-
[show abstract]
[hide abstract]
ABSTRACT: Mon1 protein is involved in cytoplasm-to-vacuole trafficking, vacuolar morphology and autophagy, and is required for homotypic vacuole fusion in Saccharomyces cerevisiae. Here we identify MoMON1 from Magnaporthe oryzae as an orthologue of S. cerevisiae MON1, essential for the morphology of the vacuole and vesicle fusion. Target gene deletion of MoMON1 resulted in accumulation of small punctuate vacuoles in the hypha and hypersensitivity to monensin, an antibiotic that blocks intracellular protein transport. The ΔMomon1 mutant exhibited significantly reduced aerial hyphal development and poor conidiation. Conidia of ΔMomon1 were able to differentiate appressoria. However, ΔMomon1 was non-pathogenic on rice leaves, even after wound inoculation. In addition, ΔMomon1 was slightly hypersensitive to Congo red and SDS, but not to cell wall degrading enzymes, suggesting significant alterations in its cell wall. The autophagy process was blocked in the ΔMomon1 mutant. Taken together, our results suggest that MoMON1 has an essential function in vacuolar assembly, autophagy, fungal development and pathogenicity in M. oryzae.
Research in Microbiology 01/2013; · 2.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The mutualism pattern of the dark septate endophyte (DSE) Harpophora oryzae in rice roots and its biocontrol potential in rice blast disease caused by Magnaporthe oryzae were investigated. Fluorescent protein-expressing H. oryzae was used to monitor the colonization pattern. Hyphae invaded from the epidermis to the inner cortex, but not into the root stele. Fungal colonization increased with root tissue maturation, showing no colonization in the meristematic zone, slight colonization in the elongation zone, and heavy colonization in the differentiation zone. H. oryzae adopted a biotrophic lifestyle in roots accompanied by programmed cell death. Real-time PCR facilitated the accurate quantification of fungal growth and the respective plant response. The biocontrol potential of H. oryzae was visualized by inoculation with eGFP-tagged M. oryzae in rice. H. oryzae protected rice from M. oryzae root invasion by the accumulation of H2O2 and elevated antioxidative capacity. H. oryzae also induced systemic resistance against rice blast. This systemic resistance was mediated by the OsWRKY45-dependent salicylic acid (SA) signaling pathway, as indicated by the strongly upregulated expression of OsWRKY45. The colonization pattern of H. oryzae was consistent with the typical characteristics of DSEs. H. oryzae enhanced local resistance by reactive oxygen species (ROS) and high antioxidative level and induced OsWRKY45-dependent SA-mediated systemic resistance against rice blast.
PLoS ONE 01/2013; 8(4):e61332. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Plant pathogenic fungi utilize a series of complex infection structures, in particular the appressorium, to gain entry to and colonize plant tissue. As a consequence of the accumulation of huge quantities of glycerol in the cell the appressorium generates immense intracellular turgor pressure allowing the penetration peg of the appressorium to penetrate the leaf cuticle. Autophagic processes are ubiquitous in eukaryotic cells and facilitate the bulk degradation of macromolecules and organelles. The study of autophagic processes has been extended from the model yeast Saccharomyces cerevisiae to pathogenic fungi such as the rice blast fungus Magnaporthe oryzae. Significantly, null mutants for the expression of M. oryzae autophagy gene homologs lose their pathogenicity for infection of host plants. Clarification of the functions and network of interactions between the proteins expressed by M. oryzae autophagy genes will lead to a better understanding of the role of autophagy in fungal pathogenesis and help in the development of new strategies for disease control.
