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Pathobiology of the senescence-accelerated mouse (SAM).

Routine postmortem examinations and the pathobiological features revealed by systematically designed studies have shown several pathologic phenotypes that are often characteristic enough to differentiate among the various SAM strains: senile amyloidosis in SAMP1, -P2, -P7, -P9, -P10, and -P11; secondary amyloidosis in SAMP2 and -P6; contracted kidney in SAMP1, -P2, -P10, and -P11; immunoblastic lymphoma in SAMR1 and -R4; histiocytic sarcoma in SAMR1 and -R4; ovarian cysts in SAMR1; impaired immune response in SAMP1, -P2, and -P8; hyperinflation of the lungs in SAMP1; hearing impairment in SAMP1; degenerative temporomandibular joint disease in SAMP3; senile osteoporosis in SAMP6; deficits in learning and memory in SAMP8 and -P10; emotional disorders in SAMP8 and -P10; cataracts in SAMP9; and brain atrophy in SAMP10. These are all age-associated pathologies, the incidence and severity of which increase with advancing age. The SAM model in which these pathobiological features have been carefully monitored will be a valuable tool in the clarification of the pathogenic mechanisms of age-associated pathologies and in the research for effective methods to modulate or ameliorate these pathologies.

Aging↗

Management and design of the maintenance of SAM mouse strains: an animal model for accelerated senescence and age-associated disorders.

The Senescence-Accelerated Mouse (SAM) was established by inbreeding and pedigree selection based on the life span, degree of senescence, as well as the incidence and degree of several age-associated disorders. At first, SAM strains were developed under conventional conditions, but now some strains are also maintained under specific pathogen-free conditions. There are many methods used to maintain such strains of mice; our methods will be introduced as one example of how to develop and maintain strains of mice used in aging research.

Aging↗

Global regulation of Hox gene expression in C. elegans by a SAM domain protein.

Polycomb group (PcG)-mediated repression of C. elegans Hox genes has not been demonstrated, and genes homologous to components of one of the PcG complexes (PRC1) have not been identified in the C. elegans genome. We find that a mechanism of general Hox gene repression exists in C. elegans, carried out in part by SOP-2, a protein related to, but not orthologous with, any PcG protein. sop-2 mutations lead to widespread ectopic expression of Hox genes and homeotic transformations. SOP-2 contains a SAM domain, a self-associating protein domain found in other repressors, including a core component of PRC1 and ETS transcription factors. Phylogenetic analysis indicates that this domain is more closely related to those of the ETS family than to those of PcG proteins. The results suggest that global repression of Hox genes has been taken over by a different branch of the SAM domain family during the evolution of nematodes.

Amino Acid Sequence↗

Ultra-sensitive imaging and interfacial analysis of patterned hydrophilic SAM surfaces using energy dissipation chemical force microscopy.

Energy dissipation chemical force microscopy has been used to analyze the dissipative properties of chemically similar regions of hydroxyl- and carboxyl-terminated SAMs on gold with a hydroxyl-terminated tip. Energy dissipation imaging quantitatively isolates dissipative interfacial interactions from topography, producing a significantly more informative image than phase imaging. Also, energy dissipation force curves probed the rheological properties of the tip-sample interaction. Viscosity of the confined water increased slightly over that of the bulk, and SAM deformation was found to have a longer retardation time than restructuring of interfacial ions and solvent during tip-sample contact.

Journal Article↗

Controlling DNA orientation on mixed ssDNA/OEG SAMs.

We present and characterize a mixed self-assembled monolayer (SAM) consisting of single-stranded oligonucleotide (ssDNA)- and oligo(ethylene glycol) (OEG)-terminated thiols. The ssDNA/OEG SAMs are prepared by simultaneous coadsorption from a common thiol solution over a broad range of compositions. Electron spectroscopy for chemical analysis (ESCA) is used to measure the surface coverage of ssDNA, whereas surface plasmon resonance (SPR) sensor is used to measure the hybridization of complementary ssDNA and protein resistance. Through the complementary use of these techniques, we find that the composition of OEG in the assembly solution controls a key parameter: the surface coverage of ssDNA on the surface. There is evidence that it influences the orientation of the immobilized ssDNA probes. Lower OEG concentrations yield a surface with higher ssDNA coverage and less favorable orientation, whereas higher OEG concentrations produce a surface with lower DNA coverage and more favorable orientation. Competition between these two effects controls the hybridization efficiency of the ssDNA surface. Compared to ssDNA surfaces prepared with other diluent thiols, the use of OEG improves the protein resistance of the surface, making it more broadly applicable.

