Thermal inactivation and conformational lock studies on glucose oxidase

In this study, the dissociative thermal inactivation and conformational lock theories are applied for the homodimeric enzyme glucose oxidase (GOD) in order to analyze its structure. For this purpose, the rate of activity reduction of glucose oxidase is studied at various temperatures using b-D-glucose as the substrate by incubation of enzyme at various temperatures in the wide range between 40 and 70 �C using UV–Vis spectrophotometry. It was observed that in the two ranges of temperatures, the enzyme has two different forms. In relatively low temperatures, the enzyme is in its dimeric state and has normal activity. In high temperatures, the activity almost disappears and it aggregates. The above achievements are confirmed by dynamic light scattering. The experimental parameter ‘‘n’’ as the obvious number of conformational locks at the dimer interface of glucose oxidase is obtained by kinetic data, and the value is near to two. To confirm the above results, the X-ray crystallography structure of the enzyme, GOD (pdb, 1gal), was also studied. The secondary and tertiary structures of the enzyme to track the thermal inactivation were studied by circular dichroism and fluorescence spectroscopy, respectively. We proposed a mechanism model for thermal inactivation of GOD based on the absence of the monomeric form of the enzyme by circular dichroism and fluorescence spectroscopy

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen

Y-box-binding proteins are members of the human cold-shock domain protein superfamily, which includes dbpA, dbpB/YB-1, and dbpC/contrin. dbpC/contrin is a germ cell-specific Y-box-binding protein and is suggested to function as a nuclear transcription factor and RNA-binding protein in the cytoplasm. Whereas ubiquitous dbpB/YB-1 expression has been well studied in various types of human carcinomas as a prognostic or predictive marker, the dbpC/contrin expression in human tumour cells has not been reported. In this report, we provide the first evidence showing that dbpC was highly expressed in human testicular seminoma and ovarian dysgerminomas, and in carcinomas in other tissues and that its expression in normal tissues is nearly restricted to germ cells and placental trophoblasts. These results indicate that dbpC/contrin would be a potentially novel cancer/testis antigen

Temporal estimation with two moving objects: overt and covert pursuit

The current study examined temporal estimation in a prediction motion task where participants were cued to overtly pursue one of two moving objects, which could either arrive first, i.e., shortest [time to contact (TTC)] or second (i.e., longest TTC) after a period of occlusion. Participants were instructed to estimate TTC of the first-arriving object only, thus making it necessary to overtly pursue the cued object while at the same time covertly pursuing the other (non-cued) object. A control (baseline) condition was also included in which participants had to estimate TTC of a single, overtly pursued object. Results showed that participants were able to estimate the arrival order of the two objects with very high accuracy irrespective of whether they had overtly or covertly pursued the first-arriving object. However, compared to the single-object baseline, participants’ temporal estimation of the covert object was impaired when it arrived 500 ms before the overtly pursued object. In terms of eye movements, participants exhibited significantly more switches in gaze location during occlusion from the cued to the non-cued object but only when the latter arrived first. Still, comparison of trials with and without a switch in gaze location when the non-cued object arrived first indicated no advantage for temporal estimation. Taken together, our results indicate that overt pursuit is sufficient but not necessary for accurate temporal estimation. Covert pursuit can enable representation of a moving object’s trajectory and thereby accurate temporal estimation providing the object moves close to the overt attentional focus

Human Embryonic Stem Cells Differentiated to Lung Lineage-Specific Cells Ameliorate Pulmonary Fibrosis in a Xenograft Transplant Mouse Model

Our aim was to differentiate human (h) embryonic stem (ES) cells into lung epithelial lineage-specific cells [i.e., alveolar epithelial type I (AEI) and type II (AEII) cells and Clara cells] as the first step in the development of cell-based strategies to repair lung injury in the bleomycin mouse model of idiopathic pulmonary fibrosis (IPF). A heterogeneous population of non-ciliated lung lineage-specific cells was derived by a novel method of embryoid body (EB) differentiation. This differentiated human cell population was used to modulate the profibrotic phenotype in transplanted animals.Omission or inclusion of one or more components in the differentiation medium skewed differentiation of H7 hES cells into varying proportions of AEI, AEII, and Clara cells. ICG-001, a small molecule inhibitor of Wnt/β-catenin/Creb-binding protein (CBP) transcription, changed marker expression of the differentiated ES cells from an AEII-like phenotype to a predominantly AEI-like phenotype. The differentiated cells were used in xenograft transplantation studies in bleomycin-treated Rag2γC(-/-) mice. Human cells were detected in lungs of the transplanted groups receiving differentiated ES cells treated with or without ICG-001. The increased lung collagen content found in bleomycin-treated mice receiving saline was significantly reduced by transplantation with the lung-lineage specific epithelial cells differentiated from ES cells. A significant increase in progenitor number was observed in the airways of bleomycin-treated mice after transplantation of differentiated hES cells.This study indicates that ES cell-based therapy may be a powerful novel approach to ameliorate lung fibrosis

