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101.
102.
Braham Dhillon Nicolas Feau Andrea L. Aerts Stéphanie Beauseigle Louis Bernier Alex Copeland Adam Foster Navdeep Gill Bernard Henrissat Padmini Herath Kurt M. LaButti Anthony Levasseur Erika A. Lindquist Eline Majoor Robin A. Ohm Jasmyn L. Pangilinan Amadeus Pribowo John N. Saddler Monique L. Sakalidis Ronald P. de Vries Igor V. Grigoriev Stephen B. Goodwin Philippe Tanguay Richard C. Hamelin 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(11):3451-3456
Some of the most damaging tree pathogens can attack woody stems, causing lesions (cankers) that may be lethal. To identify the genomic determinants of wood colonization leading to canker formation, we sequenced the genomes of the poplar canker pathogen, Mycosphaerella populorum, and the closely related poplar leaf pathogen, M. populicola. A secondary metabolite cluster unique to M. populorum is fully activated following induction by poplar wood and leaves. In addition, genes encoding hemicellulose-degrading enzymes, peptidases, and metabolite transporters were more abundant and were up-regulated in M. populorum growing on poplar wood-chip medium compared with M. populicola. The secondary gene cluster and several of the carbohydrate degradation genes have the signature of horizontal transfer from ascomycete fungi associated with wood decay and from prokaryotes. Acquisition and maintenance of the gene battery necessary for growth in woody tissues and gene dosage resulting in gene expression reconfiguration appear to be responsible for the adaptation of M. populorum to infect, colonize, and cause mortality on poplar woody stems.Domestication of forest trees, in contrast to agricultural crops, has become prevalent only during the last few centuries and often encompasses a transition from wild, complex ecosystems to homogeneous and intensively managed plantations that are frequently composed of a single tree species (1). The recent ability to use modern genetic and genomic techniques with conventional breeding promises to speed up tree domestication (2). Poplar has emerged as an extremely versatile tree with natural attributes favorable to its domestication. The ease of vegetative propagation and the breeding of interspecific hybrids with broad adaptability, improved growth, and disease resistance has contributed to the widespread use of poplar for a variety of commercial products, including lumber, paper, and bioenergy feedstock (3). One of the challenges of poplar domestication has been the emergence of pathogens that were innocuous in their natural pathosystems, but can cause severe losses in plantations. Native poplars still vastly outnumber planted trees, and this large reservoir of a naturally coevolved pathosystem in close proximity to intensively managed clonal plantations could destabilize the host–pathogen equilibrium, leading to new disease epidemics (4).A native endemic fungus on northeastern and north-central North American poplars, Mycosphaerella populorum (anamorph = Sphaerulina musiva; class Dothideomycetes) occurs in natural stands of native Populus deltoides, causing necrotic foliar lesions, but rarely resulting in early defoliation (5). With the introduction of exotic poplar species at the beginning of the 20th century and the intensification of hybrid poplar cultivation in North America, M. populorum has emerged as a stem-infecting pathogen, causing stem cankers that lead to weakening and breakage of the tree trunk, often resulting in plantation failure (Fig. 1A) (6, 7). The pathogen can attack a broad range of susceptible hybrid poplars and has also expanded its geographic range. It has recently been reported, to our knowledge, for the first time west of the Rocky Mountains and in Argentina and Brazil (6–8). This disease has become the most important factor limiting poplar plantations in eastern North America and could threaten the poplar industry worldwide (6, 9).Open in a separate windowFig. 1.M. populorum and M. populicola symptoms and divergence time estimate. (A, Top Left) M. populorum branch canker and leaf spots on a P. deltoides × P. trichocarpa clone. (Top Right) M. populicola leaf-spot symptoms on P. trichocarpa. (Bottom) M. populorum stem canker on P. deltoides × P. maximowiczii (Left) and P. deltoides × P. trichocarpa (Right) that caused the trunk to break at the canker. Photo provided by Harry Kope. (B) Maximum-likelihood phylogeny of M. populorum, M. populicola, and 16 other ascomycete fungi. All nodes received a bootstrap support of 100% except one, indicated with a 94% value. Colored stars: calibration points in million years (SI Appendix, Phylogenomic Analysis).A sister species to this pathogen, Mycosphaerella populicola (anamorph = S. populicola; class Dothideomycetes), is also endemic on native poplars, causing a leaf spot symptom on Populus balsamifera and Populus trichocarpa, but has a much broader geographical distribution than M. populorum (6, 10). This pathogen is considered a lower threat to poplar plantations because it does not cause stem cankers under natural conditions or in plantations and it has a narrow host range (11).To identify genetic factors underlying the canker symptom, we sequenced and compared the genomes of these two closely related pathogens with different natural host ranges and etiological characteristics. This provided a unique opportunity to contrast the evolutionary consequences of the adaptation of a tree pathogen to different hosts and the ability to gradually transition from natural to domesticated ecosystems. Our results show that the genome of M. populorum has evolved a broader battery of genes and has acquired genes through horizontal transfer that are absent in its sister species. These genes are enriched in functions that allow M. populorum to infect woody tissues. 相似文献
103.
