To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
Witherite originates from the biochemical sedimentation of barium in sea water. Due to the complexity of the metallogenic environment, witherite appears in many morphologies. However, the relationship between its diverse morphologies and its mineralisation environment is not well understood. In this paper, Ca2+, a common substitute for Ba2+, and mixed protein (egg white) were used to simulate the inorganic and organic environments of witherite mineralisation, respectively. Comparison of samples prepared under different conditions showed that Ca2+ and egg white have relatively independent regulatory effects on the mineralisation of witherite particles. Egg white primarily limits the growth of the nanocrystals, while Ca2+ directs their non-isodiametric growth. Results shows that Ca2+ is distributed along a gradient in nanocrystalline witherite particles, with the Ca2+ content being proportional to the diameter of the nanocrystals. The results of this study shed light on the different roles of organic matter and inorganic ions in the formation of witherite and offer insight into the genesis of its various morphologies.
A new developed spatially targeted mollusciciding technology for snail control was utilised in a research site. This study aims to analyse whether this technology can achieve rational effectiveness compared with the routine method. Snail density was monitored every spring and autumn from 2010 to 2017 at the research site and routine mollusciciding for snail control was then performed. After snail density monitoring in spring 2018, spatially targeted mollusciciding technology was adopted. Log-linear regression and nonlinear regression models were used for snail density prediction in autumn 2018 and the predicted value was compared with the actual snail density in autumn 2018 to verify the effectiveness of the spatially targeted mollusciciding. Monitoring results showed that overall snail density in the research site decreased from 2010 to 2018. The monitored snail density in autumn 2018 was 0.014/0.1 m2. Predicted by the log-linear regression model, the snail density in autumn 2018 would be 0.028 (95% CI 0.11–0.072)/0.1 m2. Predicted by the nonlinear regression model, the snail density growth in autumn 2018 in contrast to spring 2018 would be 79.79% (95% CI 54.81%–104.77%) and the actual value was 55.56%. Therefore, the effectiveness of the first application of spatially targeted mollusciciding was acceptable. However, the validation of its sustainable effectiveness still needs a replicated study comparing areas where targeted and untargeted methods are applied simultaneously and both snail abundance and human infection are monitored.
The sedimentologic fingerprinting in detrital deposit is vital to reconstruct sedimentary environments and discriminate sources. In this study, grain size and microtextural characteristics of quartz from the late Pleistocene hard clay in the Yangtze River delta (YRD) were analyzed by using a laser particle size analyzer and a scanning electron microscope. Subaqueous quartz from the Yangtze River and Yellow River sediments and eolian quartz from the Chinese Loess Plateau loess were also analyzed by scanning electron microscopy to obtain the microtextural characteristics. Quartz grains of the hard clay were characterized by poor sorting, fine skew, bimodal grain-size distributions, and numerous eolian microtextures. The comparison of the quartz grain characteristics of the hard clay with these in eolian loess indicated that the hard clay belonged to an eolian deposition. Moreover, the fine quartz grains of the hard clay were dominated by eolian microtextural characteristics, representing long-distance transportation. The coarse quartz grains of the hard clay exhibited more subaqueous microtextural characteristics, which indicated that the coarse fraction of the hard clay was derived from the proximal source regions in the YRD. The determination of buried eolian deposition with multiple sources in the YRD implies a southward westerly jet stream, strengthened eolian dust transportation, and extensive aridification in the YRD due to the increased Northern Hemisphere ice sheets in Marine Oxygen Isotope Stage 2.
Bile acids (BA) have emerged as signalling molecules regulating intestinal physiology. The importance of intestinal microbiota in production of secondary BA, for example, lithocholic acid (LCA) which impairs enterocyte proliferation and permeability, triggered us to determine the effects of oral probiotics on intestinal BA metabolism. Piglets were weaned at 28 d of age and allocated into control (CON, n 14) or probiotic (PRO, n 14) group fed 50 mg of Lactobacillus plantarum daily, and gut microbiota and BA profile were determined. To test the potential interaction of LCA with bacteria endotoxins in inducing damage of enterocytes, IPEC-J2 cells were treated with LCA, lipopolysaccharide (LPS) and LCA + LPS and expressions of genes related to inflammation, antioxidant capacity and nutrient transport were determined. Compared with the CON group, the PRO group showed lower total LCA level in the ileum and higher relative abundance of the Lactobacillus genus in faeces. In contrast, the relative abundances of Bacteroides, Clostridium_sensu_stricto_1, Parabacteroides and Ruminococcus_1, important bacteria genera in BA biotransformation, were all lower in the PRO than in the CON group. Moreover, PRO piglets had lower postprandial glucagon-like peptide-1 level, while higher glucose level than CON piglets. Co-administration of LPS and LCA led to down-regulated expression of glucose and peptide transporter genes in IPEC-J2 cells. Altogether, oral L. plantarum altered BA profile probably by modulating relative abundances of gut microbial genera that play key roles in BA metabolism and might consequently impact glucose homoeostasis. The detrimental effect of LCA on nutrient transport in enterocytes might be aggravated under LPS challenge.
