Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study.

Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion magnetic resonance imaging [MRI]). A better understanding of pleiotropy across modalities could inform us on the integration of brain function, micro- and macrostructure. Here we show extensive genetic overlap across neuroimaging modalities at a locus and gene level in the UK Biobank (N = 34,029) and ABCD Study (N = 8607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI in a genome-wide association study (GWAS) with the Multivariate Omnibus Statistical Test (MOSTest), we boost the discovery of loci and genes beyond previously identified effects for each modality individually. Cross-modality genes are involved in fundamental biological processes and predominantly expressed during prenatal brain development. We additionally boost prediction of psychiatric disorders by conditioning independent GWAS on our multimodal multivariate GWAS. These findings shed light on the shared genetic mechanisms underlying variation in brain morphology, functional connectivity, and tissue composition.

Effects of parecoxib on postoperative cognitive dysfunction and serum levels of NSE and S100ß in elderly patients undergoing surgery.

OBJECTIVE: To investigate the effects of parecoxib on postoperative cognitive dysfunction, and serum levels of neuron-specific enolase (NSE) and S100ß protein (S100ß) in elderly patients undergoing surgery. PATIENTS AND METHODS: The retrospective cohort study method was used to collect the clinical data of 94 elderly patients who underwent elective orthopedic and general anesthesia surgery in our hospital from September 2020 to February 2022. 94 patients were divided into the control group (47 cases) and the study group (47 cases), according to different intervention methods. In the study group, 40 mg of parecoxib was injected intravenously into patients 30 min before the induction of anesthesia, and the patients in the control group were given the same dose of normal saline intravenously before the operation. The basic clinical data of the patients were collected. The levels of the indexes before operation and 6 hours after operation were compared between the two groups, including the Montreal Cognitive Scale (MoCA) score, inflammatory factor indicators [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), monocyte chemokine-1 (MCP-1), and inducible nitric oxide synthase (iNOS)], serum cortisol (CORT), beta-amyloid (ß-AP), adiponectin (ADP), NSE, and S100ß. RESULTS: No significant differences in the preoperative MoCA score, TNF-α, IL-6, CRP, IL-10, IL-1ß, MCP-1, iNOS, CORT, ß-AP, ADP, NSE, and S100ß levels were observed between the two groups (p>0.05). The postoperative MoCA score in the study group was significantly higher than that in the control group (p<0.05). The postoperative levels of TNF-α, IL-6, CRP and IL-1ß in the study group were significantly lower than those in the control group (p<0.05), and the postoperative levels of IL-10, MCP-1 and iNOS in the study group were significantly higher than those in the control group (p<0.05). CONCLUSIONS: Parecoxib can notably inhibit the levels of postoperative inflammatory cytokines, improve neurological dysfunction, and reduce the occurrence of postoperative cognitive dysfunction in patients. The contents of serum NSE and S100ß have potential value in the diagnosis of postoperative cognitive dysfunction in elderly patients.

Distinct Regionalization Patterns of Cortical Morphology are Associated with Cognitive Performance Across Different Domains.

Cognitive performance in children is predictive of academic and social outcomes; therefore, understanding neurobiological mechanisms underlying individual differences in cognition during development may be important for improving quality of life. The belief that a single, psychological construct underlies many cognitive processes is pervasive throughout society. However, it is unclear if there is a consistent neural substrate underlying many cognitive processes. Here, we show that a distributed configuration of cortical surface area and apparent thickness, when controlling for global imaging measures, is differentially associated with cognitive performance on different types of tasks in a large sample (N = 10 145) of 9-11-year-old children from the Adolescent Brain and Cognitive DevelopmentSM (ABCD) study. The minimal overlap in these regionalization patterns of association has implications for competing theories about developing intellectual functions. Surprisingly, not controlling for sociodemographic factors increased the similarity between these regionalization patterns. This highlights the importance of understanding the shared variance between sociodemographic factors, cognition and brain structure, particularly with a population-based sample such as ABCD.

