Mechanisms underlying pituitary hypoplasia and failed cell specification in Lhx3-deficient mice

AbstractThe LIM homeodomain transcription factor, LHX3, is essential for pituitary development in mouse and man. Lhx3 engineered null mice have profound pituitary hypoplasia that we find is attributable to an increase in cell death early in pituitary development. Dying cells are localized to regions of TPIT expression indicating that cell death may contribute to the severe reduction in differentiated corticotrope cells and lower expression of the corticotrope transcription factors, TPIT and NEUROD1. Lhx3 deficiency also results in dorsal ectopic expression of transcription factors characteristic of gonadotropes, SF1 and ISL1, but no gonadotropin expression. This apparent disturbance of cell differentiation may be due, in part, to loss of NOTCH2. NOTCH2 is normally expressed in the pituitary at the boundary between dorsal, proliferating cells and ventral, differentiating cells and is important for maintaining dorsal–ventral patterning in other organs. Thus, Lhx3 contributes significantly to pituitary development by maintaining normal dorsal–ventral patterning, cell survival, and normal expression of corticotrope-specific transcription factors, which are necessary for repressing ectopic gonadotrope differentiation

Tumor and mutation suppressing plant extract

A compound derived from an extract of vegetative tissue of plants of the Genus Shortia demonstrates antitcarcinogenic potential by inhibiting the growth and development formation of tumors in living tissue in response to an organism known to cause the initiation of tumors in living tissue and by reducing mutation rates in living tissues exposed to a known mutagen

The skeletal phenotype of chondroadherin deficient mice

Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their a2b1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3–6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the a1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth

Assessment of cognitive self-statements during marital problem solving: A comparison of two methods

Twenty maritally distressed couples (DC) and 20 nondistressed couples (NDC) were recruited and asked to undertake 10 minutes of problem-solving discussions, which were videotaped. Each individual partner’s cognitive self-statements during the interaction were assessed using two methods: video-assisted recall (VR) and thought listing (TL). Reported cognitions from each method were content- analysed and classified into five categories: partner- referent positive, partner- referent negative, self-referent positive, self- referent negative, and other. Proportions of reported cognitions falling into each category were analysed in two separate two-way MANOVAs (marital distress/ nondistress x sex) for the VR and TL measures. Results of each MANOVA indicated a highly significant effect of marital distress on cognitions, and a significant effect of sex on the VR but not the TL measure. Discriminant analyses showed that the VR and TL methods both discriminated between DC and NDC groups. Post hoc univariate ANOVAs indicated that DC had significantly higher proportions of negative partner- referent cognitions, and lower proportions of positive partner- referent cognitions, than NDC while problem solving. The relative merits of each cognitive assessment method, and their potential use in increasing marital therapy effectiveness, are discussed

Chromosomal localization of the zinc finger protein 15, Zfp15 , on Mouse Chromosome 4

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47024/1/335_2004_Article_BF00352424.pd

Management of radioactive material safety programs at medical facilities. Final report

A Task Force, comprising eight US Nuclear Regulatory Commission and two Agreement State program staff members, developed the guidance contained in this report. This report describes a systematic approach for effectively managing radiation safety programs at medical facilities. This is accomplished by defining and emphasizing the roles of an institution`s executive management, radiation safety committee, and radiation safety officer. Various aspects of program management are discussed and guidance is offered on selecting the radiation safety officer, determining adequate resources for the program, using such contractual services as consultants and service companies, conducting audits, and establishing the roles of authorized users and supervised individuals; NRC`s reporting and notification requirements are discussed, and a general description is given of how NRC`s licensing, inspection and enforcement programs work

All hormone-producing cell types of the pituitary intermediate and anterior lobes derive from prop1-expressing progenitors

Mutations in PROP1, the most common known cause of combined pituitary hormone deficiency in humans, can result in the progressive loss of all hormones of the pituitary anterior lobe. In mice, Prop1 mutations result in the failure to initiate transcription of Pou1f1 (also known as Pit1) and lack somatotropins, lactotropins, and thyrotropins. The basis for this species difference is unknown. We hypothesized that Prop1 is expressed in a progenitor cell that can develop into all anterior lobe cell types, and not just the somatotropes, thyrotropes, and lactotropes, which are collectively known as the PIT1 lineage. To test this idea, we produced a transgenic Prop1-cre mouse line and conducted lineage-tracing experiments of Prop1-expressing cells. The results reveal that all hormone-secreting cell types of both the anterior and intermediate lobes are descended from Prop1-expressing progenitors. The Prop1-cre mice also provide a valuable genetic reagent with a unique spatial and temporal expression for generating tissue-specific gene rearrangements early in pituitary gland development. We also determined that the minimal essential sequences for reliable Prop1 expression lie within 10 kilobases of the mouse gene and demonstrated that human PROP1 can substitute functionally for mouse Prop1. These studies enhance our understanding of the pathophysiology of disease in patients with PROP1 mutations.Fil: Davis, Shannon W.. University of South Carolina; Estados UnidosFil: Keisler, Jessica L.. University of South Carolina; Estados UnidosFil: Pérez Millán, María Inés. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schade, Vanessa. University of Michigan; Estados UnidosFil: Camper, Sally A.. University of Michigan; Estados Unido

