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Efficient photosynthesis requires a balance of ATP and NADPH production/consumption in chloroplasts, and the exportation of reducing equivalents from chloroplasts is important for balancing stromal ATP/NADPH ratio. Here, we showed that the overexpression of purple acid phosphatase 2 on the outer membranes of chloroplasts and mitochondria can streamline the production and consumption of reducing equivalents in these two organelles, respectively. A higher capacity of consumption of reducing equivalents in mitochondria can indirectly help chloroplasts to balance the ATP/NADPH ratio in stroma and recycle NADP+, the electron acceptors of the linear electron flow (LEF). A higher rate of ATP and NADPH production from the LEF, a higher capacity of carbon fixation by the Calvin–Benson–Bassham (CBB) cycle and a greater consumption of NADH in mitochondria enhance photosynthesis in the chloroplasts, ATP production in the mitochondria and sucrose synthesis in the cytosol and eventually boost plant growth and seed yields in the overexpression lines.
We examined parent- and adolescent-reported executive functioning (EF) behaviors following pediatric traumatic brain injury (TBI) in the context of Online Family Problem-Solving Therapy (OFPST) and moderators of change in EF behaviors.
In total, 274 families were randomized to OFPST or an internet resource comparison group. Parents and adolescents completed the Behavior Rating Inventory of Executive Function at four time points. Mixed models were used to examine EF behaviors, assessing the effects of visit, treatment group, rater, TBI severity, age, socioeconomic status, and family functioning.
Parents rated their adolescents’ EF as poorer (F(3,1156) = 220.15, p < .001; M = 58.11, SE = 0.73) than adolescents rated themselves (M = 51.81, SE = 0.73). Across raters, EF behaviors were poorer for adolescents whose parents had less education (F(3,1156) = 8.60, p = .003; M = 56.76, SE = 0.98) than for those with more education (M = 53.16, SE = 0.88). Age at baseline interacted with visit (F(3,1156) = 5.05, p = .002), such that families of older adolescents reported improvement in EF behaviors over time. Family functioning also interacted with visit (F(3, 1156) = 2.61, p = .049), indicating more improvement in EF behaviors over time in higher functioning families. There were no effects of treatment or TBI severity.
We identified a discrepancy between parent- and adolescent-reported EF, suggesting reduced awareness of deficits in adolescents with TBI. We also found that poorer family functioning and younger age were associated with poorer recovery after TBI, whereas adolescents of parents with less education were reported as having greater EF deficits across time points.
Glutamine synthetase (GS) and glutamate synthase (GOGAT) play a central role in plant nitrogen (N) metabolism. In order to study the effect of powdery mildew (Blumeria graminis f. sp. tritici, Bgt) on N metabolism, field experiments were carried out to evaluate GS and GOGAT activity, GS expression and grain protein content (GPC) in susceptible (Xi'nong 979) and resistant (Zhengmai 103) wheat cultivars under three treatments. The three treatments were no inoculation (CK), inoculated once with Bgt (MP) and inoculated nine times with Bgt (HP). For Xi'nong 979, the activities of GS and GOGAT in grains as well as GS activity in flag leaves increased at 10–15 days after anthesis (DAA), and decreased significantly at 15 or 20–30 DAA in HP and MP. However, GS activity in grains decreased from 20 DAA, which was later than that of flag leaves (15 DAA). At the same time, GS expression in grains was up-regulated at early stage, with GS1 at 10 DAA and GS2 at 15 DAA, followed by a continuous down-regulation. This result indicated that GS and GOGAT activity as well as GS expression were inhibited by powdery mildew, indicating that N metabolism in grains was inhibited at 20–30 DAA. The current study also found out that the yield of the susceptible cultivar decreased significantly, while its GPC increased obviously in HP. It was shown that the increase of GPC was not due to the enhancement of N metabolism, but due to the passive increase caused by yield reduction.
