Severe phenotype with cis-acting heterozygous PMP22 mutations

We report on a 20-year-old male with severe Charcot-Marie-Tooth (CMT) disease and a de novo deletion (c.281delG, p.G94AfsX17) on the paternal PMP22 allele harboring c.353C>T (p.T118M). RNA-based sequence analysis confirmed the absence of nonsense-mediated decay and the presence of the mutant transcripts in Epstein-Barr virus-transformed lymphoblastoid cells of our patient. His clinical findings included early onset of polyneuropathy, loss of muscle mass with distal pareses, hammer toes, and progressive scoliosis. There was no neuropsychological alteration. Our results suggest that the deletion c.281delG alone is responsible for the severe CMT phenotype. To the best of our knowledge, this is the second report on a proven paternal origin of a de novo single-base mutation in the PMP22 gene.

DHEA induces 11 -HSD2 by acting on CCAAT/enhancer-binding proteins

11beta-Hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2 catalyze the interconversion of inactive and active glucocorticoids. Impaired regulation of these enzymes has been associated with obesity, diabetes, hypertension, and cardiovascular disease. Previous studies in animals and humans suggested that dehydroepiandrosterone (DHEA) has antiglucocorticoid effects, but the underlying mechanisms are unknown. In this study, DHEA treatment markedly increased mRNA expression and activity of 11beta-HSD2 in a rat cortical collecting duct cell line and in kidneys of C57BL/6J mice and Sprague-Dawley rats. DHEA-treated rats tended to have reduced urinary corticosterone to 11-dehydrocorticosterone ratios. It was found that CCAAT/enhancer-binding protein-alpha (C/EBP-alpha) and C/EBP-beta regulated HSD11B2 transcription and that DHEA likely modulated the transcription of 11beta-HSD2 in a phosphatidylinositol-3 kinase/Akt-dependent manner by increasing C/EBP-beta mRNA and protein expression. Moreover, it is shown that C/EBP-alpha and C/EBP-beta differentially regulate the expression of 11beta-HSD1 and 11beta-HSD2. In conclusion, DHEA induces a shift from 11beta-HSD1 to 11beta-HSD2 expression, increasing conversion from active to inactive glucocorticoids. This provides a possible explanation for the antiglucocorticoid effects of DHEA.

Mössbauer, X-ray and Magnetic Studies of Black Sand from the Italian Mediterranean Sea

The study of natural magnetic sands is instrumental to investigate the geological aspects of their formation and of the origin of their territory. In particular, Mössbauer spectroscopy provides unique information on their iron content and on the oxidation state of iron in their mineral composition. The Italian coast on the Mediterranean Sea near Rome is known for the presence of highly magnetic black sands of volcanic origin. A study of the room temperature Mössbauer spec- trum, powder X-ray diffraction, energy dispersive X-ray spectroscopy, and magnetic measurements of a sample of black magnetic sand collected on the seashore of the town of Ladispoli is performed. This study reveals magnetite as main constituent with iron in both tetrahedral and octahedral sites. Minor constituents are the iron minerals hematite and ilmenite, the iron containing minerals diopsite, gossular, and allanite, as well as ubiquitous sanidine, quartz, and calcite.

Implementing fisher Black's simple discounting rule

We propose a simple implementation of Black’s (1988) elegant rule for discounting uncertain future cash flows. Black’s rule avoids the thorny problem of estimating an appropriate risk-adjusted discount rate. Instead, the rule calls for discounting conditional mean cash flows at appropriate riskless interest rates. Our contribution in this article is to describe and illustrate a method of estimating the conditional mean cash flows called for in Black’s rule. The method is quite flexible with respect to the types of information available concerning the distributions of future cash flows. We argue that this approach to computing present values offers a theoretically sound and generally feasible addition to the toolbox of financial managers.

Electroelasticity of charged black branes

We present the first-order corrected dynamics of fluid branes carrying higher-form charge by obtaining the general form of their equations of motion to pole-dipole order in the absence of external forces. Assuming linear response theory, we characterize the corresponding effective theory of stationary bent charged (an)isotropic fluid branes in terms of two sets of response coefficients, the Young modulus and the piezoelectric moduli. We subsequently find large classes of examples in gravity of this effective theory, by constructing stationary strained charged black brane solutions to first order in a derivative expansion. Using solution generating techniques and bent neutral black branes as a seed solution, we obtain a class of charged black brane geometries carrying smeared Maxwell charge in Einstein-Maxwell-dilaton gravity. In the specific case of ten-dimensional space-time we furthermore use T-duality to generate bent black branes with higher-form charge, including smeared D-branes of type II string theory. By subsequently measuring the bending moment and the electric dipole moment which these geometries acquire due to the strain, we uncover that their form is captured by classical electroelasticity theory. In particular, we find that the Young modulus and the piezoelectric moduli of our strained charged black brane solutions are parameterized by a total of 4 response coefficients, both for the isotropic as well as anisotropic cases.

How fluids bend: the elastic expansion for higher-dimensional black holes

Hydrodynamics can be consistently formulated on surfaces of arbitrary co-dimension in a background space-time, providing the effective theory describing long-wavelength perturbations of black branes. When the co-dimension is non-zero, the system acquires fluid-elastic properties and constitutes what is called a fluid brane. Applying an effective action approach, the most general form of the free energy quadratic in the extrinsic curvature and extrinsic twist potential of stationary fluid brane configurations is constructed to second order in a derivative expansion. This construction generalizes the Helfrich-Canham bending energy for fluid membranes studied in theoretical biology to the case in which the fluid is rotating. It is found that stationary fluid brane configurations are characterized by a set of 3 elastic response coefficients, 3 hydrodynamic response coefficients and 1 spin response coefficient for co-dimension greater than one. Moreover, the elastic degrees of freedom present in the system are coupled to the hydrodynamic degrees of freedom. For co-dimension-1 surfaces we find a 8 independent parameter family of stationary fluid branes. It is further shown that elastic and spin corrections to (non)-extremal brane effective actions can be accounted for by a multipole expansion of the stress-energy tensor, therefore establishing a relation between the different formalisms of Carter, Capovilla-Guven and Vasilic-Vojinovic and between gravity and the effective description of stationary fluid branes. Finally, it is shown that the Young modulus found in the literature for black branes falls into the class predicted by this approach - a relation which is then used to make a proposal for the second order effective action of stationary blackfolds and to find the corrected horizon angular velocity of thin black rings.