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排序方式: 共有772条查询结果,搜索用时 15 毫秒
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Shobana Sekar Livia Tomasini Christos Proukakis Taejeong Bae Logan Manlove Yeongjun Jang Soraya Scuderi Bo Zhou Maria Kalyva Anahita Amiri Jessica Mariani Fritz J. Sedlazeck Alexander E. Urban Flora M. Vaccarino Alexej Abyzov 《Genome research》2020,30(12):1695
Somatic mosaicism, manifesting as single nucleotide variants (SNVs), mobile element insertions, and structural changes in the DNA, is a common phenomenon in human brain cells, with potential functional consequences. Using a clonal approach, we previously detected 200–400 mosaic SNVs per cell in three human fetal brains (15–21 wk postconception). However, structural variation in the human fetal brain has not yet been investigated. Here, we discover and validate four mosaic structural variants (SVs) in the same brains and resolve their precise breakpoints. The SVs were of kilobase scale and complex, consisting of deletion(s) and rearranged genomic fragments, which sometimes originated from different chromosomes. Sequences at the breakpoints of these rearrangements had microhomologies, suggesting their origin from replication errors. One SV was found in two clones, and we timed its origin to ∼14 wk postconception. No large scale mosaic copy number variants (CNVs) were detectable in normal fetal human brains, suggesting that previously reported megabase-scale CNVs in neurons arise at later stages of development. By reanalysis of public single nuclei data from adult brain neurons, we detected an extrachromosomal circular DNA event. Our study reveals the existence of mosaic SVs in the developing human brain, likely arising from cell proliferation during mid-neurogenesis. Although relatively rare compared to SNVs and present in ∼10% of neurons, SVs in developing human brain affect a comparable number of bases in the genome (∼6200 vs. ∼4000 bp), implying that they may have similar functional consequences.Somatic mosaicism, the presence of more than one genotype in the somatic cells of an individual, is a prominent phenomenon in the human central nervous system. Forms of mosaicism include aneuploidies and smaller copy number variants (CNVs), structural variants (SVs), mobile element insertions, indels, and single nucleotide variants (SNVs). The developing human brain exhibits high levels of aneuploidy compared to other tissues, generating genetic diversity in neurons (Pack et al. 2005; Yurov et al. 2007; Bushman and Chun 2013). Such aneuploidy was suggested to be a natural feature of neurons, rather than a distinctive feature of neurodegeneration. However, the frequency of aneuploidy in neurons has been debated, with a separate study suggesting that aneuploidies occur in only about 2.2% of mature adult neurons (Knouse et al. 2014). They hence infer that such aneuploidy could have adverse effects at the cellular and organismal levels. Additionally, analysis of single cells from normal and pathological human brains identified large, private, and likely clonal somatic CNVs in both normal and diseased brains (Gole et al. 2013; McConnell et al. 2013; Cai et al. 2014; Knouse et al. 2016; Chronister et al. 2019; Perez-Rodriguez et al. 2019), with 3%–25% of human cerebral cortical nuclei carrying megabase-scale CNVs (Chronister et al. 2019) and deletions being twice as common as duplications (McConnell et al. 2013). Given that CNVs often arise from nonhomologous recombination and replication errors, their likely time of origin is during brain development. However, when CNVs first arise in human brain development has not yet been investigated. The present work is the first to examine this question using clonal populations of neuronal progenitor cells (NPCs) obtained from fetal human brains.Detection of CNVs in single neurons is challenging, given the need to amplify DNA. Such amplification may introduce artifacts that could, in turn, be misinterpreted as CNVs. In order to address this technical limitation, Hazen et al. reprogrammed adult postmitotic neurons using somatic cell nuclear transfer (SCNT) of neuronal nuclei into enucleated oocytes (Hazen et al. 2016). These oocytes then made sufficient copies of the neuronal genome allowing for whole-genome sequencing (WGS), thus eliminating the need for amplification in vitro. Using this method, they identified a total of nine structural variants in six neurons from mice, three of which were complex rearrangements. However, it is not possible to extend such studies to humans, given the ethical issues involved, besides the technical challenges in obtaining and cloning adult neurons. To circumvent the need of single-cell DNA amplification or nuclear cloning, we examined clonal cell populations obtained from neural progenitor cells from the frontal region of the cerebral cortex (FR), parietal cortex (PA) and basal ganglia (BG) and describe here the discovery and analysis of mosaic SVs in these NPCs (Bae et al. 2018). These clones were sequenced at 30× coverage (much higher than most previous single-cell studies), allowing identification of SVs other than large deletions and duplications as well as precise breakpoint resolution. 相似文献
