Ubiquitin Regulation: The Histone Modifying Enzyme\u27s Story

Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned and precisely regulated at the level of protein turnover by ubiquitin-proteasomal processing. Here, we focus on recent progress centered on the mechanisms regulating ubiquitination of histone modifying enzymes, including ubiquitin proteasomal degradation and the reverse process of deubiquitination. We will also discuss the potential pathophysiological significance of these processes

The Landscape of Histone Modification in Cancer Metastasis

Metastasis represents one of the most devastating aspects of cancer. Epithelial to mesenchymal transition (EMT) has been shown to play a critical role in tumorigenic metastasis. During metastatic progression, both genetic and epigenetic modifications endow cancer cells with properties that modulate the capacity for metastatic success. Histone modification is profoundly altered in cancer cells and contributes to cancer metastasis by controlling different metastatic phenotypes. Here, we first review histone modifications and discuss their roles in EMT and metastasis, with a particular focus on histone methylation and acetylation. Second, we review the major histone modification enzymes that control chromatin in cancer metastasis. Third, we discuss the transcriptional regulation concerted by these enzymes with EMT transcription factors at different molecular layers. Finally, we discuss pharmacologic manipulation of histone modification enzymes for metastasis treatment. A comprehensive understanding of histone modification in metastasis will not only provide new insights into our knowledge of cancer progression and metastasis, but also offer a novel approach for the development of innovative therapeutic strategies

Tackle Epithelial-Mesenchymal Transition with Epigenetic Drugs in Cancer

Epithelial-mesenchymal Transition (EMT) is a de-differentiation process in which epithelial cells lose their epithelial properties to acquire mesenchymal features. EMT is essential for embryogenesis and wound healing but is aberrantly activated in pathological conditions like fibrosis and cancer. Tumor-associated EMT contributes to cancer cell initiation, invasion, metastasis, drug resistance and recurrence. This dynamic and reversible event is governed by EMT-transcription factors (EMT-TFs) with epigenetic complexes. In this review, we discuss recent advances regarding the mechanisms that modulate EMT in the context of epigenetic regulation, with emphasis on epigenetic drugs, such as DNA demethylating reagents, inhibitors of histone modifiers and non-coding RNA medication. Therapeutic contributions that improve epigenetic regulation of EMT will translate the clinical manifestation as treating cancer progression more efficiently

Properties of V1 Neurons Tuned to Conjunctions of Visual Features: Application of the V1 Saliency Hypothesis to Visual Search behavior

From a computational theory of V1, we formulate an optimization problem to investigate neural properties in the primary visual cortex (V1) from human reaction times (RTs) in visual search. The theory is the V1 saliency hypothesis that the bottom-up saliency of any visual location is represented by the highest V1 response to it relative to the background responses. The neural properties probed are those associated with the less known V1 neurons tuned simultaneously or conjunctively in two feature dimensions. The visual search is to find a target bar unique in color (C), orientation (O), motion direction (M), or redundantly in combinations of these features (e.g., CO, MO, or CM) among uniform background bars. A feature singleton target is salient because its evoked V1 response largely escapes the iso-feature suppression on responses to the background bars. The responses of the conjunctively tuned cells are manifested in the shortening of the RT for a redundant feature target (e.g., a CO target) from that predicted by a race between the RTs for the two corresponding single feature targets (e.g., C and O targets). Our investigation enables the following testable predictions. Contextual suppression on the response of a CO-tuned or MO-tuned conjunctive cell is weaker when the contextual inputs differ from the direct inputs in both feature dimensions, rather than just one. Additionally, CO-tuned cells and MO-tuned cells are often more active than the single feature tuned cells in response to the redundant feature targets, and this occurs more frequently for the MO-tuned cells such that the MO-tuned cells are no less likely than either the M-tuned or O-tuned neurons to be the most responsive neuron to dictate saliency for an MO target

Photoacoustic Identification of Laser-induced Microbubbles as Light Scattering Centers for Optical Limiting in Liquid Suspension of Graphene Nanosheets

