Charge Characteristics of Agouti-Related Protein Implicate Potent Involvement of Heparan Sulfate Proteoglycans in Metabolic Function.

The endogenous melanocortin peptide agouti-related protein (AgRP) plays a well-known role in foraging, but its contribution to metabolic regulation is less understood. Mature AgRP(83-132) has distinct residues for melanocortin receptor binding and heparan sulfate interactions. Here, we show that AgRP increases ad libitum feeding and operant responding for food in mice, decreases oxygen consumption, and lowers body temperature and activity, indicating lower energy expenditure. AgRP increased the respiratory exchange ratio, indicating a reduction of fat oxidation and a shift toward carbohydrates as the primary fuel source. The duration and intensity of AgRP's effects depended on the density of its positively charged amino acids, suggesting that its orexigenic and metabolic effects depend on its affinity for heparan sulfate. These findings may have major clinical implications by unveiling the critical involvement of interactions between AgRP and heparan sulfate to the central regulation of energy expenditure, fat utilization, and possibly their contribution to metabolic disease

Expression of c-fos in Amygdala and Conditioned Immunosuppression

By using c-fos protein production as a marker of neuronal activation, the present work attempts to localize the various subdivisions within the amygdala that may participate in the neural mechanism of conditioned immunosuppression (CIS) in a conditioned taste aversion (CTA) paradigm. CTA and CIS were established by intake of saccharin as the conditioned stimulus (CS) with an injection of cyclophosphamide as an unconditioned stimulus (UCS).After animals were re-exposed to CS alone at intervals of 5 or 30 days after two trials of CS-UCS pairing, both CTA and CIS were assessed and the expression of c-fos protein in the amygdala nucleus was also observed correspondingly. The results showed that CTA occurred on both day 5 and day 30 after conditioning but CIS occurred only on day 5 after conditioning. Furthermore, it was found dense c-fos expression in the amygdaloid central (CeA) in the CS group was observed at the 5 days interval and moderate c-fos immunoreactive inductions at the 30 days interval after re-exposure to CS. In the UCS group, low level of c-fos immunoreactive productions in the CeA were detected at either interval testing. By comparing the results of the 5th day with the 30th day, it suggests that the CeA is an important nucleus related to the modulation of CIS

Optimization and Economic Analysis of Green Public Building Envelope Structure in Chongqing

This article entitled "Optimization and Economic Analysis of Green Public Building Envelope Structure in Chongqing", Authors, Zhiwei Yang Jihuan Chen Xilin Lei Xinran Lin and Shaoting Zhang, published in Volume 19, pp. 77-85 retracted by the authors due to serious similarity problem

Evaluation of vernacular landscape attraction for traditional village tourism: A case study of Yongfeng Village in Lanzhou

In the context of rural revitalization, the benign development of traditional village tourism is of great significance to the implementation of Rural Revitalization Strategy in China. Taking Yongfeng Village in Lanzhou as the research object, this paper discusses the evaluation method of vernacular landscape attraction. Through the research on the internal and external environment and historical culture of Yongfeng village, this paper constructed the rural landscape attraction system and evaluation index. With the help of the effective data of the questionnaire survey, this paper made an empirical calculation of the rural landscape attraction intensity of Yongfeng Village by using the methods of AHP and factor analysis. The results show that: (1) the protection and rational use of historical and cultural resources is the core content to improve the attractiveness of rural tourism landscape; (3) the internal space is the connotation externalization of the attraction of rural landscape, Renovating the historical built-up environment is the material basis for attracting tourists’ in-depth experience. Therefore, the effective way to enhance the attraction is to activate and integrate the material and non-material rural landscape resources of traditional villages

Roles of BDNF, dopamine D-3 receptors, and their interactions in the expression of morphine-induced context-specific locomotor sensitization