Multiple neurotrophic factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2, nerve growth factor (NGF) and insulin-like growth factor(IGF)-1, have been shown to play important roles in the pathophysiology of mood disorders. However, insufficient clinical data supporting the importance of these neurotrophic factors in mood disorders, especially manic episode, have made inconclusive to make a connection between these factors and the disorder.
This study intended to investigate possible peripheral biomarkers in serum of manic episode of bipolar disorder.
We aimed to investigate whether or not serum levels of VEGF, FGF-2, NGF and IGF-1 varied in manic state.
Serum levels of VEGF, FGF-2, NGF and IGF-1 were examined in 70 drug-naïve patients with manic episode of bipolar disorder (BM) as well as 50 healthy controls, using an ELISA method.
The mean serum levels of VEGF, FGF-2, NGF and IGF-1 were 168.13±225.61pg/ml, 279.09±378.62pg/ml, 61.38±171.67pg/ml and 162.01±72.00ng/ml in BM patients, and 140.80±143.71pg/ml, 275.46±235.29pg/ml, 36.34±15.14pg/ml and 138.90±80.11ng/ml in healthy controls, respectively. Serum levels of FGF-2, NGF and IGF-1 in patients were significantly higher than those in healthy controls (Z=−2.896, P=0.004; Z=− 2.050, P=0.040; Z=−2.188, P=0.029; respectively), although there was no statistical difference in the serum levels of VEGF between two groups (Z=-0.468, P=0.639). Moreover, serum levels of NGF in patients correlated with the duration of disorder (rs=−0.241, P=0.044).
The increase in serum levels of FGF-2, NGF and IGF-1 in manic state may reflect a neuroprotective role for these factors, and these factors may be considered biological markers for manic episode.
Bioinformatic investigations indicate that has-mir-206 (microRNA-206, miRNA-206) could regulate BDNF protein synthesis by interfering with BDNF mRNA translation, which is disrupted in bipolar disorder (BPD).
This study is to investigate whether miRNA-206 gene variants were associated with BPD susceptibility in a Han Chinese population.
342 patients who met DSM-IV criteria for bipolar disorder type I (BPD-I) or type II (BPD-II) and 386 matched health controls were enrolled into this study. the miRNA-206 gene and +/-500bp were selected for gene sequencing. for the case-control genetic comparisons, differences in the genotype and allele distributions between patients and controls were examined using Pearson's χ2 test.
Gene sequencing showed that there are two polymorphisms rs16882131(C/T) and rs62408583 (A/C) located at the upstream of miRNA-206 gene, which are complete linkage disequilibrium. the association analysis showed that there was no significant difference for genotype frequencies (χ2 = 2.075, df = 2, P = 0.354) or for allele frequencies (χ2 = 0.041, df = 1, P = 0.839) between BPD patients and controls. Similarly, no significant difference was found between BPD-I patients and controls (genotype χ2 = 1.411, df = 2, P = 0.494; allele χ2 = 0.380, df = 1, P = 0.538). However, there was significant difference between BPD-II patients and controls (genotype χ2 = 7.933, df = 2, P = 0.019; allele χ2 = 5.403, df = 1, P = 0.020).
Our findings do not support that BPD susceptibility was associated with miRNA-206 gene polymorphisms in the studied Han Chinese population. the association between miRNA-206 gene polymorphisms and bipolar disorder type II is needed to be carefully interpreted. Further studies are necessary to elucidate the involvement miRNA-206 in the pathophysiology of BPD.
Major depressive disorder (MDD) is a prevalent mental disorder characterized by impairments in affect, behaviour and cognition. Previous studies have indicated that the anterior cingulate cortex (ACC) may play an essential role in the pathophysiology of depression. In this study, we systematically identified changes in functional connectivity (FC) for ACC subdivisions that manifest in MDD and further investigated the relationship between these changes and the clinical symptoms of depression.
