VAMP-2 is a surrogate cerebrospinal fluid marker of Alzheimer-related cognitive impairment in adults with Down syndrome

Altres ajuts: Fundació la Marató de TV3/20141210There is an urgent need for objective markers of Alzheimer's disease (AD)-related cognitive impairment in people with Down syndrome (DS) to improve diagnosis, monitor disease progression, and assess response to disease-modifying therapies. Previously, GluA4 and neuronal pentraxin 2 (NPTX2) showed limited potential as cerebrospinal fluid (CSF) markers of cognitive impairment in adults with DS. Here, we compare the CSF profile of a panel of synaptic proteins (Calsyntenin-1, Neuroligin-2, Neurexin-2A, Neurexin-3A, Syntaxin-1B, Thy-1, VAMP-2) to that of NPTX2 and GluA4 in a large cohort of subjects with DS across the preclinical and clinical AD continuum and explore their correlation with cognitive impairment. We quantified the synaptic panel proteins by selected reaction monitoring in CSF from 20 non-trisomic cognitively normal controls (mean age 44) and 80 adults with DS grouped according to clinical AD diagnosis (asymptomatic, prodromal AD or AD dementia). We used regression analyses to determine CSF changes across the AD continuum and explored correlations with age, global cognitive performance (CAMCOG), episodic memory (modified cued-recall test; mCRT) and CSF biomarkers, CSF Aβ ratio, CSF Aβ, CSF p-tau, and CSF NFL. P values were adjusted for multiple testing. In adults with DS, VAMP-2 was the only synaptic protein to correlate with episodic memory (delayed recall adj.p =.04) and age (adj.p =.0008) and was the best correlate of CSF Aβ (adj.p =.0001), p-tau (adj.p < .0001), and NFL (adj.p < .0001). Compared to controls, mean VAMP-2 levels were lower in asymptomatic adults with DS only (adj.p =.02). CSF levels of Neurexin-3A, Thy-1, Neurexin-2A, Calysntenin-1, Neuroligin-2, GluA4, and Syntaxin-1B all strongly correlated with NPTX2 (p <.0001), which was the only synaptic protein to show reduced CSF levels in DS at all AD stages compared to controls (adj.p <.002). These data show proof-of-concept for CSF VAMP-2 as a potential marker of synapse degeneration that correlates with CSF AD and axonal degeneration markers and cognitive performance

Simulation of effective fracture length of prepad acid fracturing considering multiple leak-off effect

For the purpose of improving the accuracy and effectiveness of acid fracturing design for carbonate reservoirs with developed natural fractures, an acidizing fluid flow and reaction model taking the multiple leak-off effect of natural fracture, wormhole and matrix into account was established according to the liquid phase reaction equilibrium principle and the local reaction equilibrium principle after the dynamic change of fracture geometry in the process of fracture created by prepad fluid was simulated in the classical pseudo-three dimensional mathematical model of fracture propagation. Then, the acid fracturing stimulation of a case well on site was taken as an example. The newly developed model was used to simulate the filtration process of acidizing fluid in fractures and the dynamic etching morphology of acidic rocks during the acidizing fluid injection of prepad acid fracturing. The effective length of etched fractures was determined by analyzing the concentration change of acidizing fluid along the direction of hydraulic fracture length and the threshold concentration of residual acidizing fluid comprehensively, and then it was compared with the interpretation result of pressure buildup test. And the following research results were obtained. First, in the process of acid fracturing in fractured–porous reservoirs, the acidizing fluid filtration velocity along the direction of fracture length is not constant and the filtration velocity curve fluctuates in a serrated shape. And the acidizing fluid filtration velocity where etched wormholes meet natural fractures is commonly higher than that in matrix. Second, acidizing fluid is lost seriously and the effective distance of acidizing fluid gets short significantly during the acid fracturing of fractured–porous reservoirs. Third, acid fracturing in the verification well is remarkable in blockage removing and stimulation, and its well test interpretation results are consistent with the simulation interpretation results provided by the newly developed mathematical model. It is indicated that this newly developed model is reliable. In conclusion, the mathematical model of prepad acid fracturing which considers multiple leak-off effect is more suitable for acid fracturing simulation of fractured–porous reservoirs. Keywords: Carbonate rock, Reservoir, Natural facture, Wormhole, Prepad acid fracturing, Acidizing fluid filtration, Effective fracture length, Fractured–porous, Acid fracturing simulatio

