lemmingA encodes the Apc11 subunit of the APC/C in Drosophila melanogaster that forms a ternary complex with the E2-C type ubiquitin conjugating enzyme, Vihar and Morula/Apc2

Background

The spindle assembly checkpoint (SAC) inhibits anaphase progression in the presence of insufficient kinetochore-microtubule attachments, but cells can eventually override mitotic arrest by a process known as mitotic slippage or adaptation. This is a problem for cancer chemotherapy using microtubule poisons.

Results

Here we describe mitotic slippage in yeast bub2?? mutant cells that are defective in the repression of precocious telophase onset (mitotic exit). Precocious activation of anaphase promoting complex/cyclosome (APC/C)-Cdh1 caused mitotic slippage in the presence of nocodazole, while the SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage, sister-chromatid separation and chromosome missegregation), in addition to telophase onset (mitotic exit), during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C-Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of insufficient kinetochore-microtubule attachments.

Conclusions

The sequential activation of APC/C-Cdc20 to APC/C-Cdh1 during mitosis is central to accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre-anaphase) causes mitotic slippage in SAC-activated cells. For the prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in humans.     

Clinical characteristics predicting internal neurofibromas in 357 children with neurofibromatosis-1: results from a cross-selectional study

ABSTRACT: OBJECTIVE: To identify clinical characteristics associated with internal neurofibromas in children with NF1, as a means of ensuring the early identification of patients at high risk for malignant peripheral nerve-sheath tumors developed from preexisting internal neurofibromas.Patients and methodsWe used data from two NF1 populations, in France and North America, respectively. The French database comprised 1083 patients meeting NIH diagnostic criteria for NF1 and the Neurofibromatosis Institute Database of North America comprised 703 patients. Patients younger than 17 years of age were eligible for our study if they had been evaluated for internal neurofibromas using computed tomography and/or magnetic resonance imaging. Clinical characteristics associated with internal neurofibromas by univariate analysis (P [LESS-THAN OR EQUAL TO] 0.15) were entered into a multiple logistic regression model after checking for potential interactions and confounding. Multiple imputation was used for missing values. RESULTS: Among the 746 children in the two databases, 357 (48%) met our inclusion criteria. Their mean age was 7.7 [PLUS-MINUS SIGN] 5.0 years and there were 192 (53.8%) males. Internal neurofibromas were present in 35 (9.8%) patients. Internal neurofibromas developed earlier in females than in males and their prevalence increased during adolescence. Factors independently associated with internal neurofibromas were age (OR = 1.16 [1.07-1.27]), xanthogranulomas (OR = 5.85 [2.18-15.89]) and presence of both subcutaneous and plexiform neurofibromas (OR = 6.80 [1.52-30.44]). CONCLUSIONS: Several easily recognizable clinical characteristics indicate a high risk of internal neurofibromas in children with NF1 and, therefore, a need for very close monitoring.     

Morphological phylogenetic analysis of the Africana genus (Nematoda: Heterakidae)

A morphological phylogenetic hypothesis of the relationships among the species of Africana is provided. The phylogenetic analysis suggests that Squamata or Amphibia were ancestral hosts for species of Africana, with dispersal events to Testudinidae; a second transfer to amphibians is also suggested. On the basis of biological data for these parasites and the paleogeographic reconstructions, a South American origin for Africana spp. is indicated, with subsequent dispersal events to Africa. It is further proposed that Chamaleonidae acquired species of Africana after their 'out-of-Madagascar' dispersal events to Africa.     

Interstitial fluid flow in the osteon with spatial gradients of mechanical properties: a finite element study

Bone remodelling is the process that maintains bone structure and strength through adaptation of bone tissue mechanical properties to applied loads. Bone can be modelled as a porous deformable material whose pores are filled with cells, organic material and interstitial fluid. Fluid flow is believed to play a role in the mechanotransduction of signals for bone remodelling. In this work, an osteon, the elementary unit of cortical bone, is idealized as a hollow cylinder made of a deformable porous matrix saturated with an interstitial fluid. We use Biot’s poroelasticity theory to model the mechanical behaviour of bone tissue taking into account transverse isotropic mechanical properties. A finite element poroelastic model is developed in the COMSOL Multiphysics software. Elasticity equations and Darcy’s law are implemented in this software; they are coupled through the introduction of an interaction term to obtain poroelasticity equations. Using numerical simulations, the investigation of the effect of spatial gradients of permeability or Poisson’s ratio is performed. Results are discussed for their implication on fluid flow in osteons: (i) a permeability gradient affects more the fluid pressure than the velocity profile; (ii) focusing on the fluid flow, the key element of loading is the strain rate; (iii) a Poisson’s ratio gradient affects both fluid pressure and fluid velocity. The influence of textural and mechanical properties of bone on mechanotransduction signals for bone remodelling is also discussed.     