The use of a submerged inlet is advantageous in modern aircrafts because of its low drag resistance, small radar cross section and ease of maintenance. Although it is well known that the forebody boundary layer deteriorates the aerodynamic performance of a submerged inlet, the level of impact has not yet been fully quantified. To quantify the forebody boundary-layer effect, a submerged diverter was designed to remove a portion of the low-energy boundary flow. The flow pattern and aerodynamic performance of a submerged inlet, with and without the diverter, were investigated by wind-tunnel experimentation and numerical simulations. The effects of mass flow, free stream speed, angle-of-attack and sideslip angle on the aerodynamic characteristics of the inlet with and without the submerged diverter were studied, over an operating envelope of M0 = 0.3 ∼ 0.6,
. The results indicate that both the total pressure loss and the circumferential distortion can be significantly reduced with the removal of the forebody boundary-layer low-energy flow. Meanwhile, the main mechanisms for losses in the submerged inlet were also analysed.
ABSTRACT IMPACT: Screening the effect of thousands of non-coding genetic variants will help identify variants important in the etiology of diseases OBJECTIVES/GOALS: Massively parallel reporter assays (MPRAs) can experimentally evaluate the impact of genetic variants on gene expression. In this study, our objective was to systematically evaluate the functional activity of 3’-UTR SNPs associated with neurological disorders and use those results to help understand their contributions to disease etiology. METHODS/STUDY POPULATION: To choose variants to evaluate with the MPRA, we first gathered SNPs from the GWAS Catalog that were associated with any neurological disorder trait with p-value < 10-5. For each SNP, we identified the region that was in linkage disequilibrium (r2 > 0.8) and retrieved all the common 3’-UTR SNPs (allele-frequency > 0.05) within that region. We used an MPRA to measure the impact of these 3’-UTR variants in SH-SY5Y neuroblastoma cells and a microglial cell line. These results were then used to train a deep-learning model to predict the impact of variants and identify features that contribute to the predictions. RESULTS/ANTICIPATED RESULTS: Of the 13,515 3’-UTR SNPs tested, 400 and 657 significantly impacted gene expression in SH-SY5Y and microglia, respectively. Of the 84 SNPs significantly impacted in both cells, the direction of impact was the same in 81. The direction of eQTL in GTEx tissues agreed with the assay SNP effect in SH-SY5Y cells but not microglial cells. The deep-learning model predicted sequence activity level correlated with the experimental activity level (Spearman’s corr = 0.45). The deep-learning model identified several predictive motifs similar to motifs of RNA-binding proteins. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that MPRAs can be used to evaluate the effect of non-coding variants, and the results can be used to train a machine learning model and interpret its predictions. Together, these can help identify causal variants and further understand the etiology of diseases.
ABSTRACT IMPACT: Our study will integrate state-of-the-art methods in pathogen genomics, epidemiology, and geospatial analysis to identify both host- and pathogen-factors driving the MDR-TB transmission and the study outcome can inform the design of targeted interventions OBJECTIVES/GOALS: The emergence of multidrug-resistant tuberculosis (MDR-TB) poses serious challenges for the global eradication of tuberculosis. Recent research has shown that transmission is now the dominant driver of MDR-TB. However, our limited understanding of where and among whom MDR-TB is transmitted hampers efforts to control person-to-person spread. METHODS/STUDY POPULATION: We used several analytic approaches to characterize the dynamics of MDR-TB transmission in Shanghai, China. We identified all culture-confirmed MDR cases between 2009-2016 in the city and 1) estimated individual-level risk factors for MDR disease; 2) mapped the TB cases by their home addresses and used a Bayesian spatial disease mapping method to identify regions with an elevated risk of MDR-TB; and 3) we sequenced all MDR isolates to understand whether transmission explained variance in risk that was not attributable to the distribution of individual or location-specific risk variates. RESULTS/ANTICIPATED RESULTS: There were 1034 MDR-TB cases among 16,315 culture-confirmed TB cases during the study period. Bayesian disease mapping identified spatial heterogeneity of MDR-TB and determined four hotspots with an elevated risk of MDR-TB, none of which were fully explained by individual or regional-covariates (Figure 1). Sequencing revealed that more than 40% of the MDR-TB strains were in genomic clusters, indicating recent MDR-TB transmission. Most importantly, MDR-TB cases in three of the four large clades (>8 isolates) were spatially concentrated in three strain-specific hotspots (Figure 2). DISCUSSION/SIGNIFICANCE OF FINDINGS: With the combination of traditional epidemiological tools, geographical, and genomic methods, this study revealed multiple loci of transmission of specific MDR-TB clades within a single city. Identification of where and among whom MDR-TB is transmitted can inform the design of targeted interventions.
