Glioblastomas stem-like cells (GSCs) by invading the brain parenchyma, remains after resection and radiotherapy and the tumoral microenvironment become stiffer. GSC invasion is reported as stiffness ...sensitive and associated with altered N-glycosylation pattern. Glycocalyx thickness modulates integrins mechanosensing, but details remain elusive and glycosylation enzymes involved are unknown. Here, we studied the association between matrix stiffness modulation, GSC migration and MGAT5 induced N-glycosylation in fibrillar 3D context.
To mimic the extracellular matrix fibrillar microenvironments, we designed 3D-ex-polyacrylonitrile nanofibers scaffolds (NFS) with adjustable stiffnesses by loading multiwall carbon nanotubes (MWCNT). GSCs neurosphere were plated on NFSs, allowing GSCs migration and MGAT5 was deleted using CRISPR-Cas9.
We found that migration of GSCs was maximum at 166 kPa. Migration rate was correlated with cell shape, expression and maturation of focal adhesion (FA), Epithelial to Mesenchymal Transition (EMT) proteins and (β1,6) branched N-glycan binding, galectin-3. Mutation of MGAT5 in GSC inhibited N-glycans (β1-6) branching, suppressed the stiffness dependence of migration on 166 kPa NFS as well as the associated FA and EMT protein expression.
MGAT5 catalysing multibranched N-glycans is a critical regulators of stiffness induced invasion and GSCs mechanotransduction, underpinning MGAT5 as a serious target to treat cancer.
Main conclusion
We have developed long term stable high yielding rice lines, Hybrid Mimics, from commercial hybrids. The vigour of the Mimic and the hybrid are developmental changes. These Mimics ...could substitute for hybrid seed for planting.
We have used two pre-existing high-yielding hybrid systems (
FLY1
and
DY527
) to develop Hybrid Mimics. In the
FLY1
hybrid system we selected, under field conditions, F6 lines which have high grain yields and biomass equivalent to the F1 hybrids, stable over subsequent F7, F8 and later generations. We have termed these lines Hybrid Mimics. The mimics are mostly homozygous as a consequence of selfing in each generation. We have repeated this selection procedure in the second independent hybrid system
DY527,
producing Mimics with similar characteristics to the F1 hybrid. In both hybrid systems the selection criterion, based on the phenotype of the F1 hybrid, results in the Mimics having grain yield and biomass similar to that of the F1 hybrid. In each generation of the breeding program the plant population has increased phenotypic homogeneity. The genomes of the Mimic plants do not contain any common heterozygous segments negating claims that the vigour of hybrids depends upon heterozygosity of particular loci. Both hybrids and Mimics have early germination and commence photosynthesis before the parents, providing enhanced growth which is maintained throughout the life cycle. The biochemical parameters of photosynthesis in the hybrids and Mimics do not differ from those of the parents. Grain quality and resistance to the two major diseases, bacterial blight and rice blast are similar in the Mimics and hybrids. The Mimics overcome the major disadvantage of hybrids where F2 phenotypic segregation prevents their use as a crop beyond the F1 generation.
Hybrid mimics and hybrid vigor in Arabidopsis Wang, Li; Greaves, Ian K; Groszmann, Michael ...
Proceedings of the National Academy of Sciences - PNAS,
09/2015, Letnik:
112, Številka:
35
Journal Article
Recenzirano
Odprti dostop
F1 hybrids can outperform their parents in yield and vegetative biomass, features of hybrid vigor that form the basis of the hybrid seed industry. The yield advantage of the F1 is lost in the F2 and ...subsequent generations. In Arabidopsis, from F2 plants that have a F1-like phenotype, we have by recurrent selection produced pure breeding F5/F6 lines, hybrid mimics, in which the characteristics of the F1 hybrid are stabilized. These hybrid mimic lines, like the F1 hybrid, have larger leaves than the parent plant, and the leaves have increased photosynthetic cell numbers, and in some lines, increased size of cells, suggesting an increased supply of photosynthate. A comparison of the differentially expressed genes in the F1 hybrid with those of eight hybrid mimic lines identified metabolic pathways altered in both; these pathways include down-regulation of defense response pathways and altered abiotic response pathways. F6 hybrid mimic lines are mostly homozygous at each locus in the genome and yet retain the large F1-like phenotype. Many alleles in the F6 plants, when they are homozygous, have expression levels different to the level in the parent. We consider this altered expression to be a consequence of transregulation of genes from one parent by genes from the other parent. Transregulation could also arise from epigenetic modifications in the F1. The pure breeding hybrid mimics have been valuable in probing the mechanisms of hybrid vigor and may also prove to be useful hybrid vigor equivalents in agriculture.
