Relazione tra idrostratigrafia e idrochimica all'interno del Gruppo Acquifero A in Pianura Padana centrale

La realizzazione di cinque sezioni stratigrafiche nel territorio padano, orientate SSW-NNE e con profondità di circa 200 m, ha consentito lo studio della successione sedimentaria tardo-quaternaria della Pianura Padana centrale e dei suoi acquiferi, in particolare quelli più superficiali. La ricostruzione, ottenuta utilizzando le stratigrafie di pozzi per acqua fornite dall’archivio del Servizio Geologico, Sismico e dei Suoli di Regione Emilia-romagna, ha permesso di evidenziare una ciclicità deposizionale del 4° ordine, controllata da fattori glacio-eustatici. Grazie al riconoscimento di cicli trasgressivo-regressivi sono stati individuati cinque subsintemi corrispondenti ad altrettanti complessi acquiferi. La ricostruzione di pattern ciclici all’interno del Bacino Padano ha permesso la ricostruzione geometrica dei corpi sedimentari di channel-belt del Fiume Po, spessi corpi sabbiosi confinati da materiale impermeabile in cui sono contenute le falde acquifere. Alle informazioni stratigrafiche e litologiche si è unito lo studio delle caratteristiche idrochimiche ed isotopiche degli acquiferi, in modo tale da ottenere una chiave di lettura integrata dei depositi padani. Basandosi sulle diverse caratteristiche isotopiche delle acque è possibile risalire alla provenienza delle acque negli acquiferi. In questo modo si ottengono informazioni circa le modalità di ricarica dell'acquifero e la sorgente della ricarica. Un'applicazione secondaria di questo metodo è la verifica della vulnerabilità degli acquiferi padani. Lo studio delle facies idrochimiche è stato sovrapposto a quello dei valori isotopici delle acque, con l'obiettivo di definire una correlazione tra i due fattori chimici all’interno degli acquiferi. L'obiettivo di questa correlazione è quello di identificare la provenienza di un'acqua di ricarica senza la necessità di dati di natura isotopica.

Determinazione dei valori di fondo di Arsenico nella falda freatica delle provincia di Ferrara e Considerazioni sulla sua origine.

L’acquifero superficiale della Provincia di Ferrara è caratterizzato dalla presenza di una diffusa contaminazione da Arsenico. Per dare una risposta a questo fenomeno gli Enti della Provincia e del Comune hanno deciso di intraprendere uno studio volto alla determinazione dei valori di fondo del metalloide ed al miglioramento della comprensione del fenomeno. Il lavoro ha portato alla creazione di tre database con i dati presenti negli archivi provinciali inerenti: ubicazione e caratteristiche dei piezometri, dati idrochimici, concentrazione di Arsenico. L’acquifero superficiale è l’A0, olocenico, che si presenta eterogeneo per via della sua evoluzione geologica. Da uno studio stratigrafico ed idrogeologico si è visto come l’area sia costituita, andando da Ovest verso Est, da corpi alluvionali-deltizio-costieri olocenici in eteropia di facies. L’area centro-orientale è caratterizzata da un ciclo sedimentario trasgressivo-regressivo caratterizzato, nella parte superiore, dalla progradazione di un antico delta del Po. In tale ambiente si sono andati formando depositi ricchi in materia organica e in torba. Questi possono assumere una rilevante importanza nello spiegare il fenomeno, poiché possono svolgere sia il ruolo di sorgente dell’Arsenico che di redox driver attraverso la loro decomposizione. Elaborando i dati sono emersi elementi che sembrano confermare l’azione di un meccanismo di dissoluzione riduttiva che rilascia l’Arsenico, come mostrato dai cross plot tra Arsenico e Potenziale Redox, Ferro e Potenziale Redox, Arsenico e Ferro, Ferro e Manganese. L’area è stata suddivisa in tre zone, in cui la centrale corrisponde all’area ricca in materia organica. Sulla base delle tre aree individuate si è proceduto alla creazione di tre popolazioni di dati sottoposte ad analisi statistica. Quindi si è dimostrata l’assenza di contaminazione antropica, si sono esclusi i dati non significativi, si sono trattati i non detected e si sono individuati ed eliminati gli outlier. Infine si è proceduto alla determinazione della migliore distribuzione per ogni popolazione. Fatto ciò si è calcolato il 95° percentile, che è stato assunto come valore di fondo dell’area. Si è visto come tutti i tre valori di fondo superassero la CSC ed in particolare il valore di fondo dell’area centrale risultasse nettamente superiore agli altri due, superando la CSC di circa 10 volte. Questo ad ulteriore conferma della possibile azione della torba nel rilascio di Arsenico.