Identification and Phylogenetic Analysis of the <i>R2R3-MYB</i> Subfamily in <i>Brassica napus</i>

The R2R3-MYB sub-family proteins are composed of most members of MYB (v-Myb avian myeloblastosis viral oncogene homolog) protein, a plant-specific transcription factor (TF) that is classified into four classes depending on the number of MYB repeats. R2R3-MYB TFs are involved in physiological and biochemical processes. However, the functions of the Brassica napus R2R3-MYB genes are still mainly unknown. In this study, 35 Brassica napus MYB (BnaMYB) genes were screened in the genome of Brassica napus, and details about their physical and chemical characteristics, evolutionary relationships, chromosome locations, gene structures, three-dimensional protein structures, cis-acting promoter elements, and gene duplications were uncovered. The BnaMYB genes have undergone segmental duplications and positive selection pressure, according to evolutionary studies. The same subfamilies have similar intron–exon patterns and motifs, according to the genes’ structure and conserved motifs. Additionally, through cis-element analysis, many drought-responsive and other stress-responsive cis-elements have been found in the promoter regions of the BnaMYB genes. The expression of the BnaMYB gene displays a variety of tissue-specific patterns. Ten lignin-related genes were chosen for drought treatment. Our research screened four genes that showed significant upregulation under drought stress, and thus may be important drought-responsive genes. The findings lay a new foundation for understanding the complex mechanisms of BnaMYB in multiple developmental stages and pathways related to drought stress in rapeseed

Land Use Change and Its Impact on Landscape Ecological Risk in Typical Areas of the Yellow River Basin in China

The basic premise of regional ecological construction would be to scientifically and effectively grasp the characteristics of land use change and its impact on landscape ecological risk. The research objects of this paper are the typical areas of the Yellow River Basin in China and “process-change-drive” as the logical main line. Moreover, this paper is based on multi-period land use remote sensing data from 2000 to 2020, the regional land use change process and influencing factors are identified, the temporal and spatial evolution and response process of landscape ecological risk are discussed, and the land use zoning control strategy to reduce ecological risk is put forward. The results indicated: (1) The scale and structure of land use show the characteristics of “many-to-one” and “one-to-many”; (2) the process of land use change is affected by the alternation of multiple factors. The natural environment and socio-economic factors dominate in the early stage and the location and policy factors have a significant impact in the later stage; (3) the overall landscape ecological risk level and conversion rate show a trend of “high in the southeast, low in the northwest”, shift from low to high and landscape ecological risks gradually increase; and (4) in order to improve the regional ecological safety and according to the characteristics of landscape ecological risk and spatial heterogeneity, we should adopt the management and control zoning method and set different levels of control intensity (from key intensity to strict intensity to general intensity), and develop differentiated land use control strategies

Demonstration of Ultra-High-Q Silicon Microring Resonators for Nonlinear Integrated Photonics

A reflowing photoresist and oxidation smoothing process is used to fabricate ultra-high-Q silicon microring resonators based on multimode rib waveguides. Over a wide range of wavelengths near 1550 nm, the average Q-factor of a ring with 1.2-μm-wide waveguides reaches up to 1.17 × 106, with a waveguide loss of approximately 0.28 dB/cm. For a resonator with 1.5-μm-wide waveguides, the average Q-factor reaches 1.20 × 106, and the waveguide loss is 0.27 dB/cm. Moreover, we theoretically and experimentally show that a reduction in the waveguide loss significantly improves the conversion efficiency of four-wave mixing. A high four-wave mixing conversion efficiency of −17.0 dB is achieved at a pump power of 6.50 dBm

