Double deletion of orexigenic neuropeptide Y and dynorphin results in paradoxical obesity in mice

Objective

Orexigenic neuropeptide Y (NPY) and dynorphin (DYN) regulate energy homeostasis. Single NPY or dynorphin deletion reduces food intake or increases fat loss. Future developments of obesity therapeutics involve targeting multiple pathways. We hypothesised that NPY and dynorphin regulate energy homeostasis independently, thus double NPY and dynorphin ablation would result in greater weight and/or fat loss than the absence of NPY or dynorphin alone.

Design and methods

We generated single and double NPY and dynorphin knockout mice (NPYΔ, DYNΔ, NPYDYNΔ) and compared body weight, adiposity, feeding behaviour, glucose homeostasis and brown adipose tissue uncoupling protein-1 (UCP-1) expression to wildtype counterparts.

Results

Body weight and adiposity were significantly increased in NPYDYNΔ, but not in NPYΔ or DYNΔ. This was not due to increased food intake or altered UCP-1 expression, which were not significantly altered in double knockouts. NPYDYNΔ mice demonstrated increased body weight loss after a 24-h fast, with no effect on serum glucose levels after glucose injection.

Conclusions

Contrary to the predicted phenotype delineated from single knockouts, double NPY and dynorphin deletion resulted in heavier mice, with increased adiposity, despite no significant changes in food intake or UCP-1 activity. This indicates that combining long-term opioid antagonism with blockade of NPY-ergic systems may not produce anti-obesity effects.     

骨关节炎中影响软骨细胞凋亡的因素

目的:近年来国外对骨关节炎的发生及发展机制有许多研究成果,骨关节炎中软骨细胞凋亡影响因素的研究颇具新意。资料来源:应用计算机检索Medline1985-01/2004-12与骨关节炎中软骨细胞凋亡相关的文献,检索词“osteoarthritis,chondrocyte,apoptosis”并限定文献语种为English。资料选择:对资料的摘要进行阅读初审,选取包括试验组和对照组的文献,开始查找全文。纳入标准:①随机对照试验。②试验包括对照组。排除标准:①没有设立对照组的文献。②综述类文献、Meta分析、重复研究。资料提炼:共收集到111篇关于骨关节炎中软骨细胞凋亡影响因素的试验,纳入符合标准的文献35篇。排除的文献为综述类文献28篇和重复研究48篇。35篇文献多为软骨细胞体外培养有关的试验,分别对各种凋亡影响因素进行评价。资料综合:在骨关节炎患者和老年人的软骨中,由于细胞外基质成分降解或通过高级糖基化、酪氨酸亚硝基化等修饰作用破坏了正常的细胞外基质从而使软骨细胞发生炎症反应并促进其死亡。各种机械性刺激是软骨细胞功能的重要调节因素,施加机械压力的加速率也决定软骨损伤和软骨细胞死亡的类型与程度。经某些细胞因子作用的正常软骨和分离培养的软骨细胞产生高水平的NO,而NO产物又能诱导软骨细胞死亡。肿瘤坏死因子受体超家族成员与相应的死亡配体结合能激活凋亡信号通路,当存在其他前凋亡因子或缺乏某些促存活因子时肿瘤坏死因子α能诱导软骨细胞凋亡。正是由于能量代谢受损使软骨细胞对其他的致死因子变得更加敏感。在发育和骨关节疾病相关过程中,软骨细胞的死亡虽然有p53的参与,但其精确的机制有待阐明,同时没有足够的直接证据表明c-myc能够影响软骨细胞的存活或死亡。结论:骨关节炎中影响软骨细胞凋亡的因素很多,机制复杂,许多因素导致软骨细胞凋亡的通路有待进一步阐明。     

A novel reference coordinate system to locate the inferomedial point of the transverse-sigmoid sinus junction

Background

A coordinate system was previously developed to identify landmarks on the skull surface to help locate the transverse-sigmoid sinus junction in order to reduce surgical morbidity in retrosigmoid craniotomy; however, in practice we found that this system has important flaws.

Objective

To develop and evaluate a novel reference coordinate system to precisely locate the inferomedial point of the transverse-sigmoid sinus junction (IMTS) and evaluate the effect of gender and skull side (left or right).

Methods

Forty-two adult skulls (84 sides) were obtained for analyses. The X-axis was defined by point A (where the upper edge of the zygomatic arch joins with the frontal process of the zygomatic bone) and point B (where the upper edge of the zygomatic arch blends posterosuperiorly into the supramastoid crest). The Y-axis was defined by the line perpendicular to the X-axis and extending across the tip of the mastoid. The x and y coordinates of IMTS (IMTS-x and IMTS-y) were measured in this coordinate system.

Results

There were 20 male skulls and 22 female skulls. The mean IMTS-x measurements were significantly higher on the right side compared with the left side in both males and females. For the left skull side, the mean IMTS-y measurements were significantly lower in females compared with males.

Conclusion

This novel reference coordinate system may be a reliable and practical method for identifying the IMTS during retrosigmoid craniotomy. There are significant differences in location of the axes with regard to gender and skull side.     

Detection of deception based on fMRI activation patterns underlying the production of a deceptive response and receiving feedback about the success of the deception after a mock murder crime

The ability of a deceiver to track a victim’s ongoing judgments about the truthfulness of the deceit can be critical for successful deception. However, no study has yet investigated the neural circuits underlying receiving a judgment about one’s lie. To explore this issue, we used a modified Guilty Knowledge Test in a mock murder situation to simultaneously record the neural responses involved in producing deception and later when judgments of that deception were made. Producing deception recruited the bilateral inferior parietal lobules (IPLs), right ventral lateral prefrontal (VLPF) areas and right striatum, among which the activation of the right VLPF contributed mostly to diagnosing the identities of the participants, correctly diagnosing 81.25% of ‘murderers’ and 81.25% of ‘innocents’. Moreover, the participant’s response when their deception was successful uniquely recruited the right middle frontal gyrus, bilateral IPLs, bilateral orbitofrontal cortices, bilateral middle temporal gyrus and left cerebellum, among which the right IPL contributed mostly to diagnosing participants’ identities, correctly diagnosing 93.75% of murderers and 87.5% of innocents. This study shows that neural activity associated with being a successful liar (or not) is a feasible indicator for detecting lies and may be more valid than neural activity associated with producing deception.     

Isolation and characterization of 57 novel polynucleotide microsatellites from yellow catfish (Pelteobagrus fulvidraco) genome for genetic analysis

Yellow catfish (Pelteobagrus fulvidraco) is one of the important economic freshwater fish in Eastern Asia. In recent years, the wild resources were decreased sharply due to overfishing and pollution. It is necessary to conserve the wild stocks for the sustainable use of the species. In this study, 200 microsatellite markers were isolated from yellow catfish genome using Roche 454 pyrosequencing method. Among these markers, 57 exhibited polymorphism in yellow catfish population collected from Songhua River in China. The number of alleles ranged from 2 to 13 and the number of effect alleles ranged from 1.112 to 8.980. The observed heterozygosity (H _o) and the expected heterozygosity (H _e) varied from 0.106 to 0.957 and from 0.102 to 0.898, respectively. Most loci conformed to Hardy–Weinberg equilibrium with the exclusion of five loci. These polymorphic loci will be valuable for population genetic structure and genetic conservation for the P. fulvidraco.