The Mouse Genome Database (MGD) forms the core of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a model organism database resource for the laboratory mouse. MGD provides ...essential integration of experimental knowledge for the mouse system with information annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genotype (sequence) through phenotype information, including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships among genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent improvements in MGD discussed here include the enhancement of phenotype resources, the re-development of the International Mouse Strain Resource, IMSR, the update of mammalian orthology datasets and the electronic publication of classic books in mouse genetics.
Retinal arrestin (S-antigen) inactivates the phototransduction cascade by binding to light-activated phosphorylated rhodopsin and thereby "arresting" coupling to the G protein transducin. ...beta-Arrestin (beta arr), a ubiquitous arrestin homolog, acts analogously to desensitize the beta 2-adrenergic receptor by disrupting Gs receptor interaction. In an attempt to identify additional "arrestins" which might regulate the multitude of G protein-coupled receptors, we have isolated two bovine brain cDNAs which encode polypeptide variants of an arrestin homolog which we have designated arrestin3 (arr3). The open reading frames of these two cDNAs are identical except that the long form, arr3L, contains an 11-amino-acid insert between residues 361 and 362. Arr3 is more closely related to bovine beta arr (78% identity) than to bovine visual arrestin (56% identity). Polymerase chain reaction amplification of RNA and immunoblotting of lysates with an arr3-specific antibody suggest that the short form, arr3S, is the major form of arr3 in all bovine tissues and that it is most abundant in the spleen. Furthermore, polymerase chain reaction amplification of beta arr mRNA indicates that in several tissues (lung, liver, spleen, and pituitary), the major form of beta arr lacks 8 amino acids which are present in brain beta arr. Immunoblotting with an antibody which recognizes beta arr and arr3 with equal sensitivity demonstrates that beta arr (either the long or the short polypeptide) is the major arrestin in all (non-photoreceptor bearing) tissues examined. These observations suggest that in some tissues, as many as four arrestin homolog variants may play a role in the regulation of G protein-coupled receptors.
Multiple endocrine neoplasia type 1 (MEN1) is a promising model to understand endocrine and other tumors. Its most common endocrine expressions are tumors of parathyroids, entero-pancreatic ...neuro-endocrine tissue, and anterior pituitary. Recently, collagenomas and multiple angiofibromas of the dermis also have been recognized as very common. MEN1 can be characterized from different perspectives: (a) as a hormone (parathyroid hormone, gastrin, prolactin, etc.) excess syndrome with excellent therapeutic options; (b) as a syndrome with sometimes lethal outcomes from malignancy of entero-pancreatic neuro-endocrine or foregut carcinoid tissues; or (c) as a disorder than can give insight about cell regulation in the endocrine, the dermal, and perhaps other tissue systems. The
MEN1 gene was identified recently by positional cloning, a comprehensive strategy of narrowing the candidate interval and evaluating all or most genes in that interval. This discovery has opened new approaches to basic and clinical issues. Germline
MEN1 mutations have been identified in most MEN1 families. Germline
MEN1 mutations were generally not found in families with isolated hyperparathyroidism or with isolated pituitary tumor. Thus, studies with the MEN1 gene helped establish that mutation of other gene(s) is likely causative of these two MEN1 phenocopies.
MEN1 proved to be the gene most frequent L4 mutated in common-variety, nonhereditary parathyroid tumor, gastrinoma, insulinoma, or bronchial carcinoid. For example, in common-variety parathyroid tumors, mutation of several other genes (such as
cyclin D1 and
P53) has been found, but much less frequently than
MEN1 mutation. The majority of germline and somatic
MEN1 mutations predicted truncation of the encoded protein (menin). Such inactivating mutations strongly supported prior predictions that
MEN1 is a tumor suppressor gene insofar as stepwise mutational inactivation of both copies can release a cell from normal growth suppression. Menin is principally a nuclear protein; menin interacts with junD. Future studies, such as discovery of menin’s metabolic pathway, could lead to new opportunities in cell biology and in tumor therapy.
We report the detection of absorption by interstellar hydroxyl cations and water cations, along the sight-line to the bright continuum source W49N. We have used Herschel's HIFI instrument, in dual ...beam switch mode, to observe the 972 GHz N = 1–0 transition of OH+ and the 1115 GHz 111–000 transition of ortho-H2O+. The resultant spectra show absorption by ortho-H2O+, and strong absorption by OH+, in foreground material at velocities in the range 0 to 70 km s-1 with respect to the local standard of rest. The inferred OH+/H2O+ abundance ratio ranges from ~3 to ~15, implying that the observed OH+ arises in clouds of small molecular fraction, in the 2–8% range. This conclusion is confirmed by the distribution of OH+ and H2O+ in Doppler velocity space, which is similar to that of atomic hydrogen, as observed by means of 21 cm absorption measurements, and dissimilar from that typical of other molecular tracers. The observed OH+/H abundance ratio of a few ×10-8 suggests a cosmic ray ionization rate for atomic hydrogen of 0.6–2.4×10-16 s-1, in good agreement with estimates inferred previously for diffuse clouds in the Galactic disk from observations of interstellar H3+ and other species.
