PTEN is frequently mutated in prostate cancer. The tumor suppressor function of PTEN is attributed to its lipid phosphatase activity that counters PI3K action. Here, we report a PTEN-ARID4B-PI3K axis ...in which PTEN inhibits expression of ARID4B, while ARID4B is a transcriptional activator of the PI3K subunit genes PIK3CA and PIK3R2 that are crucial for activation of the PI3K/AKT pathway. Reciprocal binding of ARID4B and histone H1 to the PIK3CA and PIK3R2 promoters modulates chromatin condensation, suggesting a mechanism by which ARID4B activates these promoters. Functional analyses reveals that ARID4B is required for prostate tumorigenesis when PTEN is deficient. The biological significance is further substantiated by the existence of a PTEN/ARID4B/PIK3CA three-gene signature that improves the predictive power for prostate cancer recurrence in patients. In summary, we identify ARID4B as a master regulator in the PTEN-PI3K pathway, thus providing a potential therapeutic target for prostate cancer carrying PTEN mutations.
The three homologous members of the p160 SRC family (SRC1, SRC2 and SRC3) mediate the transcriptional functions of nuclear receptors and other transcription factors, and are the most studied of all ...the transcriptional co-activators. Recent work has indicated that the SRCgenes are subject to amplification and overexpression in various human cancers. Some of the molecular mechanisms responsible for SRC overexpression, along with the mechanisms by which SRCs promote breast and prostate cancer cell proliferation and survival, have been identified, as have the specific contributions of individual SRC family members to spontaneous breast and prostate carcinogenesis in genetically manipulated mouse models. These studies have identified new challenges for cancer research and therapy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We investigated the electronic structure of the layered transition-metal dichalcogenides VS2 and VSe2 by first-principles calculations. Both compounds exhibit metal-insulator transitions when ...crossing over from the bulk to the two-dimensional monolayer. In the monolayer limit, the Coulomb interaction is enhanced due to the dimension reduction, leading to the insulating state. Moreover, these monolayers are found to be ferromagnetic, supplying excellent candidates for ferromagnetic insulators. When increasing the thickness, the few-layer structure turns metallic and presents large anomalous Hall conductivity (∼100 S/cm), which oscillates with respect to the thickness due to the size effect. Our findings presents profound materials, such as ferromagnetic insulators and anomalous Hall ferromagnets, for the spintronic application.
Autism, a pervasive neurodevelopmental disorder manifested by deficits in social behavior and interpersonal communication, and by stereotyped, repetitive behaviors, is inexplicably biased towards ...males by a ratio of ∼4∶1, with no clear understanding of whether or how the sex hormones may play a role in autism susceptibility. Here, we show that male and female hormones differentially regulate the expression of a novel autism candidate gene, retinoic acid-related orphan receptor-alpha (RORA) in a neuronal cell line, SH-SY5Y. In addition, we demonstrate that RORA transcriptionally regulates aromatase, an enzyme that converts testosterone to estrogen. We further show that aromatase protein is significantly reduced in the frontal cortex of autistic subjects relative to sex- and age-matched controls, and is strongly correlated with RORA protein levels in the brain. These results indicate that RORA has the potential to be under both negative and positive feedback regulation by male and female hormones, respectively, through one of its transcriptional targets, aromatase, and further suggest a mechanism for introducing sex bias in autism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • HDAC1 and HDAC7 are downstream effectors of miR-34a pathway in breast cancer. • Deacetylation of HSP70 K246 by HDAC1 and HDAC7 regulates therapy resistance. • Deacetylation of HSP70 K246 ...promotes therapy resistance by inhibiting autophagy. • The miR-34a–HDAC1/HDAC7–HSP70 K246 axis is a potential therapy resistant pathway.
Prospects of spintronics based on 2D materials Feng, Yuan Ping; Shen, Lei; Yang, Ming ...