The Impact of the Shallow-Trench Isolation Effect on Flicker Noise of Source Follower MOSFETs in a CMOS Image Sensor.

The flicker noise of source follower transistors is the dominant noise source in image sensors. This paper reports a systematic study of the shallow trench isolation effect in transistors with different sizes under high temperature conditions that correspond to the quantity of empty defect sites. The effects of shallow trench isolation sidewall defects on flicker noise characteristics are investigated. In addition, the low-frequency noise and subthreshold swing degrade simultaneously in accordance to the device gate width scaling. Both serious subthreshold leakage and considerable noise can be attributed to the high trap density near the STI edge. Consequently, we propose a coincidental relationship between the noise level and the subthreshold characteristic; its trend is identical to the experiments and simulation results.

Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Direct observation of the Dirac nodes lifting in semimetallic perovskite SrIrO3 thin films.

Perovskite SrIrO3 has long been proposed as an exotic semimetal induced by the interplay between the spin-orbit coupling and electron correlations. However, its low-lying electronic structure is still lacking. We synthesize high-quality perovskite SrIrO3 (100) films by means of oxide molecular beam epitaxy, and then systemically investigate their low energy electronic structure using in-situ angle-resolved photoemission spectroscopy. We find that the hole-like bands around R and the electron-like bands around U(T) intersect the Fermi level simultaneously, providing the direct evidence of the semimetallic ground state in this compound. Comparing with the density functional theory, we discover that the bandwidth of states near Fermi level is extremely small, and there exists a pronounced mixing between the Jeff = 1/2 and Jeff = 3/2 states. Moreover, our data reveal that the predicted Dirac degeneracy protected by the mirror-symmetry, which was theoretically suggested to be the key to realize the non-trivial topological properties, is actually lifted in perovskite SrIrO3 thin films. Our findings pose strong constraints on the current theoretical models for the 5d iridates.

Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species.

Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial-mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally, in silico and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.

The main effects, epistatic effects and environmental interactions of QTLs on the cooking and eating quality of rice in a doubled-haploid line population.

Amylose content (AC), gel consistency (GC) and gelatinazation temperature (GT) are three important traits that influence the cooking and eating quality of rice. The objective of this study was to characterize the genetic components, including main-effect quantitative trait loci (QTLs), epistatic QTLs and QTL-by-environment interactions (QEs), that are involved in the control of these three traits. A population of doubled haploid (DH) lines derived from a cross between two indica varieties Zhenshan 97 and H94 was used, and data were collected from a field experiment conducted in two different environments. A genetic linkage map consisting of 218 simple sequence repeat (SSR) loci was constructed, and QTL analysis performed using QTLMAPPER 1.6: resolved the genetic components into main-effect QTLs, epistatic QTLs and QEs. The analysis detected a total of 12 main-effect QTLs for the three traits, with a QTL corresponding to the Wx locus showing a major effect on AC and GC, and a QTL corresponding to the Alk locus having a major effect on GT. Ten digenic interactions involving 19 loci were detected for the three traits, and six main-effect QTLs and two pairs of epistatic QTLs were involved in QEs. While the main-effect QTLs, especially the ones corresponding to known major loci, apparently played predominant roles in the genetic basis of the traits, under certain conditions epistatic effects and QEs also played important roles in controlling the traits. The implications of the findings for rice quality improvement are discussed.

A statistical approach to estimate O3 uptake of ponderosa pine in a mediterranean climate.

