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211.
Beta‐diversity metrics of the upper digestive tract microbiome are associated with body mass index 下载免费PDF全文
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Richelle Sopko You Bin Lin Kalpana Makhijani Brandy Alexander Norbert Perrimon Katja Brückner 《PLoS genetics》2015,11(3)
In multicellular organisms, cell number is typically determined by a balance of intracellular signals that positively and negatively regulate cell survival and proliferation. Dissecting these signaling networks facilitates the understanding of normal development and tumorigenesis. Here, we study signaling by the Drosophila PDGF/VEGF Receptor (Pvr) in embryonic blood cells (hemocytes) and in the related cell line Kc as a model for the requirement of PDGF/VEGF receptors in vertebrate cell survival and proliferation. The system allows the investigation of downstream and parallel signaling networks, based on the ability of Pvr to activate Ras/Erk, Akt/TOR, and yet-uncharacterized signaling pathway/s, which redundantly mediate cell survival and contribute to proliferation. Using Kc cells, we performed a genome wide RNAi screen for regulators of cell number in a sensitized, Pvr deficient background. We identified the receptor tyrosine kinase (RTK) Insulin-like receptor (InR) as a major Pvr Enhancer, and the nuclear hormone receptors Ecdysone receptor (EcR) and ultraspiracle (usp), corresponding to mammalian Retinoid X Receptor (RXR), as Pvr Suppressors. In vivo analysis in the Drosophila embryo revealed a previously unrecognized role for EcR to promote apoptotic death of embryonic blood cells, which is balanced with pro-survival signaling by Pvr and InR. Phosphoproteomic analysis demonstrates distinct modes of cell number regulation by EcR and RTK signaling. We define common phosphorylation targets of Pvr and InR that include regulators of cell survival, and unique targets responsible for specialized receptor functions. Interestingly, our analysis reveals that the selection of phosphorylation targets by signaling receptors shows qualitative changes depending on the signaling status of the cell, which may have wide-reaching implications for other cell regulatory systems. 相似文献
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Attenuation of microRNA‐16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy 下载免费PDF全文
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Background
Bipolar disorder types I (BD I) and II (BD II) behave differently in clinical manifestations, normal personality traits, responses to pharmacotherapies, biochemical backgrounds and neuroimaging activations. How the varied emotional states of BD I and II are related to the comorbid personality disorders remains to be settled.Methods
We therefore administered the Plutchick – van Praag Depression Inventory (PVP), the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32), and the Parker Personality Measure (PERM) in 37 patients with BD I, 34 BD II, and in 76 healthy volunteers.Results
Compared to the healthy volunteers, patients with BD I and II scored higher on some PERM styles, PVP, MDQ and HCL-32 scales. In BD I, the PERM Borderline style predicted the PVP scale; and Antisocial predicted HCL-32. In BD II, Borderline, Dependant, Paranoid (-) and Schizoid (-) predicted PVP; Borderline predicted MDQ; Passive-Aggressive and Schizoid (-) predicted HCL-32. In controls, Borderline and Narcissistic (-) predicted PVP; Borderline and Dependant (-) predicted MDQ.Conclusion
Besides confirming the different predictability of the 11 functioning styles of personality disorder to BD I and II, we found that the prediction was more common in BD II, which might underlie its higher risk of suicide and poorer treatment outcome. 相似文献217.
