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Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:
1. determine the extent to which this is altered in schizophrenia and
2. use a verbal fluency paradigm.
This is relevant since:
1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and
2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.
Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.
The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.
Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.
Compare baseline and 6-month follow-up plasma and cerebrospinal fluid (CSF) levels of amyloid β peptides 1–40 (Aβ1–40) and 1–42 (Aβ1–42), total tau protein (T-tau) and phosphorylated tau at threonine 231 (P-tau231) in patients with Alzheimer's disease (AD) and vascular dementia (VD).
21 patients with AD and 7 patients with VD based on the criteria of Diagnostic Statistical Manual 4th edition were assessed at baseline and 7 with AD and 6 with VD were re-assessed 6 months later. Assessments included the Mini-Mental State Exam (MMSE), the Global Deteriorate Scale (GDS), plasma and CSF levels of Aβ1–40 and Aβ1–42, and CSF levels of T-tau and P-tau231 (using a sandwich enzyme-linked immunosorbent assay).
At baseline there were significant differences between AD and VD patients in the mean CSF levels of T-tau (t=2.580, P=0.016), P-tau231 (t=4.014, P=0.000) and Aβ1–40 (t=2.766, P=0.010). At baseline in AD patients, duration of illness was negatively correlated with CSF P-tau231 levels (r=-0.485, P=0.026), MMSE scores (r=-0.565, P=0.008) and GDS scores (r=-0.482, P=0.027); and CSF Aβ1–42 levels were positively correlated to MMSE scores (r=0.565, P=0.008) and negatively correlated with GDS scores (r=-0.634, P=0.002). In the AD patients plasma Aβ1–40 levels increased significantly over the 6-month follow-up period (t=-2.735, P=0.041).
Plasma Aβ1–40 levels increased significantly in AD patients after 6-months of follow-up, that means levels of plasma Aβ1–40 could imply the development of Alzheimer disease. Moreover, CSF P-tau231 and CSF Aβ1–42 levels are associated with the severity of dementia and cognitive impairment.
Explore the relationship between levels of plasma Aβ1–40, Aβ1–42 and heat shock protein 70 (HSP70) in patients with Alzheimer disease (AD) and vascular dementia (VD) and in elderly non-demented controls.
23 patients with AD and 21 patients with VD who meet diagnostic criteria of the Diagnostic Statistical Manual 4th edition and 20 control subjects were enrolled, administered the Mini-Mental State Exam (MMSE) and the Activity of Daily Living (ADL) inventory and their levels of plasma Aβ1–40, Aβ1–42 and HSP70 were measured by sandwich enzyme-linked immunosorbent assay.
The levels of plasma Aβ1–40, Aβ1–42 and the Aβ1–40/Aβ1–42 ratio were not significantly different across groups, but levels of plasma HSP70 in VD patients was significantly higher than in AD patients and in normal controls (3.19 vs 1.91 vs 1.43ng/ml, respectively; F=6.464, P=0.003). In the AD group MMSE scores were inversely correlated with ADL scores (r=-0.617, P=0.002) and with levels of plasma HSP70 (r=-0.437, P=0.037); but HSP70 levels were positively correlated with age (r=0.616, P=0.002) and with plasma Aβ1–40 (r=0.497, P=0.016) in AD group. In the VD group levels of plasma HSP70 were positively correlated with plasma Aβ1–40 (r=0.436, P=0.048).
Our findings provide further evidence that high plasma HSP70 levels may play a role in the diagnosis and differential diagnosis of AD. HSP70 levels in AD patients is inversely associated with cognitive performance and positively correlated with plasma Aβ1–40. Plasma HSP70 in VD patients is significantly elevated and positively correlated with plasma Aβ1–40.
Chlamydia trachomatis (CT) infection has been a major public health threat globally. Monitoring and prediction of CT epidemic status and trends are important for programme planning, allocating resources and assessing impact; however, such activities are limited in China. In this study, we aimed to apply a seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence of CT infection in Shenzhen city, China. The monthly incidence of CT between January 2008 and June 2019 in Shenzhen was used to fit and validate the SARIMA model. A seasonal fluctuation and a slightly increasing pattern of a long-term trend were revealed in the time series of CT incidence. The monthly CT incidence ranged from 4.80/100 000 to 21.56/100 000. The mean absolute percentage error value of the optimal model was 8.08%. The SARIMA model could be applied to effectively predict the short-term CT incidence in Shenzhen and provide support for the development of interventions for disease control and prevention.
