Wigginspalmer8836

Birdsong learning, like human speech, depends on the early memorization of auditory models, yet how initial auditory experiences are formed and consolidated is unclear. In songbirds, a putative cortical locus is the caudomedial nidopallium (NCM), and one mechanism to facilitate auditory consolidation is 17β-estradiol (E2), which is associated with human speech-language development, and is abundant in both NCM and human temporal cortex. Circulating and NCM E2 levels are dynamic during learning, suggesting E2's involvement in encoding recent auditory experiences. Therefore, we tested this hypothesis in juvenile male songbirds using a comprehensive assessment of neuroanatomy, behavior, and neurophysiology. First, we found that brain aromatase expression, and thus the capacity to synthesize neuroestrogens, remains high in the auditory cortex throughout development. Further, while systemic estrogen synthesis blockade suppressed juvenile song production, neither systemic nor unilateral E2 synthesis inhibition in NCM disrupted eventual song imitation. Surprisingly, early life neuroestrogen synthesis blockade in NCM enhanced the neural representations of both the birds' own song and the tutor song in NCM and a downstream sensorimotor region, HVC, respectively. selleck Taken together, these findings indicate that E2 plays a multifaceted role during development, and that, contrary to prediction, tutor song memorization is unimpaired by unilateral estrogen synthesis blockade in the auditory cortex.Neuronal excitability is classified as type I, II, or III, according to the responses of electronic activities, which play different roles. In the present paper, the effect of an excitatory autapse on type III excitability is investigated and compared to type II excitability in the Morris-Lecar model, based on Hopf bifurcation and characteristics of the nullcline. The autaptic current of a fast-decay autapse produces periodic stimulations, and that of a slow-decay autapse highly resembles sustained stimulations. Thus, both fast- and slow-decay autapses can induce a resting state for type II excitability that changes to repetitive firing. However, for type III excitability, a fast-decay autapse can induce a resting state to change to repetitive firing, while a slow-decay autapse can induce a resting state to change to a resting state following a transient spike instead of repetitive spiking, which shows the abnormal phenomenon that a stronger excitatory effect of a slow-decay autapse just induces weaker responses. Our results uncover a novel paradoxical phenomenon of the excitatory effect, and we present potential functions of fast- and slow-decay autapses that are helpful for the alteration and maintenance of type III excitability in the real nervous system related to neuropathic pain or sound localization.A natural low-methoxyl pectin (LAHP), was extracted with oxalic acid solution from dried heads of sunflower (Helianthus annuus L.). The single-factor experiments and response surface methodology (RSM) were used to optimize LAHP extraction conditions. The extraction yield of LAHP was 18.83 ± 0.21%, and the uronic acid content was 85.43 ± 2.9% obtained under the optimized conditions (temperature of 96 °C, time of 1.64 h, oxalic acid concentration of 0.21%). Experimentally obtained values were in agreement with those predicted by RSM model, indicating suitability of the employed model and the success of RSM in optimizing the extraction conditions. LAHP has been characterized by ash content, degree of esterification (DE), galacturonic acid (GalA) content, molecular weight and intrinsic viscosity meanwhile commercial low-methoxyl pectin (CLMP) as comparison. This study finds out a potential source of natural LMP which expands the application scope of sunflower heads. It is an efficient reuse of waste resources and provides a novel thought to explore the natural resources for food and pharmaceutical applications.Tumor invasion underlies further metastasis, the leading cause for cancer-related deaths. Deregulation of microRNAs has been identified associated with the malignant behavior of various cancers, including lung adenocarcinoma (LUAD), the major subtype of lung cancer. Here, we showed the significantly positive correlation between miR-629-5p level and tumor invasion in LUAD specimens (n = 49). In a human LUAD metastasis mouse model, H1650 cells (high level of miR-629-5p) were more aggressive than A549 cells (low level of miR-629-5p) in vivo, including higher incidence of vascular invasion and pulmonary colonization. Ectopic expression of miR-629-5p in A549 cells also increased their invasive capability. Then we identified that miR-629-5p promotes LUAD invasion in a mode of dual regulation via tumor cells invasion and endothelial cells permeability, respectively. In tumor cells, miR-629-5p enhanced motility and invasiveness of tumor cells by directly targeting PPWD1 (a cyclophilin), which clinically related to tumor invasion in LUAD specimens. Restoring PPWD1 protein significantly attenuated the invasion-promoting effects of miR-629-5p. Besides, exosomal-miR-629-5p secreted from tumor cells could be transferred to endothelial cells and increased endothelial monolayers permeability by suppressing CELSR1 (a nonclassic-type cadherin), which had a low level in the endothelial cells of invasive LUAD specimens. Activating the expression of CELSR1 in endothelial cells markedly blocked the effect of miR-629-5p. Our study suggests the dual roles of miR-629-5p in tumor cells and endothelial cells for LUAD invasion, implying a therapeutic option to targeting miR-629-5p using the "one stone, two birds" strategy in LUAD.Activation of the Hedgehog (Hh) signaling pathway by mutations within its components drives the growth of several cancers. However, the role of Hh pathway activation in lung cancers has been controversial. Here, we demonstrate that the canonical Hh signaling pathway is activated in lung stroma by Hh ligands secreted from transformed lung epithelia. Genetic deletion of Shh, the primary Hh ligand expressed in the lung, in KrasG12D/+;Trp53fl/fl autochthonous murine lung adenocarcinoma had no effect on survival. Early abrogation of the pathway by an anti-SHH/IHH antibody 5E1 led to significantly worse survival with increased tumor and metastatic burden. Loss of IHH, another Hh ligand, by in vivo CRISPR led to more aggressive tumor growth suggesting that IHH, rather than SHH, activates the pathway in stroma to drive its tumor suppressive effects-a novel role for IHH in the lung. Tumors from mice treated with 5E1 had decreased blood vessel density and increased DNA damage suggestive of reactive oxygen species (ROS) activity.