The rotating instability in a contra-rotating axial flow compressor is investigated by experiments. Twenty-four pressure sensors were installed on the casing to capture the unsteady flow in the rotor tip region simultaneously. A double-phase-locking technique suitable for the contra-rotating compressor was proposed to characterise the static pressure contours of the rotor tip. The mean and root-mean-square pressure contours indicate that rotating instability occurs before the rotating stall happened, and the rotor tip clearance vortex is located upstream of the rear rotor leading edge plane before stall. Fourier spectrum shows that rotating instability and rotating stall both happened under the stall condition, and the frequency band of rotating instability does not change with the flow rate. In the front rotor, the frequency of rotating instability is half of the blade passing frequency. It is verified that the modal estimation method can be implemented by using the average azimuthal phase velocity, which significantly reduced the number of pressure sensors required. Modal estimation results show that each peak of the rotating instability frequency band corresponds to a unique dominant circumferential mode. By optimising average azimuthal phase velocity, an improved modal estimation method is obtained, which can further improve the reliability of the modal estimation results.
To investigate the influences of dietary riboflavin (RF) addition on nutrient digestion and rumen fermentation, eight rumen cannulated Holstein bulls were randomly allocated into four treatments in a repeated 4 × 4 Latin square design. Daily addition level of RF for each bull in control, low RF, medium RF and high RF was 0, 300, 600 and 900 mg, respectively. Increasing the addition level of RF, DM intake was not affected, average daily gain tended to be increased linearly and feed conversion ratio decreased linearly. Total tract digestibilities of DM, organic matter, crude protein (CP) and neutral-detergent fibre (NDF) increased linearly. Rumen pH decreased quadratically, and total volatile fatty acids (VFA) increased quadratically. Acetate molar percentage and acetate:propionate ratio increased linearly, but propionate molar percentage and ammonia-N content decreased linearly. Rumen effective degradability of DM increased linearly, NDF increased quadratically but CP was unaltered. Activity of cellulase and populations of total bacteria, protozoa, fungi, dominant cellulolytic bacteria, Prevotella ruminicola and Ruminobacter amylophilus increased linearly. Linear increase was observed for urinary total purine derivatives excretion. The data suggested that dietary RF addition was essential for rumen microbial growth, and no further increase in performance and rumen total VFA concentration was observed when increasing RF level from 600 to 900 mg/d in dairy bulls.
The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented threat to mental health. Herein, we assessed the impact of COVID-19 on subthreshold depressive symptoms and identified potential mitigating factors.
Participants were from Depression Cohort in China (ChiCTR registry number 1900022145). Adults (n = 1722) with subthreshold depressive symptoms were enrolled between March and October 2019 in a 6-month, community-based interventional study that aimed to prevent clinical depression using psychoeducation. A total of 1506 participants completed the study in Shenzhen, China: 726 participants, who completed the study between March 2019 and January 2020 (i.e. before COVID-19), comprised the ‘wave 1’ group; 780 participants, who were enrolled before COVID-19 and completed the 6-month endpoint assessment during COVID-19, comprised ‘wave 2’. Symptoms of depression, anxiety and insomnia were assessed at baseline and endpoint (i.e. 6-month follow-up) using the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI), respectively. Measures of resilience and regular exercise were assessed at baseline. We compared the mental health outcomes between wave 1 and wave 2 groups. We additionally investigated how mental health outcomes changed across disparate stages of the COVID-19 pandemic in China, i.e. peak (7–13 February), post-peak (14–27 February), remission plateau (28 February−present).
COVID-19 increased the risk for three mental outcomes: (1) depression (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.04–1.62); (2) anxiety (OR = 1.47, 95% CI: 1.16–1.88) and (3) insomnia (OR = 1.37, 95% CI: 1.07–1.77). The highest proportion of probable depression and anxiety was observed post-peak, with 52.9% and 41.4%, respectively. Greater baseline resilience scores had a protective effect on the three main outcomes (depression: OR = 0.26, 95% CI: 0.19–0.37; anxiety: OR = 1.22, 95% CI: 0.14–0.33 and insomnia: OR = 0.18, 95% CI: 0.11–0.28). Furthermore, regular physical activity mitigated the risk for depression (OR = 0.79, 95% CI: 0.79–0.99).