Hiba Alsaadon Peter Kruzliak Arthur Smardencas Alan Hayes Michael Bader Peter Angus Chandana Herath Anthony Zulli 《International journal of experimental pathology》2015,96(3):183-187
A growing body of evidence suggests that the vascular actions of Ang-(1-7) appear to involve increased production of nitric oxide (NO), an important vasodilator, through the activation of MasR, thus indicating the involvement of the MasR in preventing endothelial dysfunction. However, it is unknown whether the MasR could be involved in the progression of the next step in atherosclerosis, neo-intimal formation. To determine whether the deletion of the MasR is involved in the development of intimal thickening in an in vitro model. Mice [three background controls (C57Bl/6) and 3 MasR (−/−)] were killed and the aortas excised and cleaned of connective tissue and cut into 3 mm rings. Rings were placed in an organ culture medium for 5 weeks, embedded in paraffin, cut at 5 μm and stained with haematoxylin and eosin and Masson’s trichrome. In addition, aortic reactivity was measured in organ baths. After 5 weeks of culture, the intima:media ratio increased in the aortas from MasR (−/−) mice compared to the control group by 4.5-fold (P < 0.01). However, no significant difference in nuclei area count (cell proliferation) between the MasR (−/−) mice and control group was observed (0.87 ± 0.29% vs. 0.94 ± 0.18%, respectively, P = ns). Functional studies showed only a minor vasoconstrictive and full vasodilative response. This study shows that the deletion of the MasR causes marked increase in the aortic intima:media ratio, which is not due to generalized cellular proliferation. These results provide a functional role for the MasR in atherogenesis. 相似文献
104.
Adverse effects of environmental toxicants, octylphenol and bisphenol A, on male reproductive functions in pubertal rats 总被引:4,自引:0,他引:4
It has been proposed that a global decline in sperm counts, semen quality, and several male reproductive disorders are associated
with exposure to environmental chemicals. Thus, the present study examined the effects of two estrogenic chemicals, octylphenol
(OP) and bisphenol A (BPA), on epididymal sperm counts and sperm motility, luteinizing hormone (LH)-releasing hormone (LHRH)-stimulated
plasma LH and steroid hormones, insulin-like growth factor I (IGF-I), and accessory reproductive organs in pubertal male Wistar
rats. Fifty-day-old rats in the OP group (n=11) and BPA group (n=11) received daily sc injections of the respective chemical at a dose of 3 mg/kg bw dissolved in 0.2 mL DMSO. Rats in the
control group (DMSO group; n=10) received 0.2 mL DMSO alone. After 2 wk of treatment, a jugular blood sample was taken, and, on the next day, a second
blood sample was taken 1 h after an sc injection of LHRH (250 ng). After 5 wk of treatment, rats were deeply anesthetized
and heart blood was collected. Epididymal sperm motility and sperm head counts were determined. LHRH increased plasma LH to
higher levels in all groups, but the increases were significant (p<0.01) in the BPA and OP groups. However, despite higher LH levels after LHRH injection, the incremental responses of testosterone
and progesterone in the OP and BPA groups were small compared to those in the DMSO group, which showed a small LH response.
After 5 wk of treatment, plasma testosterone levels were significantly (p<0.01) reduced in the OP and BPA groups and this was accompanied by reduced (p<0.05) epididymal sperm counts. However, the chemical-treated groups had high basal progesterone levels. No significant effects
of chemicals on sperm motility parameters were noted. The chemical-induced increases (p<0.05) of the weight of ventral prostate gland were coincided with elevated plasma IGF-I levels in the BPA (p<0.05) and OP (p<0.01) groups. The present results demonstrated that OP and BPA can reduce sperm counts resulting from lowered plasma testosterone
in male rats just after puberty. The enlarged ventral prostate gland may possibly be associated with increased plasma IGF-I,
raising the possibility of a link between these chemicals and prostate diseases because IGF-I has been implicated in the pathogenesis
of human prostate cancers. 相似文献
105.
