The Effects of Aging on Conflict Detection

Several cognitive changes characterize normal aging; one change regards inhibitory processing and includes both conflict monitoring and response suppression. We attempted to segregate these two aspects within a Go/No-go task, investigating three age categories. Accuracy, response times and event-related potentials (ERPs) were recorded. The ERP data were analyzed, and the Go and No-go trials were separated; in addition, the trials were organized in repeat trials (in which the subjects repeated the action delivered in the previous trial) and switch trials (in which the subjects produced a response opposite to the previous response). We assumed that the switch trials conveyed more conflict than the repeat trials. In general, the behavioral data and slower P3 latencies confirmed the well-known age-related speed/accuracy trade-off. The novel analyses of the repeat vs. switch trials indicated that the age-related P3 slowing was significant only for the high conflict condition; the switch-P3 amplitude increased only in the two older groups. The ‘aging switch effect’ on the P3 component suggests a failure in the conflict conditions and likely contributes to a generalized dysfunction. The absence of either a switch effect in the young group and the P3 slowing in middle-aged group indicate that switching was not particularly demanding for these participants. The N2 component was less sensitive to the repeat/switch manipulation; however, the subtractive waves also enhanced the age effects in this earlier time window. The topographic maps showed other notable age effects: the frontal No-go N2 was nearly undetectable in the elderly; in the identical time window, a large activity in the posterior and prefrontal scalp regions was observed. Moreover, the prefrontal activity showed a negative correlation with false alarms. These results suggest that the frontal involvement during action suppression becomes progressively dysfunctional with aging, and additional activity was required to reach a good level of accuracy.     

Helix aspersa as sentinel of development damage for biomonitoring purpose: A validation study

Environmental health has always been threatened by the bioaccumulation of heavy metals in the terrestrial ecosystem, affecting its quality and safety. The aim of this review is to investigate the effects of heavy metal soil contamination, using the land snail Helix aspersa as a bioindicator. H. aspersa, a common species of land snail present in the area, has been used as a bioindicator of metal contamination and represents a promising ecological indicator. Various land snails species have become popular in microcosm studies because they accumulate high concentrations of certain trace metals. They express contamination as a whole through ingestion of polluted foods, such as live plants, microorganisms, soil, and water and also through cutaneous contact and from the polluted air they breathe. Land snails are considered appropriate sentinel species because trace metals tend to accumulate in their digestive gland to allow biomonitoring of metal pollution. Different experiments demonstrate that exposure in areas chronically polluted with metals, especially with lead, often causes changes in reproduction, with a variation in the mineral composition in the snail's eggs and also in its development, due to increased energy expenses associated with detoxi?cation and the excretion process.     

Cerebral Circulation Time is Prolonged and Not Correlated with EDSS in Multiple Sclerosis Patients: A Study Using Digital Subtracted Angiography

Literature has suggested that changes in brain flow circulation occur in patients with multiple sclerosis. In this study, digital subtraction angiography (DSA) was used to measure the absolute CCT value in MS patients and to correlate its value to age at disease onset and duration, and to expand disability status scale (EDSS). DSA assessment was performed on eighty MS patients and on a control group of forty-four age-matched patients. CCT in MS and control groups was calculated by analyzing the angiographic images. Lesion and brain volumes were calculated in a representative group of MS patients. Statistical correlations among CCT and disease duration, age at disease onset, lesion load, brain volumes and EDSS were considered. A significant difference between CCT in MS patients (mean = 4.9s; sd = 1.27s) and control group (mean = 2.8s; sd = 0.51s) was demonstrated. No significant statistical correlation was found between CCT and the other parameters in all MS patients. Significantly increased CCT value in MS patients suggests the presence of microvascular dysfunctions, which do not depend on clinical and MRI findings. Hemodynamic changes may not be exclusively the result of a late chronic inflammatory process.     

Age-Related Differences in the Accuracy of Web Query-Based Predictions of Influenza-Like Illness

BackgroundWeb queries are now widely used for modeling, nowcasting and forecasting influenza-like illness (ILI). However, given that ILI attack rates vary significantly across ages, in terms of both magnitude and timing, little is known about whether the association between ILI morbidity and ILI-related queries is comparable across different age-groups. The present study aimed to investigate features of the association between ILI morbidity and ILI-related query volume from the perspective of age.MethodsSince Google Flu Trends is unavailable in Italy, Google Trends was used to identify entry terms that correlated highly with official ILI surveillance data. All-age and age-class-specific modeling was performed by means of linear models with generalized least-square estimation. Hold-out validation was used to quantify prediction accuracy. For purposes of comparison, predictions generated by exponential smoothing were computed.ResultsFive search terms showed high correlation coefficients of > .6. In comparison with exponential smoothing, the all-age query-based model correctly predicted the peak time and yielded a higher correlation coefficient with observed ILI morbidity (.978 vs. .929). However, query-based prediction of ILI morbidity was associated with a greater error. Age-class-specific query-based models varied significantly in terms of prediction accuracy. In the 0–4 and 25–44-year age-groups, these did well and outperformed exponential smoothing predictions; in the 15–24 and ≥ 65-year age-classes, however, the query-based models were inaccurate and highly overestimated peak height. In all but one age-class, peak timing predicted by the query-based models coincided with observed timing.ConclusionsThe accuracy of web query-based models in predicting ILI morbidity rates could differ among ages. Greater age-specific detail may be useful in flu query-based studies in order to account for age-specific features of the epidemiology of ILI.     

