Achalasia.

SummaryAchalasia is a rare motility disorder of the oesophagus characterised by loss of enteric neurons leading to absence of peristalsis and impaired relaxation of the lower oesophageal sphincter. Although its cause remains largely unknown, ganglionitis resulting from an aberrant immune response triggered by a viral infection has been proposed to underlie the loss of oesophageal neurons, particularly in genetically susceptible individuals. The subsequent stasis of ingested food not only leads to symptoms of dysphagia, regurgitation, chest pain, and weight loss, but also results in an increased risk of oesophageal carcinoma. At present, pneumatic dilatation and Heller myotomy combined with an anti-reflux procedure are the treatments of choice and have comparable success rates. Per-oral endoscopic myotomy has recently been introduced as a new minimally invasive treatment for achalasia, but there have not yet been any randomised clinical trials comparing this option with pneumatic dilatation and Heller myotomy

Essential role for non-canonical poly(A) polymerase GLD4 in cytoplasmic polyadenylation and carbohydrate metabolism

Regulation of gene expression at the level of cytoplasmic polyadenylation is important for many biological phenomena including cell cycle progression, mitochondrial respiration, and learning and memory. GLD4 is one of the non-canonical poly(A) polymerases that regulates cytoplasmic polyadenylation-induced translation, but its target mRNAs and role in cellular physiology is not well known. To assess the full panoply of mRNAs whose polyadenylation is controlled by GLD4, we performed an unbiased whole genome-wide screen using poy(U) chromatography and thermal elution. We identified hundreds of mRNAs regulated by GLD4, several of which are involved in carbohydrate metabolism including GLUT1, a major glucose transporter. Depletion of GLD4 not only reduced GLUT1 poly(A) tail length, but also GLUT1 protein. GLD4-mediated translational control of GLUT1 mRNA is dependent of an RNA binding protein, CPEB1, and its binding elements in the 3 UTR. Through regulating GLUT1 level, GLD4 affects glucose uptake into cells and lactate levels. Moreover, GLD4 depletion impairs glucose deprivation-induced GLUT1 up-regulation. In addition, we found that GLD4 affects glucose-dependent cellular phenotypes such as migration and invasion in glioblastoma cells. Our observations delineate a novel post-transcriptional regulatory network involving carbohydrate metabolism and glucose homeostasis mediated by GLD4

Optimization of ribosome profiling using low-input brain tissue from fragile X syndrome model mice

Dysregulated protein synthesis is a major underlying cause of many neurodevelopmental diseases including fragile X syndrome. In order to capture subtle but biologically significant differences in translation in these disorders, a robust technique is required. One powerful tool to study translational control is ribosome profiling, which is based on deep sequencing of mRNA fragments protected from ribonuclease (RNase) digestion by ribosomes. However, this approach has been mainly applied to rapidly dividing cells where translation is active and large amounts of starting material are readily available. The application of ribosome profiling to low-input brain tissue where translation is modest and gene expression changes between genotypes are expected to be small has not been carefully evaluated. Using hippocampal tissue from wide type and fragile X mental retardation 1 (Fmr1) knockout mice, we show that variable RNase digestion can lead to significant sample batch effects. We also establish GC content and ribosome footprint length as quality control metrics for RNase digestion. We performed RNase titration experiments for low-input samples to identify optimal conditions for this critical step that is often improperly conducted. Our data reveal that optimal RNase digestion is essential to ensure high quality and reproducibility of ribosome profiling for low-input brain tissue

The Intersection of GERD, Aspiration, and Lung Transplantation

Lung transplantation is a radical but life-saving treatment option for patients with end-stage lung diseases, such as idiopathic pulmonary fibrosis (IPF) and scleroderma. In light of the proposed association and controversy linking gastroesophageal reflux disease (GERD) to IPF and lung transplant outcome, the American Gastroenterological Association convened during the DDW in Washington in May 2015 a multidisciplinary group of experts in the field of GERD and lung transplantation to make considerations about the care of these patients based on available data and subsequent expert panel discussion at this symposium. The following topics were discussed: (1) pathophysiology of GERD-induced pulmonary symptoms, (2) GERD evaluation before and after lung transplantation, (3) outcome of lung transplantation for IPF and scleroderma, and (4) role of laparoscopic fundoplication before or after lung transplantation

Cytoplasmic polyadenylation and cytoplasmic polyadenylation element-dependent mRNA regulation are involved in Xenopus retinal axon development.

