Time-resolved excited state energetics of the solvated electron in sodium-doped water clusters.

The energetics and dynamics of the first electronically excited state of solvated electron in sodium-doped water clusters has been studied, by means of time-resolved electron spectra created in a pump-probe fs-laser experiment. The Na ··· (H2O)n clusters were excited by pulses at a wavelength of 795 nm, while ionization was achieved at a wavelength of 398 nm, and the overall cross-correlation fwhm was about 50 fs. Mass-resolved electron spectra were taken using photoelectron-photoion coincidence (PEPICO) spectroscopy for cluster sizes ranging from n = 1 up to 22. The electron spectra give new insights into the dynamics of the excited state of solvated electrons in Na ··· (H2O)n clusters. These dynamics are compared to known results for water cluster anions. In both cases, the observed dynamics are a combination of solvent rearrangement and internal energy conversion.

Ultrafast photo-excitation dynamics in isolated, neutral water clusters.

Using the efficient nonlinear conversion scheme which was recently developed in our group [M. Beutler, M. Ghotbi, F. Noack, and I. V. Hertel, Opt. Lett. 134, 1491 (2010); M. Ghotbi, M. Beutler, and F. Noack, ibid 35, 3492 (2010)] to provide intense sub-50 fs vacuum ultraviolet laser pulses we have performed the first real time study of ultrafast, photo-induced dynamics in the electronically excited Ã-state of water clusters (H(2)O)(n) and (D(2)O)(n) , n=2-10. Three relevant time scales, 1.8-2.5, 10-30, and 50-150 fs, can be distinguished which-guided by the available theoretical results-are attributed to H (D)-ejection, OH (OD) dissociation, and a nonadiabatic transition through a conical intersection, respectively. While a direct quantitative comparison is only very preliminary, the present results provide a crucial test for future modeling of excited state dynamics in water clusters, and should help to unravel some of the many still unresolved puzzles about water.

Enhancement of optical processes in coupled plasmonic nanocavities [Invited].

We present detailed experimental and numerical investigations of resonances in deep nanogroove gratings in metallic substrates. These plasmonic nanocavity gratings feature enhanced fields within the grooves that enable a large enhancement of linear and nonlinear optical processes. This enhancement relies on both localized and propagating surface plasmons on the nanopatterned surface. We show that the efficiency of optical processes such as Raman scattering and four-wave mixing is dramatically enhanced by plasmonic nanocavity gratings.

Steplike intensity threshold behavior of extreme ionization in laser-driven xenon clusters.

The generation of highly charged Xe(q+) ions up to q=24 is observed in Xe clusters embedded in helium nanodroplets and exposed to intense femtosecond laser pulses (λ=800 nm). Laser intensity resolved measurements show that the high-q ion generation starts at an unexpectedly low threshold intensity of about 10(14) W/cm2. Above threshold, the Xe ion charge spectrum saturates quickly and changes only weakly for higher laser intensities. Good agreement between these observations and a molecular dynamics analysis allows us to identify the mechanisms responsible for the highly charged ion production and the surprising intensity threshold behavior of the ionization process.

Ultrafast dynamics in Na-doped water clusters and the solvated electron.

The lifetimes of the first electronically excited state of (H(2)O)(n)...Na and (D(2)O)(n)...Na clusters up to n = 40 have been measured by two-color pump-probe spectroscopy (800 and 400 nm) with 35 fs laser pulses. The excited-state lifetime decreases rapidly from 1.2 ps at n = 2 to approximately 100 fs at n > or = 10. For (D(2)O)(n)...Na, the average lifetime is about 3.6 times longer. The fast energy redistribution is explained by conversion of the electronic excitation into vibrations of the ground state. A simple model based on Fermi's Golden Rule predicts the observed trends but fails to reproduce the observed lifetimes quantitatively. The longer lifetimes for deuterated clusters are discussed in the framework of the famous energy gap law and indicate that the stretching modes of water play an important role in the energy-transfer process.

Distribution of Borna disease virus antigen and RNA in tissues of naturally infected bicolored white-toothed shrews, Crocidura leucodon, supporting their role as reservoir host species.

Borna disease is a severe viral-induced disorder of the central nervous system of horses, sheep, and a few other animal species, occurring in certain areas of central Europe. Pathogenesis and epidemiology of natural Borna disease virus (BDV) infections are still not fully understood; several unique epidemiologic features, however, point toward the existence of BDV reservoir populations other than the final hosts. In this study, 69 mice and 12 shrews were trapped and examined. The virus distribution was investigated in detail in 2 BDV-positive bicolored white-toothed shrews, Crocidura leucodon, by immunohistochemistry and TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR). RT-PCR amplification products were sequenced, and the sequences were compared. These shrews had been collected in a BDV-endemic geographical region using live traps and did not show obvious clinical or pathological disease signs. BDV antigen and nucleic acid were identified in several organs, including the brain, mainly in nerve tissue and neurons, respectively, but also in parenchymal cells (eg, hepatocytes, Leydig cells) and epithelial cells, particularly of the respiratory and urogenital tract.