In highly polluted sites, stomatal behavior is sluggish with respect to light, vapor pressure deficit, and internal CO2 concentration (Ci) and poorly described by existing models. Statistical models were developed to estimate stomatal conductance (gs) of 40-year-old ponderosa pine at three sites differing in pollutant exposure for the purpose of calculating O3 uptake. Gs was estimated using julian day, hour of day, pre-dawn xylem potential and photosynthetic photon flux density (PPFD). The median difference between estimated and observed field gs did not exceed 10 mmol H2O m(-2) s(-1), and estimated gs within 95% confidence intervals. 03 uptake was calculated from hourly estimated gs, hourly O3 concentration, and a constant to correct for the difference in diffusivity between water vapor and 03. The simulation model TREGRO was also used to calculate the cumulative 03 uptake at all three sites. 03 uptake estimated by the statistical model was higher than that simulated by TREGRO because gas exchange rates were proportionally higher. O3 exposure and uptake were significantly correlated (r2>0.92), because O3 exposure and gs were highly correlated in both statistical and simulation models.

Cloning and characterization of hMAP126, a new member of mitotic spindle-associated proteins.

One novel gene product, hMAP126, was demonstrated to interact with p29 in the yeast two-hybrid assay. The full-length cDNA of hMAP126 has been obtained and encodes a protein of 1120 amino acids. Multiple tissue Northern blot analysis showed that hMAP126 was abundantly expressed in the testis. Polyclonal antiserum against hMAP126 was raised and affinity-purification of anti-hMAP126 antibodies was performed. The subcellular distribution of hMAP126 was localized to the mitotic spindle. Furthermore, hMAP126 was identified to be post-translationally modified and phosphorylated by p34(cdc2) kinase in vitro. Taken together, we have isolated a novel protein, hMAP126, which may be involved in the functional and dynamic regulation of mitotic spindles.

[Identification of synthetic adhesives by simultaneous pyrolysis methylation gas chromatography].

At present, pyrolysis gas chromatography (Py-GC) is an effective analytical method for trace synthetic adhesives. Synthetic adhesives are usually composed of polar components. Thus, the polar pyrolysis products are normally difficult to measure by Py-GC due to their partial or complete adsorption in the pyrolysis zone, injection system or capillary column and the accuracy of results is seriously affected. Simultaneous pyrolysis methylation gas chromatography (Py-Me-GC) is a fast analytical method which was developed in recent years for polar compounds. The five synthetic adhesives have been identified by using Py-Me-GC in our study. Analytical conditions were: filament pyrolysis apparatus, flame ionization detector (FID), gas chromatograph, FFAP capillary column (30 m x 0.25 mm i.d.) and a quaternary ammonium salt as methylating agent. Major peaks of the products of pyrolysis were analysed qualitatively by GC/MS and comparisons were also made between the results by Py-Me-GC and those by Py-GC. The information gained from the components of substances by Py-Me-GC is more than that by Py-GC. The method is suitable for identifying synthetic adhesives of trace evidence in forensic science.

Migration in a socialist transitional economy: heterogeneity, socioeconomic and spatial characteristics of migrants in China and Guangdong province.

The peculiar features of China's socialist transitional economy, including the coexistence of "plan" and "nonplan" mechanisms, the hukou institution, uneven spatial development, and gendered constraints and opportunities, have brought about a high degree of heterogeneity among population movements. Using the 1990 Census data on reasons for migration, and an empirical analysis of both national patterns and migration in Guangdong, the author documents the socioeconomic characteristics and spatial patterns of major types of migration, focusing on migration for employment in industry and business, male migration due to job transfer, and female marriage migration. The author argues that the multitude of migration types, and the contrasts among them, are products of the combination of state-planning and market mechanisms. The findings highlight institutional explanations for migration, and show that the "plan"/"nonplan" dichotomy is more meaningful that the economic-social dichotomy for understanding population movements in China.

Age estimation using a modified HPLC determination of ratio of aspartic acid in dentin.

Diastereomeric dipeptides were derived from the amino acid enantiomers in dentin by O-phthalaldehyde-N-acetyl-L-cysteine. The products were separated using high performance liquid chromatography (HPLC) and detected by fluorescence detector. A short analysis time (total analysis time was 15 min, including retention time, sample derivatization time and column regeneration time) was used. The sensitivity of detection was 1 pmol and high resolution (Rs = 1.5) was reached. We determined the D/L ratio of aspartic acid in dentin of 28 first premolars. The correlation value between the D/L ratio of aspartic acid and actual age was 0.9887; errors of +/- 1 year accounted for 46.4%, and no error exceeded 5 years.

