Development and cross-amplification of thirty microsatellite loci in five diploid and polyploid Central Asian species of Palearctic green toads (Bufo viridis subgroup)

We report 30 polymorphic microsatellite markers for five species of Palearctic green toads (Bufo viridis subgroup): 23 in the diploid B. latastii, 19 in diploid B. turanensis, 20 in diploid B. shaartusiensis, 27 in tetraploid B. pewzowi, and 30 in triploid B. baturae. Genetic diversity at these loci, measured for 10-18 individuals per species, ranged from 2 to 19 alleles. These microsatellite loci will be useful for conservation plans (genetic diversity, population structure, evolutionary units), inheritance patterns, and evolution of green toads.

The Same, but Different: Central Banks, Regulatory Agencies, and the Politics of Delegation to Independent Authorities

Independent regulatory agencies are the institutional foundations of the regulatory state that, during the past 15 years, has gained prominence throughout Europe. This article studies the rise of independent authorities in European countries by comparing regulatory agencies and central banks. Delegation to independent central banks and to independent regulatory agencies is similar in many respects. In both cases, agents are deliberately made independent from political principals through a specific institutional design. Moreover, it has been argued that delegation to both central banks and regulatory agencies is linked to the need for policy-makers to improve the credibility of policy commitments, to the wish of incumbent politicians to tie the hands of future majorities, and to the extent to which the institutional contexts safeguard policy stability. Through an analysis of the formal independence of central banks and regulatory agencies in Western Europe, this article identifies an empirical puzzle that casts doubts on the accuracy of current explanations. Veto players and the uncertainty of incumbent policy-makers in respect to their re-election prospects matter for delegation to both central banks and regulatory agencies, but in opposite ways. Making sense of these anomalies is necessary to achieve a better understanding of delegation to independent authorities.

DNA banking for plant breeding, biotechnology and biodiversity evaluation.

The manipulation of DNA is routine practice in botanical research and has made a huge impact on plant breeding, biotechnology and biodiversity evaluation. DNA is easy to extract from most plant tissues and can be stored for long periods in DNA banks. Curation methods are well developed for other botanical resources such as herbaria, seed banks and botanic gardens, but procedures for the establishment and maintenance of DNA banks have not been well documented. This paper reviews the curation of DNA banks for the characterisation and utilisation of biodiversity and provides guidelines for DNA bank management. It surveys existing DNA banks and outlines their operation. It includes a review of plant DNA collection, preservation, isolation, storage, database management and exchange procedures. We stress that DNA banks require full integration with existing collections such as botanic gardens, herbaria and seed banks, and information retrieval systems that link such facilities, bioinformatic resources and other DNA banks. They also require efficient and well-regulated sample exchange procedures. Only with appropriate curation will maximum utilisation of DNA collections be achieved.

The Regulation of Foreign Banks in Switzerland (1956-1972)

The Swiss financial centre witnessed an important shift during the 1960s: the number of foreign banks and their importance in relation to the domestic banking sector significantly increased. Faced with this rapid development, Swiss bank representatives and political and monetary authorities reacted strongly. This paper investigates the evolution of the regulatory response by Swiss banking policy actors to the proliferation of foreign financial in- stitutions. In 1969, those reactions led to the adoption of a discriminatory regime, setting higher entry barriers for foreign banks than for domestic institutions. After examining possible reasons for the attractiveness of Switzerland to foreign banks, this paper will analyse the concerns and fears of the domestic banking sector and its regulators. In this regard, it appears that issues such as mere competition, preservation of the international reputation of the Swiss banks and anti-inflationary monetary policy were central to the chosen regulatory regime. Moreover, this paper shows that foreign banks were used as scapegoats in the evolution of the Swiss system of banking supervision. They were more tightly regulated, yet the general framework remained very lax.

Central nervous system stimulants and sport practice.

BACKGROUND AND OBJECTIVES: Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport. METHODS: Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine. RESULTS: CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti-doping laboratories statistics and the media, and their potentially serious adverse effects. CONCLUSIONS: Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced.