Sequences From First Settlers Reveal Rapid Evolution in Icelandic mtDNA Pool

A major task in human genetics is to understand the nature of the evolutionary processes that have shaped the gene pools of contemporary populations. Ancient DNA studies have great potential to shed light on the evolution of populations because they provide the opportunity to sample from the same population at different points in time. Here, we show that a sample of mitochondrial DNA (mtDNA) control region sequences from 68 early medieval Icelandic skeletal remains is more closely related to sequences from contemporary inhabitants of Scotland, Ireland, and Scandinavia than to those from the modern Icelandic population. Due to a faster rate of genetic drift in the Icelandic mtDNA pool during the last 1,100 years, the sequences carried by the first settlers were better preserved in their ancestral gene pools than among their descendants in Iceland. These results demonstrate the inferential power gained in ancient DNA studies through the application of population genetics analyses to relatively large samples

Cancer mortality trends in the Umbria region of Italy 1978–2004: a joinpoint regression analysis

BACKGROUND: The aim of the present paper was to analyse cancer mortality in the Umbria region, from 1978 to 2004. Mortality trends depend on a number of factors including exposures, health system interventions, and possibly artefact (e.g. classification change, variations of data completeness). Descriptive data on mortality only allow for generation of hypotheses to explain observed trends. Some clues on the respective role of possible mortality determinants may be found comparing mortality with incidence and survival data. METHODS: Mortality data for the periods 1978–1993 and 1994–2004 were supplied by the National Institute of Statistics (ISTAT) and the Regional Causes of Death Registry (ReNCaM) respectively. Sex and site-specific mortality time trends were analysed by the "joinpoint regression" method. RESULTS: For all sites combined, in both sexes, the standardised rate was first increasing before the end of the eighties and decreasing thereafter. Gastric cancer mortality showed a different trend by gender; that is the rate constantly decreased over the period among females while, for males, it was first increasing up to 1985 and decreasing thereafter. Liver cancer trend showed a pattern similar to gastric cancer. Large bowel cancer showed a gender specific trend, that is it was increasing among males and stable among females. Also lung cancer mortality varied by gender: it started to decline after 1989 among males but was steadily increasing over the study period among women. A decreasing trend for female breast cancer mortality began in 1994. Prostate cancer mortality trend is the only one showing two significant joinpoints: mortality decreased up to 1990, then it increased up to 1998 and, finally, was decreasing. CONCLUSION: Overall cancer mortality was decreasing in both sexes in Umbria and this favourable trend will probably continue and further improve since population screening against breast, cervix, and large bowel cancers were recently introduced. Besides gastric cancer, tobacco-related cancers and prostate cancer mainly contributed to mortality reduction in males, whereas breast cancer mainly contributed to declining mortality in females

Hybrid crystalline-ITO/metal nanowire mesh transparent electrodes and their application for highly flexible perovskite solar cells

Here, we propose crystalline indium tin oxide/metal nanowire composite electrode (c-ITO/metal NW-GFRHybrimer) films as a robust platform for flexible optoelectronic devices. A very thin c-ITO overcoating layer was introduced to the surface-embedded metal nanowire (NW) network. The c-ITO/metal NW-GFRHybrimer films exhibited outstanding mechanical flexibility, excellent optoelectrical properties and thermal/chemical robustness. Highly flexible and efficient metal halide perovskite solar cells were fabricated on the films. The devices on the c-ITO/AgNW- and c-ITO/CuNW-GFRHybrimer films exhibited power conversion efficiency values of 14.15% and 12.95%, respectively. A synergetic combination of the thin c-ITO layer and the metal NW mesh transparent conducting electrode will be beneficial for use in flexible optoelectronic applications

Neuroticism Modifies Psychophysiological Responses to Fearful Films

Background: Neuroticism is a personality component frequently found in anxious and depressive psychiatric disorders. The influence of neuroticism on negative emotions could be due to its action on stimuli related to fear and sadness, but this remains debated. Our goal was thus to better understand the impact of neuroticism through verbal and physiological assessment in response to stimuli inducing fear and sadness as compared to another negative emotion (disgust).¦Methods: Fifteen low neurotic and 18 high neurotic subjects were assessed on an emotional attending task by using film excerpts inducing fear, disgust, and sadness. We recorded skin conductance response (SCR) and corrugator muscle activity (frowning) as indices of emotional expression.¦Results: SCR was larger in high neurotic subjects than in low neurotics for fear relative to sadness and disgust. Moreover, corrugator activity and SCR were larger in high than in low neurotic subjects when fear was induced.¦Conclusion: After decades of evidence that individuals higher in neuroticism experience more intense emotional reactions to even minor stressors, our results indicate that they show greater SCR and expressive reactivity specifically to stimuli evoking fear rather than to those inducing sadness or disgust. Fear processing seems mainly under the influence of neuroticism. This modulation of autonomic activity by neurotics in response to threat/fear may explain their increased vulnerability to anxious psychopathologies such as PTSD (post traumatic stress disorder)