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.     

Coordinated expression of functionally diverse fructosyltransferase genes is associated with fructan accumulation in response to low temperature in perennial ryegrass

* Fructan is the major nonstructural carbohydrate reserve in temperate grasses. To understand regulatory mechanisms in fructan synthesis and adaptation to cold environments, the isolation, functional characterization and genetic mapping of fructosyltransferase (FT) genes in perennial ryegrass (Lolium perenne) are described. * Six cDNAs (prft1-prft6) encoding FTs were isolated from cold-treated ryegrass plants, and three were positioned on a perennial ryegrass linkage map. Recombinant proteins were produced in Pichia pastoris and enzymatic activity was characterized. Changes in carbohydrate levels and mRNA levels of FT genes during cold treatment were also analysed. * One gene encodes sucrose-sucrose 1-fructosyltransferase (1-SST), and two gene encode fructan-fructan 6G-fructosyltransferase (6G-FFT). Protein sequences for the other genes (prfts 1, 2 and 6) were similar to sucrose-fructan 6-fructosyltransferase (6-SFT). The 1-SST and prft1 genes were colocalized with an invertase gene on the ryegrass linkage map. The mRNA levels of prft1 and prft2 increased gradually during cold treatment, while those of the 1-SST and 6G-FFT genes first increased, but then decreased before increasing again during a longer period of cold treatment. * Thus at least two different patterns of gene expression have developed during the evolution of functionally diverse FT genes, which are associated in a coordinated way with fructan synthesis in a cold environment.     

Wear paths produced by individual hip-replacement patients--a large-scale, long-term follow-up study

Wear particle accumulation is one of the main contributors to osteolysis and implant failure in hip replacements. Altered kinematics produce significant differences in wear rates of hip replacements in simulator studies due to varying degrees of multidirectional motion. Gait analysis data from 153 hip-replacement patients 10-years post-operation were used to model two- and three-dimensional wear paths for each patient. Wear paths were quantified in two dimensions using aspect ratios and in three dimensions using the surface areas of the wear paths, with wear-path surface area correlating poorly with aspect ratio. The average aspect ratio of the patients wear paths was 3.97 (standard deviation=1.38), ranging from 2.13 to 10.86. Sixty percent of patients displayed aspect ratios between 2.50 and 3.99. However, 13% of patients displayed wear paths with aspect ratios >5.5, which indicates reduced multidirectional motion. The majority of total hip replacement (THR) patients display gait kinematics which produce multidirectional wear paths, but a significant minority display more linear paths.     

A highly modified stygobiont diving beetle of the genus Copelatus (Coleoptera,Dytiscidae): taxonomy and cladistic analysis based on mitochondrial DNA sequences

Abstract. We report the discovery of a new species of Copelatus that is morphologically highly modified for life in groundwater. Copelatus abditus sp.n. was collected from a 4 m deep bore in central Australia. It was placed in Copelatinae based on morphological evidence. This is the first known stygobiont diving beetle that does not belong to the subfamily Hydroporinae. Sequences from the mitochondrial DNA cytochrome oxidase 1, 16S rRNA, tRNAL and NADH dehydrogenase subunit 1 genes suggest that the species belongs to the subgenus Papuadytes, the morphological apomorphies of which are reduced in the new groundwater species. Copelatus (Papuadytes) abditus very much resembles other world stygobiont dytiscids, which all belong to the subfamily Hydroporinae. We suggest that this striking convergence is due to similar selective pressures imposed on all groundwater beetles. We suggest a scenario in which species from temporary habitats evade drought by entering the hyporheic zone, and may be driven to a subterranean existence by desertification of their ancestral habitats, as can be observed in Australia.     

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.     

