Temporal stability of stimulus representation increases along rodent visual cortical hierarchies

Cortical representations of brief, static stimuli become more invariant to identity-preserving transformations along the ventral stream. Likewise, increased invariance along the visual hierarchy should imply greater temporal persistence of temporally structured dynamic stimuli, possibly complemented by temporal broadening of neuronal receptive fields. However, such stimuli could engage adaptive and predictive processes, whose impact on neural coding dynamics is unknown. By probing the rat analog of the ventral stream with movies, we uncovered a hierarchy of temporal scales, with deeper areas encoding visual information more persistently. Furthermore, the impact of intrinsic dynamics on the stability of stimulus representations grew gradually along the hierarchy. A database of recordings from mouse showed similar trends, additionally revealing dependencies on the behavioral state. Overall, these findings show that visual representations become progressively more stable along rodent visual processing hierarchies, with an important contribution provided by intrinsic processing

A mode-of-action ontology model for safety evaluation of chemicals: outcome of a series of workshops on repeated dose toxicity

Repeated dose toxicity evaluation aims at assessing the occurrence of adverse effects following chronic or repeated exposure to chemicals. Non-animal approaches have gained importance in the last decades because of ethical considerations as well as due to scientific reasons calling for more human-based strategies. A critical aspect of this challenge is linked to the capacity to cover a comprehensive set of interdependent mechanisms of action, link them to adverse effects and interpret their probability to be triggered in the light of the exposure at the (sub)cellular level. Inherent to its structured nature, an ontology addressing repeated dose toxicity could be a scientific and transparent way to achieve this goal. Additionally, repeated dose toxicity evaluation through the use of a harmonized ontology should be performed in a reproducible and consistent manner, while mimicking as accurately as possible human physiology and adaptivity. In this paper, the outcome of a series of workshops organized by Cosmetics Europe on this topic is reported. As such, this manuscript shows how experts set critical elements and ways of establishing a mode-of-action ontology model as a support to risk assessors aiming to perform animal-free safety evaluation of chemicals based on repeated dose toxicity data

A21 HIV-1 sub-subtype F1 outbreak among MSM in Belgium

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Mate Value and Self-Esteem: Evidence from Eight Cultural Groups

This paper explores self-perceived mate value (SPMV), and its association with self-esteem, in eight cultures. 1066 participants, from 8 cultural groups in 7 countries, rated themselves on 24 SPMVs and completed a measure of self-esteem. Consistent with evolutionary theory, women were more likely to emphasise their caring and passionate romantic nature. In line with previous cross-cultural research, characteristics indicating passion and romance and social attractiveness were stressed more by respondents from individualistic cultures, and those higher on self-expression (rather than survival) values; characteristics indicative of maturity and confidence were more likely to be mentioned by those from Traditional, rather than Secular, cultures. Contrary to gender role theory, societal equality had only limited interactions with sex and SPMV, with honesty of greater significance for male self-esteem in societies with unequal gender roles. These results point to the importance of cultural and environmental factors in influencing self-perceived mate qualities, and are discussed in relation to broader debates about the impact of gender role equality on sex differences in personality and mating strategies

Trends and predictors of transmitted drug resistance (TDR) and clusters with TDR in a local Belgian HIV-1 epidemic

We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures

Prediction of Preterm Deliveries from EHG Signals Using Machine Learning

There has been some improvement in the treatment of preterm infants, which has helped to increase their chance of survival. However, the rate of premature births is still globally increasing. As a result, this group of infants are most at risk of developing severe medical conditions that can affect the respiratory, gastrointestinal, immune, central nervous, auditory and visual systems. In extreme cases, this can also lead to long-term conditions, such as cerebral palsy, mental retardation, learning difficulties, including poor health and growth. In the US alone, the societal and economic cost of preterm births, in 2005, was estimated to be $26.2 billion, per annum. In the UK, this value was close to £2.95 billion, in 2009. Many believe that a better understanding of why preterm births occur, and a strategic focus on prevention, will help to improve the health of children and reduce healthcare costs. At present, most methods of preterm birth prediction are subjective. However, a strong body of evidence suggests the analysis of uterine electrical signals (Electrohysterography), could provide a viable way of diagnosing true labour and predict preterm deliveries. Most Electrohysterography studies focus on true labour detection during the final seven days, before labour. The challenge is to utilise Electrohysterography techniques to predict preterm delivery earlier in the pregnancy. This paper explores this idea further and presents a supervised machine learning approach that classifies term and preterm records, using an open source dataset containing 300 records (38 preterm and 262 term). The synthetic minority oversampling technique is used to oversample the minority preterm class, and cross validation techniques, are used to evaluate the dataset against other similar studies. Our approach shows an improvement on existing studies with 96% sensitivity, 90% specificity, and a 95% area under the curve value with 8% global error using the polynomial classifier

The growth pattern of transplanted normal and nodular hepatocytes

Overt neoplasia is often the end result of a long biological process beginning with the appearance of focal lesions of altered tissue morphology. While the putative clonal nature of focal lesions has often been emphasized, increasing attention is being devoted to the possible role of an altered growth pattern in the evolution of carcinogenesis. Here we compare the growth patterns of normal and nodular hepatocytes in a transplantation system that allows their selective clonal proliferation in vivo. Rats were pre-treated with retrorsine, which blocks the growth of resident hepatocytes, and were then transplanted with hepatocytes isolated from either normal liver or hepatocyte nodules. Both cell types were able to proliferate extensively in the recipient liver, as expected. However, their growth pattern was remarkably different. Clusters of normal hepatocytes integrated in the host liver, displaying a normal histology; however, transplanted nodular hepatocytes formed new hepatocyte nodules, with altered morphology and sharp demarcation from surrounding host liver. Both the expression and distribution of proteins involved in cell polarity, cell communication, and cell adhesion, including connexin 32, E-cadherin, and matrix metalloproteinase-2, were altered in clusters of nodular hepatocytes. Furthermore, we were able to show that down-regulation of connexin 32 and E-cadherin in nodular hepatocyte clusters was independent of growth rate. These results support the concept that a dominant pathway towards neoplastic disease in several organs involves defect(s) in tissue pattern formation