Comparison of Internal Ribosome Entry Site (IRES) and Furin-2A (F2A) for Monoclonal Antibody Expression Level and Quality in CHO Cells

10.1371/journal.pone.0063247PLoS ONE85

Mercury Accumulation in Tree Rings: Observed Trends in Quantity and Isotopic Composition in Shenandoah National Park, Virginia

Recent studies have shown that mercury (Hg) concentrations in tree rings have the potential to archive historical Hg exposure from local, regional, and global sources. The southeastern United States has received elevated Hg deposition, yet no studies have evaluated tree ring Hg in this region. Here, we quantify Hg accumulation and isotopic composition in tree rings collected in Shenandoah National Park, Virginia. Cores were collected from three individuals of three tree species—white oak (Quercus alba), northern red oak (Quercus rubra), and pitch pine (Pinus rigida)—within the northern, central, and southern areas of the Park (n = 27 cores). The cores were analyzed for Hg content in 10‐year increments, with some cores dating back to the early 1800s. Overall, tree ring Hg concentrations (ranging from below detection to 4.4 ng/g) were similar to other studies and varied between species, with pitch pine having higher concentrations than the deciduous species. The most notable feature of the tree ring Hg time series was a peak that occurred during the 1930s through 1950s, coinciding with the use of Hg at a local industrial facility. Atmospheric modeling indicates that potential emissions from the plant likely had a stronger impact on the southern region of the Park, consistent with the latitudinal gradient in tree ring Hg concentrations. Mass‐dependent and mass‐independent fractionation of Hg isotopes suggests contributions from both regional anthropogenic and local industrial sources during this period. This study demonstrates the potential usefulness of tree ring dendrochemistry for identifying historical sources of atmospheric Hg exposure.Key PointsTree ring mercury levels in Shenandoah National Park, Virginia, were similar to those measured in other North American forestsTree ring mercury peaked during the 1930s to 1950s, coinciding with mercury use at an industrial facility near the southern end of the ParkMercury isotopes suggest a local source at this time, demonstrating the potential of dendrochemistry to identify historical sourcesPlain Language SummaryFor many years scientists have used tree rings to reconstruct past climate. Increasingly, tree rings are being used to document the historical exposure of trees to pollutants. In this study, we cored trees in Shenandoah National Park, Virginia, dated the tree rings, and then measured the amount of mercury stored within decadal core increments. We were surprised to find that mercury levels peaked in the 1930s to 1950s, even though global mercury emissions continued to rise throughout the past century, mostly as a by‐product of energy production. Our findings suggest that the trees were exposed to a local pollutant source during this earlier time period, perhaps from a nearby industrial plant that used mercury in the production of rayon. By examining the chemistry of wood within tree rings, we can get a clearer picture of when and where human activities have affected air pollution over recent centuries.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153685/1/jgrg21576_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153685/2/jgrg21576.pd

WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growth

We examined the role of WNT signaling in pituitary development by characterizing the pituitary phenotype of three WNT knockout mice and assessing the expression of WNT pathway components. Wnt5a mutants have expanded domains of Fgf10 and bone morphogenetic protein expression in the ventral diencephalon and a reduced domain of LHX3 expression in Rathke's pouch. Wnt4 mutants have mildly reduced cell differentiation, reduced POU1F1 expression, and mild anterior lobe hypoplasia. Wnt4 , Wnt5a double mutants exhibit an additive pituitary phenotype of dysmorphology and mild hypoplasia. Wnt6 mutants have no obvious pituitary phenotype. We surveyed WNT expression and identified transcripts for numerous Wnts , Frizzleds , and downstream pathway members in the pituitary and ventral diencephalon. These findings support the emerging model that WNT signaling affects the pituitary gland via effects on ventral diencephalon signaling, and suggest additional Wnt genes that are worthy of functional studies. Developmental Dynamics 237:1006–1020, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58083/1/21511_ftp.pd