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Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse.
Infection with the human immunodeficiency virus (HIV) results in immunosuppression and depletion of circulating CD4+ T cells. Since the thymus is the primary organ in which T cells mature it is of interest to examine the effects of HIV infection in this tissue. HIV infection has been demonstrated in the thymuses of infected individuals and thymocytes have been previously demonstrated to be susceptible to HIV infection both in vivo, using the SCID-hu mouse, and in vitro. The present study sought to determine which subsets of thymocytes were infected in the SCID-hu mouse model and to evaluate HIV-related alterations in the thymic microenvironment. Using two different primary HIV isolates, infection was found in CD4+/CD8+ double positive thymocytes as well as in both the CD4+ and CD8+ single positive subsets of thymocytes. The kinetics of infection and resulting viral burden differed among the three thymocyte subsets and depended on which HIV isolate was used for infection. Thymic epithelial (TE) cells were also shown to endocytose virus and to often contain copious amounts of viral RNA in the cytoplasm by in situ hybridization, although productive infection of these cells could not be definitively shown. Furthermore, degenerating TE cells were observed even without detection of HIV in the degenerating cells. Two striking morphologic patterns of infection were seen, involving either predominantly thymocyte infection and depletion, or TE cell involvement with detectable cytoplasmic viral RNA and/or TE cell toxicity. Thus, a variety of cells in the human thymus is susceptible to HIV infection, and infection with HIV results in a marked disruption of the thymic microenvironment leading to depletion of thymocytes and degeneration of TE cells
Vanishing of phase coherence in underdoped Bi_2Sr_2CaCu_2O_8+d
Coherent time-domain spectroscopy is used to measure the screening and
dissipation of high-frequency electromagnetic fields in a set of underdoped
Bi_2Sr_2CaCu_2O_8+d thin films. The measurements provide direct evidence for a
phase-fluctuation driven transition from the superconductor to normal state,
with dynamics described well by the Berezinskii-Kosterlitz-Thouless theory of
vortex-pair unbinding.Comment: Nature, Vol. 398, 18 March 1999, pg. 221 4 pages with 4 included
figure
Observation of spin Coulomb drag in a two-dimensional electron gas
An electron propagating through a solid carries spin angular momentum in
addition to its mass and charge. Of late there has been considerable interest
in developing electronic devices based on the transport of spin, which offer
potential advantages in dissipation, size, and speed over charge-based devices.
However, these advantages bring with them additional complexity. Because each
electron carries a single, fixed value (-e) of charge, the electrical current
carried by a gas of electrons is simply proportional to its total momentum. A
fundamental consequence is that the charge current is not affected by
interactions that conserve total momentum, notably collisions among the
electrons themselves. In contrast, the electron's spin along a given spatial
direction can take on two values, "up" and "down", so that the spin current and
momentum need not be proportional. Although the transport of spin polarization
is not protected by momentum conservation, it has been widely assumed that,
like the charge current, spin current is unaffected by electron-electron (e-e)
interactions. Here we demonstrate experimentally not only that this assumption
is invalid, but that over a broad range of temperature and electron density,
the flow of spin polarization in a two-dimensional gas of electrons is
controlled by the rate of e-e collisions
A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport
Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports
The effect of time since measles vaccination and age at first dose on measles vaccine effectiveness - A systematic review.
BACKGROUND: In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We aimed to assess whether measles vaccine effectiveness (VE) waned over time, and if so, whether differentially in measles-eliminated and measles-endemic settings. METHODS: We performed a systematic literature review of studies that reported VE and time since vaccination with measles-containing vaccine (MCV). We extracted information on case definition (clinical symptoms and/or laboratory diagnosis), method of vaccination status ascertainment (medical record or vaccine registry), as well as any biases which may have arisen from cold chain issues and a lack of an age at first dose of MCV. We then used linear regression to evaluate VE as a function of age at first dose of MCV and time since MCV. RESULTS: After screening 14,782 citations, we identified three full-text articles from measles-eliminated settings and 33 articles from measles-endemic settings. In elimination settings, two-dose VE estimates increased as age at first dose of MCV increased and decreased as time since MCV increased; however, the small number of studies available limited interpretation. In measles-endemic settings, one-dose VE increased by 1.5% (95% CI 0.5, 2.5) for every month increase in age at first dose of MCV. We found no evidence of waning VE in endemic settings. CONCLUSIONS: The paucity of data from measles-eliminated settings indicates that additional studies and approaches (such as studies using proxies including laboratory correlates of protection) are needed to answer the question of whether VE in measles-eliminated settings wanes. Age at first dose of MCV was the most important factor in determining VE. More VE studies need to be conducted in elimination settings, and standards should be developed for information collected and reported in such studies