Adsorption↗

HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells.

SH3 and SAM domains are protein interaction motifs that are predominantly seen in signaling molecules, adaptors, and scaffold proteins. We have identified a novel family of putative adaptor genes that includes HACS1. HACS1 encodes a 441 amino acid protein that is differentially expressed in hematopoietic cells and has restricted expression in human tissues. Its SH3 domain is most similar to the same motif in Crk and its SAM domain shares homology with a family of uncharacterized putative scaffold and adaptor proteins. HACS1 maps to human chromosome 21q11.2 in a region that is frequently disrupted by translocation events in hematopoietic malignancies. Polyclonal antibodies against HACS1 recognized a 49.5 kDa protein whose mRNA is expressed in human immune tissues, bone marrow, heart, lung, placenta and brain. Cell lines and primary cells from acute myeloid leukemias and multiple myeloma patients express HACS1. Immunostaining and cellular fractionation studies localized the HACS1 protein predominantly to the cytoplasm.

Adaptor Proteins, Vesicular Transport↗

Disorganised self-assembled monolayers (SAMs): the incorporation of amphiphilic molecules.

A new approach for designing a voltammetric selective electrode is presented. The approach is based on the formation of a disorganised inert self-assembled monolayer (SAM), in which an amphiphilic molecule is incorporated. The latter serves as the selectivity factor, which extracts the analyte. The purpose of these experiments is to study the parameters that affect the capability of a monolayer to host amphiphiles. As model systems we focused on the incorporation of simple amphiphilic molecules (quaternary alkyl ammonium salts), electroactive amphiphiles (dialkylviologens) and a macrocycle ligand (tetramethylcyclam) into octadecyl silane monolayers formed on indium tin oxide (ITO) and purposely made disorganised alkanethiols on gold. We find that basically, the incorporation of amphiphiles into a hydrophobic inert SAM resembles a reversed stationary phase in liquid chromatography and this configuration can be used for designing selective electrodes.

Journal Article↗

Ultrastructural changes in microvessel with age in the hippocampus of senescence-accelerated mouse (SAM)-P/10.

Microvessels in the hippocampus of aged SAM-P/10 (14 months old) showed the following ultrastructural changes compared with those of young-mature controls (3 months old): (1) the majority of capillaries had lost the smooth contours typical of young cases; (2) the luminal surface of capillaries showed irregularity; (3) the endothelial cytoplasm was thicker; (4) vesicles appeared more frequently in the endothelium; (5) interendothelial tight junctions and basement membranes, however, seemed to show no significant abnormalities; (6) pericytes, especially those of arterioles and venules, contained many enlarged cytoplasmic inclusions with honeycomb-like vacuoles; (7) the area of glial perivascular end feet was greater. These morphological findings raise the possibility of impaired blood-brain barrier function and microhemodynamic disturbances in aged SAM-P/10 hippocampus.

Aging↗

Differential gene expression detection using penalized linear regression models: the improved SAM statistics.

UNLABELLED: Differential gene expression detection using microarrays has received lots of research interests recently. Many methods have been proposed, including variants of F-statistics, non-parametric approaches and empirical Bayesian methods etc. The SAM statistics has been shown to have good performance in empirical studies. SAM is more like an ad hoc shrinkage method. The idea is that for small sample microarray data, it is often useful to pool information across genes to improve efficiency. Under Bayesian framework Smyth formally derived the test statistics with shrinkage using the hierarchical models. In this paper we cast differential gene expression detection in the familiar framework of linear regression model. Commonly used test statistics correspond to using least squares to estimate the regression parameters. Based on the vast literature of research on linear models, we can naturally consider other alternatives. Here we explore the penalized linear regression. We propose the penalized t-/F-statistics for two-class microarray data based on [Formula: see text] penalty. We will show that the penalized test statistics intuitively makes sense and through applications we illustrate its good performance. AVAILABILITY: Supplementary information including program codes, more detailed analysis results and R functions for the proposed methods can be found at http://www.biostat.umn.edu/~baolin/research CONTACT: baolin@biostat.umn.edu SUPPLEMENTARY INFORMATION: http://www.biostat.umn.edu/~baolin/research.