To evaluate the short term efficacy of a community based physical therapy (PT) program for people with rheumatoid arthritis (RA) through a single blind randomized controlled trial.
Adults with active ...RA were referred by their physician for community based PT. Participants were randomized to either an immediate intervention group experimental group (EG) or a wait list control group (CG). The intervention was a standardized program of education and exercise consisting of at least 4 visits or 3 h of PT over 6 weeks. Baseline, 6, and 12 week assessments were by a blinded independent assessor. The primary outcome instrument was the Stanford Arthritis Self-Efficacy Scale (SES) and secondary outcome measures included the ACREU Rheumatoid Arthritis Knowledge Questionnaire (KQ) and visual analog scale for pain (VAS). Duration of morning stiffness, grip strength, and tender joint count were also collected at each assessment. Outcome analysis was conducted using analysis of variance.
Of 150 eligible and randomized participants, 127 completed the study according to protocol. Baseline analysis showed no differences between the EG and CG for demographics, disease status, or other characteristics. At the 6 week assessment, primary outcome analysis for those who completed the protocol identified a mean change (improvement) of 13.5% in the EG and 5.8% in the CG, representing a 7.7% difference in change scores between the 2 groups F(1,121) = 6.03; p = 0.015. A statistically significant difference in change scores was also identified for the KQ F(1,120) = 6.67; p = 0.011, but not for the VAS. Disease status measures did not change, except for duration of morning stiffness, which improved by 68.8 min in the EG and 8.3 min in the CG (F(1,121) = 4.50; p = 0.036.
Four hours of a community based PT intervention delivered over 6 weeks significantly improved self-efficacy, disease management knowledge and morning stiffness in people with RA.
Efficient gene transfer with extended gene expression is essential for successful treatment of skin diseases using gene therapy. Previously we evaluated a physical gene transfer method (gene gun ...delivery) for its ability to transfect the epidermis in vivo. In this study, we tested two viral vectors for their ability to transduce murine epidermis through topical application. Both an adenoviral vector and a herpes simplex virus (HSV) amplicon vector transduced murine epidermis with high efficiency after topical application. Differences in amount and duration of transgene expression were compared between these two vectors. Quantitative analysis of reporter lacZ gene expression showed that the viral vector-mediated gene transfers were superior to gene-gun delivery of plasmid DNA. Significant necrosis and cytotoxicity, however, were observed in the HSV-treated skin. In addition, we show that murine epidermis developed hyperkeratosis and acanthosis 4 d after an adenoviral vector containing a human TGF-α expression unit was applied topically. Finally we demonstrate the feasibility of transduction of fetal skin in utero by intraamniotic injection of an adenovirus vector.
When stresses and hassles challenge our abilities to cope, we frequently turn to family, friends, and partners for help. Yet social support from close relational partners does not uniformly benefit ...recipients or their relationships. By probing the communication processes that link enactments of social support to participants' reactions, this book provides new explanations for when and how receiving social support will be evaluated as helpful and relationally satisfying. The author's research addresses a variety of types of relationships and stresses, including young adult friends and romantic partners coping with the stresses of university life; adult friends, family and spouses responding to everyday hassles' and married couples coping with chronic health conditions. This innovative program of research combines qualitative and quantitative methods to develop a distinctive communication-based framework for understanding why the content, form, style, and sequence of talk matter for our evaluations of the help we receive from others.
We have recently mapped the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and ...cardiovascular system, to chromosome 16p 13.1. Here we report further data on the fine-mapping and genomic structure of this locus. Haplotype analysis of informative PXE families narrowed the locus to an interval of less than 500 kb located between markers D16B9621 and D16S764. Three overlapping YAC clones were found to cover this region through YAC-STS content mapping. An overlapping BAC contig was then constructed to cover this interval and the surrounding region. About 80% of this chromosomal region has been fully sequenced using the BAC shotgun technique. Gene content and sequence analysis predicted four genes (MRP1, MRP6, PM5, and a novel transcript) and two pseudogenes (ARA and PKDI) within this interval. By screening a somatic cell hybrid panel we were able to precision-map the breakpoint of Cy185 and the starting point of a chromosomal duplication within 20 kb of BAC A962B4. The present data further refine the localization of PXE, provide additional physical cloning resources, and will aid in the eventual identification of the genetic defect causing PXE.
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