Alzheimer’s disease protein relevance analysis using human and mouse model proteomics data

The principles governing genotype-phenotype relationships are still emerging (Jovanovic, Science, 2015, 347 (6,226), 1,259,038; Buccitelli et al., Nature Reviews Genetics, 2020, 21 (10), 630–44; Öztürk et al., Nature Communications, 2022, 131), 6,153), and detailed translational as well as transcriptomic information is required to understand complex phenotypes, such as the pathogenesis of Alzheimer’s disease. For this reason, the proteomics of Alzheimer disease (AD) continues to be studied extensively. Although comparisons between data obtained from humans and mouse models have been reported, approaches that specifically address the between-species statistical comparisons are understudied. Our study investigated the performance of two statistical methods for identification of proteins and biological pathways associated with Alzheimer’s disease for cross-species comparisons, taking specific data analysis challenges into account, including collinearity, dimensionality reduction and cross-species protein matching. We used a human dataset from a well-characterized cohort followed for over 22 years with proteomic data available. For the mouse model, we generated proteomic data from whole brains of CVN-AD and matching control mouse models. We used these analyses to determine the reliability of a mouse model to forecast significant proteomic-based pathological changes in the brain that may mimic pathology in human Alzheimer’s disease. Compared with LASSO regression, partial least squares discriminant analysis provided better statistical performance for the proteomics analysis. The major biological finding of the study was that extracellular matrix proteins and integrin-related pathways were dysregulated in both the human and mouse data. This approach may help inform the development of mouse models that are more relevant to the study of human late-onset Alzheimer’s disease

Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for a new heavy charged vector boson $W^\prime$ decaying to an electron-neutrino pair in $p\bar{p}$ collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on $\sigma\cdot{\cal B}(W^\prime\to e\nu)$. Assuming standard model couplings to fermions and the neutrino from the $W^\prime$ boson decay to be light, we exclude a $W^\prime$ boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR

Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

Transformation of PVP coated silver nanoparticles in a simulated wastewater treatment process and the effect on microbial communities

Extent: 18p.Background: Manufactured silver nanoparticles (AgNPs) are one of the most commonly used nanomaterials in consumer goods and consequently their concentrations in wastewater and hence wastewater treatment plants are predicted to increase. We investigated the fate of AgNPs in sludge that was subjected to aerobic and anaerobic treatment and the impact of AgNPs on microbial processes and communities. The initial identification of AgNPs in sludge was carried out using transmission electron microscopy (TEM) with energy dispersive X-ray (EDX) analysis. The solid phase speciation of silver in sludge and wastewater influent was then examined using X-ray absorption spectroscopy (XAS). The effects of transformed AgNPs (mainly Ag-S phases) on nitrification, wastewater microbial populations and, for the first time, methanogenesis was investigated. Results: Sequencing batch reactor experiments and anaerobic batch tests, both demonstrated that nitrification rate and methane production were not affected by the addition of AgNPs [at 2.5 mg Ag L-1 (4.9 g L-1 total suspended solids, TSS) and 183.6 mg Ag kg -1 (2.9 g kg-1 total solids, TS), respectively]. The low toxicity is most likely due to AgNP sulfidation. XAS analysis showed that sulfur bonded Ag was the dominant Ag species in both aerobic (activated sludge) and anaerobic sludge. In AgNP and AgNO3 spiked aerobic sludge, metallic Ag was detected (~15%). However, after anaerobic digestion, Ag(0) was not detected by XAS analysis. Dominant wastewater microbial populations were not affected by AgNPs as determined by DNA extraction and pyrotag sequencing. However, there was a shift in niche populations in both aerobic and anaerobic sludge, with a shift in AgNP treated sludge compared with controls. This is the first time that the impact of transformed AgNPs (mainly Ag-S phases) on anaerobic digestion has been reported. Conclusions: Silver NPs were transformed to Ag-S phases during activated sludge treatment (prior to anaerobic digestion). Transformed AgNPs, at predicted future Ag wastewater concentrations, did not affect nitrification or methanogenesis. Consequently, AgNPs are very unlikely to affect the efficient functioning of wastewater treatment plants. However, AgNPs may negatively affect sub-dominant wastewater microbial communities.Casey L Doolette, Mike J McLaughlin, Jason K Kirby, Damien J Batstone, Hugh H Harris, Huoqing Ge and Geert Corneli

