variation in the pharmacogenes we tested, nor was it associated with health anxiety or neuroticism.
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http://dx.doi.org/10.3389/fgene.2019.01199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901912PMC
November 2019

Clinical Practice Guideline to Improve Locomotor Function Following Chronic Stroke, Incomplete Spinal Cord Injury, and Brain Injury.

J Neurol Phys Ther 2020 01;44(1):49-100

Department of Physical Medicine and Rehabilitation, Indiana University, Indianapolis (T.G.H., C.E.H.); Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, Illinois (T.G.H.); Department of Physical Therapy, University of Delaware, Newark (D.S.R., A.M.); Kessler Institute for Rehabilitation, West Orange, New Jersey (I.G.W., A.M., D.H.); Rutgers, New Jersey Medical School, Newark (I.G.W.); Infinity Rehab, Wilsonville, Oregon (P.L.S.); Department of Physical Therapy, University of Florida, Gainesville and Brooks Rehabilitation Center, Jacksonville, Florida (E.J.F., K.A.H.); Department of Physical Therapy, Wayne State University, Detroit, Michigan (N.E.F.); Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, Massachusetts (K.L.H.); Program in Physical Therapy, Washington University in St Louis, St Louis, Missouri (C.L.H.); Department of Physical Therapy, A.T. Still University, Mesa, Arizona (J.V.L.); and Sheltering Arms Hospital, Mechanicsville, Virginia (A.W.).

Background: Individuals with acute-onset central nervous system (CNS) injury, including stroke, motor incomplete spinal cord injury, or traumatic brain injury, often experience lasting locomotor deficits, as quantified by decreases in gait speed and distance walked over a specific duration (timed distance). The goal of the present clinical practice guideline was to delineate the relative efficacy of various interventions to improve walking speed and timed distance in ambulatory individuals greater than 6 months following these specific diagnoses.

Methods: A systematic review of the literature published between 1995 and 2016 was performed in 4 databases for randomized controlled clinical trials focused on these specific patient populations, at least 6 months postinjury and with specific outcomes of walking speed and timed distance. For all studies, specific parameters of training interventions including frequency, intensity, time, and type were detailed as possible. Recommendations were determined on the basis of the strength of the evidence and the potential harm, risks, or costs of providing a specific training paradigm, particularly when another intervention may be available and can provide greater benefit.

Results: Strong evidence indicates that clinicians should offer walking training at moderate to high intensities or virtual reality-based training to ambulatory individuals greater than 6 months following acute-onset CNS injury to improve walking speed or distance. In contrast, weak evidence suggests that strength training, circuit (ie, combined) training or cycling training at moderate to high intensities, and virtual reality-based balance training may improve walking speed and distance in these patient groups. Finally, strong evidence suggests that body weight-supported treadmill training, robotic-assisted training, or sitting/standing balance training without virtual reality should not be performed to improve walking speed or distance in ambulatory individuals greater than 6 months following acute-onset CNS injury to improve walking speed or distance.

Discussion: The collective findings suggest that large amounts of task-specific (ie, locomotor) practice may be critical for improvements in walking function, although only at higher cardiovascular intensities or with augmented feedback to increase patient's engagement. Lower-intensity walking interventions or impairment-based training strategies demonstrated equivocal or limited efficacy.

Limitations: As walking speed and distance were primary outcomes, the research participants included in the studies walked without substantial physical assistance. This guideline may not apply to patients with limited ambulatory function, where provision of walking training may require substantial physical assistance.

Summary: The guideline suggests that task-specific walking training should be performed to improve walking speed and distance in those with acute-onset CNS injury although only at higher intensities or with augmented feedback. Future studies should clarify the potential utility of specific training parameters that lead to improved walking speed and distance in these populations in both chronic and subacute stages following injury.

Disclaimer: These recommendations are intended as a guide for clinicians to optimize rehabilitation outcomes for persons with chronic stroke, incomplete spinal cord injury, and traumatic brain injury to improve walking speed and distance.
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http://dx.doi.org/10.1097/NPT.0000000000000303DOI Listing
January 2020

The Three Ps: Psychiatry, Pharmacy, and Pharmacogenomics, a Brief Report From New Zealand.