Cognitive theories implicate information‐processing biases in the etiology of anxiety disorders. Results of attention‐bias studies in posttraumatic stress disorder (PTSD) have been inconsistent, ...suggesting biases towards and away from threat. Within‐subject variability of attention biases in posttraumatic patients may be a useful marker for attentional control impairment and the development of posttrauma symptoms. This study reports 2 experiments investigating threat‐related attention biases, mood and anxiety symptoms, and attention‐bias variability following trauma. Experiment 1 included 3 groups in a cross‐sectional design: (a) PTSD, (b) trauma‐exposed without PTSD, and (c) healthy controls with no trauma or Axis I diagnoses. Greater attention‐bias variability was found in the PTSD group compared to the other 2 groups (ηp2=.23); attention‐bias variability was significantly and positively correlated (r = .37) with PTSD symptoms. Experiment 2 evaluated combat‐exposed and nonexposed soldiers before and during deployment. Attention‐bias variability did not differentiate groups before deployment, but did differentiate groups during deployment (ηp2=.16); increased variability was observed in groups with acute posttraumatic stress symptoms and acute depression symptoms only. Attention‐bias variability could be a useful marker for attentional impairment related to threat cues associated with mood and anxiety symptoms after trauma exposure.
抽象
Traditional and Simplified Chinese s by AsianSTSS
標題：注意力偏差的變動和創傷後壓力症症狀
撮要：認知理論指出焦慮症的起源會是資訊處理偏差。創傷後壓力症(PTSD)的注意力偏差研究未有一致的結果，或許是偏差可以是接近或遠離威脅。受創病人注意力偏差的個體內變化可能是注意力控制障礙和創傷後症狀的標記。本研究報告兩個試驗，檢測創傷後威脅相關的注意力偏差，情緒和焦慮症狀，和注意力偏差的變動。試驗1包括橫斷面設計內三個組別：(a)PTSD，(b)經歷創傷但未有PTSD，和(c)沒有創傷或軸1診斷的健康對照組。對比其他兩組(n2p=.23)PTSD有更高注意力偏差的變動；而注意力偏差的變動與PTSD症狀呈顯着的正相連(r=.37)。試驗2評估經歷戰鬥及非經歷士兵在派駐前及期間的狀況。注意力偏差變動未能辨別派駐前組別，但可分辨派駐期間的組別(n2p=.16)；添加的變動只見於急性創傷後壓力症狀和急性抑鬱症狀組別。注意力偏差的變動可以是經歷創傷後情緒和焦慮症狀相連威脅暗示的注意力障礙的有效標記。
标题：注意力偏差的变动和创伤后压力症症状
撮要：认知理论指出焦虑症的起源会是信息处理偏差。创伤后压力症(PTSD)的注意力偏差研究未有一致的结果，或许是偏差可以是接近或远离威胁。受创病人注意力偏差的个体内变化可能是注意力控制障碍和创伤后症状的标记。本研究报告两个试验，检测创伤后威胁相关的注意力偏差，情绪和焦虑症状，和注意力偏差的变动。试验1包括横断面设计内三个组别：(a)PTSD，(b)经历创伤但未有PTSD，和(c)没有创伤或轴1诊断的健康对照组。对比其他两组(n2p=.23)PTSD有更高注意力偏差的变动；而注意力偏差的变动与PTSD症状呈显着的正相连(r=.37)。试验2评估经历战斗及非经历士兵在派驻前及期间的状况。注意力偏差变动未能辨别派驻前组别，但可分辨派驻期间的组别(n2p=.16)；添加的变动只见于急性创伤后压力症状和急性忧郁症状组别。注意力偏差的变动可以是经历创伤后情绪和焦虑症状相连威胁暗示的注意力障碍的有效标记。
Mice with null mutations in specific Golgi glycosyltransferases show evidence of glycan compensation where missing carbohydrate epitopes are found on biosynthetically related structures. Repetitive ...saccharide sequences within the larger glycan structures are functional epitopes recognized by animal lectins. These studies provide the first in vivo support for the existence of a feedback system that maintains and regulates glycan epitope density in cells. Receptor regulation by lectin–glycan interactions and the Golgi provides a mechanism for the adaptation of cell surface receptors and solute transporters in response to environmental cues and intracellular signaling. We suggest that other posttranslational modification systems might have similar conditional features regulated by density-dependent ligand–epitope interactions.