Sub-regional ACC FC was estimated in 41 first-episode medication-naïve MDD patients compared to 43 healthy controls. The relationships between depressive symptom severity and aberrant FC of ACC subdivisions were investigated. In addition, we conducted a meta-analysis to generate the distributions of MDD-related abnormal regions from previously reported results and compared them to FC deficits revealed in this study.
In MDD patients, the subgenual and perigenual ACC demonstrated decreased FC with the posterior regions of the default network (DN), including the posterior inferior parietal lobule and posterior cingulate cortex. FC of these regions was negatively associated with the Automatic Thoughts Questionnaire scores and largely overlapped with previously reported abnormal regions. In addition, reduced FC between the caudal ACC and precuneus was negatively correlated with the Hamilton Anxiety Scale scores. We also found increased FC between the rostral ACC and dorsal medial prefrontal cortex.
Our findings confirmed that functional interaction changes in different ACC sub-regions are specific and associated with distinct symptoms of depression. Our findings provide new insights into the role of ACC sub-regions and DN in the pathophysiology of MDD.
The study investigated antioxidant effects of Se on resilience to diquat-induced oxidative stress in nursery pigs. Thirty-five weaned pigs were individually housed and randomly assigned to one of the five treatments. Pigs were (1) fed a basal diet and intraperitoneally injected with sterile saline (negative control), (2) fed the basal diet and injected with diquat solution (positive control, PC), or fed the basal diet supplemented with 0·3 mg Se/kg as (3) sodium selenite (SS), (4) soyabean protein-chelated Se (SC) or (5) selenised yeast (SY) and intraperitoneally injected with diquat. Pigs were fed the experimental diets for 17 d and injected with diquat at 10 mg/kg body weight or saline on the 11th day of the study (day 0 post-injection (PI)). Diquat exposure induced acute stress and innate immune activation (P < 0·05) at 6 h PI and compromised (P < 0·05) plasma glutathione peroxidase activity on day 2 PI, which was accompanied by an increase in plasma malondialdehyde at 6 h and day 2 PI (P < 0·10). Organic Se, particularly SY, enhanced (P < 0·05) endogenous antioxidant activity in various aspects compared with the PC group. The growth rate and feed intake from day 0 to day 7 PI were significantly lower in the PC, SS and SC groups than the NC group (P < 0·05). Untargeted metabolomics analysis revealed that twenty-two hepatic metabolites (false discovery rate < 0·15) associated with lipid and cellular antioxidant metabolism were altered by diquat. SY restored hepatic metabolic profiles in some but not all samples.
A dual-arm space robot has large potentials in on-orbit servicing. However, there exist multiple dynamic coupling effects between the two arms, each arm, and the base, bringing great challenges to the trajectory planning and dynamic control of the dual-arm space robotic system. In this paper, we propose a dynamic coupling modeling and analysis method for a dual-arm space robot. Firstly, according to the conservation principle of the linear and angular momentum, the dynamic coupling between the base and each manipulator is deduced. The dynamic coupling factor is then defined to evaluate the dynamic coupling degree. Secondly, the dynamic coupling equations between the two arms, each arm, and the base are deduced, respectively. The dynamic coupling factor is suitable not only for single-arm space robots but also for multi-arm space robot systems. Finally, the multiple coupling effects of the dual-arm space robotic system are analyzed in detail through typical cases. Simulation results verified the proposed method.
Affective temperaments have been considered antecedents of major depressive disorder (MDD). However, little is known about how the covariation between alterations in brain activity and distinct affective temperaments work collaboratively to contribute to MDD. Here, we focus on the insular cortex, a critical hub for the integration of subjective feelings, emotions, and motivations, to examine the neural correlates of affective temperaments and their relationship to depressive symptom dimensions.
Twenty-nine medication-free patients with MDD and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Patients also received assessments of the Hamilton Depression Rating Scale (HDRS). We used multivariate analyses of partial least squares regression and partial correlation analyses to explore the associations among the insular activity, affective temperaments, and depressive symptom dimensions.
A profile (linear combination) of increased fractional amplitude of low-frequency fluctuations (fALFF) of the anterior insular subregions (left dorsal agranular–dysgranular insula and right ventral agranuar insula) was positively associated with an affective-temperament (depressive, irritable, anxious, and less hyperthymic) profile. The covariation between the insula-fALFF profile and the affective-temperament profile was significantly correlated with the sleep disturbance dimension (especially the middle and late insomnia scores) in the medication-free MDD patients.
