OPDA/dn-OPDA actions: biosynthesis, metabolism, and signaling.

Plants cannot move, so they have evolved sophisticated strategies that integrate the external environmental cues and internal signaling networks for adaptation to dynamic circumstances. Cis-(+)-12-oxo-phytodienoic acid (OPDA) and 2,3-dinor-OPDA (dn-OPDA), the cyclopentenone-containing oxylipins, ubiquitously occur in the green lineage to orchestrate a series of growth and developmental processes as well as various stress and defense responses. OPDA/dn-OPDA are precursors of jasmonate (JA) biosynthesis in vascular plants. Dn-OPDA and its isomer also serve as bioactive JAs perceived by the coronatine insensitive 1/jasmonate ZIM-domain (COI1/JAZ) co-receptor complex in bryophytes and lycophytes. In addition, OPDA/dn-OPDA display signaling activities independent of (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile) and COI1 in both vascular and non-vascular plants. In this review, we discuss recent advances in the biosynthesis, metabolism, and signaling of OPDA/dn-OPDA, and provide an overview of the evolution of OPDA/dn-OPDA actions to obtain a deeper understanding of the pervasive role of OPDA/dn-OPDA in the plant life cycle.

Hypospadias prevalence by severity and associated risk factors: A population-based active surveillance analysis.

INTRODUCTION: Hypospadias is one of the most common congenital anomalies. Trends of hypospadias prevalence by severity are not well reported. Most prevalence studies consist of pooled data from different countries or states suffer from low data quality due to inconsistent methodologies, limited variables, and lack of categorization of hypospadias severity. OBJECTIVE: The objective of this study is to examine the prevalence of hypospadias by degrees of severity and associated risk factors using combined data sources from a stable and well-defined population. STUDY DESIGN: The study population includes infants born with hypospadias to mothers residing in Arkansas from 1997 to 2016. Cases were identified from an active population-based surveillance program of birth defects. Identified hypospadias cases from surveillance data were linked to birth certificate and to a clinical database. These two data sources provide more details on the location of the defect and maternal and infant characteristics. The prevalence and 95% confidence intervals were calculated using total male live births as denominator. Chi-square test was used to assess the association of nominal variables. Logistic regression was used to calculate adjusted odds ratio. RESULTS: A total 3230 hypospadias cases were identified from 1997 to 2016. The overall prevalence is 83.0 per 10,000 male births. A majority of cases (56.7%) were classified as first degree with the others having second degree (22.8%), third degree (4.7%) or not otherwise specified (15.6%). The highest prevalence of hypospadias was observed among Non-Hispanic whites. Higher prevalence also was observed among mothers in the older age group with no prenatal care in the first trimester and with gestational hypertension or diabetes. Premature or small for gestational age infants tend to have higher prevalence across all levels of severity. The number of hypospadias cases increased over time. After maternal age, race and education were adjusted, higher risk persisted for infants of restricted fetal growth, mothers with gestational hypertension or diabetes and the cohort of 2013-2016. CONCLUSION: There is an increase of hypospadias cases in Arkansas. Several maternal and infant characteristics associated with higher prevalence for all levels of severity are worth further investigation.

VA-TIRFM-based SM kymograph analysis for dwell time and colocalization of plasma membrane protein in plant cells.

