Nervous System Regionalization Entails Axial Allocation before Neural Differentiation

Neural induction in vertebrates generates a CNS that extends the rostral-caudal length of the body. The prevailing view is that neural cells are initially induced with anterior (forebrain) identity; caudalizing signals then convert a proportion to posterior fates (spinal cord). To test this model, we used chromatin accessibility to define how cells adopt region-specific neural fates. Together with genetic and biochemical perturbations, this identified a developmental time window in which genome-wide chromatin-remodeling events preconfigure epiblast cells for neural induction. Contrary to the established model, this revealed that cells commit to a regional identity before acquiring neural identity. This "primary regionalization" allocates cells to anterior or posterior regions of the nervous system, explaining how cranial and spinal neurons are generated at appropriate axial positions. These findings prompt a revision to models of neural induction and support the proposed dual evolutionary origin of the vertebrate CNS

Study of doubly strange systems using stored antiprotons

Bound nuclear systems with two units of strangeness are still poorly known despite their importance for many strong interaction phenomena. Stored antiprotons beams in the GeV range represent an unparalleled factory for various hyperon-antihyperon pairs. Their outstanding large production probability in antiproton collisions will open the floodgates for a series of new studies of systems which contain two or even more units of strangeness at the P‾ANDA experiment at FAIR. For the first time, high resolution γ-spectroscopy of doubly strange ΛΛ-hypernuclei will be performed, thus complementing measurements of ground state decays of ΛΛ-hypernuclei at J-PARC or possible decays of particle unstable hypernuclei in heavy ion reactions. High resolution spectroscopy of multistrange Ξ−-atoms will be feasible and even the production of Ω−-atoms will be within reach. The latter might open the door to the |S|=3 world in strangeness nuclear physics, by the study of the hadronic Ω−-nucleus interaction. For the first time it will be possible to study the behavior of Ξ‾+ in nuclear systems under well controlled conditions

Ab initio and experimental studies on the hetero-Diels-Alder and cheletropic additions of sulfur dioxide to (E)-1-methoxybutadiene: A mechanism involving three molecules of SO2

Kinetics on the cheletropic addition of sulfur dioxide to (E)-1-methoxybutadiene (1) to give the corresponding sulfolene 2 (2-methoxy-2,5-dihydrothiophene-1,1-dioxide) gave the rate law d[2]/dt = k[1] [SO2](x) with x = 2.6 +/- 0.2 at 198 K. Under these conditions, no sultine 3 [(2RS,6RS)-6-methoxy-3,6-dihydro-1,2-oxathiin-2-oxide] resulting from a hetero-Diels-Alder addition was observed, and the cheletropic elimination 2 --> 1 + SO2 did not occur. Ab initio and DFT quantum calculations confirmed that the cheletropic addition 1 + SO2 --> 2 follows two parallel mechanisms, one involving two molecules of SO2 and the transition structure with DeltaG(double dagger) = 18.2 +/- 0.2 kcal/mol at 198 K (exptl); 22.5-22.7 kcal/mol [B3LYP/6-31G(d,p)], the other one involving three molecules of SO2 with DeltaG(double dagger) = 18.9 +/- 0.1 kcal/mol at 198 K (exptl); 19.7 kcal/mol [B3LYP/6-31G(d,p)]. The mechanism involving only one molecule of SO2 in the transition structure requires a higher activation energy, DeltaG(double dagger) = 25.2 kcal/mol [B3LYP/6-31G(d,p)]. Comparison of the geometries and energetics of the structures involved into the 1 + SO2 --> 2, 3 and 1 + 2SO(2) --> 2, 3 + SO2 reactions obtained by ab initio and DFT methods suggest that the latter calculation techniques can be used to study the cycloadditions of sulfur dioxide. The calculations predict that the hetero-Diels-Alder addition 1 + SO2 --> 3 also prefers a mechanism in which three molecules of SO2 are involved in the cycloaddition transition structure. At 198 K and in SO2 solutions, the entropy cost (TDeltaS(double dagger)) is overcompensated by the specific solvation by SO2 in the transition structures of both the cheletropic and hetero-Diels-Alder reactions of (E)-1-methoxybutadiene with SO2

