A time‐specific encrypted range query scheme that has the following properties is proposed. (1) The proposed scheme has trapdoor privacy and data privacy so that a semi‐honest cloud is not able to ...get any useful information from given ciphertexts and given tokens that are used for searching ranges. (2) Unlike most of the other studies which report that the cloud server stores single encrypted keyword/element in the database, in our solution, the cloud server stores encrypted multi‐keywords/ranges in the database. Therefore, the semi‐honest cloud compares ciphertexts to tokens as ranges based on a predefined threshold ϕ value. This approach decreases the cloud search time since the cloud compares ranges to ranges (multi‐keywords with multi‐keywords) not points to points (not a keyword with a keyword). Thus, the proposed scheme is efficient based on searching ranges on ciphertexts. (3) Moreover, the communication cost between users and the cloud is decreased from O(n) to O(log n), where n is the size of a range. Users send logarithmic size information to the cloud server instead of sending linear size information.
As the process that silences gene expression ensues during development, the stage is set for the activity of Polycomb-repressive complex 2 (PRC2) to maintain these repressed gene profiles. PRC2 ...catalyzes a specific histone posttranslational modification (hPTM) that fosters chromatin compaction. PRC2 also facilitates the inheritance of this hPTM through its self-contained "write and read" activities, key to preserving cellular identity during cell division. As these changes in gene expression occur without changes in DNA sequence and are inherited, the process is epigenetic in scope. Mutants of mammalian PRC2 or of its histone substrate contribute to the cancer process and other diseases, and research into these aberrant pathways is yielding viable candidates for therapeutic targeting. The effectiveness of PRC2 hinges on its being recruited to the proper chromatin sites; however, resolving the determinants to this process in the mammalian case was not straightforward and thus piqued the interest of many in the field. Here, we chronicle the latest advances toward exposing mammalian PRC2 and its high maintenance.
Chromatin domains and their associated structures must be faithfully inherited through cellular division to maintain cellular identity. However, accessing the localized strategies preserving ...chromatin domain inheritance, specifically the transfer of parental, pre-existing nucleosomes with their associated post-translational modifications (PTMs) during DNA replication, is challenging in living cells. We devised an inducible, proximity-dependent labeling system to irreversibly mark replication-dependent H3.1 and H3.2 histone-containing nucleosomes at desired loci in mouse embryonic stem cells so that their fate after DNA replication could be followed. Strikingly, repressed chromatin domains are preserved through local re-deposition of parental nucleosomes. In contrast, nucleosomes decorating active chromatin domains do not exhibit such preservation. Notably, altering cell fate leads to an adjustment of the positional inheritance of parental nucleosomes that reflects the corresponding changes in chromatin structure. These findings point to important mechanisms that contribute to parental nucleosome segregation to preserve cellular identity.
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•CRISPR-biotinylation system to track parental nucleosome segregation at single loci•Biotinylation of replication-dependent histone H3 nucleosomes exclusively in G1/S•Parental nucleosomes redeposit locally in repressed chromatin domains•Parental nucleosomes disperse in the case of active chromatin domains
A method to track the deposition of nucleosomes in a locus-specific manner shows that nucleosomes in repressive chromatin domains are locally re-deposited following DNA replication, whereas the locations of nucleosomes in active chromatin domains are not preserved.
Erk1/2 activation contributes to mouse ES cell pluripotency. We found a direct role of Erk1/2 in modulating chromatin features required for regulated developmental gene expression. Erk2 binds to ...specific DNA sequence motifs typically accessed by Jarid2 and PRC2. Negating Erk1/2 activation leads to increased nucleosome occupancy and decreased occupancy of PRC2 and poised RNAPII at Erk2-PRC2-targeted developmental genes. Surprisingly, Erk2-PRC2-targeted genes are specifically devoid of TFIIH, known to phosphorylate RNA polymerase II (RNAPII) at serine-5, giving rise to its initiated form. Erk2 interacts with and phosphorylates RNAPII at its serine 5 residue, which is consistent with the presence of poised RNAPII as a function of Erk1/2 activation. These findings underscore a key role for Erk1/2 activation in promoting the primed status of developmental genes in mouse ES cells and suggest that the transcription complex at developmental genes is different than the complexes formed at other genes, offering alternative pathways of regulation.
