715 research outputs found
Spatially and genetically distinct African trypanosome virulence variants defined by host interferon-g response
We describe 2 spatially distinct foci of human African trypansomiasis in eastern Uganda. The Tororo and Soroti foci of <i>Trypanosoma brucei rhodesiense</i> infection were genetically distinct as characterized by 6 microsatellite and 1 minisatellite polymorphic markers and were characterized by differences in disease progression and host-immune response. In particular, infections with the Tororo genotype exhibited an increased frequency of progression to and severity of the meningoencephalitic stage and higher plasma interferon (IFN)–γ concentration, compared with those with the Soroti genotype. We propose that the magnitude of the systemic IFN-γ response determines the time at which infected individuals develop central nervous system infection and that this is consistent with the recently described role of IFN-γ in facilitating blood-brain barrier transmigration of trypanosomes in an experimental model of infection. The identification of trypanosome isolates with differing disease progression phenotypes provides the first field-based genetic evidence for virulence variants in T. <i>brucei rhodesiense</i>
Effects of Intra- and Interpatch Host Density on Egg Parasitism by Three Species of Trichogramma
Host-foraging responses to different intra- and interpatch densities were used to assess three Trichogramma spp. (Hymenoptera: Trichogrammatidae) Trichogramma deion Pinto and Oatman, T. ostriniae Pang and Chen, and T. pretiosum Riley — as potential biological control agents for the Indian meal moth, Plodia interpunctella Hübner (Lepidoptera: Pyralidae). Single naïve females were allowed 6 h to forage in Plexiglas arenas with four different spatial arrangements of host eggs, nine single-egg patches), nine four-egg patches, 36 single-egg patches, and 36 four-egg patches. No significant differences were found among species in the number of patches parasitized. As expected, all three species parasitized the most eggs in the 36 four-egg patch treatment and the least in the nine single-egg patch treatment. T. deion parasitized significantly more eggs than T. pretiosum on the nine four-egg patches. T. ostriniae parasitized significantly more patches when intrapatch density was greater, regardless of interpatch density. In contrast, T. deion only parasitized more patches at the greater intrapatch density when the interpatch density was low. Patch density had no effect on T. pretiosum. The spatial pattern of parasitism was more aggregated for T. deion and T. ostriniae in the 36 four-egg patches treatment compared to the 36 single-egg patches treatment. Therefore, intrapatch density was more important than interpatch density for T. ostriniae, and potentially for T. deion, but not for T. pretiosum. T. deion may be the best candidate for augmentative biological control because it parasitized either slightly or significantly more eggs than the other two species in all four treatments. Furthermore, the pattern of parasitism by T. deion in the 36 four-egg patches treatment was the most aggregated among the three species, suggesting a more thorough searching pattern. In contrast, T. pretiosum had the least aggregated pattern of parasitism and therefore may have used a more random foraging pattern
Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response
Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance.
Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF.
Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value
EB1 Is Required for Spindle Symmetry in Mammalian Mitosis
Most information about the roles of the adenomatous polyposis coli protein (APC) and its binding partner EB1 in mitotic cells has come from siRNA studies. These suggest functions in chromosomal segregation and spindle positioning whose loss might contribute to tumourigenesis in cancers initiated by APC mutation. However, siRNA-based approaches have drawbacks associated with the time taken to achieve significant expression knockdown and the pleiotropic effects of EB1 and APC gene knockdown. Here we describe the effects of microinjecting APC- or EB1- specific monoclonal antibodies and a dominant-negative EB1 protein fragment into mammalian mitotic cells. The phenotypes observed were consistent with the roles proposed for EB1 and APC in chromosomal segregation in previous work. However, EB1 antibody injection also revealed two novel mitotic phenotypes, anaphase-specific cortical blebbing and asymmetric spindle pole movement. The daughters of microinjected cells displayed inequalities in microtubule content, with the greatest differences seen in the products of mitoses that showed the severest asymmetry in spindle pole movement. Daughters that inherited the least mobile pole contained the fewest microtubules, consistent with a role for EB1 in processes that promote equality of astral microtubule function at both poles in a spindle. We propose that these novel phenotypes represent APC-independent roles for EB1 in spindle pole function and the regulation of cortical contractility in the later stages of mitosis. Our work confirms that EB1 and APC have important mitotic roles, the loss of which could contribute to CIN in colorectal tumour cells
Evidence for the Decay
We present a search for the ``wrong-sign'' decay D0 -> K+ pi- pi+ pi- using 9
fb-1 of e+e- collisions on and just below the Upsilon(4S) resonance. This decay
can occur either through a doubly Cabibbo-suppressed process or through mixing
to a D0bar followed by a Cabibbo-favored process. Our result for the
time-integrated wrong-sign rate relative to the decay D0 -> K- pi+ pi- pi+ is
(0.0041 +0.0012-0.0011(stat.) +-0.0004(syst.))x(1.07 +-0.10)(phase space),
which has a statistical significance of 3.9 standard deviations.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Hadronic Mass Moments in Inclusive Semileptonic B Meson Decays
We have measured the first and second moments of the hadronic mass-squared
distribution in B -> X_c l nu, for P(lepton) > 1.5 GeV/c. We find <M_X^2 -
M_D[Bar]^2> = 0.251 +- 0.066 GeV^2, )^2 > = 0.576 +- 0.170
GeV^4, where M_D[Bar] is the spin-averaged D meson mass.