Lassa fever (LF) is increasingly recognised as an important rodent-borne viral haemorrhagic fever presenting a severe public health threat to sub-Saharan West Africa. In 2017–18, LF caused an unprecedented epidemic in Nigeria and the situation was worsening in 2018–19. This work aims to study the epidemiological features of epidemics in different Nigerian regions and quantify the association between reproduction number (R) and state rainfall. We quantify the infectivity of LF by the reproduction numbers estimated from four different growth models: the Richards, three-parameter logistic, Gompertz and Weibull growth models. LF surveillance data are used to fit the growth models and estimate the Rs and epidemic turning points (τ) in different regions at different time periods. Cochran's Q test is further applied to test the spatial heterogeneity of the LF epidemics. A linear random-effect regression model is adopted to quantify the association between R and state rainfall with various lag terms. Our estimated Rs for 2017–18 (1.33 with 95% CI 1.29–1.37) was significantly higher than those for 2016–17 (1.23 with 95% CI: (1.22, 1.24)) and 2018–19 (ranged from 1.08 to 1.36). We report spatial heterogeneity in the Rs for epidemics in different Nigerian regions. We find that a one-unit (mm) increase in average monthly rainfall over the past 7 months could cause a 0.62% (95% CI 0.20%–1.05%)) rise in R. There is significant spatial heterogeneity in the LF epidemics in different Nigerian regions. We report clear evidence of rainfall impacts on LF epidemics in Nigeria and quantify the impact.
In the livestock husbandry compensatory growth may be explored as a means to improve nutrient utilization, to reduce gut health problems due to excess protein intake, to simplify feeding strategies and thus to improve production efficiencies. This study investigated the effects of early protein restriction (EPR) and early antibiotic intervention (EAI) on growth performance, intestinal morphology, colonic bacteria, metabolites and mucosal gene expressions during the restriction phase and re-alimentation phase. A total of 64 piglets (10.04 ± 0.73 kg) were randomly divided into four treatment groups according to a 2 × 2 factorial arrangement with two levels of proteins (14% v. 20%) and two levels of antibiotics (0 v. 50 mg/kg kitasamycin and 20 mg/kg colistin sulphate). After a 30-day restriction phase with four kinds of diets, all groups were fed the same diets for another 74 days. The results showed that EPR decreased BW, average daily gain (ADG), average daily feed intake in the restriction phase (P < 0.01) and increased ADG on days 66 to 104 of the late re-alimentation phase. Early protein restriction could decrease the villus height in the jejunum (P < 0.05), while shifting to the same diets restored the villus height. Meanwhile, during the re-alimentation phase, pigs in the protein restriction groups had increased concentrations of total short chain fatty acids (P < 0.05), and modified the abundances of Firmicutes and Bacteroidetes in the colon. Furthermore, the lower microbial diversity caused by EPR was improved, and gene expression analysis indicated a better barrier function in the colon. During the whole trial, EAI had no interaction with EPR and played a dispensable role in compensatory growth. Collectively, the retardation of growth caused by EPR can be compensated for in the later stages of pig raising, and accompanied by altered intestinal morphology, microbial composition.
Proximal environments could facilitate smoking cessation among low-income smokers by making cessation appealing to strive for and tenable.
We sought to examine how home smoking rules and proximal environmental factors such as other household members' and peers' smoking behaviors and attitudes related to low-income smokers' past quit attempts, readiness, and self-efficacy to quit.
This analysis used data from Offering Proactive Treatment Intervention (OPT-IN) (randomized control trial of proactive tobacco cessation outreach) baseline survey, which was completed by 2,406 participants in 2011/12. We tested the associations between predictors (home smoking rules and proximal environmental factors) and outcomes (past-year quit attempts, readiness to quit, and quitting self-efficacy).
Smokers who lived in homes with more restrictive household smoking rules, and/or reported having ‘important others’ who would be supportive of their quitting, were more likely to report having made a quit attempt in the past year, had greater readiness to quit, and greater self-efficacy related to quitting.