Ho Young Yune Sung Phil Chung Yoo Seok Park Hyun Soo Chung Hye Sun Lee Jong Wook Lee Jong Woo Park Je Sung You Incheol Park Hahn Shick Lee 《PloS one》2015,10(3)
Background
The post-resuscitation phase after out-of-hospital cardiac arrest (OHCA) is characterised by a systemic inflammatory response (e.g., severe sepsis), for which the immature granulocyte count is a diagnostic marker. In this study we evaluated the prognostic significance of the delta neutrophil index (DNI), which is the difference in leukocyte subfractions as assessed by an automated blood cell analyser, for early mortality after OHCA.Materials and Methods
OHCA records from the emergency department cardiac arrest registry were retrospectively analysed. Patients who survived at least 24 h after return of spontaneous circulation were included in the analysis. We evaluated mortality and cerebral performance category scores at 30 days.Results
A total of 83 patients with OHCA were included in the study. Our results showed that DNI >8.4% on day 1 (hazard ratio [HR], 3.227; 95% CI, 1.485–6.967; p = 0.001) and DNI >10.5% on day 2 (HR, 3.292; 95% CI, 1.662–6.519; p<0.001) were associated with increased 30-day mortality in patients with OHCA. Additionally, DNI >8.4% on day 1 (HR, 2.718; 95% CI, 1.508–4.899; p<0.001) and DNI >10.5% on day 2 (HR, 1.709; 95% CI, 1.051–2.778; p = 0.02) were associated with worse neurologic outcomes 30 days after OHCA.Conclusion
A higher DNI is a promising prognostic marker for 30-day mortality and neurologic outcomes after OHCA. Our findings indicate that patients with elevated DNI values after OHCA might be closely monitored so that appropriate treatment strategies can be implemented. 相似文献218.
Kwangsun Yoo Sun Ju Chung Ho Sung Kim Oh-hyeon Choung Young-Beom Lee Mi-Jung Kim Sooyeoun You Yong Jeong 《PloS one》2015,10(4)
Background
Recently, non-motor symptoms of Parkinson’s disease (PD) have been considered crucial factors in determining a patient’s quality of life and have been proposed as the predominant features of the premotor phase. Researchers have investigated the relationship between non-motor symptoms and the motor laterality; however, this relationship remains disputed. This study investigated the neural connectivity correlates of non-motor and motor symptoms of PD with respect to motor laterality.Methods
Eight-seven patients with PD were recruited and classified into left-more-affected PD (n = 44) and right-more affected PD (n = 37) based on their MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale) motor examination scores. The patients underwent MRI scanning, which included resting fMRI. Brain regions were labeled as ipsilateral and contralateral to the more-affected body side. Correlation analysis between the functional connectivity across brain regions and the scores of various symptoms was performed to identify the neural connectivity correlates of each symptom.Results
The resting functional connectivity centered on the ipsilateral inferior orbito-frontal area was negatively correlated with the severity of non-motor symptoms, and the connectivity of the contralateral inferior parietal area was positively correlated with the severity of motor symptoms (p < 0.001, |r| > 0.3).Conclusions
These results suggest that the inferior orbito-frontal area may play a crucial role in non-motor dysfunctions, and that the connectivity information may be utilized as a neuroimaging biomarker for the early diagnosis of PD. 相似文献219.
Objective
To determine the clinicopathologic and immunohistochemical predictors of the persistence/recurrence of cervical intraepithelial neoplasia (CIN) after cervical conization.Methods
Medical records of 502 patients who received cervical conization treatment of CIN between 2005 and 2012 were reviewed. The clinicopathologic parameters were analyzed using Cox hazard regression. Fifty patients with CIN persistence/recurrence were matched to 50 cases without CIN persistence/recurrence. These 100 cervical specimens were assessed for expression of insulin-like growth factor II messenger RNA (mRNA)-binding protein 3 (IMP3), targeting protein for xenopus kinesin-like protein 2 (TPX2), and programmed cell death-1 ligand-1 (PD-L1) using immunohistochemical staining.Results
Multivariate analysis found that the independent predictors of CIN persistence/recurrence were positive surgical margin (hazard ratio 5.777, 95% confidence interval 2.334–14.301, p < 0.001) and human papilloma virus persistence for 6 months (hazard ratio 20.685, 95% confidence interval 7.350–57.657, p < 0.001). Co-expression of TPX2 and PD-L1 was significantly higher in CIN persistence/recurrence group than the group without CIN persistence/recurrence (p = 0.013). The depth of glandular involvement (GI) was less than 3mm in about 86.8% (59/68) CIN2-3 lesions, However, No statistically significant associations between GI and persistence/recurrence were observed (P = 0.58).Conclusion
Positive surgical margin, HPV persistence, and expression of both TPX2 and PD-L1 are associated with persistence/recurrence of cervical intraepithelial neoplasia after cervical conization. 相似文献220.
Pengfei Cai Geoffrey N. Gobert Hong You Mary Duke Donald P. McManus 《PLoS neglected tropical diseases》2015,9(7)