From rifting to passive margin - The examples of the Red Sea, Central Atlantic and Alpine Tethys

Evolution of the Red Sea/Gulf of Suez and the Central Atlantic rift systems shows that an initial, transtensive rifting phase, affecting a broad area around the future zone of crustal separation, was followed by a pre-oceanic rifting phase during which extensional strain was concentrated on the axial rift zone. This caused lateral graben systems to become inactive and they evolved into rift-rim basins. The transtensive phase of diffuse crustal extension is recognized in many intra-continental rifts. If controlling stress systems relax, these rifts abort and develop into palaeorifts. If controlling stress systems persist, transtensive rift systems can enter the pre-oceanic rifting stage, during which the rift zone narrows and becomes asymmetric as a consequence of simple-shear deformation at shallow crustal levels and pure shear deformation at lower crustal and mantle-lithospheric levels. Preceding crustal separation, extensional denudation of the lithospheric mantle is possible. Progressive lithospheric attenuation entails updoming of the asthenosphere and thermal doming of the rift shoulders. Their uplift provides a major clastic source for the rift basins and the lateral rift-rim basins. Their stratigraphic record provides a sensitive tool for dating the rift shoulder uplift. Asymmetric rifting leads to the formation of asymmetric continental margins, corresponding in a simple-shear model to an upper plate and a conjugate lower plate margin, as seen in the Central Atlantic passive margins of the United States and Morocco. This rifting model can be successfully applied to the analysis of the Alpine Tethys palaeo-margins (such as Rif and the Western Alps).

Influence of age, risk factors, and cardiovascular and renal disease on arterial stiffness: clinical applications.

Age is the main clinical determinant of large artery stiffness. Central arteries stiffen progressively with age, whereas peripheral muscular arteries change little with age. A number of clinical studies have analyzed the effects of age on aortic stiffness. Increase of central artery stiffness with age is responsible for earlier wave reflections and changes in pressure wave contours. The stiffening of aorta and other central arteries is a potential risk factor for increased cardiovascular morbidity and mortality. Arterial stiffening with aging is accompanied by an elevation in systolic blood pressure (BP) and pulse pressure (PP). Although arterial stiffening with age is a common situation, it has now been confirmed that older subjects with increased arterial stiffness and elevated PP have higher cardiovascular morbidity and mortality. Increase in aortic stiffness with age occurs gradually and continuously, similarly for men and women. Cross-sectional studies have shown that aortic and carotid stiffness (evaluated by the pulse wave velocity) increase with age by approximately 10% to 15% during a period of 10 years. Women always have 5% to 10% lower stiffness than men of the same age. Although large artery stiffness increases with age independently of the presence of cardiovascular risk factors or other associated conditions, the extent of this increase may depend on several environmental or genetic factors. Hypertension may increase arterial stiffness, especially in older subjects. Among other cardiovascular risk factors, diabetes type 1 and 2 accelerates arterial stiffness, whereas the role of dyslipidemia and tobacco smoking is unclear. Arterial stiffness is also present in several cardiovascular and renal diseases. Patients with heart failure, end stage renal disease, and those with atherosclerotic lesions often develop central artery stiffness. Decreased carotid distensibility, increased arterial thickness, and presence of calcifications and plaques often coexist in the same subject. However, relationships between these three alterations of the arterial wall remain to be explored.

Intellectual outcome in children and adolescents with acute lymphoblastic leukaemia treated with chemotherapy alone: age- and sex-related differences.

One of the most relevant concerns in long-term survivors of paediatric acute lymphoblastic leukaemia (ALL) is the development of neuropsychological sequelae. The majority of the published studies report on patients treated with chemotherapy and prophylactic central nervous system (CNS) irradiation, little is known about the outcome of patients treated with chemotherapy-only regimens. Using the standardised clinical and neuropsychological instruments of the SPOG Late Effects Study, the intellectual performance of 132 paediatric ALL patients treated with chemotherapy only was compared to that of 100 control patients surviving from diverse non-CNS solid tumours. As a group, ALL and solid tumour survivors showed normal and comparable intellectual performances (mean global IQ 104.6 in both groups). The percentage of patients in the borderline range (global IQ between 70 and 85) was comparable and not higher as expected (10% cases and 13% controls, expected 16%). Only 2 (2%) of the former ALL and 1 (1%) of the solid tumour patients were in the range of mental retardation (global IQ<70). Former known risk factors described in children treated with prophylactic CNS irradiation, like a younger age at diagnosis of ALL and female gender, remained valid in chemotherapy-only treated patients. The abandonment of prophylactic CNS irradiation and its replacement by a more intensive systemic and intrathecal chemotherapy led to a reduction, but not the disappearance of late neuropsychological sequelae.