Cell Line, Tumor↗

Crystallization and preliminary crystallographic studies of a SAM domain at the C-terminus of human p73alpha.

p73 is a recently discovered homologue of the tumour suppressor p53 and contains all three functional domains of p53. The alpha-splice variant of p73 (p73alpha) contains an additional structural domain near its C--terminus that has sequence homology with the sterile alpha-motif (SAM) domain. This domain is considered to be responsible for mediating protein-protein interactions. Pyramidal crystals of human p73alpha SAM domain were obtained by the hanging-drop vapour-diffusion method with ammonium dihydrogen orthophosphate as the precipitant. The crystals diffract to 2.54 A resolution and belong to the tetragonal space group P4(1)2(1)2, with unit-cell parameters a = b = 32.02, c = 133.84 A. The structure was solved by molecular replacement using the NMR structure of the same protein as the search model.

Amino Acid Motifs↗

Oral senile amyloidosis in senescence accelerated mouse (SAM).

Oral senile amyloidosis in senescence accelerated mouse (SAM) was examined for two SAM sublines (P/2/Iw and R/1/Iw) and for various ages by light microscopy, immunohistochemistry, and electron microscopy. The amyloid deposition, identified by green birefrigence following Congo red stain, was observed only in P/2/Iw. In P/2/Iw, no amyloid deposition was found at age 6 months; however, frequency and extent of such deposits increased with advancing age. Distribution of amyloid deposition was as follows: along papillary layers of mucous epithelium in the tongue, the gingiva, the palate, and the buccal mucosa; foci in connective tissues; along vessels, muscles, and minor salivary glands. Immunohistochemically, the amyloid deposition was positive with anti-ASSAM serum being raised against a unique amyloid protein ASSAM which probably induced "senile systemic amyloidosis". P/2/Iw is useful as an animal model of oral senile amyloidosis.

Aging↗

Effects of yukmi, an herbal formula, on the liver of senescence accelerated mice (SAM) exposed to oxidative stress.

The effects of yukmi (Decoction of six plants including rehmannia), an herbal formula, were studied on liver oxidant damage induced by paraquat (PQ) administered intravenously in the senescence accelerated mice (SAM-P/8). The activities of superoxide dismutase (SOD) and catalase as two major antioxidant enzymes and lipid peroxidation levels were determined for six days. Data show that the activities of hepatic SODs and catalase were increased by oral administration of yukmi extracts following PQ pretreatment. Herbal medicine effectively blocked the PQ-induced effects on liver malondialdehyde (MDA) levels. For the histopathological changes in SAM-P/8 liver, yukmi extracts inhibited PQ-induced damage to the hepatic mitochondria and their membranes. Data suggest that yukmi extracts may be useful in protecting against oxidative damage.

Aging↗

Alveolar bone loss of senescence-accelerated mouse (SAM).

SAM-R/1/Iw (senescence-accelerated mouse, resistant) and P/2/Iw (senescence-accelerated mouse, prone) under a conventional environment and eating standard pellets were examined for alveolar bone loss and the presence of periodontitis around maxillary and mandibular molars as a function of age. Neither SAM strain manifested a chronic periodontitis similar to that in humans, and no obvious plaque and calculus were observed. However, in both strains, 15% of M3 was lost after 13 months of age, and alveolar bone loss gradually increased with advancing age. Though there was no significant difference in the incidence of M3 loss between the two strains, P/2/Iw showed a higher alveolar bone loss around all molars than did R/1/Iw after one month of age throughout their life span. For M1, the difference in alveolar bone loss between P/2/Iw and R/1/Iw was significant, and it was probably caused by the difference in degree of molar eruption. Other factors, such as occlusal trauma and gingivitis, may play some role in alveolar bone loss.

Aging↗

Review and standardization of cell phone exposure calculations using the SAM phantom and anatomically correct head models.

