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replication or death: distinct fates of pathogenic leptospira strain lai within macrophages of human or mouse origin.pathogenic leptospires evoke severe diseases in humans but only cause mild chronic or asymptomatic infection in many host animals. the reasons for this diversity of infection remain unclear. here, we demonstrated that leptospira interrogans serovar lai strain lai had a similar ability to adhere to and enter primary and immortal (thp-1 and j774a.1) macrophages from human and mouse, but its intracellular fate in human macrophages differed markedly from that in mouse. the leptospires resided within ...201019587003
proteome analysis of leptospira interrogans virulent strain.leptospirosis is a worldwide zoonotic infection of human and veterinary concern. caused by pathogenic spirochetes of the genus leptospira, the disease presents greater incidence in tropical and subtropical regions. the identification of proteins that could be involved in the bacteria host interactions may facilitate the search for immune protective antigens. we report the proteomic analysis of leptospira interrogans serovar pomona virulent strain lpf cultured from kidney and liver of infected ha ...200919590580
proteome-wide cellular protein concentrations of the human pathogen leptospira interrogans.mass-spectrometry-based methods for relative proteome quantification have broadly affected life science research. however, important research directions, particularly those involving mathematical modelling and simulation of biological processes, also critically depend on absolutely quantitative data--that is, knowledge of the concentration of the expressed proteins as a function of cellular state. until now, absolute protein concentration measurements of a considerable fraction of the proteome ( ...200919606093
leptospirosis research: fast, easy and reliable enumeration of mobile leptospires.leptospirosis caused by leptospira interrogans is the most widespread zoonosis and a major public health problem worldwide. based on light-scattering and absorption, quantification of leptospires using uv-vis spectroscopy was used as an indirect counting technique by measuring the optical density and comparing this to automated direct counting using a counting chamber in combination with imaging and analyzing software. two serovars, bangkok and copenhagenii, from log-phase growth were used for t ...200919621128
bayesian inference for within-herd prevalence of leptospira interrogans serovar hardjo using bulk milk antibody testing.leptospirosis is the most widespread zoonosis throughout the world and human mortality from severe disease forms is high even when optimal treatment is provided. leptospirosis is also one of the most common causes of reproductive losses in cattle worldwide and is associated with significant economic costs to the dairy farming industry. herds are tested for exposure to the causal organism either through serum testing of individual animals or through testing bulk milk samples. using serum results ...200919628639
tlr4- and tlr2-mediated b cell responses control the clearance of the bacterial pathogen, leptospira interrogans.leptospirosis is a widespread zoonosis caused by pathogenic leptospira interrogans that are transmitted by asymptomatic infected rodents. leptospiral lipoproteins and lps have been shown to stimulate murine cells via tlrs 2 and 4. host defense mechanisms remain obscure, although tlr4 has been shown to be involved in clearing leptospira. in this study, we show that double (tlr2 and tlr4) knockout (dko) mice rapidly died from severe hepatic and renal failure following leptospira inoculation. strik ...200919635914
a serological survey of leptospirosis in cattle of rural communities in the province of kwazulu-natal, south africa.a serological survey of leptospirosis in cattle originating from rural communities of the province of kwazulu-natal (kzn) in south africa was carried out between march 2001 and december 2003. the survey was designed as a 2-stage survey, using the local diptank as the primary sampling point. in total, 2021 animals from 379 diptanks in 33 magisterial districts were sampled and tested with the microscopic agglutination test (mat). the apparent prevalence at district level was adjusted for clusterin ...200919653519
crystal structure and acyl chain selectivity of escherichia coli lpxd, the n-acyltransferase of lipid a biosynthesis.lpxd catalyzes the third step of lipid a biosynthesis, the r-3-hydroxyacyl-acp-dependent n-acylation of udp-3-o-(acyl)-alpha-d-glucosamine, and is a target for new antibiotic development. here we report the 2.6 a crystal structure of the escherichia coli lpxd homotrimer (eclpxd). as is the case in chlamydia trachomatis lpxd (ctlxpd), each eclpxd chain consists of an n-terminal uridine-binding region, a left-handed parallel beta-helix (lbetah), and a c-terminal alpha-helical domain. the backbones ...200919655786
global proteome analysis of leptospira interrogans.comparative global proteome analyses were performed on leptospira interrogans serovar copenhageni grown under conventional in vitro conditions and those mimicking in vivo conditions (iron limitation and serum presence). proteomic analyses were conducted using itraq and lc-esi-tandem mass spectrometry complemented with two-dimensional gel electrophoresis and maldi-tof mass spectrometry. a total of 563 proteins were identified in this study. altered expression of 65 proteins, including upregulatio ...200919663501
innovations in host and microbial sialic acid biosynthesis revealed by phylogenomic prediction of nonulosonic acid structure.sialic acids (sias) are nonulosonic acid (nulo) sugars prominently displayed on vertebrate cells and occasionally mimicked by bacterial pathogens using homologous biosynthetic pathways. it has been suggested that sias were an animal innovation and later emerged in pathogens by convergent evolution or horizontal gene transfer. to better illuminate the evolutionary processes underlying the phenomenon of sia molecular mimicry, we performed phylogenomic analyses of biosynthetic pathways for sias and ...200919666579
an imprint method for detecting leptospires in the hamster model of vaccine-mediated immunity for leptospirosis.in determining the efficacy of new vaccine candidates for leptospirosis, the primary end point is death and an important secondary end point is sterilizing immunity. however, evaluation of this end point is often hampered by the time-consuming demands and complexity of methods such as culture isolation (ci). in this study, we evaluated the use of an imprint (or touch preparation) method (im) in detecting the presence of leptospires in tissues of hamsters infected with leptospira interrogans sero ...200919679685
wild boars as sources for infectious diseases in livestock and humans.wild boars (sus scrofa) are indigenous in many countries in the world. these free-living swine are known reservoirs for a number of viruses, bacteria and parasites that are transmissible to domestic animals and humans. changes of human habitation to suburban areas, increased use of lands for agricultural purposes, increased hunting activities and consumption of wild boar meat have increased the chances of exposure of wild boars to domestic animals and humans. wild boars can act as reservoirs for ...200919687039
