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The frequency of extreme events has changed, having a direct impact on human lives. Regional climate models help us to predict these regional climate changes. This work presents an atmosphere–ocean coupled regional climate system model (RCSM; with the atmospheric component COSMO-CLM and the ocean component NEMO) over the European domain, including three marginal seas: the Mediterranean, North, and Baltic Sea. To test the model, we evaluate a simulation of more than 100 years (1900–2009) with a spatial grid resolution of about 25 km. The simulation was nested into a coupled global simulation with the model MPI-ESM in a low-resolution configuration, whose ocean temperature and salinity were nudged to the ocean–ice component of the MPI-ESM forced with the NOAA 20th Century Reanalysis (20CR). The evaluation shows the robustness of the RCSM and discusses the added value by the coupled marginal seas over an atmosphere-only simulation. The coupled system is stable for the complete 20th century and provides a better representation of extreme temperatures compared to the atmosphere-only model. The produced long-term dataset will help us to better understand the processes leading to meteorological and climate extremes. [ABSTRACT FROM AUTHOR]

The frequency of extreme events has changed, having a direct impact on human lives. Regional climate models help us to predict these regional climate changes. This work presents an atmosphere-ocean coupled regional climate system model (RCSM, with the atmospheric component COSMO-CLM and the ocean component NEMO) over the European domain, including three marginal seas: the Mediterranean, the North and the Baltic Seas. To test the model, we evaluate a simulation of more than one hundred years (1900-2009) with a spatial grid resolution of about 25 km. The simulation was nested into a coupled global simulation with the model MPI-ESM, whose ocean temperature and salinity was nudged to an MPI-ESM ocean-ice component forced with the 20th Century Reanalysis (20CR). The evaluation shows the robustness of the RCSM and discusses the added value by the coupled marginal seas over an atmosphere-only simulation. The coupled system runs stable for the complete 20th century and provides a better representation of extreme temperatures compared to the atmosphere-only model. The produced long-term dataset will allow an improved study of extreme events, helping us to better understand the processes leading to meteorological and climate extremes and their prediction. [ABSTRACT FROM AUTHOR]

Abstract Wilson's disease (WD) is a genetic metabolic disease strictly associated with liver cirrhosis. In this review, the genetic bases of the disease are discussed, with emphasis on the role of ATP7B (the Wilson disease protein) dysfunction as a determinant factor of systemic copper overload. Regarding the different multiple mutations described in WD patients, the peculiarity of Sardinian population is highlighted, Sardinians carrying a rare deletion in the promoter (5′ UTR) of the WD gene. The role of epigenetic changes in the clinical presentation and evolution of liver disease in WD patients is also discussed, nutrition probably representing a relevantly risk factor in WD patients. The role of transmission electron microscopy in the diagnosis of WD-related liver disease is underlined. Mitochondrial changes, increased peroxisomes fat droplets, lipolysosomes and intranuclear glycogen inclusions are reported as the most frequent ultrastructural changes in the liver of WD carriers. The role of histochemical stains for copper is analyzed, and the Timm's method is suggested as the most sensitive one for revealing hepatic copper overload in all stage of WD. The marked variability of the histological liver changes occurring in WD is underlined simple steatosis may represent the only pathological changes, frequently associated with glycogenated nuclei. Mallory-Denk bodies lipogranulomas alcoholic and non-alcoholic fatty liver disease ending with bridging fibrosis and cirrhosis. Finally, the reversal of fibrosis as a possible therapeutic objective in WD is discussed. Graphical abstract This article highlights the molecular mechanisms underlying copper trafficking inside the hepatocyte, focusing on the role of hCtr1 (the copper transporter 1) and the copper metallochaperone Atox1 in copper transfer from the sinusoidal lumen toward the Golgi Apparatus where the ATP7B (Wilson disease protein) is located. Unlabelled Image Highlights • Altered copper metabolism and liver overload • Open questions regarding the relationships between copper storage and liver disease • Morphology role is to identify the structural and ultrastructural aspects. • Liver histology and Wilson disease, non-alcoholic fatty liver disease, viral hepatitis [ABSTRACT FROM AUTHOR]

