Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A.

Mutations in the CACNA1A gene, encoding the α1 subunit of the voltage-gated calcium channel CaV2.1 (P/Q-type), have been associated with three neurological phenotypes: familial and sporadic hemiplegic migraine type 1 (FHM1, SHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). We report a child with congenital ataxia, abnormal eye movements and developmental delay who presented severe attacks of hemiplegic migraine triggered by minor head traumas and associated with hemispheric swelling and seizures. Progressive cerebellar atrophy was also observed. Remission of the attacks was obtained with acetazolamide. A de novo 3bp deletion was found in heterozygosity causing loss of a phenylalanine residue at position 1502, in one of the critical transmembrane domains of the protein contributing to the inner part of the pore. We characterized the electrophysiology of this mutant in a Xenopus oocyte in vitro system and showed that it causes gain of function of the channel. The mutant CaV2.1 activates at lower voltage threshold than the wild type. These findings provide further evidence of this molecular mechanism as causative of FHM1 and expand the phenotypic spectrum of CACNA1A mutations with a child exhibiting severe SHM1 and non-episodic ataxia of congenital onset.

Chemical etching without acids: from early etching solutions to today's corrosive salts

Conferència impartida a l'Accademia di Belle Arti di Bologna en motiu de de les jornades "Atossico incisione e la sua introduzione in istruzione superiore", del 25 al 27 de gener del 2011 a Bologna

Opposite impacts of dietary versus supplemental calcium on cardiovascular health.

Commentary on: Li K, Kaaks R, Linseisen J, et al . Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European prospective investigation into cancer and nutrition study (EPIC-Heidelberg). Heart 2012; 98 :920 - 5

Estimation of soil nitrate in the spring as a basis for adjustment of nitrogen fertiliser rates

Selostus: Maassa olevan nitraattitypen arviointi simulointimallin avulla

The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals.

Collective evidence indicates that motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is non-cell-autonomous and requires the interaction with the neighboring astrocytes. Recently, we reported that a subpopulation of spinal cord astrocytes degenerates in the microenvironment of motor neurons in the hSOD1(G93A) mouse model of ALS. Mechanistic studies in vitro identified a role for the excitatory amino acid glutamate in the gliodegenerative process via the activation of its inositol 1,4,5-triphosphate (IP(3))-generating metabotropic receptor 5 (mGluR5). Since non-physiological formation of IP(3) can prompt IP(3) receptor (IP(3)R)-mediated Ca(2+) release from the intracellular stores and trigger various forms of cell death, here we investigated the intracellular Ca(2+) signaling that occurs downstream of mGluR5 in hSOD1(G93A)-expressing astrocytes. Contrary to wild-type cells, stimulation of mGluR5 causes aberrant and persistent elevations of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in the absence of spontaneous oscillations. The interaction of IP(3)Rs with the anti-apoptotic protein Bcl-X(L) was previously described to prevent cell death by modulating intracellular Ca(2+) signals. In mutant SOD1-expressing astrocytes, we found that the sole BH4 domain of Bcl-X(L), fused to the protein transduction domain of the HIV-1 TAT protein (TAT-BH4), is sufficient to restore sustained Ca(2+) oscillations and cell death resistance. Furthermore, chronic treatment of hSOD1(G93A) mice with the TAT-BH4 peptide reduces focal degeneration of astrocytes, slightly delays the onset of the disease and improves both motor performance and animal lifespan. Our results point at TAT-BH4 as a novel glioprotective agent with a therapeutic potential for ALS.

Changes in Aortic Pulse Wave Velocity in Hypertensive Postmenopausal Women: Comparison Between a Calcium Channel Blocker vs Angiotensin Receptor Blocker Regimen.

J Clin Hypertens (Greenwich). 2012;14:773-778. ©2012 Wiley Periodicals, Inc. Postmenopausal women are at greater risk for hypertension-related cardiovascular disease. Antihypertensive therapy may help alleviate arterial stiffness that represents a potential modifiable risk factor of hypertension. This randomized controlled study investigated the difference between an angiotensin receptor blocker and a calcium channel blocker in reducing arterial stiffness. Overall, 125 postmenopausal hypertensive women (age, 61.4±6 years; systolic blood pressure/diastolic blood pressure [SBP/DBP], 158±11/92±9 mm Hg) were randomized to valsartan 320 mg±hydrochlorothiazide (HCTZ) (n=63) or amlodipine 10 mg±HCTZ (n=62). The primary outcome was carotid-to-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Both treatments lowered peripheral blood pressure (BP) (-22.9/-10.9 mm Hg for valsartan and -25.2/-11.7 mm Hg for amlodipine, P=not significant) and central BP (-15.7/-7.6 mm Hg for valsartan and -19.2/-10.3 mm Hg for amlodipine, P<.05 for central DBP). Both treatments similarly reduced the carotid-femoral PWV (-1.9 vs -1.7 m/s; P=not significant). Amlodipine was associated with a higher incidence of peripheral edema compared with the valsartan group (77% vs 14%, P<.001). BP lowering in postmenopausal women led to a reduction in arterial stiffness as assessed by PWV measurement. Both regimens reduced PWV to a similar degree after 38 weeks of treatment despite differences in central BP lowering, suggesting that the effect of valsartan on PWV is mediated through nonhemodynamic effects.

