Stratigraphic, sedimentological and palaeoenvironmental constraints on the rise of the Urgonian platform in the western Swiss Jura

Urgonian-type carbonates are a characteristic feature of many late Early Cretaceous shallow-marine, tropical and subtropical environments. The presence of typical photozoan carbonate-producing communities including corals and rudists indicates the prevalence of warm, transparent and presumably oligotrophic conditions in a period otherwise characterized by the high density of globally occurring anoxic episodes. Of particular interest, therefore, is the exploration of relationships between Urgonian platform growth and palaeoceanographic change. In the French and Swiss Jura Mountains, the onset and evolution of the Urgonian platform have been controversially dated, and a correlation with other, better dated, successions is correspondingly difficult. It is for this reason that the stratigraphy and sedimentology of a series of recently exposed sections (Eclepens, Vaumarcus and Neuchatel) and, in addition, the section of the Gorges de l'Areuse were analysed. Calcareous nannofossil biostratigraphy, the evolution of phosphorus contents of bulk rock, a sequence-stratigraphic interpretation and a correlation of drowning unconformities with better dated sections in the Helvetic Alps were used to constrain the age of the Urgonian platform. The sum of the data and field observations suggests the following evolution: during the Hauterivian, important outward and upward growth of a bioclastic and oolitic carbonate platform is documented in two sequences, separated by a phase of platform drowning during the late Early Hauterivian. Following these two phases of platform growth, a second drowning phase occurred during the latest Hauterivian and Early Barremian, which was accompanied by significant platform erosion and sediment reworking. The Late Barremian witnessed the renewed installation of a carbonate platform, which initiated with a phase of oolite production, and which progressively evolved into a typical Urgonian carbonate platform colonized by corals and rudists. This phase terminated at the latest in the middle Early Aptian, due to a further drowning event. The evolution of this particular platform segment is compatible with that of more distal and well-dated segments of the same northern Tethyan platform preserved in the Helvetic zone of the Alps and in the northern subalpine chains (Chartreuse and Vercors).

A unique Permian-Triassic boundary section from the Neotethyan Hawasina Basin, Central Oman Mountains

In the Wadi Wasit area (Central Oman Mountains), Dienerian breccias are widespread. These breccias consist mostly of Guadalupian reefal blocks, often dolomitised, and some rare small-sized blocks of lowermost Triassic bivalve-bearing limestones. A unique block, with a size of about 200 m(3), including Permian and earliest Triassic faunas has been studied in detail. The so-called Wadi Wasit block consists of three major lithological units. A basal unstratified grey limestone is rich in various reef-building organisms (rugose corals, calcareous sponges, stromatoporoids) and has been dated as Middle Permian. It is disconformably overlain by well- and thin-bedded light grey to yellowish coloured limestones rich in molluscs. Two major lithologies (Coquina Limestone respectively Bioclastic Limestone unit) characterise the shelly limestones, their contact seems gradual. These two units are well-dated; they are of Griesbachian age and contain three conodont zones, the Parvus Zone, the Staeschei Zone and the Sosioensis Zone, and two ammonoid zones, the Ophiceras tibeticum Zone and an 'unnamed interval'. The third unit consists of a grey marly limestone containing Neospathodus kummeli (basal Dienerian). It is the first record of well-dated basal Triassic sediments in the Arabian Peninsula. The Coquina Limestone is dominated by the bivalve Promyalina with some Claraia and Eumorphotis. This bivalve association is interpreted as a pioneering opportunistic assemblage. Towards the top of the Bioclastic Limestone unit, the faunal diversity increases and contains probably more than 20 taxa of bivalves, microgastropods, crinoids, brachiopods, ammonoids, echinoid spines, ostracods and conodonts. The generic diversity of this biofacies exceeds by far any other Griesbachian assemblage known. Our data give new evidence for the geodynamical history for the distal carbonate shelf bordering the Hawasina Basin. A break in the sedimentation characterises the Late Permian. The basal Triassic shows a steady transgression and the breccias may record a distinct gravitational collapse of platform margins linked with sea-level low stand at the end of Induan time (late Dienerian-basal Smithian). delta(13)C(carb) isotopic analyses were performed and yield typical Permian values of around 4parts per thousand for the Reefal Limestone, with a strong negative shift across the Permian-Triassic boundary. During the Griesbachian values shift positively from 0.5 to 3.1parts per thousand parallel to an increase in faunal diversity and probably primary productivity. The detailed faunal analysis and the discovery of an unexpected diversity give,us a new understanding of the recovery of the Early Triassic marine ecosystem.

