Reconciliation of the Surface Brightness Fluctuations and Type Ia Supernovae Distance Scales

We present Hubble Space Telescope measurements of surface brightness fluctuations (SBF) distances to early-type galaxies that have hosted Type Ia supernovae (SNIa). The agreement in the relative SBF and SNIa multicolor light curve shape and delta-m_15 distances is excellent. There is no systematic scale error with distance, and previous work has shown that SBF and SNIa give consistent ties to the Hubble flow. However, we confirm a systematic offset of about 0.25 mag in the distance zero points of the two methods, and we trace this offset to their respective Cepheid calibrations. SBF has in the past been calibrated with Cepheid distances from the H_0 Key Project team, while SNIa have been calibrated with Cepheid distances from the team composed of Sandage, Saha, and collaborators. When the two methods are calibrated in a consistent way, their distances are in superb agreement. Until the conflict over the ``long'' and ``short'' extragalactic Cepheid distances among many galaxies is resolved, we cannot definitively constrain the Hubble constant to better than about 10%, even leaving aside the additional uncertainty in the distance to the Large Magellanic Cloud, common to both Cepheid scales. However, recent theoretical SBF predictions from stellar population models favor the Key Project Cepheid scale, while the theoretical SNIa calibration lies between the long and short scales. In addition, while the current SBF distance to M31/M32 is in good agreement with the RR Lyrae and red giant branch distances, calibrating SBF with the longer Cepheid scale would introduce a 0.3 mag offset with respect to the RR Lyrae scale.Comment: 13 pages, 3 PostScript figures, LaTeX with AASTeX 5.02 and natbib.sty v7.0 (included). Accepted for publication in The Astrophysical Journa

Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy. Results show that local or systemic administration of 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI) dose-dependently suppressed CIPN mechanical and cold allodynia. Orally administered PrNMI also dose-dependently suppressed CIPN allodynia symptoms in both male and female rats without any CNS side effects. Co-administration with selective cannabinoid receptor subtype blockers revealed that PrNMI's anti-allodynic effects are mediated by CB1 receptor (CB1R) activation. Expression of CB2Rs was reduced in dorsal root ganglia from CIPN rats, whereas expression of CB1Rs and various endocannabinoid synthesizing and metabolizing enzymes was unaffected. Daily PrNMI treatment of CIPN rats for two weeks showed a lack of appreciable tolerance to PrNMI's anti-allodynic effects. In an operant task which reflects cerebral processing of pain, PrNMI also dose-dependently suppressed CIPN pain behaviors. Our results demonstrate that PRCBs exemplified by PrNMI may represent a viable option for the treatment of CIPN pain symptoms

SarS, a SarA Homolog Repressible by agr, Is an Activator of Protein A Synthesis in Staphylococcus aureus

The expression of protein A (spa) is repressed by global regulatory loci sarA and agr. Although SarA may directly bind to the spa promoter to downregulate spa expression, the mechanism by which agr represses spa expression is not clearly understood. In searching for SarA homologs in the partially released genome, we found a SarA homolog, encoding a 250-amino-acid protein designated SarS, upstream of the spa gene. The expression of sarS was almost undetectable in parental strain RN6390 but was highly expressed in agr and sarA mutants, strains normally expressing high level of protein A. Interestingly, protein A expression was decreased in a sarS mutant as detected in an immunoblot but returned to near-parental levels in a complemented sarS mutant. Transcriptional fusion studies with a 158- and a 491-bp spa promoter fragment linked to the xylE reporter gene disclosed that the transcription of the spa promoter was also downregulated in the sarS mutant compared with the parental strain. Interestingly, the enhancement in spa expression in an agr mutant returned to a near-parental level in the agr sarS double mutant but not in the sarA sarS double mutant. Correlating with this divergent finding is the observation that enhanced sarS expression in an agr mutant was repressed by the sarA locus supplied in trans but not in a sarA mutant expressing RNAIII from a plasmid. Gel shift studies also revealed the specific binding of SarS to the 158-bp spa promoter. Taken together, these data indicated that the agr locus probably mediates spa repression by suppressing the transcription of sarS, an activator of spa expression. However, the pathway by which the sarA locus downregulates spa expression is sarS independent

Prospectus, October 26, 1983

LEARNING LAB IS A LIFE SAVER; News Digest; What to do about childhood stress; Braille room fills needs of the blind; PC Happenings; Did you know that?; How to reorganize homemaking chores; TV results; Pumpkin Contest; Health Information; C.A.A.R.; WPCD quizzes high schools; Register for spring semester; Apples remain fave fruit; Be cool in case of fire; Rural Illinois growth increases; Cowboy Brock programs sports; Pulitzer winner visits C-U; Quality circles solve problems; Oktoberfest is today; Around Parkland; The truth behind Halloween is haunting; Brighten a Soldier\u27s Christmas; Interesting story ideas brighten series; Passion at Krannert; Zelig restores Allen\u27s stature; Classified; Krannert adds on; Fast Freddy statistics; Fast Freddy Contest; Bowling scoreshttps://spark.parkland.edu/prospectus_1983/1007/thumbnail.jp