Characteristics of malaria transmission in Kataragama, Sri Lanka: a focus for immuno-epidemiological studies 总被引:7,自引:0,他引:7
C Mendis A C Gamage-Mendis A P De Zoysa T A Abhayawardena R Carter P R Herath K N Mendis 《The American journal of tropical medicine and hygiene》1990,42(4):298-308
Parasitological and entomological parameters of malaria transmission were monitored for 17 months in 3,625 residents in a Plasmodium vivax malaria endemic region in southern Sri Lanka; the study area consisted of 7 contiguous villages where routine national malaria control operations were being conducted. Malaria was monitored in every resident; fever patients were screened and 4 periodical mass blood surveys were conducted. An annual malaria incidence rate of 23.1% was reported during the period: 9.3% was due to P. vivax and 13.8% was due to P. falciparum; there had been a recent epidemic of the latter in this region, whereas the P. falciparum incidence rate in the previous 10 years had been negligible. There was a wide seasonal fluctuation in the malaria incidence, with the peak incidence closely following the monsoon rains. The prevalence of malaria due to both species detected at the 4 mass blood surveys ranged from 0.98% (at low transmission) to 2.35% (at peak transmission periods). Adults and children developed acute clinical manifestations of malaria. Entomological measurements confirmed a low degree of endemicity with estimated inoculation rates of 0.0029 and 0.0109 (infectious bites/man/night) for P. vivax and P. falciparum, respectively. Several anopheline species contributed to the transmission, and the overall man biting rates (MBR) showed a marked seasonal variation. Malaria at Kataragama, typical of endemic areas of Sri Lanka, thus presents characteristics of "unstable" transmission. Malaria was clustered in the population. There was a low clinical tolerance to P. falciparum malaria, to which most had only been at risk, compared to P. vivax, to which most had had a life-long exposure. 相似文献
106.
Steven C. Herath Thorsten Lion Moritz Klein David Stenger Claudia Scheuer Jörg H. Holstein Philipp Mörsdorf Mika F.R. Rollmann Tim Pohlemann Michael D. Menger Tina Histing 《Journal of orthopaedic research》2015,33(12):1880-1887
Cilostazol, a selective phosphodiesterase‐3 inhibitor, is known to control cyclic adenosine monophosphate (c‐AMP) and to stimulate angiogenesis through upregulation of pro‐angiogenic factors. There is no information, however, whether cilostazol affects fracture healing. We, therefore, studied the effect of cilostazol on callus formation and biomechanics during fracture repair. Bone healing was analyzed in a murine femur fracture stabilized with an intramedullary screw. Radiological, biomechanical, histomorphometric, histochemical, and protein biochemical analyses were performed at 2 and 5 weeks after fracture. Twenty‐five mice received 30 mg/kg body weight cilostazol p.o. daily. Controls (n = 24) received equivalent amounts of vehicle. In cilostazol‐treated animals radiological analysis at 2 weeks showed an improved healing with an accelerated osseous bridging compared to controls. This was associated with a significantly higher amount of bony tissue and a smaller amount of cartilage tissue within the callus. Western blot analysis showed a higher expression of cysteine‐rich protein 61 (CYR61), bone morphogenetic protein (BMP)‐4, and receptor activator of NF‐kappaB ligand (RANKL). At 5 weeks, improved fracture healing after cilostazol treatment was indicated by biomechanical analyses, demonstrating a significant higher bending stiffness compared to controls. Thus, cilostazol improves fracture healing by accelerating both bone formation and callus remodeling. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1880–1887, 2015. 相似文献
107.
108.
109.
Herath NI Kew MC Walsh MD Young J Powell LW Leggett BA MacDonald GA 《Journal of gastroenterology and hepatology》2002,17(3):301-307
Chromosome 9p21, a locus comprising the tumor suppressor genes (TSG) p16(INK4a) and p14(ARF), is a common region of loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC). p14(ARF) shares exon 2 with p16 in a different reading frame. p14 binds to MDM2 resulting in a stabilization of functional p53. This study examined the roles of p14, p16 and p53 in hepatocarcinogenesis, in 37 Australian and 24 South African patients. LOH at 9p21 and 17p13.1, p14 and p16 mutation analysis, p14 and p16 promoter methylation and p14, p16 and p53 protein expression was examined. LOH at 9p21 was detected more frequently in South African HCC (P = 0.04). Comparable rates of p53 LOH were observed in Australian and South African HCC (10/22, 45%vs 13/22, 59%, respectively). Hypermethylation of the p14 promoter was more prevalent in Australian HCC than in South African HCC (17/37, 46%vs 7/24, 29%, respectively). In Australian HCC the prevalence of p14 methylation increased with age (P = 0.03). p16 promoter methylation was observed in 12/37 (32%) and 6/24 (25%) in Australian and South African HCC, respectively. Loss of p16 protein expression was detected in 14/36 Australian HCC whereas p53 protein expression was detected in 9/36. Significantly, a reciprocal relationship between 9p21 LOH and p14 promoter hypermethylation was observed (P < or = 0.05). No significant association between p14 and p53 was seen in this study. The reciprocal relationship identified indicates different pathways of tumorigenesis and likely reflects different etiologies of HCC in the two countries. 相似文献
110.