The functional and structural interactions between v-{\it mos\/} proteins and cell cycle control elements

The v-mos gene of Moloney murine sarcoma virus (Mo-MuSv) encodes a serine/threonine protein kinase capable of inducing cellular transformation. The c-mos protein is an important cell cycle regulator that functions during meiotic cell division cycles in germ cells. The overall function of c-mos in controlling meiosis is becoming better understood but the role of v-mos in malignant transformation of cells is largely unknown.^ In this study, v-mos protein was shown to be phosphorylated by M phase kinase in vitro and in vivo. The kinase activity and neoplastic transforming ability of v-mos is positively regulated by the phosphorylation. Together with the earlier finding of activation of M phase kinase by c-mos, these results raise the possibility of mutual regulation between M phase kinase and mos kinases.^ In addition to its functional interaction with the M phase kinase, the v-mos protein was shown to be present in the same protein complex with a cyclin-dependent kinase (cdk). In addition, an antibody that recognizes the cdk proteins was shown to co-precipitate the v-mos proteins in the interphase and mitotic cells transformed by p85$\sp{\rm gag-mos}$. Cdk proteins have been shown to be associated with nonmitotic cyclins which are potential oncogenes. The perturbation of cdk kinase or the activation of non-mitotic cyclins as oncogenes by v-mos could contribute directly to v-mos induced cellular transformation. v-mos proteins were also shown to interact with tubulin and vimentin, the essential components of microtubules and type IV intermediate filaments, respectively. The organizations of both microtubules and intermediate filaments are cell cycle-regulated. These results suggest that the v-mos kinase could be directly involved in inducing morphological changes typically seen in transformed cells.^ The interactions between the v-mos protein and these cell cycle control elements in regards to v-mos induced neoplastic transformation are discussed in detail in the text. ^

Identification of two vitamin D response elements in the rat osteopontin gene

Studies to elucidate the function of vitamin D have demonstrated an important role in regulating bone-related cells, including osteoblasts and osteoclasts. A seemingly paradoxical observation is that 1,25(OH)$\sb2$D$\sb3$, the active metabolite of vitamin D, stimulates bone resorption, yet regulates transcription of genes expressed by osteoblasts. One mechanism that could explain these actions is the upregulation of transcription of osteoblast-specific genes. These gene products could then act as effectors to influence osteoclastic activity. We hypothesized that molecular signals could be deposited directly into the mineralized matrix in the form of noncollagenous proteins, such as osteopontin (OPN). The structure, biosynthesis and localization of OPN suggest that it could function to mediate the molecular "cross talk" between osteoblasts and osteoclasts in response to 1,25(OH)$\sb2$D$\sb3$. To begin to address this hypothesis, elucidation of the molecular mechanisms of action involved in the transactivation of OPN by 1,25(OH)$\sb2$D$\sb3$ is essential.^ In the present study, the rat opn gene was isolated and characterized. Functional analysis by transient transfection of the 5$\sp\prime$ flanking sequences of the rat opn gene fused to the luciferase gene demonstrated that OPN is transcriptionally upregulated by 1,25(OH)$\sb2$D$\sb3$, mediated through two vitamin D response elements (VDRE). Both proximal and distal VDREs are structurally similar (two imperfect direct repeats separated by a 3 nucleotide spacer) and bind protein complexes that include the VDR and retinoid-X receptor (RXR). Isolated VDRE expression constructs produce functional activity of equivalent magnitude of responsiveness to 1,25(OH)$\sb2$D$\sb3$. However, expression constructs containing either VDRE and at least 200 bp of 5$\sp\prime$ and 3$\sp\prime$ flanking sequence demonstrated that the distal VDRE produces an amplitude of response significantly higher than the proximal VDRE. We conclude that the transcriptional upregulation of the opn gene by 1,25(OH)$\sb2$D$\sb3$ involves the transactivation of two VDREs, while maximal responsiveness requires interaction of the VDREs with additional cis-elements contained in the 5$\sp\prime$ sequence. ^