immunoproteomic analysis of outer membrane proteins and extracellular proteins of actinobacillus pleuropneumoniae jl03 serotype 3.actinobacillus pleuropneumoniae is the causative agent of porcine contagious pleuropneumonia, a highly contagious respiratory infection in pigs, and all the 15 serotypes are able to cause disease. current vaccines including subunit vaccines could not provide satisfactory protection against a. pleuropneumoniae. in this study, the immunoproteomic approach was applied to the analysis of extracellular and outer membrane proteins of a. pleuropneumoniae jl03 serotype 3 for the identification of novel ...200919695095
a novel fibronectin type iii module binding motif identified on c-terminus of leptospira immunoglobulin-like protein, ligb.infection by pathogenic strains of leptospira hinges on the pathogen's ability to adhere to host cells via extracellular matrix such as fibronectin (fn). previously, the immunoglobulin-like domains of leptospira lig proteins were recognized as adhesins binding to n-terminal domain (ntd) and gelatin binding domain (gbd) of fn. in this study, we identified another fn-binding motif on the c-terminus of the leptospira adhesin ligb (ligbctv), residues 1708-1712 containing sequence lipad with a beta-s ...200919699715
immune response and prophylactic efficacy of smegmosomes in a hamster model of leptospirosis.leptospirosis is an important zoonotic disease worldwide. subunit vaccines are an attractive intervention strategy against this disease, but potent, non-toxic adjuvants are necessary components to any effective vaccine. among various adjuvant candidates, liposomes have garnered recent attention for their capacity as carriers of vaccines. in the present study we prepared novel liposomes using total polar lipids from the nonpathogenic bacterium, mycobacterium smegmatis (designated smegmosomes). th ...200919715780
disruption of the bmei0066 gene attenuates the virulence of brucella melitensis and decreases its stress tolerance.brucella melitensis is a facultative intracellular pathogen. an operon composed of bmei0066, which encodes a two-component response regulator cenr, and bmei0067, which encodes a camp-dependent protein kinase regulatory subunit, has been predicted to exist in many bacterial species. however, little is known about the function of this operon. in order to characterize this operon and assess its role in virulence, we constructed a marked deletion mutant of bmei0066. the mutant was less able to withs ...200919742243
development and validation of a real-time pcr for detection of pathogenic leptospira species in clinical materials.available serological diagnostics do not allow the confirmation of clinically suspected leptospirosis at the early acute phase of illness. several conventional and real-time pcrs for the early diagnosis of leptospirosis have been described but these have been incompletely evaluated. we developed a sybr green-based real-time pcr targeting secy and validated it according to international guidelines. to determine the analytical specificity, dna from 56 leptospira strains belonging to pathogenic, no ...200919763264
a microbiological and serological study of leptospirosis among pigs in the morogoro municipality, tanzania.serological and microbiological studies on leptospirosis in pigs from morogoro municipality, tanzania were carried out between october 2007 and may 2008. serum samples (n = 385) from apparently healthy pigs were tested by microscopic agglutination test for antibodies against live cultures of six known leptospira interrogans serovars: pomona, icterohaemorrhagiae, ballum, tarassovi, grippotyphosa and hardjo. significant positive titres were detected in 4.42% (17/385) of all the tested serum sample ...201019763865
functional analysis of the helicobacter pylori flagellar switch proteins.helicobacter pylori uses flagellum-mediated chemotaxis to promote infection. bacterial flagella change rotational direction by changing the state of the flagellar motor via a subcomplex referred to as the switch. intriguingly, the h. pylori genome encodes four switch complex proteins, flim, flin, fliy, and flig, instead of the more typical three of escherichia coli or bacillus subtilis. our goal was to examine whether and how all four switch proteins participate in flagellation. previous work de ...200919767432
molecular characterization of the pl40 protein in leptospira interrogans.leptospirosis is a widespread zoonotic disease caused by pathogenic leptospires. the identification of outer membrane proteins (omps) conserved among pathogenic leptospires, which are exposed on the leptospiral surface and expressed during mammalian infection, has become a major focus of leptospirosis research. pl40, a 40 kda protein coded by the la3744 gene in leptospira interrogans, was found to be unique to leptospira. triton x-114 fractionation and flow cytometry analyses indicate that pl40 ...200919767845
molecular analysis of leptospira spp. isolated from humans by restriction fragment length polymorphism, real-time pcr and pulsed-field gel electrophoresis.a total of 17 leptospira clinical strains isolated from humans in croatia were serologically and genetically analysed. for serovar identification, the microscopic agglutination test (mat) and pulsed-field gel electrophoresis (pfge) were used. to identify isolates on genomic species level, pcr-based restriction fragment length polymorphism (rflp) and real-time pcr were performed. mat revealed the following serogroup affinities: grippotyphosa (seven isolates), icterohaemorrhagiae (eight isolates) ...200919780841
increase in seroprevalence of canine leptospirosis and its risk factors, ontario 1998-2006.canine leptospirosis has been described as having re-emerged in north america around the mid-1990s, with a change in the epidemiology of the infecting serovars responsible for the disease emergence. a retrospective case-control study was conducted to examine the re-emergence of seroprevalent cases of canine leptospirosis in ontario using serology submission records from 1406 dogs from january 1, 1998 to december 31, 2006. the data collected [results of the microscopic agglutination test (mat), v ...200919794888
protein typing of major outer membrane lipoproteins from chinese pathogenic leptospira spp. and characterization of their immunogenicity.leptospirosis, caused by different leptospira species, is one of the most widespread zoonotic infections worldwide. here we expressed three major leptospiral lipoproteins and examined their immunogenicity. all the pathogenic leptospira strains tested possess the lipl21, lipl32 and lipl41 genes, but the latter two can be further divided into different gene types (lipl32-1, lipl32-2, lipl41-1, lipl41-2). microscopic agglutination test revealed that rlipls antisera had extensive cross-immunoaggluti ...200919796723
nationwide survey of leptospira antibodies in dogs in japan: results from microscopic agglutination test and enzyme-linked immunosorbent assay.leptospirosis is an infectious disease caused by leptospira interrogans sensu lato and is common in both humans and animals. in the present study, serum samples were collected from 801 dogs across all 47 prefectures in japan, and evaluated with a microscopic agglutination test (mat), using 5 major l. interrogans serovars (icterohaemorrhagiae, canicola, autumnalis, hebdomadis, and australis) as antigens, and an enzyme-linked immunosorbent assay (elisa) using recombinant ompl1 protein as the antig ...200919801899
