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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.
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.
Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).
Materials and Methods
Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.
Most patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.
These data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.
Beryl from Xuebaoding, Sichuan Province, western China is known for its unusual tabular habit and W–Sn–Be paragenesis in a greisen-type deposit. The crystals are typically colourless transparent to pale blue, often with screw dislocations of hexagonal symmetry on the (0001) crystal faces. Combining electron microprobe analyses and laser ablation inductively coupled plasma mass spectrometry with single-crystal X-ray diffraction (XRD), correlated with Raman and micro-infrared (IR) spectroscopy and imaging, the crystal chemical characteristics are determined. The contents of Na+ (0.24–0.38 atoms per formula unit (apfu)) and Li+ up to 0.38 apfu are at the high end compared to beryl from other localities worldwide. Li+ substitution for Be2+ on the tetrahedral (T2) site is predominantly charge balanced by Na+ on the smaller channel (C2) site, with Na+ ranging from 91.5% to 99.7% (apfu) of the sum of all other alkali elements. Cs+ and minor Rb+ and K+ primarily charge balance the minor M2+ substitution for Al3+ at the A site; all iron at the A site is suggested to be trivalent. The a axis ranges from 9.2161(2) to 9.2171(4) Å, with unit-cell volume from 678.03(3) to 678.48(7) Å3. The c/a ratio of 1.0002–1.0005 is characteristic for T2-type beryl with unit-cell parameters controlled primarily by Be2+ substitution. Transmission micro-IR vibrational spectroscopy and imaging identifies coordination of one or two water molecules to Na+ (type IIs and type IId, respectively) as well as alkali free water (type I). Based on IR absorption cross section and XRD a C1 site water content of 0.4–0.5 apfu is derived, i.e. close to 50% site occupancy. Secondary crystal phases with a decrease in Fe and Mg, yet increase in Na, suggest early crystallisation of aquamarine, with goshenite being late. With similar crystal chemistry to beryl of columnar habit from other localities worldwide, the tabular habit of Xuebaoding beryl seems to be unrelated to chemical composition and alkali content.
There is a lack of mental health promotion and treatment services targeting HIV-positive men who have sex with men (HIVMSM) in China. The aim of this study was to evaluate the mental health promotion efficacy of an online intervention that combined Three Good Things (TGT) with electronic social networking (TGT-SN) and an intervention that used TGT only (TGT-only), compared with a control group.
We conducted a randomised controlled trial among HIVMSM in Chengdu, China. The participants were randomly assigned to the TGT-SN, TGT-only, and control groups. The participants in the TGT-SN group were divided into five social network groups and asked to post brief messages to the group about three good things that they had experienced and for which they felt grateful. The participants in the TGT-only group were only required to write down their three good things daily without sharing them with others. The control group received information about mental health promotion once a week for a month. The primary outcome was probable depression. Secondary outcomes were anxiety, positive and negative affect, gratitude, happiness and social support. These outcomes were assessed at baseline, 1, 3, 6 and 12 months after the intervention. Repeated-measures analyses were conducted using generalised estimation equations. The study was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-13003252).
Between June 2013 and May 2015, 404 participants were enrolled and randomly assigned to either the TGT-SN (n = 129), TGT-only (n = 139) or control group (n = 136). The main effects of TGT-SN (adjusted odds ratio (aOR) = 0.75, 95% CI 0.52–1.09; p = 0.131) and TGT-only (aOR = 0.83, 95% CI 0.57–1.21; p = 0.332) in reducing depression were statistically non-significant. The participants of the TGT-SN group showed significantly lower anxiety symptoms (aOR = 0.62, 95% CI 0.43–0.89; p = 0.009) and negative affect (β = −1.62, 95% CI 2.98 to −0.26; p = 0.019) over time compared with those of the control group. No significant main effect was found for any secondary outcomes for the TGT-only group.
The novel intervention combining the TGT exercise with electronic social networking was found effective in reducing anxiety and negative affect among HIVMSM.
Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.
Laboratory experiments are conducted to investigate the mechanism controlling the formation of stable and unstable acoustic fountains at the free surface of a quiescent body of water. Fountains are induced by focused ultrasonic, a new modality that allows for better spatiotemporal control of water flow. Particle image velocimetry was used to characterize the induced flow field in the vicinity of the ultrasonic focal spot. We used two types of ultrasonic transducers with distinct wave frequencies. We examined three fountain formation regimes by varying the pressure level of the transducers, namely weak, intermediate (stable) and highly forced fountains (explosive). Between different regimes, the fountain height underwent a step-change in response to the increase in acoustic pressure. A force estimation obtained from the flow field shows that the magnitude of axial momentum flux is orders of magnitude lower than that of gravity and surface tension, indicating that the dominant driving force for the fountain generation is the acoustic radiation force (Nightingale et al., Ultrasound Med. Biol., vol. 28, 2002, pp. 227–235). We propose a simple model to estimate the shape of a stable fountain; it accounts for the applied acoustic pressure, gravity, surface tension and axial momentum. The model neglects viscous force, which precludes capturing the intermediate fountain surface curvature. However, the model successfully predicts the geometry of the weak and intermediate fountains.