BACKGROUND: Translation in axons is required for growth cone chemotropic responses to many guidance cues. Although locally synthesized proteins are beginning to be identified, how specific mRNAs are selected for translation remains unclear. Control of poly(A) tail length by cytoplasmic polyadenylation element (CPE) binding protein 1 (CPEB1) is a conserved mechanism for mRNA-specific translational regulation that could be involved in regulating translation in axons. RESULTS: We show that cytoplasmic polyadenylation is required in Xenopus retinal ganglion cell (RGC) growth cones for translation-dependent, but not translation-independent, chemotropic responses in vitro, and that inhibition of CPE binding through dominant-negative interference severely reduces axon outgrowth in vivo. CPEB1 mRNA transcripts are present at low levels in RGCs but, surprisingly, CPEB1 protein was not detected in eye or brain tissue, and CPEB1 loss-of-function does not affect chemotropic responses or pathfinding in vivo. UV cross-linking experiments suggest that CPE-binding proteins other than CPEB1 in the retina regulate retinal axon development. CONCLUSION: These results indicate that cytoplasmic polyadenylation and CPE-mediated translational regulation are involved in retinal axon development, but that CPEB1 may not be the key regulator of polyadenylation in the developing retina.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The Velocity Function of Galaxies

We present a galaxy circular velocity function, Psi(log v), derived from existing luminosity functions and luminosity-velocity relations. Such a velocity function is desirable for several reasons. First, it enables an objective comparison of luminosity functions obtained in different bands and for different galaxy morphologies, with a statistical correction for dust extinction. In addition, the velocity function simplifies comparison of observations with predictions from high-resolution cosmological N-body simulations. We derive velocity functions from five different data sets and find rough agreement among them, but about a factor of 2 variation in amplitude. These velocity functions are then compared with N-body simulations of a LCDM model (corrected for baryonic infall) in order to demonstrate both the utility and current limitations of this approach. The number density of dark matter halos and the slope of the velocity function near v_*, the circular velocity corresponding to an ~L_* spiral galaxy, are found to be comparable to that of observed galaxies. The primary sources of uncertainty in construction of Psi(log v) from observations and N-body simulations are discussed and explanations are suggected to account for these discrepancies.Comment: Latex. 28 pages, 4 figures. Accepted by Ap

Barrett's esophagus: prevalence–incidence and etiology–origins

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86957/1/j.1749-6632.2011.06042.x.pd

Proposed initiative would study Earth's weathering engine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94818/1/eost14765.pd

The Grizzly, December 6, 1994

Beetlemania Hits Ursinus • Strassburger Appointed President • Unrest in the Baltics Continues • Ursinus Birthday Card Unveiled • Jeffrey Dahmer Dead • Philadelphia Teen Slain as Result of Inner City Rivalries • Lectures, Friendships, and Giving Up Shop • The Holidays Mean More Than Just Christmas • Alumna Spotlight: The Life of a Doctor • The Java Trench: More Than Just Coffee • Indigo Girls Delight Philly Fans • Intramural Updatehttps://digitalcommons.ursinus.edu/grizzlynews/1349/thumbnail.jp

Natural-abundance radiocarbon as a tracer of assimilation of petroleum carbon by bacteria in salt marsh sediments

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 70 (2006): 1761-1771, doi:10.1016/j.gca.2005.12.020.The natural abundance of radiocarbon (14C) provides unique insight into the source and cycling of sedimentary organic matter. Radiocarbon analysis of bacterial phospholipid lipid fatty acids (PLFAs) in salt-marsh sediments of southeast Georgia (USA) – one heavily contaminated by petroleum residues – was used to assess the fate of petroleum-derived carbon in sediments and incorporation of fossil carbon into microbial biomass. PLFAs that are common components of eubacterial cell membranes (e.g., branched C15 and C17, 10-methyl-C16) were depleted in 14C in the contaminated sediment (mean Δ14C value of +25 ± 19 ‰ for bacterial PLFAs) relative to PLFAs in uncontaminated “control” sediment (Δ14C = +101 ± 12‰). We suggest that the 14C-depletion in bacterial PLFAs at the contaminated site results from microbial metabolism of petroleum and subsequent incorporation of petroleum-derived carbon into bacterial membrane lipids. A mass balance calculation indicates that 6-10% of the carbon in bacterial PLFAs at the oiled site could derive from petroleum residues. These results demonstrate that even weathered petroleum may contain components of sufficient lability to be a carbon source for biomass production by marsh sediment microorganisms. Furthermore, a small but significant fraction of fossil carbon is assimilated even in the presence of a much larger pool of presumably more-labile and faster-cycling carbon substrates.This study was supported by Georgia Sea Grant (RR100-221/926784), the National Science Foundation (OCE-9911678) and NOSAMS (thanks to J. M. Hayes)