Analisi della composizione micropaleontologica di campioni di sedimento marino prelevati in Antartide

Nel presente lavoro di tesi è stata studiata dal punto di vista micropaleontologico una successione sedimentaria (carota C98) campionata nel Mare di Ross durante la campagna ANTA95 nell’ambito del progetto congiunto Korea -Italia Ross Slope, finanziato dal ProgrammaNazionale di Ricerca in Antartide (PNRA). L’indagine ha riguardato lo studio quantitativo delle associazioni a foraminiferi planctonici e bentonici con l’obiettivo di ricostruire gli scenari paleoambientali e paleoclimatici di quest’area durante il tardo Quaternario. In relazione alle associazioni di foraminiferi ed in base alla biostratigrafia a diatomee, l’intervallo studiato si è deposto durante lo stadio isotopico 5. La presenza di Neogloboquadrina pachyderma ad avvolgimento destrorso, associata ad un aumento delle forme bentoniche è stata messa in relazione con le fasi più calde dello stadio isotopico 5 in cui l’ambiente di mare aperto era caratterizzato da alta produttività primaria in superficie e presenza di materia organica sul fondale permettendo lo sviluppo dei foraminiferi bentonici sul fondale. Al contrario la presenza di intervalli con ridotto numero di specie e aumento della specie Miliammina arenacea è stata correlata con le fasi più fredde dello stadio isotopico 5, associate anche ad a un aumento della corrente fredda, salata HSSW che è una massa d’acqua e determina la corrosione dei carbonati. Il limite inferiore dello stadio isotopico 5 (passaggio stadio isotopico 6/ 5) è caratterizzato da un graduale aumento delle specie e del numero di individui con presenza di clasti centimetrici evidenziando un riscaldamento climatico e la presenza di icebergs. Il limite superiore dell’intervallo studiato (passaggio stadio isotopico 5/4) presenta una drastica riduzione di Foraminiferi bentonici probabilmente dovuta alla presenza di copertura glaciale.

Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency

Aortic dilatation/dissection (AD) can occur spontaneously or in association with genetic syndromes, such as Marfan syndrome (MFS; caused by FBN1 mutations), MFS type 2 and Loeys-Dietz syndrome (associated with TGFBR1/TGFBR2 mutations), and Ehlers-Danlos syndrome (EDS) vascular type (caused by COL3A1 mutations). Although mutations in FBN1 and TGFBR1/TGFBR2 account for the majority of AD cases referred to us for molecular genetic testing, we have obtained negative results for these genes in a large cohort of AD patients, suggesting the involvement of additional genes or acquired factors. In this study we assessed the effect of COL3A1 deletions/duplications in this cohort. Multiplex ligation-dependent probe amplification (MLPA) analysis of 100 unrelated patients identified one hemizygous deletion of the entire COL3A1 gene. Subsequent microarray analyses and sequencing of breakpoints revealed the deletion size of 3,408,306 bp at 2q32.1q32.3. This deletion affects not only COL3A1 but also 21 other known genes (GULP1, DIRC1, COL5A2, WDR75, SLC40A1, ASNSD1, ANKAR, OSGEPL1, ORMDL1, LOC100129592, PMS1, MSTN, C2orf88, HIBCH, INPP1, MFSD6, TMEM194B, NAB1, GLS, STAT1, and STAT4), mutations in three of which (COL5A2, SLC40A1, and MSTN) have also been associated with an autosomal dominant disorder (EDS classical type, hemochromatosis type 4, and muscle hypertrophy). Physical and laboratory examinations revealed that true haploinsufficiency of COL3A1, COL5A2, and MSTN, but not that of SLC40A1, leads to a clinical phenotype. Our data not only emphasize the impact/role of COL3A1 in AD patients but also extend the molecular etiology of several disorders by providing hitherto unreported evidence for true haploinsufficiency of the underlying gene.

Cardiovascular surgery in Marfan syndrome: implications of new molecular concepts in thoracic aortic disease

Acute dissection and rupture of aortic aneurysms comprise for 1-2% of all deaths in industrialized countries. Dilation of the aorta is caused by a multitude of mechanisms including inherited connective tissue disorders such as Marfan syndrome (MFS). MFS is one of the most common inherited connective tissue disorders affecting 1 in 5000 individuals. Although the phenotype of MFS can be quite variable, aneurysmal dilation of the aortic root and consecutive acute aortic dissection is the leading cause of death in this patient population. Over the past years it has been shown that a comprehensive understanding of this disorder provides greater understanding of vascular wall biology and identifies pathways relevant to aortic aneurysms and dissection in general. The current review discusses the surgical management of patients with MFS with a special emphasis on indications for surgery in this complex group of patients.

