Synthesis, base pairing properties and trans-lesion synthesis by reverse transcriptases of oligoribonucleotides containing the oxidatively damaged base 5-hydroxycytidine

The synthesis of a caged RNA phosphoramidite building block containing the oxidatively damaged base 5-hydroxycytidine (5-HOrC) has been accomplished. To determine the effect of this highly mutagenic lesion on complementary base recognition and coding properties, this building block was incorporated into a 12-mer oligoribonucleotide for Tm and CD measurements and a 31-mer template strand for primer extension experiments with HIV-, AMV- and MMLV-reverse transcriptase (RT). In UV-melting experiments, we find an unusual biphasic transition with two distinct Tm's when 5-HOrC is paired against a DNA or RNA complement with the base guanine in opposing position. The higher Tm closely matches that of a C-G base pair while the lower is close to that of a C-A mismatch. In single nucleotide extension reactions, we find substantial misincorporation of dAMP and to a lesser extent dTMP, with dAMP almost equaling that of the parent dGMP in the case of HIV-RT. A working hypothesis for the biphasic melting transition does not invoke tautomeric variability of 5-HOrC but rather local structural perturbations of the base pair at low temperature induced by interactions of the 5-HO group with the phosphate backbone. The properties of this RNA damage is discussed in the context of its putative biological function.

Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach

The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders.

Use of audiovisual messages from land user to land user for sharing knowledge about SLM: experiences from a pilot project in Kenya and Tajikistan

The global World Overview of Conservation Approaches and Technologies (WOCAT) initiative has developed standardised tools and methods to compile and evaluate knowledge available about SLM. This knowledge is now combined and enriched with audiovisual information in order to give a voice to land users, reach a broad range of stakeholders, and assist in scaling up SLM to reverse trends of degradation, desertification, and drought. Five video products, adapted to the needs of different target groups, are created and embedded in already existing platforms for knowledge sharing of SLM such as the WOCAT database and Google Earth application. A pilot project was carried out in Kenya and Tajikistan to verify ideas and tools while at the same time assessing the usefulness of the suggested products on the ground. Video has the potential to bridge the gap between different actor groups and enable communication and sharing on different levels and scales: locally, regionally, and globally. Furthermore, it is an innovative tool to link local and scientific knowledge, raise awareness, and support advocacy for SLM. Keywords: Sustainable Land Management (SLM), knowledge sharing, audiovisual messages, video, World Overview of Conservation Approaches and Technologies (WOCAT)

Use of multi-media for spreading the experiences

The global World Overview of Conservation Approaches and Technologies (WOCAT) initiative has developed standardised tools and methods to compile and evaluate knowledge available about SLM. This knowledge is now combined and enriched with audiovisual information in order to give a voice to land users, reach a broad range of stakeholders, and assist in scaling up SLM to reverse trends of degradation, desertification, and drought. Five video products, adapted to the needs of different target groups, are created and embedded in already existing platforms for knowledge sharing of SLM such as the WOCAT database and Google Earth application. A pilot project was carried out in Kenya and Tajikistan to verify ideas and tools while at the same time assessing the usefulness of the suggested products on the ground. Video has the potential to bridge the gap between different actor groups and enable communication and sharing on different levels and scales: locally, regionally, and globally. Furthermore, it is an innovative tool to link local and scientific knowledge, raise awareness, and support advocacy for SLM.

A Food Recognition System for Diabetic Patients based on an Optimized Bag of Features Model

Computer vision-based food recognition could be used to estimate a meal's carbohydrate content for diabetic patients. This study proposes a methodology for automatic food recognition, based on the Bag of Features (BoF) model. An extensive technical investigation was conducted for the identification and optimization of the best performing components involved in the BoF architecture, as well as the estimation of the corresponding parameters. For the design and evaluation of the prototype system, a visual dataset with nearly 5,000 food images was created and organized into 11 classes. The optimized system computes dense local features, using the scale-invariant feature transform on the HSV color space, builds a visual dictionary of 10,000 visual words by using the hierarchical k-means clustering and finally classifies the food images with a linear support vector machine classifier. The system achieved classification accuracy of the order of 78%, thus proving the feasibility of the proposed approach in a very challenging image dataset.

The dual impact of gender and the influence of timing of parenthood on men’s and women’s career development: Longitudinal findings

This study investigated the impact of gender, the gender-related self-concept (agency and communion), and the timing of parenthood on objective career success of 1,015 highly educated professionals. Hypotheses derived from a dual-impact model of gender and career-related processes were tested in a 5-wave longitudinal study over a time span of 10 years starting with participants’ career entry. In line with our hypotheses we found that the communal component of the gender self-concept had an impact on parenthood, and the agentic component influenced work hours and objective career success (salary, status) of both women and men. Parenthood had a negative direct influence on women’s work hours and a negative indirect influence on women’s objective career success. Women who had their first child around career entry were relatively least successful over the observation period. Men’s career success was independent of parenthood. Sixty-five percent of variance in women’s career success and 33% of variance in men’s career success was explained by the factors analyzed here. Mothers with partners working full time reduced their work hours more than mothers with partners not working full time. A test for a possible reverse influence of career success on the decision to become a parent revealed no effect for men and equivocal effects for women. We conclude that the transition to parenthood still is a crucial factor for women’s career development both from an external gender perspective (expectations, gender roles) and from an internal perspective (gender-related self-concept).

Generation of long, fully modified, and serum-resistant oligonucleotides by rolling circle amplification

Rolling Circle Amplification (RCA) is an isothermal enzymatic method generating single-stranded DNA products consisting of concatemers containing multiple copies of the reverse complement of the circular template precursor. Little is known on the compatibility of modified nucleoside triphosphates (dN*TPs) with RCA, which would enable the synthesis of long, fully modified ssDNA sequences. Here, dNTPs modified at any position of the scaffold were shown to be compatible with rolling circle amplification, yielding long (>1 kb), and fully modified single-stranded DNA products. This methodology was applied for the generation of long, cytosine-rich synthetic mimics of telomeric DNA. The resulting modified oligo-nucleotides displayed an improved resistance to fetal bovine serum.

Moving along the mental number line: Interactions between whole-body motion and numerical cognition

Active head turns to the left and right have recently been shown to influence numerical cognition by shifting attention along the mental number line. In the present study, we found that passive whole-body motion influences numerical cognition. In a random-number generation task (Experiment 1), leftward and downward displacement of participants facilitated small number generation, whereas rightward and upward displacement facilitated the generation of large numbers. Influences of leftward and rightward motion were also found for the processing of auditorily presented numbers in a magnitude-judgment task (Experiment 2). Additionally, we investigated the reverse effect of the number-space association (Experiment 3). Participants were displaced leftward or rightward and asked to detect motion direction as fast as possible while small or large numbers were auditorily presented. When motion detection was difficult, leftward motion was detected faster when hearing small number and rightward motion when hearing large number. We provide new evidence that bottom-up vestibular activation is sufficient to interact with the higher-order spatial representation underlying numerical cognition. The results show that action planning or motor activity is not necessary to influence spatial attention. Moreover, our results suggest that self-motion perception and numerical cognition can mutually influence each other.