389 research outputs found
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
Keck-I MOSFIRE spectroscopy of compact star-forming galaxies at z2: 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 with star
formation rates of SFR100M y and masses of
log(M/M). Their high integrated gas velocity dispersions of
=230 km s, as measured from emission
lines of H and [OIII], and the resultant
M relation and MM all
match well to those of compact quiescent galaxies at , as measured from
stellar absorption lines. Since log(M/M)
dex, these compact SFGs appear to be dynamically relaxed and more evolved,
i.e., more depleted in gas and dark matter (13\%) than their
non-compact SFG counterparts at the same epoch. Without infusion of external
gas, depletion timescales are short, less than 300 Myr. This discovery
adds another link to our new dynamical chain of evidence that compact SFGs at
are already losing gas to become the immediate progenitors of
compact quiescent galaxies by .Comment: 12 pages, 7 figures, submitted to Ap
by M Sprenger Rapid communications HIV and AIDS in the European Union, 2009 4
D Tubin-Delic, on behalf of the outbreak control team Surveillance and outbreak reports Control of a multi-hospital outbreak of KPC-producing Klebsiella pneumonia
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
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
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
Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for <i>Elovl2</i> in glucose-induced insulin secretion.
In type 2 diabetes (T2D), pancreatic β cells become progressively dysfunctional, leading to a decline in insulin secretion over time. In this study, we aimed to identify key genes involved in pancreatic beta cell dysfunction by analyzing multiple mouse strains in parallel under metabolic stress.
Male mice from six commonly used non-diabetic mouse strains were fed a high fat or regular chow diet for three months. Pancreatic islets were extracted and phenotypic measurements were recorded at 2 days, 10 days, 30 days, and 90 days to assess diabetes progression. RNA-Seq was performed on islet tissue at each time-point and integrated with the phenotypic data in a network-based analysis.
A module of co-expressed genes was selected for further investigation as it showed the strongest correlation to insulin secretion and oral glucose tolerance phenotypes. One of the predicted network hub genes was <i>Elovl2</i> , encoding Elongase of very long chain fatty acids 2. <i>Elovl2</i> silencing decreased glucose-stimulated insulin secretion in mouse and human β cell lines.
Our results suggest a role for <i>Elovl2</i> in ensuring normal insulin secretory responses to glucose. Moreover, the large comprehensive dataset and integrative network-based approach provides a new resource to dissect the molecular etiology of β cell failure under metabolic stress
A Call for Action: The Application of the International Health Regulations to the Global Threat of Antimicrobial Resistance
Stephen Harbarth and colleagues argue that the International Health Regulations
(IHR) should be applied to the global health threat of antimicrobial
resistance
Diverse protostellar evolutionary states in the young cluster AFGL961
We present arcsecond resolution mid-infrared and millimeter observations of
the center of the young stellar cluster AFGL961 in the Rosette molecular cloud.
Within 0.2 pc of each other, we find an early B star embedded in a dense core,
a neighboring star of similar luminosity with no millimeter counterpart, a
protostar that has cleared out a cavity in the circumcluster envelope, and two
massive, dense cores with no infrared counterparts. An outflow emanates from
one of these cores, indicating a deeply embedded protostar, but the other is
starless, bound, and appears to be collapsing. The diversity of states implies
either that protostellar evolution is faster in clusters than in isolation or
that clusters form via quasi-static rather than dynamic collapse. The existence
of a pre-stellar core at the cluster center shows that that some star formation
continues after and in close proximity to massive, ionizing stars.Comment: 22 pages, 7 figures, accepted for publication in Ap
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