EC Electronic Communications and Competition Law

Telecommunications have developed at an incredible speed over the last couple of decades. The decreasing size of our phones and the increasing number of ways in which we can communicate are barely the only result of this (r)evolutionary development. The latter has indeed multiple implications. The change of paradigm for telecommunications regulation, epitomised by the processes of liberalisation and reregulation, was not sufficient to answer all regulatory questions pertinent to communications. Today, after the transition from monopoly to competition, we are faced perhaps with an even harder regulatory puzzle, since we must figure out how to regulate a sector that is as dynamic and as unpredictable as electronic communications have proven to be, and as vital and fundamental to the economy and to society at large. The present book addresses the regulatory puzzle of contemporary electronic communications and suggests the outlines of a coherent model for their regulation. The search for such a model involves essentially deliberations on the question "Can competition law do it all?", since generic competition rules are largely seen as the appropriate regulatory tool for the communications domain. The latter perception has been the gist of the 2002 reform of the European Community (EC) telecommunications regime, which envisages a withdrawal of sectoral regulation, as communications markets become effectively competitive and ultimately bestows the regulation of the sector upon competition law only. The book argues that the question of whether competition law is the appropriate tool needs to be examined not in the conventional contexts of sector specific rules versus competition rules or deregulation versus regulation but in a broader governance context. Consequently, the reader is provided with an insight into the workings and specific characteristics of the communications sector as network-bound, converging, dynamic and endowed with a special societal role and function. A thorough evaluation of the regulatory objectives in the communications environment contributes further to the comprehensive picture of the communications industry. Upon this carefully prepared basis, the book analyses the communications regulatory toolkit. It explores the interplay between sectoral communications regulation, competition rules (in particular Article 82 of the EC Treaty) and the rules of the World Trade Organization (WTO) relevant to telecommunications services. The in-depth analysis of multilevel construct of EC communications law is up-to-date and takes into account important recent developments in the EC competition law in practice, in particular in the field of refusal to supply and tying, of the reform of the EC electronic communications framework and new decisions of the WTO dispute settlement body, such as notably the Mexico-Telecommunications Services Panel Report. Upon these building elements, an assessment of the regulatory potential of the EC competition rules is made. The conclusions drawn are beyond the scope of the current situation of EC electronic communications and the applicable law and explore the possible contours of an optimal regulatory framework for modern communications. The book is of particular interest to communications and antitrust law experts, as well as policy makers, government agencies, consultancies and think-tanks active in the field. Experts on other network industries (such as electricity or postal communications) can also profit from the substantial experience gathered in the communications sector as the most advanced one in terms of liberalisation and reregulation.

Impacts of a word-picture training on literacy skills in elementary school children and youths with intellectual disabilities

Objective: There is convincing evidence that phonological, orthographic and semantic processes influence children’s ability to learn to read and spell words. So far only a few studies investigated the influence of implicit learning in literacy skills. Children are sensitive to the statistics of their learning environment. By frequent reading they acquire implicit knowledge about the frequency of letter patterns in written words, and they use this knowledge during reading and spelling. Additionally, semantic connections facilitate to storing of words in memory. Thus, the aim of the intervention study was to implement a word-picture training which is based on statistical and semantic learning. Furthermore, we aimed at examining the training effects in reading and spelling in comparison to an auditory-visual matching training and a working memory training program. Participants and Methods: One hundred and thirty-two children aged between 8 and 11 years participated in training in three weekly session of 12 minutes over 8 weeks, and completed other assessments of reading, spelling, working memory and intelligence before and after training. Results: Results revealed in general that the word-picture training and the auditory-visual matching training led to substantial gains in reading and spelling performance in comparison to the working-memory training. Although both children with and without learning difficulties profited in their reading and spelling after the word-picture training, the training program led to differential effects for the two groups. After the word-picture training on the one hand, children with learning difficulties profited more in spelling as children without learning difficulties, on the other hand, children without learning difficulties benefit more in word comprehension. Conclusions: These findings highlight the need for frequent reading trainings with semantic connections in order to support the acquisition of literacy skills.

Getting the big picture: Development of spatial scaling abilities

Spatial scaling is an integral aspect of many spatial tasks that involve symbol-to-referent correspondences (e.g., map reading, drawing). In this study, we asked 3–6-year-olds and adults to locate objects in a two-dimensional spatial layout using information from a second spatial representation (map). We examined how scaling factor and reference features, such as the shape of the layout or the presence of landmarks, affect performance. Results showed that spatial scaling on this simple task undergoes considerable development, especially between 3 and 5 years of age. Furthermore, the youngest children showed large individual variability and profited from landmark information. Accuracy differed between scaled and un-scaled items, but not between items using different scaling factors (1:2 vs. 1:4), suggesting that participants encoded relative rather than absolute distances.

[The effectiveness of rare earth elements as a possible alternative growth promoter for pigs and poultry].

