Dendrites are a major determinant of how neurons integrate and process incoming information, and thus, they play a vital role in the functional properties of neural circuits. During the past 30 years, it has become clear that the functional organization of the adult neocortex (and other parts of the brain) is dynamic and can change in response to experimental manipulations that affect cortical activity patterns. A variety of changes in the cortical microcircuit, including changes in synaptic function, neuronal membrane properties, and axonal trajectories, are associated with these functional changes. In this review, the authors discuss changes in the structure of dendrites in the adult neocortex, the sorts of experimental manipulations that induce these changes, and some possible molecular mechanisms that may underlie the changes. 相似文献
Microglial activation and macrophage infiltration into the CNS are common features of CNS autoimmune disease and of chronic
neurodegenerative diseases. Because these cells largely express an overlapping set of common macrophage markers, it has been
difficult to separate their respective contributions to disease onset and progression. This problem is further confounded
by the many types of macrophages that have been termed microglia. Several approaches, ranging from molecular profiling of
isolated cells to the generation of irradiation chimeric rodent models, are now beginning to generate rudimentary definitions
distinguishing the various types of microglia and macrophages found within the CNS and the potential roles that these cells
may play in health and disease. 相似文献
Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion. 相似文献
Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.
Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI])?=?0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value?=?0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.
Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC. 相似文献
Injecting drug use is commonly reported among gay and bisexual men in Australia. We examined the prevalence and covariates of injecting drug use among men participating in the Sydney Gay Community Periodic Survey between 2004–06 and 2011. In 2004–06, data was collected about which drugs were injected, while in 2011, data was collected about hepatitis C (HCV) and esoteric sexual practices. In 2004–06, 5.6 % of men reported injecting drugs in the previous 6 months; 3.4 % reported methamphetamine injection and 0.4 % heroin injection. In 2011, men who injected drugs were less likely to be employed full-time, and more likely to be HCV-positive, HIV-positive, to have used party drugs for sex, and to have engaged in esoteric sexual practices. The strong associations between injecting drug use, sexual risk practices and blood-borne virus infection suggests the need for combined sexual health and harm reduction services for gay and bisexual men who inject drugs. 相似文献
Results: Flies reared on low quality food exhibit decreased pigmentation, which can be phenocopied by inhibiting expression of the Insulin receptor (InR) throughout the entire fly during mid to late pupation. The loss of Insulin signaling through PI3K/Akt and FOXO in the epidermis underlying the developing adult cuticle causes a similar decrease in adult pigmentation, suggesting that Insulin signaling acts in a cell autonomous manner to regulate cuticle melanization. In addition, TOR signaling increases pigmentation in a cell autonomous manner, most likely through increased S6K activity. 相似文献