Deep RNA-Seq to Unlock the Gene Bank of Floral Development in <i>Sinapis arvensis</i>

<div><p><i>Sinapis arvensis</i> is a weed with strong biological activity. Despite being a problematic annual weed that contaminates agricultural crop yield, it is a valuable alien germplasm resource. It can be utilized for broadening the genetic background of Brassica crops with desirable agricultural traits like resistance to blackleg (<i>Leptosphaeria maculans</i>), stem rot (<i>Sclerotinia sclerotium</i>) and pod shatter (caused by FRUITFULL gene). However, few genetic studies of <i>S. arvensis</i> were reported because of the lack of genomic resources. In the present study, we performed <i>de novo</i> transcriptome sequencing to produce a comprehensive dataset for <i>S. arvensis</i> for the first time. We used Illumina paired-end sequencing technology to sequence the <i>S. arvensis</i> flower transcriptome and generated 40,981,443 reads that were assembled into 131,278 transcripts. We de novo assembled 96,562 high quality unigenes with an average length of 832 bp. A total of 33,662 full-length ORF complete sequences were identified, and 41,415 unigenes were mapped onto 128 pathways using the KEGG Pathway database. The annotated unigenes were compared against <i>Brassica rapa</i>, <i>B. oleracea</i>, <i>B. napus</i> and <i>Arabidopsis thaliana</i>. Among these unigenes, 76,324 were identified as putative homologs of annotated sequences in the public protein databases, of which 1194 were associated with plant hormone signal transduction and 113 were related to gibberellin homeostasis/signaling. Unigenes that did not match any of those sequence datasets were considered to be unique to <i>S. arvensis</i>. Furthermore, 21,321 simple sequence repeats were found. Our study will enhance the currently available resources for Brassicaceae and will provide a platform for future genomic studies for genetic improvement of Brassica crops.</p></div

Gene Ontology (GO) analysis of transcriptome associated with flower development of <i>S. arvensis</i>.

<p>(The percentage and distribution of top-level GO-terms were portrayed in the three categories: Biological process, Cellular component and Molecular function.). Gene Ontology classifications of assembled unigenes, and 76,324 unigenes with significant similarity in Nr protein databases were assigned to gene ontology classifications.</p

Cytological and molecular analysis of Nsa

Nsa cytoplasmic male sterility (CMS) is a novel Brassica napus male sterility system derived from Sinapis arvensis cytoplasm. Nsa CMS results in defective pollen production due to S. arvensis mitochondrial gene failure/incompatibility in the anthers, requiring nuclear genes to restore fertility. From ultramicroscopic observation of anther sections, we concluded that the induction of sterility begins at the pollen (microspore) mother cell stage. Most pollen mother cells do not undergo the first meiotic division and dissociate before the tetrad stage. At the tetrad stage, abortion was observed for all uninucleate pollen. Dysfunction of mitchondrial gene(s) leads to cell vacuolization in the anther tapetum and middle layer cells. Early programmed cell death (PCD) of the tapetum and anther middle layer cells is the main reason for pollen mother cell abortion. Due to this early pollen abortion, the sterility of Nsa CMS is stable and complete. Southern blotting of DNA from the Nsa male-sterile line, its maintainer and restorer lines, as well as the two parental lines (B. napus cv. Zhongshuang 4 and S. arvensis var. Yeyou 18) involved in the somatic hybridization, suggested that the cytoplasm of the Nsa CMS line was from S. arvensis and that of the restorer line was a rearrangement of both parental lines. Nsa CMS shows great potential for hybrid seed production in rapeseed. Our results provide clues to identify novel male-sterility (S) and restorer (R) genes as well as elucidate the mechanism underlying interactions between the S and R genes