Mixtures of Rare Earth Elements (REE) have been used as animal growth-promoters on a large scale in China during the last 20 years. Numerous studies carried out in China claim it produces quite sensational growth-promoting effects in all categories of farm animals. To explore the question of whether REE's might prove suitable as a growth-promoter under western keeping conditions, feeding experiments were performed on pigs and poultry. The animals received a typical diet, supplemented with REE salts in concentrations between 75 and 300 mg/kg feed. Weight-gain, feed-intake, feed-conversion and (where applicable) laying parameters were observed. It was shown that in pigs receiving feed supplemented with REEs, an increase in daily weight gain of up to 19% and an improvement in feed-conversion of up to 11% can be achieved, whereas, for poultry, no positive effects on growth or productivity of the animals could be observed. Testing of important organs via Neutron Activating Analysis (NAA) showed a minute accumulation of REE, principally in liver and bones. Analysis of the poultry gut-flora, using selective media, showed that the main microorganism populations of the alimentary canal were unaffected by feed-supplementation with REE.

Impacts of a word-picture training on reading in youth with mixed intellectual disabilities. A waiting-list control group comparison

Individuals with intellectual disabilities (ID) often struggle with learning how to read. Reading difficulties seem to be the most common secondary condition of ID. Only one in five children with mild or moderate ID achieves even minimal literacy skills. However, literacy education for children and adolescents with ID has been largely overlooked by researchers and educators. While there is little research on reading of children with ID, many training studies have been conducted with other populations with reading difficulties. The most common approach of acquiring literacy skills consists of sophisticated programs that train phonological skills and auditory perception. Only few studies investigated the influence of implicit learning on literacy skills. Implicit learning processes seem to be largely independent of age and IQ. Children are sensitive to the statistics of their learning environment. By frequent word reading they acquire implicit knowledge about the frequency of single letters and letter patterns in written words. Additionally, semantic connections not only improve the word understanding, but also facilitate storage of words in memory. Advances in communication technology have introduced new possibilities for remediating literacy skills. Computers can provide training material in attractive ways, for example through animations and immediate feedback .These opportunities can scaffold and support attention processes central to learning. Thus, the aim of this intervention study was to develop and implement a computer based word-picture training, which is based on statistical and semantic learning, and to examine the training effects on reading, spelling and attention in children and adolescents (9-16 years) diagnosed with mental retardation (general IQ  74). Fifty children participated in four to five weekly training sessions of 15-20 minutes over 4 weeks, and completed assessments of attention, reading, spelling, short-term memory and fluid intelligence before and after training. After a first assessment (T1), the entire sample was divided in a training group (group A) and a waiting control group (group B). After 4 weeks of training with group A, a second assessment (T2) was administered with both training groups. Afterwards, group B was trained for 4 weeks, before a last assessment (T3) was carried out in both groups. Overall, the results showed that the word-picture training led to substantial gains on word decoding and attention for both training groups. These effects were preserved six weeks later (group A). There was also a clear tendency of improvement in spelling after training for both groups, although the effect did not reach significance. These findings highlight the fact that an implicit statistical learning training in a playful way by motivating computer programs can not only promote reading development, but also attention in children with intellectual disabilities.

Gas composition of the main volatile elements in protoplanetary discs and its implication for planet formation

Context. Direct observations of gaseous exoplanets reveal that their gas envelope has a higher C/O ratio than that of the host star (e.g., Wasp 12-b). This has been explained by considering that the gas phase of the disc could be inhomogeneous, exceeding the stellar C/O ratio in regions where these planets formed; but few studies have considered the drift of the gas and planet migration. Aims. We aim to derive the gas composition in planets through planet formation to evaluate if the formation of giant planets with an enriched C/O ratio is possible. The study focusses on the effects of different processes on the C/O ratio, such as the disc evolution, the drift of gas, and planet migration. Methods. We used our previous models for computing the chemical composition, together with a planet formation model, to which we added the composition and drift of the gas phase of the disc, which is composed of the main volatile species H2O, CO, CO2, NH3, N2, CH3OH, CH4, and H2S, H2 and He. The study focusses on the region where ice lines are present and influence the C/O ratio of the planets. Results. Modelling shows that the condensation of volatile species as a function of radial distance allows for C/O enrichment in specific parts of the protoplanetary disc of up to four times the solar value. This leads to the formation of planets that can be enriched in C/O in their envelope up to three times the solar value. Planet migration, gas phase evolution and disc irradiation enables the evolution of the initial C/O ratio that decreases in the outer part of the disc and increases in the inner part of the disc. The total C/O ratio of the planets is governed by the contribution of ices accreted, suggesting that high C/O ratios measured in planetary atmospheres are indicative of a lack of exchange of material between the core of a planet and its envelope or an observational bias. It also suggests that the observed C/O ratio is not representative of the total C/O ratio of the planet.