The liver is a major hematopoietic organ during embryonic and fetal development in humans. Its hematopoietic activity starts during the first weeks of gestation and continues until birth. During this period the liver is colonized by undifferentiated hematopoietic stem cells (HSCs) that gradually differentiate and once mature, enter the circulatory system through the hepatic sinusoids, this process is called hepatic hematopoiesis. The morphology of hepatic hematopoiesis, has been studied in humans through the years, and led to a characterization of all the cell types that make up these phenomena. Studies on murine models also helped to describe the extent of hepatic hematopoiesis at different gestational ages. Using this knowledge, we attempted to describe how hepatic hematopoiesis morphologically evolves as gestation progresses, in human embryos and fetuses. Thus, we observed a total of 32 tissue specimens obtained from the livers of embryos and fetuses at different gestational ages. Basing our observations on the four stages of liver hematopoiesis identified by Sasaki and Sonoda in mice, we also described four consecutive stages of liver hematopoiesis in humans, which resulted to be highly similar to those described in murine models. [ABSTRACT FROM AUTHOR]

Heavy precipitation affected Central Europe in May/June 2013, triggering damaging floods both on the Danube and the Elbe rivers. Based on a modelling approach with COSMO-CLM, moisture fluxes, backward trajectories, cyclone tracks and precipitation fields are evaluated for the relevant time period 30 May--2 June 2013.Weidentify potential moisture sources and quantify their contribution to the flood event focusing on the Danube basin through sensitivity experiments: Control simulations are performed with undisturbed ERA-Interim boundary conditions, while multiple sensitivity experiments are driven with modified evaporation characteristics over selected marine and land areas. Two relevant cyclones are identified both in reanalysis and in our simulations, which moved counter-clockwise in a retrograde path from Southeastern Europe over Eastern Europe towards the northern slopes of the Alps. The control simulations represent the synoptic evolution of the event reasonably well. The evolution of the precipitation event in the control simulations shows some differences in terms of its spatial and temporal characteristics compared to observations. The main precipitation event can be separated into two phases concerning the moisture sources. Our modelling results provide evidence that the two main sources contributing to the event were the continental evapotranspiration (moisture recycling; both phases) and the North Atlantic Ocean (first phase only). The Mediterranean Sea played only a minor role as a moisture source. This study confirms the importance of continental moisture recycling for heavy precipitation events over Central Europe during the summer half year. [ABSTRACT FROM AUTHOR]

The preterm kidney cannot be simply considered as a kidney small in size: as compared to the adult kidney, the developing organ of the preterm infant is characterized by marked differences regarding the architecture and cell components. At macroscopy, fine linear demarcations indenting the renal surface characterize the fetal and preterm kidney. At microscopy, multiple major architectural changes differentiate the developing kidney from the adult one: a large capsule with a high cellularity; the branching ureteric bud, extending from the hilum towards the renal capsule; striking morphological differences among superficial (just born) and deep (more mature) glomeruli; persistence of remnants of the metanephric mesenchyme in the hylum; incomplete differentiation of developing proximal and distal tubules. At cellular level, kidneys of preterm infants are characterized by huge amounts of stem/precursor cells showing different degrees of differentiation, admixed with mature cell types. The most striking difference between the preterm and adult kidney is represented by the abundance of stem/progenitor cells in the former. Multiple stem cell niches may be identified in the preterm kidney, including the capsule, the sub-capsular nephrogenic zone, the cap mesenchyme embracing the ureteric bud tips, the cortical and medullary interstitium, and the hilar zone in proximity of the ureteric origin. The sub-capsular area represents the major stem cell niche in the prenatal kidney. It has been defined "blue strip", due to the scarcity of cytoplasm of the undifferentiated stem/progenitors, which appear as small cells arranged in a solid pattern. All these data taken together, the morphological approach to the analysis of the preterm kidney appears completely different from that typically utilized in kidney biopsies from adult subjects. Such a different structure should be taken into account when evaluating renal function in a preterm infant in clinical practice. Moreover, a better knowledge of molecular biology of the blue strip stem/ progenitor cells could be at the basis of a new "endogenous" regenerative medicine, finalized to maintain and protect the nephrogenic potential of preterm infants till the 36th week of post-conceptional age, allowing them to escape oligonephronia and chronic kidney disease later in life. [ABSTRACT FROM AUTHOR]

