Two genes are responsible for Griscelli syndrome at the same 15q21 locus

Griscelli syndrome is a rare autosomal recessive disease characterized by pigment dilution, variable cellular immunodeficiency, and an acute phase of uncontrolled T lymphocyte and macrophage activation. We previously mapped the disease locus to 15q21 and showed that a MyoVa gene (HGMW-approved symbol MYO5A) defect leads to Griscelli syndrome. We report a second MyoVa mutation in a new patient, confirming this first finding. However, in four other Griscelli syndrome patients analyzed, the MYOVA protein is expressed, and no mutation can be detected in the MyoVa gene coding sequence, even in the alternatively spliced region for which exon-intron boundaries were characterized. Linkage analysis performed in 15 Griscelli families thus far studied confirms the first localization. However, fine haplotype analysis in three families strongly suggests the existence of a second gene at the same locus for Griscelli syndrome less than 7.3 cM distant from the MyoVa gene.     

Antirotavirus Immunoglobulin A Neutralizes Virus In Vitro after Transcytosis through Epithelial Cells and Protects Infant Mice from Diarrhea

Rotaviruses are the major cause of severe diarrhea in infants and young children worldwide. Due to their restricted site of replication, i.e., mature enterocytes, local intestinal antibodies have been proposed to play a major role in protective immunity. Whether secretory immunoglobulin A (IgA) antibodies alone can provide protection against rotavirus diarrhea has not been fully established. To address this question, a library of IgA monoclonal antibodies (MAbs) previously developed against different proteins of rhesus rotavirus was used. A murine hybridoma “backpack tumor” model was established to examine if a single MAb secreted onto mucosal surfaces via the normal epithelial transport pathway was capable of protecting mice against diarrhea upon oral challenge with rotavirus. Of several IgA and IgG MAbs directed against VP8 and VP6 of rotavirus, only IgA VP8 MAbs (four of four) were found to protect newborn mice from diarrhea. An IgG MAb recognizing the same epitope as one of the IgA MAbs tested failed to protect mice from diarrhea. We also investigated if antibodies could be transcytosed in a biologically active form from the basolateral domain to the apical domain through filter-grown Madin-Darby canine kidney (MDCK) cells expressing the polymeric immunoglobulin receptor. Only IgA antibodies with VP8 specificity (four of four) neutralized apically administered virus. The results support the hypothesis that secretory IgA antibodies play a major role in preventing rotavirus diarrhea. Furthermore, the results show that the in vivo and in vitro methods described are useful tools for exploring the mechanisms of viral mucosal immunity.     

Termites Facilitate Methane Oxidation and Shape the Methanotrophic Community

Termite-derived methane contributes 3 to 4% to the total methane budget globally. Termites are not known to harbor methane-oxidizing microorganisms (methanotrophs). However, a considerable fraction of the methane produced can be consumed by methanotrophs that inhabit the mound material, yet the methanotroph ecology in these environments is virtually unknown. The potential for methane oxidation was determined using slurry incubations under conditions with high (12%) and in situ (∼0.004%) methane concentrations through a vertical profile of a termite (Macrotermes falciger) mound and a reference soil. Interestingly, the mound material showed higher methanotrophic activity. The methanotroph community structure was determined by means of a pmoA-based diagnostic microarray. Although the methanotrophs in the mound were derived from populations in the reference soil, it appears that termite activity selected for a distinct community. Applying an indicator species analysis revealed that putative atmospheric methane oxidizers (high-indicator-value probes specific for the JR3 cluster) were indicative of the active nest area, whereas methanotrophs belonging to both type I and type II were indicative of the reference soil. We conclude that termites modify their environment, resulting in higher methane oxidation and selecting and/or enriching for a distinct methanotroph population.     

Influence of plaque calcifications on coronary stent fracture: A numerical fatigue life analysis including cardiac wall movement

Coronary stent fracture is still an unresolved issue in the field of minimally invasive cardiovascular interventions due to its high rate of incidence and uncertain clinical consequences. Recent studies, based on clinical data, proved that there are several factors which can be identified as independently responsible of coronary stent fracture. Among these, calcifications, which increase the local stiffness and heterogeneity of atherosclerotic plaques, seem to play a major role. From a mechanical point of view, stent fracture in coronary arteries is triggered by the cyclic loading of pulsatile blood pressure combined with the movement of cardiac wall.     