Molecular characterization of EZH2 mutant patients with myelodysplastic/myeloproliferative neoplasms.

Mutations in the epigenetic regulator gene EZH2 are frequently observed in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN; 10-13%) and are associated with a poor outcome. To gain more insight into EZH2 pathology, we sought to genetically characterize a cohort of 41 EZH2-mutated MDS/MPN patients using targeted deep next-generation sequencing (NGS), colony-forming progenitor assays and transcriptome analysis. Stable short hairpin RNA (shRNA)-mediated downregulation of EZH2 was performed in MDS-derived F-36P, MOLM-13 and OCI-M2 cells to study EZH2-specific changes. Targeted NGS revealed a complex pattern of mutations with a total of 190 individual mutations. EZH2 mutations frequently co-occur with TET2 (58%), RUNX1 (40%) and ASXL1 (34%) mutations. Colony assays indicated EZH2 mutations to be mostly early events in leukemogenesis and showed a complex mutational hierarchy. Gene expression data revealed a number of differently expressed genes between EZH2 wild-type and mutant patients including known EZH2 targets. Comparison of patient transcriptome to EZH2-downregulated cell line data revealed several genes as novel EZH2 targets, showing opposite as well as unidirectional regulation between cell lines and patients. Some genes, such as CXXC5, ETS1 and VAV3 have previously been implied to have a role in leukemogenesis. Their precise role in MDS/MPN needs to be further investigated.

Identification of the Beagle 2 lander on Mars.

The 2003 Beagle 2 Mars lander has been identified in Isidis Planitia at 90.43° E, 11.53° N, close to the predicted target of 90.50° E, 11.53° N. Beagle 2 was an exobiology lander designed to look for isotopic and compositional signs of life on Mars, as part of the European Space Agency Mars Express (MEX) mission. The 2004 recalculation of the original landing ellipse from a 3-sigma major axis from 174 km to 57 km, and the acquisition of Mars Reconnaissance Orbiter High Resolution Imaging Science Experiment (HiRISE) imagery at 30 cm per pixel across the target region, led to the initial identification of the lander in 2014. Following this, more HiRISE images, giving a total of 15, including red and blue-green colours, were obtained over the area of interest and searched, which allowed sub-pixel imaging using super high-resolution techniques. The size (approx. 1.5 m), distinctive multilobed shape, high reflectivity relative to the local terrain, specular reflections, and location close to the centre of the planned landing ellipse led to the identification of the Beagle 2 lander. The shape of the imaged lander, although to some extent masked by the specular reflections in the various images, is consistent with deployment of the lander lid and then some or all solar panels. Failure to fully deploy the panels-which may have been caused by damage during landing-would have prohibited communication between the lander and MEX and commencement of science operations. This implies that the main part of the entry, descent and landing sequence, the ejection from MEX, atmospheric entry and parachute deployment, and landing worked as planned with perhaps only the final full panel deployment failing.

NOX4-driven ROS formation mediates PTP inactivation and cell transformation in FLT3ITD-positive AML cells.

Activating mutations of FMS-like tyrosine kinase 3 (FLT3), notably internal tandem duplications (ITDs), are associated with a grave prognosis in acute myeloid leukemia (AML). Transforming FLT3ITD signal transduction causes formation of reactive oxygen species (ROS) and inactivation of the protein-tyrosine phosphatase (PTP) DEP-1/PTPRJ, a negative regulator of FLT3 signaling. Here we addressed the underlying mechanisms and biological consequences. NADPH oxidase 4 (NOX4) messenger RNA and protein expression was found to be elevated in FLT3ITD-positive cells and to depend on FLT3ITD signaling and STAT5-mediated activation of the NOX4 promoter. NOX4 knockdown reduced ROS levels, restored DEP-1 PTP activity and attenuated FLT3ITD-driven transformation. Moreover, Nox4 knockout (Nox4(-/-)) murine hematopoietic progenitor cells were refractory to FLT3ITD-mediated transformation in vitro. Development of a myeloproliferative-like disease (MPD) caused by FLT3ITD-transformed 32D cells in C3H/HeJ mice, and of a leukemia-like disease in mice transplanted with MLL-AF9/ FLT3ITD-transformed murine hematopoietic stem cells were strongly attenuated by NOX4 downregulation. NOX4-targeting compounds were found to counteract proliferation of FLT3ITD-positive AML blasts and MPD development in mice. These findings reveal a previously unrecognized mechanism of oncoprotein-driven PTP oxidation, and suggest that interference with FLT3ITD-STAT5-NOX4-mediated overproduction of ROS and PTP inactivation may have therapeutic potential in a subset of AML.