Liquid suspensions of carbon nanotubes, graphene and transition metal dichalcogenides have exhibited excellent performance in optical limiting. However, the underlying mechanism has remained elusive and is generally ascribed to their superior nonlinear optical properties such as nonlinear absorption or nonlinear scattering. Using graphene as an example, we show that photo-thermal microbubbles are responsible for the optical limiting as strong light scattering centers: graphene sheets absorb incident light and become heated up above the boiling point of water, resulting in vapor and microbubble generation. This conclusion is based on direct observation of bubbles above the laser beam as well as a strong correlation between laser-induced ultrasound and optical limiting. In-situ Raman scattering of graphene further confirms that the temperature of graphene under laser pulses rises above the boiling point of water but still remains too low to vaporize graphene and create graphene plasma bubbles. Photo-thermal bubble scattering is not a nonlinear optical process and requires very low laser intensity. This understanding helps us to design more efficient optical limiting materials and understand the intrinsic nonlinear optical properties of nanomaterials

Localized concentration reversal of lithium during intercalation into nanoparticles.

Nanoparticulate electrodes, such as Li x FePO4, have unique advantages over their microparticulate counterparts for the applications in Li-ion batteries because of the shortened diffusion path and access to nonequilibrium routes for fast Li incorporation, thus radically boosting power density of the electrodes. However, how Li intercalation occurs locally in a single nanoparticle of such materials remains unresolved because real-time observation at such a fine scale is still lacking. We report visualization of local Li intercalation via solid-solution transformation in individual Li x FePO4 nanoparticles, enabled by probing sub-angstrom changes in the lattice spacing in situ. The real-time observation reveals inhomogeneous intercalation, accompanied with an unexpected reversal of Li concentration at the nanometer scale. The origin of the reversal phenomenon is elucidated through phase-field simulations, and it is attributed to the presence of structurally different regions that have distinct chemical potential functions. The findings from this study provide a new perspective on the local intercalation dynamics in battery electrodes

Separate cortical stages in amodal completion revealed by functional magnetic resonance adaptation

<p>Abstract</p> <p>Background</p> <p>Objects in our environment are often partly occluded, yet we effortlessly perceive them as whole and complete. This phenomenon is called visual amodal completion. Psychophysical investigations suggest that the process of completion starts from a representation of the (visible) physical features of the stimulus and ends with a completed representation of the stimulus. The goal of our study was to investigate both stages of the completion process by localizing both brain regions involved in processing the physical features of the stimulus as well as brain regions representing the completed stimulus.</p> <p>Results</p> <p>Using fMRI adaptation we reveal clearly distinct regions in the visual cortex of humans involved in processing of amodal completion: early visual cortex – presumably V1 -processes the local contour information of the stimulus whereas regions in the inferior temporal cortex represent the completed shape. Furthermore, our data suggest that at the level of inferior temporal cortex information regarding the original local contour information is not preserved but replaced by the representation of the amodally completed percept.</p> <p>Conclusion</p> <p>These findings provide neuroimaging evidence for a multiple step theory of amodal completion and further insights into the neuronal correlates of visual perception.</p

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

<p>Abstract</p> <p>Background</p> <p>Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.</p> <p>Methods</p> <p>As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip^®Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.</p> <p>Results</p> <p>A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.</p> <p>Conclusions</p> <p>PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.</p

Feed-Forward Segmentation of Figure-Ground and Assignment of Border-Ownership

Figure-ground is the segmentation of visual information into objects and their surrounding backgrounds. Two main processes herein are boundary assignment and surface segregation, which rely on the integration of global scene information. Recurrent processing either by intrinsic horizontal connections that connect surrounding neurons or by feedback projections from higher visual areas provide such information, and are considered to be the neural substrate for figure-ground segmentation. On the contrary, a role of feedforward projections in figure-ground segmentation is unknown. To have a better understanding of a role of feedforward connections in figure-ground organization, we constructed a feedforward spiking model using a biologically plausible neuron model. By means of surround inhibition our simple 3-layered model performs figure-ground segmentation and one-sided border-ownership coding. We propose that the visual system uses feed forward suppression for figure-ground segmentation and border-ownership assignment