Publications by authors named "R Douglas Wilson"

8,810 Publications

  • Page 1 of 1

Simple and reliable protocol for identifying talented junior players in team sports using small-sided games.

Scand J Med Sci Sports 2021 Apr 12. Epub 2021 Apr 12.

School of Biological Sciences, The University of Queensland, St Lucia, QLD, 4072, Australia.

We designed and tested a protocol for measuring the performance of individuals in small-sided soccer games. We tested our protocol on three different groups of youth players from elite Brazilian football academies. Players in each group played a series of 3v3 games, in which individuals were randomly assigned into new teams and against new opponents for each game. We calculated each individual's average individual goals scored, goals scored by team-mates, goals conceded, and net team goals per game. Our protocol was consistent across days and repeatable across groups, with ICCs of 0.57 to 0.69 for average net goals per game across testing days. Players could achieve high success by scoring goals or ensuring their team concede few goals. We also calculated the first and second dimension of a principal component analysis based on each player's number of goals scored, goals scored by team-mates, and number of goals conceded per game. Players that were overall high performers had higher PC scores, while PC scores represented the type of contribution made by a player to overall performance. Positive PC values were indicative of high number of individual goals while negative values were associated with more goals from team-mates and fewer conceded goals. Our design allows coaches and scouts to easily collect a robust metric of individual performance using randomly-designed, small-sided games. We also provide simulations that allows one to apply our methodology for individual talent identification to other small-sided games in any team sport.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/sms.13969DOI Listing
April 2021

High-speed quantitative optical imaging of absolute metabolism in the rat cortex.

Neurophotonics 2021 Apr 8;8(2):025001. Epub 2021 Apr 8.

University of California, Beckman Laser Institute, Irvine, California, United States.

Quantitative measures of blood flow and metabolism are essential for improved assessment of brain health and response to ischemic injury. We demonstrate a multimodal technique for measuring the cerebral metabolic rate of oxygen ( ) in the rodent brain on an absolute scale ( ). We use laser speckle imaging at 809 nm and spatial frequency domain imaging at 655, 730, and 850 nm to obtain spatiotemporal maps of cerebral blood flow, tissue absorption ( ), and tissue scattering ( ). Knowledge of these three values enables calculation of a characteristic blood flow speed, which in turn is input to a mathematical model with a "zero-flow" boundary condition to calculate absolute . We apply this method to a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation. With this model, the zero-flow condition occurs during entry into CA. The values calculated with our method are in good agreement with those measured with magnetic resonance and positron emission tomography by other groups. Our technique provides a quantitative metric of absolute cerebral metabolism that can potentially be used for comparison between animals and longitudinal monitoring of a single animal over multiple days. Though this report focuses on metabolism in a model of ischemia and reperfusion, this technique can potentially be applied to far broader types of acute brain injury and whole-body pathological occurrences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1117/1.NPh.8.2.025001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027868PMC
April 2021

The role of body mass index on quality indicators following minimally-invasive radical prostatectomy.

Investig Clin Urol 2021 Mar 31. Epub 2021 Mar 31.

Department of Urology, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA.

Purpose: We sought to determine the role of body mass index (BMI) on quality indicators, such as length of stay and readmission. The National Surgical Quality Improvement Program (NSQIP) database was queried to examine the effect of obesity, defined as BMI >30, on outcomes after Minimally Invasive Radical Retropubic Prostatectomy (MI-RRP).

Materials And Methods: Utilizing the NSQIP database, patient records were identified using the Current Procedural Terminology (CPT) code 55866 (laparoscopy, surgical prostatectomy, radical retropubic) during a 10-year period (2007-2017). Obesity was classified according to the CDC classification. Chi-square tests were utilized to evaluate BMI distribution by surgery year. Logistic regression was used to evaluate the relationship of BMI with length of stay (LOS) and hospital readmission within 30 days, after controlling for preoperative variables.

Results: Records of 49,238 patients who have undergone MI-RRP during 2007-2017 were evaluated. Mean yearly BMI rose from 28.5 to 29.2, while the percentage of surgical patients with BMI >30 rose by 5% (33% to 38%; p<0.0001) over the study period. Obese patients demonstrated higher morbidity, prolonged LOS, and increased readmission rates after MI-RRP. Obesity severity correlated negatively with quality indicators in a graded fashion.

