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Natalie Groves Imogen OKeeffe Wendy Lee Alexandra Toft Daniel Blackmore Saurabh Bandhavkar Elizabeth J. Coulson Perry F. Bartlett Dhanisha J. Jhaveri 《Developmental neurobiology》2019,79(9-10):868-879
Brain‐derived neurotrophic factor (BDNF) signaling plays a major role in the regulation of hippocampal neurogenesis in the adult brain. While the majority of studies suggest that this is due to its effect on the survival and differentiation of newborn neurons, it remains unclear whether this signaling directly regulates neural precursor cell (NPC) activity and which of its two receptors, TrkB or the p75 neurotrophin receptor (p75NTR) mediates this effect. Here, we examined both the RNA and protein expression of these receptors and found that TrkB but not p75NTR receptors are expressed by hippocampal NPCs in the adult mouse brain. Using a clonal neurosphere assay, we demonstrate that pharmacological blockade of TrkB receptors directly activates a distinct subpopulation of NPCs. Moreover, we show that administration of ANA‐12, a TrkB‐selective antagonist, in vivo either by systemic intraperitoneal injection or by direct infusion within the hippocampus leads to an increase in the production of new neurons. In contrast, we found that NPC‐specific knockout of p75NTR had no effect on the proliferation of NPCs and did not alter neurogenesis in the adult hippocampus. Collectively, these results demonstrate a novel role of TrkB receptors in directly regulating the activity of a subset of hippocampal NPCs and suggest that the transient blockade of these receptors could be used to enhance adult hippocampal neurogenesis. 相似文献
124.
In mammals, paternal and maternal pronuclei undergo profound chromatin reorganisation upon fertilisation. How these events
are orchestrated within centromeric regions to ensure proper chromosome segregation in the following cellular divisions is
unknown. In this study, we followed the dynamic unfolding of the centromeric regions, i.e. the centric and pericentric satellite
repeats, by DNA fluorescent in situ hybridization (FISH) during the first cell cycle up to the two-cell stage. The distinct
chromatin from female and male gametes both undergo rapid remodelling and reach a zygotic organisation in which the satellites
occupy restricted spatial domains surrounding the nucleolar precursor body. A transition from this zygotic to a somatic cell-like
organisation takes place during the two-cell stage. Using 3D immuno-FISH, we find that, whereas maternal pericentric regions
are marked with H3K9me3, H4K20me3 and HP1β, paternal ones only showed HP1β marking. Thus, despite different chromatin features,
male and female pronuclei organise their centromeric regions in the same way within the nuclei to align chromosomes on the
metaphase plate and segregate them appropriately. Our findings highlight the importance of ensuring a proper centromere function
while preserving the distinction of parental genome origin during the return to totipotency in the zygote.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
125.
Tymchuk WE Sundström LF Devlin RH 《Evolution; international journal of organic evolution》2007,61(5):1225-1237
The purpose of this study was to examine, using a rainbow trout (Oncorhynchus mykiss) model system, the fitness consequences of three generations of introgression of genotypes adapted to two different environments (culture and nature). The experiments also isolated the influence of competitive interactions and risk of predation on the relative growth and survival of the wild and backcrossed lines. Line crosses representing fast-growing pure domestic (D), slow-growing pure wild (W), domestic x wild hybrids (F1), F1 x wild backcrosses (B1), and B1 x wild backcrosses (B2) were generated and reared under (1) culture conditions, (2) seminatural conditions with competition among genotypes, and (3) seminatural conditions under risk of predation. Survival of the fry in a seminatural environment with competition fit an additive model of gene action with the domestic fish having the highest survival and the wild fish the lowest, but under risk of predation outbreeding depression was suggested by low survival of the B2 lines. Evidence of a trade-off in growth and survival under risk of predation along with observations of genetically determined behavioral differences among the strains may provide some explanation for the observed differences in survival among the strains. This information is relevant to improving our evolutionary understanding of the interaction among genomes, and the influence of environment, during hybridization events. Results from this experiment indicate that alteration of phenotype likely played a prominent role in the reduced fitness experienced by progeny produced after three generations of introgression, supporting the theory that disruption of genotypes selected for adaptation to local conditions may be a primary cause of outbreeding depression in species such as salmon. 相似文献