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Fifty patients with endoscopically proven pyloric-prepyloric ulcers (PU/PPU) and 50 with duodenal ulcers (DU) completed a six-week double-blind clinical trial initially comprising 124 patients. The antacid-treated patients received 10 ml of an antacid suspension seven times a day (buffering 367.5 mmol acid). Healing rate after three weeks of treatment was 74% in the antacid and 42% in the placebo group (p less than 0.01). After six weeks the corresponding figures were 96 and 68% (p less than 0.001). Regarding the PU/PPU and DU subgroups we found significant differences compared to placebo in the PU/PPU group only. Antacids caused a significantly faster and more perceptible pain relief than placebo. We found no significant correlation between ulcer healing and smoking habits. Regression analyses showed that, besides antacids, ulcer size and peak acid output influenced the healing rate significantly. 相似文献
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Anahita Jalilvand Katelyn A. Levene Kejal Shah Bradley Needleman Sabrena F. Noria 《Surgery for obesity and related diseases》2021,17(5):921-930
BackgroundStudies on early postoperative readmissions after bariatric surgery (BS) have examined readmissions as a single entity, regardless of urgency. Strategies to lower nonurgent readmissions would reduce unnecessary hospital utilization.ObjectivesTo identify predictors of urgent readmissions (UR) versus nonurgent readmissions (NUR) at 30 days post-BS.SettingSingle academic institution.MethodsPatients undergoing primary BS over 2 years (n = 589) were retrospectively reviewed. Baseline demographic, medical, and hospitalization data were compared between readmitted patients, stratified by urgency, and nonreadmitted patients. Multivariate regression models of UR and NUR were created using variables with a P value ≤ .2 on univariate analyses. A P value ≤ .05 was considered statistically significant.ResultsThere were 39 documented instances of 30-day readmissions, of which 44% (n = 17) were NUR; NUR patients were more likely to be female (100% versus 78.2% male; P = .03) and trended toward being younger, experiencing ≥2 perioperative complications, and having a longer index hospital length of stay (LOS). Patients with URs had a higher baseline BMI (52.5 ± 11.4 kg/m2 versus 48.7 ± 8.3 kg/m2, respectively; P = .04), were more likely to have sleep apnea (77.3% versus 56.1%, respectively; P = .05), had a longer LOS (3 versus 2 d, respectively; P = .007), and were more likely to have ≥2 postoperative complications (46% versus 17.0%, respectively; P = .003) compared with those with an NUR. Independent predictors of NUR included public insurance (odds ratio [OR] = 3.7; 95% confidence interval [CI], 1.17–11.67; P = .03), younger age (OR = 1.05; 95% CI, 1–1.01; P = .04), and female sex, while URs were independently predicted by LOS (OR = 1.3; 95% CI, 1.04–1.5; P = .02).ConclusionsPublic insurance appears to be associated with NURs, while LOS predicts URs after BS. This suggests an important dichotomy within readmissions based on urgency, which has important implications for targeted quality initiatives. 相似文献
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Natural Convection Heat Transfer in a Porous Cavity with Sinusoidal Temperature Distribution Using Cu/Water Nanofluid: Double MRT Lattice Boltzmann Method
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Hasan Sajjadi Amin Amiri Delouei Rasul Mohebbi Mohsen Izadi & Sauro Succi 《Communications In Computational Physics》2021,29(1):292-318
In this study, natural convection flow in a porous cavity with sinusoidal
temperature distribution has been analyzed by a new double multi relaxation time
(MRT) Lattice Boltzmann method (LBM). We consider a copper/water nanofluid filling a porous cavity. For simulating the temperature and flow fields, D2Q5 and D2Q9
lattices are utilized respectively, and the effects of different Darcy numbers (Da) (0.001-0.1) and various Rayleigh numbers (Ra) ($10^3$-$10^5$) for porosity ($ε$) between 0.4 and 0.9
have been considered. Phase deviation ($θ$) changed from 0 to $π$ and the volume fraction
of nanoparticles (Ø) varied from 0 to 6%. The present results show a good agreement
with the previous works, thus confirming the reliability the new numerical method
proposed in this paper. It is indicated that the heat transfer rate increases at increasing
Darcy number, porosity, Rayleigh number, the volume fraction of nanoparticles and
phase deviation. However, the most sensitive parameter is the Rayleigh number. The
maximum Nusselt deviation is 10%, 32% and 33% for Ra=$10^3$, $10^4$ and $10^5$, respectively, with $ε = 0.4$ to $ε = 0.9$. It can be concluded that the effect of Darcy number on
the heat transfer rate increases at increasing Rayleigh number, yielding a maximum
enhancement of the average Nusselt number around 12% and 61% for Ra=$10^3$ and
Ra=$10^5$, respectively. 相似文献
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The effect of nicotine on core body temperature was studied in mice. Intraperitoneal (i.p.) injection of nicotine (0.5, 1 and 2 mg/kg) induced a dose-dependent hypothermia. The response was inhibited by reserpine (5 mg/kg), the centrally active nicotinic receptor antagonist mecamylamine (0.1-1 mg/kg) and the D-2 dopamine receptor antagonist sulpiride (25-100 mg/kg). The β-adrenoceptor antagonist propranolol (5 and 10 mg/kg) and the serotonergic blocker methysergide (5 and 10 mg/kg) did not inhibit but increased the nicotine response. The α-adrenoceptor antagonist phenoxybenzamine, the antimuscarinic agent atropine, the D-1 dopamine receptor antagonist SCH 23390, the peripheral dopamine antagonist domperidone and the peripheral nicotinic antagonist hexamethonium did not alter the nicotine-induced hypothermia. It is concluded that nicotine may cause a fall in core body temperature through a central dopaminergic mechanism. 相似文献
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