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Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
This paper mainly focuses on the cooperative control of formation configuration for multiple flight vehicles in the three-dimensional space. Considering the external disturbance of the system, the adaptive non-singular terminal sliding mode control law (NTSMC) is designed based on the virtual leader-follower method, which aims to ensure that each flight vehicle reaches the expected terminal position in a limited time and meet the configuration constraints. Further considering the first-order dynamic characteristic of the autopilot, a novel second-order sliding mode control (SOSMC) law is deduced with using the estimated information of sliding mode disturbance observer. The proposed control method ensures that all flight vehicles form the required space formation configuration simultaneously at a pre-designed time, and the chattering phenomenon of the sliding mode surface and acceleration response that nears the equilibrium point is effectively weaken. The stability of the proposed control law is verified by theoretical analysis and lots of mathematical simulations. The results show that the control algorithm in this paper can be used to guidance the formation controller design of multiple flight vehicles in the mid-guidance phase to some extent, and thus the cooperative flight stability of the system can be effectively improved.
Modern electron microscopy permits scientists to study the fine detail of cells and tissues, using both two-dimensional and three-dimensional imaging modalities. However, achieving optimal preservation of ultrastructure for a variety of biological samples remains a challenge. Here, we describe practical methods to preserve the fine structure of mouse skeletal muscle and sciatic nerve and to obtain high-resolution images of mitochondria in cultured cells, flow-sorted T-cells, and mouse urothelium. We also propose an effective and economical workflow for three-dimensional electron microscopy in the context of a microscopy core facility.
The current study investigated associations between variation in the bovine perilipin-2 gene (PLIN2) and milk traits (milk fat content, milk protein content, milk yield and milk fatty acid (FA) component levels) in 409 New Zealand pasture-grazed Holstein-Friesian × Jersey-cross (HF × J-cross or Kiwicross™) cows. Five nucleotide sequence variants were found in three regions of the gene, including c.17C>T in exon 2, c.53A>G in exon 3, c.595+23G>A and c.595+104_595+108del in intron 5, and c.*302T>C in the 3′-untranslated region. The c.*302T>C substitution produces two nucleotide sequence variants (A5 and B5), and this variation was associated with variation in milk protein content and milkfat composition for C10:0, C11:0, C12:0, C13:0 and C16:0 FA and medium-chain fatty acid (MCFA) and long-chain fatty acid (LCFA) groups. After correcting for the effect of variation in the diacylglycerol acyl-CoA acyltransferase 1 gene (DGAT1) that results in the amino acid substitution p.K232A, variation in the FA binding protein 4 gene (FABP4) and variation in the stearoyl-CoA desaturase (Δ-9-desaturase) gene (SCD) that results in the amino acids substitution p.A293V, significant differences between A5A5 and B5B5 cows were found for C10:0, C11:0, C12:0, C13:0, C16:0, and the MCFA, LCFA, total saturated FA and C10:1 index groups. This suggests that nucleotide sequence variation in PLIN2 may be affecting milk FA component levels.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Considering the decision-making requirements of airport, airlines and passengers, a bilevel programming model which contains two parts was proposed in this paper. One part is to improve the utilization of gates of the airport (upper level), so the objective function of the upper level to the minimum overall variance of slack time between two consecutive air crafts at the same gate. The other part looks at maximize the airline revenue and passengers more conveniently and comfortably (lower level). The lower level has two objective functions — the minimum passenger transfer failure and the minimum passenger average transfer time, respectively. According to the latest data of an airport in Eastern China, the adaptive genetic algorithm is used to solve the above-mentioned bilevel optimisation problems. The numerical experiment shows that the model not only reduces the variance of the relaxation time, but also optimises the flight gate allocation and achieves the initial goal.
Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.
Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.
Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.
These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.
Most previous researches indicated that impaired inhibition to emotional stimuli could be one of the important cognitive characteristics of depression individuals. The antisaccade tasks which composed of prosaccade task (PS) and antisaccade task (AS) were often used to investigate response inhibition.
This study aimed to investigate the volition inhibition toward emotional stimuli in depressed mood undergraduates (DM).
Subjects were grouped as 21 DM and 25 non-depressed undergraduates (ND) on the Beck Depression Inventory and Self-rating Depression Scale. The antisaccade tasks were conducted to examine the inhibition abilities by varying the arousal level of volition (low and high) of the tasks, with happy, neutral and sad facial expressions as stimuli.
