Rare B decays and Tevatron top-pair asymmetry

The recent Tevatron result on the top quark forward-backward asymmetry, which deviates from its standard model prediction by 3.4$\sigma$, has prompted many authors to build new models to account for this anomaly. Among the various proposals, we find that those mechanisms which produce $t\bar t$ via $t$- or $u$-channel can have a strong correlation to the rare B decays. We demonstrate this link by studying a model with a new charged gauge boson, $W'$. In terms of the current measurements on $B\to \pi K$ decays, we conclude that the branching ratio for $B^-\to \pi^- \bar K^0$ is affected most by the new effects. Furthermore, using the world average branching ratio for the exclusive B decays at $2\sigma$ level, we discuss the allowed values for the new parameters. Finally, we point out that the influence of the new physics effects on the direct CP asymmetry in B decays is insignificant.Comment: 15 page, 6 figures, typos corrected and references added, final version to appear journa

N-Acetylcholinesterase-Induced Apoptosis in Alzheimer's Disease

Background: Alzheimer’s disease (AD) involves loss of cholinergic neurons and Tau protein hyper-phosphorylation. Here, we report that overexpression of an N-terminally extended ‘‘synaptic’ ’ acetylcholinesterase variant, N-AChE-S is causally involved in both these phenomena. Methodology and Principal Findings: In transfected primary brain cultures, N-AChE-S induced cell death, morphological impairments and caspase 3 activation. Rapid internalization of fluorescently labeled fasciculin-2 to N-AChE-S transfected cells indicated membranal localization. In cultured cell lines, N-AChE-S transfection activated the Tau kinase GSK3, induced Tau hyper-phosphorylation and caused apoptosis. N-AChE-S-induced cell death was suppressible by inhibiting GSK3 or caspases, by enforced overexpression of the anti-apoptotic Bcl2 proteins, or by AChE inhibition or silencing. Moreover, inherent N-AChE-S was upregulated by stressors inducing protein misfolding and calcium imbalances, both characteristic of AD; and in cortical tissues from AD patients, N-AChE-S overexpression coincides with Tau hyper-phosphorylation. Conclusions: Together, these findings attribute an apoptogenic role to N-AChE-S and outline a potential value to ACh

Identifying Alternative Hyper-Splicing Signatures in MG-Thymoma by Exon Arrays

BACKGROUND: The vast majority of human genes (>70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. METHODOLOGY/PRINCIPAL FINDINGS: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. CONCLUSIONS/SIGNIFICANCE: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatibility gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF(2) and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MG-thymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches

Blood transcriptomics of drug-na\uefve sporadic Parkinson's disease patients

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. METHODS: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). RESULTS: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. CONCLUSIONS: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention

Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions

Mental stress modifies both cholinergic neurotransmission and alternative splicing in the brain, via incompletely understood mechanisms. Here, we report that stress changes brain microRNA (miR) expression and that some of these stress-regulated miRs regulate alternative splicing. Acute and chronic immobilization stress differentially altered the expression of numerous miRs in two stress-responsive regions of the rat brain, the hippocampal CA1 region and the central nucleus of the amygdala. miR-134 and miR-183 levels both increased in the amygdala following acute stress, compared to unstressed controls. Chronic stress decreased miR-134 levels, whereas miR-183 remained unchanged in both the amygdala and CA1. Importantly, miR-134 and miR-183 share a common predicted mRNA target, encoding the splicing factor SC35. Stress was previously shown to upregulate SC35, which promotes the alternative splicing of acetylcholinesterase (AChE) from the synapse-associated isoform AChE-S to the, normally rare, soluble AChE-R protein. Knockdown of miR-183 expression increased SC35 protein levels in vitro, whereas overexpression of miR-183 reduced SC35 protein levels, suggesting a physiological role for miR-183 regulation under stress. We show stress-induced changes in miR-183 and miR-134 and suggest that, by regulating splicing factors and their targets, these changes modify both alternative splicing and cholinergic neurotransmission in the stressed brain

Feebly-interacting particles: FIPs 2020 workshop report

With the establishment and maturation of the experimental programs searching for new physics with sizeable couplings at the LHC, there is an increasing interest in the broader particle and astrophysics community for exploring the physics of light and feebly-interacting particles as a paradigm complementary to a New Physics sector at the TeV scale and beyond. FIPs 2020 has been the first workshop fully dedicated to the physics of feebly-interacting particles and was held virtually from 31 August to 4 September 2020. The workshop has gathered together experts from collider, beam dump, fixed target experiments, as well as from astrophysics, axions/ALPs searches, current/future neutrino experiments, and dark matter direct detection communities to discuss progress in experimental searches and underlying theory models for FIPs physics, and to enhance the cross-fertilisation across different fields. FIPs 2020 has been complemented by the topical workshop Physics Beyond Colliders meets theory, held at CERN from 7 June to 9 June 2020. This document presents the summary of the talks presented at the workshops and the outcome of the subsequent discussions held immediately after. It aims to provide a clear picture of this blooming field and proposes a few recommendations for the next round of experimental results

