PDX-1 is required for pancreatic out-growth and differentiation of the rostral duodenum

It has been proposed that the Xenopus homeobox gene, XlHbox8, is involved in endodermal differentiation during pancreatic and duodenal development (Wright, C. V. E., Schnegelsberg, P. and De Robertis, E. M. (1988). Development 105, 787-794). To test this hypothesis directly, gene targeting was used to make two different null mutations in the mouse XlHbox8 homolog, pdx-1. In the first, the second pdx-1 exon, including the homeobox, was replaced by a neomycin resistance cassette. In the second, a lacZ reporter was fused in-frame with the N terminus of PDX-1, replacing most of the homeodomain. Neonatal pdx-1-/- mice are apancreatic, in confirmation of previous reports (Jonsson, J., Carlsson, L., Edlund, T. and Edlund, H. (1994). Nature 371, 606-609). However, the pancreatic buds do form in homozygous mutants, and the dorsal bud undergoes limited proliferation and outgrowth to form a small, irregularly branched, ductular tree. This outgrowth does not contain insulin or amylase-positive cells, but glucagon-expressing cells are found. The rostral duodenum shows a local absence of the normal columnar epithelial lining, villi, and Brunner’s glands, which are replaced by a GLUT2-positive cuboidal epithelium resembling the bile duct lining. Just distal of the abnormal epithelium, the numbers of enteroendocrine cells in the villi are greatly reduced. The PDX-1/b-galactosidase fusion allele is expressed in pancreatic and duodenal cells in the absence of functional PDX-1, with expression continuing into perinatal stages with similar boundaries and expression levels. These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors

The Detection of Incipient Caries with Tracer Dyes

The purpose of this study was to determine the increase in color contrast produced by the use of a tracer dye in detection of incipient caries lesions with transillumination. Twenty four caries-free first premolars were immersed in an acid gelatin for production of artificial incipient caries lesions. After the lesions had developed, these teeth were photographed by transillumination. Two photographs were taken of each tooth. The first photograph showed the lesion without dye. A blue tracer dye was then added and absorbed by the lesion, and a second photograph was taken. The data on the color difference were obtained by use of a reflectance colorimeter and showed a four-fold increase between the lesion and surrounding area with the dye. A two-way analysis of variance was used for the statistical interpretation. The color difference between the lesion without the dye and then with the dye was significant. The use of the blue tracer dye, therefore, significantly increased the contrast in the images of the artificial incipient lesions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68289/2/10.1177_00220345890680021101.pd

New rat model that phenotypically resembles autosomal recessive polycystic kidney disease

Numerous murine models of polycystic kidney disease (PKD) have been described. While mouse models are particularly well suited for investigating the molecular pathogenesis of PKD, rats are well established as an experimental model of renal physiologic processes. Han:SPRD-CY: rats have been proposed as a model for human autosomal dominant PKD. A new spontaneous rat mutation, designated wpk, has now been identified. In the mutants, the renal cystic phenotype resembles human autosomal recessive PKD (ARPKD). This study was designed to characterize the clinical and histopathologic features of wpk/wpk mutants and to map the wpk locus. Homozygous mutants developed nephromegaly, hypertension, proteinuria, impaired urine-concentrating capacity, and uremia, resulting in death at 4 wk of age. Early cysts were present in the nephrogenic zone at embryonic day 19. These were localized, by specific staining and electron microscopy, to differentiated proximal tubules, thick limbs, distal tubules, and collecting ducts. In later stages, the cysts were largely confined to collecting ducts. Although the renal histopathologic features are strikingly similar to those of human ARPKD, wpk/wpk mutants exhibited no evidence of biliary tract abnormalities. The wpk locus maps just proximal to the CY: locus on rat chromosome 5, and complementation studies demonstrated that these loci are not allelic. It is concluded that the clinical and renal histopathologic features of this new rat model strongly resemble those of human ARPKD. Although homology mapping indicates that rat wpk and human ARPKD involve distinct genes, this new rat mutation provides an excellent experimental model to study the molecular pathogenesis and renal pathophysiologic features of recessive PKD

Measurement of the Proton and Deuteron Spin Structure Functions g2 and Asymmetry A2

We have measured the spin structure functions g2p and g2d and the virtual photon asymmetries A2p and A2d over the kinematic range 0.02 < x < 0.8 and 1.0 < Q^2 < 30(GeV/c)^2 by scattering 38.8 GeV longitudinally polarized electrons from transversely polarized NH3 and 6LiD targets.The absolute value of A2 is significantly smaller than the sqrt{R} positivity limit over the measured range, while g2 is consistent with the twist-2 Wandzura-Wilczek calculation. We obtain results for the twist-3 reduced matrix elements d2p, d2d and d2n. The Burkhardt-Cottingham sum rule integral - int(g2(x)dx) is reported for the range 0.02 < x < 0.8.Comment: 12 pages, 4 figures, 1 tabl

Measurements of the Q2Q^2-Dependence of the Proton and Neutron Spin Structure Functions g1p and g1n