leptospira interrogans binds to human cell surface receptors including proteoglycans.leptospirosis is a global public health problem, primarily in the tropical developing world. the pathogenic mechanisms of the causative agents, several members of the genus leptospira, have been underinvestigated. the exception to this trend has been the demonstration of the binding of pathogenic leptospires to the extracellular matrix (ecm) and its components. in this work, interactions of leptospira interrogans bacteria with mammalian cells, rather than the ecm, were examined. the bacteria bou ...200919805539
cryo-electron tomography elucidates the molecular architecture of treponema pallidum, the syphilis spirochete.cryo-electron tomography (cet) was used to examine the native cellular organization of treponema pallidum, the syphilis spirochete. t. pallidum cells appeared to form flat waves, did not contain an outer coat and, except for bulges over the basal bodies and widening in the vicinity of flagellar filaments, displayed a uniform periplasmic space. although the outer membrane (om) generally was smooth in contour, om extrusions and blebs frequently were observed, highlighting the structure's fluidity ...200919820083
[identification of immunoreactive antigens of leptospira interrogans].a batch of 28 llama (lama gama) sera from jujuy province in argentina was studied in order to identify immune reactive antigens to leptospira interrogans. different antigenic preparations from the bacterium were used to study the immune reactivity by the microagglutination (mat), elisa and western immunoblot tests. a control pool of positive bovine sera was used. all the llama sera were negative to mat as well as to elisa. two of the llama sera and the positive bovine sera pool rendered positive ...200919831309
visual proteomics of the human pathogen leptospira interrogans.systems biology conceptualizes biological systems as dynamic networks of interacting elements, whereby functionally important properties are thought to emerge from the structure of such networks. owing to the ubiquitous role of complexes of interacting proteins in biological systems, their subunit composition and temporal and spatial arrangement within the cell are of particular interest. 'visual proteomics' attempts to localize individual macromolecular complexes inside of intact cells by templ ...200919838170
destruction of spirochete borrelia burgdorferi round-body propagules (rbs) by the antibiotic tigecycline.persistence of tissue spirochetes of borrelia burgdorferi as helices and round bodies (rbs) explains many erythema-lyme disease symptoms. spirochete rbs (reproductive propagules also called coccoid bodies, globular bodies, spherical bodies, granules, cysts, l-forms, sphaeroplasts, or vesicles) are induced by environmental conditions unfavorable for growth. viable, they grow, move and reversibly convert into motile helices. reversible pleiomorphy was recorded in at least six spirochete genera (>1 ...200919843691
the crystal structure of the novobiocin biosynthetic enzyme novp: the first representative structure for the tylf o-methyltransferase superfamily.novp is an s-adenosyl-l-methionine-dependent o-methyltransferase that catalyzes the penultimate step in the biosynthesis of the aminocoumarin antibiotic novobiocin. specifically, it methylates at 4-oh of the noviose moiety, and the resultant methoxy group is important for the potency of the mature antibiotic: previous crystallographic studies have shown that this group interacts directly with the target enzyme dna gyrase, which is a validated drug target. we have determined the high-resolution c ...201019857499
the crystal structure of the novobiocin biosynthetic enzyme novp: the first representative structure for the tylf o-methyltransferase superfamily.novp is an s-adenosyl-l-methionine-dependent o-methyltransferase that catalyzes the penultimate step in the biosynthesis of the aminocoumarin antibiotic novobiocin. specifically, it methylates at 4-oh of the noviose moiety, and the resultant methoxy group is important for the potency of the mature antibiotic: previous crystallographic studies have shown that this group interacts directly with the target enzyme dna gyrase, which is a validated drug target. we have determined the high-resolution c ...201019857499
functional characterization of borrelia spielmanii outer surface proteins that interact with distinct members of the human factor h protein family and with plasminogen.acquisition of complement regulator factor h (cfh) and factor h-like protein 1 (cfhl1) from human serum enables borrelia spielmanii, one of the etiological agents of lyme disease, to evade complement-mediated killing by the human host. up to three distinct complement regulator-acquiring surface proteins (crasps) may be expressed by serum-resistant b. spielmanii, each exhibiting an affinity for cfh and/or cfhl1. here, we describe the functional characterization of the 15-kda crasps of b. spielman ...201019858303
functional characterization of borrelia spielmanii outer surface proteins that interact with distinct members of the human factor h protein family and with plasminogen.acquisition of complement regulator factor h (cfh) and factor h-like protein 1 (cfhl1) from human serum enables borrelia spielmanii, one of the etiological agents of lyme disease, to evade complement-mediated killing by the human host. up to three distinct complement regulator-acquiring surface proteins (crasps) may be expressed by serum-resistant b. spielmanii, each exhibiting an affinity for cfh and/or cfhl1. here, we describe the functional characterization of the 15-kda crasps of b. spielman ...201019858303
the pure cultivation of spirochaeta icterohaemorrhagiae (inada).pure cultures of the spirochaetal causative agent of the disease known as weil's disease, or febrile icterus, in japan, have been obtained by us in a solid, a semisolid, and a fluid medium. the spirochaeta thus isolated remains pathogenic for guinea pigs for many generations. up to the present time we have succeeded through the courtesy of professor nagayo, dr. konuma, and dr. ishihara, in cultivating three different strains. the spirochaeta is a facultative anaerobe. the solid and semisolid cul ...191619868006
the prophylaxis of weil's disease (spirochaetosis icterohaemorrhagica).we have already described briefly the portals of entry and of excretion of the pathogenic spirochetes. we may mention here that we have twice prevented epidemics by disinfection of the ground and the removal of the inundated water in certain places in coal mines. in one mine 19 out of 50 workmen, and in another 9 out of 30 workmen came down with weil's disease in about 2 weeks. we have already pointed out that the period during which the pathogenic spirochetes are excreted in the urine continues ...191619868055
the serum treatment of weil's disease (spirochaetosis icterohaemorrhagica).horses immunized with cultures of spirochaeta icterohaemorrhagiae yield an immune serum having therapeutic properties. with rare exceptions the serum destroys completely the spirochetes contained in the circulating blood. the development of antibodies is promoted by the serum injections. the number of spirochetes in the organs is reduced by the treatment. secondary manifestations due to the serum are slight and disappear promptly. the ultimate effects of the serum treatment on the symptoms and f ...191619868056
spirochaeta icterohaemorrhagiae in american wild rats and its relation to the japanese and european strains : first paper.the principal points brought out in the present article are the following. 1. wild rats captured in this country carry in their kidneys a spirochete which possesses the morphological and pathogenic properties characteristic of spirochata icterohamorrhagia discovered by inada in the japanese form of infectious jaundice. 2. cultures of the american, belgian, and japanese strains of the spirochete were obtained by a special technique described, the first two strains having been cultivated artificia ...191719868121
