Genes contributing to prion pathogenesis Tamgüney, Gültekin; Giles, Kurt; Glidden, David V ...
Journal of general virology,
07/2008, Volume:
89, Issue:
Pt 7
Journal Article
Peer reviewed
Open access
Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrP(C)) to a misfolded, pathogenic isoform (PrP(Sc)). Prion inoculation experiments in mice ...expressing homologous PrP(C) molecules on different genetic backgrounds displayed different incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes, because their products either colocalize with PrP, are associated with Alzheimer's disease, are elevated during prion disease, or function in PrP-mediated signalling, PrP glycosylation, or protein maintenance. Whereas some of the candidates tested may have a role in the normal function of PrP(C), our data show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1), and transgenic overexpression of human superoxide dismutase 1 (SOD1) prolonged incubation times by 13, 16 and 19 %, respectively.
For FDA approved SLIT in 2014-2015 (1355 patients), two Grade 3 SRs were reported, one involving pharyngeal edema and another involving throat tightening and lower respiratory symptoms; both ...reactions were treated with epinephrine.
To examine patient- and provider-level factors associated with receiving attention-deficit/hyperactivity disorder (ADHD) medication treatment in a community care setting. We hypothesized that the ...likelihood of ADHD medication receipt would be lower in groups with specific patient sociodemographic (eg, female sex, race other than white) and clinical (eg, comorbid conditions) characteristics as well as physician characteristics (eg, older age, more years since completing training).
A retrospective cohort study was conducted with 577 children (mean age, 7.8 years; 70% male) presenting for ADHD to 50 community-based practices. The bivariate relationship between each patient- and physician-level predictor and whether the child was prescribed ADHD medication was assessed. A multivariable model predicting ADHD medication prescription was conducted using predictors with significant (P < .05) bivariate associations.
Sixty-nine percent of children were prescribed ADHD medication in the year after initial presentation for ADHD-related concerns. Eleven of 31 predictors demonstrated a significant (P < .05) bivariate relationship with medication prescription. In the multivariable model, being male (OR, 1.34; 95% CI, 1.01-1.78; P = .02), living in a neighborhood with higher medical expenditures (OR, 1.11 for every $100 increase; 95% CI, 1.03-1.21; P = .005), and higher scores on parent inattention ratings (OR, 1.06; 95% CI, 1.03-1.10; P < .0001) increased the likelihood of ADHD medication prescription.
We found that some children, based on sociodemographic and clinical characteristics, are less likely to receive an ADHD medication prescription. An important next step will be to examine the source and reasons for these disparities in an effort to develop strategies for minimizing treatment barriers.
Many insect families have evolved to produce and detect complex singing patterns for the purposes of mating, display of dominance, predator escape, and other needs. While the mechanisms of sound ...production by insects have been thoroughly studied, man-machine exploitation of such mechanisms has remained unreported. We therefore describe a method to modulate the frequency spectrum in the chirp call of a singing insect, Gampsocleis gratiosa （Orthoptera： Tettigoniidae）, a large katydid indigenous to China and commonly known as Guo Guo or Chinese Bush Cricket. The chirp modulation was achieved through the contact of a ribbon of lonic Polymer-Metal Composite （IPMC） against wing of the insect. The IPMC effectively served as an actuator when a small DC voltage was applied to the ribbon＇s faces. By applying a sequential on/off voltage waveform to the IPMC ribbon, the katydid＇s chirp was modulated in a corresponding manner. This configuration can be used as part of a broader application of using singing insects to harness their acoustic power to produce and propagate machine-induced messages into the acoustic environment.
Background: Executive control of cognition, emotion, and behavior are disrupted in the manic state of bipolar disorder. Whereas frontal systems are implicated in such dysfunction, the localization of ...functional brain abnormalities in the manic state is not well understood.
Methods: We utilized a high-sensitivity H
2
150 positron emission tomography technique to investigate regions of increased brain activity in mania, compared to euthymia, in bipolar disorder.
Results: The principal findings were manic state-related increased activity in left dorsal anterior cingulate, and left head of caudate.
Conclusions: The findings suggest that the manic state of bipolar disorder may be associated with heightened activity in a frontal cortical–subcortical neural system that includes the anterior cingulate and caudate.
A windowless hydrogen gas target of nominal thickness 1019 cm−2 is an essential component of the DarkLight experiment, which is designed to utilize the megawatt electron beam at an Energy Recovery ...Linac (ERL). The design of such a target is challenging because the pressure drops by many orders of magnitude between the central, high-density section of the target and the surrounding beamline, resulting in laminar, transitional, and finally molecular flow regimes. The target system was assembled and operated at Jefferson Lab’s Low Energy Recirculator Facility (LERF) in 2016, and subsequently underwent several revisions and calibration tests at MIT Bates in 2017. The system at dynamic equilibrium was simulated in COMSOL to provide a better understanding of its optimal operation at other working points. We have determined that a windowless gas target with sufficiently high density for DarkLight’s experimental needs is feasible in an ERL environment.
●Ontogeny assignment from the database registry lacks sensitivity and specificity.●Ontogeny stratifies the outcome of AML with myelodysplasia-related gene mutations.
Accurate classification and risk ...stratification is critical for clinical decision making in AML patients. In the newly proposed World Health Organization (WHO) and International Consensus classifications (ICC) of hematolymphoid neoplasms, the presence of myelodysplasia-related (MR) gene mutations is included as one of the diagnostic criteria of AML, myelodysplasia-related (AML-MR), largely based on the assumption that these mutations are specific for AML with an antecedent myelodysplastic syndrome. ICC also prioritizes MR gene mutations over ontogeny (as defined by clinical history). Furthermore, European LeukemiaNet (ELN) 2022 stratifies these MR gene mutations to the adverse-risk group. By thoroughly annotating a cohort of 344 newly diagnosed AML patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), we show that ontogeny assignment based on database registry lacks accuracy. MR gene mutations are frequently seen in de novo AML. Among MR gene mutations, only EZH2 and SF3B1 were associated with an inferior outcome in a univariate analysis. In a multivariate analysis, AML ontogeny had independent prognostic values even after adjusting for age, treatment, allo-transplant and genomic classes or ELN risks. Ontogeny also stratified the outcome of AML with MR gene mutations. Finally, de novo AML with MR gene mutations did not show an adverse outcome. In summary, our study emphasizes the importance of accurate ontogeny designation in clinical studies, demonstrates the independent prognostic value of AML ontogeny and questions the current classification and risk stratification of AML with MR gene mutations.
In this letter, we advocate recognizing the genus Fusarium as the sole name for a group that includes virtually all Fusarium species of importance in plant pathology, mycotoxicology, medicine, and ...basic research. This phylogenetically guided circumscription will free scientists from any obligation to use other genus names, including teleomorphs, for species nested within this clade, and preserve the application of the name Fusarium in the way it has been used for almost a century. Due to recent changes in the International Code of Nomenclature for algae, fungi, and plants, this is an urgent matter that requires community attention. The alternative is to break the longstanding concept of Fusarium into nine or more genera, and remove important taxa such as those in the F. solani species complex from the genus, a move we believe is unnecessary. Here we present taxonomic and nomenclatural proposals that will preserve established research connections and facilitate communication within and between research communities, and at the same time support strong scientific principles and good taxonomic practice.
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