Temporal properties of dual-peak responses of mouse retinal ganglion cells and effects of inhibitory pathways

Dual-peak responses of retinal ganglion cells (RGCs) are observed in various species, previous researches suggested that both response peaks were involved in retinal information coding. In the present study, we investigated the temporal properties of the dual-peak responses recorded in mouse RGCs elicited by spatially homogeneous light flashes and the effect of the inhibitory inputs mediated by GABAergic and/or glycinergic pathways. We found that the two peaks in the dual-peak responses exhibited distinct temporal dynamics, similar to that of short-latency and long-latency single-peak responses respectively. Pharmacological studies demonstrated that the application of exogenous GABA or glycine greatly suppressed or even eliminated the second peak of the cells’ firing activities, while little change was induced in the first peak. Co-application of glycine and GABA led to complete elimination of the second peak. Moreover, application of picrotoxin or strychnine induced dual-peak responses in some cells with transient responses by unmasking a second response phase. These results suggest that both GABAergic and glycinergic pathways are involved in the dual-peak responses of the mouse RGCs, and the two response peaks may arise from distinct pathways that would converge on the ganglion cells.     

Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development

Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A₂-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent “first hit”, rendering IUGR intestine susceptible to further injury, infection, or inflammation.     

Combining Amplitude Spectrum Area with Previous Shock Information Using Neural Networks Improves Prediction Performance of Defibrillation Outcome for Subsequent Shocks in Out-Of-Hospital Cardiac Arrest Patients

Objective

Quantitative ventricular fibrillation (VF) waveform analysis is a potentially powerful tool to optimize defibrillation. However, whether combining VF features with additional attributes that related to the previous shock could enhance the prediction performance for subsequent shocks is still uncertain.

Methods

A total of 528 defibrillation shocks from 199 patients experienced out-of-hospital cardiac arrest were analyzed in this study. VF waveform was quantified using amplitude spectrum area (AMSA) from defibrillator''s ECG recordings prior to each shock. Combinations of AMSA with previous shock index (PSI) or/and change of AMSA (ΔAMSA) between successive shocks were exercised through a training dataset including 255shocks from 99patientswith neural networks. Performance of the combination methods were compared with AMSA based single feature prediction by area under receiver operating characteristic curve(AUC), sensitivity, positive predictive value (PPV), negative predictive value (NPV) and prediction accuracy (PA) through a validation dataset that was consisted of 273 shocks from 100patients.

Results

A total of61 (61.0%) patients required subsequent shocks (N = 173) in the validation dataset. Combining AMSA with PSI and ΔAMSA obtained highest AUC (0.904 vs. 0.819, p<0.001) among different combination approaches for subsequent shocks. Sensitivity (76.5% vs. 35.3%, p<0.001), NPV (90.2% vs. 76.9%, p = 0.007) and PA (86.1% vs. 74.0%, p = 0.005)were greatly improved compared with AMSA based single feature prediction with a threshold of 90% specificity.

Conclusion

In this retrospective study, combining AMSA with previous shock information using neural networks greatly improves prediction performance of defibrillation outcome for subsequent shocks.     

Locating structures and evolution pathways of reconstructed rutile TiO<Subscript>2</Subscript>(011) using genetic algorithm aided density functional theory calculations

Titanium dioxide (TiO₂) is an important metal oxide that has been used in many different applications. TiO₂ has also been widely employed as a model system to study basic processes and reactions in surface chemistry and heterogeneous catalysis. In this work, we investigated the (011) surface of rutile TiO₂ by focusing on its reconstruction. Density functional theory calculations aided by a genetic algorithm based optimization scheme were performed to extensively sample the potential energy surfaces of reconstructed rutile TiO₂ structures that obey (2?×?1) periodicity. A lot of stable surface configurations were located, including the global-minimum configuration that was proposed previously. The wide variety of surface structures determined through the calculations performed in this work provide insight into the relationship between the atomic configuration of a surface and its stability. More importantly, several analytical schemes were proposed and tested to gauge the differences and similarities among various surface structures, aiding the construction of the complete pathway for the reconstruction process.     

