P-Element Homing Is Facilitated by engrailed Polycomb-Group Response Elements in Drosophila melanogaster

P-element vectors are commonly used to make transgenic Drosophila and generally insert in the genome in a nonselective manner. However, when specific fragments of regulatory DNA from a few Drosophila genes are incorporated into P-transposons, they cause the vectors to be inserted near the gene from which the DNA fragment was derived. This is called P-element homing. We mapped the minimal DNA fragment that could mediate homing to the engrailed/invected region of the genome. A 1.6 kb fragment of engrailed regulatory DNA that contains two Polycomb-group response elements (PREs) was sufficient for homing. We made flies that contain a 1.5kb deletion of engrailed DNA (enΔ1.5) in situ, including the PREs and the majority of the fragment that mediates homing. Remarkably, homing still occurs onto the enΔ1. 5 chromosome. In addition to homing to en, P[en] inserts near Polycomb group target genes at an increased frequency compared to P[EPgy2], a vector used to generate 18,214 insertions for the Drosophila gene disruption project. We suggest that homing is mediated by interactions between multiple proteins bound to the homing fragment and proteins bound to multiple areas of the engrailed/invected chromatin domain. Chromatin structure may also play a role in homing

The MOSFIRE Deep Evolution Field (MOSDEF) Survey: Rest-Frame Optical Spectroscopy for ~1500 H-Selected Galaxies at 1.37 < z < 3.8

In this paper we present the MOSFIRE Deep Evolution Field (MOSDEF) survey. The MOSDEF survey aims to obtain moderate-resolution (R=3000-3650) rest-frame optical spectra (~3700-7000 Angstrom) for ~1500 galaxies at 1.37<z<3.80 in three well-studied CANDELS fields: AEGIS, COSMOS, and GOODS-N. Targets are selected in three redshift intervals: 1.37<z<1.70, 2.09<z<2.61, and 2.95<z<3.80, down to fixed H_AB (F160W) magnitudes of 24.0, 24.5 and 25.0, respectively, using the photometric and spectroscopic catalogs from the 3D-HST survey. We target both strong nebular emission lines (e.g., [OII], Hbeta, [OIII], 5008, Halpha, [NII], and [SII]) and stellar continuum and absorption features (e.g., Balmer lines, Ca-II H and K, Mgb, 4000 Angstrom break). Here we present an overview of our survey, the observational strategy, the data reduction and analysis, and the sample characteristics based on spectra obtained during the first 24 nights. To date, we have completed 21 masks, obtaining spectra for 591 galaxies. For ~80% of the targets we derive a robust redshift from either emission or absorption lines. In addition, we confirm 55 additional galaxies, which were serendipitously detected. The MOSDEF galaxy sample includes unobscured star-forming, dusty star-forming, and quiescent galaxies and spans a wide range in stellar mass (~10^9-10^11.5 Msol) and star formation rate (~10^0-10^3 Msol/yr). The spectroscopically confirmed sample is roughly representative of an H-band limited galaxy sample at these redshifts. With its large sample size, broad diversity in galaxy properties, and wealth of available ancillary data, MOSDEF will transform our understanding of the stellar, gaseous, metal, dust, and black hole content of galaxies during the time when the universe was most active.Comment: Accepted for publication in ApJS; 28 pages, 19 figures; MOSDEF spectroscopic redshifts available at http://mosdef.astro.berkeley.edu/Downloads.htm

A contemporaneous infrared flash from a long gamma-ray burst: an echo from the central engine

The explosion that results in a cosmic gamma-ray burst (GRB) is thought to produce emission from two physical processes -- the activity of the central engine gives rise to the high-energy emission of the burst through internal shocking and the subsequent interaction of the flow with the external environment produces long-wavelength afterglow. While afterglow observations continue to refine our understanding of GRB progenitors and relativistic shocks, gamma-ray observations alone have not yielded a clear picture of the origin of the prompt emission nor details of the central engine. Only one concurrent visible-light transient has been found and was associated with emission from an external shock. Here we report the discovery of infrared (IR) emission contemporaneous with a GRB, beginning 7.2 minutes after the onset of GRB 041219a. Our robotic telescope acquired 21 images during the active phase of the burst, yielding the earliest multi-colour observations of any long-wavelength emission associated with a GRB. Analysis of an initial IR pulse suggests an origin consistent with internal shocks. This opens a new possibility to study the central engine of GRBs with ground-based observations at long wavelengths.Comment: Accepted to Nature on March 1, 2005. 9 pages, 4 figures, nature12.cls and nature1.cls files included. This paper is under press embargo until print publicatio