Isolated myocardial abscess causing coronary artery rupture and fatal hemopericardium.

We report a rare case of cardiac tamponade caused by hemopericardium secondary to erosion and rupture of a coronary artery by an adjacent solitary myocardial abscess. The resulting tamponade led to the sudden death of this 46-year-old man. Antemortem blood culture and the postmortem microscopic examination of the myocardial abscess revealed the causative agent to be Staphylococcus aureus. Hemopericardium due to ventricular wall rupture secondary to a myocardial abscess has been infrequently reported, but, to our knowledge, only one other report of hemopericardium due to coronary artery rupture related to myocardial abscess has been published.

Mixed pulmonary blastoma and carcinosarcoma.

Pulmonary blastomas and carcinosarcomas are uncommon tumours, accounting for less than 1% of all lung neoplasms. Three previously described mixed epithelial and mesenchymal tumours having both adult and embryonal elements were termed 'transitional'. We report a similar case and evaluate the application of the term 'transitional tumour'.

The temporal and spatial dynamics of income and population growth in Ohio, 1950-1990.

"This paper focuses on spatial variation of growth within a state. Using Ohio as a case study, two hypotheses are extracted from the literature. First, the theories of polarization and polarization reversal suggest that in the old industrial core the leading sector role of manufacturing has diminished in old manufacturing poles, and that income growth trends differ substantially between these old poles and new centres of development. Second, the theories of suburbanization and migration reversals suggest that population growth is contingent upon level of urbanization, and that the relationship has changed drastically between the pre-1970s, 1970s, and post-1970s periods." (SUMMARY IN FRE AND GER)

Polyamines mediate androgenic stimulation of calcium fluxes and membrane transport in rat heart myocytes.

The androgenic steroid hormone testosterone induced an early (less than 30-60 seconds) stimulation of endocytosis, hexose transport, and amino acid transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, 2-deoxyglucose, and alpha-aminoisobutyrate, respectively, in rat ventricle cubes and acutely isolated ventricular myocytes. This stimulation was time- and concentration-dependent and was maximal at 10(-9) to 10(-8) M testosterone, consistent with androgen-receptor mediation. EGTA (2.5 mM), La3+ (1 mM), and verapamil (100 microM) ablated the hormonal response. The calcium ionophore A23187 (10 microM) induced an acute stimulation of endocytosis, amino acid transport, and hexose transport which was not further increased by testosterone (10(-8) M), suggesting a common effector pathway. Testosterone (10(-8) M) also evoked a rapid (less than 30 seconds) stimulation of 45Ca influx and efflux. Testosterone (10(-8) M) induced a rapid (less than 5 seconds) transient increase in ornithine decarboxylase (ODC) activity peaking (twofold to threefold) at 60 seconds, and an early (15 seconds) transient accumulation of polyamines peaking at 60 seconds in isolated myocytes. The specific, irreversible ODC inhibitor alpha-difluoromethylornithine (DFMO, 5-10 mM) blocked the testosterone-evoked increase in ODC activity and polyamine levels and the stimulation of Ca2+ fluxes, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5-1 mM), the ODC product, reversed DFMO inhibition and restored the increase in polyamines, 45Ca fluxes, and Ca2+-dependent membrane transport processes. These results demonstrate that rapid, transient ODC-regulated polyamine synthesis is essential for androgenic stimulation of Ca2+ fluxes and membrane transport processes in ventricular myocytes. These findings support a model for signal transduction in which newly synthesized polyamines serve as intracellular messengers to regulate transmembrane Ca2+ movements, Ca2+-dependent membrane transport functions, and other Ca2+- and polyamine-sensitive processes in cardiac myocytes.