Eight [Ir(bpy)Cp*Cl]+-type complexes (bpy= bipyridine, Cp*=1,2,3,4,5-pentamethylcyclopentadienyl) containing differently substituted bipyridine ligands were synthesized and characterized. Cyclic voltammetry (CV) of the complexes in Ar-saturated acetonitrile solutions showed that the redox behavior of the complexes could be fine tuned by the electronic properties of the substituted bipyridine ligands. Further CV in CO2-saturated MeCN/H2O (9:1, v/v) solutions showed catalytic currents for CO2 reduction. In controlled potential electrolysis experiments (MeCN/MeOH (1:1, v/v), Eapp=−1.80 V vs Ag/AgCl), all of the complexes showed moderate activity in the electrocatalytic reduction of CO2 with good stability over at least 15 hours. This electrocatalytic process was selective toward formic acid, with only traces of dihydrogen or carbon monoxide and occasionally formaldehyde as byproducts. However, the turnover frequencies and current efficiencies were quite low. No direct correlation between the redox potentials of the complexes and their catalytic activity was observed. [ABSTRACT FROM AUTHOR]

The development of a novel benzimidazole-derived bidentate P,N-ligand and its application in Ir-catalyzed hydrogenation is described. The ligand backbone was obtained through a one-pot tandem hydroformylation-cyclization sequence and the enantiomers of the generated alcohol were separated by chiral HPLC. By comparing the experimentally obtained CD spectra of the enantiomers with the simulated spectra generated from time-dependent DFT calculations, the absolute configuration could be obtained. The chiral alcohols could further be isolated on a larger scale after transesterification by using Candida Antarctica lipase B (Novozym 435) and could subsequently be converted into the corresponding chiral P,N-ligand by reaction with ClPPh2. The coordination properties of the racemic P,N-ligand were investigated and the molecular structure of the RhI complex [(P,N)Rh(CO)Cl] was determined by X-ray crystal structure analysis. The corresponding chiral cationic IrI complex was used as catalyst for the enantioselective hydrogenation of prochiral N-phenyl-(1-phenylethylidene)amine and trans-α-methylstilbene. For the N-aryl-substituted imine, enantiomeric excesses of only 10 % were obtained, whereas the unfunctionalized olefin could be hydrogenated with enantiomeric excesses of up to 90 %. Interestingly, the modular synthetic access to the P,N-hybrid system described here allows facile modification of the ligand structure, which should extend the scope of such novel P,N-ligands for asymmetric catalytic conversions to a large extent in the future. [ABSTRACT FROM AUTHOR]

The synthesis of asymmetrically substituted 2,2′:6′,2′′-terpyridines is reported. First, palladium-catalyzed CH arylation of pyridine N-oxides with substituted bromopyridines gave 2,2′-bipyridine N-oxides, which were further arylated in a second step to form 2,2′:6′,2′′-terpyridine N-oxides. Yields of up to 77 % were obtained with N-oxides bearing an electron-withdrawing ethoxycarbonyl substituent in the 4-position. Pd(OAc)2 with either P( tBu)3 or P( o-tolyl)3 was used as the catalyst. Cyclometalated complexes derived from Pd(OAc)2 and these phosphines were also effective. K3PO4 as the base gave better results than K2CO3. Subsequent deoxygenation with H2 and Pd/C as the catalyst gave the asymmetrically substituted 2,2′:6′,2′′-terpyridines in near quantitative yield. This reaction sequence significantly reduces the number of steps required in comparison with known cross-coupling methods and therefore allows convenient and scalable access to substituted terpyridines. [ABSTRACT FROM AUTHOR]

Both enantiomers of the novel benzimidazole-derived bidentate P,N-ligand (I) are synthesized (not shown) and applied to Ir-catalyzed hydrogenation reactions. [ABSTRACT FROM AUTHOR]

The convenient and scalable synthesis of the title compounds is accomplished in fewer steps compared to known cross-coupling methods. [ABSTRACT FROM AUTHOR]