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Woods WS Boettcher JM Zhou DH Kloepper KD Hartman KL Ladror DT Qi Z Rienstra CM George JM 《The Journal of biological chemistry》2007,282(47):34555-34567
Alpha-synuclein (AS) is an intrinsically unstructured protein in aqueous solution but is capable of forming beta-sheet-rich fibrils that accumulate as intracytoplasmic inclusions in Parkinson disease and certain other neurological disorders. However, AS binding to phospholipid membranes leads to a distinct change in protein conformation, stabilizing an extended amphipathic alpha-helical domain reminiscent of the exchangeable apolipoproteins. To better understand the significance of this conformational change, we devised a novel bacteriophage display screen to identify protein binding partners of helical AS and have identified 20 proteins with roles in diverse cellular processes related to membrane trafficking, ion channel modulation, redox metabolism, and gene regulation. To verify that the screen identifies proteins with specificity for helical AS, we further characterized one of these candidates, endosulfine alpha (ENSA), a small cAMP-regulated phosphoprotein implicated in the regulation of insulin secretion but also expressed abundantly in the brain. We used solution NMR to probe the interaction between ENSA and AS on the surface of SDS micelles. Chemical shift perturbation mapping experiments indicate that ENSA interacts specifically with residues in the N-terminal helical domain of AS in the presence of SDS but not in aqueous buffer lacking SDS. The ENSA-related protein ARPP-19 (cAMP-regulated phosphoprotein 19) also displays specific interactions with helical AS. These results confirm that the helical N terminus of AS can mediate specific interactions with other proteins and suggest that membrane binding may regulate the physiological activity of AS in vivo. 相似文献
128.
John M. Boettcher Kevin L. Hartman Daniel T. Ladror Zhi Qi Wendy S. Woods Julia M. George Chad M. Rienstra 《Biomolecular NMR assignments》2007,1(2):167-169
13C, 15N, and 1H chemical shift assignments are presented for the cAMP-regulated phosphoprotein endosulfine-alpha in its free and micelle-bound
states. Secondary chemical shift analysis demonstrates formation of four helices in the micelle-bound state, which are not
present in the absence of detergent. 相似文献
129.
130.
Xolalpa W Vallecillo AJ Lara M Mendoza-Hernandez G Comini M Spallek R Singh M Espitia C 《Proteomics》2007,7(18):3332-3341
Binding and activation of human plasminogen (Plg) to generate the proteolytic enzyme plasmin (Plm) have been associated with the invasive potential of certain bacteria. In this work, proteomic analysis together with ligand blotting assays identified several major Plg-binding spots in Mycobacterium tuberculosis soluble extracts (SEs) and culture filtrate proteins. The identity of 15 different proteins was deduced by N-terminal and/or MS and corresponded to DnaK, GroES, GlnA1, Ag85 complex, Mpt51, Mpt64, PrcB, MetK, SahH, Lpd, Icl, Fba, and EF-Tu. Binding of Plg to recombinant M. tuberculosis DnaK, GlnA1, and Ag85B was further confirmed by ELISA and ligand blotting assays. The binding was inhibited by epsilon-aminocaproic acid, indicating that the interaction involved lysine residues. Plg bound to recombinant mycobacterial proteins was activated to Plm by tissue-type Plg activator. In contrast with recombinant proteins, M. tuberculosis SE enhanced several times the Plg activation mediated by the activator. Interestingly, GlnA1 was able to bind the extracellular matrix (ECM) protein fibronectin. Together these results show that M. tuberculosis posses several Plg receptors suggesting that bound Plg to bacteria surface, can be activated to Plm, endowing bacteria with the ability to break down ECM and basal membranes proteins contributing to tissue injury in tuberculosis. 相似文献