the distribution in the human body of spirochaeta icterohaemorrhagiae. 191719868152
the rat as a carrier of spirochaeta icterohaemorrhagiae, the causative agent of weil's disease (spirochaetosis icterohaemorrhagica).1. on the basis of these findings, we conclude that the extermination of rats and field mice is a highly important prophylactic measure against weil's disease. 2. the chemical composition of soil and water plays animportant part in the development of spirochoeta icterohoemorrhagioe, and consequently in the spread of the disease of which it is the causative agent.191719868153
distribution of spirochaeta icterohaemorrhagiae in the organs after intravenous serum treatment.on the basis of these findings we believe that we are justified in saying that the immune serum of weil's disease is capable of destroying the spirochetes found within the organs in man, with the exception of the kidneys, and that the action of the serum upon the spirochetes is spirochetolytic and spirocheticidal. the scattered spirochetes in the kidney, on the other hand, are resistant to the action of the immune serum. the spirochetes disappear almost completely from the organs during the conv ...191819868206
morphological characteristics and nomenclature of leptospira (spirochaeta) icterohaemorrhagiae (inada and ido).the present study deals with the morphology and systematic position of the causative agent of infectious jaundice. there are several features which are not found in any of the hitherto known genera of spirochaetoidea which led me to give this organism an independent generic name, leptospira, denoting the peculiar minute elementary spirals running throughout the body. the absence of a definite terminal flagellum or any flagella, and the remarkable flexibility of the terminal or caudal portion of ...191819868227
further study on the cultural conditions of leptospira (spirochaeta) icterohaemorrhagiae.1. the presence of suitable animal or human serum is essential for the cultivation of leptospira icterohaemorrhagiae. 2. the nutrient value of serum is considerably reduced by heating to 60 degrees c. for 30 minutes and is destroyed by boiling (100 degrees c). filtration through a berkefeld filter does not diminish the nutrient value of the serum. 3. the cultural value of different animal sera varies considerably. it is entirely absent from the sera of the rat and the pig. the sera of the rabbit ...191819868228
the survival of leptospira (spirochaeta) icterohaemorrhagiae in nature; observations concerning microchemical reactions and intermediary hosts.1. leptospira icterohaemorrhagiae is unable to grow in the urine, either with or without the addition of suitable culture ingredients, the acidity of the urine being detrimental to the growth. it survives less than 24 hours, unless the urine is neutralized or slightly alkalized, when the period of survival is somewhat longer. if suitable nutrient ingredients are added to the neutralized or slightly alkalized urine, the organism is able to grow for about 10 days, after which multiplication ceases ...191819868229
spirochaeta hebdomadis, the causative agent of seven day fever (nanukayami) : first paper.a new species of spirochete which we have called spirochaeta hebdomadis has been described as the specific etiological agent of seven day fever, a disease prevailing in the autumn in fukuoka and other parts of japan. this spirochete is distinguishable from spirochaeta icterohaemorrhagiae to which it presents certain similarities. young guinea pigs are susceptible to inoculation with the blood of patients and to pure cultures of the spirochete, and those developing infection exhibit definite symp ...191819868269
etiology of yellow fever : ii. transmission experiments on yellow fever.by injecting into guinea pigs the blood of yellow fever cases occurring in guayaquil a group of symptoms and lesions closely resembling those observed in human yellow fever were induced in a limited number of instances. of 74 guinea pigs inoculated with specimens of blood from 27 cases of yellow fever, 8, representing 6 cases, came down with the symptoms; namely, a marked rise of temperature after a period of incubation averaging 3 to 6 days, with simultaneous suffusion of the capillaries, parti ...191919868337
etiology of yellow fever : iii. symptomatology and pathological findings in animals experimentally infected.studies are reported on the type of disease induced in guinea pigs, dogs, and monkeys by inoculating them (1) with the blood or organ emulsions of guinea pigs or other susceptible animals experimentally infected with leptospira icteroides, and (2) with a pure culture of the organism. particular attention has been given in these experiments to the clinical features of the experimental infection in the various animals and to the pathological changes resulting from the infection. the symptoms and p ...191919868338
etiology of yellow fever : iv. the acquired immunity of guinea pigs against leptospira icteroides after the inoculation of blood of yellow fever patients.the majority of guinea pigs inoculated with the blood of yellow fever patients escaped a fatal infection. there were a number of instances in which the inoculation of yellow fever blood induced in these animals a temporary febrile reaction on the 4th or 5th day, followed in some cases by slight jaundice, but with a rapid return to normal. most of these guinea pigs when later inoculated with an organ emulsion of a passage strain of leptospira icteroides resisted the infection. on the other hand, ...191919868341
etiology of yellow fever : vi. cultivation, morphology, virulence, and biological properties of leptospira icteroides.by the employment of methods designed to promote the growth both of aerobic and anaerobic organisms, particularly those belonging to the class of spirochetes, it was possible to obtain a pure culture of a delicate organism, the morphological features of which place it in the genus leptospira. on three occasions, that is, from three out of eleven cases of yellow fever, the organism was directly cultivated. these three strains were found to induce the characteristic symptoms and lesions when teste ...191919868342
etiology of yellow fever : v. properties of blood serum of yellow fever patients in relation to leptospira icteroides.the serum from a number of persons recovering from yellow fever in guayaquil was studied with a view to establishing its possible immunological relationship with a strain of leptospira icteroides derived from one of the yellow fever patients. for this purpose the serum of convalescents was mixed either with an organ emulsion of a passage strain, or with a culture of the organism, and inoculated intraperitoneally into guinea pigs. the pfeiffer reaction was first studied, and then the animals were ...191919868347
etiology of yellow fever : vii. demonstration of leptospira icteroides in the blood, tissues, and urine of yellow fever patients and of animals experimentally infected with the organism.examinations of fresh blood from yellow fever patients by means of the dark-field microscope, made in more than twenty-seven cases, revealed in three cases the presence of leptospira icteroides. in no instance was a large number of organisms found, a long search being required before one was encountered. the injection of the blood into guinea pigs from two of the three positive cases induced in the animals a fatal infection, while the blood from the third positive case failed to infect the guine ...191919868352