On Pentecost Monday, 9 June 2014, a severe linearly organized mesoscale convective system (MCS) hit Belgium and western Germany. This storm was one of the most severe thunderstorms in Germany in decades. The synoptic-scale and mesoscale characteristics of this storm are analyzed based on remote sensing data and in situ measurements. Moreover, the forecast potential of the storm is evaluated using sensitivity experiments with a regional climate model. The key ingredients for the development of the Pentecost storm were the concurrent presence of low-level moisture, atmospheric conditional instability, and wind shear. The synoptic and mesoscale analysis shows that the outflow of a decaying MCS above northern France triggered the storm, which exhibited the typical features of a bow echo like a bookend vortex and a rear-inflow jet. This resulted in hurricane-force wind gusts (reaching 40 m s−1) along a narrow swath in the Rhine–Ruhr region leading to substantial damage. Operational numerical weather prediction models mostly failed to forecast the storm, but high-resolution regional model hindcasts enable a realistic simulation of the storm. The model experiments reveal that the development of the bow echo is particularly sensitive to the initial wind field and the lower-tropospheric moisture content. Adequate initial and boundary conditions are therefore essential for realistic numerical forecasts of such a bow echo event. It is concluded that the Pentecost storm exhibited a comparable structure and a similar intensity to observed bow echo systems in the United States. [ABSTRACT FROM AUTHOR]

Objective. Evaluation of neuronal changes in an animal experimental model of normocapnic hypoxia- reoxygenation. Materials and Methods. Fifty male piglets were the study subjects; normocapnic hypoxia was induced in 40 piglets and ten were shamoperated (controls). When bradycardia and/or severe hypotension occurred, reoxygenation was initiated. Animals were allocated in 4 groups according to the oxygen concentration, they were resuscitated with 18%, 21%, 40%, and 100% O2. Persisting asystole despite 10 minutes of cardiopulmonary resuscitation and return of spontaneous circulation were the endpoints of the experiment. Surviving animals were euthanized and brain cortex samples were collected, hematoxylin and eosin-stained, and examined for apoptotic bodies observing 10 consecutive high power fields. Results.Histological examination of the control group did not showany pathological change. On the contrary, apoptosis of neurons was found in 87.5% of treated animals. When specimens were examined according to the oxygen concentration used for resuscitation, we found marked intergroup variability; a higher percentage of apoptotic neurons was observed in piglets of group 4 (100% oxygen) compared to the others (P = 0.001). Conclusions. This preliminary data shows that normocapnic hypoxia and reoxygenation in Landrace/Large White piglets resulted in significant histological changes in the brain cortex. The degree of pathological changes in cortical neurons was significantly associated with the oxygen concentration used for reoxygenation, with a higher percentage of apoptotic neurons being observed in piglets reoxygenated with 100% compared to 18% O2 and to 21% O2. [ABSTRACT FROM AUTHOR]

The identification of the different cell types involved in human nephrogenesis, when solely based on morphology, may lead to errors in its interpretation, given the complexity of the histological picture of the fetal and of the newborn kidney. In this study, the most recent works utilizing immunhistochemistry for the identification of the multiple cell types involved in human nephrogenesis are reviewed. The role of WT1, MUC1, Thymosin beta 10, Thymosin beta 4, CD10 and CD44 in the different phases of glomerulogenesis and of tubulogenesis is here described, with particular emphasis on their expression in the early phases of nephrogenesis. On the basis of our data, immunohistochemistry appears to be a useful tool in the study of human nephrogenesis, giving new data on the different steps of the differentiation of metanephric mesenchyme towards the multiple cell types characterizing the mature human kidney. Moreover, allowing a better knowledge of the protein products involved in the generation of new nephrons, immunohistochemistry could open new perspectives in the field of renal regenerating medicine, evidencing the factors able to prolong nephrogenesis after birth, helping us to reach our goal: allowing newborn kidneys to restore their nephron endowment, escaping susceptibility to hypertension and renal disease in adulthood. [ABSTRACT FROM AUTHOR]

CD10 was first identified in tumor cells of acute lymphoblastic leukemia. Most studies on CD10 expression have dealt with tumor pathology. Since no data are available for specific role in the fetal kidney, this study aimed at investigating CD10 expression during the different phases of renal embryogenesis. To this end, the expression of CD10 was evaluated in the kidney of two human fetus and in three newborns. In both fetuses, immunostaining for CD10 was compartmentalized and mainly concentrated in the mid-deep cortex. Reactivity for CD10 was stronger in the glomerular epithelium, in proximal tubules and in metanephric mesenchymal cells. At 25 weeks of gestation, CD10 was also detected in the subcapsular regions, including some pretubular aggregates of cap mesenchymal cells and renal vesicles. At 34 weeks of gestation, we observed an increased immunoreactivity for CD10 in visceral and parietal glomerular epithelium. At 39 weeks of gestation, CD10 was also expressed in the collecting tubules and in the Henle loops. Our data show a strong expression of CD10 in all stage of human kidney development, characterized by dynamic changes and support the hypothesis that CD10 plays a relevant role in renal embryogenesis. [ABSTRACT FROM AUTHOR]

