GUCY2C maintains intestinal LGR5+ stem cells by opposing ER stress

Long-lived multipotent stem cells (ISCs) at the base of intestinal crypts adjust their phenotypes to accommodate normal maintenance and post-injury regeneration of the epithelium. Their long life, lineage plasticity, and proliferative potential underlie the necessity for tight homeostatic regulation of the ISC compartment. In that context, the guanylate cyclase C (GUCY2C) receptor and its paracrine ligands regulate intestinal epithelial homeostasis, including proliferation, lineage commitment, and DNA damage repair. However, a role for this axis in maintaining ISCs remains unknown. Transgenic mice enabling analysis of ISCs (Lgr5-GFP) in the context of GUCY2C elimination (Gucy2c-/-) were combined with immunodetection techniques and pharmacological treatments to define the role of the GUCY2C signaling axis in supporting ISCs. ISCs were reduced in Gucy2c-/- mice, associated with loss of active Lgr5+ cells but a reciprocal increase in reserve Bmi1+ cells. GUCY2C was expressed in crypt base Lgr5+ cells in which it mediates canonical cyclic (c) GMPdependent signaling. Endoplasmic reticulum (ER) stress, typically absent from ISCs, was elevated throughout the crypt base in Gucy2c-/- mice. The chemical chaperone tauroursodeoxycholic acid resolved this ER stress and restored the balance of ISCs, an effect mimicked by the GUCY2C effector 8Br-cGMP. Reduced ISCs in Gucy2c-/-mice was associated with greater epithelial injury and impaired regeneration following sub-lethal doses of irradiation. These observations suggest that GUCY2C provides homeostatic signals that modulate ER stress and cell vulnerability as part of the machinery contributing to the integrity of ISCs. © Kraft et al

A Population Of Non-Recycled Pulsars Originating In Globular Clusters

We explore the enigmatic population of long-period, apparently non-recycled pulsars in globular clusters, building on recent work by Boyles et al. This population is difficult to explain if it formed through typical core-collapse supernovae, leading many authors to invoke electron capture supernovae. While Boyles et al. dealt only with non-recycled pulsars in clusters, we focus on the pulsars that originated in clusters but then escaped into the field of the Galaxy due to the kicks they receive at birth. The magnitude of the kick induced by electron capture supernovae is not well known, so we explore various models for the kick velocity distribution and size of the population. The most realistic models are those where the kick velocity is 10 km s–1 and where the number of pulsars scales with the luminosity of the cluster (as a proxy for cluster mass). This is in good agreement with other estimates of the electron capture supernovae kick velocity. We simulate a number of large-area pulsar surveys to determine if a population of pulsars originating in clusters could be identified as being separate from normal disk pulsars. We find that the spatial and kinematical properties of the population could be used, but only if large numbers of pulsars are detected. In fact, even the most optimistic surveys carried out with the future Square Kilometer Array are likely to detect \u3c10% of the total population, so the prospects for identifying these as a separate group of pulsars are presently poor

Measurement of complex fragments and clues to the entropy production from 42-137-MeV/nucleon Ar + Au

Intermediate-rapidity fragments with A=1-14 emitted from 42-137-MeV/nucleon Ar + Au have been measured. Evidence is presented that these fragments arise from a common moving source. Entropy values are extracted from the mass distributions by use of quantum statistical and Hauser-Feshbach theories. The extracted entropy values of S/A≈2-2.4 are much smaller than the values expected from measured deuteron-to-proton ratios, but are still considerably higher than theoretically predicted values

Going Beyond Promoting: Preparing Students to Creatively Solve Future Problems

While we cannot know what problems the future will bring, we can be almost certain that solving them will require creativity. In this article we describe how our course, a first-year undergraduate mathematics course, supports creative problem solving. Creative problem solving cannot be learned through a single experience, so we provide our students with a blend of experiences. We discuss how the course structure enables creative problem solving through class instruction, during class activities, during out of class assessments, and during in class assessments. We believe this course structure increases student comfort with solving open-ended and ill-defined problems similar to what they will encounter in the real world

Light particle spectra from 35 MeV/nucleon 12C-induced reactions on 197Au

Energy spectra for p, d, t, 3He, 4He, and 6He from the reaction 12C+197Au at 35 MeV/nucleon are presented. A common intermediate rapidity source is identified using a moving source fit to the spectra that yields cross sections which are compared to analogous data at other bombarding energies and to several different models. The excitation function of the composite to proton ratios is compared with quantum statistical, hydrodynamic, and thermal models

Values of Exemplary Jesuit College Graduates

What values do undergraduates adopt and internalize as a result of their college experiences at a Catholic Jesuit college/university? In an attempt to answer this question, the authors chose 21 exemplary graduates from 2000-2007 at a Catholic, Jesuit college in the northeastern part of the United States and conducted a ten question intensive interview with each of them. After transcribing and coding the interviews, it was discovered that these graduates had a strong grasp of such Jesuit ideals as “men and women for others,” “educating the whole person,” “cura personalis,” and “magis,” but apparently a weaker grasp of the more recent Jesuit emphasis on diversity and social justice. Faculty and members of the campus ministry staff had a strong influence on helping these graduates to develop a better sense of Jesuit values. Campus ministry activities, service and immersion trips, and research with faculty helped those interviewed to learn and practice Jesuit values

Gene Expression Profiling of Bronchoalveolar Lavage Cells Preceding a Clinical Diagnosis of Chronic Lung Allograft Dysfunction.

BackgroundChronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.MethodsIn a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD) >2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated).ResultsThe cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells). Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively) into incipient CLAD and CLAD-free categories.ConclusionsThese findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted

Winter 1993 observations of oceanography and sediment transport at the LEO-15 site

The NOAA National Underseas Research Program at Rutgers University is establishing a Long-term Ecosystem Observatory off New Jersey in 15 meters of water. As part of a bottom boundary layer study at this site, WHOI deployed a bottom instrument frame during the winter of 1993-94. The bottom instrument carried a current meter, a vertical array of optical back scattering sensors, temperature, pressure and conductivity sensors and an Acoustical Backscattering Sensor. The deployment was partially successful as the acoustic system failed. The other instrumentation worked well for 3 weeks returning data on winter conditions at the site. The extreme winter waves ended the experiment by tipping the instrument over on its side. The optical instrumentation was calibrated with sediment from the site, and the results from the experiment presented.Funding was provided by the National Oceanic and Atmospheric Administration through Contract No. 4-25020 to Rutgers/SUNY National Underseas Research Program