Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biology, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 27-29).The endoplasmic reticulum (ER) is responsible for the folding and processing of approximately one third of proteins in eukaryotic cells, and homeostasis in this compartment is tightly regulated. The Unfolded Protein Response, or UPR, is activated in response to perturbations in protein folding in the ER, collectively termed ER stress. This compensatory mechanism, mediated by IRE-1, PERK- 1/PEK-1 and ATF-6 in metazoans, resolves an overcrowded ER lumen in part through the increase of protein degradation and folding. Typical studies focus on activation of the UPR in response to characterized chemical agents that potently alter ER function or protein stability and folding, leaving physiological or native roles for the UPR relatively uncharacterized. Richardson et al previously demonstrated a role for the UPR in innate immunity in C elegans. Here, in an effort to understand this role, we demonstrate that intestinal expression of XBP-1 is sufficient to overcome PMK-1 dependent larval lethality on a lawn of pathogenic Pseudomonas aeruginosa. Further, we demonstrate that XBP-1 deficiency results in constitutive ER stress even in the absence of pathogenic infection. This elevated ER stress is reflected by increased activities of both IRE- 1 and PEK-1 under physiological conditions. Our data suggest that negative feedback loops involving the activation of IRE-1-XBP-1 and PEK-1 pathways serve essential roles not only at the extremes of ER stress but also in the maintenance of ER homeostasis under physiological conditions.by Stephanie A. Kinkel.S.M

ESUR guidelines for MR imaging of the sonographically indeterminate adnexal mass: an algorithmic approach

A significant proportion of adnexal masses detected by sonography are indeterminate. Either their organ of origin is uncertain or it is unclear whether their nature is benign or malignant. MR imaging of the sonographically indeterminate adnexal mass can resolve most of these uncertainties. Most indeterminate masses result from common benign conditions and women with such masses can avoid unnecessary or inappropriate surgery. For the minority of women whose masses are malignant, use of MR imaging rather than a ‘wait and watch’ strategy of repeat ultrasound (US) results in a more timely diagnosis. There are simple diagnostic steps in the MR imaging assessment which direct an algorithmic and problem-solving approach based on signal characteristics and morphology. MR imaging should provide a more timely diagnosis and, thereby, guide the management of the patient with reduced costs of investigation and treatment

Prospective study of 310 patients: can early CT predict the severity of acute pancreatitis?

Background: This study was designed to determine the most important early CT parameters predictive of acute pancreatitis severity. Methods: Three hundred and seventy-one consecutive patients with acute abdominal pain and hyperamylasemia were enrolled. Three hundred and ten of the 371 patients met our inclusion criteria. Acute pancreatitis severity was evaluated using the 1992 Atlanta criteria. Different CT parameters were reported from the admission abdominal CT by two radiologists blinded from any clinical parameter, but the patients' age and gender. These variables were fitted in a binary logistic regression model. Results: Acute pancreatitis was mild in 80% cases, severe in 20% cases and lethal in 12.69% cases. The following CT parameters were significantly associated with the severity of acute pancreatitis: the objective size of the pancreas (P=0.001), the peripancreatic fat abnormalities (P=0.001) and the extent of necrosis (P=0.007). Moreover, the age of the patient revealed itself a highly significant (P=0.001) indicator of disease severity. The association of the four CT criteria eventually showed a sensitivity of 73% and a specificity of 81% to predict acute pancreatitis severity. Conclusion: Although these criteria correlated with disease severity, our study identified that morphological CT criteria cannot be used to triage patients with severe and mild acute pancreatiti

The Oxygen Abundance of Nearby Galaxies from Sloan Digital Sky Survey Spectra

We have derived the oxygen abundance for a sample of nearby galaxies in the Data Release 5 of the Sloan Digital Sky Survey (SDSS) which possess at least two independent spectra of one or several HII regions with a detected [OIII]4363 auroral line. Since, for nearby galaxies, the [OII]3727 nebular line is out of the observed wavelength range, we propose a method to derive (O/H)_ff abundances using the classic Te method coupled with the ff relation. (O/H)_7325 abundances have also been determined, based on the [OII]7320,7330 line intensities, and using a small modification of the standard Te method. The (O/H)_ff and (O/H)_7325 abundances have been derived with both the one- and two-dimensional t_2 - t_3 relations. It was found that the (O/H)_ff abundances derived with the parametric two-dimensional t_2 - t_3 relation are most reliable. Oxygen abundances have been determined in 29 nearby galaxies, based on 84 individual abundance determinations in HII regions. Because of our selection methods, the metallicity of our galaxies lies in the narrow range 8.2 < 12 + log (O/H) < 8.4. The radial distribution of oxygen abundances in the disk of the spiral galaxy NGC 4490 is determined for the first time.Comment: 39 pages, 10 figures, 4 tables, accepted for publication in the Astrophysical Journa

Staging of endometrial cancer with MRI: Guidelines of the European Society of Urogenital Imaging

The purpose of this study was to define guidelines for endometrial cancer staging with MRI. The technique included critical review and expert consensus of MRI protocols by the female imaging subcommittee of the European Society of Urogenital Radiology, from ten European institutions, and published literature between 1999 and 2008. The results indicated that high field MRI should include at least two T2-weighted sequences in sagittal, axial oblique or coronal oblique orientation (short and long axis of the uterine body) of the pelvic content. High-resolution post-contrast images acquired at 2min ± 30 s after intravenous contrast injection are suggested to be optimal for the diagnosis of myometrial invasion. If cervical invasion is suspected, additional slice orientation perpendicular to the axis of the endocervical channel is recommended. Due to the limited sensitivity of MRI to detect lymph node metastasis without lymph node-specific contrast agents, retroperitoneal lymph node screening with pre-contrast sequences up to the level of the kidneys is optional. The likelihood of lymph node invasion and the need for staging lymphadenectomy are also indicated by high-grade histology at endometrial tissue sampling and by deep myometrial or cervical invasion detected by MRI. In conclusion, expert consensus and literature review lead to an optimized MRI protocol to stage endometrial cance

Staging of endometrial cancer with MRI: guidelines of the european society of urogenital imaging

The purpose of this study was to define guidelines for endometrial cancer staging with MRI. The technique included critical review and expert consensus of MRI protocols by the female imaging subcommittee of the European Society of Urogenital Radiology, from ten European institutions, and published literature between 1999 and 2008. The results indicated that high field MRI should include at least two T2-weighted sequences in sagittal, axial oblique or coronal oblique orientation (short and long axis of the uterine body) of the pelvic content. High-resolution postcontrast images acquired at 2 min ± 30 s after intravenous contrast injection are suggested to be optimal for the diagnosis of myometrial invasion. If cervical invasion is suspected, additional slice orientation perpendicular to the axis of the endocervical channel is recommended. Due to the limited sensitivity of MRI to detect lymph node metastasis without lymph nodespecific contrast agents, retroperitoneal lymph node screening with pre-contrast sequences up to the level of the kidneys is optional. The likelihood of lymph node invasion and the need for staging lymphadenectomy are also indicated by high-grade histology at endometrial tissue sampling and by deep myometrial or cervical invasion detected by MRI. In conclusion, expert consensus and literature review lead to an optimized MRI protocol to stage endometrial cancer