Conclusions: Obesity rates in patients undergoing MI-RRP increased from 2007-2017. Obese patients are at increased risk of morbidity, prolonged LOS, and readmission within 30 days, following MI-RRP. These patients should not be excluded from MI-RRP; rather, physicians should discuss these increased risks with their patients. Proper weight loss strategies should be instituted preoperatively to mitigate these risks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4111/icu.20200411DOI Listing
March 2021

The NIH Somatic Cell Genome Editing program.

Nature 2021 Apr 7;592(7853):195-204. Epub 2021 Apr 7.

Department of Neurosurgery, Yale University, New Haven, CT, USA.

The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-021-03191-1DOI Listing
April 2021

Molecular classification of a complex structural rearrangement of the RB1 locus in an infant with sporadic, isolated, intracranial, sellar region retinoblastoma.

Acta Neuropathol Commun 2021 Apr 7;9(1):61. Epub 2021 Apr 7.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.

Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40478-021-01164-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025529PMC
April 2021

Targeting nucleotide metabolism enhances the efficacy of anthracyclines and anti-metabolites in triple-negative breast cancer.

NPJ Breast Cancer 2021 Apr 6;7(1):38. Epub 2021 Apr 6.

Medicine, Dentistry and Biomedical Sciences: Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.

Triple-negative breast cancer (TNBC) remains the most lethal breast cancer subtype with poor response rates to the current chemotherapies and a lack of additional effective treatment options. We have identified deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) as a critical gatekeeper that protects tumour DNA from the genotoxic misincorporation of uracil during treatment with standard chemotherapeutic agents commonly used in the FEC regimen. dUTPase catalyses the hydrolytic dephosphorylation of deoxyuridine triphosphate (dUTP) to deoxyuridine monophosphate (dUMP), providing dUMP for thymidylate synthase as part of the thymidylate biosynthesis pathway and maintaining low intracellular dUTP concentrations. This is crucial as DNA polymerase cannot distinguish between dUTP and deoxythymidylate triphosphate (dTTP), leading to dUTP misincorporation into DNA. Targeting dUTPase and inducing uracil misincorporation during the repair of DNA damage induced by fluoropyrimidines or anthracyclines represents an effective strategy to induce cell lethality. dUTPase inhibition significantly sensitised TNBC cell lines to fluoropyrimidines and anthracyclines through imbalanced nucleotide pools and increased DNA damage leading to decreased proliferation and increased cell death. These results suggest that repair of treatment-mediated DNA damage requires dUTPase to prevent uracil misincorporation and that inhibition of dUTPase is a promising strategy to enhance the efficacy of TNBC chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-021-00245-5DOI Listing
April 2021

Review of the Breathability and Filtration Efficiency of Common Household Materials for Face Masks.

ACS Nano 2021 Apr 6. Epub 2021 Apr 6.

Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia 30307, United States.

The World Health Organization and the United States Centers for Disease Control have recommended universal face masking by the general public to slow the spread of COVID-19. A number of recent studies have evaluated the filtration efficiency and pressure differential (an indicator of breathability) of various, widely available materials that the general public can use to make face masks at home. In this review, we summarize those studies to provide guidance for both the public to select the best materials for face masks and for future researchers to rigorously evaluate and report on mask material testing. Of the tested fabric materials and material combinations with adequate breathability, most single and multilayer combinations had a filtration efficiency of <30%. Most studies evaluating commonly available mask materials did not follow standard methods that would facilitate comparison across studies, and materials were often described with too few details to allow consumers to purchase equivalent materials to make their own masks. To improve the usability of future study results, researchers should use standard methods and report material characteristics in detail.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c10146DOI Listing
April 2021

Bilateral cerebellar hemorrhagic infarcts as an early presentation following opioid-induced toxic encephalopathy in an adult patient.

Radiol Case Rep 2021 May 20;16(5):1207-1210. Epub 2021 Mar 20.

Division of Neuroradiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

In the midst of the national opioid crisis, it is necessary for emergency physicians and radiologists to be familiar with presentations of opioid-related complications. We describe a case report of a 51-year-old female who developed bilateral cerebellar hemorrhages following opioid and benzodiazepine overdose. Malignant cerebellar edema is a rare but recognized complication following opiate overdose in children or chronic heroin toxicity. However, acute cerebellar involvement is rarely reported in adults. We feel that clinicians and radiologists should keep in mind the possibility of opioid toxic encephalopathy in their differential for adults with acute bilateral cerebellar infarcts and/or hemorrhages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radcr.2021.02.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010571PMC
May 2021

Phylogenomics reveals ancient and contemporary gene flow contributing to the evolutionary history of sea ducks (Tribe Mergini).