BACKGROUND: The plasma membrane (PM) proteins function in a highly dynamic state, including protein trafficking and protein homeostasis, to regulate various biological processes. The dwell time and colocalization of PM proteins are considered to be two important dynamic features determining endocytosis and protein interactions, respectively. Dwell-time and colocalization detected using traditional fluorescence microscope techniques are often misestimated due to bulk measurement. In particular, analyzing these two features of PM proteins at the single-molecule level with spatiotemporal continuity in plant cells remains greatly challenging. RESULTS: We developed a single molecular (SM) kymograph method, which is based on variable angle-total internal reflection fluorescence microscopy (VA-TIRFM) observation and single-particle (co-)tracking (SPT) analysis, to accurately analyze the dwell time and colocalization of PM proteins in a spatial and temporal manner. Furthermore, we selected two PM proteins with distinct dynamic behaviors, including AtRGS1 (Arabidopsis regulator of G protein signaling 1) and AtREM1.3 (Arabidopsis remorin 1.3), to analyze their dwell time and colocalization upon jasmonate (JA) treatment by SM kymography. First, we established new 3D (2D+t) images to view all trajectories of the interest protein by rotating these images, and then we chose the appropriate point without changing the trajectory for further analysis. Upon JA treatment, the path lines of AtRGS1-YFP appeared curved and short, while the horizontal lines of mCherry-AtREM1.3 demonstrated limited changes, indicating that JA might initiate the endocytosis of AtRGS1. Analysis of transgenic seedlings coexpressing AtRGS1-YFP/mCherry-AtREM1.3 revealed that JA induces a change in the trajectory of AtRGS1-YFP, which then merges into the kymography line of mCherry-AtREM1.3, implying that JA increases the colocalization degree between AtRGS1 and AtREM1.3 on the PM. These results illustrate that different types of PM proteins exhibit specific dynamic features in line with their corresponding functions. CONCLUSIONS: The SM-kymograph method provides new insight into quantitively analyzing the dwell time and correlation degree of PM proteins at the single-molecule level in living plant cells.

Phase separation of the nuclear pore complex facilitates selective nuclear transport to regulate plant defense against pathogen and pest invasion.

The nuclear pore complex (NPC), the sole exchange channel between the nucleus and cytoplasm, is composed of several subcomplexes, among which the central barrier determines the permeability/selectivity of the NPC to dominate the nucleocytoplasmic trafficking essential for many important signaling events in yeast and mammals. How plant NPC central barrier controls selective transport is a crucial question remaining to be elucidated. In this study, we uncovered that phase separation of the central barrier is critical for the permeability and selectivity of plant NPC in the regulation of various biotic stresses. Phenotypic assays of nup62 mutants and complementary lines showed that NUP62 positively regulates plant defense against Botrytis cinerea, one of the world's most disastrous plant pathogens. Furthermore, in vivo imaging and in vitro biochemical evidence revealed that plant NPC central barrier undergoes phase separation to regulate selective nucleocytoplasmic transport of immune regulators, as exemplified by MPK3, essential for plant resistance to B. cinerea. Moreover, genetic analysis demonstrated that NPC phase separation plays an important role in plant defense against fungal and bacterial infection as well as insect attack. These findings reveal that phase separation of the NPC central barrier serves as an important mechanism to mediate nucleocytoplasmic transport of immune regulators and activate plant defense against a broad range of biotic stresses.

Prevalence and descriptive epidemiology of Turner syndrome in the United States, 2000-2017: A report from the National Birth Defects Prevention Network.

The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000-2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 female live births (95% CI = 3.0-3.3, program range: 1.0-10.4), and 1.9 for live birth and stillbirth (≥20 weeks gestation) cases (95% CI = 1.8-2.1, program range: 0.2-3.9). Prevalence was lowest among cases born to non-Hispanic Black women compared to non-Hispanic White women (PR = 0.5, 95% CI = 0.4-0.6). Coarctation of the aorta was the most common defect (11.6% of cases), and across the cohort, individuals without hypoplastic left heart had a five-year survival probability of 94.6%. The findings from this population-based study may inform surveillance practices, prenatal counseling, and diagnosis. We also identified racial and ethnic disparities in prevalence, an observation that warrants further investigation.

Jasmonate-based warfare between the pathogenic intruder and host plant: who wins?

Plants and microbial pathogens often engage in a fierce war that determines their survival. Host plants have evolved sophisticated regulatory mechanisms to fine-tune defense responses to counter attacks from pathogens, while pathogens often hijack the lipid-derived phytohormone jasmonate to cause hormonal signaling imbalances for efficient infection. This review focuses on the jasmonate-based warfare between host plants and pathogenic intruders, and further discusses approaches to uncouple plant growth and defense tradeoffs in crop breeding.