Front Psychiatry 2019 20;10:690. Epub 2019 Sep 20.

Gene Structure and Function Lab, Carney Centre for Pharmacogenomics, Department of Pathology & Biomedical Science, University of Otago, Christchurch, New Zealand.

We describe a case series of 22 individuals who were referred to our laboratory by a pharmacist based in a mental health hospital, for pharmacogenetic analysis due to severe or unexpected adverse drug reactions (ADRs) to psychiatric medication. The participants were genotyped for common variation in the , , and genes, using Sanger sequencing. We tested variants in these genes as they have the strongest evidence with respect to altering the pharmacokinetics of commonly prescribed psychiatric medicine. Looking specifically at the subset of 18 European study participants, we observed a comparatively high but non-significant rate of pharmacogenetic variants, compared to allele frequency surveys in unselected population samples. For , we observed an elevated frequency of both poor (17%) and intermediate (33%) metabolizers when compared with previously reported frequencies (6% and 12% respectively). For , we observed an increased frequency of intermediate (33%) and ultra-rapid (17%) metabolizers compared to expected frequencies (21% and 4% respectively). For , the frequency of intermediate metabolizers (22%) was elevated compared to the expected population frequency (11%). While sample size is a major limitation of this brief report, we can conclude that patients with adverse reactions to antidepressant or antipsychotic drugs selected by a specialist mental health pharmacist appear to have a relatively high rate of genetic variants in pharmacogenes known to affect the pharmacokinetics of these drugs. The selective application of such pharmacogenetic tests by clinical pharmacists may be a valuable approach to clarify the basis for adverse or unusual responses to medication, and to guide ongoing prescribing decisions for this group of patients.
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http://dx.doi.org/10.3389/fpsyt.2019.00690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764017PMC
September 2019

A multiplex pharmacogenetics assay using the MinION nanopore sequencing device.

Pharmacogenet Genomics 2019 11;29(9):207-215

Department of Pathology and Biomedical Science, University of Otago, Christchurch.

Objectives: The MinION nanopore sequencing device opens the opportunity to cost-effective and point-of-care DNA sequencing. As a proof of principle, we developed a multiplex assay targeting pharmacogenetic variants related to clopidogrel and warfarin, the two commonly used drugs that show response variability due to genetic polymorphisms.

Methods: Six reference and 78 clinical DNA samples were amplified by PCR to generate 15 amplicons targeting 27 key variants. These products were then barcoded to enable sample multiplexing in one sequencing run. Four variant calling tools (marginCaller, VarScan 2, nanopolish, Clairvoyante) were used to compare genotyping accuracy.

Results: In our cohort, 81 out of 84 samples were successfully sequenced and genotyped. Using nanopolish as the variant calling tool achieved accuracy >95% for all except two variants. A known single base deletion (CYP2C9*6) was successfully detected.

Conclusion: While minor misgenotyping issues exist, this work demonstrates that drug-specific or broad pharmacogenetic screening assays using small PCR amplicons are possible on the MinION sequencing device.
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http://dx.doi.org/10.1097/FPC.0000000000000385DOI Listing
November 2019

Nanopore sequencing of the pharmacogene allows simultaneous haplotyping and detection of duplications.

Pharmacogenomics 2019 09;20(14):1033-1047

Department of Pathology & Biomedical Science, University of Otago, Christchurch, New Zealand.

Long read sequencing offers the promise of overcoming some of the challenges in accurate genotyping of complex genes, along with the advantage of straightforward variant phasing. We have established methods for sequencing and haplotyping of the whole gene using nanopore sequencing. 32 samples covering various haplotypes including gene duplication were sequenced on the GridION platform. Haplotypes of 52 alleles matched accurately to known star (*) allele subvariants, with the remaining 12 being assigned as new alleles, or new subvariants of known alleles. Duplicated alleles could be detected by analyzing the allelic balance. Nanopore sequencing of offers a high throughput method for accurate haplotyping, detection of new variants and determination of duplicated alleles.
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http://dx.doi.org/10.2217/pgs-2019-0080DOI Listing
September 2019

Characterizing 3D inflorescence architecture in grapevine using X-ray imaging and advanced morphometrics: implications for understanding cluster density.