Clinical and genetic findings in a large cohort of patients with congenital myopathies due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene

RYR1 mutations are the most common cause of structural congenital myopathies and may exhibit both dominant and recessive inheritance. Histopathological findings are variable and include central cores, multi-minicores, type 1 predominance/ uniformity, fibre type disproportion, increased internal nucleation and fatty and connective tissue. Until recently, diagnostic RYR1 sequencing was limited to mutational hotspots due to the large size of the gene. Since the introduction of full RYR1 sequencing in 2007 we have detected pathogenic mutations in 77 families: 39 had dominant inheritance and 38 recessive inheritance. In some cases with presumably recessive inheritance, only one heterozygous mutation inherited from an asymptomatic parent was identified. Of 28 dominant mutations, 6 were novel; 37 of the 59 recessive mutations were also novel. Dominant mutations were more frequently in recognized hotspot regions, while recessive mutations were distributed throughout the coding sequence. Dominant mutations were predominantly missense, whereas recessive mutations included many nonsense and splice mutations expected to result in reduced RyR1 protein. There was wide clinical variability in patients with both dominant and recessive inheritance. As a group, those with dominant mutations were generally more mildly affected than those with recessive inheritance, who had earlier onset and were weaker with more functional limitations. Extraocular muscle involvement was almost exclusively observed in the recessive group. Bulbar involvement was also more prominent in this group, resulting in a larger number requiring gastrostomy insertion. In conclusion, genomic sequencing of the entire RYR1 leads to the detection of many novel mutations, but may miss large genetic rearrangements in some cases. Assigning pathogenicity to novel mutations is often difficult and interpretation of genetic results in the context of clinical, histological and, increasingly, muscle MRI findings is essential.

Le conseil génétique: aspects théoriques et pratique en prénatal [Genetic counselling: theoretical aspects and prenatal practice]

Le conseil génétique doit fournir aux individus une information médicale précise et un soutien psychologique. L'importance des principes d'autonomie et de confidentialité, dogmes du conseil génétique, est renforcée par la nouvelle loi suisse (LAGH). Dans certains pays, une grande partie du conseil génétique est assurée par des conseillers en génétique non médecins ayant une formation postgraduée spécifique. Le conseil génétique joue un rôle grandissant dans différents domaines de la médecine. En particulier, il est indispensable dans le contexte du prénatal où les couples reçoivent des informations complexes et doivent bénéficier d’un soutien pour prendre une décision. Genetic counselling provides families with accurate medical information and psychological support. Respect and concern for the emotional well-being should be taken into account while discussing genetics aspects and recurrence risks. The importance of autonomy and confidentiality, central to genetic counselling, is reinforced by the new Swiss law (LAGH). In many countries, most of the genetic counselling is provided by genetic counsellors who have a specialised post-graduate training. Genetic counselling plays an increasing role in different medical specialities. In particular, it is essential in the context of prenatal and pre-conceptual care, where couples are confronted to complex information and should have access to appropriate support during the decision-making process

Expression and developmental regulation of Ehk-1, a neuronal Elk-like receptor tyrosine kinase in brain.

Protein tyrosine kinases are pivotal in central nervous tissue development and maintenance. Here we focus on the expression of Ehk-1, a novel Elk-related receptor tyrosine kinase. Ehk-1 gene expression is observed in the developing and adult central nervous system and is highly regulated throughout development at both the messenger RNA and protein levels. Three messenger RNA transcripts of 8.5, 5.9 and 5.1 kb are detectable in the rat brain and a variety of splice possibilities have been identified. However, a major protein species of around M(r) 120,000 predominates throughout development. Ehk-1 messenger RNA and protein levels are highest in the first postnatal week. By in situ messenger RNA hybridization the gene is expressed by all neurons of the adult brain, but mostly in the hippocampus, cerebral cortex and large neurons of the deep cerebellar nuclei, as well as the Purkinje and granular cells of the cerebellum. At earlier stages of development, transcripts are most prominent in the periventricular germinal layers of the brain. Immunohistochemistry reveals a pronounced membrane associated protein expression in immature neurons. In the adult animal, peak reactivity was found in the neuropil with sparing of most perikarya. The spatial and temporal pattern of ehk-1 gene expression suggests a role in both the development and maintenance of differentiated neurons of the central nervous system.

Insulin and NPY pathways and the control of GnRH function and puberty onset.