A case of simultaneous bilateral herpetic epithelial keratitis.

The patient, a 56-year-old man, presented with dendritic keratitis in the right eye and geographic keratitis in the left, with decreased corneal sensation in both eyes. The virus isolated from both eyes was identified as herpes simplex virus (HSV-1) by the indirect immunofluorescent method using anti-HSV-1 monoclonal antibody. Antibody tests of paired sera suggested that the epithelial lesions were not primary but recurrent. No significant difference was observed in DNA cleavage patterns between the virus isolates obtained bilaterally.

The role of polyamines in beta-adrenergic stimulation of calcium influx and membrane transport in rat heart.

The beta-adrenergic agonist 1-isoproterenol induced an early (less than 1 min) stimulation of endocytosis, amino acid transport and hexose transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, alpha-aminoisobutyrate and 2-deoxyglucose, respectively, in rat ventricle cubes. This stimulation was time- and concentration-dependent and was maximum at 10(-8) M isoproterenol. The beta-adrenergic antagonist propranolol blocked isoproterenol stimulation of membrane transport, thereby confirming beta-adrenoceptor mediation; 2.5 mM EGTA, 1 mM LaCl2 and 100 microM verapamil blocked the hormonal response without affecting basal transport. The calcium ionophore A23187 caused an acute stimulation of endocytosis, hexose and amino acid transport. Isoproterenol rapidly (less than 30 s) stimulated 45Ca2+ influx. These data suggest that stimulus-response (stimulus-"transport") coupling is mediated by a rise in cytosolic Ca2+ concentration. A rapid (less than 30 to 60 s) increase in ornithine decarboxylase (ODC) activity, followed by an early (less than 1 to 2 min), sustained increase in putrescine, spermidine and spermine concentrations was evoked by 10(-7) M isoproterenol. The ODC inhibitor alpha-difluoromethylornithine (DFMO, 5 mM) suppressed the isoproterenol-induced increase in ODC and polyamine levels and the stimulation of 45Ca influx, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5 mM) negated DFMO inhibition and restored the increase in polyamines, 45Ca influx, endocytosis, and transport of hexose and amino acid. These data suggest that polyamine synthesis is involved in isoproterenol stimulation of Ca2+ influx and membrane transport functions in ventricular myocardium. These findings are consistent with a model for signal transduction and stimulus-response coupling in which polyamines function as intracellular messengers to generate cytosolic Ca2+ signals by stimulating Ca2+ influx.

Coupled NaCl transport: cotransport or parallel ion exchange?

In recent years it has become apparent that at least part of the transcellular movements of Na and Cl are linked by a process or processes which couple the entry of Na to Cl across the apical cell membrane of the intestinal cell. In some tissues, eg, gallbladder and renal tubule, this coupled transport of Na and Cl may be the predominant electrolyte-transporting mechanism. Studies in rabbit ileal brush-border membrane vesicles present evidence for a coupled NaCl process that has the same ionic specificities and similar kinetics as the processes demonstrated by influx techniques across the apical membrane of the intact epithelium. However, the vesicles also exhibit Na:H and Cl:HCO3 exchange processes and the inhibitors thought to be specific for either the NaCl cotransport system (loop diuretics), for the Na:H exchange (high-dose amiloride), or for the Cl:HCO3 exchange (disulfonic stilbenes such as SITS or DIDS), do not prove to be so. It is possible that all three processes could be present in intestinal brush-border membranes. Furthermore, the techniques of isolating vesicles could uncouple or otherwise inhibit the coupled NaCl process. Nonetheless, the preponderance of evidence at this time indicates that parallel ion exchangers of Na:H and Cl:HCO3, as initially suggested by Turnberg et al [4], account for coupled NaCl transport in rabbit ileum. Additional studies will be necessary to determine if this is the only mechanism in the intestinal apical membrane and whether this conclusion applies to other tissues such as gallbladder and renal tubule.