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Neuroimaging- and machine-learning-based brain-age prediction of schizophrenia is well established. However, the diagnostic significance and the effect of early medication on first-episode schizophrenia remains unclear.
To explore whether predicted brain age can be used as a biomarker for schizophrenia diagnosis, and the relationship between clinical characteristics and brain-predicted age difference (PAD), and the effects of early medication on predicted brain age.
The predicted model was built on 523 diffusion tensor imaging magnetic resonance imaging scans from healthy controls. First, the brain-PAD of 60 patients with first-episode schizophrenia, 60 healthy controls and 21 follow-up patients from the principal data-set and 40 pairs of individuals in the replication data-set were calculated. Next, the brain-PAD between groups were compared and the correlations between brain-PAD and clinical measurements were analysed.
The patients showed a significant increase in brain-PAD compared with healthy controls. After early medication, the brain-PAD of patients decreased significantly compared with baseline (P < 0.001). The fractional anisotropy value of 31/33 white matter tract features, which related to the brain-PAD scores, had significantly statistical differences before and after measurements (P < 0.05, false discovery rate corrected). Correlation analysis showed that the age gap was negatively associated with the positive score on the Positive and Negative Syndrome Scale in the principal data-set (r = −0.326, P = 0.014).
The brain age of patients with first-episode schizophrenia may be older than their chronological age. Early medication holds promise for improving the patient's brain ageing. Neuroimaging-based brain-age prediction can provide novel insights into the understanding of schizophrenia.
We examined the in vitro developmental competence of parthenogenetic activation (PA) oocytes activated by an electric pulse (EP) and treated with various concentrations of AZD5438 for 4 h. Treatment with 10 µM AZD5438 for 4 h significantly improved the blastocyst formation rate of PA oocytes in comparison with 0, 20, or 50 µM AZD5438 treatment (46.4% vs. 34.5%, 32.3%, and 24.0%, respectively; P < 0.05). The blastocyst formation rate was higher in the group treated with AZD5438 for 4 h than in the groups treated with AZD5438 for 2 or 6 h (42.8% vs. 38.6% and 37.2%, respectively; P > 0.05). Furthermore, 66.67% of blastocysts derived from these AZD5438-treated PA oocytes had a diploid karyotype. The blastocyst formation rate of PA and somatic cell nuclear transfer (SCNT) embryos was similar between oocytes activated by an EP and treated with 2 mM 6-dimethylaminopurine for 4 h and those activated by an EP and treated with 10 µM AZD5438 for 4 h (11.11% vs. 13.40%, P > 0.05). In addition, the level of maturation-promoting factor (MPF) was significantly decreased in oocytes activated by an EP and treated with 10 µM AZD5438 for 4 h. Finally, the mRNA expression levels of apoptosis-related genes (Bax and Bcl-2) and pluripotency-related genes (Oct4, Nanog, and Sox2) were checked by RT-PCR; however, there were no differences between the AZD5438-treated and non-treated control groups. Our results demonstrate that porcine oocyte activation via an EP in combination with AZD5438 treatment can lead to a high blastocyst formation rate in PA and SCNT experiments.
We investigated the effect of human induced pluripotent stem cell (hiPS) medium on porcine somatic cell nuclear transfer and bovine in vitro fertilized early blastocysts, in comparison with North Carolina State University (NCSU)-37 medium and in vitro culture (IVC)-II medium. After 2 days of culture, the diameter of the portion of the blastocyst that was extruded from the zona pellucid dramatically differed between porcine blastocysts cultured in hiPS medium and those cultured in NCSU-37 medium (221.47 ± 38.94 μm versus 481.87 ± 40.61 μm, P < 0.01). Moreover, the diameter of the portion of the blastocyst significantly differed between bovine blastocysts cultured in hiPS medium and those cultured in IVC-II medium (150.30 ± 29.49 μm versus 195.58 ± 41.59 μm, P < 0.01). Furthermore, the total number of cells per porcine and bovine blastocyst was more than two-fold higher in blastocysts cultured in hiPS medium than in those cultured in NCSU-37 medium (44.33 ± 5.28 and 143.33 ± 16.05, P < 0.01) or IVC-II medium (172.12 ± 45.08 and 604.83 ± 242.64, P < 0.01), respectively. These results indicate that hiPS medium markedly improves the quality of porcine and bovine blastocysts.
This paper provides a brief outline of the current, detailed inter-disciplinary work on the Xiaoyangquiao section, trying to expose all the aspects for reference tied to the Global Single Stratigraphic Point (GSSP) Concept for defining the Cambrian–Ordovician Boundary. The 45 m critical interval of this section outcrops very well along the steep bank of a stream and is free from folding, faulting, intrusions, and has not been affected by weathering. Colour alternation of conodonts and acritarchs, and crystallinity indices of illite all indicate a maximum thermal grade of 100 °C. The lithofacies, being of great lateral persistence for a hundred kilometres, consists mainly of a rhythmical sequence of lime mudstone and shales deposited in a moderately deep outer shelf environment of quiet water, well below the normal storm wave base. Chemical investigation of the rocks demonstrates strong positive correlation between A12O3 content and those of K2O, MgO, Fe2O3, TiO2, Be, Cr, Co, Ni, Zn and Ba, indicating these components are tied to the clay fractions. A stable depositional environment is demonstrated by the uniform chemistries through the boundary interval. Close to the boundary itself P2O5 contents are low, indicating continuous sedimentation at fairly substantial rates.