Energy balance exerts a critical influence on reproductive function. Leptin and insulin are among the metabolic factors signaling the nutritional status of an individual to the hypothalamus, and their role in the overall modulation of the activity of GnRH neurons is increasingly recognized. As such, they participate to a more generalized phenomenon: the signaling of peripheral metabolic changes to the central nervous system. The physiological importance that the interactions occurring between peripheral metabolic factors and the central nervous system bear for the control of food intake is increasingly recognized. The central mechanisms implicated are the focus of attention of very many research groups worldwide. We review here the experimental data that suggest that similar mechanisms are at play for the metabolic control of the neuroendocrine reproductive function. It is appearing that metabolic signals are integrated at the levels of first-order neurons equipped with the proper receptors, ant that these neurons send their signals towards hypothalamic GnRH neurons which constitute the integrative element of this network.

Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice.

BACKGROUND: Food allergy has reached an epidemic level in westernized countries and although central mechanisms have been described, the variability associated with genetic diversity underscores the still unresolved complexity of these disorders. OBJECTIVE: To develop models of food allergy and oral tolerance, both strictly induced by the intestinal route, and to compare antigen-specific responses. METHODS: BALB/c mice were mucosally sensitized to ovalbumin (OVA) in the presence of the mucosal adjuvant cholera toxin, or tolerized by intra-gastric administrations of OVA alone. Antibody titres and cytokines were determined by ELISA, and allergic status was determined through several physiologic parameters including decline in temperature, diarrhoea, mast cell degranulation and intestinal permeability. RESULTS: OVA-specific antibodies (IgE, IgGs and IgA in serum and feces) were produced in sensitized mice exclusively. Upon intra-gastric challenge with OVA, sensitized mice developed anaphylactic reactions associated with a decline of temperature, diarrhoea, degranulation of mast cells, which were only moderately recruited in the small intestine, and increased intestinal permeability. Cytokines produced by immune cells from sensitized mice included T-helper type 2 cytokines (IL-5, IL-13), but also IL-10, IFN-gamma and IL-17. In contrast, all markers of allergy were totally absent in tolerized animals, and yet the latter were protected from subsequent sensitization, demonstrating that oral tolerance took place efficiently. CONCLUSION: This work allows for the first time an appropriate comparison between sensitized and tolerized BALB/c mice towards OVA. It highlights important differences from other models of allergy, and thus questions some of the generally accepted notions of allergic reactions, such as the protective role of IFN-gamma, the importance of antigen-specific secretory IgA and the role of mucosal mast cells in intestinal anaphylaxis. In addition, it suggests that IL-17 might be an effector cytokine in food allergy. Finally, it demonstrates that intestinal permeability towards the allergen is increased during challenge.

Impact of pharmacist care in the management of cardiovascular disease risk factors: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Pharmacists may improve the clinical management of major risk factors for cardiovascular disease (CVD) prevention. A systematic review was conducted to determine the impact of pharmacist care on the management of CVD risk factors among outpatients. METHODS: The MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials that involved pharmacist care interventions among outpatients with CVD risk factors. Two reviewers independently abstracted data and classified pharmacists' interventions. Mean changes in blood pressure, total cholesterol, low-density lipoprotein cholesterol, and proportion of smokers were estimated using random effects models. RESULTS: Thirty randomized controlled trials (11 765 patients) were identified. Pharmacist interventions exclusively conducted by a pharmacist or implemented in collaboration with physicians or nurses included patient educational interventions, patient-reminder systems, measurement of CVD risk factors, medication management and feedback to physician, or educational intervention to health care professionals. Pharmacist care was associated with significant reductions in systolic/diastolic blood pressure (19 studies [10 479 patients]; -8.1 mm Hg [95% confidence interval {CI}, -10.2 to -5.9]/-3.8 mm Hg [95% CI,-5.3 to -2.3]); total cholesterol (9 studies [1121 patients]; -17.4 mg/L [95% CI,-25.5 to -9.2]), low-density lipoprotein cholesterol (7 studies [924 patients]; -13.4 mg/L [95% CI,-23.0 to -3.8]), and a reduction in the risk of smoking (2 studies [196 patients]; relative risk, 0.77 [95% CI, 0.67 to 0.89]). While most studies tended to favor pharmacist care compared with usual care, a substantial heterogeneity was observed. CONCLUSION: Pharmacist-directed care or in collaboration with physicians or nurses improve the management of major CVD risk factors in outpatients.