Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells

IL-2 is the primary growth factor for promoting survival and proliferation of activated T cells that occurs following engagement of the Janus Kinase (JAK)1-3/and Signal Transducer and Activator of Transcription (STAT) 5 signaling pathway. STAT5 has two isoforms: STAT5A and STAT5B ( commonly referred to as STAT5) which, in T cells, play redundant roles transcribing cell cycle and survival genes. As such, inhibition of STAT5 by a variety of mechanisms can rapidly induce apoptosis in certain lymphoid tumor cells, suggesting that it and its target genes represent therapeutic targets to control certain lymphoid diseases. To search for these molecules we aligned IL-2 regulated genes detected by Affymetrix gene expression microarrays with the STAT5 cistrome identified by chip-on-ChIP analysis in an IL-2-dependent human leukemia cell line, Kit225. Select overlapping genes were then validated using qRT(2)PCR medium-throughput arrays in human PHA-activated PBMCs. Of 19 putative genes, one key regulator of T cell receptor signaling, PDE4B, was identified as a novel target, which was readily up-regulated at the protein level (3 h) in IL-2 stimulated, activated human PBMCs. Surprisingly, only purified CD8+ primary T-cells expressed PDE4B, but not CD4+ cells. Moreover, PDE4B was found to be highly expressed in CD4+ lymphoid cancer cells, which suggests that it may represent a physiological role unique to the CD8+ and lymphoid cancer cells and thus might represent a target for pharmaceutical intervention for certain lymphoid diseases

Monsoon versus Uplift in Southwestern China–Late Pliocene Climate in Yuanmou Basin, Yunnan

Yuanmou Basin of Yunnan, SW China, is a famous locality with hominids, hominoids, mammals and plant fossils. Based on the published megaflora and palynoflora data from Yuanmou Basin, the climate of Late Pliocene is reconstructed using the Coexistence Approach. The results indicate a warm and humid subtropical climate with a mean annual temperature of ca. 16–17°C and a mean annual precipitation of ca. 1500–1600 mm in the Late Pliocene rather than a dry, hot climate today, which may be due to the local tectonic change and gradual intensification of India monsoon. The comparison of Late Pliocene climate in Eryuan, Yangyi, Longling, and Yuanmou Basin of Yunnan Province suggests that the mean annual temperatures generally show a latitudinal gradient and fit well with their geographic position, while the mean annual precipitations seem to be related to the different geometries of the valleys under the same monsoon system

SrCo1−xTixO3−δ perovskites as excellent catalysts for fast degradation of water contaminants in neutral and alkaline solutions

Perovskite-like oxides SrCo1−xTixO3−δ (SCTx, x = 0.1, 0.2, 0.4, 0.6) were used as heterogeneous catalysts to activate peroxymonosulfate (PMS) for phenol degradation under a wide pH range, exhibiting more rapid phenol oxidation than Co3O4 and TiO2. The SCT0.4/PMS system produced a high activity at increased initial pH, achieving optimized performance at pH  ≥ 7 in terms of total organic carbon removal, the minimum Co leaching and good catalytic stability. Kinetic studies showed that the phenol oxidation kinetics on SCT0.4/PMS system followed the pseudo-zero order kinetics and the rate on SCT0.4/PMS system decreased with increasing initial phenol concentration, decreased PMS amount, catalyst loading and solution temperature. Quenching tests using ethanol and tert-butyl alcohol demonstrated sulfate and hydroxyl radicals for phenol oxidation. This investigation suggested promising heterogeneous catalysts for organic oxidation with PMS, showing a breakthrough in the barriers of metal leaching, acidic pH, and low efficiency of heterogeneous catalysis

Quantifying Quality of Life and Disability of Patients with Advanced Schistosomiasis Japonica

Advanced schistosomiasis japonica, an extreme form of chronic schistosomiasis that occurs in Asia, is more serious than the advanced hepatosplenic disease of schistosomiasis encountered in Africa and the Americas. The advanced schistosomiasis japonica is a chronic disabling condition associated with portal hypertension, splenomegaly, ascites, and gastro-oesophageal variceal bleeding, or with severe growth retardation or granulomatous disease of the large intestine. However, the actual disability caused by advanced schistosomiasis japonica is unknown. We carried out a patient-based quality-of-life evaluation employing a standardized and widely used questionnaire (known as “EQ-5D plus”), coupled with ultrasonography and laboratory tests on advanced schistosomiasis japonica cases in a hyperendemic area of China. Among 215 confirmed cases of advanced schistosomiasis japonica, we found an overall disability weight of 0.447 with age-specific weights ranging from 0.378 to 0.510. Importantly, advanced schistosomiasis japonica is not only associated with heavy disability weights, but also with high morbidity and poor self-reported quality of life. Our results provide valuable data for the current revision of the Global Burden of Disease (GBD) study, as well as for evidence-based decision-making in China's national schistosomiasis control program

Prevalence and Associated Factors of Dyslipidemia in the Adult Chinese Population

