The multiplicity of alternative splicing decisions in Caenorhabditis elegans is linked to specific intronic regulatory motifs and minisatellites

Background: alternative splicing diversifies the pool of messenger RNA molecules encoded by individual genes. This diversity is particularly high when multiple splicing decisions cause a combinatorial arrangement of several alternate exons. We know very little on how the multiple decisions occurring during the maturation of single transcripts are coordinated and whether specific sequence elements might be involved.Results: here, the Caenorhabditis elegans genome was surveyed in order to identify sequence elements that might play a specific role in the regulation of multiple splicing decisions. The introns flanking alternate exons in transcripts whose maturation involves multiple alternative splicing decisions were compared to those whose maturation involves a single decision. Fifty-eight penta-, hexa-, and hepta-meric elements, clustered in 17 groups, were significantly over-represented in genes subject to multiple alternative splicing decisions. Most of these motifs relate to known splicing regulatory elements and appear to be well conserved in the related species Caenorhabditis briggsae. The usage of specific motifs is not linked to the gene product function, but rather depends on the gene structure, since it is influenced by the distance separating the multiple splicing decision sites. Two of these motifs are part of the CeRep25B minisatellite, which is also over-represented at the vicinity of alternative splicing regions. Most of the remaining motifs are not part of repeated sequence elements, but tend to occur in specific heterologous pairs in genes subject to multiple alternative splicing decisions.Conclusions: the existence of specific intronic sequence elements linked to multiple alternative splicing decisions is intriguing and suggests that these elements might have some specialized regulatory role during splicing

Molecules empowering animals to sense and respond to temperature in changing environments

Adapting behavior to thermal cues is essential for animal growth and survival. Indeed, each and every biological and biochemical process is profoundly affected by temperature and its extremes can cause irreversible damage. Hence, animals have developed thermotransduction mechanisms to detect and encode thermal information in the nervous system and acclimation mechanisms to finely tune their response over different timescales. While temperature-gated TRP channels are the best described class of temperature sensors, recent studies highlight many new candidates, including ionotropic and metabotropic receptors. Here, we review recent findings in vertebrate and invertebrate models, which highlight and substantiate the role of new candidate molecular thermometers and reveal intracellular signaling mechanisms implicated in thermal acclimation at the behavioral and cellular levels

Pathophysiology of Asthma and Chronic Obstuctive Pulmonary Disease (COPD)

“Asthma is a disease characterized by an increased responsiveness of the trachea and bronchi to various stimuli and manifested by a widespread narrowing of the airways that changes in severity either spontaneously or in response to therapy.” The airway narrowing is the end result of some combination of bronchial muscle contraction, tissue inflammation, mucosal edema, and luminal occlusion by cellular debris and thickened secretions. During the last decade, basic and applied research has shed light on the physiology of the above changes and has led to breakthroughs in therapy and the more rational use of older and newer therapeutic agents, both separately and together

Biaxial fragmentation of thin silicon oxide coatings on poly(ethylene terephthalate)

Crack patterns of 53 nm and 103 nm thick silicon oxide coatings on poly(ethylene terephthalate) films are analyzed under equibiaxial stress loading, by means of a bulging cell mounted under an optical microscope with stepwise pressurization of film specimens. The biaxial stress and strain are modeled from classical elastic membrane equations, and an excellent agreement is obtained with a finite element method. In the large pressure range, the derivation of the biaxial strain from force equilibrium considerations are found to reproduce accurately the measured data up to 25% strain. The examination of the fragmentation process of the coating under increasing pressure levels reveals that the crack onset strain of the oxide coating is similar to that measured under uniaxial tension. The fragmentation of the coating under biaxial tension is also characterized by complex dynamic phenomena which image the peculiarities of the stress field, resulting in considerable broadening of the fragment size distribution. The evolution of the average fragment area as a function of biaxial stress in the early stages of the fragmentation process is analyzed using Weibull statistics to describe the coating strengt

