Quantum and Classical Optics–Emerging Links

Quantum optics and classical optics are linked in ways that are becoming apparent as a result of numerous recent detailed examinations of the relationships that elementary notions of optics have with each other. These elementary notions include interference, polarization, coherence, complementarity and entanglement. All of them are present in both quantum and classical optics. They have historic origins, and at least partly for this reason not all of them have quantitative definitions that are universally accepted. This makes further investigation into their engagement in optics very desirable. We pay particular attention to effects that arise from the mere co-existence of separately identifiable and readily available vector spaces. Exploitation of these vector-space relationships are shown to have unfamiliar theoretical implications and new options for observation. It is our goal to bring emerging quantum–classical links into wider view and to indicate directions in which forthcoming and future work will promote discussion and lead to unified understanding

Sequence-Specific DNA Recognition by Steroidogenic Factor 1: A Helix at the Carboxy-Terminus of the DNA Binding Domain is Necessary for Complex Stability

Abbreviated title: Structure-Function of SF1-DNA Interactions Key words: SF1; nuclear hormone receptor; DNA recognition; NMR; solution structure Disclosure of Potential Conflicts of Interest: K.E.M. has consulted for World Book Science Inc., has equity interests in Ligand Pharmaceuticals Inc., and received lecture fees from Serono Inc., but has no conflicts with entities directly related to the material being published. All other authors have nothing to disclose. This is an un-copyedited author manuscript copyrighted by The Endocrine Society. This may not be duplicated or reproduced, other than for personal use or within the rule of "Fair Use of Copyrighted Materials" (section 107, Title 17, U.S. Code) without permission of the copyright owner, The Endocrine Society. From the time of acceptance following peer review, the full text of this manuscript is made freely available by The Endocrine Society at http://www.endojournals.org/. The final copy edited article can be found at http://www.endojournals.org/. The Endocrine Society disclaims any responsibility or liability for errors or omissions in this version of the manuscript or in any version derived from it by the National Institutes of Health or other parties. base-pair DNA sequences as a monomer. Here we describe the solution structure of the SF1 DBD in complex with an atypical sequence in the proximal promoter region of the inhibingene that encodes a subunit of a reproductive hormone. SF1 forms a specific complex with the DNA through a bipartite motif binding to the major and minor grooves through the core DBD and the N-terminal segment of the FTZ-F1 box, respectively, in a manner previously described for two other monomeric receptors, NGFI-B and ERR2. However, unlike these receptors, SF1 harbors a helix in the C-terminal segment of the FTZ-F1 box that interacts with both the core DBD and DNA and serves as an important determinant of stability of the complex. We propose that the FTZ-F1 helix along with the core DBD serves as a platform for interactions with coactivators and other DNA-bound factors in the vicinity.

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Community Violence and Youth: Affect, Behavior, Substance Use, and Academics

Community violence is recognized as a major public health problem (WHO, World Report on Violence and Health,2002) that Americans increasingly understand has adverse implications beyond inner-cities. However, the majority of research on chronic community violence exposure focuses on ethnic minority, impoverished, and/or crime-ridden communities while treatment and prevention focuses on the perpetrators of the violence, not on the youth who are its direct or indirect victims. School-based treatment and preventive interventions are needed for children at elevated risk for exposure to community violence. In preparation, a longitudinal, community epidemiological study, The Multiple Opportunities to Reach Excellence (MORE) Project, is being fielded to address some of the methodological weaknesses presented in previous studies. This study was designed to better understand the impact of children’s chronic exposure to community violence on their emotional, behavioral, substance use, and academic functioning with an overarching goal to identify malleable risk and protective factors which can be targeted in preventive and intervention programs. This paper describes the MORE Project, its conceptual underpinnings, goals, and methodology, as well as implications for treatment and preventive interventions and future research