Dependence of ultrasonic attenuation on bone mass and microstructure in bovine cortical bone

The development of the axial transmission technique now enables in vivo evaluation of cortical bone quality, which plays an important role in bone fragility. Cortical bone is a complex multiscale material, which may be made of different types of microstructure. The interaction between ultrasound and cortical bone remains unclear and most studies have been confined to wave speed analysis. The first aim of this study is to investigate the dependence of the frequency-dependent attenuation on the type of bone microstructure. The second goal is to determine whether broadband ultrasonic attenuation (BUA) is related to volumetric bone mineral density (vBMD) and mass density. Parallelepipedic samples of bovine cortical bone were cut from three specimens and tested in the axial, radial and tangential directions using an ultrasonic transmission device. BUA was evaluated over a 1-MHz wide bandwidth around 4MHz. In addition, the microstructure of each sample was determined using an optical microscope. BUA values measured in porotic microstructure are significantly higher than in Haversian microstructure. The lowest BUA values are obtained for plexiform microstructure. For all structures, BUA in the axial direction is significantly smaller than in the radial and tangential directions. Moreover, BUA is correlated with both vBMD and density (determination coefficient (R2) equal to 0.44 and 0.65, respectively, in the axial direction). BUA variations can be explained by scattering and viscoelastic mechanisms. This study suggests that BUA measurements have the potential to discriminate among different cortical bone microstructures in addition to providing material properties.     

Short-term responses of leaf growth rate to water deficit scale up to whole-plant and crop levels: an integrated modelling approach in maize

Physiological and genetic studies of leaf growth often focus on short-term responses, leaving a gap to whole-plant models that predict biomass accumulation, transpiration and yield at crop scale. To bridge this gap, we developed a model that combines an existing model of leaf 6 expansion in response to short-term environmental variations with a model coordinating the development of all leaves of a plant. The latter was based on: (1) rates of leaf initiation, appearance and end of elongation measured in field experiments; and (2) the hypothesis of an independence of the growth between leaves. The resulting whole-plant leaf model was integrated into the generic crop model APSIM which provided dynamic feedback of environmental conditions to the leaf model and allowed simulation of crop growth at canopy level. The model was tested in 12 field situations with contrasting temperature, evaporative demand and soil water status. In observed and simulated data, high evaporative demand reduced leaf area at the whole-plant level, and short water deficits affected only leaves developing during the stress, either visible or still hidden in the whorl. The model adequately simulated whole-plant profiles of leaf area with a single set of parameters that applied to the same hybrid in all experiments. It was also suitable to predict biomass accumulation and yield of a similar hybrid grown in different conditions. This model extends to field conditions existing knowledge of the environmental controls of leaf elongation, and can be used to simulate how their genetic controls flow through to yield.     

A novel moderately halophilic bacterium for decolorizing azo dye under high salt condition

Halomonas sp strain GTW was newly isolated from coastal sediments contaminated by chemical wastewater and was identified to be a member of the genus Halomonas by 16S rDNA sequence analysis and physical and biochemical tests. The optimal decolorization conditions were as follows: temperature 30°C, pH 6.5.0–8.5, NaCl 10–20% (w/v) and the optimal carbon source was yeast exact. The results of experiments demonstrated that the bacteria could decolorize different azo dyes under high salt concentration conditions, and the decolorization rate of five tested azo dyes could be above 90% in 24 h. The exploitation of the salt-tolerant bacteria in the bio-treatment system would be a great improvement of conventional biological treatment systems and the bio-treatment concept.     

