Until recently, Histoplasma capsulatum was believed to harbour three varieties, var. capsulatum (chiefly a New World human pathogen), var. duboisii (an African human pathogen) and var. farciminosum ...(an Old World horse pathogen), which varied in clinical manifestations and geographical distribution. We analysed the phylogenetic relationships of 137 individuals representing the three varieties from six continents using DNA sequence variation in four independent protein‐coding genes. At least eight clades were idengified: (i) North American class 1 clade; (ii) North American class 2 clade; (iii) Latin American group A clade; (iv) Latin American group B clade; (v) Australian clade; (vi) Netherlands (Indonesian?) clade; (vii) Eurasian clade and (viii) African clade. Seven of eight clades represented genetically isolated groups that may be recognized as phylogenetic species. The sole exception was the Eurasian clade which originated from within the Latin American group A clade. The phylogenetic relationships among the clades made a star phylogeny. Histoplasma capsulatum var. capsulatum individuals were found in all eight clades. The African clade included all of the H. capsulatum var. duboisii individuals as well as individuals of the other two varieties. The 13 individuals of var. farciminosum were distributed among three phylogenetic species. These findings suggest that the three varieties of Histoplasma are phylogenetically meaningless. Instead we have to recognize the existence of genetically distinct geographical populations or phylogenetic species. Combining DNA substitution rates of protein‐coding genes with the phylogeny suggests that the radiation of Histoplasma started between 3 and 13 million years ago in Latin America.
Campylobacter coli is a food-borne pathogen associated increasingly with human gastroenteritis. C. coli has a high prevalence in swine, but is isolated also from cattle and poultry. Multilocus ...sequence typing (MLST) systems have been developed to differentiate C. coli strains. Although substantial allelic diversity was identified across all seven C. coli MLST loci, no correlations were made in two previous studies between allele or sequence type (ST) and the source of the organism. However, this may be due to either the relatively small number or the low diversity of C. coli strains used to validate both MLST studies. This study describes the typing of 488 C. coli strains from 4 different food animal sources (cattle, chickens, swine and turkeys), collected at different times over a 6 year period from different USA geographical locations. A total of 149 STs were identified. The 185 swine strains were the most diverse, possessing 82 STs. The cattle strains were the most clonal; 52/63 (83 %) strains possessed a single ST (ST-1068). A subpopulation of C. coli strains, collected primarily from turkeys, was identified, containing both C. coli- and Campylobacter jejuni-associated MLST alleles, specifically the C. jejuni allele aspA103. The majority of STs and alleles were host associated, i.e. found primarily in strains from a single food-animal source. Only 12/149 (8 %) STs were found in multiple sources. Additionally, the majority (34/46, 74 %) of major (n>5) alleles were more prevalent in certain hosts (swine, poultry). The presence of host-associated C. coli MLST alleles could lead potentially to more efficient source tracking in this species, especially in the trace-back of both sporadic and outbreak human clinical C. coli strains to animal sources.
In established multiple sclerosis, magnetization transfer ratio (MTR) histograms reveal abnormalities of normal-appearing white matter (NAWM) and grey matter (NAGM). The aim of this study was to ...investigate for such abnormalities in a large cohort of patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Magnetization transfer imaging was performed on 100 patients (67 women, 33 men, median age 32 years) a mean of 19 weeks (SD 3.8, range 12–33 weeks) after symptom onset with a clinically isolated syndrome and in 50 healthy controls (34 women, 16 men, median age 32.5 years). SPM99 software was used to generate segmented NAWM and NAGM MTR maps. The volumes of T2 lesions, white matter and grey matter were calculated. Eighty-one patients were followed up clinically and with conventional MRI after 3 years (n = 61) or until they developed multiple sclerosis if this occurred sooner (n = 20). Multiple regression analysis was used to investigate differences between patients and controls with age, gender and volume measures as covariates to control for potential confounding effects. The MTR histograms for both NAWM and NAGM showed a reduction in the mean (NAWM, 38.14 versus 38.33, P = 0.001; NAGM 32.29 versus 32.50, P = 0.009; units in pu) and peak location, with a left shift in the histogram. Mean NAWM and NAGM MTR were also reduced in the patients who developed clinically definite multiple sclerosis and multiple sclerosis according to the McDonald criteria but not in the 24 patients with normal T2-weighted brain magnetic resonance imaging (MRI). MTR abnormalities occur in the NAWM and NAGM at the earliest clinical stages of multiple sclerosis.