Autophagy 08/2012; 8(10):1415-25. · 7.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Autophagy (macroautophagy), a highly conserved eukaryotic mechanism, is a non-selective degradation process, helping to maintain a balance between the synthesis, degradation and subsequent recycling of macromolecules to overcome various stress conditions. The term autophagy denotes any cellular process which involves the delivery of cytoplasmic material to the lysosome for degradation. Autophagy, in filamentous fungi plays a critical role during cellular development and pathogenicity. Autophagy, like the mitogen-activated protein (MAP) kinase cascade and nutrient-sensing cyclic AMP (cAMP) pathway, is also an important process for appressorium turgor accumulation in order to penetrate the leaf surface of host plant and destroy the plant defense. Yeast, an autophagy model, has been used to compare the multi-valued functions of ATG (autophagy-related genes) in different filamentous fungi. The autophagy machinery in both yeast and filamentous fungi is controlled by Tor kinase and both contain two distinct phosphatidylinositol 3-kinase complexes. In this review, we focus on the functions of ATG genes during pathogenic development in filamentous fungi.
Microbiological Research 05/2012; 167(6):339-45. · 2.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Plant–fungal symbiotic associations are ubiquitously distributed in natural plant communities. Besides the well-studied mycorrhizal
symbiosis and grass systemic clavicipitaceous endophytes, recently, nonsystemic and horizontally transmitted fungal endophytes
serving as plant symbionts have been increasingly recognized. Pure culture isolation and culture-independent molecular methods
indicate that all parts of healthy plant tissues potentially harbor diverse and previously unknown fungal lineages. Limited
evidence also supports a hypothesis that endophytic mycobiota dynamics may have a role in evolution of plants. High variability
or “balanced antagonism” can be generally characterized with host–endophyte interactions, which implies that the outcome of
symbiotic interactions can fall within a continuum ranging from mutualism to commensalism, and ultimately pathogenicity. Despite
this complicated system, admittedly, fungal endophytes really endow the host with an extended phenotype. Accumulating facts
illustrate that plant nutrition acquisition, metabolism, and stress tolerance may be strengthened or modulated via fungal
symbionts. Piriformospora indica, a member of the order Sebacinales, simultaneously confers host resistance to biotic and abiotic stress. The ecological relevance
of other fungal groups, including foliar endophytes, root dark septate endophytes (DSEs), some opportunistic and avirulent
microsymbionts (for example, Trichoderma and Fusarium), and even uncultured fungi structurally and physiologically integrated with host tissues, are also being deeply exploited.
Production of bioactive metabolites by fungi, overexpression of stress-related enzymes, and induced resistance in hosts upon
fungal colonization are responsible for direct or indirect beneficial effects to hosts. More knowledge of endophyte-mediated
enhancement of host performance and fitness will offer alternatively valuable strategies for plant cultivation and breeding.
Meanwhile, with unprecedented loss of biodiversity, discovery of indigenously novel symbiotic endophytes from natural habitats
is urgently needed. In addition, we present some approaches and suggestions for studying host–endophyte interactions.
KeywordsFungal endophytes-Symbiosis-Stress tolerance-Diversity-Metabolism
Journal of Plant Growth Regulation 04/2012; 29(1):116-126. · 2.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Through bioassay-guided fractionation, the EtOAc extract of a culture broth of the endophytic fungus Phoma species ZJWCF006 in Arisaema erubescens afforded a new α-tetralone derivative, (3S)-3,6,7-trihydroxy-α-tetralone (1), together with cercosporamide (2), β-sitosterol (3), and trichodermin (4). The structures of compounds were established on the basis of spectroscopic analyses. Compounds 1, 2, and 3 were obtained from Phoma species for the first time. Additionally, the compounds were subjected to bioactivity assays, including antimicrobial activity, against four plant pathogenic fungi (Fusarium oxysporium, Rhizoctonia solani, Colletotrichum gloeosporioides, and Magnaporthe oryzae) and two plant pathogenic bacteria (Xanthomonas campestris and Xanthomonas oryzae), as well as in vitro antitumor activities against HT-29, SMMC-772, MCF-7, HL-60, MGC80-3, and P388 cell lines. Compound 1 showed growth inhibition against F. oxysporium and R. solani with EC₅₀ values of 413.22 and 48.5 μg/mL, respectively. Additionally, compound 1 showed no cytotoxicity, whereas compound 2 exhibited cytotoxic activity against the six tumor cell lines tested, with IC₅₀ values of 9.3 ± 2.8, 27.87 ± 1.78, 48.79 ± 2.56, 37.57 ± 1.65, 27.83 ± 0.48, and 30.37 ± 0.28 μM, respectively. We conclude that endophytic Phoma are promising sources of natural bioactive and novel metabolites.