Search for heavy bottom-like quarks decaying to an electron or muon and jets in ppˉp\bar{p} collisions at s=1.96\sqrt{s}=1.96 TeV

We report the most sensitive direct search for pair production of fourth-generation bottom-like chiral quarks ($b'$) each decaying promptly to $tW$. We search for an excess of events with an electron or muon, at least five jets (one indentified as due to a $b$ or $c$ quark) and an imbalance of transverse momentum using data from $p\bar{p}$ collisions collected by the CDF II detector at Fermilab with an integrated luminosity of 4.8 fb$^{-1}$. We observe events consistent with background expectation and calculate upper limits on the $b'$ pair production cross section ($\sigma_{b\bar{b'}}\lesssim 30$ fb for $m_{b'}>$375 GeV/$c^2$) and exclude $m_{b'}<372$ \gevcc at 95% confidence level.Comment: For submission to PR

First Measurement of the Angular Coefficients of Drell-Yan e(+)e(-) Pairs in the Z Mass Region from p(p)over-bar Collisions at root s=1.96 TeV

We report on the first measurement of the angular distributions of final state electrons in p (p) over bar -> gamma*/Z -> e(+)e(-) + X events produced in the Z boson mass region at root s = 1.96 TeV. The data sample collected by the CDF II detector for this result corresponds to 2.1 fb(-1) of integrated luminosity. The angular distributions are studied as a function of the transverse momentum of the electron-positron pair and show good agreement with the Lam-Tung relation, consistent with a spin-1 description of the gluon, and demonstrate that, at high values of the transverse momentum, Z bosons are produced via quark-antiquark annihilation and quark-gluon Compton processes

First Search for Multijet Resonances in root s=1.96 TeV p(p)over-bar Collisions

We present the first model independent search for three-jet hadronic resonances within multijet events in root s = 1.96 TeV p (p) over bar collisions at the Fermilab Tevatron using the CDF II detector. Pair production of supersymmetric gluinos and squarks with hadronic R-parity violating decays is employed as an example of a new physics benchmark for this signature. Selection criteria based on the kinematic properties of an ensemble of jet combinations within each event help to extract signal from copious QCD background. No significant excess outside the top quark mass window is observed in data with an integrated luminosity of 3.2 fb(-1). We place 95% confidence level limits on the production cross section sigma(p (p) over bar -> XX') X BR((g) over tilde(g) over tilde -> 3 jet + 3 jet) where X, X' = (g) over tilde, (q) over tilde, or (sic), with (q) over tilde, (sic) -> (g) over tilde + jet, as a function of gluino mass, in the range of 77 GeV/c(2) to 240 GeV/c(2)

Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8− Positive (AT8+) Tau in Alzheimer’s Disease

Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer’s disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples. Comparisons were also made between neurons isolated from AD brain sections expressing pathogenic hyperphosphorylated AT8- positive (AT8+) tau and non-AT8+ AD neurons using double labeling techniques. The mRNA expression data showed unique patterns of metabolic pathway expression between the subtypes of captured neurons that involved membrane based solute transporters, redox factors, and arginine and methionine metabolic pathways. We also identified the expression levels of a novel metabolic gene, Radical-S-Adenosyl Domain1 ( RSAD1 ) and its corresponding protein, Rsad1, that impact methionine usage and radical based reactions. Immunohistochemistry was used to identify specific protein expression levels and their cellular location in NeuN+ and AT8+ neurons. APOE4 vs APOE3 genotype-specific and sex-specific gene expression differences in these metabolic pathways were also observed when comparing neurons from individuals with AD to age-matched individuals