Fine map of the Gct1 spontaneous ovarian granulosa cell tumor locus

The spontaneous development of juvenile-onset, ovarian granulosa cell (GC) tumors in the SWR/Bm (SWR) inbred mouse strain is a model for juvenile-type GC tumors that appear in infants and young girls. GC tumor susceptibility is supported by multiple Granulosa cell tumor (Gct) loci, but the Gct1 locus on Chr 4 derived from SWR strain background is fundamental for GC tumor development and uniquely responsive to the androgenic precursor dehydroepiandrosterone (DHEA). To resolve the location of Gct1 independently from other susceptibility loci, Gct1 was isolated in a congenic strain that replaces the distal segment of Chr 4 in SWR mice with a 47 × 10(6)-bp genomic segment from the Castaneus/Ei (CAST) strain. SWR females homozygous for the CAST donor segment were confirmed to be resistant to DHEA- and testosterone-induced GC tumorigenesis, indicating successful exchange of CAST alleles (Gct1(CA)) for SWR alleles (Gct1(SW)) at this tumor susceptibility locus. A series of nested, overlapping, congenic sublines was created to fine-map Gct1 based on GC tumor susceptibility under the influence of pubertal DHEA treatment. Twelve informative lines have resolved the Gct1 locus to a 1.31 × 10(6)-bp interval on mouse Chr 4, a region orthologous to human Chr 1p36.22. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00335-012-9439-6) contains supplementary material, which is available to authorized users

The Vehicle, Fall 1988

Table of Contents Cover LetterBob Zordanipage 3 Letter to Harrington StreetBob Zordanipage 4 The Only TruthBob Zordanipage 5 They\u27d Gone to a MovieMatt Mansfieldpage 6 The LocketMonica Grothpage 6 The Sleep of BabesMonica Grothpage 7 Techni-Color Characters in a Black and White TownMonica Grothpage 8 The HorseRodger Patiencepage 9 ValaciaRobyn Kerrpage 10 Gatsby\u27s LightJim Reedpage 11 Millions of MeJim Reedpage 12 View from the StreetsSteven M. Beamerpage 13 When Headlights on the HighwayMichael Salempage 23 Concrete AffairsMichael Salempage 24 The Middle of the StreetMichael Salempage 25 Scent of a StormMichael Salempage 26 The FishermanAngie Geraldpage 27 OrgansPatrick Peterspage 33 CarpentryPatrick Peterspage 34 FishingPatrick Peterspage 35 Autumn Poem for a Friend In a Printing PlantPatrick Peterspage 36https://thekeep.eiu.edu/vehicle/1051/thumbnail.jp

The Vehicle, Fall 1988

Table of Contents Cover LetterBob Zordanipage 3 Letter to Harrington StreetBob Zordanipage 4 The Only TruthBob Zordanipage 5 They\u27d Gone to a MovieMatt Mansfieldpage 6 The LocketMonica Grothpage 6 The Sleep of BabesMonica Grothpage 7 Techni-Color Characters in a Black and White TownMonica Grothpage 8 The HorseRodger Patiencepage 9 ValaciaRobyn Kerrpage 10 Gatsby\u27s LightJim Reedpage 11 Millions of MeJim Reedpage 12 View from the StreetsSteven M. Beamerpage 13 When Headlights on the HighwayMichael Salempage 23 Concrete AffairsMichael Salempage 24 The Middle of the StreetMichael Salempage 25 Scent of a StormMichael Salempage 26 The FishermanAngie Geraldpage 27 OrgansPatrick Peterspage 33 CarpentryPatrick Peterspage 34 FishingPatrick Peterspage 35 Autumn Poem for a Friend In a Printing PlantPatrick Peterspage 36https://thekeep.eiu.edu/vehicle/1051/thumbnail.jp

Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed

The Vehicle, Spring 1988

Contents CitizenCraig Titleypage 3 Justice DistributionAngie Geraldpage 4 Letter from My MotherDan Von Holtenpage 6 The Fool and His LadyRodger Patiencepage 7 What Big IsBob Zordanipage 8 Blind ArchitectureJim Reedpage 9 Ah, What a Funny Thing These EyesCraig Titleypage 10 FarmingPatrick Peterspage 11 The CowSteven M. Beamerpage 13 The Enigma of My ExistenceAngie Kathpage 14 Neon TeethMichael Salempage 15 Zombie PoseidonMichael Salempage 16 From: Letters from the Linder BuildingPatrick Peters, Bob Zordani, Dan Von Holtenpage 17 A Man of Jackson IV (City Dweller)Steven M. Beamerpage 19 11:45 p.m. FridayElizabeth McMeekanpage 20 Mr. Siegel-January 1967Timothy J. McCarthypage 21 She had a look about herA bag man of Jackson pauses for a portraitSteven M. Beamerpage 22 Citybed (Homeless of Chicago)Steven M. Beamerpage 23 Electra and the Eighteen WheelerTammy Veachpage 24 OrderRhonda Ealypage 28 Grave Mill ISteven M. Beamerpage 29 The Party (A Social Event in 80 Words or Less)Groucho Smithpage 30 Graceland and Elvis Presley EarmuffsCraig Titleypage 31 Learning to ForageDan Von Holtenpage 33 One Last Peanut at Gateway CenterReflections of Three with DeCicco and LadySteven M. Beamerpage 34 Letter from the MidwestPatrick Peterspage 35 WoodwindJim Reedpage 36 Excerpts from Notebook AustraliaKeith Schusterpage 37 Letter from the DesertPatrick Peterspage 40 Tinted Blue, Waiting for an Uptown TaxiMichael Salempage 42 Voice and Earth: A Review of The Invention of the Telephone by Bruce GuernseyDan Von Holtenpage 43https://thekeep.eiu.edu/vehicle/1052/thumbnail.jp

The Vehicle, Spring 1988

Contents CitizenCraig Titleypage 3 Justice DistributionAngie Geraldpage 4 Letter from My MotherDan Von Holtenpage 6 The Fool and His LadyRodger Patiencepage 7 What Big IsBob Zordanipage 8 Blind ArchitectureJim Reedpage 9 Ah, What a Funny Thing These EyesCraig Titleypage 10 FarmingPatrick Peterspage 11 The CowSteven M. Beamerpage 13 The Enigma of My ExistenceAngie Kathpage 14 Neon TeethMichael Salempage 15 Zombie PoseidonMichael Salempage 16 From: Letters from the Linder BuildingPatrick Peters, Bob Zordani, Dan Von Holtenpage 17 A Man of Jackson IV (City Dweller)Steven M. Beamerpage 19 11:45 p.m. FridayElizabeth McMeekanpage 20 Mr. Siegel-January 1967Timothy J. McCarthypage 21 She had a look about herA bag man of Jackson pauses for a portraitSteven M. Beamerpage 22 Citybed (Homeless of Chicago)Steven M. Beamerpage 23 Electra and the Eighteen WheelerTammy Veachpage 24 OrderRhonda Ealypage 28 Grave Mill ISteven M. Beamerpage 29 The Party (A Social Event in 80 Words or Less)Groucho Smithpage 30 Graceland and Elvis Presley EarmuffsCraig Titleypage 31 Learning to ForageDan Von Holtenpage 33 One Last Peanut at Gateway CenterReflections of Three with DeCicco and LadySteven M. Beamerpage 34 Letter from the MidwestPatrick Peterspage 35 WoodwindJim Reedpage 36 Excerpts from Notebook AustraliaKeith Schusterpage 37 Letter from the DesertPatrick Peterspage 40 Tinted Blue, Waiting for an Uptown TaxiMichael Salempage 42 Voice and Earth: A Review of The Invention of the Telephone by Bruce GuernseyDan Von Holtenpage 43https://thekeep.eiu.edu/vehicle/1052/thumbnail.jp

CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice.