The major biological events, the biostratigraphic framework, and the stratigraphic range of conodont, graptolite, trilobite, and acritarch taxa are illustrated briefly with diagrams. Following the majority views of the Calgary Plenary Session, the boundary level is to be chosen at a point marked by the First Appearance Datum (FAD) of the selected conodont taxon or taxa in the vicinity of the level close to, but below, the first influx of nematophorous graptolites. The following four points marked by the incoming of conodont taxon or taxa are recommended for consideration of the ‘Golden Spike'‘: (1) FAD of Cordylodus intermedius at 5.28 m below the first influx of nematophorous graptolites; (2) FAD of Hirsutodontus simpler–Cordylodus drucei–Albiconus postcostatus at 5.23 m; (3) FAD of Semiacontiodus lavadamensis–Utahconus utahensis–Monocostodus sevierensis at 3.85 m; (4) FAD of Cordylodus lindstromi at 2.23 m. For the following reasons the FAD of H. simplex–C. drucei–A. postcostatus is favoured: (1) the taxa are all distinct and widely dispersed; (2) intensive evolutionary change took place in conodonts, graptolites, trilobites and acritarchs prior to or after this point; all the fossil groups occur together, providing correlation with many regions throughout the world; (3) the point is in a position between the previously widely accepted boundary levels based on graptolites and trilobites; (4) the proposed point lies within a thin, laterally persistent, rhythmical sequence. The FAD of Cordylodus lindstromi is also a favourable point, sharing many advantages mentioned above. But this point is less satisfactory in being defined by the FAD of a single taxon C. lindstromi which also has an extremely small population size.
An isochron age of 500.7 ± 7.4 Ma is determined from clay fractions of mudstones 8.5 m below the proposed point by means of the Rubidium–Strontium method.
The ɛND signature determined from conodonts, trilobites hyolithids and acrotretid brachiopods has a mean value of −6.7, comparable with that of the coeval oceanic water mass occupying southeastern North America and Europe, and indicating that northeastern China bordered the same ocean. The mean Tdm model age determined was 1.26 Ga at the time of sedimentation, compatible with the mean Tdm model age of approximately 1.1 Ga for the Pacific Ocean today. The relatively low value of the Tdm model age indicates a substantial input from young orogenic volcanic island arcs and terranes.
Macrophages from the head kidney (HK) and peripheral blood leucocytes were isolated fromCyprinus carpio by Percoll gradient density centrifugation, cultured in vitro and exposed to different concentrations of the immunomodulator lentinan. To evaluate the immunostimulating effects of lentinan, proliferation of the peripheral blood leucocytes, respiratory burst of macrophages and interleukin-1β (IL-1β) gene mRNA expression of macrophages were investigated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], NBT (nitroblue tetrazolium) reduction, Griess reaction and real-time polymerase chain reaction (PCR). Results showed that proliferation of peripheral blood leucocytes after 24 h incubation by the induction of lentinan at 100 and 1000 μg/ml was markedly stimulated. Lentinan at 1, 100 and 1000 μg/ml could significantly induce superoxide anions in macrophages. Production of nitric oxide by HK macrophages after 96 h incubation by lentinan showed that it had no conspicuous effect on nitrogen burst activity of macrophages. Moreover, it inhibited the nitrogen burst activity at higher doses. The expression of IL-1β in the HK macrophages after 24 h of polysaccharide stimulation showed that lentinan stimulated IL-1β expression in the head kidney in carp. Lentinan can modulate the immune response of C. carpio.
It is still unclear whether nuclear envelope breakdown and premature chromosome condensation are essential for the reprogramming of the donor nucleus following somatic nuclear transfer. To address this, we determined the ability of delayed-activated or simultaneously activated porcine oocytes to undergo nuclear remodelling and development following somatic cell nuclear transfer. A small microtubule aster was observed in association with decondensed chromatin following nuclear transfer, suggesting the introduction of a somatic cell centrosome. In the delayed-activated condition, most fibroblast nuclei divided into two chromosome masses and two pronuclear-like structures following transfer into oocytes. In contrast, fibroblast nuclei in the simultaneously activated condition formed a large, swollen, pronuclear-like structure. Microtubule asters were organised in the vicinity of the nucleus regardless of the number of nuclei. More reconstructed oocytes developed to the blastocyst stage in the delayed-activated condition than in the simultaneously activated condition (p < 0.05). Nine piglets were born from two recipient sows following transfer of delayed-activated reconstructed oocytes, while none developed to full term in the simultaneously activated condition. Fingerprint analysis showed that the PCR-RFLP patterns of the nine offspring were identical to that of the donor pig. These results suggest that the activation of recipient oocytes during nuclear transfer probably relates to the nuclear remodelling process, which can affect the ability of embryos created by somatic cell nuclear transfer to develop.
To enhance the probability of reprogramming somatic cell nuclei, fibroblast cells from an adult male rabbit and a 12-day-old fetus were fused with oocytes at the second metaphase. The chromosomes of recipient oocytes were then removed by treatment with demecolcine for 1 or 2 h after fusion. Demecolcine treatment of fused oocytes induced membrane protrusions that contained all the maternal chromosomes, thus making it possible to remove the chromosomes. The potential of nuclear-transferred oocytes to develop into blastocysts was high (48% and 59%) and the average cell number of the blastocysts was large (149 and 159) 96 h after in vitro culture. The proportions of nuclear-transferred oocytes enucleated 1 h after fusion and implanted after transfer to pseudopregnant recipients were relatively high (2.8% and 4.9%) compared with our previous reports (1.7%: Yin et al., 2000; 0.6% and 1.0%: Yin et al., 2002a) where donor cells were fused with previously enucleated oocytes. Of 34 adult somatic cell implantation sites, 6 had fetuses on day 12 or 14 of pregnancy, but none of the fetuses had a heart beat or developed to term. None of the nuclear-transferred oocytes whose chromosomes were removed 2 h after demecolcine treatment implanted after transfer to recipients. The possible reasons why the high-quality nuclear-transferred oocytes did not develop to term are discussed.
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