A repeated GGA motif is critical for the activity and stability of the riboregulator RsmY of Pseudomonas fluorescens.

The riboregulator RsmY of Pseudomonas fluorescens strain CHA0 is an example of small regulatory RNAs belonging to the global Rsm/Csr regulatory systems controlling diverse cellular processes such as glycogen accumulation, motility, or formation of extracellular products in various bacteria. By binding multiple molecules of the small regulatory protein RsmA, RsmY relieves the negative effect of RsmA on the translation of several target genes involved in the biocontrol properties of strain CHA0. RsmY and functionally related riboregulators have repeated GGA motifs predicted to be exposed in single-stranded regions, notably in the loops of hairpins. The secondary structure of RsmY was corroborated by in vivo cleavage with lead acetate. RsmY mutants lacking three or five (out of six) of the GGA motifs showed reduced ability to derepress the expression of target genes in vivo and failed to bind the RsmA protein efficiently in vitro. The absence of GGA motifs in RsmY mutants resulted in reduced abundance of these transcripts and in a shorter half-life (< or = 6 min as compared with 27 min for wild type RsmY). These results suggest that both the interaction of RsmY with RsmA and the stability of RsmY strongly depend on the GGA repeats and that the ability of RsmY to interact with small regulatory proteins such as RsmA may protect this RNA from degradation.

Simulation methods with extended stability for stiff biochemical kinetics

Background: With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. Results: In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK) τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes.Conclusions: The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.

Y-chromosome diversity in native mexicans reveals continental transition of genetic structure in the Americas

The genetic characterization of Native Mexicans is important to understand multiethnic based features influencing the medical genetics of present Mexican populations, as well as to the reconstruct the peopling of the Americas. We describe the Y-chromosome genetic diversity of 197 Native Mexicans from 11 populations and 1,044 individuals from 44 Native American populations after combining with publicly available data. We found extensive heterogeneity among Native Mexican populations and ample segregation of Q-M242* (46%) and Q-M3 (54%) haplogroups within Mexico. The northernmost sampled populations falling outside Mesoamerica (Pima and Tarahumara) showed a clear differentiation with respect to the other populations, which is in agreement with previous results from mtDNA lineages. However, our results point toward a complex genetic makeup of Native Mexicans whose maternal and paternal lineages reveal different narratives of their population history, with sex-biased continental contributions and different admixture proportions. At a continental scale, we found that Arctic populations and the northernmost groups from North America cluster together, but we did not find a clear differentiation within Mesoamerica and the rest of the continent, which coupled with the fact that the majority of individuals from Central and South American samples are restricted to the Q-M3 branch, supports the notion that most Native Americans from Mesoamerica southwards are descendants from a single wave of migration. This observation is compatible with the idea that present day Mexico might have constituted an area of transition in the diversification of paternal lineages during the colonization of the Americas.

Prise en charge des jeunes patients avec endocrinopathies pediatriques chroniques: les défis d'une transition souvent difficile [Caring for patients with pediatric endocrinopathies and diabetes into adulthood: challenges of an often difficult transition].

The success of therapies for a number of pediatric disorders has posed new challenges for the long-term follow-up of adolescents with chronic endocrinopathies. Unfortunately, too many patients are lost during the transfer from pediatric to adult clinics. The transition process should be well-organized and include the young person and family. Recognizing the special needs of these adolescents is an important step in developing patient-centered approaches to care that enable patients to develop autonomy and self care skills. Key elements in this process include structured policies and guidelines, communication and close collaboration between pediatric and adult clinics, and integrating nurse clinicians in the transition process to help close the gaps in care.

The control of microtubule stability in vitro and in transfected cells by MAP1B and SCG10.

