Role for A-Type Lamins in Herpesviral DNA Targeting and Heterochromatin Modulation

Posttranslational modification of histones is known to regulate chromatin structure and transcriptional activity, and the nuclear lamina is thought to serve as a site for heterochromatin maintenance and transcriptional silencing. In this report, we show that the nuclear lamina can also play a role in the downregulation of heterochromatin and in gene activation. Herpes simplex virus DNA initiates replication in replication compartments near the inner edge of the nucleus, and histones are excluded from these structures. To define the role of nuclear lamins in HSV replication, we examined HSV infection in wild-type and A-type lamin–deficient (Lmna−/−) murine embryonic fibroblasts (MEFs). In Lmna−/− cells, viral replication compartments are reduced in size and fail to target to the nuclear periphery, as observed in WT cells. Chromatin immunoprecipitation and immunofluorescence studies demonstrate that HSV DNA is associated with increased heterochromatin in Lmna−/− MEFs. These results argue for a functional role for A-type lamins as viral gene expression, DNA replication, and growth are reduced in Lmna−/− MEFs, with the greatest effect on viral replication at low multiplicity of infection. Thus, lamin A/C is required for targeting of the viral genome and the reduction of heterochromatin on viral promoters during lytic infection. The nuclear lamina can serve as a molecular scaffold for DNA genomes and the protein complexes that regulate both euchromatin and heterochromatin histone modifications

Wafer bonding and layer transfer processes for 4-junction high efficiency solar cells

A four-junction cell design consisting of InGaAs, InGeAsP, GaAs, and Ga0.5In0.5P subcells could reach 1 x AMO efficiencies of 35.4%. but relies on the integration of non-lattice-matched materials. Wafer bonding and layer transfer processes show promise in the fabrication of InP/Si epitaxial templates for growth of the bottom InGaAs and InGaAsP subcells on a Si support substrate. Subsequent wafer bonding and layer transfer of a thin Ge layer onto the lower subcell stack can serve as an epitaxial template for GaAs and Ga0.5In0.5P subcelis. Present results indicate that optically active III/V compound semiconductors can be grown on both Ge/Si and InP/Si heterostructures. Current-voltage electrical characterization of the interfaces of these structures indicates that both InP/Si and Ge/Si interfaces have specific resistances lower than 0.1 Ωcm^2 for heavily doped wafer bonded interfaces, enabling back surface power extraction from the finished cell structure

The Cosmic Web Imager: An integral field spectrograph for the Hale Telescope at Palomar Observatory: Instrument design and first results

We describe the Cosmic Web Imager (CWI), a UV-VIS integral field spectrograph designed for the Hale 200" telescope at the Palomar Observatory. CWI has been built specifically for the observation of diffuse radiation. The instrument field of view is 60" x 40" with spectral resolving power of R ~5000 and seeing limited spatial resolution. It utilizes volume phase holographic gratings and is intended to cover the spectral range 3800Å to 9500Å with an instantaneous bandwidth of ~450Å. CWI saw first light in July 2009, and conducted its first successful scientific observations in May 2010

Non-FG mediated transport of the large pre-ribosomal subunit through the nuclear pore complex by the mRNA export factor Gle2

Multiple export receptors passage bound pre-ribosomes through nuclear pore complexes (NPCs) by transiently interacting with the Phe-Gly (FG) meshwork of their transport channels. Here, we reveal how the non-FG interacting yeast mRNA export factor Gly-Leu-FG lethal 2 (Gle2) functions in the export of the large pre-ribosomal subunit (pre-60S). Structure-guided studies uncovered conserved platforms used by Gle2 to export pre-60S: an uncharacterized basic patch required to bind pre-60S, and a second surface that makes non-FG contacts with the nucleoporin Nup116. A basic patch mutant of Gle2 is able to function in mRNA export, but not pre-60S export. Thus, Gle2 provides a distinct interaction platform to transport pre-60S to the cytoplasm. Notably, Gle2's interaction platforms become crucial for pre-60S export when FG-interacting receptors are either not recruited to pre-60S or are impaired. We propose that large complex cargos rely on non-FG as well as FG-interactions for their efficient translocation through the nuclear pore complex channe

Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion.

Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple-negative" breast cancer (TNBC). Because phosphatases regulate the function of kinase signaling pathways, in this study, we investigated whether phosphatases are also differentially expressed in ER-negative compared to those in ER-positive breast cancers. We compared RNA expression in 98 human breast cancers (56 ER-positive and 42 ER-negative) to identify phosphatases differentially expressed in ER-negative compared to those in ER-positive breast cancers. We then examined the effects of one selected phosphatase, dual specificity phosphatase 4 (DUSP4), on proliferation, cell growth, migration and invasion, and on signaling pathways using protein microarray analyses of 172 proteins, including phosphoproteins. We identified 48 phosphatase genes are significantly differentially expressed in ER-negative compared to those in ER-positive breast tumors. We discovered that 31 phosphatases were more highly expressed, while 11 were underexpressed specifically in ER-negative breast cancers. The DUSP4 gene is underexpressed in ER-negative breast cancer and is deleted in approximately 50 % of breast cancers. Induced DUSP4 expression suppresses both in vitro and in vivo growths of breast cancer cells. Our studies show that induced DUSP4 expression blocks the cell cycle at the G1/S checkpoint; inhibits ERK1/2, p38, JNK1, RB, and NFkB p65 phosphorylation; and inhibits invasiveness of TNBC cells. These results suggest that that DUSP4 is a critical regulator of the growth and invasion of triple-negative breast cancer cells

Organization of Valence-Encoding and Projection-Defined Neurons in the Basolateral Amygdala

The basolateral amygdala (BLA) mediates associative learning for both fear and reward. Accumulating evidence supports the notion that different BLA projections distinctly alter motivated behavior, including projections to the nucleus accumbens (NAc), medial aspect of the central amygdala (CeM), and ventral hippocampus (vHPC). Although there is consensus regarding the existence of distinct subsets of BLA neurons encoding positive or negative valence, controversy remains regarding the anatomical arrangement of these populations. First, we map the location of more than 1,000 neurons distributed across the BLA and recorded during a Pavlovian discrimination task. Next, we determine the location of projection-defined neurons labeled with retrograde tracers and use CLARITY to reveal the axonal path in 3-dimensional space. Finally, we examine the local influence of each projection-defined populations within the BLA. Understanding the functional and topographical organization of circuits underlying valence assignment could reveal fundamental principles about emotional processing. Basolateral amygdala (BLA) neurons distinctly encode cues predicting rewards or punishments, but how does form give rise to function? Beyeler et al. overlay anatomical projection target, location of neurons in a 3D map, and encoding properties during cue discrimination. The influence on local networks differs across projection-defined BLA populations. Keywords: reward; aversion; topography; tracing; connectivity; network; channelrhodopsin; phototagging; photoexcitation; photoinhitionNational Institute of Mental Health (U.S.) (Grant R01-MH102441)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Award DP2-DK-102256

Interference effects in two-photon ATI by multiple orders high harmonics with random or locked phases

We numerically study 2-photon processes using a set of harmonics from a Ti:Sapphire laser and in particular interference effects in the Above Threshold Ionization spectra. We compare the situation where the harmonic phases are assumed locked to the case where they have a random distribution. Suggestions for possible experiments, using realistic parameters are discussed.Comment: 11 pages, 13 figures, LaTe

An examination of writing pauses in the handwriting of children with Developmental Coordination Disorder.

This article has been made available through the Brunel Open Access Publishing Fund.Difficulties with handwriting are reported as one of the main reasons for the referral of children with Developmental Coordination Disorder (DCD) to healthcare professionals. In a recent study we found that children with DCD produced less text than their typically developing (TD) peers and paused for 60% of a free-writing task. However, little is known about the nature of the pausing; whether they are long pauses possibly due to higher level processes of text generation or fatigue, or shorter pauses related to the movements between letters. This gap in the knowledge-base creates barriers to understanding the handwriting difficulties in children with DCD. The aim of this study was to characterise the pauses observed in the handwriting of English children with and without DCD. Twenty-eight 8-14 year-old children with a diagnosis of DCD participated in the study, with 28 TD age and gender matched controls. Participants completed the 10 min free-writing task from the Detailed Assessment of Speed of Handwriting (DASH) on a digitising writing tablet. The total overall percentage of pausing during the task was categorised into four pause time-frames, each derived from the literature on writing (250 ms to 2 s; 2-4 s; 4-10 s and >10 s). In addition, the location of the pauses was coded (within word/between word) to examine where the breakdown in the writing process occurred. The results indicated that the main group difference was driven by more pauses above 10 s in the DCD group. In addition, the DCD group paused more within words compared to TD peers, indicating a lack of automaticity in their handwriting. These findings may support the provision of additional time for children with DCD in written examinations. More importantly, they emphasise the need for intervention in children with DCD to promote the acquisition of efficient handwriting skill