Submillimeter three-dimensional coronary MR angiography with real-time navigator correction: comparison of navigator locations.

Three-dimensional free-breathing coronary magnetic resonance angiography was performed in eight healthy volunteers with use of real-time navigator technology. Images acquired with the navigator localized at the right hemidiaphragm and at the left ventricle were objectively compared. The diaphragmatic navigator was found to be superior for vessel delineation of middle to distal portions of the coronary arteries.

PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells.

Magnetostratigraphy of the Miocene continental deposits of the Montes de Castejón (central Ebro basin, Spain): geochronological and paleoenvironmental implications

A detailed magnetostratigraphic study has been carried out in the early to middle Miocene distal alluvial and lacustrine sediments of the Montes de Castejón (central Ebro Basin). The study was based on the analysis of 196 magnetostratigraphic sites sampled along a stratigraphic interval of about 240 meters. Local magnetostratigraphy yielded a sequence of 12 magnetozones (6 normal and 6 reverse) which could be correlated with the Geomagnetic Polarity Time Scale (GPTS) interval C5Cr to C5AD (between 17 and 14.3 Ma.). The sampled sedimentary sequences include the boundary between two tectosedimentary units (TSU, T5 and T6) already defined in the Ebro Basin. The magnetostratigraphy of the Montes de Castejón allows to date the T5/T6 TSU boundary at 16.14 Ma, within chron C5Cn.1n. This magnetostratigraphy also allows us to analyse in detail as well as to discuss the variations in sedimentation rates through space and time between different lacustrine environments: Outer carbonate lacustrine fringes and distal alluvial plains (Montes de Castejón sections) show higher sedimentation rates than offshore lacustrine areas (San Caprasio section, 50 km east of Montes de Castejón).

Sedimentos prodeltaicos en el Delta emergido del Llobregat

La unidad de limos intermedios del delta del Llobregat corresponde a un ambiente prodeltaico en el que se han identificado, por comparación al modelo actual, subambientes de prodelta proximal, medio y medio-distal. Su agua intersticial es sinsedimentaria, hallándose en la actualidad parcialmente diluida.

A nucleosome-dependent static loop potentiates estrogen-regulated transcription from the Xenopus vitellogenin B1 promoter in vitro.

We describe the transcriptional potentiation in estrogen responsive transcription extracts of the Xenopus vitellogenin B1 gene promoter through the formation of a positioned nucleosome. Nuclease digestion and hydroxyl radical cleavage indicate that strong, DNA sequence-directed positioning of a nucleosome occurs between -300 and -140 relative to the start site of transcription. Deletion of this DNA sequence abolishes the potentiation of transcription due to nucleosome assembly. The wrapping of DNA around the histone core of the nucleosome positioned between -300 and -140 creates a static loop in which distal estrogen receptor binding sites are brought close to proximal promoter elements. This might facilitate interactions between the trans-acting factors themselves and/or RNA polymerase. Such a nucleosome provides an example of how chromatin structure might have a positive effect on the transcription process.

Mutations in the epithelial Na+ channel ENaC outer pore disrupt amiloride block by increasing its dissociation rate.

The epithelial Na+ channel ENaC mediates transepithelial Na+ transport in the distal kidney, the colon, and the lung and is a key element for the maintenance of Na+ balance and the regulation of blood pressure. Mutagenesis studies have identified residues alphaS583 and the homologous betaG525 and gammaG537 in the outer pore entrance that are critical for ENaC block by the K+-sparing diuretic amiloride. The aim of the present study was to determine first, whether these residues are part of the amiloride binding site, and second, whether they are general determinants of ENaC block by amiloride and its derivatives. Kinetic analysis of the association and dissociation rates of amiloride and benzamil to ENaC showed that mutation of residue alphaS583C and the homologous betaG525C increased the dissociation rate of the drugs from the binding site, with little changes in their association rate. Thus, these mutations destabilize the binding interaction between the blockers and the receptor on the channel, favoring the unbinding of the ligand. This strongly suggests that they are part of the binding site. Because mutations of alphaS583, betaG525, and gammaG537 have similar effects on amiloride, benzamil, and triamterene block, we conclude that these three ENaC blockers share a common receptor within the ion channel pore.