We reviewed articles using computational RF dosimetry to compare the Specific Anthropomorphic Mannequin (SAM) to anatomically correct models of the human head. Published conclusions based on such comparisons have varied widely. We looked for reasons that might cause apparently similar comparisons to produce dissimilar results. We also looked at the information needed to adequately compare the results of computational RF dosimetry studies. We concluded studies were not comparable because of differences in definitions, models, and methodology. Therefore we propose a protocol, developed by an IEEE standards group, as an initial step in alleviating this problem. The protocol calls for a benchmark validation study comparing the SAM phantom to two anatomically correct models of the human head. It also establishes common definitions and reporting requirements that will increase the comparability of all computational RF dosimetry studies of the human head.

Artifacts↗

Depressive behavior and alterations in receptors for dopamine and 5-hydroxytryptamine in the brain of the senescence accelerated mouse (SAM)-P10.

The senescence accelerated mouse (SAM) is known as a murine model of aging. SAM consists of senescence accelerated-prone mouse (SAMP) and senescence accelerated-resistant mouse (SAMR). Previous studies reported that SAMP10 exhibits age-related learning impairments and behavioral depression in a tail suspension test after 7 months. We investigated the changes in emotional behavior in a forced swimming test and in receptors for dopamine and 5-hydroxytryptamine (5-HT) in SAMP10. SAMP10 at 8 months showed an increase of immobility in the test compared with SAMR1. Treatment with desipramine (25 mg/kg, i.p., 3 days) in SAMP10 caused a decrease in immobility. In the cortex from SAMP10, [3H]quinpirole binding to D2/D3 dopamine receptors increased significantly compared with control SAMR1. In the hippocampus from SAMP10, [3H]8-hydroxy DPAT binding to 5-HT1A receptor increased. In midbrains from SAMP10, bindings of [3H]quinpirole and [3H]8-hydroxy DPAT increased. [3H]SCH23390 binding to D1/D5 receptors and [3H]ketanserin binding to 5-HT2 receptor in brain regions examined in SAMP10 were similar to those in SAMR1. The present findings represent the first neurochemical evidence of an increase of D2/D3 and 5-HT1A receptors in SAMP10. SAMP10 may be a useful model of aging associated depressive behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

SAM Complex Coordinator and Multidimensional Pursuit Test: annotated bibliographies.

A brief description of the SAM Complex Coordinator (Mashburn Apparatus) and the SAM Multidimensional Pursuit Test (MDP or MPT) and annotated bibliographies including 144 and 51 citations respectively are presented. All references are annotated as to subject matter within six categories; Factor Analytic-Task Taxonomy, Aircrew Selection-Classification, Learning Phenomena, Stress Effects, History and Development, General Reviews.

Aerospace Medicine↗

[Studies on aging through analysis of the glucose metabolism related to the ATP--production of the senescence accelerated mouse (SAM)].

It is thought that the senescence accelerated mouse (SAM) strains are very useful for examination of the aging mechanism. In particular, SAMP8 is useful since this substrain shows age-related deterioration of learning ability. One of the most attractive hypotheses of aging is that aging is a result of long-term exposure to free radicals generated through the glucose metabolism, and it is possible that oxygen radicals might be involved in the aging mechanism of SAM. In the present study, to elucidate the relation between free radicals and aging acceleration in SAMP8, we examined the changes in food intake, body weight and spontaneous motor activity. Biochemical analyses of blood glucose, cholesterol, triglyceride, total protein and albumin in SAMP8 and R1 mice were also performed. In addition, the amounts of ATP, creatine phosphate (Cr-P) and lipid peroxide in the brains of SAMP8 and R1 mice were measured. As for SAMP8, an increase in food intake and a decrease in body weight and spontaneous motor activity were observed as compared with SAMR1 control mice. These results may indicate that energy metabolism is abnormal in SAMP8. The lipid peroxide level in the brain of SAMP8 at 3 months of age was significantly lower than that of the control mice. However, the ATP and Cr-P amounts in the SAMP8 brain were same as those in the control mice at the same age. These results suggest that generation of free radicals decreases due to lowered glucose metabolism and that the amount of ATP production in the brain of SAMP8 is lower than that of the control mice. In conclusion the aging of SAMP8 may result from a decrease of the glucose metabolism and of the utilization of ATP rather than from injury caused by free radicals induced through the glucose metabolism.

Adenosine Triphosphate↗