Uterine fibroids or leiomyomas are the most common benign gynaecological tumours; up to 25–30% of women may be diagnosed with fibroids during their lifetime . Women with uterine fibroids may be asymptomatic, or they may present with menstrual symptoms such as menorrhagia and dysmenorrhoea, pressure symptoms, infertility, recurrent miscarriage or complications during pregnancy like red degeneration.
We study the evolution of unidirectional water waves from a randomly forced input condition with uncorrelated Fourier components. We examine the kurtosis of the linearised free surface as a convenient proxy for the probability of a rogue wave. We repeat the laboratory experiments of Onorato et al. (Phys. Rev. E, vol. 70, 2004, 067302), both experimentally and numerically, and extend the parameter space in our numerical simulations. We consider numerical simulations based on the modified nonlinear Schrödinger equation and the fully nonlinear water wave equations, which are in good agreement. For low steepness, existing analytical models based on the nonlinear Schrödinger equation (NLS) are found to be accurate. For cases which are steep or have very narrow bandwidths, these analytical models over-predict the rate at which excess kurtosis develops. In these steep cases, the kurtosis in both our experiments and numerical simulations peaks before returning to an equilibrium level. Such transient maxima are not predicted by NLS-based analytical models. Above a certain threshold of steepness, the steady-state value of kurtosis is primarily dependent on the spectral bandwidth. We also examine how the average shape of extreme events is modified by nonlinearity over the evolution distance, showing significant asymmetry during the initial evolution, which is greatly reduced once the spectrum has reached equilibrium. The locations of the maxima in asymmetry coincide approximately with the locations of the maxima in kurtosis.
This article builds on the ambiguous concept of the autonomy of universities with three historical turns in two dominant types of universities in the world – the Anglo-Saxon and American models, represented by the British and American institutions, and the Continental models, including the recently emerging Chinese University 3.0. Based on empirical data from two comparative case studies with a documentary analysis approach, I investigate the structure of the zhong-yong model of self-mastery, demonstrating how it may differ from the Western models and offering cultural interpretations for these nuances. The article concludes that self-mastery in the Chinese context provides an additional form of autonomy which is rooted in the pragmatic Confucian concept of zhong-yong. It is also found that through the pragmatism of self-mastery, the zhong-yong model enables Chinese universities to directly serve the state and, at the same time, to legitimate the priority given to their development by state power, thus creating abundant space and resources for them to fully unfold their potentialities. With multilayered and multidirectional power relationships, this model of governance has enabled Chinese universities to radically transform themselves in a short period of time and will allow them to eventually become global leaders, although they may have to sacrifice autonomous freedom in some ways.
The characteristic traits of maize (Zea mays L.) leaves affect light interception and photosynthesis. Measurement or estimation of individual leaf area has been described using discontinuous equations or bell-shaped functions. However, new maize hybrids show different canopy architecture, such as leaf angle in modern maize which is more upright and ear leaf and adjacent leaves which are longer than older hybrids. The original equations and their parameters, which have been used for older maize hybrids and grown at low plant densities, will not accurately represent modern hybrids. Therefore, the aim of this paper was to develop a new empirical equation that captures vertical leaf distribution. To characterize the vertical leaf profile, we conducted a field experiment in Jilin province, Northeast China from 2015 to 2018. Our new equation for the vertical distribution of leaf profile describes leaf length, width or leaf area as a function of leaf rank, using parameters for the maximum value for leaf length, width or area, the leaf rank at which the maximum value is obtained, and the width of the curve. It thus involves one parameter less than the previously used equations. By analysing the characteristics of this new equation, we identified four key leaf ranks (4, 8, 14 and 20) for which leaf parameter values need to be quantified in order to have a good estimation of leaf length, width and area. Together, the method of leaf area estimation proposed here adds versatility for use in modern maize hybrids and simplifies the field measurements by using the four key leaf ranks to estimate vertical leaf distribution in maize canopy instead of all leaf ranks.