Increased renal responsiveness to vasopressin and enhanced V2 receptor signaling in RGS2-/- mice.

The antidiuretic effect of vasopressin is mediated by V2 receptors (V2R) that are located in kidney connecting tubules and collecting ducts. This study provides evidence that V2R signaling is negatively regulated by regulator of G protein signaling 2 (RGS2), a member of the family of RGS proteins. This study demonstrates that (1) RGS2 expression in the kidney is restricted to the vasopressin-sensitive part of the nephron (thick ascending limb, connecting tubule, and collecting duct); (2) expression of RGS2 is rapidly upregulated by vasopressin; (3) the vasopressin-dependent accumulation of cAMP, the principal messenger of V2R signaling, is significantly higher in collecting ducts that are microdissected from the RGS2(-/-) mice compared with their wild-type littermates; and (4) analysis of urine output of mice that were exposed to water restriction followed by acute water loading revealed that RGS2(-/-) mice exhibit an increased renal responsiveness to vasopressin. It is proposed that RGS2 is involved in negative feedback regulation of V2R signaling.

Sleep deprivation (SD) on focal brain ischemia in the rat : effects of different SD protocols

Sleep-wake disturbances are frequently observed in stroke patients and are associated with poorer functional outcome. Until now the effects of sleep on stroke evolution are unknown. The purpose of the present study was to evaluate the effects of three sleep deprivation (SD) protocols on brain damages after focal cerebral ischemia in a rat model. Permanent occlusion of distal branches of the middle cerebral artery was induced in adult rats. The animals were then subjected to 6h SD, 12h SD or sleep disturbances (SDis) in which 3 x 12h sleep deprivation were performed by gentle handling. Infarct size and brain swelling were assessed by Cresyl violet staining, and the number of damaged cells was measured by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Behavioral tests, namely tape removal and cylinder tests, were performed for assessing sensorimotor function. In the 6h SD protocol, no significant difference (P > 0.05) was found either in infarct size (42.5 ± 30.4 mm3 in sleep deprived animals vs. 44.5 ± 20.5 mm3 in controls, mean ± s.d.), in brain swelling (10.2 ± 3.8 % in sleep deprived animals vs. 11.3 ± 2.0 % in controls) or in number of TUNEL-positive cells (21.7 ± 2.0/mm2 in sleep deprived animals vs. 23.0 ± 1.1/mm2 in controls). In contrast, 12h sleep deprivation increased infarct size by 40 % (82.8 ± 10.9 mm3 in SD group vs. 59.2 ± 13.9 mm3 in control group, P = 0.008) and number of TUNEL-positive cells by 137 % (46.8 ± 15/mm in SD group vs. 19.7 ± 7.7/mm2 in control group, P = 0.003). There was no significant difference (P > 0.05) in brain swelling (12.9 ± 6.3 % in sleep deprived animals vs. 11.6 ± 6.0 % in controls). The SDis protocol also increased infarct size by 76 % (3 x 12h SD 58.8 ± 20.4 mm3 vs. no SD 33.8 ± 6.3 mm3, P = 0.017) and number of TUNEL-positive cells by 219 % (32.9 ± 13.2/mm2 vs. 10.3 ± 2.5/mm2, P = 0.008). Brain swelling did not show any difference between the two groups (24.5 ± 8.4 % in SD group vs. 16.7 ± 8.9 % in control group, p > 0.05). Both behavioral tests did not show any concluding results. In summary, we demonstrate that sleep deprivation aggravates brain damages in a rat model of stroke. Further experiments are needed to unveil the mechanisms underlying these effects.

Treatment of gastroduodenal Crohn's disease.

Symptomatic gastroduodenal manifestations of Crohn's disease (CD) are rare, with less than 4% of patients being clinically symptomatic. Gastroduodenal involvement may, however, be found endoscopically in 20% and in up to 40% of cases histologically, most frequently as Helicobacter pylori-negative focal gastritis, usually in patients with concomitant distal ileal disease. In practice, the activity of concomitant distal CD usually determines the indication for therapy, except in the presence of obstructive gastroduodenal symptoms. With the few data available, it seems correct to say that localized gastroduodenal disease should be treated with standard medical therapy used for more distal disease, with the exception of sulfasalazine and mesalanine with pH-dependent release. Presence of symptoms of obstruction needs aggressive therapy. If medical therapy with steroids and immunomodulatory drugs does not alleviate the symptoms, balloon dilation and surgery are the options to consider.