Selective and Irreversible Inhibitors of Aphid Acetylcholinesterases: Steps Toward Human-Safe Insecticides

Aphids, among the most destructive insects to world agriculture, are mainly controlled by organophosphate insecticides that disable the catalytic serine residue of acetylcholinesterase (AChE). Because these agents also affect vertebrate AChEs, they are toxic to non-target species including humans and birds. We previously reported that a cysteine residue (Cys), found at the AChE active site in aphids and other insects but not mammals, might serve as a target for insect-selective pesticides. However, aphids have two different AChEs (termed AP and AO), and only AP-AChE carries the unique Cys. The absence of the active-site Cys in AO-AChE might raise concerns about the utility of targeting that residue. Herein we report the development of a methanethiosulfonate-containing small molecule that, at 6.0 µM, irreversibly inhibits 99% of all AChE activity extracted from the greenbug aphid (Schizaphis graminum) without any measurable inhibition of the human AChE. Reactivation studies using β-mercaptoethanol confirm that the irreversible inhibition resulted from the conjugation of the inhibitor to the unique Cys. These results suggest that AO-AChE does not contribute significantly to the overall AChE activity in aphids, thus offering new insight into the relative functional importance of the two insect AChEs. More importantly, by demonstrating that the Cys-targeting inhibitor can abolish AChE activity in aphids, we can conclude that the unique Cys may be a viable target for species-selective agents to control aphids without causing human toxicity and resistance problems

Post-LS3 Experimental Options in ECN3

The Experimental Cavern North 3 (ECN3) is an underground experimental cavern on the CERN Pr\'evessin site. ECN3 currently hosts the NA62 experiment, with a physics programme devoted to rare kaon decays and searches of hidden particles approved until Long Shutdown 3 (LS3). Several options are proposed on the longer term in order to make best use of the worldwide unique potential of the high-intensity/high-energy proton beam extracted from the Super Proton Synchrotron (SPS) in ECN3. The current status of their study by the CERN Physics Beyond Colliders (PBC) Study Group is presented, including considerations on beam requirements and upgrades, detector R&D and construction, schedules and cost, as well as physics potential within the CERN and worldwide landscape.Comment: 113 pages, 39 figure

On the Flavor Structure of Natural Composite Higgs Models & Top Flavor Violation

Abstract: We explore the up flavor structure of composite pseudo Nambu-Goldstone-boson Higgs models, where we focus on the flavor anarchic minimal SO(5) case. We identify the different sources of flavor violation in this framework and emphasise the differences from the anarchic Randall-Sundrum scenario. In particular, the fact that the flavor symmetry does not commute with the symmetries that stabilize the Higgs potential may constrain the flavor structure of the theory. In addition, we consider the interplay between the fine tuning of the model and flavor violation. We find that generically the tuning of this class of models is worsen in the anarchic case due to the contributions from the additional fermion resonances. We show that, even in the presence of custodial symmetry, large top flavor violating rate are naturally expected. In particular, t \u2192 cZ branching ratio of order of 10 125 is generic for this class of models. Thus, this framework can be tested in the next run of the LHC as well as in other future colliders. We also find that the top flavor violation is weakly correlated with the increase amount of fine tuning. Finally, other related flavor violation effects, such as t \u2192 ch and in the D system, are found to be too small to be observed by the current and near future colliders. \ua9 2014, The Author(s)

Search for axion-like particles through nuclear Primakoff production using the GlueX detector

We report on the results of the first search for the production of axion-like particles (ALP) via Primakoff production on nuclear targets using the GlueX detector. This search uses an integrated luminosity of 100 pb$^{-1}\cdot$nucleon on a $^{12}$C target, and explores the mass region of 200 < $m_a$ < 450 MeV via the decay $X\rightarrow\gamma\gamma$. This mass range is between the $\pi^0$ and $\eta$ masses, which enables the use of the measured $\eta$ production rate to obtain absolute bounds on the ALP production with reduced sensitivity to experimental luminosity and detection efficiency. We find no evidence for an ALP, consistent with previous searches in the quoted mass range, and present limits on the coupling on the scale of $O$(1 TeV). We further find that the ALP production limit we obtain is hindered by the peaking structure of the non-target-related dominant background in GlueX, which we treat by using data on $^4$He to estimate and subtract these backgrounds. We comment on how this search can be improved in a future higher-statistics dedicated measurement