The results showed that at the low volition level in the AS condition, the correct saccade latency in the DM were significant slower than the ND; The DM had reliable higher direction error rates in response to emotional facial expressions, especially for sad expressions. However, all of the differences disappeared in the high volition level antisaccade tasks. The amplitude errors data were not influenced by emotional facial expressions, and there were no group differences across tasks.
These results indicated the DM showed slower speed of cognitive processing and impaired inhibition abilities toward emotional faces than the ND, particularly for sad faces, but these abilities will be repaired in the high arousal level of volition, which enlighten us that training the DM's volition level of inhibition could prove to be an effective strategy to alleviate depression.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.
To explore the feature of functional connectivity of default mode network (DMN), central-executive network(CEN), and salience network (SN) in patients with schizophrenia during a resting state by functional magnetic resonance imaging (fMRI).
The SPM8, DPARSFA, conn, REST softwares combined with data-driven region of interest analysis were used to compare the functional connectivity (FC) of the DMN, CEN, and SN in 74 patients with schizophrenia(SZ) and 79 age- and gender-matched normal controls(NC). Medial prefrontal cortex(MPFC)was selected as seed region for identifying DMN and CEN; right anterior insula(rAI) for SN.
Compared with NC, SZ showed increased FC with bilateral dorsolateral prefrontal cortex(DLPFC) and bilateral putamen of the MPFC, and increased FC with left middle frontal cortex and precuneus/ posterior cingulate cortex(Pcu/PCC) of the rAI. SZ also showed enhanced interconnectivity strengths of CEN-DMN, CEN-SN, and DMN-SN(p>0.05). Correlation analyses showed that the increased FC between MPFC and left DLPFC significantly negatively correlated with PANSS-negative symptoms(r=-0.224,p=0.030) and increased FC between rAI and Pcu/PCC significantly correlated with PANSS-positve symptoms (r=0.243,p=0.020).
This study provides evidence for resting state functional abnormalities of DMN, CEN, and SN in schizophrenia patients. These aberrant functional connectivities in some key brain regions of the three network could be responsible for the schizophrenic symptoms.
Planning ability as a critical component of executive function has been used to investigate prefrontal cortex (PFC) function in Schizophrenia patients by several neuroimaging studies. However, the changes of PFC activation after effective antipsychotic treatment are still unclear.
The aim of this study is to explore whether there is any variation in the prefrontal hemodynamic response during Tower of London test after 6 weeks’ antipsychotic treatment in schizophrenia patients, and the relationship between the changes in PFC activation and some demographic factors as well as the severity of the patients’ psychiatric symptoms.
40 patients with first-episode schizophrenia were recruited for the present study. 28-channel NIRS (near infrared spectroscopy) was used to measure changes in hemoglobin concentration in the prefrontal cortical surface area during Tower of London (TOL) test—a classic neuropsychological test for planning abilities. The patients were examined before treatment and after six weeks’ treatment with second-generation antipsychotic medicines.
After the short-term treatment, the patients’ TOL test performance and the activations in PFC during the task period did not differ from baseline (P>0.05), although the psychiatric symptoms of the patients were improved significantly(positive subscale score 18.25±2.86 & 12.75±2.60; general psychopathology 33.67±3.65 & 27.00±3.67; PANSS total score 72.25±7.07 & 55.42±7.53; P<0.001).
It suggests that the impairment of cognitive function and the function of the PFC of schizophrenia patients would not be improved with the improvement of psychiatric symptoms, as further support the hypothesis that PFC damage is a durable impairment for schizophrenia.
The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.
Compared to healthy controls, adults with major depressive disorder (MDD) showed stronger activation in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in resolving emotional conflict. Whether subthreshold depression (StD) at an advanced age is also accompanied by similar changes in brain activation in coping with emotional conflict remained unknown.
By using face-word Stroop task, the current study explored the neural correlates of emotional interference processing in old adults with StD.
Participants were 19 community-dwelling older adults with StD assessed by the Center for Epidemiologic Studies Depression scale (CES-D) scores. We collected magnetic resonance images of their brain compared to images of 18 healthy aged-matched adults. We used SPM to analyze differences in brain activations in emotional interference processing between the two groups.
Results showed that elderly individuals with StD have stronger activation in DLPFC, ACC, default mode network (DMN) and visual extrastriate cortex compared to healthy controls. Furthermore, the brain activations of the DLPFC, DMN and visual extrastriate cortex were significantly associated with participants’ behavioral interference effect in StD.