Adipocytokines, which are secreted during fetal development by both mothers and fetuses, may influence fetal lung development, but little human data are available. We used data from the HOME Study to investigate the associations of cord blood adipocytokine concentrations with children’s lung forced expiratory volume (FEV1; N = 160) and their risk of wheeze (N = 281). We measured umbilical cord serum adipocytokine concentrations using enzyme-linked immunosorbent assays and FEV1 using a portable spirometer at ages 4 and 5 to calculate the percent predicted FEV1 (%FEV1). Parents completed standardized questionnaires of their child’s wheeze symptoms every 6 months from birth to age 5, then again at ages 6 and 8. We used multivariable linear mixed models and modified Poisson regression with generalized estimating equations to estimate associations of adipocytokine concentrations (log2-transformed) with children’s %FEV1 and the risk of wheeze, respectively, adjusting for sociodemographic, perinatal, and child factors. Cord serum leptin was not associated with children’s %FEV1. Higher cord serum adiponectin concentrations were associated with higher %FEV1 in girls (β = 3.1, 95% confidence interval [CI]: 0.6, 5.6), but not in boys (β = −1.3, 95% CI: −5.9, 3.3) (sex × adiponectin p-value = 0.05). Higher leptin was associated with lower risk of wheeze in girls (RR = 0.74, 95% CI: 0.66, 0.84), but not boys (RR = 0.87, 95% CI: 0.69, 1.11) (sex × leptin p-value = 0.01). In contrast, higher adiponectin concentrations were associated with lower risk of wheeze (RR = 0.84, 95% CI: 0.73, 0.96) in both boys and girls. These data suggest that fetal adipocytokines may impact lung development and function in early childhood. Future studies are needed to confirm these findings and explore the mechanisms underlying these associations.
This study describes a procedural blank assessment of the ultraviolet photochemical oxidation (UV oxidation) method that is used to measure carbon isotopes of dissolved organic carbon (DOC) at the National Ocean Sciences Accelerator Mass Spectrometry Facility (NOSAMS). A retrospective compilation of Fm and δ13C results for secondary standards (OX-II, glycine) between 2009 and 2018 indicated that a revised blank correction was required to bring results in line with accepted values. The application of a best-fit mass-balance correction yielded a procedural blank of 22.0 ± 6.0 µg C with Fm of 0.30 ± 0.20 and δ13C of –32.0 ± 3.0‰ for this period, which was notably higher and more variable than previously reported. Changes to the procedure, specifically elimination of higher organic carbon reagents and improved sample and reactor handling, reduced the blank to 11.0 ± 2.75 µg C, with Fm of 0.14 ± 0.10 and δ13C of –31.0 ± 5.5‰. A thorough determination of the entire sample processing blank is required to ensure accurate isotopic compositions of seawater DOC using the UV oxidation method. Additional efforts are needed to further reduce the procedural blank so that smaller DOC samples can be analyzed, and to increase sample throughput.
Microwaves are a form of electromagnetic radiation commonly used for telecommunications, navigation and food processing. More recently microwave technologies have found applications in fibre-reinforced polymer composites, which are increasingly used in aircraft structures. Microwave energy can be applied with low power (up to milliwatts) for non-destructive testing and high power (up to kilowatts) for heating/curing purposes. The state-of-the-art applications at high power include curing, three-dimensional (3D) printing, joining and recycling, whereas low-power microwave techniques can provide quality checks, strain sensing and damage inspection. Low-power microwave testing has the advantage of being non-contact, there is no need for surface transducers or couplants, it is operator friendly and relatively inexpensive; high-power microwave energy can offer volumetric heating, reduced processing time and energy saving with no ionising hazards. In this paper the recent research progress is reviewed, identifying achievements and challenges. First, the critical electromagnetic properties of composites that are closely related to the heating and sensing performance are discussed. Then, representative case studies are presented. Finally, the trends are outlined, including intelligent/automated inspection and solid-state heating.
Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.
Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance.
The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252).
Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes.
The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.
We report key learning from the public health management of the first two confirmed cases of COVID-19 identified in the UK. The first case imported, and the second associated with probable person-to-person transmission within the UK. Contact tracing was complex and fast-moving. Potential exposures for both cases were reviewed, and 52 contacts were identified. No further confirmed COVID-19 cases have been linked epidemiologically to these two cases. As steps are made to enhance contact tracing across the UK, the lessons learned from earlier contact tracing during the country's containment phase are particularly important and timely.
Toxoplasma gondii rhoptry protein TgROP18 is a polymorphic virulence effector that targets immunity-related GTPases (IRGs) in rodents. Given that IRGs are uniquely diversified in rodents and not in other T. gondii intermediate hosts, the role of TgROP18 in manipulating non-rodent cells is unclear. Here we show that in human cells TgROP18I interacts with the interferon-gamma-inducible protein N-myc and STAT interactor (NMI) and that this is a property that is unique to the type I TgROP18 allele. Specifically, when expressed ectopically in mammalian cells only TgROP18I co-immunoprecipitates with NMI in IFN-γ-treated cells, while TgROP18II does not. In parasites expressing TgROP18I or TgROP18II, NMI only co-immunoprecipitates with TgROP18I and this is associated with allele-specific immunolocalization of NMI on the parasitophorous vacuolar membrane (PVM). We also found that TgROP18I reduces NMI association with IFN-γ-activated sequences (GAS) in the IRF1 gene promoter. Finally, we determined that polymorphisms in the C-terminal kinase domain of TgROP18I are required for allele-specific effects on NMI. Together, these data further define new host pathway targeted by TgROP18I and provide the first function driven by allelic differences in the highly polymorphic ROP18 locus.