To determine the prevalence, associated factors, awareness and control of dyslipidemia in Chinese living in Greater Beijing, we measured the serum cholesterol concentration in 3251 Chinese adults (age: 45 to 89 years) as participants of the population-based Beijing Eye Study 2006. Additional information on treatment of dyslipidemia was obtained using a standard questionnaire. The mean concentrations of total, HDL cholesterol, LDL cholesterol and triglycerides were 4.92±1.01 mmol/L, 1.61±0.36 mmol/L, 2.88±0.85 mmol/L, and 1.76±1.29 mmol/L, respectively. Prevalence of dyslipidemia was 56.1±0.9%%. Presence of dyslipidemia was significantly associated with increasing age (odds ratio (OR):1.02; 95% confidence interval (CI): 1.01, 1.03), female gender (OR:1.51; 95%CI: 1.25, 1.83), urban region (OR:1.82; 95%CI: 1.30, 2.55), body mass index (OR:1.13; 95%CI: 1.10, 1.15), income (OR:1.11; 95%CI:1.02, 1.21), blood glucose concentration (OR:1.10; 95%CI:1.05, 1.16), diastolic blood pressure (OR:1.02; 95%CI: 1.01, 1.03), and smoking (OR:1.23; 1.01, 1.51). Among those who had dyslipidemia, the proportion of subjects who were aware, treated and controlled was 50.9%, 23.8%, and 39.91%, respectively. The awareness rate was associated with urban region (P = 0.001; OR: 6.50), body mass index (P = 0.001; OR:1.06), and income (P = 0.02; OR:1.14). The data suggest that dyslipidemia may be present in about 56% of the population aged 45+ years in Greater Beijing. Factors likely associated with dyslipidemia were higher age, female gender, urban region, higher body mass index, higher income, higher blood concentration of glucose, higher diastolic blood pressure, and smoking. In the examined study population, treatment rate was 24% with about 60% of the treated subjects still having uncontrolled dyslipidemia

Carbon Nanotube Solar Cells

We present proof-of-concept all-carbon solar cells. They are made of a photoactive side of predominantly semiconducting nanotubes for photoconversion and a counter electrode made of a natural mixture of carbon nanotubes or graphite, connected by a liquid electrolyte through a redox reaction. The cells do not require rare source materials such as In or Pt, nor high-grade semiconductor processing equipment, do not rely on dye for photoconversion and therefore do not bleach, and are easy to fabricate using a spray-paint technique. We observe that cells with a lower concentration of carbon nanotubes on the active semiconducting electrode perform better than cells with a higher concentration of nanotubes. This effect is contrary to the expectation that a larger number of nanotubes would lead to more photoconversion and therefore more power generation. We attribute this to the presence of metallic nanotubes that provide a short for photo-excited electrons, bypassing the load. We demonstrate optimization strategies that improve cell efficiency by orders of magnitude. Once it is possible to make semiconducting-only carbon nanotube films, that may provide the greatest efficiency improvement

Does sex matter in the associations between classic risk factors and fatal coronary heart disease in populations from the Asia-Pacific region?

Background: There is much interest in promoting healthy heart awareness among women. However, little is known about the reasons behind the lower rates of heart disease among women compared with men, and why this risk difference diminishes with age. Previous comparative studies have generally had insufficient numbers of women to quantify such differences reliably. Methods: We carried out an individual participant data meta-analysis of 39 cohort studies (32 from Asian countries and 7 from Australia and New Zealand). Cox models were used to estimate hazard ratios (HR) for coronary death, comparing men to women. Further adjustments were made for several proven coronary risk factors to quantify their contributions to the sex differential. Sex interactions were tested for the same risk factors. Results: During 4 million person-years of follow-up, there were 1989 (926 female) deaths from coronary heart disease (CHD). The age-adjusted and study-adjusted male/female HR (95% confidence interval [95% CI]) was 2.05 (1.89-2.22). At baseline, 54% of men vs. 7% of women were current smokers; hence, adjustment for smoking explained the largest component (20%) of this HR. A significant sex interaction was observed between systolic blood pressure (SBP) and CHD mortality such that a 10 mm Hg increase was associated with a 15% greater increase in the relative risk (RR) of coronary death in women compared with men (p = 0.002). Conclusions: Only a small amount of the sex differential in coronary death could be explained by differences in the prevalence of classic risk factors. Alternative explanations are required to explain the age-related attenuation of the sex difference in CHD risk. © Mary Ann Liebert, Inc.published_or_final_versio

Emotion-Related Visual Mismatch Responses in Schizophrenia: Impairments and Correlations with Emotion Recognition.

BACKGROUND AND OBJECTIVES:Mismatch negativity (MMN) is an event-related potential (ERP) measure of preattentional sensory processing. While deficits in the auditory MMN are robust electrophysiological findings in schizophrenia, little is known about visual mismatch response and its association with social cognitive functions such as emotion recognition in schizophrenia. Our aim was to study the potential deficit in the visual mismatch response to unexpected facial emotions in schizophrenia and its association with emotion recognition impairments, and to localize the sources of the mismatch signals. EXPERIMENTAL DESIGN:The sample comprised 24 patients with schizophrenia and 24 healthy control subjects. Controls were matched individually to patients by gender, age, and education. ERPs were recorded using a high-density 128-channel BioSemi amplifier. Mismatch responses to happy and fearful faces were determined in 2 time windows over six regions of interest (ROIs). Emotion recognition performance and its association with the mismatch response were also investigated. PRINCIPAL OBSERVATIONS:Mismatch signals to both emotional conditions were significantly attenuated in patients compared to controls in central and temporal ROIs. Controls recognized emotions significantly better than patients. The association between overall emotion recognition performance and mismatch response to the happy condition was significant in the 250-360 ms time window in the central ROI. The estimated sources of the mismatch responses for both emotional conditions were localized in frontal regions, where patients showed significantly lower activity. CONCLUSIONS:Impaired generation of mismatch signals indicate insufficient automatic processing of emotions in patients with schizophrenia, which correlates strongly with decreased emotion recognition

Association Study of the β2-Adrenergic Receptor Gene Polymorphisms and Hypertension in the Northern Han Chinese

Background: The beta 2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population. Methodology/Principal Findings: This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95% CI [1.059-1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95% CI [1.121-1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95% CI [1.059-2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95% CI [1.056-1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95% CI [1.258-2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk. Conclusions/Significances: We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.Multidisciplinary SciencesSCI(E)7ARTICLE4null