Chronic Cough and Eosinophilic Esophagitis: An Uncommon Association
An increasing number of children, usually with gastrointestinal symptoms, is diagnosed with eosinophilic esophagitis (EE), and a particular subset of these patients complains of airway manifestations. We present the case of a 2-year-old child with chronic dry cough in whom EE was found after a first diagnosis of gastroesophageal reflux disease (GERD) due to pathological 24-hour esophageal pH monitoring. Traditional allergologic tests were negative, while patch tests were diagnostic for cow's milk allergy. We discuss the intriguing relationship between GERD and EE and the use of patch test for the allergologic screening of patients
Ion-Abrasion Scanning Electron Microscopy Reveals Surface-Connected Tubular Conduits in HIV-Infected Macrophages
HIV-1-containing internal compartments are readily detected in images of thin sections from infected cells using conventional transmission electron microscopy, but the origin, connectivity, and 3D distribution of these compartments has remained controversial. Here, we report the 3D distribution of viruses in HIV-1-infected primary human macrophages using cryo-electron tomography and ion-abrasion scanning electron microscopy (IA-SEM), a recently developed approach for nanoscale 3D imaging of whole cells. Using IA-SEM, we show the presence of an extensive network of HIV-1-containing tubular compartments in infected macrophages, with diameters of ∼150–200 nm, and lengths of up to ∼5 µm that extend to the cell surface from vesicular compartments that contain assembling HIV-1 virions. These types of surface-connected tubular compartments are not observed in T cells infected with the 29/31 KE Gag-matrix mutant where the virus is targeted to multi-vesicular bodies and released into the extracellular medium. IA-SEM imaging also allows visualization of large sheet-like structures that extend outward from the surfaces of macrophages, which may bend and fold back to allow continual creation of viral compartments and virion-lined channels. This potential mechanism for efficient virus trafficking between the cell surface and interior may represent a subversion of pre-existing vesicular machinery for antigen capture, processing, sequestration, and presentation
Ethnicity and gender related differences in extended intraesophageal pH monitoring parameters in infants: a retrospective study
BACKGROUND: Gastroesophageal reflux disease (GERD) is believed to be more common in adult males as compared to females. It also has been shown in adults to be more common in Caucasians. We wanted to determine ethnicity and gender related differences for extended pH monitoring parameters in infancy. METHODS: Extended pH monitoring data (EPM) from infants <1 year of age were reviewed. Results were classified in two groups, as control and Gastroesophageal reflux disease (GERD) group based on the reflux index (RI). The GERD group had RI of equal to or more than 5% of total monitoring period. The parameters of RI, total number of episodes of pH < 4, and the number of episodes with pH < 4 lasting more than 5 minutes were compared by genders and by ethnic groups, Caucasians and African American (AA). RESULTS: There were 569 infants, 388 controls, 181 with GERD (320 males, 249 females; 165 Caucasians, 375 AA). No statistical difference in EPM parameters was detected between genders in both groups. However, Caucasian infants had a significantly higher incidence of GERD than AA infants (p = 0.036). On stratifying by gender, Caucasian females had a significantly higher number of reflux episodes >5 minutes as compared to AA females in the control group (p = 0.05). Furthermore, Caucasian females with GERD showed an overall higher trend for all parameters. Caucasian males had a trend for higher mean number of reflux episodes as compared to AA males in the control group (p = 0.09). CONCLUSION: Although gender specific control data do not appear warranted in infants undergoing EPM, ethnic differences related to an overall increased incidence of pathologic GERD in Caucasian infants should be noted
Resonance in the electron-doped high-Tc superconductor Pr0.88LaCe0.12CuO(4-delta)
In conventional superconductors, the interaction that pairs the electrons to
form the superconducting state is mediated by lattice vibrations (phonons). In
high-transition temperature (high-Tc) copper oxides, it is generally believed
that magnetic excitations play a fundamental role in the superconducting
mechanism because superconductivity occurs when mobile 'electrons' or 'holes'
are doped into the antiferromagnetic parent compounds. Indeed, a sharp magnetic
excitation termed "resonance" has been observed by neutron scattering in a
number of hole-doped materials. The resonance is intimately related to
superconductivity, and its interaction with charged quasi-particles observed by
photoemission, optical conductivity, and tunneling suggests that it plays a
similar role as phonons in conventional superconductors. However, the relevance
of the resonance to high-Tc superconductivity has been in doubt because so far
it has been found only in hole-doped materials. Here we report the discovery of
the resonance in electron-doped superconducting Pr0.88LaCe0.12CuO(4-delta) (Tc
= 24 K). We find that the resonance energy (Er) is proportional to Tc via Er =
5.8kBTc (kB is the Boltzmann's constant) for all high-Tc superconductors
irrespective of electron- or hole-doping (Fig. 1e). Our results demonstrate
that the resonance is a fundamental property of the superconducting copper
oxides and therefore must play an essential role in the mechanism of
superconductivity.Comment: PDF file with 4 Figure
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