G protein-coupled receptors are dynamic regulators of digestion and targets for digestive diseases

G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins. Within the gastrointestinal tract, GPCRs expressed by epithelial cells sense contents of the lumen, and GPCRs expressed by epithelial cells, myocytes, neurons, and immune cells participate in communication amongst cells. GPCRs control digestion, mediate digestive diseases, and coordinate repair and growth. GPCRs are the target of over one third of therapeutic drugs, including many drugs used to treat digestive diseases. Recent advances in structural, chemical, and cell biology research have revealed that GPCRs are not static binary switches that operate from the plasma membrane to control a defined set of intracellular signals. Rather, GPCRs are dynamic signaling proteins that adopt distinct conformations and subcellular distributions when associated with different ligands and intracellular effectors. An understanding of the dynamic nature of GPCRs has provided insights into the mechanism of activation and signaling of GPCRs, and has revealed opportunities for drug discovery. We review the allosteric modulation, biased agonism, oligomerization, and compartmentalized signaling of GPCRs that control digestion and digestive diseases. We highlight the implications of these concepts for the development of selective and effective drugs to treat diseases of the gastrointestinal tract

Informationist Support for a Study of the Role of Proteases and Peptides in Cancer Pain

Two supplements were awarded to the New York University Health Sciences Libraries from the National Library of Medicine\u27s informationist grant program. These supplements funded research support in a number of areas, including data management and bioinformatics, two fields that the library had recently begun to explore. As such, the supplements were of particular value to the library as a testing ground for these newer services. This paper will discuss a supplement received in support of a grant from the National Institute of Dental and Craniofacial Research (PI: Brian Schmidt) on the role of proteases and peptides in cancer pain. A number of barriers were preventing the research team from maximizing the efficiency and effectiveness of their work. A critical component of the research was to identify which proteins, from among hundreds identified in collected samples, to include in preclinical testing. This selection involved laborious and prohibitively time-consuming manual searching of the literature on protein function. Additionally, the research team encompassed ten investigators working in two different cities, which led to issues around the sharing and tracking of both data and citations. The supplement outlined three areas in which the informationists would assist the researchers in overcoming these barriers: 1) creating an automated literature searching system for protein function discovery, 2) introducing tools and associated workflows for sharing citations, and 3) introducing tools and workflows for sharing data and specimens

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice.

In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2-78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR-associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high-dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop

A Light Echo from Type Ia SN 1995E?

We identify a light echo candidate from Hubble Space Telescope (HST) imaging of NGC 2441, the host galaxy of the Type Ia supernova 1995E. From the echo's angular size and the estimated distance to the host galaxy, we find a distance of 207 ± 35 pc betwe

Cosmological Results from High-z Supernovae

The High-z Supernova Search Team has discovered and observed 8 new supernovae in the redshift interval z=0.3-1.2. These independent observations, confirm the result of Riess et al. (1998a) and Perlmutter et al. (1999) that supernova luminosity distances imply an accelerating universe. More importantly, they extend the redshift range of consistently observed SN Ia to z~1, where the signature of cosmological effects has the opposite sign of some plausible systematic effects. Consequently, these measurements not only provide another quantitative confirmation of the importance of dark energy, but also constitute a powerful qualitative test for the cosmological origin of cosmic acceleration. We find a rate for SN Ia of 1.4+/-0.5E-04 h^3/Mpc^3/yr at a mean redshift of 0.5. We present distances and host extinctions for 230 SN Ia. These place the following constraints on cosmological quantities: if the equation of state parameter of the dark energy is w=-1, then H0 t0 = 0.96+/-0.04, and O_l - 1.4 O_m = 0.35+/-0.14. Including the constraint of a flat Universe, we find O_m = 0.28+/-0.05, independent of any large-scale structure measurements. Adopting a prior based on the 2dF redshift survey constraint on O_m and assuming a flat universe, we find that the equation of state parameter of the dark energy lies in the range -1.48-1, we obtain w<-0.73 at 95% confidence. These constraints are similar in precision and in value to recent results reported using the WMAP satellite, also in combination with the 2dF redshift survey.Comment: 50 pages, AAS LateX, 15 figures, 15 tables. Accepted for publication by Astrophysical Journa