Should aortic arch replacement be performed during initial surgery for aortic root aneurysm in patients with Marfan syndrome?

OBJECTIVES: The aim of this study was to investigate whether total arch replacement (TAR) during initial surgery for root aneurysm should be routinely performed in patients with Marfan syndrome (MFS). METHODS: Retrospective analysis of 94 consecutive MFS patients fulfilling Ghent criteria who underwent 148 aortic surgeries and were followed at this institution during the past 16 years. RESULTS: The mean follow-up interval was 8.8 ± 7 years. Initial presentation was acute aortic dissection (AAD) in 35% of patients (76% Type A and 24% Type B) and aneurismal disease in 65%. TAR was performed in 8% of patients during initial surgery for AAD (otherwise a hemi-arch replacement was performed) and 1.6% in elective root repair. Secondary TAR had to be performed in only 3% of patients without, but in 33% following AAD (33% Type A and 33% Type B; P = 0.0001). Thirty-day, 6-month, 1-year and overall mortalities were 3.2, 5.3, 6.4 and 11.7%, respectively. Operative and 30-day mortalities in secondary aortic arch replacement were zero. Secondary TAR after AAD did not increase the need for the replacement of the entire thoracoabdominal aorta during follow-up compared with patients without secondary TAR (37 vs 40%, P = 1.0). CONCLUSIONS: MFS patients undergoing elective root repair have small risk of reinterventions on the aortic arch, and primary prophylactic replacement does not seem to be justified. In patients with AAD, the need for reinterventions is precipitated by the dissection itself and not by limiting the procedure to the hemi-arch replacement in the emergency setting. Limiting surgery to the aortic root, ascending aorta and proximal aortic arch is associated with low mortality in MFS patients presenting with AAD.

Paleoenvironment and Paleoecology of a Late Paleocene High-Latitude Terrestrial Succession, Arkose Ridge Formation at Box Canyon, Southern Talkeetna Mountains, Alaska

Paleogene sedimentary rocks of the Arkose Ridge Formation (Talkeetna Mountains, Alaska) preserve a record of a fluvial-lacustrine depositional environment and its forested ecosystem in an active basin among the convergent margin tectonic processes that shaped southern Alaska. An -800 m measured succession at Box Canyon indicates braid-plain deposition with predominantly gravelly deposits low in the exposure to sandy and muddy facies associations below an overlying lava flow sequence. U-Pb geochronology on zircons from a tuff and a sandstone within the measured section, as well as an Ar/Ar date from the overlying lava constrain the age of the sedimentary succession to between similar to 59 Ma and 48 Ma Fossil plant remains occur throughout the Arkose Ridge Formation as poorly-preserved coalified woody debris and fragmentary leaf impressions. At Box Canyon, however, a thin la-custrine depositional lens of rhythmically laminated mudrocks yielded fish fossils and a well-preserved floral assemblage including foliage and reproductive organs representing conifers, sphenopsids, monocots, and dicots. Leaf physiognomic methods to estimate paleoclimate were applied to the dicot leaf collection and indicate warm temperate paleotemperatures (-11-15 +/- -4 degrees C MAT) and elevated paleoprecipitation (-120 cm/yr MAP) estimates as compared to modem conditions; results that are parallel with previously published estimates from the partly coeval Chickaloon Formation deposited in more distal depositional environments in the same basin. The low abundance of leaf herbivory in the Box Canyon dicot assemblage (-9% of leaves damaged) is also similar to the results from assemblages in the meander-plain depositional systems of the Chickaloon. This new suite of data informs models of the tectonostratigraphic evolution of southern Alaska and the developing understanding of terrestrial paleoecology and paleoclimate at high latitudes during the Late Paleocene-Early Eocene greenhouse climate phase. (c) 2014 Elsevier B.V. All rights reserved.

Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders

Very recently, heterozygous mutations in the genes encoding transforming growth factor beta receptors I (TGFBR1) and II (TGFBR2) have been reported in Loeys-Dietz aortic aneurysm syndrome (LDS). In addition, dominant TGFBR2 mutations have been identified in Marfan syndrome type 2 (MFS2) and familial thoracic aortic aneurysms and dissections (TAAD). In the past, mutations of these genes were associated with atherosclerosis and several human cancers. Here, we report a total of nine novel and one known heterozygous sequence variants in the TGFBR1 and TGFBR2 genes in nine of 70 unrelated individuals with MFS-like phenotypes who previously tested negative for mutations in the gene encoding the extracellular matrix protein fibrillin-1 (FBN1). To assess the pathogenic impact of these sequence variants, in silico analyses were performed by the PolyPhen, SIFT, and Fold-X algorithms and by means of a 3D homology model of the TGFBR2 kinase domain. Our results showed that in all but one of the patients the pathogenic effect of at least one sequence variant is highly probable (c.722C > T, c.799A > C, and c.1460G > A in TGFBR1 and c.773T > G, c.1106G > T, c.1159G > A, c.1181G > A, and c.1561T > C in TGFBR2). These deleterious alleles occurred de novo or segregated with the disease in the families, indicating a causative association between the sequence variants and clinical phenotypes. Since TGFBR2 mutations found in patients with MFS-related disorders cannot be distinguished from heterozygous TGFBR2 mutations reported in tumor samples, we emphasize the importance of segregation analysis in affected families. In order to be able to find the mutation that is indeed responsible for a MFS-related phenotype, we also propose that genetic testing for sequence alterations in TGFBR1 and TGFBR2 should be complemented by mutation screening of the FBN1 gene.

Large genomic fibrillin-1 (FBN1) gene deletions provide evidence for true haploinsufficiency in Marfan syndrome

Mutations in the FBN1 gene are the major cause of Marfan syndrome (MFS), an autosomal dominant connective tissue disorder, which displays variable manifestations in the cardiovascular, ocular, and skeletal systems. Current molecular genetic testing of FBN1 may miss mutations in the promoter region or in other noncoding sequences as well as partial or complete gene deletions and duplications. In this study, we tested for copy number variations by successively applying multiplex ligation-dependent probe amplification (MLPA) and the Affymetrix Human Mapping 500 K Array Set, which contains probes for approximately 500,000 single-nucleotide polymorphisms (SNPs) across the genome. By analyzing genomic DNA of 101 unrelated individuals with MFS or related phenotypes in whom standard genetic testing detected no mutation, we identified FBN1 deletions in two patients with MFS. Our high-resolution approach narrowed down the deletion breakpoints. Subsequent sequencing of the junctional fragments revealed the deletion sizes of 26,887 and 302,580 bp, respectively. Surprisingly, both deletions affect the putative regulatory and promoter region of the FBN1 gene, strongly indicating that they abolish transcription of the deleted allele. This expectation of complete loss of function of one allele, i.e. true haploinsufficiency, was confirmed by transcript analyses. Our findings not only emphasize the importance of screening for large genomic rearrangements in comprehensive genetic testing of FBN1 but, importantly, also extend the molecular etiology of MFS by providing hitherto unreported evidence that true haploinsufficiency is sufficient to cause MFS.

Paleoenvironmental reconstructions from cave sediments of the Moravian Karst, Czech Republic / by Pavel Sroubek.

This thesis presents a paleoclimatic/paleoenvironmental study conducted on clastic cave sediments of the Moravian Karst, Czech Republic. The study is based on environmental magnetic techniques, yet a wide range of other scientific methods was used to obtain a clearer picture of the Quaternary climate. My thesis also presents an overview of the significance of cave deposits for paleoclimatic reconstructions, explains basic environmental magnetic techniques and offers background information on the study area – a famous karst region in Central Europe with a rich history. In Kulna Cave magnetic susceptibility variations and in particular variations in pedogenic susceptibility yield a detailed record of the palaeoenvironmental conditions during the Last Glacial Stage. The Kulna long-term climatic trends agree with the deep-sea SPECMAP record, while the short-term oscillations correlate with rapid changes in the North Atlantic sea surface temperatures. Kulna Cave sediments reflect the intensity of pedogenesis controlled by short-term warmer events and precipitation over the mid-continent and provide a link between continental European climate and sea surface temperatures in the North Atlantic during the Last Glacial Stage. Given the number of independent climate proxies determined from the entrance facies of the cave and their high resolution, Kulna is an extremely important site for studying Late Pleistocene climate. In the interior of Spiralka Cave, a five meter high section of fine grained sediments deposited during floods yields information on the climatic and environmental conditions of the last millenium. In the upper 1.5 meters of this profile, mineral magnetic and other non-magnetic data indicate that susceptibility variations are controlled by the concentration of magnetite and its magnetic grain size. Comparison of our susceptibility record to the instrumental record of winter temperature anomalies shows a remarkable correlation. This correlation is explained by coupling of the flooding events, cultivation of land and pedogenetic processes in the cave catchment area. A combination of mineral magnetic and geochemical proxies yields a detail picture of the rapidly evolving climate of the near past and tracks both natural and human induced environmental changes taking place in the broader region.