Applied Microbiology and Biotechnology 08/2011; 93(3):1231-9. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Autophagy is a highly conserved process in lower to higher eukaryotic organisms, and occurs in many types of cells as tissues are remodeled during development. In this study, we investigated the functional role of the Trichoderma reesei TrATG5 gene, which encodes an essential protein required for autophagy. TrATG5 is conserved in structure and function in the filamentous fungi and might clearly rescue the pathogenicity function of MgATG5 in Magnaporthe oryzae. Target gene disruption was used to study the functions of TrATG5. It was found that the autophagic process was blocked in the TrATG5 deletion mutant. The mutant was sensitive to nutrient starvation, with abnormal conidiophores and reduced production of conidia. This new evidence might help to elucidate the molecular machinery of autophagy in filamentous fungi.
Research in Microbiology 06/2011; 162(8):756-63. · 2.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Magnaporthe oryzae is an important plant pathogenic fungus that greatly threatens the world's food security. Both genome-wide and individual gene studies have shown that the pathogenicity of the fungus is severely dependent on the intracellular autophagy process during appressoria development. This protocol discusses a systematic methodology to discover and monitor autophagy-related (ATG) genes in M. oryzae.
Autophagy 05/2011; 7(5):525-30. · 7.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Magnaporthe oryzae has been used as a model fungal pathogen to study the molecular basis of plant-fungus interactions due to its economic and genetic importance. In this study, we identified a novel gene, Moplaa, which is the homologue of Homo sapiens PLAA encoding a phospholipase A(2)-activating protein. Moplaa is conserved in some eukaryotic organisms by multiple alignment analysis. The function of the Moplaa gene was studied using the gene target replacement method. The Moplaa deletion mutant exhibited retarded growth and conidial germination, reduced conidiation, appressorial turgor pressure and pathogenicity to rice CO-39. Reintroduction of the gene restored defects of the Moplaa deletion mutant.
Microbiological Research 04/2011; 167(1):8-13. · 2.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ecological niches in the rhizosphere and phyllosphere of grasses capable of sustaining endophytes have been extensively studied. In contrast, little information regarding the identity and functions of endophytic fungi in stems is available. In this study, we investigated the taxonomic affinities, diversity, and host specificities of culturable endophytes in stems of wild rice (Oryza granulata) in China. Seventy-four isolates were recovered. Low recovery rate (11.7%) indicated that there were relatively few sites for fungal infection. Identification using morphology, morphospecies sorting, and molecular techniques resulted in classification into 50 taxa, 36 of which were recovered only once. Nucleotide sequence similarity analysis indicated that 30% of the total taxa recovered were highly divergent from known species and thus may represent lineages new to science. Most of the taxa were classified as members of the classes Sordariomycetes or Dothideomycetes (mainly in Pleosporales). The presence of Arthrinium and Magnaporthaceae species, most often associated with poaceous plants, suggested a degree of host specificity. A polyphasic approach was employed to identify two Muscodor taxa based on (i) ITS and RPB2 phylogenies, (ii) volatile compounds produced, and (iii) an in vitro bioassay of antifungal activity. This to our knowledge is only the second report regarding the isolation of Muscodor spp. in China. Therefore, we hypothesize that wild plants represent a huge reservoir of unknown fungi. The prevalence, novelty, and species-specificity of unique isolates necessitate a reevaluation of their contribution to ecosystem function and fungal biodiversity.
The Journal of Microbiology 02/2011; 49(1):15-23. · 1.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chaetomium siamense sp. nov., isolated from soil in a pineapple plantation in Thailand, is described and illustrated. The new species is similar to C. cupreum in having superficial globose or ovate ascomata with red circinate ascomatal hairs but can be distinguished by its fusiform ascospores with two apical germ pores. Phylogenetic analysis of ITS rDNA sequence data also supports C. siamense as distinct. Investigation of the secondary metabolites of C. siamense led to the isolation of one new (chaetoviridin G) and seven known compounds (ergosterol, 24(R)-5α,8α-epidioxyergosta-6-22-diene-3β-ol, ergosterylplamitate, cochliodone D, chaetoviridin A, chaetoviridin F, chrysophanol).