Hypoxia enhances proliferation and stemness of human adipose-derived mesenchymal stem cells

The aim of the study was to obtain the highest number of multipotent adipose-derived mesenchymal stem cells (ADMSCs) by using culture conditions which favour cell expansion without loss of mesenchymal stem cells (MSC)-like properties. Based on the assumption that stem cells reside in niches characterized by hypoxic condition, we investigated if the low oxygen tension may improve the proliferation and stemness of ADMSCs. Intact adipose tissue was resected from eight subjects, and the stromal vascular fraction was obtained by using type II collagenase. The heterogeneity of cellular lineages was confirmed by immunophenotypic analysis that showed the presence of leukocytes (CD45+), endothelial cells (CD34+), and pericytes (CD140+). The immunophenotype of confluent ADMSCs was similar to that of bone marrow-derived MSCs, except for the expression of CD34, which was variable (donor-dependent) and inversely correlated to the CD36 expression. ADMSCs showed a high clonal efficiency (94.5 ± 1 %) and were able to generate osteoblastic, chondrocytic and adipocytic lineages. ADMSCs were cultured under normoxic (21 % O₂) and hypoxic (1 % O₂) conditions, and we found that hypoxia significantly favoured ADMSC proliferation and preserved the expression of stemness genes, i.e. Nanog and Sox2. Since hypoxia reflects the microenvironment in which ADMSCs must proliferate and differentiate, the culture in hypoxic condition allows to better understand the biology of these cells and their regenerative potential. Low oxygen concentrations promote cell proliferation and stemness, thus enriching the pool of cells potentially able to differentiate into multi-lineages, and extending the possibility of a long-term expansion.     

Transfected Poly(I:C) Activates Different dsRNA Receptors,Leading to Apoptosis or Immunoadjuvant Response in Androgen-independent Prostate Cancer Cells

Despite the effectiveness of surgery or radiation therapy for the treatment of early-stage prostate cancer (PCa), there is currently no effective strategy for late-stage disease. New therapeutic targets are emerging; in particular, dsRNA receptors Toll-like receptor 3 (TLR3) and cytosolic helicases expressed by cancer cells, once activated, exert a pro-apoptotic effect in different tumors. We previously demonstrated that the synthetic analog of dsRNA poly(I:C) induces apoptosis in the androgen-dependent PCa cell line LNCaP in a TLR3-dependent fashion, whereas only a weak apoptotic effect is observed in the more aggressive and androgen-independent PCa cells PC3 and DU145. In this paper, we characterize the receptors and the signaling pathways involved in the remarkable apoptosis induced by poly(I:C) transfected by Lipofectamine (in-poly(I:C)) compared with the 12-fold higher free poly(I:C) concentration in PC3 and DU145 cells. By using genetic inhibition of different poly(I:C) receptors, we demonstrate the crucial role of TLR3 and Src in in-poly(I:C)-induced apoptosis. Therefore, we show that the increased in-poly(I:C) apoptotic efficacy is due to a higher binding of endosomal TLR3. On the other hand, we show that in-poly(I:C) binding to cytosolic receptors MDA5 and RIG-I triggers IRF3-mediated signaling, leading uniquely to the up-regulation of IFN-β, which likely in turn induces increased TLR3, MDA5, and RIG-I proteins. In summary, in-poly(I:C) activates two distinct antitumor pathways in PC3 and DU145 cells: one mediated by the TLR3/Src/STAT1 axis, leading to apoptosis, and the other one mediated by MDA5/RIG-I/IRF3, leading to immunoadjuvant IFN-β expression.     

Identification and characterization of a novel salt‐tolerant esterase from a Tibetan glacier metagenomic library

A salt‐tolerant esterase, designated H9Est, was identified from a metagenomic library of the Karuola glacier. H9Est gene comprised 1071 bp and encoded a polypeptide of 357 amino acids with a molecular mass of 40 kDa. Sequence analysis revealed that H9Est belonged to the family IV of bacterial lypolitic enzyme. H9Est was overexpressed in Escherichia coli and the purified enzyme showed hydrolytic activity towards p‐nitrophenyl esters with carbon chain from 2 to 8. The optimal esterase activity was at 40°C and pH 8.0 and the enzyme retained its activity towards some miscible organic solvents such as polyethylene glycol. A three‐dimensional model of H9Est revealed that S200, D294, and H324 formed the H9Est catalytic triad. Circular Dichroism spectra and molecular dynamic simulation indicated that the esterase had a wide denaturation temperature range and flexible loops that would be beneficial for H9Est performance at low temperatures while retaining heat‐resistant features. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:890–899, 2015