etiology of yellow fever : viii. presence of a leptospira in wild animals in guayaquil and its relation to leptospira icterohaemorrhagiae and leptospira icteroides.by the inoculation of guinea pigs intraperitoneally with the emulsions of kidneys from wild rats and mice captured in guayaquil, it was found that 67 per cent of the wild rats tested harbored in their kidneys a leptospira which produced in guinea pigs symptoms and lesions identical with those produced by leptospira icterohamorrhagia derived either from patients suffering from infectious jaundice in japan or europe, or from wild rats caught in new york. immune sera were prepared in rabbits by inj ...191919868353
etiology of yellow fever : ix. mosquitoes in relation to yellow fever.the foregoing experiments show that symptoms and lesions closely resembling those of yellow fever in man may be induced in guinea pigs by the bite of female stegomyias that have previously sucked the blood of a yellow fever patient or of an animal experimentally infected with leptospira icteroides. with mosquitoes infected directly from a yellow fever patient the infectivity seems to become manifest after a longer period of incubation than with those infected with the animal blood. in the former ...191919868367
etiology of yellow fever : x. comparative immunological studies on leptospira icteroides and leptospira icterohaemoorrhagiae.it has been previously reported that a filterable microorganism belonging to the genus leptospira has been recovered from the blood or organs of human beings suffering from the disease known as yellow fever in guayaquil, and that the organism, which has been termed leptospira icteroides, induces in certain experimental animals the characteristic symptoms and lesions observed in the patients from whom it was isolated. it has also been previously shown that the serum from patients recovering from ...192019868393
etiology of yellow fever : xi. serum treatment of animals infected with leptospira icteroides.the use ot a polyvalent immune serum ot nign potency in tne treatment of an experimental infection of guinea pigs with leptospira icteroides was found to be of definite advantage in checking the progress of the infection. when administered during the period of incubation the serum was found capable of completely preventing the development of the disease, although on subsequent examination hemorrhagic lesions of greater or less number and extent were found in the lungs of the guinea pigs which su ...192019868394
etiology of yellow fever : xii. chemotherapy versus serotherapy in experimental infection with leptospira icteroides.in several series of experiments guinea pigs were variously infected with different amounts of leptospira icteroides, either in the form of culture, organ emulsion from infected guinea pigs, or a mixture of both. the infecting materials were of different grades of virulence; in some series the amount given was near a single lethal dose, in others a subminimum lethal dose was given, i.e. causing mild infection with recovery in the majority of animals, and in still others the animals were injected ...192019868452
immunological studies with a strain of leptospira isolated from a case of yellow fever in merida, yucatan.identification of the leptospira isolated from a case of yellow fever in merida was accomplished by means of an anti-icteroides immune serum prepared in a horse with several guayaquil strains of leptospira icteroides. the immune serum showed a protective action of high titer against the merida strain, thus establishing its efficacy as a therapeutic agent against this strain. polyvalent anti-icteroides immune serum prepared in the horse or monovalent anti-icteroides immune serums prepared in the ...192019868465
experimental studies on yellow fever in northern peru.fourteen typical cases of yellow fever were studied in northern peru during an epidemic occurring in 1920, nine in payta in march and april, and five in morropon and piura in april and may. the method of investigation was similar to that previously employed, but as the laboratory facilities were very meager certain changes were required. although in payta the work was handicapped by the lack of electric light, the scarcity of water and animal food, the unsuitability of the guinea pigs for inocul ...192119868492
immunology of the peruvian strains of leptospira icteroides.serum from yellow fever convalescents from payta, piura, and morropon gave a positive pfeiffer reaction with the strains of leptospira icteroides isolated in guayaquil and merida. the serum also protected the guinea pigs from these strains in the majority of instances. the pfeiffer reaction was complete with all recent convalescents (7 to 36 days) but slight or partial in some instances with serum derived from individuals who had had the attack of yellow fever 10 months previously. the virulence ...192119868493
etiology of yellow fever : xiii. behavior of the heart in the experimental infection of guinea pigs and monkeys with leptospira icteroides and leptospira icterohaemorrhagiae.1. slowing of the heart occurred in monkeys and guinea pigs during the febrile period of the experimental infection due to leptospira icteroides. a similar reaction took place in animals inoculated with leptospira icterohoemorrhagioe. 2. the mechanism of slowing was usually due to slowing of the whole heart. 3. once incomplete heart block was seen. changes in the ventricular complex occurred four times.192119868529
etiology of yellow fever : xiv. duration of the protective effect of anti-icteroides immune serum after subcutaneous inoculation into animals.analysis of the records of instances in which non-immune persons contracted yellow fever notwithstanding vaccination shows that the onset of disease occurs soon after vaccination, the longest period being 13 days. since the average incubation period in yellow fever is 6 days, it seems that infection must have taken place in some instances during the period while protection was developing. these instances led to a study of the possibility of immediate protection by means of the anti-icteroides se ...192219868677
a comparison of the spirochete of yellow fever (leptospira icteroides noguchi) with the leptospira of weil's disease.the most noteworthy point observed in our studies is the extraordinary duration of life and the relatively meagre requirements for sustenance of leptospira icteroides. it is conceivable that under natural conditions opportunities might arise for the prolonged existence of leptospira icteroides, so that possibly after a lapse of years, the disease might reappear without introduction from outside. at any rate, the great viability of leptospira icteroides must be considered in this connection. a de ...192819869411
lsa63, a newly identified surface protein of leptospira interrogans binds laminin and collagen iv.leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease that affects populations worldwide. we have identified in proteomic studies a protein that is encoded by the gene lic10314 and expressed in virulent strain of l. interrogans serovar pomona. this protein was predicted to be surface exposed by psort program and contains a p83/100 domain identified by blast analysis that is conserved in protein antigens of several strains of borrelia and treponema spp. the proteins ...201019879894