Adjustments to proximal environments, including strengthening household smoking rules, might encourage cessation even if other household members are smokers.
Cognitive dysfunction is a symptomatic domain identified across many mental disorders. Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational and functional disability. Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD. Most antidepressants have not been developed and/or evaluated for their ability to directly and independently ameliorate cognitive deficits. Multiple interacting neurobiological mechanisms (eg, neuroinflammation) are implicated as subserving cognitive deficits in MDD. A testable hypothesis, with preliminary support, posits that improving performance across cognitive domains in individuals with MDD may improve psychosocial function, workplace function, quality of life, and other patient-reported outcomes, independent of effects on core mood symptoms. Herein we aim to (1) provide a rationale for prioritizing cognitive deficits as a therapeutic target, (2) briefly discuss the neurobiological substrates subserving cognitive dysfunction, and (3) provide an update on current and future treatment avenues.
Methods for the control of molecular deposition and orientation are critical for the development of organic electronic devices. Here, we show the fabrication of ribbons of the optical material polydiacetylene (PDA) using a controlled evaporative self-assembly method. The ability to form these ribbons is highly dependent on both the side groups on the PDA as well as the solvent used in the preparation. Arrays of ribbons of one type of PDA, poly[1,6-di(N-carbazolyl)-2,4-hexadiyne], with widths on the order of 1–2 µm and lengths of 100s of micrometers, could be successfully obtained with good orientation.
Vegetable and grain amaranths represent a vital source of micronutrients and protein in Asia and Africa. However, various foliar lepidopteran pests and stem-mining weevils hinder amaranth production. Insect-resistant cultivars can enhance the productivity of this crop. Here, we report on the performances of amaranth varieties screened for their resistance to insect pests under the field conditions at The World Vegetable Center stations in Asia and sub-Saharan Africa. We conducted two preliminary screening trials with a total of 263 entries from around the world in Taiwan and a third preliminary screening trial with 49 African-indigenous entries in Tanzania. Promising entries from these preliminary trials were collectively evaluated in an advanced screening trial in Tanzania, to identify lines resistant to foliar and stem-boring pests in East Africa. Four entries exhibited moderate resistance to foliar pests: TZ51 and TZ53 (Amaranthus cruentus), TZ34 (A. dubius) and TZ39 (Amaranthus sp.). Five entries showed moderate resistance to stem weevils: TZ06 and TZ27 (A. cruentus), TZ52 (A. graecizans), TZ59 (A. palmeri) and TZ07 (Amaranthus sp.). Lepidopteran pests affecting leaves were reared to adulthood and identified as Spoladea recurvalis (Crambidae), Spodoptera exigua (Noctuidae) and Spodoptera littoralis (Noctuidae). Stem weevil larvae were also reared and identified as: Neocleonus sannio Herbst, Gasteroclisus pr. rhomboidalis Boheman, Hypolixus pr. haerens Boheman and Baradine sp. (Curculionidae). These results highlight key amaranth pests in East Africa and identify insect-resistant entries that will be useful in breeding programmes and resistance studies.
In North America, the raccoon-associated variant of rabies virus (RRV) is of special concern, given its relatively rapid spread throughout the eastern USA and its potential public health impact due to high raccoon host densities in urban areas. Northward expansion of this epizootic included an outbreak in the Canadian province of Quebec in 2006–2009 due to trans-border spread from the State of Vermont. To inform a more proactive approach to future control efforts, this study uses phylogenetic analyses to explore the role of geography and alternative carnivore hosts in the dynamics of RRV spread within Vermont. Specifically, we sought to examine whether striped skunks, a species frequently infected by RRV, could be part of the maintenance host community. Whole genome sequencing of 160 RRV samples from Vermont and neighbouring US states were used for fine-scale phylogeographic analyses. Results, together with the complete surveillance record of raccoon rabies since its entry into Vermont in 1994, document incursions by two distinct viral lineages and identify topographical features of the landscape which have significantly influenced viral spread, resulting in a complex distribution pattern of viral variants throughout the state. Results of phylogenetic cluster analysis and discrete state reconstruction contained some evidence of skunk-to-skunk and skunk-to-raccoon transmission but overall failed to support a role for skunks as alternative maintenance hosts.