In neurons, the regulation of microtubules plays an important role for neurite outgrowth, axonal elongation, and growth cone steering. SCG10 family proteins are the only known neuronal proteins that have a strong destabilizing effect, are highly enriched in growth cones and are thought to play an important role during axonal elongation. MAP1B, a microtubule-stabilizing protein, is found in growth cones as well, therefore it was important to test their effect on microtubules in the presence of both proteins. We used recombinant proteins in microtubule assembly assays and in transfected COS-7 cells to analyze their combined effects in vitro and in living cells, respectively. Individually, both proteins showed their expected activities in microtubule stabilization and destruction respectively. In MAP1B/SCG10 double-transfected cells, MAP1B could not protect microtubules from SCG10-induced disassembly in most cells, in particular not in cells that contained high levels of SCG10. This suggests that SCG10 is more potent to destabilize microtubules than MAP1B to rescue them. In microtubule assembly assays, MAP1B promoted microtubule formation at a ratio of 1 MAP1B per 70 tubulin dimers while a ratio of 1 SCG10 per two tubulin dimers was needed to destroy microtubules. In addition to its known binding to tubulin dimers, SCG10 binds also to purified microtubules in growth cones of dorsal root ganglion neurons in culture. In conclusion, neuronal microtubules are regulated by antagonistic effects of MAP1B and SCG10 and a fine tuning of the balance of these proteins may be critical for the regulation of microtubule dynamics in growth cones.

Review of Stability Berm Alternatives for Environmentally Senstitive Areas, 2005

Stability berms are commonly constructed where roadway embankments cross soft or unstable ground conditions. Under certain circumstances, the construction of stability berms cause unfavorable environmental impacts, either directly or indirectly, through their effect on wetlands, endangered species habitat, stream channelization, longer culvert lengths, larger right-of-way purchases, and construction access limits. Due to an ever more restrictive regulatory environment, these impacts are problematic. The result is the loss of valuable natural resources to the public, lengthy permitting review processes for the department of transportation and permitting agencies, and the additional expenditures of time and money for all parties. The purpose of this project was to review existing stability berm alternatives for potential use in environmentally sensitive areas. The project also evaluates how stabilization technologies are made feasible, desirable, and cost-effective for transportation projects and determines which alternatives afford practical solutions for avoiding and minimizing impacts to environmentally sensitive areas. An online survey of engineers at state departments of transportation was also conducted to assess the frequency and cost effectiveness of the various stabilization technologies. Geotechnical engineers that responded to the survey overwhelmingly use geosynthetic reinforcement as a suitable and cost-effective solution for stabilizing embankments and cut slopes. Alternatively, chemical stabilization and installation of lime/cement columns is rarely a remediation measure employed by state departments of transportation.

Empirical Tests of Impacts of Rationing: The Case of Poland in Transition, February 2000

This study tests the theory of rationing, examining changes in household consumption behavior during the transition to a market economy in Poland, 1987–92. A model of consumption under rationing is developed and fitted to prereform quarterly data from the Polish Household Budget Survey. Virtual prices, prices at which consumers would have voluntarily chosen the rationed levels of goods, are derived for food and housing. The prereform Almost Ideal Demand System (AIDS) model with rationing is estimated. Estimates from the virtual AIDS yield plausible values for price and income elasticities. The AIDS model (without rationing) is also fitted to postreform quarterly household survey data for comparison and evaluation. When the two sets of results are compared, the impacts of rationing are consistent with the theory. Own-price elasticities for nonrationed goods are larger after the reform, and there is increased complementarity and decreased substitutability for the nonrationed goods. The results for Poland show a 75 percent decline in real household welfare over the transition and this welfare loss is one-third the value obtained using reported prices.

Lithuania’s Food Demand During Economic Transition, January 2000

The linear approximate version of the AIDS model is estimated using data from the Lithuanian household budget survey covering the period from July 1992 to December 1994. Price and real expenditure elasticities for twelve food groups were estimated based on the estimated coefficients of the model. Very little or nothing is known about the demand parameters of Lithuania and other former socialist countries, so the results are of intrinsic interest. Estimated expenditure elasticities were positive and statistically significant for all food groups while all own-price elasticities were negative and statistically significant, except for that of eggs which was insignificant. Results suggest that Lithuanian household consumption did respond to price and real income changes during their transition to a market-oriented economy.