Jasmonate perception: Ligand-receptor interaction, regulation, and evolution.

Phytohormones integrate external environmental and developmental signals with internal cellular responses for plant survival and multiplication in changing surroundings. Jasmonate (JA), which might originate from prokaryotes and benefit plant terrestrial adaptation, is a vital phytohormone that regulates diverse developmental processes and defense responses against various environmental stresses. In this review, we first provide an overview of ligand-receptor binding techniques used for the characterization of phytohormone-receptor interactions, then introduce the identification of the receptor COI1 and active JA molecules, and finally summarize recent advances on the regulation of JA perception and its evolution.

Post-translational modifications: emerging regulators manipulating jasmonate biosynthesis and signaling.

Jasmonate (JA) is one of the key phytohormones essential for plant development and defense processes. The core JA biosynthetic and signaling pathways have been well-characterized. Notably, post-translational modifications (PTMs), which affect the protein structures and functions, have emerged as critical mechanisms to modulate JA output at different spatiotemporal levels. Disruption of PTMs in JA biosynthesis and signaling would cause the dysfunction of vital biological processes. Here, we give an overview of the PTMs that have been identified in JA biosynthetic and signaling pathways, and provide insights into the mechanisms by which PTMs define JA responses.

Changes in Spina Bifida Lesion Level after Folic Acid Fortification in the US.

OBJECTIVE: To assess whether the severity of cases of spina bifida changed after the institution of mandatory folic acid fortification in the US. STUDY DESIGN: Six active population-based birth defects programs provided data on cases of spina bifida for 1992-1996 (prefortification period) and 1999-2016 (postfortification period). The programs contributed varying years of data. Case information included both a medical record verbatim text description of the spina bifida diagnosis and spina bifida codes (International Classification of Diseases, Clinical Modification, or a modified birth defects surveillance coding system). Comparing the prefortification and postfortification periods, aORs for case severity (upper-level lesions [cervical, thoracic] vs lower-level lesions [lumbar, sacral]) and prevalence ratios (PRs) were estimated. RESULTS: A total of 2593 cases of spina bifida (out of 7 816 062 live births) met the inclusion criteria, including 573 cases from the prefortification period and 2020 cases from the postfortification period. Case severity decreased by 70% (aOR, 0.30; 95% CI, 0.26-0.35) between the fortification periods. The decrease was most pronounced for non-Hispanic White mothers. Overall spina bifida prevalence declined by 23% (PR, 0.77; 95% CI, 0.71-0.85), with similar reductions seen across the early, mid, and recent postfortification periods. A statistically significant decrease in upper-level lesions occurred in the postfortification period compared with the prefortification period (PR, 0.28; 95% CI, 0.22-0.34), whereas the prevalence of lower-level lesions remained relatively similar (PR, 0.94; 95% CI, 0.84-1.05). CONCLUSIONS: The severity of spina bifida cases decreased after mandatory folic acid fortification in the US. Further examination is warranted to better understand the potential effect of folic acid on spina bifida severity.

The role of N-myristoylation in homeostasis of brassinosteroid signaling kinase 1.

MAIN CONCLUSION: The N-myristoylation is required for BSK1 proper plasma membrane targeting and protein turnover. Brassinosteroid (BR) signaling kinase 1 (BSK1), with a myristoylation site at its N-terminus to anchor at plasma membrane (PM), is involved in BR-regulated plant growth and flg22-triggered immunity responses. However, little is known about the role of N-myristoylation in BSK1 protein homeostasis. Here, we revealed that N-myristoylation is critical to the PM targeting and protein stability of BSK1. The N-myristoylation-deficient mutant BSK1G2A mainly distributed in the cytoplasm and retained in the endoplasmic reticulum. We further found that the BSK1G2A proteins were unstable and degraded through ATG8e-labled autophagic pathway. This study provides a new insight into the regulation of plant protein homeostasis.