Low-Cost Rural Surface Alternatives: Literature Review and Recommendations, TR-632, 2013

Freezing and thawing action induces damage to unbound gravel roads in Iowa resulting in maintenance costs for secondary road departments. Some approaches currently used by County Engineers to deal with this problem include temporarily spreading rock on the affected areas, lowering or improving drainage ditches, tiling, bridging the area with stone and geosynthetic covered by a top course of aggregate or gravel, coring boreholes and filling them with calcium chloride to melt lenses and provide drainage, and re-grading the crown to a slope of 4% to 6% to maximize spring drainage. However, most of these maintenance solutions are aimed at dealing with conditions after they occur. This study was tasked with identifying alternative approaches in the literature to mitigate the problem. An annotated bibliographic record of literature on the topic of frost-heave and thaw-weakening of gravel roads was generated and organized by topic, and all documents were assessed in terms of a suitable rating for mitigating the problem in Iowa. Over 300 technical articles were collected and selected down to about 150 relevant articles for a full assessment. The documents collected have been organized in an electronic database, which can be used as a tool by practitioners to search for information regarding the various repair and mitigation solutions, measurement technologies, and experiences that have been documented by selected domestic and international researchers and practitioners. Out of the 150+ articles, 71 articles were ranked as highly applicable to conditions in Iowa. The primary mitigation methods identified in this study included chemical and mechanical stabilization; scarification, blending, and recompaction; removal and replacement; separation, and reinforcement; geogrids and cellular confinement; drainage control and capillary barriers, and use of alternative materials. It is recommended that demonstration research projects be established to examine a range of construction methods and materials for treating granular surfaced roadways to mitigate frost-heave and thaw-weakening problems. Preliminary frost-susceptibility test results from ASTM D5916 are included for a range of Iowa materials.

Shear thinning and thixotropy of HMHEC and HEC water solutions

Steady state viscosity and thixotropy of hydrophobically modified hydroxyethyl cellulose HMHEC and nonassociative cellulose water solutions are studied. Although all the samples are shear thinning, only the HMHEC is thixotropic, since the migration of hydrophobes to micelles is controlled by diffusion. The Cross model fits steady state curves. The Mewis model, a phenomenological model that proposes that the rate of change of viscosity when the shear rate is suddenly changed is related to the difference between the steady state and current values of viscosity raised to an exponent, fits structure construction experiments when the exponent, n, is estimated to be around 2. The Newtonian assumption used by Mewis cannot be used here, however. This seems to be related to the fact that the thickening is due to bridged micelle formation, which is a slow process, and also to topological constraints and entanglements, which are rapid processes. The kinetic parameter was redefined to kn in order to make it independent of initial conditions. So, kn depends only on how the shear affects the structure. kn reaches a plateau at shear rates too low to produce structure destruction and decreases at higher shear rates.

Aggregation of liposomes induced by calcium: A structural and kinetic study

In this work, the calcium-induced aggregation of phosphatidylserine liposomes is probed by means of the analysis of the kinetics of such process as well as the aggregate morphology. This novel characterization of liposome aggregation involves the use of static and dynamic light-scattering techniques to obtain kinetic exponents and fractal dimensions. For salt concentrations larger than 5 mM, a diffusion-limited aggregation regime is observed and the Brownian kernel properly describes the time evolution of the diffusion coefficient. For slow kinetics, a slightly modified multiple contact kernel is required. In any case, a time evolution model based on the numerical resolution of Smoluchowski's equation is proposed in order to establish a theoretical description for the aggregating system. Such a model provides an alternative procedure to determine the dimerization constant, which might supply valuable information about interaction mechanisms between phospholipid vesicles.

Expansive Mineral Growth and Concrete Deterioration, HR-384, 1997

A significant question is: What role does newly-formed expansive mineral growth play in the premature deterioration of concrete? These minerals (ettringite and brucite) are formed in cement paste as a result of chemical reactions involving cement and coarse/fine aggregate. Petrographic observations and SEM/EDAX analysis were conducted in order to determine chemical and mineralogical changes in the aggregate and cement paste of samples taken from Iowa concrete highways that showed premature deterioration. Mechanisms involved in deterioration were investigated. A second objective was to investigate whether deicer solutions exacerbate the formation of expansive minerals and concrete deterioration. Magnesium in deicer solutions causes the most severe paste deterioration by forming non-cementitious magnesium silicate hydrate and brucite. Chloride in deicer solutions promotes decalcification of paste and alters ettringite to chloroaluminate. Calcium magnesium acetate (CMA) and magnesium acetate (Mg-acetate) produce the most deleterious effects on concrete, with calcium acetate (Ca-acetate) being much less severe.