The Relationship between Cell Number,Division Behavior and Developmental Potential of Cleavage Stage Human Embryos: A Time-Lapse Study

Day 3 cleavage embryo transfer is routine in many assisted reproductive technology centers today. Embryos are usually selected according to cell number, cell symmetry and fragmentation for transfer. Many studies have showed the relationship between cell number and embryo developmental potential. However, there is limited understanding of embryo division behavior and their association with embryo cell number and developmental potential. A retrospective and observational study was conducted to investigate how different division behaviors affect cell number and developmental potential of day 3 embryos by time-lapse imaging. Based on cell number at day 3, the embryos (from 104 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles, n = 799) were classified as follows: less than 5 cells (< 5C; n = 111); 5–6 cells (5–6C; n = 97); 7–8 cells (7–8C; n = 442), 9–10 cells (9–10C; n = 107) and more than 10 cells (>10C; n = 42). Division behavior, morphokinetic parameters and blastocyst formation rate were analyzed in 5 groups of day 3 embryos with different cell numbers. In <5C and 5–6C embryos, fragmentation (FR; 62.2% and 30.9%, respectively) was the main cause for low cell number. The majority of 7–8C embryos exhibited obvious normal behaviors (NB; 85.7%) during development. However, the incidence of DC in 9–10C and >10C embryos increased compared to 7–8C embryos (45.8%, 33.3% vs. 11.1%, respectively). In ≥5C embryos, FR and DC significantly reduced developmental potential, whereas <5C embryos showed little potential irrespective of division behaviors. In NB embryos, the blastocyst formation rate increased with cell number from 7.4% (<5C) to 89.3% (>10C). In NB embryos, the cell cycle elongation or shortening was the main cause for abnormally low or high cell number, respectively. After excluding embryos with abnormal division behaviors, the developmental potential, implantation rate and live birth rate of day 3 embryos increased with cell number.     

The Prognostic Value of Peak Cardiac Power Output in Chinese Patients with Chronic Heart Failure

Background

Cardiopulmonary exercise testing has been widely used to risk stratify patients with chronic heart failure (CHF). Peak oxygen consumption (peakVO₂) was regarded as a powerful predictor of survival, as it is a surrogate for peak cardiac output (CO), which by most is considered the “true” measure of heart failure. Therefore, it is reasonable to hypothesize that CO is an even stronger predictor than peak VO₂. The present study is aimed to investigate the prognostic value of peak cardiac power output (peak CPO) in comparison with peakVO₂ in Chinese patients with CHF.

Methods

Participants provided written informed consent to participate in this study. Totally 129 patients with CHF underwent symptom-limited cardiopulmonary exercise testing (CPET), with mean age 59.1±11.4 years, 87.6% male, 57.4% ischemic etiology, body mass index (BMI) 24.7±3.7 kg/m² and LVEF 38±9%. CO was measured using an inert gas rebreathing method. The primary endpoints are cardiac deaths.

Results

Over median 33.7-month follow-up, 19 cardiac deaths were reported. Among peak VO₂,VE/VCO₂ slope and Peak CPO, their area under ROC were 0.64, 0.67, 0.68, respectively (Ρ<0.05).The optimal thresholds for predicting cardiac deaths were peak VO₂≤13.4 ml.kg^-1.min^-1, and VE/VCO₂ slope≥39.3 and peak CPO≤ 1.1 respectively by ROC analysis. Finally, in patients with a peak VO2≤13.4 ml.kg^-1.min^-1 those with peak CPO>1.1W had better survival than those with peak CPO ≤ 1.1W. However, by multivariate analysis adjusted for age, sex, BMI, resting heart rate, LVMI, LVEF, Peak CPO was not an independent predictor of cardiac deaths (P> 0.05).

Conclusions

Peak CPO was not a predictor of cardiac death in Chinese CHF patients.     

Genomic location and expression analysis of expansin gene family reveals the evolutionary and functional significance in <Emphasis Type="Italic">Triticum aestivum</Emphasis>

The plant-specific expansin proteins constitute an ancient and major gene family known to have roles in regulating diverse biological processes in plants. Although the functions of many expansin genes have been identified in wheat and other species, little is known about the evolution and genomic locations of the expansin genes in wheat (Triticum aestivum). In this study, a total of 87 expansin genes were identified in the wheat genome, including 52 EXPAs, 42 EXPBs and 4 EXLAs. The EXLB gene was not found in the wheat genome. Phylogenetic tree and comparative analysis revealed amplification of the EXPBs in rice, maize and wheat. The predicted wheat expansins were distributed across 14 of 21 chromosomes with different densities, 3 tightly co-located clusters and 15 paralogous pairs, indicating that tandem duplication and segmental duplication events also played roles in the evolution of expansins in wheat. In addition, the gene structures and conserved protein domains of wheat expansins suggest high levels of conservation within the phylogenetic subgroups. Analysis of a published microarray database showed that most wheat expansin genes exhibit different expression levels in different tissues and developmental stages. To our knowledge, this is the first report of a genome-wide analysis of the wheat expansin gene family, which should provide valuable information for further elucidating the classification and putative functions of the entire gene family.     

