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- A State-by-state Investigation of Destructive Interference in Resonance Raman Spectra of Neutral Tyrosine and Tyrosinate Anion with the Simplified Sum-over-States Approach. [JOURNAL ARTICLE]
- J Phys Chem A 2014 Sep 18.
UV resonance Raman scattering is uniquely sensitive to the molecular electronic structure as well as intermolecular interactions. To better understand the relationship between electronic structure and resonance Raman cross section, we carried out combined experimental and theoretical studies of neutral tyrosine and the tyrosinate anion. We studied the Raman cross sections of four vibrational modes as a function of excitation wavelength and we analyzed them in terms of the contributions of the individual electronic states as well as of the Albrecht A and B terms. Our model, which is based on time-dependent density functional theory (TDDFT), reproduced the experimental resonance Raman spectra and Raman excitation profiles for both studied molecules with good agreement. We found that for the studied modes the contributions of Albrecht's B terms in the Raman cross sections were important across the frequency range spanning the La,b and Ba,b electronic excitations in tyrosine and tyrosinate anion. Furthermore, we demonstrated that interference with high energy states had a significant impact and could not be neglected even when in resonance with a lower-energy state. Symmetry of the vibrational modes served as an indicator of the dominance of the A or B mechanisms. Excitation profiles calculated with a damping constant estimated from linewidths of the electronic absorption bands had the best consistency with experimental results.
- Integrative Model of the Immune Response to a Pulmonary Macrophage Infection: What Determines the Infection Duration? [JOURNAL ARTICLE]
- PLoS One 2014; 9(9):e107818.
The immune mechanisms which determine the infection duration induced by pathogens targeting pulmonary macrophages are poorly known. To explore the impact of such pathogens, it is indispensable to integrate the various immune mechanisms and to take into account the variability in pathogen virulence and host susceptibility. In this context, mathematical models complement experimentation and are powerful tools to represent and explore the complex mechanisms involved in the infection and immune dynamics. We developed an original mathematical model in which we detailed the interactions between the macrophages and the pathogen, the orientation of the adaptive response and the cytokine regulations. We applied our model to the Porcine Respiratory and Reproductive Syndrome virus (PRRSv), a major concern for the swine industry. We extracted value ranges for the model parameters from modelling and experimental studies on respiratory pathogens. We identified the most influential parameters through a sensitivity analysis. We defined a parameter set, the reference scenario, resulting in a realistic and representative immune response to PRRSv infection. We then defined scenarios corresponding to graduated levels of strain virulence and host susceptibility around the reference scenario. We observed that high levels of antiviral cytokines and a dominant cellular response were associated with either short, the usual assumption, or long infection durations, depending on the immune mechanisms involved. To identify these mechanisms, we need to combine the levels of antiviral cytokines, including [Formula: see text], and [Formula: see text]. The latter is a good indicator of the infected macrophage level, both combined provide the adaptive response orientation. Available PRRSv vaccines lack efficiency. By integrating the main interactions between the complex immune mechanisms, this modelling framework could be used to help designing more efficient vaccination strategies.
- Sub-Micrometer-Scale Mapping of Magnetite Crystals and Sulfur Globules in Magnetotactic Bacteria Using Confocal Raman Micro-Spectrometry. [JOURNAL ARTICLE]
- PLoS One 2014; 9(9):e107356.
The ferrimagnetic mineral magnetite [Formula: see text] is biomineralized by magnetotactic microorganisms and a diverse range of animals. Here we demonstrate that confocal Raman microscopy can be used to visualize chains of magnetite crystals in magnetotactic bacteria, even though magnetite is a poor Raman scatterer and in bacteria occurs in typical grain sizes of only 35-120 nm, well below the diffraction-limited optical resolution. When using long integration times together with low laser power (<0.25 mW) to prevent laser induced damage of magnetite, we can identify and map magnetite by its characteristic Raman spectrum (303, 535, 665 [Formula: see text]) against a large autofluorescence background in our natural magnetotactic bacteria samples. While greigite (cubic [Formula: see text]; Raman lines of 253 and 351 [Formula: see text]) is often found in the Deltaproteobacteria class, it is not present in our samples. In intracellular sulfur globules of Candidatus Magnetobacterium bavaricum (Nitrospirae), we identified the sole presence of cyclo-octasulfur ([Formula: see text]: 151, 219, 467 [Formula: see text]), using green (532 nm), red (638 nm) and near-infrared excitation (785 nm). The Raman-spectra of phosphorous-rich intracellular accumulations point to orthophosphate in magnetic vibrios and to polyphosphate in magnetic cocci. Under green excitation, the cell envelopes are dominated by the resonant Raman lines of the heme cofactor of the b or c-type cytochrome, which can be used as a strong marker for label-free live-cell imaging of bacterial cytoplasmic membranes, as well as an indicator for the redox state.