MAK-4 and -5 supplemented diet inhibits liver carcinogenesis in mice

<p>Abstract</p> <p>Background</p> <p>Maharishi Amrit Kalash (MAK) is an herbal formulation composed of two herbal mixtures, MAK-4 and MAK-5. These preparations are part of a natural health care system from India, known as Maharishi Ayur-Veda. MAK-4 and MAK-5 are each composed of different herbs and are said to have maximum benefit when used in combination. This investigation evaluated the cancer inhibiting effects of MAK-4 and MAK-5, <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p><it>In vitro </it>assays: Aqueous extracts of MAK-4 and MAK-5 were tested for effects on <it>ras </it>induced cell transformation in the Rat 6 cell line assessed by focus formation assay. <it>In vivo </it>assays: Urethane-treated mice were put on a standard pellet diet or a diet supplemented with MAK-4, MAK-5 or both. At 36 weeks, livers were examined for tumors, sera for oxygen radical absorbance capacity (ORAC), and liver homogenates for enzyme activities of glutathione peroxidase (GPX), glutathione-S-transferase (GST), and NAD(P)H: quinone reductase (QR). Liver fragments of MAK-fed mice were analyzed for connexin (cx) protein expression.</p> <p>Results</p> <p>MAK-5 and a combination of MAK-5 plus MAK-4, inhibited <it>ras</it>-induced cell transformation. In MAK-4, MAK-5 and MAK4+5-treated mice we observed a 35%, 27% and 46% reduction in the development of urethane-induced liver nodules respectively. MAK-4 and MAK4+5-treated mice had a significantly higher ORAC value (<it>P </it>< 0.05) compared to controls (200.2 ± 33.7 and 191.6 ± 32.2 <it>vs. </it>152.2 ± 15.7 ORAC units, respectively). The urethane-treated MAK-4, MAK-5 and MAK4+5-fed mice had significantly higher activities of liver cytosolic enzymes compared to the urethane-treated controls and to untreated mice: GPX(0.23 ± 0.08, 0.21 ± 0.05, 0.25 ± 0.04, 0.20 ± 0.05, 0.21 ± 0.03 U/mg protein, respectively), GST (2.0 ± 0.4, 2.0 ± 0.6, 2.1 ± 0.3, 1.7 ± 0.2, 1.7 ± 0.2 U/mg protein, respectively) and QR (0.13 ± 0.02, 0.12 ± 0.06, 0.15 ± 0.03, 0.1 ± 0.04, 0.11 ± 0.03 U/mg protein, respectively). Livers of MAK-treated mice showed a time-dependent increased expression of cx32.</p> <p>Conclusion</p> <p>Our results show that a MAK-supplemented diet inhibits liver carcinogenesis in urethane-treated mice. The prevention of excessive oxidative damage and the up-regulation of connexin expression are two of the possible effects of these products.</p

Learning to Think Iconically in the Human and Social Sciences: Iconic Standards of Understanding as a Pivotal Challenge for Method Development

Theoretically as well as alongside an empirical research idea, this paper outlines conditions for the development of social scientific empirical methods able to further exploit the iconic potential of the image. Reconstructing the role of formal pictorial elements for the standards of understanding within the medium “image” is considered pivotal in this endeavor. Within the context of language, standards of communication have already been extensively researched. The linguistic format of the narrative, for instance, is well studied. Up to now, though, comparable formal vehicles of iconic semantics have only been examined in aesthetics and art history. Nevertheless, standards of iconic understanding are part of our implicit knowledge, are incessantly in use in everyday practice and, thus, the basis of everyday identity formation. With the help of empirical methods based on an iconic logos we can deepen our understanding of orientations, longings, and anxieties of our time that are often silently conveyed by images. Fashion will be outlined as a prototypical field, in which an empirically based development of such methods might start off

DNA Methyltransferase Controls Stem Cell Aging by Regulating BMI1 and EZH2 through MicroRNAs

Epigenetic regulation of gene expression is well known mechanism that regulates cellular senescence of cancer cells. Here we show that inhibition of DNA methyltransferases (DNMTs) with 5-azacytidine (5-AzaC) or with specific small interfering RNA (siRNA) against DNMT1 and 3b induced the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) and increased p16INK4A and p21CIP1/WAF1 expression. DNMT inhibition changed histone marks into the active forms and decreased the methylation of CpG islands in the p16INK4A and p21CIP1/WAF1 promoter regions. Enrichment of EZH2, the key factor that methylates histone H3 lysine 9 and 27 residues, was decreased on the p16INK4A and p21CIP1/WAF1 promoter regions. We found that DNMT inhibition decreased expression levels of Polycomb-group (PcG) proteins and increased expression of microRNAs (miRNAs), which target PcG proteins. Decreased CpG island methylation and increased levels of active histone marks at genomic regions encoding miRNAs were observed after 5-AzaC treatment. Taken together, DNMTs have a critical role in regulating the cellular senescence of hUCB-MSCs through controlling not only the DNA methylation status but also active/inactive histone marks at genomic regions of PcG-targeting miRNAs and p16INK4A and p21CIP1/WAF1 promoter regions