Drug seeking, craving, and relapse can be triggered by environmental stimuli that acquire motivational salience through repeated associations with the drug&#39;s effects. Previous studies indicated that the dopamine D-3 receptor (Drd3) might be involved in the expression of drug-conditioned responses in rats, and brain-derived neurotrophic factor (BDNF) could modulate Drd3 expression in the nucleus accumbens (NAc). However, the involvement of neural regions with Drd3 activation and the underlying interaction between BDNF and Drd3 in the expression of behavioral responses controlled by a drug-associated environment have remained poorly understood. The present study used a conditioning procedure to assess the roles of BDNF, Drd3, and their interactions in the NAc in the expression of morphine-induced context-specific locomotor sensitization. We showed that the expression of locomotor sensitization in the morphine-paired environment was accompanied by significantly increased expression of Drd3 mRNA and BDNF mRNA and protein levels. Both sensitized locomotion in morphine-paired rats and enhanced Drd3 mRNA were suppressed by intra-NAc infusion of anti-tyrosine kinase receptor B (TrkB) IgG. Furthermore, intra-NAc infusion of the Drd3-selective antagonist SB-277011A significantly decreased the expression of context-specific locomotor sensitization and upregulated BDNF mRNA. Altogether, these results suggest that BDNF/TrkB signaling and activation of Drd3 in the NAc are required for the expression of morphine-induced context-specific locomotor sensitization. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.</p

Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse

Abstract Substance abuse is a pressing problem with few therapeutic options. The identification of addiction resilience factors is a potential strategy to identify new mechanisms that can be targeted therapeutically. Heparan sulfate (HS) is a linear sulfated polysaccharide that is a component of the cell surface and extracellular matrix. Heparan sulfate modulates the activity and distribution of a set of negatively charged signaling peptides and proteins — known as the HS interactome — by acting as a co-receptor or alternative receptor for growth factors and other signaling peptides and sequestering and localizing them, among other actions. Here, we show that stimulants like cocaine and methamphetamine greatly increase HS content and sulfation levels in the lateral hypothalamus and that HS contributes to the regulation of cocaine seeking and taking. The ability of the HS-binding neuropeptide glial-cell-line-derived neurotrophic factor (GDNF) to increase cocaine intake was potentiated by a deletion that abolished its HS binding. The delivery of heparanase, the endo-β-D-glucuronidase that degrades HS, accelerated the acquisition of cocaine self-administration and promoted persistent responding during extinction. Altogether, these results indicate that HS is a resilience factor for cocaine abuse and a novel therapeutic target for the treatment of cocaine addiction

Acupuncture Reduces Apoptosis of Granulosa Cells in Rats with Premature Ovarian Failure Via Restoring the PI3K/Akt Signaling Pathway

Acupuncture is widely recognized as an effective therapy for premature ovarian failure (POF) in clinical, but information about its potential mechanisms is rarely explored. To investigate the mechanism, fifty SD female rats were randomly divided into normal group, POF group, POF+estradiol-valerate group (abbreviated as estradiol group), and POF+acupuncture group (abbreviated as acupuncture group). The estrous cycle of the rats was tracked by vaginal smears. Their ovaries morphology was observed by hematoxylin-eosin staining. The apoptotic level of granulosa cells was detected by in situ TUNEL fluorescence staining assay. Serum follicle-stimulating hormone (FSH) and estrogen (E2) levels were measured by enzyme-linked-immunosorbent-assay (ELISA). Protein and gene expression of PI3K, Akt, bcl-2, and bax were detected by Western blotting and qPCR. In the acupuncture and estradiol groups, compared with the POF group as controls, the apoptosis number of granulosa cells was significantly decreased (p &lt; 0.05). FSH levels were decreased, while E2 levels were increased (p &gt; 0.05). The gene and protein expression levels of PI3K, Akt, and bcl-2 were increased, while the expression levels of bax were decreased (p &lt; 0.05), and the protein expression level of p-Akt increased. There was no significant difference between the acupuncture group and the estradiol group (p &gt; 0.05). Acupuncture was able to regulate hormone levels in POF rats, up-regulate PI3K/Akt signaling pathway, and reduce the apoptosis of granulosa cells. This may be one of the mechanisms of acupuncture treating premature ovarian failure