Mol Phylogenet Evol 2021 Mar 30:107164. Epub 2021 Mar 30.

US Geological Survey, Alaska Science Center, 4210 University Dr., Anchorage, AK, 99508, USA.

Insight into complex evolutionary histories continues to build through broad comparative phylogenomic and population genomic studies. In particular, there is a need to understand the extent and scale that gene flow contributes to standing genomic diversity and the role introgression has played in evolutionary processes such as hybrid speciation. Here, we investigate the evolutionary history of the Mergini tribe (sea ducks) by coupling multi-species comparisons with phylogenomic analyses of thousands of nuclear ddRAD-seq loci, including Z-sex chromosome and autosomal linked loci, and the mitogenome assayed across all extant sea duck species in North America. All sea duck species are strongly structured across all sampled marker types (pair-wise species Φ >0.2), with clear genetic assignments of individuals to their respective species, and phylogenetic relationships recapitulate known relationships. Despite strong species integrity, we identify at least 18 putative hybrids; with all but one being late generational backcrosses. Most interesting, we provide the first evidence that an ancestral gene flow event between long-tailed ducks (Clangula hyemalis) and true Eiders (Somateria spp.) not only moved genetic material into the former species, but likely generated a novel species - the Steller's eider (Polysticta stelleri) - via hybrid speciation. Despite generally low contemporary levels of gene flow, we conclude that hybridization has and continues to be an important process that shifts novel genetic variation between species within the tribe Mergini. Finally, we outline methods that permit researchers to contrast genomic patterns of contemporary versus ancestral gene flow when attempting to reconstruct potentially complex evolutionary histories.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ympev.2021.107164DOI Listing
March 2021

Dyspnea in Chronic Low Ventricular Preload States.

Ann Am Thorac Soc 2021 04;18(4):573-581

Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, and.

Dyspnea in low-preload states is an underrecognized but growing diagnosis in patients with unexplained dyspnea. Patients can often experience debilitating symptoms at rest and with exertion, as low measured preload often leads to decreased cardiac output and ultimately dyspnea. In the present article, we performed a review of the literature and a multidisciplinary evaluation to understand the pathophysiology, diagnosis, and treatment of dyspnea in low-preload states. We explored selected etiologies and suggested an algorithm to approach unexplained dyspnea. The mainstay of diagnosis remains as invasive cardiopulmonary exercise testing. We concluded with a variety of nonpharmacological and pharmacological therapies, highlighting that a multifactorial approach may lead to the best results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202005-581CMEDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009011PMC
April 2021

When is a "breed" not a breed: the myth of the Mpwapwa cattle of Tanzania.

Authors:
R Trevor Wilson

Trop Anim Health Prod 2021 Mar 30;53(2):233. Epub 2021 Mar 30.

Bartridge House, Umberleigh, EX37 9AS, UK.

Almost all of Tanzania's huge cattle population is native Tanganyika Shorthorn Zebu (TSZ) (Bos indicus), an animal of small stature and reputably low productivity. Attempts to improve productivity started in 1925 by crossing local cattle with European (B. indicus) bulls and by disease control using TSZ cattle to produce antirinderpest serum. Efforts to create a beast adapted to central Tanzania's hot semiarid environment were initiated in the 1930s using B. indicus breed such as Red Sindhi and Sahiwal bulls from India and Bos taurus such as Ayrshires from the UK. These attempts were halted in 1940. A new programme, started in 1944, aimed to create a composite animal capable of producing 2300 kg of milk in a 305-day lactation with a calving interval of 380 days and a 250-kg carcass from a 4-year old steer. Additional genetics were introduced including Kenya Boran (B. indicus) and UK Jersey and Guernsey (B. taurus) in addition to the Ayrshire. The composite was declared a breed in 1958 but the animal was nowhere near a fixed type and genetic modification continued for many years. Development was complicated by factors including disease, drought, inadequate nutrition, the political and economic climates and lack of professional staff. Production targets were never achieved and new genetics, especially Sahiwal (B. indicus) from Kenya, continued to be introduced. By the early 21st century, the Mpwapwa animal was almost 80% Sahiwal. There has never been more than 1000 live Mpwapwa-type animals at one time and there has been little dissemination outside the original station. Declared as endangered by international organizations and within Tanzania, it could be considered that the Mpwapwa has never been a breed in the conventional sense of an animal breeding true to type with consistent production outputs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11250-021-02669-4DOI Listing
March 2021

Monitoring of heavy metal pollution in urban and rural environments across Pakistan using House crows (Corvus splendens) as bioindicator.