Fasciola gigantica cathepsin L proteinase-based synthetic peptide for immunodiagnosis and prevention of sheep fasciolosis

Sheep fasciolosis is a devastating burden for the livestock industry. We herein report on immunodiagnosis of fasciolosis, and significant protection of sheep against challenge infection with Fasciola gigantica following immunization with a peptide based on the H-Asp(110)-Lys-Ile-Asp-Trp-Arg-Glu-Ser-Gly-Tyr-Val-Thr-Glu-Val(123)-OH (Fas14p) sequence of F. gigantica cathepsin L-cysteine proteinase. This sequence was synthesized in three different forms: as N(alpha) acetylated (Ac-Asp(110)-Lys-Ile-Asp-Trp-Arg-Glu-Ser-Gly-Tyr-Val-Thr-Glu-Val(123)-OH, FasAc14p), bearing at the amino-terminus an N(alpha) acetylated cystein (Ac-Cys-Asp(110)-Lys-Ile-Asp-Trp-Arg-Glu-Ser-Gly-Tyr-Val-Thr-Glu-Val(123)-OH, FasAcCys14p), and conjugated to sequential oligopeptide carrier Ac-[Lys-Aib-Gly](4)-OH (Ac-SOC(4)) through an amide bond formed between Val(123) carboxylic group of the epitope and the lysine N(epsilon) groups of the carrier (Ac-[Lys(Fas14p)-Aib-Gly](4)-OH). Ac-[Lys(Fas14p)-Aib-Gly](4)-OH failed to readily discriminate between na?ve and infected sheep. In contrast, the free peptides reproducibly differentiated between parasite-free sheep, sheep infected with parasites other than Fasciola, and experimentally Fasciola-infected sheep. The data together indicated that the peptides might be of considerable use for discriminating between early and late, and low and high burden, sheep infection with F. gigantica. FasAc14p was chosen to determine whether a peptide based on a critical enzymatic site of cathepsin L proteinase may induce protection against challenge infection. Sheep immunization with FasAc14p peptide induced significant expression of interleukin-4 mRNA, and humoral antibodies that bound to molecule(s) on the intact surface membrane of newly excysted juvenile worms, and mediated their attrition. The immune responses were associated with significant (P < 0.02) decrease of 23.1% in worm recovery, but with no decrease in the size or maturation of worms recovered.     

Impact of Postovulatory Food Deprivation on the Ova Transport, Hormonal Profiles and Metabolic Changes in Sows

The effect of food deprivation on ova transport, hormonal profiles and metabolic changes was studied in 20 crossbred multiparous sows during their second oestrus after weaning. To determine the time of ovulation, transrectal ultrasonographic examination was performed. The sows were divided into 2 groups, one control group (C-group), which was fed according to Swedish standards, and one experimental group (E-group). The E-group sows were deprived of food from the first morning meal after ovulation until slaughter. Blood samples were collected every second hour from about 12 h before expected ovulation in the second oestrus after weaning until slaughter and were analysed for progesterone, prostaglandin F_2α-metabolite, insulin, glucose, free fatty acids and triglycerides. All sows were slaughtered approximately 48 h after ovulation and the genital tract was recovered. The isthmic part of the oviduct was divided into 3 equally long segments and flushed separately with phosphate buffered saline (PBS). Uterine horns were also flushed with PBS. A significantly greater number of ova were found in the first and second part of the isthmus in the E-group (p = 0.05) while in the C-group most of the ova were found in the third part of the isthmus or the uterus (p = 0.01). The level of prostaglandin F_2α-metabolite was significantly higher in the E-group compared with the C-group. The concentration of progesterone increased in both groups after ovulation but there were no significant differences between the groups. The other blood parameters showed that the food-deprived sows were in a catabolic state. The 48 h period of fasting results, directly or indirectly in an delayed ova transport, which may be due to a delayed relaxation in the smooth circular muscle layer of the isthmus.     

Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value

This review focuses on the mechanisms of stress response in the synovial tissue of rheumatoid arthritis. The major stress factors, such as heat stress, shear stress, proinflammatory cytokines and oxidative stress, are discussed and reviewed, focusing on their potential to induce a stress response in the synovial tissue. Several pathways of stress signalling molecules are found to be activated in the synovial membrane of rheumatoid arthritis; of these the most important examples are heat shock proteins, mitogen-activated protein kinases, stress-activated protein kinases and molecules involved in the oxidative stress pathways. The expression of these pathways in vitro and in vivo as well as the consequences of stress signalling in the rheumatoid synovium are discussed. Stress signalling is part of a cellular response to potentially harmful stimuli and thus is essentially involved in the process of synovitis. Stress signalling pathways are therefore new and promising targets of future anti-rheumatic therapies.