Application of well log tomography to the Dundee and Rogers City Limestones, Michigan Basin, USA

The Michigan Basin is located in the upper Midwest region of the United States and is centered geographically over the Lower Peninsula of Michigan. It is filled primarily with Paleozoic carbonates and clastics, overlying Precambrian basement rocks and covered by Pleistocene glacial drift. In Michigan, more than 46,000 wells have been drilled in the basin, many producing significant quantities of oil and gas since the 1920s in addition to providing a wealth of data for subsurface visualization. Well log tomography, formerly log-curve amplitude slicing, is a visualization method recently developed at Michigan Technological University to correlate subsurface data by utilizing the high vertical resolution of well log curves. The well log tomography method was first successfully applied to the Middle Devonian Traverse Group within the Michigan Basin using gamma ray log curves. The purpose of this study is to prepare a digital data set for the Middle Devonian Dundee and Rogers City Limestones, apply the well log tomography method to this data and from this application, interpret paleogeographic trends in the natural radioactivity. Both the Dundee and Rogers City intervals directly underlie the Traverse Group and combined are the most prolific reservoir within the Michigan Basin. Differences between this study and the Traverse Group include increased well control and “slicing” of a more uniform lithology. Gamma ray log curves for the Dundee and Rogers City Limestones were obtained from 295 vertical wells distributed over the Lower Peninsula of Michigan, converted to Log ASCII Standard files, and input into the well log tomography program. The “slicing” contour results indicate that during the formation of the Dundee and Rogers City intervals, carbonates and evaporites with low natural radioactive signatures on gamma ray logs were deposited. This contrasts the higher gamma ray amplitudes from siliciclastic deltas that cyclically entered the basin during Traverse Group deposition. Additionally, a subtle north-south, low natural radioactive trend in the center of the basin may correlate with previously published Dundee facies tracts. Prominent trends associated with the distribution of limestone and dolomite are not observed because the regional range of gamma ray values for both carbonates are equivalent in the Michigan Basin and additional log curves are needed to separate these lithologies.

Proteomic analysis in aortic media of patients with Marfan syndrome reveals increased activity of calpain 2 in aortic aneurysms

BACKGROUND: Marfan syndrome (MFS) is a heritable disorder of connective tissue, affecting principally skeletal, ocular, and cardiovascular systems. The most life-threatening manifestations are aortic aneurysm and dissection. We investigated changes in the proteome of aortic media in patients with and without MFS to gain insight into molecular mechanisms leading to aortic dilatation. METHODS AND RESULTS: Aortic samples were collected from 46 patients. Twenty-two patients suffered from MFS, 9 patients had bicuspid aortic valve, and 15 patients without connective tissue disorder served as controls. Aortic media was isolated and its proteome was analyzed in 12 patients with the use of 2-dimensional difference gel electrophoresis and mass spectrometry. We found higher amounts of filamin A C-terminal fragment, calponin 1, vinculin, microfibril-associated glycoprotein 4, and myosin-10 heavy chain in aortic media of MFS aneurysm samples than in controls. Regulation of filamin A C-terminal fragmentation was validated in all patient samples by immunoblotting. Cleavage of filamin A and the calpain substrate spectrin was increased in the MFS and bicuspid aortic valve groups. Extent of cleavage correlated positively with calpain 2 expression and negatively with the expression of its endogenous inhibitor calpastatin. CONCLUSIONS: Our observation demonstrates for the first time upregulation of the C-terminal fragment of filamin A in dilated aortic media of MFS and bicuspid aortic valve patients. In addition, our results present evidence that the cleavage of filamin A is highly likely the result of the protease calpain. Increased calpain activity might explain, at least in part, histological alterations in dilated aorta.