Urban and Rural Differences of Acute Cardiovascular Disease Events: A Study from the Population-Based Real-Time Surveillance System in Zhejiang,China in 2012

Zhejiang province, China, has implemented a population based, real-time surveillance system that tracks acute cardiovascular diseases (CVDs) events since 2001. This study aimed to describe the system and report CVD incidence, mortality and case-fatality between urban and rural areas in Zhejiang in 2012. The surveillance system employs a stratified random sampling method covering all permanent residents of 30 counties/districts in Zhejiang. Acute CVD events such as coronary heart disease (CHD) and stroke were defined, registered and reviewed based on the adapted MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) definitions. Data were collected from health facilities, vital registries, supplementary surveys, and additional investigations, and were checked for data quality before input in the system. We calculated the rates and compared them by gender, age and region. In 2012, the incidence, mortality and case-fatality of total acute CVD events were 367.0 (CHD 59.1, stroke 307.9), 127.1 (CHD 43.3, stroke 83.8) per 100,000 and 34.6% (CHD 73.2%, stroke 27.2%), respectively. Compared with rural areas, urban areas reported higher incidence and mortality but lower case-fatality rates for CHD (P<0.001), while lower incidence but higher mortality and case-fatality rates for stroke (P<0.001). We found significant differences on CHD and stroke epidemics between urban and rural areas in Zhejiang. Special attentions need to be given to stroke control, especially in rural areas.     

IL-33-Dependent Endothelial Activation Contributes to Apoptosis and Renal Injury in Orientia tsutsugamushi-Infected Mice

Endothelial cells (EC) are the main target for Orientia tsutsugamushi infection and EC dysfunction is a hallmark of severe scrub typhus in patients. However, the molecular basis of EC dysfunction and its impact on infection outcome are poorly understood. We found that C57BL/6 mice that received a lethal dose of O. tsutsugamushi Karp strain had a significant increase in the expression of IL-33 and its receptor ST2L in the kidneys and liver, but a rapid reduction of IL-33 in the lungs. We also found exacerbated EC stress and activation in the kidneys of infected mice, as evidenced by elevated angiopoietin (Ang) 2/Ang1 ratio, increased endothelin 1 (ET-1) and endothelial nitric oxide synthase (eNOS) expression. Such responses were significantly attenuated in the IL-33^-/- mice. Importantly, IL-33^-/- mice also had markedly attenuated disease due to reduced EC stress and cellular apoptosis. To confirm the biological role of IL-33, we challenged wild-type (WT) mice with a sub-lethal dose of O. tsutsugamushi and gave mice recombinant IL-33 (rIL-33) every 2 days for 10 days. Exogenous IL-33 significantly increased disease severity and lethality, which correlated with increased EC stress and activation, increased CXCL1 and CXCL2 chemokines, but decreased anti-apoptotic gene BCL-2 in the kidneys. To further examine the role of EC stress, we infected human umbilical vein endothelial cells (HUVEC) in vitro. We found an infection dose-dependent increase in the expression of IL-33, ST2L soluble ST2 (sST2), and the Ang2/Ang1 ratio at 24 and 48 hours post-infection. This study indicates a pathogenic role of alarmin IL-33 in a murine model of scrub typhus and highlights infection-triggered EC damage and IL-33-mediated pathological changes during the course of Orientia infection.     

包埋法固定化对硫氧化微生物菌群结构和功能的影响

【目的】为探讨包埋法固定化过程对硫氧化菌群硫化物去除能力及菌群微生物群落结构的影响,【方法】以聚乙烯醇-海藻酸钠-活性炭为载体,对硫氧化菌群进行了固定化,并采用富含硫化物的无机盐培养基,对比固定化与非固定化硫氧化菌群对硫化物的氧化去除能力。同时,利用PCR-DGGE技术,探讨硫氧化菌群在固定化前后以及在硫化物氧化去除过程中微生物群落结构变化。【结果】在对硫氧化菌群进行固定化之后,12 h之内对硫化物的最大去除能力从1000 mg/L下降为600 mg/L。硫氧化菌群的微生物群落结构发生了明显变化,但菌群中的硫氧化菌Catenococcus thiocycli未受影响,硫氧化菌Thioclava pacifica在菌群中的地位反而得到了强化。【结论】受制于底物在载体材料中的扩散迁移效率,硫氧化菌群对硫化物的氧化去除能力在固定化之后有所下降。由于不同微生物对固定化形成的微环境的适应能力以及对载体附着能力的不同,固定化对硫氧化菌群的微生物群落结构产生较大影响。