The structure functions g1p and g1n have been measured over the range 0.014 < x < 0.9 and 1 < Q2 < 40 GeV2 using deep-inelastic scattering of 48 GeV longitudinally polarized electrons from polarized protons and deuterons. We find that the Q2 dependence of g1p (g1n) at fixed x is very similar to that of the spin-averaged structure function F1p (F1n). From a NLO QCD fit to all available data we find $\Gamma_1^p - \Gamma_1^n =0.176 \pm 0.003 \pm 0.007$ at Q2=5 GeV2, in agreement with the Bjorken sum rule prediction of 0.182 \pm 0.005.Comment: 17 pages, 3 figures. Submitted to Physics Letters

Polyurethane Elastomers as Maxillofacial Prosthetic Materials

A series of polyurethane elastomers based on an aliphatic diisocyanate and a polyether macroglycol was polymerized with various crosslink densities and OH/NCO ratios. Stoichiometries yielding between 8,600 and 12,900 gm/ mole/crosslink and an OH/NCO ratio of 1.1 resulted in polymers with the low modulus, yet high strength and elongation necessary for maxillofacial applications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68299/2/10.1177_00220345780570040501.pd

Correlates of ART Use Among Newly Diagnosed HIV Positive Adolescent Girls and Young Women Enrolled in HPTN 068

Despite expanded access to HIV treatment worldwide, poor HIV care outcomes persist among adolescent girls and young women (AGYW). This study was conducted among AGYW recruited from the HPTN 068 cohort who had sero-converted to HIV during the main trial between 2011 and 2014. The aim was to examine correlates of anti-retroviral treatment (ART) use. Log binomial regression was used to estimate the crude associations between social support, stigma, and HIV status disclosure and current ART use. Adjusted analyses were also conducted controlling for age and time since diagnosis. Seventy-nine AGYW were included in this analysis. Median age of participants was 20 (range: 17 to 24) and time since diagnosis ranged from 0.5 to 4.8 years (median = 2.1). Over 75% of AGYW (n = 60) had sought HIV care at some point, with the same number reporting previous disclosure of their sero-status. However, just 43% (n = 34) of participants were on treatment at the time of the interview. Over half of participants (n = 44; 55.7%) reported social support was available to them most or all of the time, and the median stigma score was 90 (range 80–113). Adjusted analyses found higher current ART use among those who had disclosed their status (adjusted prevalence ratio (aPR): 3.19; 95% confidence interval (CI) 1.09, 9.32; p = 0.0339) and those with lower scores on the disclosure concern sub-scale of the Berger HIV Stigma Scale (aPR: 0.88; 95% CI 0.79, 0.98; p = 0.0236). ART use among AGYW living with HIV and enrolled in HPTN 068 was low despite relatively high linkage to care during the trial. Interventions aimed at minimizing individuals’ concerns about disclosure and improving onward disclosure of one’s status could further improve ART utilization among AGYW living with HIV in South Africa

Identification of pathways to high-level vancomycin resistance in Clostridioides difficile that incur high fitness costs in key pathogenicity traits

Clostridioides difficile is an important human pathogen, for which there are very limited treatment options, primarily the glycopeptide antibiotic vancomycin. In recent years, vancomycin resistance has emerged as a serious problem in several gram-positive pathogens, but high-level resistance has yet to be reported for C. difficile, although it is not known if this is due to constraints upon resistance evolution in this species. Here, we show that resistance to vancomycin can evolve rapidly under ramping selection but is accompanied by fitness costs and pleiotropic trade-offs, including sporulation defects that would be expected to severely impact transmission. We identified 2 distinct pathways to resistance, both of which are predicted to result in changes to the muropeptide terminal D-Ala-D-Ala that is the primary target of vancomycin. One of these pathways involves a previously uncharacterised D,D-carboxypeptidase, expression of which is controlled by a dedicated two-component signal transduction system. Our findings suggest that while C. difficile is capable of evolving high-level vancomycin resistance, this outcome may be limited clinically due to pleiotropic effects on key pathogenicity traits. Moreover, our data identify potential mutational routes to resistance that should be considered in genomic surveillance

Tunneling of quantum rotobreathers

We analyze the quantum properties of a system consisting of two nonlinearly coupled pendula. This non-integrable system exhibits two different symmetries: a permutational symmetry (permutation of the pendula) and another one related to the reversal of the total momentum of the system. Each of these symmetries is responsible for the existence of two kinds of quasi-degenerated states. At sufficiently high energy, pairs of symmetry-related states glue together to form quadruplets. We show that, starting from the anti-continuous limit, particular quadruplets allow us to construct quantum states whose properties are very similar to those of classical rotobreathers. By diagonalizing numerically the quantum Hamiltonian, we investigate their properties and show that such states are able to store the main part of the total energy on one of the pendula. Contrary to the classical situation, the coupling between pendula necessarily introduces a periodic exchange of energy between them with a frequency which is proportional to the energy splitting between quasi-degenerated states related to the permutation symmetry. This splitting may remain very small as the coupling strength increases and is a decreasing function of the pair energy. The energy may be therefore stored in one pendulum during a time period very long as compared to the inverse of the internal rotobreather frequency.Comment: 20 pages, 11 figures, REVTeX4 styl