high-coverage proteome analysis reveals the first insight of protein modification systems in the pathogenic spirochete leptospira interrogans.leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus leptospira that infects humans and a wide range of animals. by combining computational prediction and high-accuracy tandem mass spectra, we revised the genome annotation of leptospira interrogans serovar lai, a free-living pathogenic spirochete responsible for leptospirosis, providing substantial peptide evidence for novel genes and new gene boundaries. subsequently, we presented a high-coverage proteome ...201019918266
serological and genetic analysis of leptospirosis in patients with acute febrile illness in kandy, sri lanka.leptospirosis has emerged as an important infectious disease in sri lanka and little information is available on circulating leptospiral species and serogroups in this country. therefore, we studied circulating leptospiral species and serogroups in patients with acute febrile illness using polymerase chain reaction and the microscopic agglutination test, respectively. anti-leptospiral antibodies were detected in 26 of 107 serum samples studied (24.3%). the predominant reacting serogroups were se ...200919934544
evolutionary implication of outer membrane lipoprotein-encoding genes ompl1, upl32 and lipl41 of pathogenic leptospira species.leptospirosis is recognized as the most widespread zoonosis with a global distribution. in this study, the antigenic variation in leptospira interrogans and leptospira borgpetersenii isolated from human urine and field rat kidney was preliminarily confirmed by microscopic agglutination test using monoclonal antibodies, and was further subjected to amplification and identification of outer membrane lipoproteins with structural gene variation. sequence similarity analysis revealed that these prote ...200919944382
cohesion group approach for evolutionary analysis of aspartokinase, an enzyme that feeds a branched network of many biochemical pathways.aspartokinase (ask) exists within a variable network that supports the synthesis of 9 amino acids and a number of other important metabolites. lysine, isoleucine, aromatic amino acids, and dipicolinate may arise from the ask network or from alternative pathways. ask proteins were subjected to cohesion group analysis, a methodology that sorts a given protein assemblage into groups in which evolutionary continuity is assured. two subhomology divisions, ask(alpha) and ask(beta), have been recognize ...200919946135
a pair of ligation-independent escherichia coli expression vectors for rapid addition of a polyhistidine affinity tag to the n- or c-termini of recombinant proteins.6x his tag is one of the most widely used affinity fusion tags that facilitates detection and purification of recombinant proteins. however, the location of this tag within a particular type of protein may influence the expression, solubility, and bioactivity of the protein, and the optimal location needs to be determined experimentally. to provide a tool for rapid generation of 6x his tags at the n- or c-terminus of any recombinant protein, we have constructed a pair of escherichia coli express ...200919949695
multilocus sequence analysis for typing leptospira interrogans and leptospira kirschneri.fifty-three strains belonging to the pathogenic species leptospira interrogans and leptospira kirschneri were analyzed by multilocus sequence analysis. the species formed two distinct branches. in the l. interrogans branch, the phylogenetic tree clustered the strains into three subgroups. genogroups and serogroups were superimposed but not strictly.201019955271
evidence that two atp-dependent (lon) proteases in borrelia burgdorferi serve different functions.the canonical atp-dependent protease lon participates in an assortment of biological processes in bacteria, including the catalysis of damaged or senescent proteins and short-lived regulatory proteins. borrelia spirochetes are unusual in that they code for two putative atp-dependent lon homologs, lon-1 and lon-2. borrelia burgdorferi, the etiologic agent of lyme disease, is transmitted through the blood feeding of ixodes ticks. previous work in our laboratory reported that b. burgdorferi lon-1 i ...200919956677
epidemic dynamics at the human-animal interface.few infectious diseases are entirely human-specific: most human pathogens also circulate in animals or else originated in nonhuman hosts. influenza, plague, and trypanosomiasis are classic examples of zoonotic infections that transmit from animals to humans. the multihost ecology of zoonoses leads to complex dynamics, and analytical tools, such as mathematical modeling, are vital to the development of effective control policies and research agendas. much attention has focused on modeling pathoge ...200919965751
mechanism of substrate recognition and insight into feedback inhibition of homocitrate synthase from thermus thermophilus.homocitrate synthase (hcs) catalyzes aldol-type condensation of acetyl coenzyme a (acetyl-coa) and alpha-ketoglutarate (alpha-kg) to synthesize homocitrate (hc), which is the first and committed step in the lysine biosynthetic pathway through alpha-aminoadipate. as known in most enzymes catalyzing the first reactions in amino acid biosynthetic pathways, hcs is regulated via feedback inhibition by the end product, lysine. here, we determined the crystal structures of hcs from thermus thermophilus ...201019996101
mechanism of substrate recognition and insight into feedback inhibition of homocitrate synthase from thermus thermophilus.homocitrate synthase (hcs) catalyzes aldol-type condensation of acetyl coenzyme a (acetyl-coa) and alpha-ketoglutarate (alpha-kg) to synthesize homocitrate (hc), which is the first and committed step in the lysine biosynthetic pathway through alpha-aminoadipate. as known in most enzymes catalyzing the first reactions in amino acid biosynthetic pathways, hcs is regulated via feedback inhibition by the end product, lysine. here, we determined the crystal structures of hcs from thermus thermophilus ...201019996101
comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature.leptospirosis is a global zoonosis affecting millions of people annually. transcriptional changes in response to temperature were previously investigated using microarrays to identify genes potentially expressed upon host entry. past studies found that various leptospiral outer membrane proteins are differentially expressed at different temperatures. however, our microarray studies highlighted a divergence between protein abundance and transcript levels for some proteins. given the abundance of ...200919997626
inactivation of the fliy gene encoding a flagellar motor switch protein attenuates mobility and virulence of leptospira interrogans strain lai.pathogenic leptospira species cause leptospirosis, a zoonotic disease of global importance. the spirochete displays active rotative mobility which may contribute to invasion and diffusion of the pathogen in hosts. fliy is a flagellar motor switch protein that controls flagellar motor direction in other microbes, but its role in leptospira, and paricularly in pathogenicity remains unknown.200920003186