Transition épidémiologique et évolution des facteurs de risque cardiovasculaire aux Seychelles

Les Seychelles connaissent une transition épidémiologique accélérée, parallèlement au développement socio-économique rapide au cours des trois dernières décennies. Les ressources des Seychelles, qui reposaient traditionnellement sur la production de copra, proviennent actuellement de la pêche industrielle, du tourisme et de services. Le produit national brut par habitant était inférieur à US$ 500 en 1970 et s'élève actuellement à US$ 14'000 actuellement, ce qui place les Seychelles parmi les pays à revenu intermédiaire supérieur. L'étude de la transition aux Seychelles est non seulement intéressante dans ce contexte de transformation socio-économique rapide, mais aussi parce que des données fiables permettent de documenter cette transition depuis trois décennies. Premièrement, la population est régulièrement énumérée et les données montrent un vieillissement rapide, avec un doublement de la population adulte en 25 ans, ce qui entraîne inévitablement une augmentation du nombre total de patients souffrant de maladies chroniques. Deuxièmement, 4 enquêtes de population ont été effectuées en 25 ans (1989, 1994, 2004 et 2013). Il ressort des prévalences élevées de plusieurs facteurs de risque des malades cardiovasculaires (MCV), mais les tendances sont, heureusement, à la baisse pour les facteurs de risque « traditionnels » (tabagisme, hypertension, dyslipidémie) mais, malheureusement, à la hausse pour les facteurs métaboliques « modernes » (obésité, diabète).

Leaving the labour market: event-history analysis of the female workers' transition to housework in Denmark, Germany, Great Britain and Spain

This paper is aimed at exploring the determinants of female activity from a dynamic perspective. An event-history analysis of the transition form employment to housework has been made resorting to data from the European Household Panel Survey. Four countries representing different welfare regimes and, more specifically, different family policies, have been selected for the analysis: Britain, Denmark, Germany and Spain. The results confirm the importance of individual-level factors, which is consistent with an economic approach to female labour supply. Nonetheless, there are significant cross-national differences in how these factors act over the risk of abandoning the labour market. First, the number of trnasitions is much lower among Danish working women than among British, German or Spanish ones, revealing the relative importance of universal provision of childcare services, vis-à-vis other elements of the family policy, as time or money.

Phacomatoses et tumeurs génétiquement déterminées: la transition enfant-adulte [Phacomatosis and genetically determined tumors: the transition from childhood to adulthood]

Les phacomatoses regroupent des maladies du développement du neurectoderme, engendrant des manifestations cutanées ou du système nerveux central. Les symptômes de ces maladies peuvent affecter les individus atteints à différents moments de leur vie. Il s'agit de maladies, héréditaires ou congénitales, qui sont transmises de façon variable. Effectivement, certaines, telles que la neurofibromatose, la sclérose tubéreuse ou la maladie de von Hippel-Lindau sont autosomiques dominantes, alors que d'autres, telles que la maladie de Sturge-Weber sont sporadiques. Des transmissions autosomiques récessives liées à X ou des formes mosaïques existent également. Une revue de la littérature, comprenant les cinq phacomatoses les plus fréquemment vues par un neurochirurgien (neurofibromatose de type I et II, sclérose tubéreuse de Bourneville, maladie de Sturge-Weber-Krabbe, maladie de von Hippel-Lindau) a été effectuée en se centrant sur le diagnostic, la variabilité de la symptomatologie selon l'âge du patient et son traitement. Les cas de patients adultes et pédiatriques vus aux consultations de neurologie et neurochirurgie de l'hôpital de Lille (France) et Lausanne (Suisse), de 1961 à nos jours, ont été revus pour illustrer les différentes pathologies rencontrées, selon l'âge des patients atteints. Le phénotype de ces maladies se modifie avec l'âge, car les gènes incriminés sont des gènes impliqués dans la différentiation tissulaire et sont activés à des âges différents suivant les tissus. Le rôle du neurochirurgien sera variable selon l'âge et le syndrome du patient. Il importe de connaître les variations du phénotype de ces maladies avec l'âge ainsi que les conséquences à long terme des traitements pour proposer au patient un suivi neurochirurgical personnalisé. Phacomatoses, or neurocutaneous disorders, are a group of congenital and hereditary diseases characterized by developmental lesions of the neuroectoderm, leading to pathologies affecting the skin and the central nervous system. There is a wide range of pathologies affecting individuals at different moments of life. The genetics is variable: while neurofibromatosis 1 and 2, tuberous sclerosis and von Hippel-Lindau disease are all inherited as autosomal dominant traits, Sturge-Weber syndrome is sporadic. Other neurocutaneous disorders can be inherited as autosomal recessive traits (i.e., ataxia-telangiectasia), X-linked (i.e., incontinentia pigmenti) or explained by mosaicism (i.e., hypomelanosis of Ito, McCune-Albright syndrome). In this review, we discuss the major types of neurocutaneous disorders most frequently encountered by the neurosurgeon and followed beyond childhood. They include neurofibromatosis types 1 and 2, tuberous sclerosis, Sturge-Weber syndrome and von Hippel-Lindau disease. In each case, a review of the literature, including diagnosis, genetics and treatment will be presented. The lifespan of the disease with the implications for neurosurgeons will be emphasized. A review of cases, including both pediatric and adult patients, seen in neurosurgical practices in the Lille, France and Lausanne, Switzerland hospitals between 1961 and 2007 is presented to illustrate the pathologies seen in different age-groups. Because the genes mutated in most phacomatoses are involved in development and are activated following a timed schedule, the phenotype of these diseases evolves with age. The implication of the neurosurgeon varies depending on the patient's age and pathology. While neurosurgeons tend to see pediatric patients affected with neurofibromatosis type 1, tuberous sclerosis and Sturge-Weber syndrome, there will be a majority of adult patients with von Hippel-Lindau disease or neurofibromatosis type 2