Molecular studies of hemichordate development: a key to understanding the evolution of bilateral animals and chordates

SUMMARY Using the Hawaiian acorn worm, Ptychodera flava, we began molecular studies on the development of hemichordates, a phylum previously unstudied at this level. Here we review results garnered from the examination of a few specific genes selected to help understand the evolution of vertebrate structures. These studies suggest new ideas about the evolution of developmental mechanisms in the deuterostomes. In a seminal observation, we noted an unexpected zone of expression of the Brachyury gene in the early anterior embryonic ectoderm where the mouth will form. Typically, the Brachyury gene is closely linked to development of the notochord and is expressed around the blastopore and in the posterior mesoderm in most animals. This first expression of Brachyury at the blastopore may represent a regulatory program associated with organizing the original animal head and gut opening, as suggested by the expression of Brachyury during hypostome formation in hydra. We believe that the anterior expression of Brachyury in deuterostomes represents the cooption of the program for organizing the original animal gut opening to form the deuterostome mouth. Recent data from the trochophore larva of a polychaete show that an anterior zone of expression of Brachyury is produced in this protostome by splitting of the Brachyury field during the formation of a gut with a mouth and anus by the lateral fusion of the sides of the blastopore. The ability to initiate independently a secondary regulatory program to organize the new mouth leading to an anterior field of Brachyury expression may be a signal event in the evolution of the deuterostomes. We also noted that the P. flava homolog of T‐brain/Eomes, a gene closely related by sequence and expression around the blastopore to Brachyury and associated with development of the vertebrate brain, also exhibits early posterior expression around the blastopore and a field of de novo anterior ectoderm expression during later embryogenesis. The tissue in the zone of de novo anterior ectoderm expression of Pf‐Tbrain produces the apical organ, a larval neural structure that has been touted as an evolutionary precursor of the chordate dorsal brain. The gene regulatory mechanisms responsible for initiating the anterior zone of de novo expression of T‐brain may represent a cooption to specify early neuroectoderm of the regulatory program evolved first to drive anterior Brachyury expression for deuterostome mouth formation. It will be interesting to examine the possibilities that an ability to initiate the de novo anterior expression of the program that includes T‐brain may be a key event in the evolution of the developmental mechanisms leading to the chordate dorsal nervous system.     

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.     

Human exposure to mycotoxins in Egypt

This investigation examined the exposure of Egyptian infants to Aflatoxin M₁ (AfM₁) and of lactating mothers to Aflatoxin B₁, using AfM₁ in human milk as a biomarker for exposure to AfB₁. The presence of ochratoxin A (OA) in human milk was also investigated to determine the levels of infants exposure to OA from human milk. The results indicated that AfM₁ was found in 66 (55 %) of 120 human milk samples with a mean of 0.3 ± 0.53 ng/mL (range 0.02 to 2.09 ng/mL). OA was found in 43 (35.8 %) of 120 human milk samples with a mean of 21.1 ± 13.7 ng/mL (range 5.07 to 45.01 ng/mL), which will cause a daily intake of OA from human milk exceeding the suggested tolerable dose of 5 ng/kg_-1 of OA body weight. On the other side AfM₁ was found in 25 % of blood samples (5 out of 20 samples), at a mean of 1.18 ng/mL, but it was detected only in one urine sample (1 out of 20 samples). OA was detected only in 2 out of 13 blood samples (15.4 %) with an average 3.67 ng/mL. Whereas OA was not detected in all analyzed urine samples.     

连接性和空间相邻性在知觉组织中的关系

Palmer等人提出连接性先于经典的Gestalt规律决定视知觉的基本单元, 但是, Han等人发现在字母分辨任务中空间相邻性组织可以和连接性组织发生得一样快. 在3个实验中进一步研究连接性和空间相邻性组织的关系, 发现当视野中呈现一个或两个整体字母时, 检测由连接性和空间相邻性决定的靶目标的反应一样快. 但是, 当视野中的整体字母增多时, 检测由连接性决定的靶目标的反应比检测由空间相邻性决定的靶目标的反应快, 而且连接性的这种优势不受整体字母间距离的影响. 表明在多物体条件下决定知觉的基本单元过程中, 连接性比空间相邻性更有效. 讨论了这些结果的可能的原因.