detection of leptospira in urine using anti-leptospira-coated gold nanoparticles.serological assays for antibody detection have been widely used for leptospirosis diagnosis. however, antibody is usually undetectable during the first week after infection. detection of leptospira dna can be done by pcr but this technique requires special equipments and the cost is still relatively high. here we demonstrate that gold nanoparticles can be used to facilitate leptospira detection. gold nanoparticles were coated with rabbit antibody specific to leptospira interrogans serovar bratis ...201120015548
evaluation of a recombinant ligb protein of leptospira interrogans serovar canicola in an enzyme-linked immunosorbent assay for the serodiagnosis of bovine leptospirosis.a recombinant leptospiral lipoprotein, ligb, was evaluated for use in the diagnosis of bovine leptospirosis by enzyme-linked immunosorbent assay (rligb igg elisa). the standard reference test (microscopic agglutination test, mat) of 200 serum samples from cattle suspected of leptospirosis showed that 95 (47.5%) samples had positive agglutination titres, which ranged from 100 to 1600. in rligb igg elisa, 49% of the samples were positive. sensitivity of igg elisa for 95 bovine sera, which had mat ...201020022618
lipl53, a temperature regulated protein from leptospira interrogans that binds to extracellular matrix molecules.the regulation of gene expression by environmental signals, such as temperature and osmolarity, has been correlated with virulence. in this study, we characterize the protein lipl53 from leptospira interrogans, previously shown to react with serum sample of individual diagnosed with leptospirosis and to be up-regulated by shift to physiological osmolarity. the recombinant protein was expressed in escherichia coli system, in insoluble form, recovered by urea solubilization and further refolded by ...201020026283
risk factors associated with the seroprevalence of leptospirosis, amongst at-risk groups in and around tanga city, tanzania.the epidemiological status of human leptospirosis in tanzania has not been well defined because of a general lack of awareness of the disease and difficulties in its diagnosis. a cross-sectional seroprevalence study, using the microscopic agglutination test with a threshold titre of 1 : 160, was therefore conducted, among various occupational groups from tanga city, in november 2005. of the 199 subjects investigated, 30 (15.1%) were found to have antibodies that reacted with antigens from at lea ...200920030995
functional characterization of gdp-mannose pyrophosphorylase from leptospira interrogans serovar copenhageni.leptospira interrogans synthesizes a range of mannose-containing glycoconjugates relevant for its virulence. a prerequisite in the synthesis is the availability of the gdp-mannose, produced from mannose-1-phosphate and gtp in a reaction catalyzed by gdp-mannose pyrophosphorylase. the gene coding for a putative enzyme in l. interrogans was expressed in escherichia coli bl21(de3). the identity of this enzyme was confirmed by electrospray-mass spectroscopy, edman sequencing and immunological assays ...201020035319
ompa-like protein loa22 from leptospira interrogans serovar lai is cytotoxic to cultured rat renal cells and promotes inflammatory responses.leptospirosis renal disease is one of the common clinical manifestations of leptospirosis, including acute renal failure and tubulointerstitial nephritis. outer membrane protein a-like protein loa22 is a lipoprotein from leptospira interrogans and has been suggested to be a corresponding virulence factor. however, the role of loa22 in leptospiral nephropathy is not yet understood. in the present study, we constructed a vector and artificially expressed loa22 in escherichia coli bl21(de)plyss cel ...201020043049
lack of demonstrable memory t cell responses in humans who have spontaneously recovered from leptospirosis in the peruvian amazon.background. we tested the hypothesis that patients who have recovered from leptospirosis have peripheral blood memory t cells that are specific for leptospira or leptospira protein antigens. methods. peripheral blood mononuclear cells (pbmcs) were obtained from patients who had recovered from leptospirosis, as well as from control individuals. pbmcs were assessed for in vitro proliferation, phenotyping, and cytokine production after stimulation with different strains of leptospira, recombinant l ...201020053135
retrospective evaluation of idiopathic hematuria and associated pathology in grant's gazelles (gazella granti): 10 cases.ten cases of hematuria in grant's gazelle (gazella granti) (two male and eight female) from five institutions were examined and the clinicopathologic data summarized. five gazelles died spontaneously and five were euthanized. all gazelles had marked hematuria without pyuria. mean age at the onset of clinical signs and time of euthanasia or death was 5.0 +/- 1.4 yr and 8.2 +/- 3.7 yr, respectively. the severity of clinical signs with hematuria ranged from episodes of chronic intermittent hematuri ...200920063809
experimental leptospirosis in capybaras (hydrochaeris hydrochaeris) infected with leptospira interrogans serovar pomona.capybara (hydrochaeris hydrochaeris), the largest rodent in the world, is widely distributed in south america. these animals live in areas with abundant water, which makes them a potential reservoir for leptospira. the objective of this study was to investigate seroconversion, leptospiremia, and leptospiruria in capybaras experimentally infected with a virulent strain of leptospira interrogans serovar pomona. seven capybaras were used: one control and six infected. agglutinins against serovar po ...200920063819
identification and characterization of ompa-like proteins as novel vaccine candidates for leptospirosis.leptospira is an important infectious gram-negative bacterium causing leptospirosis in mammals. outer membrane proteins (omps) are key molecules in the interface between the cell and its environment. a group of putative leptospiral outer membrane proteins with an ompa-like domain, comprising lp0056, lp0222, lp3615, lp3685, lp4337 and lbp328, were identified by bioinformatic methods and expressed as gst-tag fusion proteins. all these recombinant proteins were screened for immune-protective potent ...201020064477
of guinea pigs and men--an unusual case of jaundice.a 21-year-old male presented at the emergency room with jaundice, itching, dry cough, malaise and weight loss of 10 kg during the preceding four weeks. eighteen months earlier, the patient had suffered an automobile accident leading to polytrauma. serological markers for viral or other causes of hepatitis were absent. for suspected secondary sclerosing cholangitis, ultrasound and ercp were performed but failed to reveal pathological findings. a liver biopsy showed cholestatic liver disease witho ...201020072994
leptospira wolffii, a potential new pathogenic leptospira species detected in human, sheep and dog.leptospirosis is the most common zoonotic disease, which is transmitted to humans through contaminated water or direct exposure to the urine of infected animals. in this study, the presence and prevalence of leptospira species in the infected samples of human (n=369) and sheep (n=75) sera and also dogs' urine (n=150), collected from four provinces of iran, were investigated by using nested-pcr/rflp assay followed by sequencing analysis. nested-pcr assay detected that 98/369 (26.5%) human, 13/75 ...201020074666
differential cytokine gene expression according to outcome in a hamster model of leptospirosis.parameters predicting the evolution of leptospirosis would be useful for clinicians, as well as to better understand severe leptospirosis, but are scarce and rarely validated. because severe leptospirosis includes septic shock, similarities with predictors evidenced for sepsis and septic shock were studied in a hamster model.201020076757