From that first moment and the first moment of the photon energy spectrum in
b -> s gamma, we find the HQET parameter lambda_1 (MS[Bar], to order 1/M^3 and
beta_0 alpha_s^2) to be -0.24 +- 0.11 GeV^2. Using these first moments and the
B semileptonic width, and assuming parton-hadron duality, we obtain |V_cb| =
0.0404 +- 0.0013.Comment: 11 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Observation of the Charmed Baryon at CLEO
The CLEO experiment at the CESR collider has used 13.7 fb of data to
search for the production of the (css-ground state) in
collisions at {\rm GeV}. The modes used to
study the are ,
, , , and
. We observe a signal of 40.49.0(stat) events
at a mass of 2694.62.6(stat)1.9(syst) {\rm MeV/}, for all modes
combined.Comment: 10 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
A Statistically Rigorous Method for Determining Antigenic Switching Networks
Many vector-borne pathogens rely on antigenic variation to prolong infections and increase their likelihood of onward transmission. This immune evasion strategy often involves mutually exclusive switching between members of gene families that encode functionally similar but antigenically different variants during the course of a single infection. Studies of different pathogens have suggested that switching between variant genes is non-random and that genes have intrinsic probabilities of being activated or silenced. These factors could create a hierarchy of gene expression with important implications for both infection dynamics and the acquisition of protective immunity. Inferring complete switching networks from gene transcription data is problematic, however, because of the high dimensionality of the system and uncertainty in the data. Here we present a statistically rigorous method for analysing temporal gene transcription data to reconstruct an underlying switching network. Using artificially generated transcription profiles together with in vitro var gene transcript data from two Plasmodium falciparum laboratory strains, we show that instead of relying on data from long-term parasite cultures, accuracy can be greatly improved by using transcription time courses of several parasite populations from the same isolate, each starting with different variant distributions. The method further provides explicit indications about the reliability of the resulting networks and can thus be used to test competing hypotheses with regards to the underlying switching pathways. Our results demonstrate that antigenic switch pathways can be determined reliably from short gene transcription profiles assessing multiple time points, even when subject to moderate levels of experimental error. This should yield important new information about switching patterns in antigenically variable organisms and might help to shed light on the molecular basis of antigenic variation
Observation of and
We have studied two-body charmless hadronic decays of mesons into the
final states phi K and phi K^*. Using 9.7 million pairs collected
with the CLEO II detector, we observe the decays B- -> phi K- and B0 -> phi K*0
with the following branching fractions: BR(B- -> phi K-)=(5.5 +2.1-1.8 +- 0.6)
x 10^{-6} and BR(B0 -> phi K*0)=(11.5 +4.5-3.7 +1.8-1.7) x 10^{-6}. We also see
evidence for the decays B0 -> phi K0 and B- -> phi K*-. However, since the
statistical significance is not overwhelming for these modes we determine upper
limits of <12.3 x 10^{-6} and <22.5 x 10^{-6} (90% C.L.) respectively.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
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