The COVID-19 pandemic exerted a highly significant and negative impact on symptoms of depression, anxiety and insomnia. Mental health outcomes fluctuated as a function of the duration of the pandemic and were alleviated to some extent with the observed decline in community-based transmission. Augmenting resiliency and regular exercise provide an opportunity to mitigate the risk for mental health symptoms during this severe public health crisis.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
Nutrition during the periconceptional period influences postnatal cardiovascular health. We determined whether in vitro embryo culture and transfer, which are manipulations of the nutritional environment during the periconceptional period, dysregulate postnatal blood pressure and blood pressure regulatory mechanisms. Embryos were either transferred to an intermediate recipient ewe (ET) or cultured in vitro in the absence (IVC) or presence of human serum (IVCHS) and a methyl donor (IVCHS+M) for 6 days. Basal blood pressure was recorded at 19–20 weeks after birth. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after varying doses of phenylephrine (PE). mRNA expression of signaling molecules involved in blood pressure regulation was measured in the renal artery. Basal MAP did not differ between groups. Baroreflex sensitivity, set point, and upper plateau were also maintained in all groups after PE stimulation. Adrenergic receptors alpha-1A (αAR1A), alpha-1B (αAR1B), and angiotensin II receptor type 1 (AT1R) mRNA expression were not different from controls in the renal artery. These results suggest there is no programmed effect of ET or IVC on basal blood pressure or the baroreflex control mechanisms in adolescence, but future studies are required to determine the impact of ET and IVC on these mechanisms later in the life course when developmental programming effects may be unmasked by age.
Did growing up as singletons (only-children) convince young adults born under China's one-child policy of the superiority of singleton status and therefore the desirability of not having more than one child? This article draws on interviews with 52 childless newlyweds in Dalian, China, to help answer this question. We found that far from convincing them of the superiority of singleton status, the feelings of loneliness experienced by singletons in childhood and adulthood have convinced most of them that it is better to have a sibling than to be a singleton and thus it is better to have two children instead of one. Moreover, interviewees who did have siblings tended to corroborate singletons’ beliefs about how valuable a sibling can be in both childhood and adulthood.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Precise instrumental calibration is of crucial importance to 21-cm cosmology experiments. The Murchison Widefield Array’s (MWA) Phase II compact configuration offers us opportunities for both redundant calibration and sky-based calibration algorithms; using the two in tandem is a potential approach to mitigate calibration errors caused by inaccurate sky models. The MWA Epoch of Reionization (EoR) experiment targets three patches of the sky (dubbed EoR0, EoR1, and EoR2) with deep observations. Previous work in Li et al. (2018) and (2019) studied the effect of tandem calibration on the EoR0 field and found that it yielded no significant improvement in the power spectrum (PS) over sky-based calibration alone. In this work, we apply similar techniques to the EoR1 field and find a distinct result: the improvements in the PS from tandem calibration are significant. To understand this result, we analyse both the calibration solutions themselves and the effects on the PS over three nights of EoR1 observations. We conclude that the presence of the bright radio galaxy Fornax A in EoR1 degrades the performance of sky-based calibration, which in turn enables redundant calibration to have a larger impact. These results suggest that redundant calibration can indeed mitigate some level of model incompleteness error.
A disruption database characterizing the current quench of disruptions with ITER-like tungsten divertor has been developed on EAST. It provides a large number of plasma parameters describing the predisruptive plasma, current quench time, eddy current, and mitigation by massive impurity injection, which shows that the current quench time strongly depends on magnetic energy and post-disruption electron temperature. Further, the energy balance and magnetic energy dissipation during the current quench phase has been well analysed. Magnetic energy is also demonstrated to be dissipated mainly by ohmic reheating and inductive coupling, and both of the two channels have great effects on current quench time. Also, massive gas injection is an efficient method to speed up the current quench and increase the fraction of impurity radiation.
Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.