The neuropsychological origins of negative syndrome of schizophrenia remain elusive. Evidence from behavioural studies, which utilised emotion-inducing pictures to elicit motivated behaviour generally reported that that schizophrenia patients experienced similar affective experience as healthy individuals but failed to translate emotional salience to motivated behaviour, a phenomenon called emotion–behaviour decoupling. However, a few studies have examined emotion–behaviour decoupling in non-psychotic high-risk populations, who are relatively unaffected by medication effects.
In this study, we examined the nature and extent of emotion–behaviour decoupling in in three independent samples (65 schizophrenia patients v. 63 controls; 40 unaffected relatives v. 45 controls; and 32 individuals with social anhedonia v. 32 controls). We administered an experimental task to examine their affective experience and its coupling with behaviour, using emotion-inducing slides, and allowed participants to alter stimulus exposure using button-pressing to seek pleasure or avoid aversion.
Schizophrenia patients reported similar affective experiences as their controls, while their unaffected relatives and individuals with high levels of social anhedonia exhibited attenuated affective experiences, in particular in the arousal aspect. Compared with their respective control groups, all of the three groups showed emotion–behaviour decoupling.
Our findings support that both genetically and behaviourally high-risk groups exhibit emotion–behaviour decoupling. The familial association apparently supports its role as a putative trait marker for schizophrenia.
Mechanisms responsible for excellent marbling in Japanese black cattle, Wagyu, remain to be established. Because both muscle cells and intramuscular adipocytes are developed from mesenchymal progenitor cells during early muscle development, we hypothesized that intramuscular progenitor cells in Wagyu cattle have attenuated myogenic capacity in favor of adipogenesis, leading to high marbling but reduced muscle growth. Biceps femoris muscle biopsy samples were obtained from both Angus (n=3) and Wagyu (n=3) cattle at 12 months of age. Compared with Angus, the density of satellite cells was much lower in Wagyu muscle (by 45.8±10%, P<0.05). Consistently, the formation of myotubes from muscle-derived progenitor cells was also lower (by 64.2±12.9%, P<0.05), but adipogenic capacity was greater in Wagyu. The average muscle fiber diameter was larger in Wagyu (by 23.9±6.8%, P=0.089) despite less muscle mass, suggesting less muscle fiber formation in Wagyu compared with Angus cattle. Because satellite cells are derived from fetal myogenic cells, the reduction in satellite cell density together with lower muscle fiber formation suggests that myogenesis was attenuated during early muscle development in Wagyu cattle. Given the shared pool of mesenchymal progenitor cells, the attenuated myogenesis likely shifts progenitor cells to adipogenesis during early development, which may contribute to high intramuscular adipocyte formation in Wagyu cattle.
The formation and evolution of wingtip vortex system generated from three wing configurations are simulated with the improved delayed detached eddy simulation (IDDES) method. Numerical results show that each layout produces an interacting wingtip vortex system. These three corresponding vortical interactions are, respectively, the interaction between wingtip vortex and its counter-rotating vortex, winglet-tip vortex, and winglet four-vortex system. The fluid entrainment of ambient fluid and vortical impulse transport resulted from inductive effect have been founded generally existing in its formation and evolution. These two dominated mechanisms account for induced drag generation. On one hand, the winglet with toed-out angle is considered capable of changing the flow field around the winglet, and decomposing the winglet-tip vortex into four small vortices. Due to quite few fluid entrainment effects, this typical four-vortex system that cannot merge and only dissipate in the near wake scarcely contributes to the induced drag. On the other hand, a potential drag reduction method is also indicated that a lower induced drag can be obtained when the merger of wingtip and winglet-tip vortex is controlled and eliminated. This investigation will offer a novel perspective to guide the design of wingtip device and method of crusing resistance reduction for aircrafts.
In this article, a series of simulations of a rotating disk system with air cooling is introduced. These simulations are performed with the realizable k-ε eddy-viscosity model. Computational results illustrate the effect of the cooling air and disk rotation on the temperature of the disk surface. The maximum rotating disk speed reaches about 78300 rpm and the range of Reynolds numbers based on rotation speed is from about 0.7 × 106 to 3 × 106. The present work shows that the flow structure in the gap, which is on the opposite side of the cooling air, is rather similar to different cooling air flows. The temperature goes up as the rotating speed increases. The temperature in this gap will first decrease when the cooling air increases under lower mass flow rate. But when the cooling air continues to increase, the temperature will rise up indicating the existence of an optimum value of the cooling flow rate.
