Forget-Me-Not

The purpose of Forget-Me-Not is to provide another level of care and comfort to those suffering from mild dementia, as well as provide further assistance for a friend, family member, or caretaker who may look after them. Research shows that timely reminders and persistent information can greatly improve the quality of life for those afflicted with mild dementia (Mokhtari et al.). Forget-Me-Not’s persistent display and wearable smart-bracelet offer a customizable and well connected system to provide these reminders. For the caretaker, a mobile application is provided in order to maintain the display and notify them of emergencies or critical events from virtually anywhere. The system is composed of four primary elements: a high contrast and easily understood display that remains in the patient’s home, a mobile application wielded by the caretaker that can control aspects of the patient’s display, a web server that holds persistent information for the system, and a wearable smart-bracelet equipped with attention grabbing elements to warn the patient of an ongoing alarm. The system is designed to be modular and extensible, thus leaving massive margins for expansion and future integration with trending technologies such as smart houses and appliances

Synovial sarcoma: when epigenetic changes dictate tumour development.

Synovial sarcoma is a highly aggressive soft tissue malignancy that often affects adolescents and young adults. It is associated with a unique chromosomal translocation that results in the formation and expression of the fusion gene SS18-SSX, which underlies its pathogenesis. Although SS18-SSX provides a potentially unique therapeutic target, all attempts to neutralise it have been unsuccessful thus far. When complete surgical removal of the tumour fails, therapy is limited to largely ineffective cytotoxic drug regimens. Nevertheless, recent discoveries about the mechanisms of SS18-SSX protein function have provided insight into potential alternative therapeutic strategies. SS18-SSX displays oncogenic activity through protein-protein interactions and participation in chromatin remodelling complexes. This review summarises our current understanding of the function of SS18-SSX and the mechanisms by which it alters the epigenetic landscape of permissive cells to induce transformation and the subsequent development of synovial sarcoma

The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.

Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β-catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β-catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation

Determination of major elements in igneous rocks using microwave plasma atomic emission spectrometry (MP-AES)

An analytical method for sample preparation of igneous rocks and subsequent determination of Si, Na, K, Ca, Mg, Al, Fe, Mn, Ba, Sr, and Ti by means of microwave induced emission spectrometry (MP-AES) was developed and validated. The proposed sample preparation procedure avoids the use of perchloric acid and provided accurate results even for silicon determination using an acid digestion with hydrofluoric acid. The determination of major elements in rocks is required for the design of classification diagrams that provides relevant information for geochemical analysis

Timing of deformation in the Sarandí del Yí Shear Zone, Uruguay: implications for the amalgamation of western Gondwana during the Neoproterozoic Brasiliano-Pan-African Orogeny

U-Pb and Hf zircon (sensitive high-resolution ion microprobe -SHRIMP- and laser ablation-inductively coupled plasma-mass spectrometry -LA-ICP-MS-), Ar/Ar hornblende and muscovite, and Rb-Sr whole rock-muscovite isochron data from the mylonites of the Sarandí del Yí Shear Zone, Uruguay, were obtained in order to assess the tectonothermal evolution of this crustal-scale structure. Integration of these results with available kinematic, structural, and microstructural data of the shear zone as well as with geochronological data from the adjacent blocks allowed to constrain the onset of deformation along the shear zone at 630-625 Ma during the collision of the Nico Pérez Terrane and the Río de la Plata Craton. The shear zone underwent dextral shearing up to 596 Ma under upper to middle amphibolite facies conditions, which was succeeded by sinistral shearing under lower amphibolite to upper greenschist facies conditions until at least 584 Ma. After emplacement of the Cerro Caperuza granite at 570 Ma, the shear zone underwent only cataclastic deformation between the late Ediacaran and the Cambrian. The Sarandí del Yí Shear Zone is thus related to the syncollisional to postcollisional evolution of the amalgamation of the Río de la Plata Craton and the Nico Pérez Terrane. Furthermore, the obtained data reveal that strain partitioning and localization with time, magmatism emplacement, and fluid circulation are key processes affecting the isotopic systems in mylonitic belts, revealing the complexity in assessing the age of deformation of long-lived shear zone

Reassessing the polyphase neoproterozoic evolution of the Punta del Este terrane, Dom Feliciano Belt, Uruguay