Mycotaxon -Ithaca Ny- 12/2010; 115:19-27. · 0.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The fungal genus Muscodor was erected on the basis of Muscodor albus, an endophytic fungus originally isolated from Cinnamomum zeylanicum. It produces a mixture of volatile organic compounds (VOCs) with antimicrobial activity that can be used as mycofumigants. The genus currently comprises five species. Here we describe the isolation and characterization of a new species of Muscodor on the basis of five endophytic fungal strains from leaves of Actinidia chinensis, Pseudotaxus chienii and an unidentified broad leaf tree in the Fengyangshan Nature Reserve, Zhejiang Province, Southeast of China. They exhibit white colonies on potato dextrose agar (PDA) media, rope-like mycelial strands, but did not sporulate. The optimum growth temperature is 25°C. The results of a phylogenetic analysis based on four loci (ITS1-5.8S-ITS2, 28S rRNA, rpb2 and tub1) are consistent with the hypothesis that these five strains belong to a single taxon. All five strains also produce volatile chemical components with antimicrobial activity in vitro, which were different from those previously described for other Muscodor species.
Fungal Biology 10/2010; 114(10):797-808. · 1.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A survey of the endophytic fungal community of wild rice (Oryza granulata) in China was conducted. Two isolates recovered from healthy roots are assumed to be dark septate endophytes (DSEs). They are morphologically similar to species from the genus Harpophora and are identified as a new species, Harpophora oryzae, based on the molecular phylogeny and morphological characteristics. A neighbor-joining tree constructed from ITS-5.8S rRNA gene regions reveals that H. oryzae forms a distinctive subclade within the genus Harpophora, and is not genetically close to other species of Harpophora. Harpophora oryzae exhibits a moderate growth rate, with a frequent production of rope-like strands. It sporulates readily on artificial medium. Phialides are usually flask or bottle shaped and occur singly along hyphae or laterally and terminally on branched, hyaline to brown conidiophores, and also form whorls on metulae. Conidiophores are mostly branched with a slightly thickened wall, varying in dimensions. Conidia are one-celled and hyaline, most of them being falcate and strongly curved. The morphological differences between Harpophora spp. and Harpophora-like anamorphs representing different orders are also discussed. An in vitro inoculation test showed that H. oryzae may contribute towards improving rice (Oryza sativa L.) growth. Microscopic inspection of roots and phylogenetic placement of isolates further confirmed that H. oryzae represents a novel member of DSEs.
FEMS Microbiology Letters 06/2010; 307(1):94-101. · 2.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Rice (Oryza sativa L.) is, on a global scale, one of the most important food crops. Although endophytic fungi and bacteria associated with rice have been investigated, little is known about the endophytic fungi of wild rice (Oryza granulate) in China. Here we studied the root endophytic mycobiota residing in roots of O. granulate by the use of an integrated approach consisting of microscopy, cultivation, ecological indices, and direct PCR. Microscopy confirmed the ubiquitousness of dark septate endophytes (DSEs) and sclerotium-like structures in root tissues. Isolations from 204 root segments from 15 wild rice plants yielded 58 isolates, for which 31 internal transcribed spacer (ITS)-based genotypes were recorded. The best BLAST match indicated that 34.5% of all taxa encountered may represent hitherto undescribed species. Most of the fungi were isolated with a very low frequency. Calculation of ecological indices and estimation of taxon accumulation curves indicated a high diversity of fungal species. A culture-independent approach was also performed to analyze the endophytic fungal community. Three individual clone libraries were constructed. Using a threshold of 90% similarity, 35 potentially different sequences (phylotypes) were found among 186 positive clones. Phylogenetic analysis showed that frequently detected clones were classified as Basidiomycota, and 60.2% of total analyzed clones were affiliated with unknown taxa. Exophiala, Cladophialophora, Harpophora, Periconia macrospinosa, and the Ceratobasidium/Rhizoctonia complex may act as potential DSE groups. A comparison of the fungal communities characterized by the two approaches demonstrated distinctive fungal groups, and only a few taxa overlapped. Our findings indicate a complex and rich endophytic fungal consortium in wild rice roots, thus offering a potential bioresource for establishing a novel model of plant-fungal mutualistic interactions.