Environ Monit Assess 2021 Mar 30;193(4):237. Epub 2021 Mar 30.

School of Science, Monash University Malaysia, Selangor Darul Ehsan, Bandar Sunway, Malaysia.

A widely distributed urban bird, the house crow (Corvus splendens), was used to assess bioavailable heavy metals in urban and rural environments across Pakistan. Bioaccumulation of arsenic (As), zinc (Zn), lead (Pb), cadmium (Cd), nickel (Ni), iron (Fe), manganese (Mn), chromium (Cr), and copper (Cu) was investigated in wing feathers of 96 crows collected from eight locations and categorized into four groups pertaining to their geographical and environmental similarities. Results revealed that the concentrations of Pb, Ni, Mn, Cu, and Cr were positively correlated and varied significantly among the four groups. Zn, Fe, Cr, and Cu regarded as industrial outputs, were observed in birds both in industrialized cities and in adjoining rural agricultural areas irrigated through the Indus Basin Irrigation System. Birds in both urban regions accrued Pb more than the metal toxicity thresholds for birds. The house crow was ranked in the middle on the metal accumulation levels in feathers between highly accumulating raptor and piscivore and less contaminated insectivore and granivore species in the studied areas,. This study suggests that the house crow is an efficient bioindicator and supports the feasibility of using feathers to discriminate the local pollution differences among terrestrial environments having different levels and kinds of anthropogenic activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10661-021-08966-7DOI Listing
March 2021

Systems Biology Analysis of the Radiation-Attenuated Schistosome Vaccine Reveals a Role for Growth Factors in Protection and Hemostasis Inhibition in Parasite Survival.

Front Immunol 2021 11;12:624191. Epub 2021 Mar 11.

Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil.

In spite of several decades of research, an effective vaccine against schistosomiasis remains elusive. The radiation-attenuated (RA) cercarial vaccine is still the best model eliciting high protection levels, although the immune mechanisms have not yet been fully characterized. In order to identify genes and pathways underlying protection we investigated patterns of gene expression in PBMC and skin draining Lymph Nodes (LN) from mice using two exposure comparisons: vaccination with 500 attenuated cercariae versus infection with 500 normal cercariae; one versus three doses. Vaccinated mice were challenged with 120 normal parasites. Integration of PBMC and LN data from the infected group revealed early up-regulation of pathways associated with Th2 skewing and polarization of IgG antibody profiles. Additionally, hemostasis pathways were downregulated in infected mice, correlating with platelet reduction, potentially a mechanism to assist parasite migration through capillary beds. Conversely, up regulation of such mechanisms after vaccination may explain parasite blockade in the lungs. In contrast, a single exposure to attenuated parasites revealed early establishment of a Th1 bias (signaling of IL-1, IFN-γ; and infection). Genes encoding chemokines and their receptors were more prominent in vaccinated mice, indicating an enhanced capacity for inflammation, potentially augmenting the inhibition of intravascular migration. Increasing the vaccinations from one to three did not dramatically elevate protection, but there was a clear shift towards antibody-mediated effectors. However, elements of the Th1 bias were still evident. Notable features after three vaccinations were markers of cytotoxicity (including IL-6 and NK cells) together with growth factors and their receptors (FGFR/VEGF/EGF) and the apoptosis pathway. Indeed, there is evidence for the development of anergy after three vaccinations, borne out by the limited responses detected in samples after challenge. We infer that persistence of a Th1 response puts a limit on expression of antibody-mediated mechanisms. This feature may explain the failure of multiple doses to drive protection towards sterile immunity. We suggest that the secretions of lung stage parasites would make a novel cohort of antigens for testing in protection experiments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.624191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996093PMC
March 2021

A preliminary study into the use of tree-ring and foliar geochemistry as bio-indicators for vehicular NO pollution in Malta.

Isotopes Environ Health Stud 2021 Mar 26:1-15. Epub 2021 Mar 26.

School of Earth and Environmental Sciences, University of St Andrews, St Andrews, UK.