Statistical trend analyses have been performed for monthly zonal average total ozone data from both TOMS and SBUV satellite sources and ground‐based instruments over the period 1978–2002 for ...detection of a “turnaround” in the previous downward trend behavior and hence evidence for the beginning of an ozone recovery. Since other climatic and geophysical changes can impact ozone behavior and can influence the detection of turnaround and recovery, we also focus on accounting for ozone variations that may be ascribed to various physical and chemical influences. Thus we include in the statistical trend modeling and analysis the effects of various dynamical and circulation variations in the atmosphere, including those associated with the quasibiennial oscillation (QBO), Arctic Oscillation (AO) and Antarctic Oscillation (AAO), and Eliassen‐Palm (EP) flux influences, as well as influences of solar cycle. A notable result of the analysis is that for latitude zones of 40° and above in both hemispheres, large positive and significant estimates of a change in trend (since 1996) are obtained (on the order of 1.5 to 3 DU per year). The dynamic index series, AO/AAO and EP flux, are found to have a substantial influence on total ozone for these higher latitudes, and significant influences of lesser magnitude are also found for lower latitudes. The feature of positive significant change in trend in total ozone over recent years, however, is obtained both without and with the dynamical index terms included in the statistical models.
We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell ...depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.
This paper, a review of the present status of existing models for particle acceleration during impulsive solar flares, was inspired by a week‐long workshop held in the Fall of 1993 at NASA Goddard ...Space Flight Center. Recent observations from Yohkoh and the Compton Gamma Ray Observatory, and a reanalysis of older observations from the Solar Maximum Mission, have led to important new results concerning the location, timing, and efficiency of particle acceleration in flares. These are summarized in the first part of the review. Particle acceleration processes are then discussed, with particular emphasis on new developments in stochastic acceleration by magnetohydrodynamic waves and direct electric field acceleration by both sub‐ and super‐Dreicer electric fields. Finally, issues that arise when these mechanisms are incorporated into the large‐scale flare structure are considered. Stochastic and super‐Dreicer acceleration may occur either in a single large coronal reconnection site or at multiple “fragmented” energy release sites. Sub‐Dreicer acceleration requires a highly filamented coronal current pattern. A particular issue that needs to be confronted by all theories is the apparent need for large magnetic field strengths in the flare energy release region.
A physical map of the human genome McPherson, J D; Marra, M; Waterston, R H ...
Nature,
02/2001, Letnik:
409, Številka:
6822
Journal Article
Recenzirano
Odprti dostop
The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium ...constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.
Acute promyelocytic leukemia (APL) is associated with a t(15;17) translocation that creates the promyelocyte-retinoic acid receptor alpha (PML-RAR alpha) fusion gene. Immunohistochemistry ...demonstrates that PML is a part of a novel macromolecular organelle (including at least three other nuclear proteins) referred to as PML oncogenic domains (PODs). In APL cells, the POD is disrupted into a microparticulate pattern as a consequence of the expression of the PML-RAR oncoprotein. RA treatment of APL cells triggers a reorganization of PML to generate normal-appearing PODs. We propose that PML-RAR is a dominant negative oncoprotein that exerts its putative leukomogenic effect by inhibiting assembly of the POD. According to this proposal, not only is the POD a novel structure, but it can be ascribed an imputed function such that its disruption leads to altered myeloid maturation; this may represent a novel oncogenic target.
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