Improving Transition Outcomes-Value of IVRS Partnership, 2004

Iowa Vocational Rehabilitation Services, a Division of the State of Iowa Department of Education, in partnership with six other state agencies, applied for and was awarded funding for “Improving Transition Outcomes for Youth with Disabilities Through the Use of intermediaries.” This Innovative State Alignment Grant is funded by the Department of Labor, Office of Disability Employment Policy. For clarity and brevity, the Iowa team chose to use “Improving Transition Outcomes” as the project name, thus providing the acronym ITO. Grant funding began October 1, 2003 with the possibility of renewal for five years.

State of Iowa Improving Transition Outcomes Resource Mapping Workshops, 2003-2004

Iowa Vocational Rehabilitation Services, a Division of the State of Iowa Department of Education, in partnership with seven other state agencies, applied for and was awarded funding for “Improving Transition Outcomes for Youth with Disabilities Through the Use of Intermediaries.” This Innovative State Alignment Grant is funded by the Department of Labor, Office of Disability Employment Policy. For clarity and brevity, the Iowa team chose to use “Improving Transition Outcomes” as the project name, thus providing the acronym ITO. Grant funding began October 1, 2003 with the possibility of renewal for five years.

Improving Transition Outcomes-An Innovative State Alignment Grant for Improving Transition Outcome for Youth with Disabilities Through the Use of Intermediaries, 2004

Iowa Vocational Rehabilitation Services, a Division of the State of Iowa Department of Education, in partnership with six other state agencies, applied for and was awarded funding for “Improving Transition Outcomes for Youth with Disabilities Through the Use of intermediaries.” This Innovative State Alignment Grant is funded by the Department of Labor, Office of Disability Employment Policy. For clarity and brevity, the Iowa team chose to use “Improving Transition Outcomes” as the project name, thus providing the acronym ITO. Grant funding began October 1, 2003 with the possibility of renewal for five years.

Italy's Path to Very Low Fertility : The Adequacy of Economic and Second Demographic Transition Theories

The deep drop of the fertility rate in Italy to among the lowest in the world challenges contemporary theories of childbearing and family building. Among high-income countries, Italy was presumed to have characteristics of family values and female labor force participation that would favor higher fertility than its European neighbors to the north. We test competing economic and cultural explanations, drawing on new nationally representative, longitudinal data to examine first union, first birth, and second birth. Our event history analysis finds some support for economic determinants of family formation and fertility, but the clear importance of regional differences and of secularization suggests that such an explanation is at best incomplete and that cultural and ideational factors must be considered.