J Exp Bot 2019 11;70(21):6261-6276

Donald Danforth Plant Science Center, St Louis, MO, USA.

Inflorescence architecture provides the scaffold on which flowers and fruits develop, and consequently is a primary trait under investigation in many crop systems. Yet the challenge remains to analyse these complex 3D branching structures with appropriate tools. High information content datasets are required to represent the actual structure and facilitate full analysis of both the geometric and the topological features relevant to phenotypic variation in order to clarify evolutionary and developmental inflorescence patterns. We combined advanced imaging (X-ray tomography) and computational approaches (topological and geometric data analysis and structural simulations) to comprehensively characterize grapevine inflorescence architecture (the rachis and all branches without berries) among 10 wild Vitis species. Clustering and correlation analyses revealed unexpected relationships, for example pedicel branch angles were largely independent of other traits. We identified multivariate traits that typified species, which allowed us to classify species with 78.3% accuracy, versus 10% by chance. Twelve traits had strong signals across phylogenetic clades, providing insight into the evolution of inflorescence architecture. We provide an advanced framework to quantify 3D inflorescence and other branched plant structures that can be used to tease apart subtle, heritable features for a better understanding of genetic and environmental effects on plant phenotypes.
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http://dx.doi.org/10.1093/jxb/erz394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859732PMC
November 2019

Contrasting signals of cardiovascular health among natriuretic peptides in subjects without heart disease.

Sci Rep 2019 08 20;9(1):12108. Epub 2019 Aug 20.

Departments of Medicine, University of Otago, Christchurch, New Zealand.

Natriuretic Peptides (NP) are important in maintaining normal cardiac and metabolic status and have been used to predict cardiovascular events. Whether plasma concentrations of NP products within the normal range reflect cardio-metabolic health is unknown. Plasma NTproANP, NTproBNP and NTproCNP and their bioactive counterparts were measured in a random sample of 348 community dwellers aged 49-51 yr without heart disease and associations sought with established vascular risk factors, echocardiographic indices and a genetic variant previously linked with BNP. Stratified by sex, each of ten vascular risk factors were positively associated with NTproCNP whereas associations with NTproBNP and NTproANP were all negative. In both sexes, higher plasma NTproCNP was associated with higher arterial elastance, lower LV stroke volume and lower LV end diastolic volume. Exactly opposite associations were found with plasma NTproBNP or NTproANP. Sex specific differences were identified: positive association of NTproBNP with LV end systolic volume and the negative association with LV elastance were found only in males. The genetic variant rs198358 was independently associated with NTproBNP but not with NTproANP. In conclusion, higher NTproCNP is likely to be an adaptive response to impaired LV relaxation whereas genetic factors likely contribute to higher NTproBNP and improved cardio-metabolic health at midlife.
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http://dx.doi.org/10.1038/s41598-019-48553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702214PMC
August 2019

Living with Two Genomes: Grafting and Its Implications for Plant Genome-to-Genome Interactions, Phenotypic Variation, and Evolution.

Annu Rev Genet 2019 12 19;53:195-215. Epub 2019 Aug 19.

Department of Botany and Plant Sciences, University of California, Riverside, California 92521, USA.

Plant genomes interact when genetically distinct individuals join, or are joined, together. Individuals can fuse in three contexts: artificial grafts, natural grafts, and host-parasite interactions. Artificial grafts have been studied for decades and are important platforms for studying the movement of RNA, DNA, and protein. Yet several mysteries about artificial grafts remain, including the factors that contribute to graft incompatibility, the prevalence of genetic and epigenetic modifications caused by exchanges between graft partners, and the long-term effects of these modifications on phenotype. Host-parasite interactions also lead to the exchange of materials, and RNA exchange actively contributes to an ongoing arms race between parasite virulence and host resistance. Little is known about natural grafts except that they can be frequent and may provide opportunities for evolutionary innovation through genome exchange. In this review, we survey our current understanding about these three mechanisms of contact, the genomic interactions that result, and the potential evolutionary implications.
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http://dx.doi.org/10.1146/annurev-genet-112618-043545DOI Listing
December 2019
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