Keck-I MOSFIRE spectroscopy of compact star-forming galaxies at z≳\gtrsim2: High velocity dispersions in progenitors of compact quiescent galaxies

We present Keck-I MOSFIRE near-infrared spectroscopy for a sample of 13 compact star-forming galaxies (SFGs) at redshift $2\leq z \leq2.5$ with star formation rates of SFR$\sim$100M$_{\odot}$ y$^{-1}$ and masses of log(M/M$_{\odot}$)$\sim10.8$. Their high integrated gas velocity dispersions of $\sigma_{\rm{int}}$=230$^{+40}_{-30}$ km s$^{-1}$, as measured from emission lines of H$_{\alpha}$ and [OIII], and the resultant M$_{\star}-\sigma_{\rm{int}}$ relation and M$_{\star}$$-$M$_{\rm{dyn}}$ all match well to those of compact quiescent galaxies at $z\sim2$, as measured from stellar absorption lines. Since log(M$_{\star}$/M$_{\rm{dyn}}$)$=-0.06\pm0.2$ dex, these compact SFGs appear to be dynamically relaxed and more evolved, i.e., more depleted in gas and dark matter ($<$13$^{+17}_{-13}$\%) than their non-compact SFG counterparts at the same epoch. Without infusion of external gas, depletion timescales are short, less than $\sim$300 Myr. This discovery adds another link to our new dynamical chain of evidence that compact SFGs at $z\gtrsim2$ are already losing gas to become the immediate progenitors of compact quiescent galaxies by $z\sim2$.Comment: 12 pages, 7 figures, submitted to Ap

Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

Homocysteine metabolism pathway is involved in the control of glucose homeostasis: a cystathionine beta synthase deficiency study in mouse

Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. We used a mouse model heterozygous for CBS (CBS+/-) that presented a mild HHcy. Other groups were supplemented with methionine in drinking water to increase the mild to intermediate HHcy, and were submitted to a high-fat diet (HFD). We measured the food intake, body weight gain, body composition, glucose homeostasis, plasma homocysteine level, and CBS activity. We evidenced a defect in the stimulated insulin secretion in CBS+/- mice with mild and intermediate HHcy, while mice with intermediate HHcy under HFD presented an improvement in insulin sensitivity that compensated for the decreased insulin secretion and permitted them to maintain a glucose tolerance similar to the CBS+/+ mice. Islets isolated from CBS+/- mice maintained their ability to respond to the elevated glucose levels, and we showed that a lower parasympathetic tone could, at least in part, be responsible for the insulin secretion defect. Our results emphasize the important role of Hcy metabolic enzymes in insulin secretion and overall glucose homeostasis

Quantum Griffiths effects and smeared phase transitions in metals: theory and experiment

In this paper, we review theoretical and experimental research on rare region effects at quantum phase transitions in disordered itinerant electron systems. After summarizing a few basic concepts about phase transitions in the presence of quenched randomness, we introduce the idea of rare regions and discuss their importance. We then analyze in detail the different phenomena that can arise at magnetic quantum phase transitions in disordered metals, including quantum Griffiths singularities, smeared phase transitions, and cluster-glass formation. For each scenario, we discuss the resulting phase diagram and summarize the behavior of various observables. We then review several recent experiments that provide examples of these rare region phenomena. We conclude by discussing limitations of current approaches and open questions.Comment: 31 pages, 7 eps figures included, v2: discussion of the dissipative Ising chain fixed, references added, v3: final version as publishe

BAG3: a multifaceted protein that regulates major cell pathways

Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that interacts with the ATPase domain of the heat shock protein (Hsp) 70 through BAG domain (110–124 amino acids). BAG3 is the only member of the family to be induced by stressful stimuli, mainly through the activity of heat shock factor 1 on bag3 gene promoter. In addition to the BAG domain, BAG3 contains also a WW domain and a proline-rich (PXXP) repeat, that mediate binding to partners different from Hsp70. These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. A growing body of evidence indicate that BAG3 is instead expressed in several tumor types. In different tumor contexts, BAG3 protein was reported to sustain cell survival, resistance to therapy, and/or motility and metastatization. In some tumor types, down-modulation of BAG3 levels was shown, as a proof-of-principle, to inhibit neoplastic cell growth in animal models. This review attempts to outline the emerging mechanisms that can underlie some of the biological activities of the protein, focusing on implications in tumor progression

Gewalt in der Schule

Vortrag auf der Tagung Bindung, Trauma und soziale Gewalt , 3.-5.12.2004 in Frankfurt am Main