Applied and environmental microbiology 03/2010; 76(5):1642-52. · 3.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Thirty-four isolates of Colletotrichum spp. including 2 species, C. gloeosporioides and C. capsici, from anthracnose on Bell pepper, Long cayenne pepper and Bird's eye chilli were isolated and their pathogenicity was proven via fruit inoculation. Pathogenicity tests divided pathogenic potential into low, medium and high virulence groups. It is clearly revealed that C. capsici from the three tested hosts expressed the highest virulent isolates. Cross-inoculation of three high virulent isolates of C. capsici in accordance with three chilli varieties showed that all isolates could produce anthracnose symptom in the same lesions. All tested isolates developed lesions after co-inoculation of all hosts. Inter simple sequence repeat (ISSR) analysis indicated that there are two distinct groups of C. gloeosporioides and C. capsici. Furthermore, genetic diversity was correlated with geographic distribution, while there was no clear relationship between genetic diversity and pathogenic variability. But it is clearly demonstrated that whereas C. gloeosporioides appears in the same geographic area as C. capsici, it causes lower disease incidence.
African journal of microbiology research 02/2010; 4:76-83. · 0.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Atg4 is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8 during the formation of autophagosomes in yeast. Here we report that MoAtg4, an Atg4 homologue in Magnaporthe oryzae, controls cell differentiation and pathogenicity by interacting with MoAtg8, an autophagic protein essential for autophagic cell death and pathogenicity. Yeast complementation assay revealed that MoATG4 can functionally complement the defects of the yeast ATG4 deletion mutant. The direct interaction between MoAtg4 and MoAtg8 was detected in both yeast two hybrid and bimolecular fluorescence complementation (BiFC) assays. We also specify a cysteine residue, Cys206, as the active residue within MoAtg4 for the cleavage of MoAtg8 in vitro. Expression pattern analysis revealed that MoATG4 gene is expressed throughout growth and development by M. oryzae and can be induced by starvation and MoAtg4 protein localized in the cytoplasm of M. oryzae. Deletion of MoATG4 in M. oryzae caused significant reduction of aerial hyphae, conidiation, perithecia formation and delay of conidial germination and appressorium formation. Furthermore, as a result of lower turgor pressure of the appressorium, the DeltaMoatg4 mutant lost its ability to penetrate rice and barley. The developmental and pathogenic phenotypes were recovered by reintroduction of an intact copy of MoATG4 into the mutant, suggesting that MoATG4 is indispensable in the development of M. oryzae and essential to pathogenicity of this fungus.
Autophagy 01/2010; 6(1):74-85. · 7.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Autophagy is a vacuolar/lysosomal cytoplasmic recycling system in eukaryotic cells. ScATG9 is indispensable for autophagy in Saccharomyces cerevisiae. Here, we deleted MgATG9, the orthologue of ScATG9, via targeted gene replacement in the phytopathogenic filamentous fungus Magnaporthe oryzae, and then analyzed the cellular distribution pattern of EGFP-MgAtg9 in the Mgatg9Delta mutant. We detected an expression profile of multiple green dots in the conidial cell inoculated in rich media and in the appressoria differentiated from the conidia in H(2)O. Concurrent with the punctation, we found some fluorescent signals localized on the central vacuole of the submerged hyphae from the conidia cultured in rich media. Next, we introduced DsRed2-MgAtg8 into the Mgatg9Delta mutant expressing EGFP-MgAtg9 and observed partial overlap at multiple sites in the conidial cell, reminiscent of that in the mammalian system. Our findings further led to the postulation that the multiple sites where the two fusions colocalized tend to merge as a central structure in the conidial cell. Finally, we tested the expression of EGFP-MgAtg9 in null mutants of MgATG1, 2, 13 and 18, respectively. We speculate that MgAtg1, 2 and 18, but not MgAtg13, is required for MgAtg9 cycling through the multiple colocalization sites to its storage pools in the conidial cell of M. oryzae, and fusion of these colocalization sites into a central structure could be governed through other unidentified mechanisms.