New stratigraphic data from the Lower Penninic between the Adula nappe and the Gotthard massif and consequences for the tectonics and the paleogeography of the Central Alps

New stratigraphic data along a profile from the Helvetic Gotthard Massif to the remnants of the North Penninic Basin in eastern Ticino and Graubunden are presented. The stratigraphic record together with existing geochemical and structural data, motivate a new interpretation of the fossil European distal margin. We introduce a new group of Triassic facies, the North-Penninic-Triassic (NPT), which is characterised by the Ladinian "dolomie bicolori". The NPT was located in-between the Briançonnais carbonate platform and the Helvetic lands. The observed horizontal transition, coupled with the stratigraphic superposition of an Helvetic Liassic on a Briaçonnais Triassic in the Luzzone-Terri nappe, links, prior to Jurassic rifting, the Briançonnais paleogeographic domain at the Helvetic Margin, south of the Gotthard. Our observations suggest that the Jurassic rifting separated the Briançonnais domain from the Helvetic margin by complex and protracted extension. The syn-rift stratigraphic record in the Adula nappe and surroundings suggests the presence of a diffuse rising area with only moderately subsiding basins above a thinned continental and proto-oceanic crust. Strong subsidence occurred in a second phase following protracted extension and the resulting delamination of the rising area. The stratigraphic coherency in the Adula's Mesozoic questions the idea of a lithospheric mélange in the eclogitic Adula nappe, which is more likely to be a coherent alpine tectonic unit. The structural and stratigraphic observations in the Piz Terri-Lunschania zone suggest the activity of syn-rift detachments. During the alpine collision these faults are reactivated (and inverted) and played a major role in allowing the Adula subduction, the "Penninic Thrust" above it and in creating the structural complexity of the Central Alps.

Neoadjuvant therapy with denosumab in a giant cell tumour. A case report

Introduction: Giant cell tumour (GCT) is a benign but locally aggressive primary osteolytic bone tumour, prone to local recurrence after surgery. Denosumab is a human antibody against RANKL, an over-expressed ligand present on normal multinucleated cells, responsible for bone destruction in GCT. We report the case of a patient with an advanced GCT of the distal radius. The lesion was treated with adjuvant denosumab , followed by curettage. Clinical case: A 28 years old patient presented with a classical honeycomb osteolytic lesion in the left distal radius. Core-needle biopsy confirmed the diagnosis of GCT. Due to the proximity to the radio-carpal joint and advanced scalloping of the metaphyseal cortical bone, joint-salvage surgery was not possible. We initiated a neo-adjuvant treatment with denosumab (XGEVA), 120mg/ week for 1 month, followed by monthly injections for 6 months. During this time, a substantial bone recorticalization, without progression of the size of the tumour was noted. No local or systemic side effects were observed. We performed intra-lesional (curettage) excision and bone grafting after 6 months. Histological analysis revealed islets (10%) of viable tumour cells within fibrous tissue. Post-op evolution was eventless. Discussion: While surgery remains the treatment of choice for GCT, joint-salvage may not always be possible in case of extensive epiphyseal involvement. The presence of osteoclast-like giant cells seems to make those lesions prone to the specific anti-RANKL treatment with denosumab. Denosumab appears to slow down tumour growth and promote recorticalization of eroded bone. It might allow less aggressive surgery in selected cases.

Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep.

Previous studies support resorbable biocomposites made of poly(L-lactic acid) (PLA) and beta-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used beta-TCP bone substitute (ChronOS, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5 mm and depths of 15 mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12 months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12 months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4 months, but not at 12 months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12 months, as well as the absence of chronic or long-term inflammation at this time point.

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Results of a 2-year study.

A Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (mu FEA), over 2 years, in postmenopausal osteoporotic women.Introduction Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk.Methods Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers.Results In the intention-to-treat population (n = 83, age: 64 +/- 8 years; lumbar T-score: -2.8 +/- 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (-0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (-1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated.Conclusions Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.