Regionalization of the nervous system requires axial allocation prior to neural lineage commitment

Neural induction in vertebrates generates a central nervous system that extends the rostral-caudal length of the body. The prevailing view is that neural cells are initially induced with anterior (forebrain) identity, with caudalising signals then converting a proportion to posterior fates (spinal cord). To test this model, we used chromatin accessibility assays to define how cells adopt region-specific neural fates. Together with genetic and biochemical perturbations this identified a developmental time window in which genome-wide chromatin remodeling events preconfigure epiblast cells for neural induction. Contrary to the established model, this revealed that cells commit to a regional identity before acquiring neural identity. This “primary regionalization” allocates cells to anterior or posterior regions of the nervous system, explaining how cranial and spinal neurons are generated at appropriate axial positions. These findings prompt a revision to models of neural induction and support the proposed dual evolutionary origin of the vertebrate central nervous system

On the Molecular Structure of Uranium Dicarbide: T-Shape versus Linear Isomers

A theoretical study of the molecular structure of uranium dicarbide has been carried out employing DFT, coupled cluster, and multiconfigurational methods. A triangular species, corresponding to a 5A 2 electronic state, has been found to be the most stable UC 2 species. A triplet linear CUC species, which has been observed in recent infrared spectroscopy experiments, lies much higher in energy. A topological analysis of the electronic density has also been carried out. The triangular species is shown to be in fact a T-shape structure with a U-C interaction which can be considered to be a closed-shell interaction.Fil: Zalazar, Maria Fernanda. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Rayon, Victor M.. Universidad de Valladolid. Facultad de Ciencias; EspañaFil: Largo, Antonio. Universidad de Valladolid. Facultad de Ciencias; Españ

An internet-based multinational study of patients receiving Amphotericin B products [Abstract]

Background: Amphotericin B (amB) has been the standard therapy for most systemic mycoses but is associated with significant adverse events (AEs) including nephrotoxicity (NT). Lipid-based formulations of amB (l-amB) have been developed to diminish these toxicities. Objectives were to estimate response to therapy, identify the incidence of NT and other AEs, and assess the use of medical resources used to monitor and treat NT and other AEs. Methods: A multinational observational study was initiated to prospectively collect data on hospitalized adult patients (pts) receiving amB or l-amB. The first day of therapy constituted the beginning of the observation period. Pts were followed until discharge. Data were entered into a relational database via the Internet using validated software. NT was defined a priori as a 50% increase in baseline serum creatinine (SCr) with a peak of 2.0mg/dl. Results: From 12/00 to 4/01, 16 European hospitals contributed data on 123 pts. 94 pts had complete records and were evaluated. 68% initially received amB, 13% lipid complex, 18% liposomal formulation, and 1% colloidal dispersion. Gender, race, and baseline SCr did not differ by therapy (59% male, 97% Caucasian, 1.0 mg/dl). AmB pts were older than l-amB pts (53 vs 45 yrs, p50.01). 14% of all pts had proven fungal infections at therapy start. 62% of these documented infections were candida. Leukemia or lymphomas were most prevalent medical conditions (79%). 8 of the 11 allogeneic bone marrow transplant pts received l-amB. 23% of amB switched to l-amB. Favorable response based on initial therapy was 60% for amB and 37% for l-amB pts. Reported AEs were 73% for amB and 40% for l-amB pts. Occurrence of NT was 23% for amB and 15% for l-amB pts. On average, any pt initially treated with amB or l-amB were ordered 1.3 or 0.7 laboratory tests, 0.1 or 0.1 imaging procedures, 5.5 or 0.3 medications, and 1.9 or 0.3 consultations due to drug-related AEs. Conclusions: Use of the Internet has to lead to efficiency in data collection. AmB and l-amB drug-related AEs occurred frequently and contributed to an increase in medical resources consumed. L-amB may reduce the incidence of certain AEs compared to amB and influence therapy costs