Emissions from traffic over the past few decades have become a significant source of air pollution. Among the pollutants emitted are nitrogen oxides (NO), exposure to which can be detrimental to public health. Recent studies have shown that nitrogen (N) stable isotope ratios in tree-rings and foliage express a fingerprint of their major N source, making them appropriate for bio-monitoring purposes. In this study, we have applied this proxy to Aleppo pines () at three distances from one of the busiest roads in Malta, a country known to suffer from intense traffic pollution. Our results showed that N and organic carbon (C) stable isotope ratios in tree-rings do not vary over the period 1980-2018 at any of the investigated sites; however, statistically significant spatial trends were apparent in both tree-rings and foliage. The roadside and transitional sites exhibited more positive N and more negative C values compared to those at a rural control site. This is likely due to the incorporation of N-enriched NO and C-depleted CO from traffic pollution. Sampled top-soil also exhibited the N trend. Our results constitute the first known application of dendrogeochemistry to atmospheric pollution monitoring in Malta.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10256016.2021.1902319DOI Listing
March 2021

Epitope Mapping of Exposed Tegument and Alimentary Tract Proteins Identifies Putative Antigenic Targets of the Attenuated Schistosome Vaccine.

Front Immunol 2020 3;11:624613. Epub 2021 Mar 3.

York Biomedical Research Institute, University of York, York, United Kingdom.

The radiation-attenuated cercarial vaccine remains the gold standard for the induction of protective immunity against . Furthermore, the protection can be passively transferred to naïve recipient mice from multiply vaccinated donors, especially IFNgR KO mice. We have used such sera versus day 28 infection serum, to screen peptide arrays and identify likely epitopes that mediate the protection. The arrays encompassed 55 secreted or exposed proteins from the alimentary tract and tegument, the principal interfaces with the host bloodstream. The proteins were printed onto glass slides as overlapping 15mer peptides, reacted with primary and secondary antibodies, and reactive regions detected using an Agilent array scanner. Pep Slide Analyzer software provided a numerical value above background for each peptide from which an aggregate score could be derived for a putative epitope. The reactive regions of 26 proteins were mapped onto crystal structures using the CCP4 molecular graphics, to aid selection of peptides with the greatest accessibility and reactivity, prioritizing vaccine over infection serum. A further eight MEG proteins were mapped to regions conserved between family members. The result is a list of priority peptides from 44 proteins for further investigation in multiepitope vaccine constructs and as targets of monoclonal antibodies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.624613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982949PMC
March 2021

Epigenome-wide association study of whole blood gene expression in Framingham Heart Study participants provides molecular insight into the potential role of CHRNA5 in cigarette smoking-related lung diseases.

Clin Epigenetics 2021 Mar 22;13(1):60. Epub 2021 Mar 22.

The Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA.

Background: DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases.

Results: We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data.

Conclusions: Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13148-021-01041-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986283PMC
March 2021

Accidents alter animal fitness landscapes.

Ecol Lett 2021 Mar 9. Epub 2021 Mar 9.

Department of Biosciences, Swansea University, Swansea, UK.

Animals alter their habitat use in response to the energetic demands of movement ('energy landscapes') and the risk of predation ('the landscape of fear'). Recent research suggests that animals also select habitats and move in ways that minimise their chance of temporarily losing control of movement and thereby suffering slips, falls, collisions or other accidents, particularly when the consequences are likely to be severe (resulting in injury or death). We propose that animals respond to the costs of an 'accident landscape' in conjunction with predation risk and energetic costs when deciding when, where, and how to move in their daily lives. We develop a novel theoretical framework describing how features of physical landscapes interact with animal size, morphology, and behaviour to affect the risk and severity of accidents, and predict how accident risk might interact with predation risk and energetic costs to dictate movement decisions across the physical landscape. Future research should focus on testing the hypotheses presented here for different real-world systems to gain insight into the relative importance of theorised effects in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ele.13705DOI Listing
March 2021

The genome of the stable fly, Stomoxys calcitrans, reveals potential mechanisms underlying reproduction, host interactions, and novel targets for pest control.

BMC Biol 2021 Mar 10;19(1):41. Epub 2021 Mar 10.

Department of Biological Sciences, University of Cincinnati, Cincinnati, OH, USA.

Background: The stable fly, Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the USA alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies.

Results: This study examines stable fly biology by utilizing a combination of high-quality genome sequencing and RNA-Seq analyses targeting multiple developmental stages and tissues. In conjunction, 1600 genes were manually curated to characterize genetic features related to stable fly reproduction, vector host interactions, host-microbe dynamics, and putative targets for control. Most notable was characterization of genes associated with reproduction and identification of expanded gene families with functional associations to vision, chemosensation, immunity, and metabolic detoxification pathways.