Prevalence of critical congenital heart defects and selected co-occurring congenital anomalies, 2014-2018: A U.S. population-based study.

BACKGROUND: Critical congenital heart defects (CCHDs) are one of the most common types of birth defects and can lead to significant morbidity and mortality along with surgical or catheter interventions within the first year of life. This report updates previously published estimates of CCHD prevalence with the latest population-based surveillance data from 19 birth defect surveillance programs. METHODS: The U.S. population-based surveillance programs submitted data on identified cases of 12 CCHDs and co-occurring cardiovascular and chromosomal birth defects from 2014 to 2018. We estimated prevalence by program type and maternal and infant characteristics. Among nine programs with active case ascertainment that collect more than live births, we estimated the percentage of co-occurring cardiovascular and chromosomal birth defects for the 12 CCHDs. RESULTS: We identified 18,587 cases of CCHD among all participating programs. Overall CCHD prevalence was 19.6 per 10,000 live births among all 19 programs and 20.2 per 10,000 live births among active programs. Among maternal racial/ethnic groups, infants/fetuses born to American Indian/Alaska Native mothers showed the highest overall prevalence for all CCHDs (28.3 per 10,000) along with eight of the 12 individual CCHDs. Among 7,726 infants/fetuses with CCHD from active case ascertainment programs, 15.8% had at least one co-occurring chromosomal birth defect. CONCLUSION: Our study provides prevalence estimates for CCHDs by maternal and infant characteristics along with co-occurrence with cardiovascular and chromosomal birth defects among infants/fetuses with CCHD using one of the largest and most recent cohorts since the implementation of widespread CCHD screening. These data can provide a basis for future research to better understand risk factors for these defects.

Differential regulation of G protein signaling in Arabidopsis through two distinct pathways that internalize AtRGS1.

In animals, endocytosis of a seven-transmembrane GPCR is mediated by arrestins to propagate or arrest cytoplasmic G protein-mediated signaling, depending on the bias of the receptor or ligand, which determines how much one transduction pathway is used compared to another. In Arabidopsis thaliana, GPCRs are not required for G protein-coupled signaling because the heterotrimeric G protein complex spontaneously exchanges nucleotide. Instead, the seven-transmembrane protein AtRGS1 modulates G protein signaling through ligand-dependent endocytosis, which initiates derepression of signaling without the involvement of canonical arrestins. Here, we found that endocytosis of AtRGS1 initiated from two separate pools of plasma membrane: sterol-dependent domains and a clathrin-accessible neighborhood, each with a select set of discriminators, activators, and candidate arrestin-like adaptors. Ligand identity (either the pathogen-associated molecular pattern flg22 or the sugar glucose) determined the origin of AtRGS1 endocytosis. Different trafficking origins and trajectories led to different cellular outcomes. Thus, in this system, compartmentation with its associated signalosome architecture drives biased signaling.

Current progress of PM-localized protein functions in jasmonate pathway.

Jasmonate (JA), a class of lipid-derived phytohormone, regulates diverse developmental processes and responses to abiotic or biotic stresses. The biosynthesis and signaling of JA mainly occur in various organelles, except for the plasma membrane (PM). Recently, several PM proteins have been reported to be associated with the JA pathway. This mini-review summarized the recent progress on the functional role of PM-localized proteins involved in JA transportation, JA-related defense responses, and JA-regulated endocytosis.

Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs.

BACKGROUND: Esophageal atresia (EA) affects around 2.3-2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions. METHODS: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s-2010s. RESULTS: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1-90.5) at 1-month, 84.5% (95% CI 83.0-85.9) at 1-year and 82.7% (95% CI 81.2-84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies. CONCLUSIONS: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies.

Dynamic spatial reorganization of BSK1 complexes in the plasma membrane underpins signal-specific activation for growth and immunity.