Wiley interdisciplinary reviews. Computational molecular science,
September/October 2017, Letnik:
7, Številka:
5
Journal Article
Recenzirano
Spintronics holds the promise for future information technologies. Devices based on manipulation of spin are most likely to replace the current silicon complementary metal‐oxide semiconductor devices ...that are based on manipulation of charge. The challenge is to identify or design materials that can be used to generate, detect, and manipulate spin. Since the successful isolation of graphene and other two‐dimensional (2D) materials, there has been a strong focus on spintronics based on 2D materials due to their attractive properties, and much progress has been made, both theoretically and experimentally. Here, we summarize recent developments in spintronics based on 2D materials. We focus mainly on materials of truly 2D nature, that is, atomic crystal layers such as graphene, phosphorene, monolayer transition metal dichalcogenides, and others, but also highlight current research foci in heterostructures or interfaces. In particular, we emphasize roles played by computation based on first‐principles methods which has contributed significantly in the designs of spintronic materials and devices. We also highlight challenges and suggest possible directions for further studies. WIREs Comput Mol Sci 2017, 7:e1313. doi: 10.1002/wcms.1313
This article is categorized under:
Structure and Mechanism > Computational Materials Science
Electronic Structure Theory > Ab Initio Electronic Structure Methods
Electronic Structure Theory > Density Functional Theory
Spin‐dependent transport property of zigzag graphene nanoribbon and schematics of theoretical design of spintronic device element (insets). The spin‐polarization and flow direction of electric current in the graphene nanoribbon can be controlled by magnetization of the electrodes and the bias voltage, allowing implementation of spin logic gates. , spin up, antiparallel magnetization; , spin down, antiparallel magnetization; , spin up, parallel magnetization; , spin down, parallel magnetization.
The existence of spontaneous magnetization in low dimensional magnetic systems has attracted intensive studies since the early 60s and research remains very active even now. Only recently, magnetic ...van der Waals (vdW) systems down to a few layers have been broadly discussed for their magnetic order ground states at finite temperature. The naturally inherited layered structure of the vdW magnetic systems possessing onsite magnetic anisotropy from band electrons can suppress the long‐range fluctuations. This provides an excellent vehicle to study the transition of magnetism to 2D limits both theoretically and experimentally. Here the current status of 2D vdW magnetic system and its potential applications are briefly summarized and discussed.
Recently, magnetic van der Waals (vdW) systems down to the single layer limit have been studied intensively. Herein, the current status of 2D vdW magnetic systems is summarized from both a theoretical and an experimental point of view. The fundamental physics of 2D magnetism are discussed, along with the future outlook and potential applications of 2D vdW magnetic systems.
MicroRNA (miRNA) are small noncoding RNAs that play vital roles in post-transcriptional gene regulation by inhibiting mRNA translation or promoting mRNA degradation. The dysregulation of miRNA has ...been implicated in numerous human diseases, including cancers. miR-34 family members (miR-34s), including miR-34a, miR-34b, and miR-34c, have emerged as the most extensively studied tumor-suppressive miRNAs. In this comprehensive review, we aim to provide an overview of the major signaling pathways and gene networks regulated by miR-34s in various cancers and highlight the critical tumor suppressor role of miR-34s. Furthermore, we will discuss the potential of using miR-34 mimics as a novel therapeutic approach against cancer, while also addressing the challenges associated with their development and delivery. It is anticipated that gaining a deeper understanding of the functions and mechanisms of miR-34s in cancer will greatly contribute to the development of effective miR-34-based cancer therapeutics.
MicroRNA (miRNA)-34 family (miR-34s), including miR-34a/b/c, is the most well studied non-coding RNAs that regulate gene expression post-transcriptionally. The miR-34s mediates the tumor suppressor ...function of p53 in the pathogenesis of breast cancer by targeting different oncogenes. This review focuses on the anti-oncogenic regulation of the miR-34s, emphasizing the major signaling pathways that are involved in the modulation of miR-34s in breast cancer. Moreover, it highlights how epigenetic modification by the p53/miR-34s axis regulates the proliferation, invasiveness, chemoresistance, and sternness of breast cancer. A better understanding of the molecular mechanisms of miR-34s will open new opportunities for the development of novel therapeutic strategies and define a new approach in identifying potential biomarkers for early diagnosis of breast cancer.
Miniaturized spectrometers have great potential for use in portable optoelectronics and wearable sensors. However, current strategies for miniaturization rely on von Neumann architectures, which ...separate the spectral sensing, storage, and processing modules spatially, resulting in high energy consumption and limited processing speeds due to the storage-wall problem. Here, we present a miniaturized spectrometer that utilizes a single SnS
/ReSe
van der Waals heterostructure, providing photodetection, spectrum reconstruction, spectral imaging, long-term image memory, and signal processing capabilities. Interface trap states are found to induce a gate-tunable and wavelength-dependent photogating effect and a non-volatile optoelectronic memory effect. Our approach achieves a footprint of 19 μm, a bandwidth from 400 to 800 nm, a spectral resolution of 5 nm, and a > 10
s long-term image memory. Our single-detector computational spectrometer represents a path beyond von Neumann architectures.
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