Liquid-infused surfaces present a novel, passive method of turbulent drag reduction. Inspired by the Nepenthes Pitcher Plant, liquid-infused surfaces utilize a lubricating fluid trapped within structured roughness to facilitate a slip at the effective surface. The conceptual idea is similar to that of superhydrophobic surfaces, which rely on a lubricating air layer, whereas liquid-infused surfaces use a preferentially wetting liquid lubricant to create localized fluid–fluid interfaces. Maintaining the presence of these slipping interfaces has been shown to be an effective method of passively reducing skin friction drag in turbulent flows. Given that liquid-infused surfaces have only recently been considered for drag reduction applications, there is no available framework to relate surface and lubricant characteristics to any resulting drag reduction. Here we use results from direct numerical simulations of turbulent channel flow over idealized, liquid-infused grooves to demonstrate that the drag reduction achieved using liquid-infused surfaces can be described using the framework established for superhydrophobic surfaces. These insights can be used to explain drag reduction results observed in experimental studies of lubricant-infused surfaces. We also demonstrate how a liquid-infused surface can reduce drag even when the viscosity of the lubricant exceeds that of the external fluid flow, which at first glance can seem counter-intuitive.
Macdunnoughia crassisigna Warren (Lepidoptera: Noctuidae) is a highly destructive herbivore that poses a serious risk to cotton, maize, soybean, and cruciferous vegetables in East Asia. Examining the effects of various biotic and abiotic factors on the flight performance of M. crassisigna is crucial for a better understanding of its trans-regional migration. In this study, the flight activity of M. crassisignai moths of different ages, under different temperatures and relative humidity (RH) levels, was evaluated by tethering individuals to computerized flight mills for a 24-h trial period. The results showed that M. crassisignai had the capacity for sustained flight and the flight ability was strongest in 3-day-old individuals, and then their flight performance decreased significantly in older moths. For both sexes, temperature had a significant effect on their flight performance, and the flight activity was relatively higher at 24–28°C than other temperatures. There was a significant effect of RH on all flight parameters of the tested moths, and the flight activity was relatively higher at RH of 60–75% than other RH levels. For 3-day-old moths under the optimum conditions (24°C and 75% RH) throughout the 24 h scotophase, their mean flight distance reached 66 km, and the mean flight duration reached 13.5 h, suggesting M. crassisigna possess strong potential to undertake long-distance migration. These findings will be helpful for developing sound forecasting systems of this pest species.
In this study, a series of numerical experiments are performed on supersonic/hypersonic flows over an adiabatic flat plate with transitionally and fully rough surfaces. The Mach numbers simulated are 4, 5, 6, and 7; the flight heights considered are 20, 24, 28, 32, and 36 km. First, a modified roughness correction is proposed and validated with the measured data for low-speed flat-plate cases. It is verified that for the equivalent sand grain heights in the intermediate and fully rough regimes, there is a good agreement with the semi-empirical formula available in the open literature. Then, this roughness correction is applied to high-speed flow regime to investigate the effects of flight heights and Mach numbers on drag for rough-wall flat-plate cases. It is found that within the roughness measured in real flight, the roughness height change has little effect on drag compared to the variations of both flight heights and Mach numbers. The drag coefficient derivation between rough-wall and smooth-wall conditions, achieves the maximum value of 0.79% for the 60 cases selected.
In this paper, we perform an absolute equation of state (EOS) measurement on the principal Hugoniot of aluminum using a near-symmetric impact method. The flyer plates are accelerated to high velocities using the laser-ramp-driven method. An aluminum flyer plate of ~25 µm is accelerated to the velocity range from 4 to 12 km/s. Then the aluminum flyer plate propagates across a vacuum gap and impacts with an aluminum step target. A line-imaging optical recording velocity interferometer for any reflector (ORVIS) is used to measure the aluminum flyer plate and the shock velocity simultaneously. Aluminum EOS data were measured with pressures range from 50 to 200 GPa. This absolute EOS measurement method may be used for studying a variety of materials.