Dopaminergic regeneration by neurturin-overexpressing c17.2 neural stem cells in a rat model of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Genetically engineered neural stem cell (NSC) lines are promising vectors for the treatment of neurodegenerative diseases, particularly Parkinson's disease (PD). Neurturin (NTN), a member of the glial cell line-derived neurotrophic factor (GDNF) family, has been demonstrated to act specifically on mesencephalic dopaminergic neurons, suggesting its therapeutic potential for PD. In our previous work, we demonstrated that NTN-overexpressing c17.2 NSCs exerted dopaminergic neuroprotection in a rat model of PD. In this study, we transplanted NTN-c17.2 into the striatum of the 6-hydroxydopamine (6-OHDA) PD model to further determine the regenerative effect of NTN-c17.2 on the rat models of PD.</p> <p>Results</p> <p>After intrastriatal grafting, NTN-c17.2 cells differentiated and gradually downregulated nestin expression, while the grafts stably overexpressed NTN. Further, an observation of rotational behavior and the contents of neurotransmitters tested by high-performance liquid chromatography showed that the regenerative effect of the NTN-c17.2 group was significantly better than that of the Mock-c17.2 group, and the regenerative effect of the Mock-c17.2 group was better than that of the PBS group. Further research through reverse-transcriptase polymerase chain reaction assays and in vivo histology revealed that the regenerative effect of Mock-c17.2 and NTN-c17.2 cell grafts may be attributed to the ability of NSCs to produce neurotrophic factors and differentiate into tyrosine hydroxylase-positive cells.</p> <p>Conclusion</p> <p>The transplantation of NTN-c17.2 can exert neuroregenerative effects in the rat model of PD, and the delivery of NTN by NSCs may constitute a very useful strategy in the treatment of PD.</p

A possible explanation of the phase diagram of cuprate superconductors

A d-p pairing curve that is consistent with the pseudogap curve observed in experiments is found on a d-p model on phonon mechanism. On the discovery we suggest that there are two pseudogaps associated with the nearly localized d-p pairs and nearly free p-p pairs. The p-p pairs look like bosons and are responsible for superconductivities.Comment: 6 pages, 3 figure

Experimental warming causes mismatches in alpine plant-microbe-fauna phenology

Long-term observations have shown that many plants and aboveground animals have changed their phenology patterns due to warmer temperatures over the past decades. However, empirical evidence for phenological shifts in alpine organisms, particularly belowground organisms, is scarce. Here, we investigate how the activities and phenology of plants, soil microbes, and soil fauna will respond to warming in an alpine meadow on the Tibetan Plateau, and whether their potential phenological changes will be synchronized. We experimentally simulate an increase in soil temperature by 2-4 degrees C according to future projections for this region. We find that warming promotes plant growth, soil microbial respiration, and soil fauna feeding by 8%, 57%, and 20%, respectively, but causes dissimilar changes in their phenology during the growing season. Specifically, warming advances soil faunal feeding activity in spring and delays it in autumn, while their peak activity does not change; whereas warming increases the peak activity of plant growth and soil microbial respiration but with only minor shifts in their phenology. Such phenological asynchrony in alpine organisms may alter ecosystem functioning and stability.Phenological shifts driven by climate change are well-studied in plants and aboveground animals, but scarcely in belowground biota. Here, the authors show that soil warming causes phenological mismatches between plants, soil microbes and soil microarthropods in an alpine meadow

High circulating CD39+ regulatory T cells predict poor survival for sepsis patients