- TDP1/TOP1 Ratio as a Promising Indicator for the Response of Small Cell Lung Cancer to Topotecan. [JOURNAL ARTICLE]
- J Cancer Sci Ther 2014 Jul 25; 6(7):258-267.
Small cell lung cancer (SCLC) is one of the most challenging tumors to treat due to high proliferation rate, early metastatic dissemination and rapid development of chemotherapy resistance. The current treatment protocols involve the use of topoisomerase 1 (TOP1) poisons such as irinotecan and topotecan in combination with platinum-based compounds. TOP1 poisons kill cancer cells by trapping TOP1 on DNA, generating lethal DNA double-strand breaks. A potential mechanism employed by cancer cells to resist killing by TOP1 poisons is to overexpress enzymes involved in the repair of TOP1-DNA breaks. Tyrosyl DNA phosphodiesterase 1 (TDP1) is a key player in this process and despite its importance, no data is currently available to correlate TDP1 protein and mRNA levels with catalytic activity in SCLC. In addition, it is not known if TDP1 and TOP1 protein levels correlate with the cellular response of SCLC to TOP1 based therapies.We report a remarkable variation in TDP1 and TOP1 protein levels in a panel of SCLC cell lines. TDP1 protein level correlates well with TDP1 mRNA and TDP1 catalytic activity, as measured by two newly developed independent activity assays, suggesting the potential utility of immunohistochemistry in assessing TDP1 levels in SCLC tissues. We further demonstrate that whilst TDP1 protein level alone does not correlate with topotecan sensitivity, TDP1/TOP1 ratio correlates well with sensitivity in 8 out of 10 cell lines examined.This study provides the first cellular analyses of TDP1 and TOP1 in SCLC and suggests the potential utility of TDP1/TOP1 ratio to assess the response of SCLC to topotecan. The establishment and validation of an easy-to-use TDP1 enzymatic assay in cell extracts could be exploited as a diagnostic tool in the clinic. These findings may help in stratifying patients that are likely to benefit from TOP1 poisons and TDP1 inhibitors currently under development.
- Treatment effect of the method of Tai Chi exercise in combination with inhalation of air negative oxygen ions on hyperlipidemia. [Journal Article]
- Int J Clin Exp Med 2014; 7(8):2309-13.
To observe the improvement effect of the treatment method of Tai Chi exercise in combination with inhalation of the air negative oxygen ions on the blood lipid indicator of the patient suffering from the hyperlipidemia.56 patients, who are diagnosed with hyperlipidemia, are the study objects and divided into an observation group and a control group by the random number method. Each group consists of 28 patients. The patients in the control group do Tai Chi exercise for about 60 min once a day; the patients in the observation group, in addition to Tai Chi exercise, are treated by inhalation of the air negative oxygen ions. Before the treatment and after 6 months' treatment, respectively test and compare body fat content, blood lipid, blood rheology and psychological adaptation as well as other indicators for these two groups of patients.In comparison with the ordinary materials of the patients in two groups before the treatment, it shows no significant difference, P>0.05; after they are respectively treated for 6 months, it is found that the testing indicators of the patients in two groups are improved to some extent, but those of the observation group are better. Compared with the improvement effect of the control group, the difference has statistical significance, P<0.05.Tai Chi Exercise can improve the blood lipid indicator of the patient suffering from hyperlipidemia to some extent, however, the treatment method, in combination with inhalation of air negative oxygen ion, can obtain better effect than that of single Tai Chi exercise. Tip: the environment of the exercise plays an important intervention role in the treatment effect.
- Microarray analysis in gastric cancer: A review. [REVIEW]
- World J Gastroenterol 2014 Sep 14; 20(34):11972-11976.
Gastric cancer is one of the most common tumors worldwide. Although several treatment options have been developed, the mortality rate is increasing. Lymph node involvement is considered the most reliable prognostic indicator in gastric cancer. Early diagnosis improves the survival rate of patients and increases the likelihood of successful treatment. The most reliable diagnostic method is endoscopic examination, however, it is expensive and not feasible in poorer countries. Therefore, many innovative techniques have been studied to develop a new non-invasive screening test and to identify specific serum biomarkers. DNA microarray analysis is one of the new technologies able to measure the expression levels of a large number of genes simultaneously. It is possible to define the gene expression profile of the tumor and to correlate it with the prognosis and metastasis formation. Several studies in the literature have been published on the role of microarray analysis in gastric cancer and the mechanisms of proliferation and metastasis formation. The aim of this review is to analyze the importance of microarray analysis and its clinical applications to better define the genetic characteristics of gastric cancer and its possible implications in a more decisive treatment.
- Expression of E6AP and PML predicts for prostate cancer progression and cancer specific death. [JOURNAL ARTICLE]
- Ann Oncol 2014 Sep 17.