Stronger brain activation in DLPFC, ACC, DMN and extrastriate cortex in old adults with StD suggests that the working efficiency of their brain is quite low and their cognitive control is impaired to some extent.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The present study identified the neural mechanism of risky decision-making in Internet gaming disorder (IGD) under a probability discounting task.
Independent component analysis was used on the functional magnetic resonance imaging data from 19 IGD subjects (22.2 ± 3.08 years) and 21 healthy controls (HC, 22.8 ± 3.5 years).
For the behavioral results, IGD subjects prefer the risky to the fixed options and showed shorter reaction time compared to HC. For the imaging results, the IGD subjects showed higher task-related activity in default mode network (DMN) and less engagement in the executive control network (ECN) than HC when making the risky decisions. Also, we found the activities of DMN correlate negatively with the reaction time and the ECN correlate positively with the probability discounting rates.
The results suggest that people with IGD show altered modulation in DMN and deficit in executive control function, which might be the reason for why the IGD subjects continue to play online games despite the potential negative consequences.
Silicon carbide (SiC) is ideally suitable as a sensor material in harsh environments. Despite the brittleness in the macroscopic scale, plasticity in SiC is observed at small component length-scales. Previous nanoindentation based study combining experiment and numerical approaches of single-crystal 6H-SiC has shown that slip activation is rather complex, and that non-basal slip could potentially dominate the plastic deformation behaviour. In this study, we investigated the local deformation response evolution of shear strain directly under and in the vicinity of the indenter tip. The results show the pyramidal slip families contribute significantly to the deformation process.
The aim of this research was to identify variation in the yak lipin-1 gene (LPIN1) and determine whether this variation affects milk traits. PCR-single stranded conformational polymorphism (PCR-SSCP) analysis was used to detect variation in the 5′ untranslated region of LPIN1 in 500 yaks from four populations: Tianzhu white yaks, Qinghai yaks, wild × domestic-cross yaks and Gannan yaks. Four unique PCR-SSCP patterns, representing four different DNA sequence variants (named A, B, C and D), were observed. These contained six single nucleotide polymorphisms. Female Gannan yaks with BC genotype produced milk with a higher fat content (P < 0.001) and total milk solids (P < 0.001), than those with the AA, AB and BB genotypes. These results would suggest that LPIN1 is having an effect on yak milk fat synthesis.
We show interlayer stacking shifts occur in transition metal dichalcogenides (TMD) bilayers due to the strain introduced during sample heating, and attributed to rippling of one layer relative to the other. The atomic structure of the interlayer stacking is studied using annular dark field scanning transmission electron microscopy with an in situ heating holder. Before heating, bilayers show uniform interlayer stacking of AA′ and AB. When heated, contrast change is seen and associated with interlayer stacking changes at the atomic scale due to ripples. When cooled down to room temperature, these contrast features disappear, confirming it is a reversible process that is not related to defects or vacancies. Because the bottom layer is attached to the in situ heating chip made from Si3N4 and the top layer is in contact with the underlying TMD layer with weak van der Waals interaction, the two layers experience different forces during thermal expansion.
In order to map quantitative trait loci (QTLs) for allometries of body compositions and metabolic traits in chicken, we phenotypically characterize the allometric growths of multiple body components and metabolic traits relative to BWs using joint allometric scaling models and then establish random regression models (RRMs) to fit genetic effects of markers and minor polygenes derived from the pedigree on the allometric scalings. Prior to statistically inferring the QTLs for the allometric scalings by solving the RRMs, the LASSO technique is adopted to rapidly shrink most of marker genetic effects to zero. Computer simulation analysis confirms the reliability and adaptability of the so-called LASSO-RRM mapping method. In the F2 population constructed by multiple families, we formulate two joint allometric scaling models of body compositions and metabolic traits, in which six of nine body compositions are tested as significant, while six of eight metabolic traits are as significant. For body compositions, a total of 14 QTLs, of which 9 dominant, were detected to be associated with the allometric scalings of drumstick, fat, heart, shank, liver and spleen to BWs; while for metabolic traits, a total of 19 QTLs also including 9 dominant be responsible for the allometries of T4, IGFI, IGFII, GLC, INS, IGR to BWs. The detectable QTLs or highly linked markers can be used to regulate relative growths of the body components and metabolic traits to BWs in marker-assisted breeding of chickens.