An oxidation of allylic and benzylic alcohols to the corresponding carboxylic acids is effected by merging a Cu-catalyzed oxidation using O2 as a terminal oxidant with a subsequent chlorite oxidation (Lindgren oxidation). The protocol was optimized to obtain pure products without chromatography or crystallization. Interception at the aldehyde stage allowed for Z/E-isomerization, thus rendering the oxidation stereoconvergent with respect to the configuration of the starting material. [ABSTRACT FROM AUTHOR]

With the incidence of end-stage renal disease increasing dramatically during the last ten years, its prevalence rising about 8% per year, chronic kidney disease (CKD) represents one of the most problematic public health problems worldwide. CKD represents a growing clinical problem that, in its terminal stages, requires renal replacement therapy. Kidney transplant has been proposed as the definitive therapy able to address the growing clinical, social and economic problems related to the increasing prevalence of end-stage kidney disease (ESKD). Traditional stem cell-based regenerative medicine, when applied to kidneys disrupted by end-stage renal disease, has been shown to be unable to regenerate the damaged organ. The theme of this work is to hypothesize a new approach to the prevention of CKD, based on the management of the huge amount of stem/progenitor cells physiologically present in the kidney of preterm babies at birth. Here a new concept of primary prevention of renal disease is suggested: a true primary prevention, starting in the perinatal period aimed at increasing the number of functioning glomeruli. This approach has been defined as “physiological regenerative medicine”, in order to underline the use of physiological tools, including endogenous renal stem cells and stem cell stimulators physiologically expressed in our cells. [ABSTRACT FROM AUTHOR]

Nephron number at birth has relevant clinical importance with implications for long-term renal health. In recent years, the podocyte depletion hypothesis has emerged as an important concept in kidney pathology. This study was aimed at verifying whether human podocyte number changes significantly during intrauterine life. To this end, 62 subjects with gestational ages ranging from 20 to 41 wk were examined. Kidney sections were stained with hematoxylin and eosin and digitally scanned at ×400 magnification. Subjects were subdivided into fetuses (gestational age ×24 wk, n = 5), preterms (gestational age ≥25 and ≤36 wk, n = 39), and full-term newborns (gestational age ≥37 wk, n = 18). The average podocyte number of 1,908 ± 645, 1,394 ± 498, and 1,126 ± 256 was, respectively, observed in fetuses, preterms, and full-term newborns. A significant main effect (P = 0.0051) of gestational age on podocyte number was observed with a significantly lower number in full-term newborns than in fetuses (P < 0.01). Intragroup variability was also observed. We speculate that variations in podocyte number could be correlated with factors such as drugs and maternal diet occurring during intrauterine life. In conclusion, this study shows, for the first time, a decreasing trend in podocyte number during gestation. [ABSTRACT FROM AUTHOR]

AimTo study the solubility of perfluorohexyloctane (F6H8) in silicone oil (polydimethylsiloxane (PDMS) 1000) and to measure the viscosity and the specific gravity of the mixture obtained (heavy silicone oil or HSO tamponade) to define the ideal ratio of these components.MethodsThe solubility diagram of the mixture was obtained with the turbidimetric method, indicating the miscibility of F6H8 and silicone oil 1000 at all the useful temperatures. The viscosity was measured in steady shear conditions by using a controlled stress rheometer (Haake RS150) and a double cone/plate (DC 60/4) system, both at 25 and 37°C for different volume per cent compositions of the mixture. The specific gravity was measured at 37°C using a digital densimeter.ResultsA mixture of F6H8 30 v% and PDMS 70 v% was found to be transparent and stable at all the useful temperatures. By combining these proportions of the two substances, a resultant density of 1.06 g/cm3 was obtained. The viscosity of the 30% F6H8 mixture was 203 mPa.s at 25°C and 163 mPa.s at 37°C respectively.ConclusionsThe ideal F6H8 and silicone oil mixture can be obtained combining 30% of F6H8 with 70% of silicone oil 1000. This mixture seems to have rheological properties useful for its use as an alternative intraocular heavy tamponade.Eye (2008) 22, 1082–1088; doi:10.1038/eye.2008.144; published online 6 June 2008 [ABSTRACT FROM AUTHOR]