► Neurocognitive dysfunction in major depression involves both biases and deficits. ► Problems with cognitive control in depression may underlie these abnormalities. ► Prefrontal cortical systems may ...be a key substrate for deficient cognitive control. ► Subcortical emotion-processing systems may be under-regulated in depression. ► Targeting neurocognitive aspects of depression may lead to new treatments.
Major depressive disorder (MDD) is a disabling medical condition associated with significant morbidity, mortality and public health costs. However, neurocircuitry abnormalities underlying depression remain incompletely understood and consequently current treatment options are unfortunately limited in efficacy. Recent research has begun to focus specifically on cognitive aspects of depression and potential neurobiological correlates. Two fundamental types of cognitive dysfunction observed in MDD are
cognitive biases, which include distorted information processing or attentional allocation toward negative stimuli, and
cognitive deficits, which include impairments in attention, short-term memory and executive functioning. In this article, we present a selective review of current research findings in these domains and examine neuroimaging research that is beginning to characterize the neurocircuitry underlying these biases and deficits. We propose that deficient cognitive functioning, attention biases and the sustained negative affect characteristic of MDD can be understood as arising in part from dysfunctional prefrontal-subcortical circuitry and related disturbances in the cognitive control of emotion. Finally, we highlight potential new pharmacological and non-pharmacological therapeutic strategies for MDD based on an evolving mechanistic understanding of the disorder.
Genetic analyses have identified three genes that control the vernalization requirement in wheat and barley;
VRN1,
VRN2 and
FT (
VRN3). These genes have now been isolated and shown to regulate not ...only the vernalization response but also the promotion of flowering by long days.
VRN1 is induced by vernalization and accelerates the transition to reproductive development at the shoot apex.
FT is induced by long days and further accelerates reproductive apex development.
VRN2, a floral repressor, integrates vernalization and day-length responses by repressing
FT until plants are vernalized. A comparison of flowering time pathways in cereals and
Arabidopsis shows that the vernalization response is controlled by different MADS box genes, but integration of vernalization and long-day responses occurs through similar mechanisms.
Hybridization in plants leads to transinteractions between the parental genomes and epigenomes that can result in changes to both 24 nt siRNA and cytosine methylation (mC) levels in the hybrid. In ...Arabidopsis the principle processes altering the hybrid methylome are Trans Chromosomal Methylation (TCM) and Trans Chromosomal deMethylation (TCdM) in which the mC pattern of a genomic segment attains the same mC pattern of the corresponding segment on the other parental chromosome. We examined two loci that undergo TCM/TCdM in the Arabidopsis C24/Landsberg erecta (Ler) F1 hybrids, which show patterns of inheritance dependent on the properties of the particular donor and recipient chromosomal segments. At At1g64790 the TCM- and TCdM-derived mC patterns are maintained in the F2 generation but are transmitted in outcrosses or backcrosses only by the C24 genomic segment. At a region between and adjacent to At3g43340 and At3g43350, the originally unmethylated Ler genomic segment receives the C24 mC pattern in the F1, which is then maintained in backcross plants independent of the presence of the parental C24 segment. In backcrosses to an unmethylated Ler allele, the newly methylated F1 Ler segment may act as a TCM source in a process comparable to paramutation in maize. TCM-derived mC patterns are associated with reduced expression of both At3g43340 and At3g43350 in F1 and F2 plants, providing support for such events influencing the transcriptome. The inheritance of the F1 mC patterns and the segregation of other genetic and epigenetic determinants may contribute to the reduced hybrid vigor in the F2 and subsequent generations.
N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS). Metabolism controls ...N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes. Activated T cells switch metabolism from oxidative phosphorylation to aerobic glycolysis and glutaminolysis. This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching. Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity. However, GlcNAc activity is limited by the lack of a cell surface transporter and requires high doses to enter cells via macropinocytosis. Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc. Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway. Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity. GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
PDF
