Natural Variation Identifies Multiple Loci Controlling Petal Shape and Size in Arabidopsis thaliana

Natural variation in organ morphologies can have adaptive significance and contribute to speciation. However, the underlying allelic differences responsible for variation in organ size and shape remain poorly understood. We have utilized natural phenotypic variation in three Arabidopsis thaliana ecotypes to examine the genetic basis for quantitative variation in petal length, width, area, and shape. We identified 23 loci responsible for such variation, many of which appear to correspond to genes not previously implicated in controlling organ morphology. These analyses also demonstrated that allelic differences at distinct loci can independently affect petal length, width, area or shape, suggesting that these traits behave as independent modules. We also showed that ERECTA (ER), encoding a leucine-rich repeat (LRR) receptor-like serine-threonine kinase, is a major effect locus determining petal shape. Allelic variation at the ER locus was associated with differences in petal cell proliferation and concomitant effects on petal shape. ER has been previously shown to be required for regulating cell division and expansion in other contexts; the ER receptor-like kinase functioning to also control organ-specific proliferation patterns suggests that allelic variation in common signaling components may nonetheless have been a key factor in morphological diversification.     

Sources of Variability in Platelet Accumulation on Type 1 Fibrillar Collagen in Microfluidic Flow Assays

Microfluidic flow assays (MFA) that measure shear dependent platelet function have potential clinical applications in the diagnosis and treatment of bleeding and thrombotic disorders. As a step towards clinical application, the objective of this study was to measure how phenotypic and genetic factors, as well as experimental conditions, affect the variability of platelet accumulation on type 1 collagen within a MFA. Whole blood was perfused over type 1 fibrillar collagen at wall shear rates of 150, 300, 750 and 1500 s⁻¹ through four independent channels with a height of 50 µm and a width of 500 µm. The accumulation of platelets was characterized by the lag time to 1% platelet surface coverage (Lag_T), the rate of platelet accumulation (V_PLT), and platelet surface coverage (SC). A cohort of normal donors was tested and the results were correlated to plasma von Willebrand factor (VWF) levels, platelet count, hematocrit, sex, and collagen receptors genotypes. VWF levels were the strongest determinant of platelet accumulation. VWF levels were positively correlated to V_PLT and SC at all wall shear rates. A longer Lag_T for platelet accumulation at arterial shear rates compared to venous shear rates was attributed to the time required for plasma proteins to adsorb to collagen. There was no association between platelet accumulation and hematocrit or platelet count. Individuals with the AG genotype of the GP6 gene had lower platelet accumulation than individuals with the AA genotype at 150 s⁻¹ and 300 s⁻¹. Recalcified blood collected into sodium citrate and corn trypsin inhibitor (CTI) resulted in diminished platelet accumulation compared to CTI alone, suggesting that citrate irreversibly diminishes platelet function. This study the largest association study of MFA in healthy donors (n = 104) and will likely set up the basis for the determination of the normal range of platelet responses in this type of assay.     

Discrete Neural Correlates for the Recognition of Negative Emotions: Insights from Frontotemporal Dementia

Patients with frontotemporal dementia have pervasive changes in emotion recognition and social cognition, yet the neural changes underlying these emotion processing deficits remain unclear. The multimodal system model of emotion proposes that basic emotions are dependent on distinct brain regions, which undergo significant pathological changes in frontotemporal dementia. As such, this syndrome may provide important insight into the impact of neural network degeneration upon the innate ability to recognise emotions. This study used voxel-based morphometry to identify discrete neural correlates involved in the recognition of basic emotions (anger, disgust, fear, sadness, surprise and happiness) in frontotemporal dementia. Forty frontotemporal dementia patients (18 behavioural-variant, 11 semantic dementia, 11 progressive nonfluent aphasia) and 27 healthy controls were tested on two facial emotion recognition tasks: The Ekman 60 and Ekman Caricatures. Although each frontotemporal dementia group showed impaired recognition of negative emotions, distinct associations between emotion-specific task performance and changes in grey matter intensity emerged. Fear recognition was associated with the right amygdala; disgust recognition with the left insula; anger recognition with the left middle and superior temporal gyrus; and sadness recognition with the left subcallosal cingulate, indicating that discrete neural substrates are necessary for emotion recognition in frontotemporal dementia. The erosion of emotion-specific neural networks in neurodegenerative disorders may produce distinct profiles of performance that are relevant to understanding the neurobiological basis of emotion processing.     