SummaryBackgroundSepsis encompasses two phases, the ‘hyper’-reactive phase and the ‘hypo’-reactive phase. The initial inflammatory stage is quickly counterbalanced by an anti-inflammatory response, which compromises the immune system, leading to immune suppression. Regulatory T cells (Tregs) have been implicated in the pathogenesis of sepsis by inducing immunosuppression; however, the role of CD39+ Tregs in the process of sepsis is uncertain. This study investigated the dynamic levels of CD39+ Tregs and their phenotypic change in sepsis.MethodsFourteen patients with systemic inflammatory response syndrome (SIRS), 42 patients with sepsis, and 14 healthy controls were enrolled. Sequential blood samples were used to analyze the numbers of CD39+ Tregs and their phenotypic changes. Survival at 28 days was used to evaluate the capacity of CD39+ Treg levels to predict mortality in sepsis patients.ResultsSepsis patients displayed a high percentage (3.13%, 1.46%, and 0.35%, respectively) and mean fluorescence intensity (MFI) (59.65, 29.7, and 24.3, respectively) of CD39+ Tregs compared with SIRS patients and healthy subjects. High-level expression of CD39+ Tregs was correlated with the severity of sepsis, which was reflected by the sepsis-related organ failure assessment score (r=0.322 and r=0.31, respectively). In addition, the expression of CD39+ Tregs was associated with survival of sepsis patients (p<0.01). By receiver-operating characteristic (ROC) curve analysis, the percentage and MFI of CD39+ Tregs showed similar sensitivities and specificities to predict mortality (74.2% and 85.1%, and 73.9% and 84.1%, respectively). Using Kaplan–Meier curves to assess the impact of CD39+ Tregs percentage and MFI on overall survival, we found that a high CD39+ Tregs percentage (p<0.001; >4.1%) and MFI (p<0.001; >49.2) were significantly associated with mortality. Phenotypically, CD39+ Tregs from sepsis patients showed high expression of CD38 and PD-1 (p<0.01 and p<0.01 respectively).ConclusionsIncreased expression of CD39+ Tregs was associated with a poor prognosis for sepsis patients, which suggests that CD39+ Treg levels could be used as a biomarker to predict the outcome of sepsis patients

Synthesis, biological evaluation, and physicochemical property assessment of 4-substituted 2-phenylaminoquinazolines as Mer tyrosine kinase inhibitors

Current results identified 4-substituted 2-phenylaminoquinazoline compounds as novel Mer tyrosine kinase (Mer TK) inhibitors with a new scaffold. Twenty-one 2,4-disubstituted quinazolines (series 4-7) were designed, synthesized, and evaluated against Mer TK and a panel of human tumor cell lines aimed at exploring new Mer TK inhibitors as novel potential antitumor agents. A new lead, 4b, was discovered with a good balance between high potency (IC50 0.68μM) in the Mer TK assay and antiproliferative activity against MV4-11 (GI50 8.54μM), as well as other human tumor cell lines (GI50<20μM), and a desirable druglike property profile with low logP value (2.54) and high aqueous solubility (95.6μg/mL). Molecular modeling elucidated an expected binding mode of 4b with Mer TK and necessary interactions between them, thus supporting the hypothesis that Mer TK might be a biologic target of this kind of new active compound

Earthquake Forecast via Neutrino Tomography

We discuss the possibility of forecasting earthquakes by means of (anti)neutrino tomography. Antineutrinos emitted from reactors are used as a probe. As the antineutrinos traverse through a region prone to earthquakes, observable variations in the matter effect on the antineutrino oscillation would provide a tomography of the vicinity of the region. In this preliminary work, we adopt a simplified model for the geometrical profile and matter density in a fault zone. We calculate the survival probability of electron antineutrinos for cases without and with an anomalous accumulation of electrons which can be considered as a clear signal of the coming earthquake, at the geological region with a fault zone, and find that the variation may reach as much as 3% for $\bar \nu_e$ emitted from a reactor. The case for a $\nu_e$ beam from a neutrino factory is also investigated, and it is noted that, because of the typically high energy associated with such neutrinos, the oscillation length is too large and the resultant variation is not practically observable. Our conclusion is that with the present reactor facilities and detection techniques, it is still a difficult task to make an earthquake forecast using such a scheme, though it seems to be possible from a theoretical point of view while ignoring some uncertainties. However, with the development of the geology, especially the knowledge about the fault zone, and with the improvement of the detection techniques, etc., there is hope that a medium-term earthquake forecast would be feasible.Comment: 6 pages, 4 figures, 1 tabl