Multiscale modelling in biofluidynamics: application to reconstructive paediatric cardiac surgery

Multiscale computing is a challenging area even in biomechanics. Application of such a methodology to quantitatively compare postoperative hemodynamics in congenital heart diseases is very promising. In the treatment of hypoplastic left heart syndrome, which is a congenital heart disease where the left ventricle is missing or very small, the necessity to feed the pulmonary and systemic circulations is obtained with an interposition shunt. Two main options are available and differ from the sites of anastomoses: (i) the systemic-to-pulmonary conduit (Blalock-Taussig shunt known as the Norwood Operation (NO)) connecting the innominate artery (NO-BT) or the aorta (NO-CS) to the right pulmonary artery and (ii) the right ventricle to pulmonary artery shunt (known as Sano operation (SO)). The proposition that the SO is superior to the NO remains controversial. 3-D computer models of the NO (NO-BT and NO-CS) and SO were developed and investigated using the finite volume method. Conduits of 3, 3.5 and 4 mm were used in the NO models, whereas conduits of 4, 5 and 6 mm were used in the SO model. The hydraulic nets (lumped resistances, compliances, inertances and elastances) which represent the systemic, coronary and pulmonary circulations and the heart were identical in the two models. A multiscale approach was adopted to couple the 3-D models with the circulation net. Computer simulation results were compared with post-operative catheterization data. Results showed that (i) there is a good correlation between predicted and observed data: higher aortic diastolic pressure, decreased pulmonary arterial pressure, lower pulmonary-to-systemic flow ratio and higher coronary perfusion pressure in SO; (ii) there is a minimal regurgitant flow in the SO conduit. The close correlation between predicted and observed clinical data supports the use of mathematical modelling, with a mandatory multiscale approach, in the design and assessment of surgical procedures.     

Zooplankton Spatial and Temporal Distribution in a Tropical Oceanic Area off West Africa

Tropical instability vortices are believed to modify the trophic food web by affecting plankton production. Such instabilities have been evidenced in a tuna fishing area of the Atlantic (10°–20° W and 2°–5° N). However, the origin of the tuna abundance remains uncertain as no data on zooplankton communities on which tuna preys are supposed to fed upon are available. This study was focused on short term spatial and diel variations of mesozooplankton communities sampled at 2° N during and after the passage of an instability wave evidenced from satellite imagery, at 4° N and at 0°, i.e. in the Equatorial divergence. Samples were collected with an opening–closing multisampler and with a WP2 net (200 μm). Copepods prevailed (86–92% of the total zooplankton) with Clausocalanidae, Oncaeidae, Corycaeidae, Calanidae, Eucalanidae as dominant families. At 0° and at 2° N during the wave, large-sized organisms constituted over 50% of total dry weight (DW). These percentages decreased after the wave and at 4° N. Zooplankton DW and densities were highest at 0° and lowest at 4° N. At 2° N after the wave, we observed a strong increase in the abundance of zooplankton which surpassed that at 0°. This increase mainly resulted from an increase in small copepods and copepodites. Our results suggest that the high production linked to the upwelling of nutrients caused by the geostrophic divergence is partly advected northward by the instability wave. The advection did not reach 4° N which displayed the characteristics of a typical tropical structure.     

L'azione fitotossica dell'Irpexil (acetidrossamoilacetato di metile) sulle piante superiori. Nota prima: Azione brachizzante ed inibizione mitotica

Abstract

The phytotoxic action of Irpexil (Methylacethydroxamoilacetate) on higher plants. 1: action on growth and mitotic inhibition.—The fungal secondary metabolite Irpexil (Methylacethydroxamoilacetate) shows a rather marked inhibiting effect on the growth of mono-and dycotiledons seedlings. Both length and fresh weight of the axial parts are affected, particularly in wheat and pea seedlings. The inhibiting effect is at least partially due to the antimitotic activity of this compound; Irpexil does not seem to interfere at any stage of the mitotic cycle, at least at moderate concentrations (up to 70 ppm).     

Contrasting Effects of GA3 Treatments on Tomato Plants Exposed to Increasing Salinity

The role of plant hormones under saline stress is critical in modulating physiological responses that will eventually lead to adaptation to an unfavorable environment. Nevertheless, the functional level of plant hormones, and their relative tissue concentration, may have a different impact on plant growth and stress tolerance at increasing salinity of the root environment. Vigorous plant growth may counteract the negative effects of salinization. In contrast, low gibberellin (GA) levels have been associated with reduced growth in response to salinity. Based on these facts and considering that the physiological basis of the cause-effect relationship between functional growth control and stress adaptation/survival is still a matter of debate, we hypothesized that exogenous applications of the plant hormone GA₃ may compensate for the salt-induced growth deficiency and consequently facilitate tomato plant adaptation to a saline environment. GA₃ application (0 or 100 mg GA₃ l⁻¹) was compared under four salinity levels, obtained by adding equal increments of NaCl:CaCl₂ (2:1 molar basis) (EC = 2.5, 6.8, 11.7, 16.7 dS m⁻¹) to the nutrient solution. GA₃ treatment reduced stomatal resistance and enhanced plant water use at low salinity. These responses were associated with an increased number of fruit per plant at harvest. However, moderate and high salinity nullified these differences. The fruit carotenoid level was generally lower in GA₃-treated plants, indicating either an inhibitory effect of GA₃ treatment on carotenoid biosynthesis or a reduced perception of the stress environment by GA₃-treated tomato plants.