Some recent models challenge the position and extension of the assumed oceanic basins formed through the break-up of Rodinia, and the tectonic processes involved in the Gondwana assembly, making the investigation of the Early Neoproterozoic record of great relevance. Within the South-American Atlantic margin, the Punta del Este Terrane (PET) of the Dom Feliciano Belt (DFB) comprises a unique Tonian to Ediacaran record, and has a strategic position to reconstruct spatio-temporal relationships with the southern African orogenic belts. Novel zircon U–Pb and Lu–Hf data from the PET basement orthogneisses display Tonian magmatic ages (805–760 Ma) and Hf isotopic signatures indicative of mainly crustal/metasedimentary sources, (Nd TDM ages: 2.2–1.9 Ga, and εHf(t): −12 to −4). The basement paragneisses yielded late Paleoproterozoic to Neoproterozoic U–Pb ages, but dominantly positive εHf(t) values. The presented results confrm the correlation of the PET with the Coastal Terrane of the Kaoko Belt, and discard the idea of the Nico Pérez Terrane as a source. Detrital zircon U–Pb and Lu–Hf data from the Rocha Formation yielded a main peak at ca. 660 Ma, with the Neoproterozoic grains showing a εHf(t) between+1 and+14. The deposition age of the Rocha Formation is constrained by the youngest detrital zircon age peak (660 Ma), and the beginning of the deposition of the Sierra de Aguirre Formation (580 Ma). The data indicate common sources with the Marmora Terrane, and it is thus proposed that the Rocha Formation belongs to the Gariep Belt, and it was juxtaposed during the Ediacaran to the DFB

Seed Embryo Development is Regulated via an AN3-MINI3 Gene Cascade

In agriculture, seed mass is one of the most important components related to seed yield. MINISEED3 (MINI3) which encodes the transcriptional activator WRKY10, is thought to be a pivotal regulator of seed mass. In Arabidopsis SHORT HYPOCOTYL UNDER BLUE1 (SHB1) associates with the promoter of MINI3, regulating embryo cell proliferation (both cell division and elongation), which, in turn, modulates seed mass. Furthermore, the recruitment of SHB1 via MINI3 to both its cognate promoter and that of IKU2 implies a two-step amplification for countering the low expression level of IKU2, which is thought to function as a molecular switch for seed cavity enlargement. However, it is largely unknown how embryo cell proliferation, which encompasses both cell division and elongation, is regulated by SHB1 and MINI3 function. Here, we show that a loss of function mutation within the transcriptional coactivator ANGUSTIFOLIA3 (AN3), increases seed mass. Further, AN3 associates with the MINI3 promoter in vivo. Genetic evidence indicates that the absence of MINI3 function suppresses the decrease of cell number observed in an3-4 mutants by regulating cell division and in turn inhibits increased cell size of the an3-4 line by controlling cell elongation. Thus, seed embryo development is modulated via an AN3-MINI3 gene cascade. This regulatory model provides a deeper understanding of seed mass regulation, which may in turn lead to increased crop yields

De novo motif identification improves the accuracy of predicting transcription factor binding sites in ChIP-Seq data analysis

Dramatic progress in the development of next-generation sequencing technologies has enabled accurate genome-wide characterization of the binding sites of DNA-associated proteins. This technique, baptized as ChIP-Seq, uses a combination of chromatin immunoprecipitation and massively parallel DNA sequencing. Other published tools that predict binding sites from ChIP-Seq data use only positional information of mapped reads. In contrast, our algorithm MICSA (Motif Identification for ChIP-Seq Analysis) combines this source of positional information with information on motif occurrences to better predict binding sites of transcription factors (TFs). We proved the greater accuracy of MICSA with respect to several other tools by running them on datasets for the TFs NRSF, GABP, STAT1 and CTCF. We also applied MICSA on a dataset for the oncogenic TF EWS-FLI1. We discovered >2000 binding sites and two functionally different binding motifs. We observed that EWS-FLI1 can activate gene transcription when (i) its binding site is located in close proximity to the gene transcription start site (up to ∼150 kb), and (ii) it contains a microsatellite sequence. Furthermore, we observed that sites without microsatellites can also induce regulation of gene expression—positively as often as negatively—and at much larger distances (up to ∼1 Mb)

The chromatin landscape of primary synovial sarcoma organoids is linked to specific epigenetic mechanisms and dependencies.

Synovial sarcoma (SyS) is an aggressive mesenchymal malignancy invariably associated with the chromosomal translocation t(X:18; p11:q11), which results in the in-frame fusion of the BAF complex gene SS18 to one of three SSX genes. Fusion of SS18 to SSX generates an aberrant transcriptional regulator, which, in permissive cells, drives tumor development by initiating major chromatin remodeling events that disrupt the balance between BAF-mediated gene activation and polycomb-dependent repression. Here, we developed SyS organoids and performed genome-wide epigenomic profiling of these models and mesenchymal precursors to define SyS-specific chromatin remodeling mechanisms and dependencies. We show that SS18-SSX induces broad BAF domains at its binding sites, which oppose polycomb repressor complex (PRC) 2 activity, while facilitating recruitment of a non-canonical (nc)PRC1 variant. Along with the uncoupling of polycomb complexes, we observed H3K27me3 eviction, H2AK119ub deposition and the establishment of de novo active regulatory elements that drive SyS identity. These alterations are completely reversible upon SS18-SSX depletion and are associated with vulnerability to USP7 loss, a core member of ncPRC1.1. Using the power of primary tumor organoids, our work helps define the mechanisms of epigenetic dysregulation on which SyS cells are dependent