Circulating transforming growth factor-beta in Marfan syndrome

BACKGROUND: Marfan syndrome (MFS) is caused by mutations in the fibrillin-1 gene and dysregulation of transforming growth factor-beta (TGF-beta). Recent evidence suggests that losartan, an angiotensin II type 1 blocker that blunts TGF-beta activation, may be an effective treatment for MFS. We hypothesized that dysregulation of TGF-beta might be mirrored in circulating TGF-beta concentrations. METHODS AND RESULTS: Serum obtained from MFS mutant mice (Fbn1(C1039G/+)) treated with losartan was analyzed for circulating TGF-beta1 concentrations and compared with those from placebo-treated and wild-type mice. Aortic root size was measured by echocardiography. Data were validated in patients with MFS and healthy individuals. In mice, circulating total TGF-beta1 concentrations increased with age and were elevated in older untreated Fbn1(C1039G/+) mice compared with wild-type mice (P=0.01; n=16; mean+/-SEM, 115+/-8 ng/mL versus n=17; mean+/-SEM, 92+/-4 ng/mL). Losartan-treated Fbn1(C1039G/+) mice had lower total TGF-beta1 concentrations compared with age-matched Fbn1(C1039G/+) mice treated with placebo (P=0.01; n=18; 90+/-5 ng/mL), and circulating total TGF-beta1 levels were indistinguishable from those of age-matched wild-type mice (P=0.8). Correlation was observed between circulating TGF-beta1 levels and aortic root diameters in Fbn1(C1039G/+) and wild-type mice (P=0.002). In humans, circulating total TGF-beta1 concentrations were elevated in patients with MFS compared with control individuals (P<0.0001; n=53; 15+/-1.7 ng/mL versus n=74; 2.5+/-0.4 ng/mL). MFS patients treated with losartan (n=55) or beta-blocker (n=80) showed significantly lower total TGF-beta1 concentrations compared with untreated MFS patients (P< or =0.05). CONCLUSIONS: Circulating TGF-beta1 concentrations are elevated in MFS and decrease after administration of losartan, beta-blocker therapy, or both and therefore might serve as a prognostic and therapeutic marker in MFS.

Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment

BACKGROUND: An increasing body of evidence suggests a possible role of suburothelial myofibroblasts (MFs) in bladder mechanosensation and in the pathophysiology of detrusor overactivity (DO). OBJECTIVE: To determine whether markers of MFs, including gap junction protein connexin43 (Cx43) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO (NDO) or idiopathic DO (IDO) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A (BoNTA). DESIGN, SETTING, AND PARTICIPANTS: Patients with NDO (n=10) or IDO (n=11) were treated in a single-centre, open-label study of intradetrusor BoNTA injections. Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder (OAB) symptoms. This study is registered with ClinicalTrials.gov, number NCT00662064. INTERVENTIONS: Bladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment. They were studied with quantitative immunofluorescence using antibodies to connexin 43 (Cx43), vimentin, and c-kit. MEASUREMENTS: Differences in Cx43, vimentin, and c-kit immunoreactivity between control subjects and NDO or IDO patients (primary outcomes). Changes in NDO or IDO, Cx43 immunoreactivity, and c-kit immunoreactivity after BoNTA treatment (secondary outcomes). RESULTS AND LIMITATIONS: Cx43 immunoreactivity was increased in both IDO and NDO patients compared to controls, but remained unchanged after BoNTA treatment. C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment. CONCLUSIONS: Increased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO. It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality. Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs.

Petrology and geochronology of "muscovite age standard" B4M

Muscovite B4M, distributed in 1961 as an age standard, was ground under ethanol. Five grain size fractions were obtained and characterized by X-ray diffraction. They display a mixing trend between a phengitic (enriched in the fraction <0.2 µm) and a muscovitic component (predominant in the fraction >20 µm). High-pressure phengite is preserved as a relict in retrograde muscovite. Electron microprobe analyses of the distributed mineral separate reveal at least four white mica populations based on Si, Al, Mg, Na, Fe and F. Rb/K ratios vary by one order of magnitude. Rb–Sr analyses link the mineralogical heterogeneity to variable Rb/Sr and 87Sr/86Sr ratios. The grain size fractions define no internal isochron. Relict fine-grained phengite gives older ages than coarse-grained retrograde greenschist facies muscovite. The inverse grain size–age relationship also characterizes 39Ar/40Ar analyses. Cl/K anticorrelates with step ages: Cl-rich coarse muscovite is younger than Cl-poor fine relict phengite. Sr and Ar preserve a similar isotopic inheritance despite peak metamorphism reaching 635±20 °C. A suitable mineral standard requires that its petrological equilibrium first be demonstrated. Relicts and retrograde reaction textures are a guarantee of isotopic disequilibrium and heterogeneous ages within single crystal at the micrometre scale.