Expression of the Xenopus laevis metallothionein gene during ontogeny.

Expression of the Xenopus laevis metallothionein (MT) gene was studied by in situ hybridization throughout development. MT mRNA was detected from the tailbud stage onwards. MT expression was observed in bucco-pharyngeal epithelium, pronephros and liver anlagen, aswell as in lens and periventricular areas of the encephalon. MT transcripts, in both larvae and adults, were detected in diverse regions of the central nervous system and in differentiating tissues implicated in detoxification processes: liver hepatocytes, small intestine epithelia and kidney tubules. These data are discussed in the context of MT functions and support a physiological role for MT in growth processes.

Cloning of the newt Pleurodeles waltlii chromosomal DNA.

Pleurodeles waltlii genomic DNA has been cloned using several phage lambda vectors. We have isolated approx. 600 000 clones, which correspond to about 20% of the total DNA sequences of this organism. This constitutes the first large gene library of a Urodele. The low yield of cloning was attributable to the abundance of highly repetitive sequences, since recombinations in the bacterial host could lead to the loss of clones. Indeed, the existence of highly repetitive sequences was directly demonstrated by hybridization between recombinants and the total genome, and some of the cloned DNA was found to be unstable. We suggest new methods for cloning the highly repetitive sequences.

Molecular cloning and expression of ferritin mRNA in heavy metal-poisoned Xenopus laevis cells.

In a search for genes transcriptionally regulated by metal ions, we have isolated a Xenopus laevis ferritin cDNA clone, XL2-17, from cadmium-poisoned XL2 cells. The large size of the corresponding ferritin mRNA (1.4 kb) is due to the presence of a 629-nucleotide 5'-untranslated region. The Xenopus ferritin sequence is highly isologous with other vertebrate ferritins. In particular, there is a complete sequence identity for the iron-responsive element (IRE) located in the 5'-untranslated region in both XL2-17 and Rana catesbeiana ferritin mRNAs. The position of this IRE is unusual since it is located 489 nucleotides from the 5' end of the ferritin mRNA. Our analysis of phylogenetic relationships among ferritins indicates that all amphibian ferritins thus far sequenced would be more closely related to the mammalian H-type ferritin than to the L-type. The level of ferritin mRNA in XL2 cells rises 10- to 15-fold following exposure of cells to cadmium or copper. This increase is due to both transcriptional and translational regulation. A 10-fold increase was also found at the protein level. These results suggest that ferritin may be a primary detoxification response to heavy metals in Xenopus cells.

Molecular cloning and expression of a metallothionein mRNA in Xenopus laevis.

Metallothioneins (MT) are expressed during early development in species of several groups. To understand MT function in developmental processes, we studied the MT system of Xenopus laevis, a model vertebrate species in experimental embryology. We first purified and sequenced the liver MT from copper-treated animals. This 62-amino-acid protein shares the main structural properties of known vertebrate MT, and is more closely related to avian than to fish or mammalian MT. Using this sequence, we designed oligonucleotide primers to amplify and isolate a MT clone from a XL2 cell line cDNA library. This 752-bp cDNA encodes a putative 62-amino-acid-long protein that is 100% identical with the sequenced MT. Zinc, cadmium, and copper ions are very efficient inducers of MT mRNA accumulation in Xenopus liver and cell lines.

Effects of pre-protein overexpression on SecB synthesis in Escherichia coli.

Protein translocation through the cytoplasmic membrane of Escherichia coli involves cytosolic chaperones. The export-dedicated chaperone SecB mediates targeting of a subset of pre-proteins. In this report, synthesis of SecB in response to plasmid-mediated overexpression of pre-proteins was studied. Overexpression of SecB-dependent pre-proteins stimulated synthesis of SecB under conditions where the cellular export capacity was saturated or uncomplexed SecB was trapped. On the contrary, overexpression of SecB-independent pre-beta-lactamase reduced the promoter activity of secB. The results suggest that uncomplexed SecB can be sequestered by synthesis of SecB-dependent pre-proteins. Furthermore, these data demonstrate the distinct action of the SecB- and signal recognition particle-dependent protein targeting pathways.

Localisation of the cell wall-associated phosphodiesterase PhoD of Bacillus subtilis.

The localisation of phosphate-starvation-induced phosphodiesterase PhoD from Bacillus subtilis was studied by analysing processing, release and immunogold labelling of the sections. Although the processing of the pre-protein was extremely slow, the major fraction of PhoD could be detected at the surface of the cell wall. The results indicate that inefficient processing of the translocated pre-protein keeps PhoD in a cell wall-associated location. The uncleaved signal peptide might function as a membrane anchor.