cytopathic effect in bhk 21 (c13) cells inoculated with leptospira interrogans serovar pomona isolated from a porcine abortion. 200920085192
burkholderia cenocepacia creates an intramacrophage replication niche in zebrafish embryos, followed by bacterial dissemination and establishment of systemic infection.bacteria belonging to the "burkholderia cepacia complex" (bcc) often cause fatal pulmonary infections in cystic fibrosis patients, yet little is know about the underlying molecular mechanisms. these gram-negative bacteria can adopt an intracellular lifestyle, although their ability to replicate intracellularly has been difficult to demonstrate. here we show that bcc bacteria survive and multiply in macrophages of zebrafish embryos. local dissemination by nonlytic release from infected cells was ...201020086083
surveys for disease agents in introduced elk in arkansas and kentucky.surveys for disease agents were conducted in introduced free-ranging elk (cervus elaphus nelsoni) in arkansas and kentucky. elk had been captured in colorado and nebraska and released in arkansas during 1981-1985. from 1997 through 2002 elk were captured in arizona, kansas, north dakota, new mexico, oregon, and utah and released in southeastern kentucky. specimens were collected from 170 hunter-killed elk in arkansas during 1998-2006, and 44 elk in kentucky during 2001-2004. significant findings ...201020090032
serological patterns of brucellosis, leptospirosis and q fever in bos indicus cattle in cameroon.brucellosis, leptospirosis and q fever are important infections of livestock causing a range of clinical conditions including abortions and reduced fertility. in addition, they are all important zoonotic infections infecting those who work with livestock and those who consume livestock related products such as milk, producing non-specific symptoms including fever, that are often misdiagnosed and that can lead to severe chronic disease. this study used banked sera from the adamawa region of camer ...201020098670
global transcriptomic response of leptospira interrogans serovar copenhageni upon exposure to serum.leptospirosis is a zoonosis of worldwide distribution caused by infection with pathogenic serovars of leptospira spp. the most common species, l. interrogans, can survive in the environment for lengthy periods of time in between infection of mammalian hosts. transmission of pathogenic leptospira to humans mostly occurs through abraded skin or mucosal surfaces after direct or indirect contact with infected animals or contaminated soil or water. the spirochete then spreads hematogenously, resultin ...201020113507
severe leptospirosis in hospitalized patients, guadeloupe.we evaluated prognostic factors for leptospirosis in 168 consecutive hospitalized patients in guadeloupe. factors independently associated with severity included chronic hypertension or chronic alcoholism, late initiation of antibacterial therapy, abnormal chest auscultation results, icterus, oligoanuria, disorders of consciousness, elevated aspartate aminotransferase levels, hyperamylasemia, and leptospira interrogans serovar icterohemorrhagiae.201020113574
the contribution of bats to leptospirosis transmission in sao paulo city, brazil.the biodiversity of potential leptospiral reservoir hosts is lower in urban than in rural environments. previous data indicate the potential for bats to act as carriers of leptospira in regions such as the amazon of south america and in australia. yet, little is known about the contribution of bats to leptospirosis in urban environments in south america. this study aimed to test the hypothesis that bats infected with leptospira are sources of leptospirosis transmission to humans in são paulo cit ...201020134010
leptospiral endostatin-like protein a is a bacterial cell surface receptor for human plasminogen.the spirochete leptospira interrogans is a highly invasive pathogen of worldwide public health importance. studies from our laboratories and another have demonstrated that l. interrogans can acquire host plasminogen on its surface. exogenous plasminogen activators can then convert bound plasminogen into the functionally active protease plasmin. in this study, we extend upon those observations and report that leptospiral endostatin-like protein a (lena) binds human plasminogen in a dose-dependent ...201020160016
decrease of plasma platelet-activating factor acetylhydrolase activity in lipopolysaccharide induced mongolian gerbil sepsis model.platelet-activating factor (paf) plays an important role in the pathogenesis of sepsis, and the level of plasma paf acetylhydrolase (ppaf-ah), which inactivates paf, decreases in sepsis patients except for the sepsis caused by severe leptospirosis. usually, increase of ppaf-ah activity was observed in lipopolysaccharide (lps)-induced syrian hamster and rat sepsis models, while contradictory effects were reported for mouse model in different studies. here, we demonstrated the in vivo effects of l ...201020169191
[a case of severe leptospirosis infection (weil's disease) in tokyo].we report a case of severe leptospirosis infection (weil's disease) in tokyo. a 54-year-old man admitted on september 14, 2006, for a 5-day inability to walk due to severe progressive bilateral leg pain, shoulder pain, and fever exhibited jaundice, conjunctival suffusion, hypoxia, and grasping pain in the bilateral leg muscles. laboratory findings showed severe liver damage, renal failure, leukocytosis, anemia, thrombocytopenia, elevated crp, hyponatremia, and hypokalemia. chest x-ray imaging sh ...201020170016
analysis of 16s rdna sequences from pathogenic leptospira serovars and use of single nucleotide polymorphisms for rapid speciation by d-hplc.leptospira have a worldwide distribution and include important zoonotic pathogens yet diagnosis and differentiation still tend to rely on traditional bacteriological and serological approaches. in this study a 1.3 kb fragment of the rrs gene (16s rdna) was sequenced from a panel of 22 control strains, representing serovars within the pathogenic species leptospira interrogans, leptospiraborgpetersenii, and leptospirakirschneri, to identify single nucleotide polymorphisms (snps). these were identi ...201020172572
inactivation of a putative flagellar motor switch protein flig1 prevents borrelia burgdorferi from swimming in highly viscous media and blocks its infectivity.the flagellar motor switch complex protein flig plays an essential role in flagella biosynthesis and motility. in most motile bacteria, only one flig homologue is present in the genome. however, several spirochete species have two putative flig genes (referred to as flig1 and flig2) and their roles in flagella assembly and motility remain unknown. in this report, the lyme disease spirochete borrelia burgdorferi was used as a genetic model to investigate the roles of these two flig homologues. it ...201020180908
asymptomatic renal colonization of humans in the peruvian amazon by leptospira.renal carriage and shedding of leptospires is characteristic of carrier or maintenance animal hosts. sporadic reports indicate that after infection, humans may excrete leptospires for extended periods. we hypothesized that, like mammalian reservoir hosts, humans develop asymptomatic leptospiruria in settings of high disease transmission such as the peruvian amazon.201020186328
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