Histone Post-translational Modification Dysregulation Contributes to Toxicity in Amyotrophic Lateral Sclerosis Proteinopathy Models

Amyotrophic Lateral Sclerosis (ALS) is the third most common adult onset neurodegenerative disorder worldwide. It is generally characterized by progressive paralysis starting at the limbs ultimately leading to death caused by respiratory failure. There is no cure and current treatments fail to slow the progression of the disease. As such, new treatment options are desperately needed. Epigenetic targets are an attractive possibility because they are reversible. Epigenetics refers to heritable changes in gene expression unrelated to changes in DNA sequence. Histone modifications, a main epigenetic mechanism, occur in many amino acid residues and include phosphorylation, acetylation, methylation as well as other chemical moieties. Recent evidence points to a possible role for epigenetic mechanisms in the etiology of ALS. Here we show that overexpression of the ALS-linked protein FUS in yeast is associated with a strong growth suppression phenotype and decreases in histone acetylation, phosphorylation and methylation. Furthermore, we show that treating these yeast with the Histone Deacetylase inhibitor Trichostatin A improves yeast growth and restores histone acetylation. We then explore how overexpression of FUS alters histone PTMs in yeast. We observed that Ipl1, the histone modifying enzyme responsible for phosphorylation at serine 10 on histone H3, and Rtt109, the histone modifying enzyme responsible for acetylation at lysine 56 on histone H3, are significantly excluded for the nucleus, while the former colocalizes with FUS. We also interrogated the binding partners of FUS by co-immunoprecipitation assays followed by identification by mass spectrometry. We identified that Nop1, a histone methyltransferase involved in rRNA biogenesis, is a binding partner of FUS. We propose that exclusion of Ipl1 from the nucleus is driving the dysregulation of histone PTMs and that reduced levels of H3K56ac and FUS-Nop1 binding are causing reduced total RNA levels, likely representing decreased rRNA which contributing to FUS overexpression toxicity. We next explored the role of histone phosphorylation in the pathology of C9orf72 ALS and identify Ipl1/Aurora B Kinase as a possible therapeutic target. We find that H3S10ph levels are significantly increased in both yeast and human in vitro models of C9orf72 ALS. Furthermore, we show that knocking down Ipl1 in yeast significantly improves growth and that Aurora B Kinase, the human homologue of Ipl1, is enriched in the nucleus of a human in vitro model of C9orf72 ALS. Overall, our results highlight a great need for the inclusion of epigenetic mechanisms in the study of neurodegeneration. We hope our work will pave the way for discovery of more effective therapies to treat patients suffering from ALS and other neurodegenerative diseases

Quantum private queries

We propose a cheat sensitive quantum protocol to perform a private search on a classical database which is efficient in terms of communication complexity. It allows a user to retrieve an item from the server in possession of the database without revealing which item she retrieved: if the server tries to obtain information on the query, the person querying the database can find it out. Furthermore our protocol ensures perfect data privacy of the database, i.e. the information that the user can retrieve in a single queries is bounded and does not depend on the size of the database. With respect to the known (quantum and classical) strategies for private information retrieval, our protocol displays an exponential reduction both in communication complexity and in running-time computational complexity.Comment: 4 pages, 1 figur

The capacity of the noisy quantum channel

An upper limit is given to the amount of quantum information that can be transmitted reliably down a noisy, decoherent quantum channel. A class of quantum error-correcting codes is presented that allow the information transmitted to attain this limit. The result is the quantum analog of Shannon's bound and code for the noisy classical channel.Comment: 19 pages, Submitted to Science. Replaced give correct references to work of Schumacher, to add a figure and an appendix, and to correct minor mistake

Energy Monitoring & Management System (EMMS)

The Energy Monitoring and Management System (EMMS) is developing an electrical power meter to help make electricity more available in energy impoverished regions of the world. The meter fills a unique niche for energy tracking and regulation within micro-grid systems. The EMMS project has partners in Burkina Faso and Zimbabwe: Open Door Development (ODD), the Institut Missiologique du Sahel (IMS), and the Theological College of Zimbabwe (TCZ). Ties are also maintained on a regular basis with IEEE Smart Village for potential future widespread system implementation. Recent work on the EMMS meter has been focused on resolving the last few remaining bugs, establishing a robust communication system, and developing a centralized server-based interface which aids with meter configuration and administration. The team has also begun several future developments which include datalogging and remote access features.https://mosaic.messiah.edu/engr2021/1004/thumbnail.jp

Experimental Demonstration of Greenberger-Horne-Zeilinger Correlations Using Nuclear Magnetic Resonance

The Greenberger-Horne-Zeilinger (GHZ) effect provides an example of quantum correlations that cannot be explained by classical local hidden variables. This paper reports on the experimental realization of GHZ correlations using nuclear magnetic resonance (NMR). The NMR experiment differs from the originally proposed GHZ experiment in several ways: it is performed on mixed states rather than pure states; and instead of being widely separated, the spins on which it is performed are all located in the same molecule. As a result, the NMR version of the GHZ experiment cannot entirely rule out classical local hidden variables. It nonetheless provides an unambiguous demonstration of the "paradoxical" GHZ correlations, and shows that any classical hidden variables must communicate by non-standard and previously undetected forces. The NMR demonstration of GHZ correlations shows the power of NMR quantum information processing techniques for demonstrating fundamental effects in quantum mechanics.Comment: Latex2.09, 8 pages, 1 eps figur

Closed timelike curves via post-selection: theory and experimental demonstration

Closed timelike curves (CTCs) are trajectories in spacetime that effectively travel backwards in time: a test particle following a CTC can in principle interact with its former self in the past. CTCs appear in many solutions of Einstein's field equations and any future quantum version of general relativity will have to reconcile them with the requirements of quantum mechanics and of quantum field theory. A widely accepted quantum theory of CTCs was proposed by Deutsch. Here we explore an alternative quantum formulation of CTCs and show that it is physically inequivalent to Deutsch's. Because it is based on combining quantum teleportation with post-selection, the predictions/retrodictions of our theory are experimentally testable: we report the results of an experiment demonstrating our theory's resolution of the well-known `grandfather paradox.Comment: 5 pages, 4 figure

EMMS: Increasing Hope and Transforming Lives Through Improved Access to Electrical Power

Developing countries often face a challenge involving energy conservation. Energy Monitoring and Management Systems (EMMS) was tasked to make an energy meter in order to provide a practical way of controlling energy consumption and create a tool for teaching energy conservation. This meter should be able to measure energy usage over a period of time and prevent further energy usage after a specified amount has been consumed. In this poster, the team will explain what they have been doing in recent semesters to work towards their goal of testing and preparing this meter for implementation in Zimbabwe this summer, as well as how they have been improving the user experience through website implementation. Funding for this work provided by The Collaboratory for Strategic Partnerships and Applied Research.https://mosaic.messiah.edu/engr2022/1005/thumbnail.jp

Analog quantum error correction

Quantum error-correction routines are developed for continuous quantum variables such as position and momentum. The result of such analog quantum error correction is the construction of composite continuous quantum variables that are largely immune to the effects of noise and decoherence.Comment: Ten pages, Te

Positioning and clock synchronization through entanglement

A method is proposed to employ entangled and squeezed light for determining the position of a party and for synchronizing distant clocks. An accuracy gain over analogous protocols that employ classical resources is demonstrated and a quantum-cryptographic positioning application is given, which allows only trusted parties to learn the position of whatever must be localized. The presence of a lossy channel and imperfect photodetection is considered. The advantages in using partially entangled states is discussed.Comment: Revised version. 9 pages, 6 figure