The FHIT gene product: tumor suppressor and genome “caretaker”

The FHIT gene at FRA3B is one of the earliest and most frequently altered genes in the majority of human cancers. It was recently discovered that the FHIT gene is not the most fragile locus in epithelial cells, the cell of origin for most Fhit-negative cancers, eroding support for past claims that deletions at this locus are simply passenger events that are carried along in expanding cancer clones, due to extreme vulnerability to DNA damage rather than to loss of FHIT function. Indeed, recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of the epithelial–mesenchymal transition. Other recent works have identified a novel role for the FHIT gene product, Fhit, as a genome “caretaker.” Loss of this caretaker function leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks. Because Fhit loss-induced DNA damage is “checkpoint blind,” cells accumulate further DNA damage during subsequent cell cycles, accruing global genome instability that could facilitate oncogenic mutation acquisition and expedite clonal expansion. Loss of Fhit activity therefore induces a mutator phenotype. Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.     

Developing an Information System for Sustainable Natural Resource Management in Alborz Watershed, Northern Iran

This article explores the potentials of systems analysis and design of information system for sustainable natural resource management. Soft and hard system analyses were performed to better understand the information needs and design of an information system for improving decision making for achieving sustainable natural resource management. In order to analyze the complex and soft systems situations for developing an effective information system, which meets related actors’ changing needs, a conceptual model inspired by soft systems methodology (SSM) was developed. This model is based on information derived from twelve farmers who were purposely selected to represent diverse conditions and 23 agricultural extension experts across the Alborz Watershed in Mazandaran Province, located in northern Iran. Since a conceptual model resulting from SSM is not in itself sufficient as the basis for the implementation of information systems, a hard system methodology was used to structure the data handling by using unified modeling language. This research has shown the promising potentiality of using soft system analysis methodology as a preliminary step to the actual design of an information system in the natural resource management situation in the watershed system level when combined with hard system analysis methods.     

A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors

Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signalling proteins, including HER-2/ErbB2, Akt, Raf-1, Bcr-Abl and mutated p53. Hsp90 inhibitors bind to Hsp90, and induce the proteasomal degradation of Hsp90 client proteins. Although Hsp90 is highly expressed in most cells, Hsp90 inhibitors selectively kill cancer cells compared to normal cells, and the Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is currently in phase I clinical trials. However, the molecular basis of the tumour selectivity of Hsp90 inhibitors is unknown. Here we report that Hsp90 derived from tumour cells has a 100-fold higher binding affinity for 17-AAG than does Hsp90 from normal cells. Tumour Hsp90 is present entirely in multi-chaperone complexes with high ATPase activity, whereas Hsp90 from normal tissues is in a latent, uncomplexed state. In vitro reconstitution of chaperone complexes with Hsp90 resulted in increased binding affinity to 17-AAG, and increased ATPase activity. These results suggest that tumour cells contain Hsp90 complexes in an activated, high-affinity conformation that facilitates malignant progression, and that may represent a unique target for cancer therapeutics.     

高等教育计算和信息技术学科面临的挑战

Despite the growth of the IT industry and the high demand for IT skills university departments seem unable to attract enough student to cater for the needs of the profession.There seems to be a misconception about the difference between IT user skills and the discipline of Computing.This article attempts to do three things:1)reinforce the view that a crisis of IT skills shortage is looming;2)reiterate the fact that computing science is an exciting discipline that is central to the knowledge economy and that career prospects in IT-related jobs are very good despite the fears surrounding outsourcing and 3)suggest that HE computing departments must be flexible enough to embrace a two-facetted challenge:a)the changing landscape of IT Skills and b)the high hopes and aspirations of the first generation of our digital-native student community.     

Analysis of the DNA sequence and duplication history of human chromosome 15

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.     

A Link-Based Similarity for Improving Community Detection Based on Label Propagation Algorithm

Community structure is one of the most best-known properties of complex networks. Finding communities help us analyze networks from a mesoscopic viewpoints instead of microscopic or macroscopic one. It helps to understand behavior grouping. Various community detection algorithms have been proposed with some shortcomings in time and space complexity, accuracy, or stability. Label Propagation Algorithm(LPA) is a popular method used for finding communities in an almost-linear time-consuming process. However, its performance is not satisfactory in some metrics such as accuracy and stability. In this paper, a new modified version of LPA is proposed to improve the stability and accuracy of the LPA by defining two concepts-nodes and link strength based on semi-local similarity-,while preserving its simplicity. In the proposed method a new initial node selection strategy, namely the tiebreak strategy, updating order and rule update are presented to solve the random behavior problem of original LPA. The proposed algorithm is evaluated on artificial and real networks. The experiments show that the proposed algorithm is close to linear time complexity with better accuracy than the original LPA and other compared methods. Furthermore, the proposed algorithm has the robustness and stability advantages while the original LPA does not have these features.     

Fras1 deficiency results in cryptophthalmos,renal agenesis and blebbed phenotype in mice

Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Postnatally, homozygous Fras1 mutants have fusion of the eyelids and digits and unilateral renal agenesis or dysplasia. The defects observed in Fras1-/- mice phenocopy those of the existing bl (blebbed) mouse mutants, which have been considered a model for the human genetic disorder Fraser syndrome. We show that bl/bl homozygous embryos are devoid of Fras1 protein, consistent with the finding that Fras1 is mutated in these mice. In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human.     

Biodegradable starch/poly (vinyl alcohol) film reinforced with titanium dioxide nanoparticles

Biodegradable starch/poly (vinyl alcohol)/nano-titanium dioxide (ST/PVA/nano-TiO₂) nanocomposite films were prepared via a solution casting method. Their biodegradability, mechanical properties, and thermal properties were also studied in this paper. A general full factorial experimental approach was used to determine effective parameters on the mechanical properties of the prepared films. ST/PVA/TiO₂ nanocomposites were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results of mechanical analysis show that ST/PVA films with higher contents of PVA have much better mechanical properties. In thermal analysis, it is found that the addition of TiO₂ nanoparticles improves the thermal stability of the films. SEM micrographs, taken from the fracture surface of samples, illustrate that the addition of PVA makes the film softer and more flexible. The results of soil burial biodegradation indicate that the biodegradability of ST/PVA/TiO₂ films strongly depends on the starch proportion in the film matrix. The degradation rate is increased by the addition of starch in the films.     

A TEM study on the microstructure of spark plasma sintered ZrB_2-based composite with nano-sized SiC dopant

Sintering behavior of ZrB₂ ceramic with nano-sized SiC dopant was studied. ZrB₂-25 vol% nano-sized SiC was selected as the starting mixture to fabricate the composite. The manufacturing process was accomplished at 1800℃ for 5 min under 25 MPa via spark plasma sintering(SPS). The as-sintered sample reached a relative density of 99%. Besides the initial phases, namely ZrB₂ and SiC, the high-resolution X-ray diffraction(HRXRD) was used to study the formation of an i...