Negative regulation of NF-κB by the ING4 tumor suppressor in breast cancer

Nuclear Factor kappa B (NF-κB) is a key mediator of normal immune response but contributes to aggressive cancer cell phenotypes when aberrantly activated. Here we present evidence that the Inhibitor of Growth 4 (ING4) tumor suppressor negatively regulates NF-κB in breast cancer. We surveyed primary breast tumor samples for ING4 protein expression using tissue microarrays and a newly generated antibody. We found that 34% of tumors expressed undetectable to low levels of the ING4 protein (n = 227). Tumors with low ING4 expression were frequently large in size, high grade, and lymph node positive, suggesting that down-regulation of ING4 may contribute to breast cancer progression. In the same tumor set, we found that low ING4 expression correlated with high levels of nuclear phosphorylated p65/RelA (p-p65), an activated form of NF-κB (p = 0.018). Fifty seven percent of ING4-low/p-p65-high tumors were lymph node-positive, indicating a high metastatic tendency of these tumors. Conversely, ectopic expression of ING4 inhibited p65/RelA phosphorylation in T47D and MCF7 breast cancer cells. In addition, ING4 suppressed PMA-induced cell invasion and NF-κB-target gene expression in T47D cells, indicating that ING4 inhibited NF-κB activity in breast cancer cells. Supportive of the ING4 function in the regulation of NF-κB-target gene expression, we found that ING4 expression levels inversely correlated with the expression of NF-κB-target genes in primary breast tumors by analyzing public gene expression datasets. Moreover, low ING4 expression or high expression of the gene signature composed of a subset of ING4-repressed NF-κB-target genes was associated with reduced disease-free survival in breast cancer patients. Taken together, we conclude that ING4 negatively regulates NF-κB in breast cancer. Consequently, down-regulation of ING4 leads to activation of NF-κB, contributing to tumor progression and reduced disease-free patient survival in breast cancer

Generation and characterization of a monoclonal anti-ING4 antibody.

<p>(<b>A</b>) Schematic diagram of ING4 protein containing a nuclear localization signal (NLS) and a plant homeodomain (PHD). Stick figures represent the ING4 fragments that were used to immunize mice. (<b>B</b>) N-terminal (AA 5–147) and C-terminal (AA 173–249) recombinant fragments of ING4 purified from bacteria visualized by SDS-PAGE gel stained with Coomassie Blue. (<b>C</b>) Detection of ING4 and HA-epitope tagged ING4 overexpressed in 293T cells by Western blot using BTIM-4 and anti-HA monoclonal antibody. * denotes smaller ING4-derived protein species recognized by the antibody. (<b>D</b>) Western blot analysis of ING4 protein expression using BTIM-4 antibody in MCF10A breast epithelial cells and T47D breast cancer cells containing pMIG (the vector control), ING4 (ING4 overexpression), shNT (non-targeting shRNA control), or shING4 (shRNA targeting ING4). Tubulin antibody was used as a loading control. (<b>E</b>) MCF10A cells transduced with pMIG (the vector control), ING4 (ING4 overexpression), shNT (non-targeting shRNA control), or shING4 (shRNA targeting ING4), and T47D cells transduced with pMIG (the vector control) or ING4 (ING4 overexpression) were immunostained with BTIM-4 anti-ING4 antibody (red) and visualized using fluorescent microscopy. 4′,6-Diamidino-2-phenylindole (DAPI) was used to stain individual cell nuclei (blue). White scale bars represent 100 µm.</p

Low <i>ING4</i> mRNA expression and ING4-regulated NF-κB-target gene signature are associated with reduced disease-free survival in the GDS806 dataset.

<p>(<b>A</b>) Dot plot analysis of ING4 transcript levels in primary breast tumors from patients who remained disease-free (DF, n = 32) and from those who recurred (REC, n = 28) from the GDS806 dataset (n = 60). (<b>B</b>) Kaplan-Meier analysis of disease-free survival based on ING4 transcript level from the GDS806 dataset. CI, confidence interval. Kaplan-Meier analysis of disease-free survival based on NF-κB-target gene signatures (<b>C</b>) 25-gene or (<b>D</b>) 14-gene signature.</p

Tumors with low ING4 and high p-p65 levels are frequently lymph node-positive.

<p>Tumors with low ING4 and high p-p65 levels are frequently lymph node-positive.</p

ING4 represses NF-κB-target gene expression.

<p>(<b>A</b>) ING4 represses expression of a luciferase reporter construct containing an NRE (NF-κB response element) promoter sequence in T47D cells. (<b>B</b>) ING4 represses expression of endogenous NF-κB-target genes, <i>IL6, IL8,</i> and <i>PTGS2</i>, evaluated by RT-qPCR. (<b>C</b>) Heat map of 35 NF-κB-target genes induced by PMA in T47D pMIG (vector) cells (red, 2^nd row). Twenty-seven of 35 genes were repressed by ING4 (green, 4^th row). Starred genes indicate those previously measured in single RT-qPCR assays. (<b>D</b>) ING4 transcript level inversely correlates with NF-κB-target gene expression in breast tumors in two independent gene expression profile data sets, GDS806 (n = 60) and GSE3521 (n = 45). GDS806 contained gene expression data for 25 of the 27 NF-κB-target genes and GSE3521 contained gene expression data for all 27 NF-κB-target genes.</p