Clinical experience with Timentin in severe hospital infections

Sixty-four severe infections in hospitalized patients were treated with intravenous Timentin. Most patients (mean age: 50-5 years, range 18-85) had serious underlying conditions such as agranulocytosis, heart failure, cancer, diabetes mellitus, chronic alcoholism or other functional or anatomical abnormalities. Forty-three episodes were bacteriologically proved, and bacteraemia was diagnosed in 18. The sites of infection were: lower respiratory tract (10), upper respiratory tract (10), soft tissues(9), urinary tract (7), bones (6), peritoneal cavity (3), meninges (1) and pelvis (1). Inaddition, 13 episodes of fever and four of septicaemia in patients with agranulocytosis were treated with Timentin plus amilcacin. Overall, 59% of the episodes were cured, 14% improved and 17% failed to respond. In 9% of cases the efficacy of the Timentin was unassessable mainly because of concurrent administration of other antimicrobials. Failure appeared to be more frequent in soft tissue and intra-abdominal infections, in patients infected with bacteria susceptibleto Timentin but resistant to ticarcillin and in patients superinfected with Timentin-resistant strains. Major side effects were haemorrhagic diathesis with platelet dysfunction (1), severe water sodium overload (1), and possibly pancreatitis (1).Other side effects were mild: catheter-related phlebitis, and abnormal but clinically insignificant laboratory test results. Timentin appears to be an effective and safebroad-spectrum combination which compares favourably with third-generation cephalosporins in the treatment of severe hospital infections. More experience is needed to decide whether the some what lower response rate in patients infected with ticarcillin-resistant strains is significan

Incidence of gallbladder lithiasis after ceftriaxone treatment

Ceftriaxone has potent activity against a broad range of Gram-positive and Gram-negative bacteria. While it is eliminated mainly by the kidney, 10-20% of the drug is eliminated in the bile and ceftriaxone salt precipitates have been described in the gallbladder of animals dosed with ceftriaxone. The purpose of the present study was to investigate the incidence of biliary lithiasis 6 and 12 months after treatment with ceftriaxone and to compare it with that in patients treated with amoxycillin/clavulanate. Biliary ultrasonography was performed at the start of treatment, at 6 months and at 12 months after the beginning of the study. One hundred patients were randomized and 74 were evaluable: 34 were given amoxycillin/clavulanate, 40 ceftriaxone. Gallbladder lithiasis developed in one patient 12 months after the amoxycillin/clavulanate treatment and in none in the ceftriaxone treatment arm. Biliary precipitate during ceftriaxone treatment was not looked for because this phenomenon was not known at the beginning of the study, but gallbladder precipitation that was seen in two patients given ceftriaxone during and at the end of treatment, respectively, resolved spontaneously. In conclusion, ceftriaxone treatment does not appear to lead to gallstone formation more often than an antibiotic that is not eliminated through the bil

Environmental stress linked to consumption of maternally derived carotenoids in brown trout embryos (Salmo trutta).

The yellow, orange, or red colors of salmonid eggs are due to maternally derived carotenoids whose functions are not sufficiently understood yet. Here, we studied the significance of naturally acquired carotenoids as maternal environmental effects during embryo development in brown trout (Salmo trutta). We collected eggs from wild females, quantified their egg carotenoid content, fertilized them in vitro in full-factorial breeding blocks to separate maternal from paternal effects, and raised 3,278 embryos singly at various stress conditions until hatching. We found significant sire effects that revealed additive genetic variance for embryo survival and hatching time. Dam effects were 5.4 times larger than these sire effects, indicating that maternal environmental effects play an important role in determining embryo stress tolerance. Of the eight pigment molecules that we targeted, only astaxanthin, zeaxanthin (that both affected egg redness), and lutein were detected above our confidence thresholds. No strong link could be observed between carotenoid content in unfertilized eggs and embryo mortality or hatching timing. However, the consumption of carotenoids during our stress treatment was negatively correlated to embryo survival among sib groups and explained about 14% of the maternal environmental variance. We conclude that maternally derived carotenoids play a role in the ability of embryos to cope with environmental stress, but that the initial susceptibility to the organic pollution was mainly determined by other factors