The resting-state spontaneous activity of the anterior insula and affective temperaments collaboratively contribute to sleep disturbances in medication-free MDD patients. The approach used in this study provides a practical way to explore the relationship of multivariate measures in investigating the etiology of mental disorders.
We present details of on-wafer-level 16-term error model calibration kits used for the characterization of W-band circuits based on a grounded coplanar waveguide (GCPW). These circuits were fabricated on a thin gallium arsenide (GaAs) substrate, and via holes, were utilized to ensure single mode propagation (i.e., eliminating the parallel-plate mode or surface mode). To ensure the accuracy of the definition for the calibration kits, multi-line thru-reflect-line (MTRL) assistant standards were also fabricated on the same wafer and measured. The same wafer also contained passive and active devices, which were measured subject to both 16-term and conventional line-reflect-reflect-match calibrations. Measurement results show that 16-term calibration kits are capable of determining the cross-talk more accurately. Other typical calibration techniques were also implemented using the standards on the GCPW calibration kits, and were compared with the MTRL calibration using a passive device under test. This revealed that the proposed GCPW GaAs calibration substrate could be a feasible alternative to conventional CPW impedance standard substrates, for on-wafer measurements at W-band and above.
When the average intermolecular distance is comparable to the size of gas molecules, the Boltzmann equation, based on the dilute gas assumption, becomes invalid. The Enskog equation was developed to account for this finite size effect that makes the collision non-local and increases the collision frequency. However, it is time-consuming to solve the Enskog equation due to its complicated structure of collision operator and high dimensionality. In this work, on the basis of the Shakhov model, a gas kinetic model is proposed to simplify the Enskog equation for non-ideal monatomic dense gases. The accuracy of the proposed Shakhov–Enskog model is assessed by comparing its solutions of the normal shock wave structures with the results of the Enskog equation obtained by the fast spectral method. It is shown that the Shakhov–Enskog model is able to describe non-equilibrium flow of dense gases, when the maximum local mean free path of gas molecules is still greater than the size of a molecular diameter. The accuracy and efficiency of the present model enable simulations of non-equilibrium flow of dense gases for practical applications.
Magnesium alloys usually lack “operative deformation slip mechanisms” because of their hexagonal close-packed structure. Therefore, the mechanical behavior of magnesium alloys at different temperatures is dictated by other deformation mechanisms such as twinning, detwinning, secondary twinning, or dynamic recrystallization (DRX). Twinning and DRX can affect the development of grain size and orientation distribution, as well as the deformation behavior of magnesium alloys. The current understanding of the mechanisms and mechanics of these different deformation modes and their implementation in crystal plasticity-based modeling are highlighted in this article. Future directions in the development of constitutive models are also discussed.
Deep learning methods have been applied to randomly generate images, such as in fashion, furniture design. To date, consideration of human aspects which play a vital role in a design process has not been given significant attention in deep learning approaches. In this paper, results are reported from a human- in-the-loop design method where brain EEG signals are used to capture preferable design features. In the framework developed, an encoder extracting EEG features from raw signals recorded from subjects when viewing images from ImageNet are learned. Secondly, a GAN model is trained conditioned on the encoded EEG features to generate design images. Thirdly, the trained model is used to generate design images from a person's EEG measured brain activity in the cognitive process of thinking about a design. To verify the proposed method, a case study is presented following the proposed approach. The results indicate that the method can generate preferred designs styles guided by the preference related brain signals. In addition, this method could also help improve communication between designers and clients where clients might not be able to express design requests clearly.
Statistical models are commonly employed in the estimation of influenza-associated excess mortality that, due to various reasons, is often underestimated by laboratory-confirmed influenza deaths reported by healthcare facilities. However, methodology for timely and reliable estimation of that impact remains limited because of the delay in mortality data reporting. We explored real-time estimation of influenza-associated excess mortality by types/subtypes in each year between 2012 and 2018 in Hong Kong using linear regression models fitted to historical mortality and influenza surveillance data. We could predict that during the winter of 2017/2018, there were ~634 (95% confidence interval (CI): (190, 1033)) influenza-associated excess all-cause deaths in Hong Kong in population ⩾18 years, compared to 259 reported laboratory-confirmed deaths. We estimated that influenza was associated with substantial excess deaths in older adults, suggesting the implementation of control measures, such as administration of antivirals and vaccination, in that age group. The approach that we developed appears to provide robust real-time estimates of the impact of influenza circulation and complement surveillance data on laboratory-confirmed deaths. These results improve our understanding of the impact of influenza epidemics and provide a practical approach for a timely estimation of the mortality burden of influenza circulation during an ongoing epidemic.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.