Conclusions: The combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-Seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and new data will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship of Stomoxys to other blood-feeding (horn flies and Glossina) and non-blood-feeding flies (house flies, medflies, Drosophila) will facilitate understanding of the evolutionary processes associated with development of blood feeding among the Cyclorrhapha.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12915-021-00975-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944917PMC
March 2021

To what degree is late life cognitive decline driven by age-relatedneuropathologies?

Brain 2021 Mar 20. Epub 2021 Mar 20.

Rush University Medical Center, Rush Alzheimer's Disease Center, Chicago, IL, USA.

The aging brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer's disease (AD), infarcts, and Lewy bodies, account for about 40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline (e.g. limbic predominant age-related TDP-43 encephalopathy [LATE-NC], hippocampal sclerosis, other cerebrovascular conditions). We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. 1,164 deceased participants from two longitudinal clinical-pathologic studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathologic examinations provided 11 pathologic indices, including markers of AD, non-AD neurodegenerative diseases (i.e. LATE-NC, hippocampal sclerosis, Lewy bodies), and cerebrovascular conditions (i.e. macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis). Mixed effects models examined the linear relation of pathologic indices with global cognitive decline, and random change point models examined the relation of the pathologic indices with the onset of terminal decline and rates of preterminal and terminal decline. Cognition declined an average of about 0.10 unit per year (estimate = -0.101, SE = 0.003, p < 0.001) with considerable heterogeneity in rates of decline (variance estimate for the person-specific slope of decline was 0.0094, p < 0.001). When considered separately, 10 of the 11 pathologic indices were associated with faster decline and accounted for between 2 and 34% of the variation in decline, respectively. When considered simultaneously, the 11 pathologic indices together accounted for a total of 43% of the variation in decline; AD-related indices accounted for 30-36% of the variation, non-AD neurodegenerative indices 4-10%, and cerebrovascular indices 3-8%. Finally, the 11 pathologic indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive aging and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awab092DOI Listing
March 2021

The Role of Serum Levels of Neurofilament Light (NfL) Chain as a Biomarker in Friedreich Ataxia.

Front Neurosci 2021 2;15:653241. Epub 2021 Mar 2.

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2021.653241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960909PMC
March 2021

College Football Overtime Outcomes: Implications for In-Game Decision-Making.

Authors:
Rick L Wilson

Front Artif Intell 2020 26;3:61. Epub 2020 Aug 26.

Department of Management Science and Information Systems, Spears School of Business, Oklahoma State University, Stillwater, OK, United States.

The use of AI and machine learning in sports is increasingly prevalent, including their use for in-game strategy and tactics. This paper reports on the use of machine learning techniques, applying it to analysis of U.S. Division I-A College Football overtime games. The present overtime rules for tie games in Division I-A college football was adopted in 1996. Previous research (Rosen and Wilson, 2007) found little to suggest that the predominantly used strategy of going on defense first was advantageous. Over the past decade, even with significant transformation of new offensive and defensive strategies, college football coaches still opt for the same conventional wisdom strategy. In revisiting this analysis of overtime games using both logistic regression and inductive learning/decision tree analysis, the study validates there remains no advantage to the defense first strategy in overtime. The study found evidence that point spread (as an indicator of team strength) and red zone offense performance of both teams were useful to predict game results. Additionally, by altering the decision-making "frame," specific scenarios are illustrated where a coach can use these machine learning discovered relationships to influence end-of-regulation game decisions that may increase their likelihood of winning whether in regulation time or in overtime.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/frai.2020.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861217PMC
August 2020

Can a Community-Based Football Program Benefit Motor Ability in Children with Autism Spectrum Disorder? A Pilot Evaluation Considering the Role of Social Impairments.

J Autism Dev Disord 2021 Mar 13. Epub 2021 Mar 13.

Deakin Child Study Centre, School of Psychology, Faculty of Health, Deakin University, Geelong, Victoria, Australia.