Growth and immunity are opposing processes that compete for cellular resources, and proper resource allocation is crucial for plant survival. BSK1 plays a key role in the regulation of both growth and immunity by associating with BRI1 and FLS2, respectively. However, it remains unclear how two antagonistic signals co-opt BSK1 to induce signal-specific activation. Here we show that the dynamic spatial reorganization of BSK1 within the plasma membrane underlies the mechanism of signal-specific activation for growth or immunity. Resting BSK1 localizes to membrane rafts as complexes. Unlike BSK1-associated FLS2 and BRI1, flg22 or exogenous brassinosteroid (BR) treatment did not decrease BSK1 levels at the plasma membrane (PM) but rather induced BSK1 multimerization and dissociation from FLS2/BSK1 or BRI1/BSK1, respectively. Moreover, flg22-activated BSK1 translocated from membrane rafts to non-membrane-raft regions, whereas BR-activated BSK1 remained in membrane rafts. When applied together with flg22, BR suppressed various flg22-induced BSK1 activities such as BSK1 dissociation from FLS2/BSK1, BSK1 interaction with MAPKKK5, and BSK translocation together with MAPKKK5. Taken together, this study provides a unique insight into how the precise control of BSK1 spatiotemporal organization regulates the signaling specificity to balance plant growth and immunity.

Prevalence of structural birth defects among infants with Down syndrome, 2013-2017: A US population-based study.

BACKGROUND: Down syndrome is the most common chromosomal disorder at birth and is often accompanied by structural birth defects. Current data on major structural defects in this population are limited. METHODS: States and territorial population-based surveillance programs submitted data on identified cases of Down syndrome and identified structural birth defects during 2013-2017. We estimated prevalence by program type and maternal and infant characteristics. Among programs with active case ascertainment, we estimated the prevalence of birth defects by organ system and for specific defects by maternal age (<35, ≥35) and infant sex. RESULTS: We identified 13,376 cases of Down syndrome. Prevalence among all programs was 12.7 per 10,000 live births. Among these children, 75% had at least one reported co-occurring birth defect diagnosis code. Among 6,210 cases identified by active programs, 66% had a cardiovascular defect with septal defects being the most common: atrial (32.5%), ventricular (20.6%), and atrioventricular (17.4%). Defect prevalence differed by infant sex more frequently than by maternal age. For example, atrioventricular septal defects were more common in female children (20.1% vs. 15.1%) while limb deficiencies were more prevalent in male children (0.4% vs. 0.1%). CONCLUSIONS: Our study provides updated prevalence estimates for structural defects, including rare defects, among children with Down syndrome using one of the largest and most recent cohorts to date. These data may aid clinical care and surveillance.

High-efficiency procedure to characterize, segment, and quantify complex multicellularity in raw micrographs in plants.

BACKGROUND: The increasing number of novel approaches for large-scale, multi-dimensional imaging of cells has created an unprecedented opportunity to analyze plant morphogenesis. However, complex image processing, including identifying specific cells and quantitating parameters, and high running cost of some image analysis softwares remains challenging. Therefore, it is essential to develop an efficient method for identifying plant complex multicellularity in raw micrographs in plants. RESULTS: Here, we developed a high-efficiency procedure to characterize, segment, and quantify plant multicellularity in various raw images using the open-source software packages ImageJ and SR-Tesseler. This procedure allows for the rapid, accurate, automatic quantification of cell patterns and organization at different scales, from large tissues down to the cellular level. We validated our method using different images captured from Arabidopsis thaliana roots and seeds and Populus tremula stems, including fluorescently labeled images, Micro-CT scans, and dyed sections. Finally, we determined the area, centroid coordinate, perimeter, and Feret's diameter of the cells and harvested the cell distribution patterns from Voronoï diagrams by setting the threshold at localization density, mean distance, or area. CONCLUSIONS: This procedure can be used to determine the character and organization of multicellular plant tissues at high efficiency, including precise parameter identification and polygon-based segmentation of plant cells.