HDAC1 inhibition by maspin abrogates epigenetic silencing of glutathione S-transferase pi in prostate carcinoma cells

Both maspin and glutathione S-transferase pi (GSTp) are implicated as tumor suppressors and downregulated in human prostate cancer. It is well established that GSTp downregulation is through DNA methylation-based silencing. We report here that maspin expression in prostate cancer cell line DU145 reversed GSTp DNA methylation, as measured by methylation- specific PCR, MethyLight assay, and bisulfite sequencing. The effect of maspin on GSTp expression was similar to that of the combination of a synthetic histone deacetylase (HDAC) inhibitor and DNA methylation inhibitor 5-aza-2'-deoxycytidine. Maspin expression also led to an increased level of acetylated histone 3, decreased level of methyl transferase, and methyl-CpG-binding domain proteins at the site of demethylated GSTp promoter DNA. Earlier, we have shown that maspin inhibits HDAC1. In PC3 cells, where both maspin and GSTp are expressed at a reduced level, maspin knockdown led to a significant reduction in GSTp expression, whereas dual knockdown of maspin and HDAC1 barely increased the level of GSTp expression. Thus, HDAC1 may play an essential role in cellular response to maspin-mediated GSTp desilencing. Maspin has been shown to increase tumor cell sensitivity to drug-induced apoptosis. Interestingly, GSTp reexpression in the absence of maspin expression perturbation blocked the phosphorylation of histone 2A.X, the induction of hypoxia-induced factor 1α (HIF-1α), and cell death of LNCaP cells under oxidative stress. Because DNA hypermethylation-based silencing may couple with and depend on histone deacetylation, our study suggests that endogenous HDAC inhibition by maspin may prevent pathologic gene silencing in prostate tumor progression.     

Developing Single Nucleotide Polymorphism (SNP) Markers for the Identification of Coffee Germplasm

Coffee is one of the most widely consumed beverages and represents a multibillion-dollar global industry. Accurate identification of coffee cultivars is essential for efficient management, exchange, and use of coffee genetic resources. To date, a universal platform that can allow data comparison across different laboratories and genotyping platforms has not been developed by the coffee research community. Using expressed sequence tags (EST) of Coffea arabica, C. canephora and C. racemosa from public databases, we developed 7538 single nucleotide polymorphism (SNP) markers and selected 180 for validation using 25 C. arabica and C. canephora accessions from Puerto Rico. Based on the validation result, we designated a panel of 55 SNP markers that are polymorphic across the two species. The average minor allele frequency and information index of this SNP panel are 0.281 and 0.690, respectively. This panel enabled the differentiation of all tested accessions of C. canephora, which accounts for 79.2 % of the total polymorphism in the samples. Only 21.8 % of the polymorphic SNPs were detected in the 12 C. arabica cultivars, which, nonetheless, were able to unambiguously differentiate the 12 Arabica cultivars into ten unique genotypes, including two synonymous groups. Several local Puerto Rican cultivars with partial Timor pedigree, including Limaní, Frontón, and TARS 18087, showed substantial genetic difference from the other common Arabica cultivars, such as Catuai, Borbón, and Mundo Nuevo. This coffee SNP panel provides robust and universally comparable DNA fingerprints, thus can serve as a genotyping tool to assist coffee germplasm management, propagation of planting material, and coffee cultivar authentication.     

Historical environmental change in Africa drives divergence and admixture of Aedes aegypti mosquitoes: a precursor to successful worldwide colonization?