This non-randomised pilot study evaluated the impact of a community football program on motor ability in children aged 5-12 years with autism spectrum disorder. Sixteen children were evaluated at baseline-and-post attendance in a football program for a varied number of weeks and compared to 19 children engaging in treatment-as-usual. Primary analyses indicated a statistically significant increase in total MABC-2, aiming and catching, and balance scores for the intervention group, with no changes in scores in the comparison group. There were no changes in manual dexterity across either group. At a between group level, the changes in aiming and catching scores were significantly greater for the intervention group. Further analyses highlighted the potential importance of social impairments regarding aiming and catching.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10803-021-04933-wDOI Listing
March 2021

Gender and the Symptom Experience before an Atrial Fibrillation Diagnosis.

West J Nurs Res 2021 Mar 12:193945921999448. Epub 2021 Mar 12.

School of Nursing, The University of British Columbia, Okanagan Campus, Kelowna, BC, Canada.

Atrial fibrillation (AF) is the most common arrhythmia in the world. Despite the increasing prevalence, there remains a limited understanding of how the pre-diagnosis symptom experience varies by gender. The purpose of this study was to retrospectively explore gender differences/similarities in the pre-diagnosis period of AF. Twenty-six adults (13 men and 13 women) were interviewed guided by the Symptom Experience in AF (SEAF). Data were analyzed using a two-step approach to thematic analysis. Women had greater challenges receiving a timely diagnosis, with 10 women (77%) experiencing symptoms ≥1 year prior to their diagnosis, in comparison to only three (23%) of the men. Women also reported more severe symptoms, less AF-related knowledge, viewed themselves as low risk for cardiovascular disease, and described how their comorbid conditions confused AF symptom evaluation. This study provides a foundational understanding of differences/similarities in the AF symptom experience by gender.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0193945921999448DOI Listing
March 2021

Annelids of the eastern Australian abyss collected by the 2017 RV 'Investigator' voyage.

Zookeys 2021 24;1020:1-198. Epub 2021 Feb 24.

South China Sea Environmental Monitoring Centre, State Oceanic Administration, Guangzhou, China.

In Australia, the deep-water (bathyal and abyssal) benthic invertebrate fauna is poorly known in comparison with that of shallow (subtidal and shelf) habitats. Benthic fauna from the deep eastern Australian margin was sampled systematically for the first time during 2017 RV 'Investigator' voyage 'Sampling the Abyss'. Box core, Brenke sledge, and beam trawl samples were collected at one-degree intervals from Tasmania, 42°S, to southern Queensland, 24°S, from 900 to 4800 m depth. Annelids collected were identified by taxonomic experts on individual families around the world. A complete list of all identified species is presented, accompanied with brief morphological diagnoses, taxonomic remarks, and colour images. A total of more than 6000 annelid specimens consisting of 50 families (47 Polychaeta, one Echiura, two Sipuncula) and 214 species were recovered. Twenty-seven species were given valid names, 45 were assigned the qualifier cf., 87 the qualifier sp., and 55 species were considered new to science. Geographical ranges of 16 morphospecies extended along the eastern Australian margin to the Great Australian Bight, South Australia; however, these ranges need to be confirmed with genetic data. This work providing critical baseline biodiversity data on an important group of benthic invertebrates from a virtually unknown region of the world's ocean will act as a springboard for future taxonomic and biogeographic studies in the area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3897/zookeys.1020.57921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930015PMC
February 2021

Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line.

Sci Rep 2021 Mar 11;11(1):5690. Epub 2021 Mar 11.

Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425-9080, USA.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived neoplasms that occur sporadically or in patients with neurofibromatosis type 1 (NF1). Preclinical research on sporadic MPNSTs has been limited as few cell lines exist. We generated and characterized a new sporadic MPNST cell line, 2XSB, which shares the molecular and genomic features of the parent tumor. These cells have a highly complex karyotype with extensive chromothripsis. 2XSB cells show robust invasive 3-dimensional and clonogenic culture capability and form solid tumors when xenografted into immunodeficient mice. High-density single nucleotide polymorphism array and whole exome sequencing analyses indicate that, unlike NF1-associated MPNSTs, 2XSB cells have intact, functional NF1 alleles with no evidence of mutations in genes encoding components of Polycomb Repressor Complex 2. However, mutations in other genes implicated in MPNST pathogenesis were identified in 2XSB cells including homozygous deletion of CDKN2A and mutations in TP53 and PTEN. We also identified mutations in genes not previously associated with MPNSTs but associated with the pathogenesis of other human cancers. These include DNMT1, NUMA1, NTRK1, PDE11A, CSMD3, LRP5 and ACTL9. This sporadic MPNST-derived cell line provides a useful tool for investigating the biology and potential treatment regimens for sporadic MPNSTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85055-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952412PMC
March 2021

Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers.