The promyelocytic leukemia (PML) tumor suppressor plays an important role in the response to a variety of cellular stressors and its expression is downregulated or lost in a range of human tumors. We have previously shown that the E3 ligase E6-associated protein (E6AP) is an important regulator of PML protein stability but the relationship and clinical impact of PML and E6AP expression in prostatic carcinoma is unknown.E6AP and PML expression was assessed in tissue microarrays from a phase I discovery cohort of 170 patients treated by radical prostatectomy for localized prostate cancer. Correlation analysis was performed between PML and E6AP expression and clinicopathological variates including PSA as a surrogate of disease recurrence. The results were confirmed in a phase II validation cohort of 318 patients with associated clinical recurrence and survival data.Survival analysis of the phase I cohort revealed that patients whose tumors showed reduced PML and high E6AP expression had reduced time to PSA relapse (p=0.012). This was confirmed in the phase II validation cohort where the expression profile of high E6AP/low PML was significantly associated with reduced time to PSA relapse (p<0.001), clinical relapse (p=0.016) and prostate cancer specific death (p=0.014). In multivariate analysis, this expression profile was an independent prognostic indicator of PSA relapse and clinical relapse independent of clinicopathologic factors predicting recurrence.This study identifies E6AP and PML as potential prognostic markers in localized prostate carcinoma and supports a role for E6AP in driving the downregulation or loss of PML expression in prostate carcinomas.
- State and Trait Effects on Individual Differences in Children's Mathematical Development. [JOURNAL ARTICLE]
- Psychol Sci 2014 Sep 17.
Substantial longitudinal relations between children's early mathematics achievement and their much later mathematics achievement are firmly established. These findings are seemingly at odds with studies showing that early educational interventions have diminishing effects on children's mathematics achievement across time. We hypothesized that individual differences in children's later mathematical knowledge are more an indicator of stable, underlying characteristics related to mathematics learning throughout development than of direct effects of early mathematical competency on later mathematical competency. We tested this hypothesis in two longitudinal data sets, by simultaneously modeling effects of latent traits (stable characteristics that influence learning across time) and states (e.g., prior knowledge) on children's mathematics achievement over time. Latent trait effects on children's mathematical development were substantially larger than state effects. Approximately 60% of the variance in trait mathematics achievement was accounted for by commonly used control variables, such as working memory, but residual trait effects remained larger than state effects. Implications for research and practice are discussed.
- Monoclonal antibodies against all known variants of EspA: development of a simple diagnostic test for enteropathogenic Escherichia coli based on a key virulence factor. [JOURNAL ARTICLE]
- J Med Microbiol 2014 Sep 17.
Enteropathogenic Escherichia coli (EPEC) are a major cause of infant diarrhoea in developing countries and a significant public health issue in industrialised countries. Currently there are no simple tests available for the diagnosis of EPEC. Serology of O-antigens is widely used routinely in many laboratories throughout the world, even though it has been known for many years to be an unreliable indicator of EPEC virulence. We have developed a simple, low-cost immunodiagnostic test based on the EspA filament, an essential virulence factor of EPEC and the related enterohaemorrhagic E. coli (EHEC). Using recombinant proteins of the five major variants of EspA as immunogens, we raised a panel of three monoclonal antibodies in mice that detects all variants of the native target in bacterial cultures. The antibodies proved suitable for application in sandwich-type assays, including ELISA and lateral flow immunoassay (LFI). Prototypes for both assays were specific for EPEC and EHEC strains when tested against a panel of control micro-organisms. We have also developed a simple, affordable culture medium, A/E medium, which optimises expression of EspA, allowing improved sensitivity of detection compared with standard Dulbecco's modified Eagle's medium. Together these reagents form the basis of robust, informative tests for EPEC for use especially in developing countries but also for routine screening in any clinical laboratory.
- Shared versus specific features of psychological symptoms and cigarettes per day: structural relations and mediation by negative- and positive-reinforcement smoking. [JOURNAL ARTICLE]
- J Behav Med 2014 Sep 18.
This study examined the extent to which shared versus specific features across multiple manifestations of psychological symptoms (depression, anxiety, ADHD, aggression, alcohol misuse) associated with cigarettes per day. Subsequently, we investigated whether negative- (i.e., withdrawal relief) and positive- (i.e., pleasure enhancement) reinforcement smoking motivations mediated relations. Adult daily smokers (N = 338) completed self-report measures and structural equation modeling was used to construct a 3-factor (low positive affect-negative affect-disinhibition) model of affective and behavioral symptoms and to test relations of each latent factor (shared features) and indicator residual (specific features) to smoking level. Shared dimensions of low positive affect, negative affect, and disinhibition associated with smoking rate. Negative-reinforcement smoking mediated the link between latent negative affect and heavier daily smoking. Specific features of psychological symptoms unique from latent factors were generally not associated with cigarettes per day. Features shared across several forms of psychological symptoms appear to underpin relations between psychological symptoms and smoking rate.