[Klippel-Trenaunay syndrome and ischemic neurologic complications]. / Syndrome de Klippel-Trenaunay et complications neurologiques ischémiques.

In 1900 Klippel and Trenaunay defined a new entity characterized by cutaneous angioma associated with varices and hypertrophy of bone and soft tissues. The syndrome is present in the earliest years and becomes accentuated as the child grows. It typically affects one half of the body. We report two cases of Klippel-Trenaunay syndrome. The first patient presented with flaccid paraplegia. On T1-weighted MRI sequences a diffuse heterogeneous high-intensity signal was visible opposite the T8 and T9 vertebral bodies. Spinal cord angiography showed occlusion of the anterior spinal artery issued from Adamkiewicz's artery, suggesting thrombosis. Serum fibrinopeptide A level was very high and compatible with hypercoagulability. The second patient presented with left hemiplegia caused by a right superficial sylvian artery infarct, and carotid angiography showed an image of right internal carotid artery dissection. These two cases suggest that Klippel-Trenaunay syndrome includes a state of hypercoagulability facilitating the occurrence of arterial thrombotic accidents, and an abnormality of the arterial wall capable of determining spontaneous dissection. A study of arterial wall-dependent coagulation factors should establish a link between these two aetiological factors. All this argues in favor of a diffuse vascular pathology, which makes this syndrome close to phakomatoses.

[Recurrent coma, papular mucinosis and benign dysglobulinemia]. / Comas répétés, mucinose papuleuse, dysglobulinémie bénigne.

A woman presented with a history of three regressive comas of undetectable etiology between the age of 52 and 57 years. An IgG lambda benign monoclonal dysglobulinemia was combined with a papular mucinosis (myxedematous lichen or the generalized form of Arndt-Gotton's scleromyxedema). In the 6 analogous cases documented in the literature the onset of coma occurred generally several weeks after an aggravation of the cutaneous lesions. The coma was preceded by an influenza-like syndrome followed by asthenia, malaise with vertigo and frequently epileptic seizures. During recovery, hallucinations and transient hepatic disorders were noted. Pruritus with pronounced hypereosinophilia preceded desquamation and regression of dermatologic lesions. These comas can lead to a fatal outcome (2 of 7 cases) or regress in 2 to 20 days usually without sequelae. The disease is probably of immunologic origin. The paraprotein or a serum factor could exert a direct toxic effect on brain. As in neurologic manifestations of malignant dysglobulinemia, explained initially by a "toxic encephalosis, clinical, angiography, biologic and immunologic data exist in favor of blood hyperviscosity. This hyperviscosity could result from polymer formation through intermediates immunoglobulins and other protein chains, or again from alteration of deformability of red cells by binding of paraprotein. Hyperviscosity syndromes are frequent in system diseases that are often associated with papular mucinosis. Whatever the exact mechanism of these "comas due to papular mucinosis", a logical choice is their treatment by immunosuppressants and plasmapheresis: in the case reported, the use of plasmapheresis as soon as premonitory signs had appeared probably prevented a fourth coma.

[Internal carotid occlusion and essential thrombocythemia. 2 cases]. / Occlusion carotidienne interne et thrombocythémie essentielle. 2 cas.

We report 2 cases of occlusion of the internal carotid artery in young, non-atherosclerotic patients with essential thrombocythemia (ET). This complication of ET seems to be rare, but is probably underdiagnosed since transient ischemia, which is frequent in ET patients, is seldom explored by angiography. The excess of thrombocytes and the thrombopathy may account for the microvascular complications, but in the absence of any other contributory factor, occlusions of large arteries, such as the ICA, is more difficult to explain.

[Hemiballismus. Hemichorea. Striatal infarction]. / Hémiballisme. Hémichorée. Infarctus striatal.

Lesions of other structures than corpus Luysii, may rarely cause hemiballism. A case is reported of hemiballism due to infarction of the territory supplied by the lenticulo-striatal arteries. CT and MR imaging showed lesions of the caudate nucleus and putamen. This suggested that the cause of the hemiballism was the suppression of the regulatory activity of the caudate nucleus on the pallidum.

[Obsessive-compulsive behavior and progressive supranuclear palsy]. / Comportement compulsif d'allure obsessionnelle et paralysie supranucléaire progressive.

A case of progressive supranuclear palsy characterized by a loss of self-activation and a compulsive behaviour of the obsessive type is reported. The pathological examination was remarkable for the intensity of pallidal lesions and their diffusion to both the external and internal segments. While the loss of self-activation seemed to result from a damaged cortico-subcortical circuit forming a limbic loop, the compulsive behaviour of the obsessive type may have resulted from the interruption of a frontal-caudal-pallidal-luysian circuit.