Increasing globalization has promoted the spread of exotic species, including disease vectors. Understanding the evolutionary processes involved in such colonizations is both of intrinsic biological interest and important to predict and mitigate future disease risks. The Aedes aegypti mosquito is a major vector of dengue, chikungunya and Zika, the worldwide spread of which has been facilitated by Ae. aegypti's adaption to human‐modified environments. Understanding the evolutionary processes involved in this invasion requires characterization of the genetic make‐up of the source population(s). The application of approximate Bayesian computation (ABC) to sequence data from four nuclear and one mitochondrial marker revealed that African populations of Ae. aegypti best fit a demographic model of lineage diversification, historical admixture and recent population structuring. As ancestral Ae. aegypti were dependent on forests, this population history is consistent with the effects of forest fragmentation and expansion driven by Pleistocene climatic change. Alternatively, or additionally, historical human movement across the continent may have facilitated their recent spread and mixing. ABC analysis and haplotype networks support earlier inferences of a single out‐of‐Africa colonization event, while a cline of decreasing genetic diversity indicates that Ae. aegypti moved first from Africa to the Americas and then to Asia. ABC analysis was unable to verify this colonization route, possibly because the genetic signal of admixture obscures the true colonization pathway. By increasing genetic diversity and forming novel allelic combinations, divergence and historical admixture within Africa could have provided the adaptive potential needed for the successful worldwide spread of Ae. aegypti.     

Interactions Between tassel seed Genes and Other Sex Determining Genes in Maize (Article was originally published in Developmental Genetics 15:155–171.)

Erin E. Irish, Jane A. Langdale, and Timothy Nelson. Interactions Between tassel seed Genes and Other Sex Determining Genes in Maize (Article was originally published in Developmental Genetics 15:155–171.) An incorrect version of Table 2 was printed in the above article. The corrected version is shown below.     

Impact of cancer surgery slowdowns on patient survival during the COVID-19 pandemic: a microsimulation modelling study

Background:With the declaration of the global pandemic, surgical slowdowns were instituted to conserve health care resources for anticipated surges in patients with COVID-19. The long-term implications on survival of these slowdowns for patients with cancer in Canada is unknown.Methods:We constructed a microsimulation model based on real-world population data on cancer care from Ontario, Canada, from 2019 and 2020. Our model estimated wait times for cancer surgery over a 6-month period during the pandemic by simulating a slowdown in operating room capacity (60% operating room resources in month 1, 70% in month 2, 85% in months 3–6), as compared with simulated prepandemic conditions with 100% resources. We used incremental differences in simulated wait times to model survival using per-day hazard ratios for risk of death. Primary outcomes included life-years lost per patient and per cancer population. We conducted scenario analyses to evaluate alternative, hypothetical scenarios of different levels of surgical slowdowns on risk of death.Results:The simulated model population comprised 22 799 patients waiting for cancer surgery before the pandemic and 20 177 patients during the pandemic. Mean wait time to surgery prepandemic was 25 days and during the pandemic was 32 days. Excess wait time led to 0.01–0.07 life-years lost per patient across cancer sites, translating to 843 (95% credible interval 646–950) life-years lost among patients with cancer in Ontario.Interpretation:Pandemic-related slowdowns of cancer surgeries were projected to result in decreased long-term survival for many patients with cancer. Measures to preserve surgical resources and health care capacity for affected patients are critical to mitigate unintended consequences.

Declaration of the global COVID-19 pandemic led to the implementation of several clinical and policy-related measures to mitigate risk to vulnerable populations and conserve health care resources. Literature from early waves of the pandemic characterized patients with cancer as a vulnerable population.^1,2 Moreover, cancer surgery can be highly resource intensive, which could strain the health care system’s ability to respond to the pandemic. Accordingly, in March 2020, the Ontario government recommended reducing the number of cancer surgeries, along with other elective surgeries performed in the province. These measures were aimed at reducing both patient morbidity and use of health care resources, primarily by decreasing routine postoperative admissions to wards and intensive care units, in anticipation of a potential surge of patients with COVID-19.³Although necessary, this initial strategy resulted in a backlog of cancer surgeries, and some patients faced longer wait times to surgical treatment.⁴ Given clear evidence showing that longer surgical wait times can increase cancer-related risk of death, there is concern for the unintended consequences of the surgical slowdowns during the COVID-19 pandemic.^5–8 International data have projected the negative impact on long-term survival associated with potential delays to cancer diagnosis or surgery across various cancer types.^9–11 Recognizing the global differences in level of infection, response to the COVID-19 pandemic and cancer survival rates, country-specific data are required to understand local consequences and better guide future responses to times of resource constraint. As such, the objective of the current study was to evaluate the long-term implications of pandemic–related cancer surgery slowdowns on cancer survival in Ontario, Canada.