Autophagy 11/2009; 5(7):946-53. · 7.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The genetic variation among 32 isolates of Rigidoporus microporus was determined using pathogenicity tests and molecular marker (intersimple sequence repeats; ISSR). Isolates were collected from six sites of two provinces in the south of Thailand. Based on the pathogenicity results, all isolates could divide into three groups depended on their virulence to rubber trees as follows: low virulent isolates, moder-ately virulent isolates and high virulent isolates. Cluster analysis based on ISSR characters grouped the isolates according to geographical origins. A dendrogram resulting from a cluster analysis showed two main distinct groups, designated as A and B rooting from outgroup. Group A contained isolates col-lected from Surat Thani province and group B those collected from Narathiwat province. There was no clear relationship between degrees of disease and geographical regions.
African journal of microbiology research 11/2009; 3:641-648. · 0.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ca(2+) is a second messenger in pathways that transduce external signals and activate cellular processes in plants and animals. Ca(2+)-mediated signal transduction is involved in key pathways that contribute to a variety of fundamental physiological processes in eukaryotic cells. However, little is known about the molecular mechanisms of Ca(2+)-mediated signal transduction in filamentous fungi. In this study, the MoCMK1 gene, encoding a putative Ca(2+)/calmodulin-dependent kinase, was identified in the rice blast fungus Magnaporthe oryzae. Three MoCMK1 deletion mutants were obtained by a targeted gene replacement. Colonies of the MoCMK1 mutants had sparse aerial hyphae and fewer conidia than the wild-type strain on complete medium. Conidial germination and appressorial formation were delayed in the DeltaMocmk1 mutants. In spray inoculation tests, DeltaMocmk1 mutants exhibited a weakened ability to infect the susceptible rice cultivar CO-39, compared to the wild-type strain Guy11. These results showed that MoCMK1 plays key roles in the pathogenicity of the rice blast fungus.
Microbiological Research 10/2009; 165(5):402-10. · 2.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Autophagy is a conserved degradation pathway that is involved in the maintenance of normal cell differentiation and development. The Saccharomyces cerevisiae ATG5 gene is an important component of the autophagy process. In this study, we identified MgATG5 as an autophagy-related gene in Magnaporthe oryzae that is homologous to ATG5. Using targeted gene replacement, an Mgatg5Delta mutant was generated and fungal autophagy was blocked. Cytological analysis revealed that the mutant had poor fungal morphogenic development, including a shortened aerial hyphae lifespan, decreased conidiation and perithecia formation, delayed conidial germination and appressorial formation, postponement of conidial cytoplasm transfer during appressorium formation, and reduction in formation of the penetration peg. Turnover of endogenous matter in the Mgatg5 mutant was also affected, as demonstrated by defects in the formation of conidial lipid droplets, and in the degradation of conidial glycogen deposits during appressorium formation. Lipid droplets and glycogen are necessary to generate adequate turgor in appressoria for invading the host surface. As a result of the decreased appressorium turgor and differentiation in the penetration peg, Mgatg5Delta pathogenicity was deficient in two host plants tested. The developmental and pathogenic phenotypes were restored by the introduction of an intact copy of MgATG5 into Mgatg5Delta, demonstrating that the MgATG5 deletion was responsible for the cellular defects. Taken together, these findings suggest that autophagy promotes cell differentiation through turnover of endogenous matter during fungal development, and is thus essential for the pathogenicity of the rice blast fungus.
Current Genetics 08/2009; 55(4):461-73. · 2.56 Impact Factor