Background: Antibiotics are among the most commonly prescribed drugs in nursing homes; urinary tract infections (UTIs) are a frequent indication. Although there is no gold standard for the diagnosis of UTIs, various criteria have been developed to inform and standardize nursing home prescribing decisions, with the goal of reducing unnecessary antibiotic prescribing. Using different published criteria designed to guide decisions on initiating treatment of UTIs (ie, symptomatic, catheter-associated, and uncomplicated cystitis), our objective was to assess the appropriateness of antibiotic prescribing among NH residents. Methods: In 2017, the CDC Emerging Infections Program (EIP) performed a prevalence survey of healthcare-associated infections and antibiotic use in 161 nursing homes from 10 states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. EIP staff reviewed resident medical records to collect demographic and clinical information, infection signs, symptoms, and diagnostic testing documented on the day an antibiotic was initiated and 6 days prior. We applied 4 criteria to determine whether initiation of treatment for UTI was supported: (1) the Loeb minimum clinical criteria (Loeb); (2) the Suspected UTI Situation, Background, Assessment, and Recommendation tool (UTI SBAR tool); (3) adaptation of Infectious Diseases Society of America UTI treatment guidelines for nursing home residents (Crnich & Drinka); and (4) diagnostic criteria for uncomplicated cystitis (cystitis consensus) (Fig. 1). We calculated the percentage of residents for whom initiating UTI treatment was appropriate by these criteria. Results: Of 248 residents for whom UTI treatment was initiated in the nursing home, the median age was 79 years [IQR, 19], 63% were female, and 35% were admitted for postacute care. There was substantial variability in the percentage of residents with antibiotic initiation classified as appropriate by each of the criteria, ranging from 8% for the cystitis consensus, to 27% for Loeb, to 33% for the UTI SBAR tool, to 51% for Crnich and Drinka (Fig. 2). Conclusions: Appropriate initiation of UTI treatment among nursing home residents remained low regardless of criteria used. At best only half of antibiotic treatment met published prescribing criteria. Although insufficient documentation of infection signs, symptoms and testing may have contributed to the low percentages observed, adequate documentation in the medical record to support prescribing should be standard practice, as outlined in the CDC Core Elements of Antibiotic Stewardship for nursing homes. Standardized UTI prescribing criteria should be incorporated into nursing home stewardship activities to improve the assessment and documentation of symptomatic UTI and to reduce inappropriate antibiotic use.
The availability of large healthcare datasets offers the opportunity for researchers to navigate the traditional clinical and translational science research stages in a nonlinear manner. In particular, data scientists can harness the power of large healthcare datasets to bridge from preclinical discoveries (T0) directly to assessing population-level health impact (T4). A successful bridge from T0 to T4 does not bypass the other stages entirely; rather, effective team science makes a direct progression from T0 to T4 impactful by incorporating the perspectives of researchers from every stage of the clinical and translational science research spectrum. In this exemplar, we demonstrate how effective team science overcame challenges and, ultimately, ensured success when a diverse team of researchers worked together, using healthcare big data to test population-level substance use disorder (SUD) hypotheses generated from preclinical rodent studies. This project, called Advancing Substance use disorder Knowledge using Big Data (ASK Big Data), highlights the critical roles that data science expertise and effective team science play in quickly translating preclinical research into public health impact.
Using a legal standard for scrutinising the regulation of food label claims, this study assessed whether consumers are misled about wholegrain (WG) content and product healthfulness based on common product labels.
First, a discrete choice experiment used pairs of hypothetical products with different amounts of WG, sugar and salt to measure effects on assessment of healthfulness; and second, a WG content comprehension assessment used actual product labels to assess respondent understanding.
Online national panel survey.
For a representative sample of US adults (n 1030), survey responses were collected in 2018 and analysed in 2019.
First, 29–47 % of respondents incorrectly identified the healthier product from paired options, and respondents who self-identified as having difficulty in understanding labels were more likely to err. Second, for actual products composed primarily of refined grains, 43–51 % of respondents overstated the WG content, whereas for one product composed primarily of WG, 17 % of respondents understated the WG content.
The frequency of consumer misunderstanding of grain product labels was high in both study components. Potential policies to address consumer confusion include requiring disclosure of WG content as a percentage of total grain content or requiring disclosure of the grams of WG v. refined grains per serving.