N Engl J Med 2021 03;384(10):924-935

From the Department of Pathology and Immunology (E.J.D., M.C.S., A.E.O.H., J.N., J.E.P., D.H.S.), McDonnell Genome Institute (M.O., R.W., S.M., A.B., S.K., J.G., F.D., R.S.F., D.H.S.), and the Divisions of Oncology (J.R., E.H., S.E.H., M.J.C., M.A.J., G.L.U., C.A.M., D.C.L., M.J.W., P.W., J.F.D., T.J.L., D.H.S.) and Biostatistics (J.D.B.), Department of Medicine, Washington University School of Medicine, St. Louis.

Background: Genomic analysis is essential for risk stratification in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Whole-genome sequencing is a potential replacement for conventional cytogenetic and sequencing approaches, but its accuracy, feasibility, and clinical utility have not been demonstrated.

Methods: We used a streamlined whole-genome sequencing approach to obtain genomic profiles for 263 patients with myeloid cancers, including 235 patients who had undergone successful cytogenetic analysis. We adapted sample preparation, sequencing, and analysis to detect mutations for risk stratification using existing European Leukemia Network (ELN) guidelines and to minimize turnaround time. We analyzed the performance of whole-genome sequencing by comparing our results with findings from cytogenetic analysis and targeted sequencing.

Results: Whole-genome sequencing detected all 40 recurrent translocations and 91 copy-number alterations that had been identified by cytogenetic analysis. In addition, we identified new clinically reportable genomic events in 40 of 235 patients (17.0%). Prospective sequencing of samples obtained from 117 consecutive patients was performed in a median of 5 days and provided new genetic information in 29 patients (24.8%), which changed the risk category for 19 patients (16.2%). Standard AML risk groups, as defined by sequencing results instead of cytogenetic analysis, correlated with clinical outcomes. Whole-genome sequencing was also used to stratify patients who had inconclusive results by cytogenetic analysis into risk groups in which clinical outcomes were measurably different.

Conclusions: In our study, we found that whole-genome sequencing provided rapid and accurate genomic profiling in patients with AML or MDS. Such sequencing also provided a greater diagnostic yield than conventional cytogenetic analysis and more efficient risk stratification on the basis of standard risk categories. (Funded by the Siteman Cancer Research Fund and others.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2024534DOI Listing
March 2021

Time Course and Magnitude of Ventilatory and Renal Acid-Base Acclimatization Following Rapid Ascent to and Residence at 3,800 m over Nine Days.

J Appl Physiol (1985) 2021 Mar 11. Epub 2021 Mar 11.

Department of Biology, Faculty of Science and Technology, Mount Royal University, Canada.

Rapid ascent to high altitude imposes an acute hypoxic and acid-base challenge, with ventilatory and renal acclimatization countering these perturbations. Specifically, ventilatory acclimatization improves oxygenation, but with concomitant hypocapnia and respiratory alkalosis. A compensatory, renally-mediated relative metabolic acidosis follows via bicarbonate elimination, normalizing arterial pH(a). The time-course and magnitude of these integrated acclimatization processes are highly variable between individuals. Using a previously-developed metric of renal reactivity (RR), indexing the change in arterial bicarbonate concentration (∆[HCO]a; renal response) over the change in arterial pressure of CO (∆PaCO; renal stimulus), we aimed to characterize changes in RR magnitude following rapid ascent and residence at altitude. Resident lowlanders (n=16) were tested at 1,045 m (Day [D]0) prior to ascent, on D2 within 24-hours of arrival, and D9 during residence at 3,800 m. Radial artery blood draws were obtained to measure acid-base variables: PaCO, [HCO]a and pHa. Compared to D0, PaCO and [HCO]a were lower on D2 (P<0.01) and D9 (P<0.01), whereas significant changes in pHa (P>0.058) and RR (P=0.056) were not detected. As pHa appeared fully compensated on D2 and RR did not increase significantly from D2 to D9, these data demonstrate renal acid-base compensation within 24-hours at moderate steady-state altitude. Moreover, RR was strongly and inversely correlated with ∆pHa on D2 and D9 (r≤-0.95; P<0.0001), suggesting that a high-gain renal response better protects pHa. Our study highlights the differential time-course, magnitude, and variability of integrated ventilatory and renal acid-base acclimatization following rapid ascent and residence at high altitude.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/japplphysiol.00973.2020DOI Listing
March 2021