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•Erk1/2 activity regulates the targeting of PRC2-Jarid2 in mouse ESCs•Erk2 binds to a cohort of PRC2-targeted developmental genes•Erk2 phosphorylates RNAPII at its serine 5 residue at developmental genes•TFIIH is present on active genes but is absent on Erk2-PRC2 developmental genes
The MAPK Erk1/2 has a direct role in the core transcriptional machinery at a specific set of genes in ESCs. Erk1/2 binds to specific DNA sequences to influence nucleosome occupancy and appears to substitute for the core transcription factor TFIIH to phosphorylate RNA polymerase II.
Abstract
In this paper, a system is proposed which uses blockchain technology in healthcare. In this system, patients can access their health records anytime from anywhere. Moreover, the patients’ ...health records are put into the blockchain anonymously. Whenever a patient visits a healthcare professional, the authorized entity filters patients’ medical report out by eliminating the patients’ sensitive information. Then, the filtered medical data are put into an off-chain database, while the address of the data is put into the blockchain with an assigned pseudo random identity of the patient. Thus, there are multi pseudo random identities for each patient. Unlike previous studies where the patients’ identities/reports were linkable, in the proposed protocol the patients’ identities are not linkable. The proposed system can also be used to show patients’ health status to some entities when a pandemic happens (e.g. COVID-19). During the COVID-19 pandemic, the patients are required to show their series of vaccinations before they travel internationally/nationally or participate in some social events. To travel or join some events, the patient needs to show only a partial medical history to the security guard without leaking any private information. Furthermore, once the anonymous medical data are put into the off-chain database, the data can be used for data mining and machine learning.
Glioblastoma (GBM) is thought to be driven by a subpopulation of cancer stem cells (CSCs) that self-renew and recapitulate tumor heterogeneity yet remain poorly understood. Here, we present a ...comparative analysis of chromatin state in GBM CSCs that reveals widespread activation of genes normally held in check by Polycomb repressors. These activated targets include a large set of developmental transcription factors (TFs) whose coordinated activation is unique to the CSCs. We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1. We show that ASCL1 is essential for the maintenance and in vivo tumorigenicity of GBM CSCs. Genome-wide binding profiles for ASCL1 and the Wnt effector LEF-1 provide mechanistic insight and suggest widespread interactions between the TF module and the signaling pathway. Our findings demonstrate regulatory connections among ASCL1, Wnt signaling, and collaborating TFs that are essential for the maintenance and tumorigenicity of GBM CSCs.
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•Epigenomic profiles of glioblastoma stem cells and comparators•An aberrant network of developmental transcription factors in cancer stem cells•ASCL1 is essential for glioblastoma stem cell maintenance and tumorigenicity•ASCL1 activates Wnt signaling by directly repressing the negative regulator DKK1
Glioblastoma brain tumors contain a highly tumorigenic subpopulation of cells with stem-like features. Using epigenomic profiling, Chi, Bernstein, and colleagues identify a set of developmental transcription factors normally repressed by Polycomb complexes that become activated in these stem-like cancer cells. One of these factors, ASCL1, is shown to be essential for glioblastoma stem cell maintenance and tumorigenicity and to function as an activator of Wnt signaling in this setting.
Abstract In a smart grid, collected electricity consumption periodically from smart meters allow entities to bill the customers, power company to operate the grid successfully, and users to control ...the use of their appliances. However, energy consumptions of users should be protected since the data provides the user’s daily habit that an adversary uses the data to extract useful information about the users. Moreover, users’ identities should not be disclosed to untrusted entities since the untrusted entities map identities to their real identities. In this paper, we propose a system that protects users’ data privacy using multi-pseudorandom identities and a randomization technique. Moreover, the proposed work provides fast authentication for smart meters to send their readings to data aggregators. Furthermore, the proposed work is based on consortium blockchain to eliminate a single point of failure and provides transparency of messages and operations. In addition, we use dynamic billing and pricing mechanism for the users to see their bills.
The organization and structure of chromatin domains are unique to individual cell lineages. Their misregulation might lead to a loss in cellular identity and/or disease. Despite tremendous efforts, ...our understanding of the formation and propagation of chromatin domains is still limited. Chromatin domains have been studied under steady-state conditions, which are not conducive to following the initial events during their establishment. Here, we present a method to inducibly reconstruct chromatin domains and follow their re-formation as a function of time. Although, first applied to the case of PRC2-mediated repressive chromatin domain formation, it could be easily adapted to other chromatin domains. The modification of and/or the combination of this method with genomics and imaging technologies will provide invaluable tools to study the establishment of chromatin domains in great detail. We believe that this method will revolutionize our understanding of how chromatin domains form and interact with each other.
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