More humans have died of tuberculosis (TB) than any other infectious disease and millions still die each year. Experts advocate for blood-based, serum protein biomarkers to help diagnose TB, which afflicts millions of people in high-burden countries. However, the protein biomarker pipeline is small. Here, we used the Diversity Outbred (DO) mouse population to address this gap, identifying five protein biomarker candidates. One protein biomarker, serum CXCL1, met the World Health Organization\u27s Targeted Product Profile for a triage test to diagnose active TB from latent M.tb infection (LTBI), non-TB lung disease, and normal sera in HIV-negative, adults from South Africa and Vietnam. To find the biomarker candidates, we quantified seven immune cytokines and four inflammatory proteins corresponding to highly expressed genes unique to progressor DO mice. Next, we applied statistical and machine learning methods to the data, i.e., 11 proteins in lungs from 453 infected and 29 non-infected mice. After searching all combinations of five algorithms and 239 protein subsets, validating, and testing the findings on independent data, two combinations accurately diagnosed progressor DO mice: Logistic Regression using MMP8; and Gradient Tree Boosting using a panel of 4: CXCL1, CXCL2, TNF, IL-10. Of those five protein biomarker candidates, two (MMP8 and CXCL1) were crucial for classifying DO mice; were above the limit of detection in most human serum samples; and had not been widely assessed for diagnostic performance in humans before. In patient sera, CXCL1 exceeded the triage diagnostic test criteria (\u3e90% sensitivity; \u3e70% specificity), while MMP8 did not. Using Area Under the Curve analyses, CXCL1 averaged 94.5% sensitivity and 88.8% specificity for active pulmonary TB (ATB) vs LTBI; 90.9% sensitivity and 71.4% specificity for ATB vs non-TB; and 100.0% sensitivity and 98.4% specificity for ATB vs normal sera. Our findings overall show that the DO mouse population can discover diagnostic-quality, serum protein biomarkers of human TB

Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice

Acute exacerbations of pulmonary fibrosis are characterized by rapid decrements in lung function. Environmental factors that may contribute to acute exacerbations remain poorly understood. We have previously demonstrated that exposure to inhaled lipopolysaccharide (LPS) induces expression of genes associated with fibrosis. To address whether exposure to LPS could exacerbate fibrosis, we exposed male C57BL/6 mice to crystalline silica, or vehicle, followed 28 days later by LPS or saline inhalation. We observed that mice receiving both silica and LPS had significantly more total inflammatory cells, more whole lung lavage MCP-1, MIP-2, KC and IL-1β, more evidence of oxidative stress and more total lung hydroxyproline than mice receiving either LPS alone, or silica alone. Blocking oxidative stress with N-acetylcysteine attenuated whole lung inflammation but had no effect on total lung hydroxyproline. These observations suggest that exposure to innate immune stimuli, such as LPS in the environment, may exacerbate stable pulmonary fibrosis via mechanisms that are independent of inflammation and oxidative stress. © 2012 Brass et al

Magnesium deficiency: effect on bone mineral density in the mouse appendicular skeleton

BACKGROUND: Dietary magnesium (Mg) deficiency in the mouse perturbs bone and mineral homeostasis. The objective of the present study was to evaluate bone mineral density of the femur in control and Mg-deficient mice. METHODS: BALB/c mice aged 28 days at study initiation were maintained on a normal or Mg deficient (0.0002% Mg) diet, and at time points 0, 2, 4 or 6 weeks bones were harvested for bone mineral density analysis. Peripheral quantitative computed tomography (pQCT) was used to assess the trabecular metaphyseal compartment and the cortical midshaft. RESULTS: Although mean total bone density of the femoral midshaft in Mg deficient mice did not differ significantly from controls throughout the study, the trabecular bone compartment showed significantly decreased mineral content after 4 (p < 0.001) and 6 weeks (p < 0.001) of Mg depletion. CONCLUSIONS: This study demonstrates the profound effect of Mg depletion on the trabecular compartment of bone, which, with its greater surface area and turnover, was more responsive to Mg depletion than cortical bone in the appendicular skeleton of the mouse