Metabolic Pathways Associated With Glycogen Storage in Chronically Active and Normal Skeletal Muscle.

To determine the pathways used for glycogen synthesis in chronically active and normal muscle, muscles from C57B1/6J dy\sp{\rm 2J}/dy\sp{\rm 2J}(dy\sp{\rm 2J}) mice were evaluated biochemically and histochemically. The gastrocnemius muscle (GAST) of the dy\sp{\rm 2J} mouse, a chronically active muscle, contained twice as much glycogen and lactate as control GAST. The dy\sp{\rm 2J} triceps muscle (TRI), which is not chronically active, showed no elevation in glycogen content. An intraperitoneal injection of \sp{14}C-lactate resulted in increased incorporation of \sp{14}C into glycogen by dy\sp{\rm 2J} compared to control GAST. Both normal and dy\sp{\rm 2J} GAST incorporated \sp{14}C into glycogen in an in situ preparation, indicating direct glycogen synthesis from lactate. Autoradiography revealed that high glycogen containing muscle fibers in the dy\sp{\rm 2J} GAST have the highest capacity for glyconeogenesis. Glycogen synthase (GS), malic enzyme (ME) and phosphoenolpyruvate carboxykinase (PEPCK) are all elevated in dy\sp{\rm 2J} GAST, but not in dy\sp{\rm 2J} TRI compared to normal controls. High glycogen fibers in the dy\sp{\rm 2J} had higher activities of GS and ME than any other fibers. The variation in glycogen content along the length of single muscle fibers increased with increasing glycogen content. However, the variation was low enough in all fiber types to allow for a single histochemical section to be a good predictor of glycogen in that fiber. Glucose uptake and glycogen synthesis from glucose (glycogenesis) were elevated in chronically active muscles, in vivo and in vitro. The diaphragm muscle had the highest rates of glucose uptake and glycogenesis. Insulin stimulation of glucose uptake and glycogenesis were enhanced in chronically active muscles from dy\sp{\rm 2J} mice. Specific inhibitors of PEPCK inhibited glyconeogenesis in skeletal muscle, demonstrating the involvement of PEPCK. Previous contractile activity had no effect on glyconeogenic rates. Glyconeogenic rates were linearly dependent on substrate concentration and had a pH optimum of 6.6. Normal and chronically active muscles utilize both lactate and glucose for glycogen synthesis. Chronically active muscles store increased amounts of glycogen. The increased glycogen may provide the chronically active muscle with some additional resistance to fatigue

Senator James O. Eastland; Herman E. Talmadge; Bob Dole; Dick Clark; Edward Zorinsky; Walter D. Huddleston; S.I. Hayakawa; James B. Allen; Dick Stone; Hubert H. Humphrey; John Melcher; George McGovern; Carl T. Curtis; Milton Young; Patrick Leahy; Jesse Helms; & Richard Lugar to President Jimmy Carter, 20 October 1977

Copy typed letter signed dated 20 October 1977 from Eastland; Herman E. Talmadge; Bob Dole; Dick Clark; Edward Zorinsky; Walter D. Huddleston; S.I. Hayakawa; James B. Allen; Dick Stone; Hubert H. Humphrey; John Melcher; George McGovern; Carl T. Curtis; Milton Young; Patrick Leahy; Jesse Helms; & Richard Lugar to Carter, re: agricultural exports, farm prices, Commodity Credit Corporation; 2 pages.https://egrove.olemiss.edu/joecorr_h/1075/thumbnail.jp

Senator James O. Eastland; Herman E. Talmadge; Bob Dole; George McGovern; James B. Allen; Milton Young; Jesse Helms; Patrick Leahy; Henry Bellmon; S.I. Hayakawa; Carl T. Curtis; Richard Lugar; John Melcher; & Dick Clark to President Jimmy Carter, 14 October 1977

Copy typed letter signed dated 14 October 1977 from Eastland; Herman E. Talmadge; Bob Dole; George McGovern; James B. Allen; Milton Young; Jesse Helms; Patrick Leahy; Henry Bellmon; S.I. Hayakawa; Carl T. Curtis; Richard Lugar; John Melcher; & Dick Clark to Carter, re: New Orleans strike of International Longshoremens Association, grain exports; 2 pages.https://egrove.olemiss.edu/joecorr_h/1069/thumbnail.jp

Bob Dole, [Carl T. Curtis, Herman E. Talmadge, James O. Eastland, S.I. Hykawa possibly] to President Jimmy Carter, 31 January 1978

Copy typed letter signed dated 31 January 1978 from Bob Dole, [Curtis, Talmadge, Eastland, Hykawa possibly] to Carter, re: European Community trade negotiations, soybeans.https://egrove.olemiss.edu/joecorr_h/1090/thumbnail.jp

The acoustic field on the forehead of echolocating Atlantic bottlenose dolphins (Tursiops truncatus)

Author Posting. © Acoustical Society of America, 2010. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 128 (2010): 1426-1434, doi:10.1121/1.3372643.Arrays of up to six broadband suction cup hydrophones were placed on the forehead of two bottlenose dolphins to determine the location where the beam axis emerges and to examine how signals in the acoustic near-field relate to signals in the far-field. Four different array geometries were used; a linear one with hydrophones arranged along the midline of the forehead, and two around the front of the melon at 1.4 and 4.2 cm above the rostrum insertion, and one across the melon in certain locations not measured by other configurations. The beam axis was found to be close to the midline of the melon, approximately 5.4 cm above the rostrum insert for both animals. The signal path coincided with the low-density, low-velocity core of the melon; however, the data suggest that the signals are focused mainly by the air sacs. Slight asymmetry in the signals were found with higher amplitudes on the right side of the forehead. Although the signal waveform measured on the melon appeared distorted, when they are mathematically summed in the far-field, taking into account the relative time of arrival of the signals, the resultant waveform matched that measured by the hydrophone located at 1 m.This work was supported by the U.S. Office of Naval Research

Loss of Cbl and Cbl-b ubiquitin ligases abrogates hematopoietic stem cell quiescence and sensitizes leukemic disease to chemotherapy.

Cbl and Cbl-b are tyrosine kinase-directed RING finger type ubiquitin ligases (E3s) that negatively regulate cellular activation pathways. E3 activity-disrupting human Cbl mutations are associated with myeloproliferative disorders (MPD) that are reproduced in mice with Cbl RING finger mutant knock-in or hematopoietic Cbl and Cbl-b double knockout. However, the role of Cbl proteins in hematopoietic stem cell (HSC) homeostasis, especially in the context of MPD is unclear. Here we demonstrate that HSC expansion and MPD development upon combined Cbl and Cbl-b deletion are dependent on HSCs. Cell cycle analysis demonstrated that DKO HSCs exhibit reduced quiescence associated with compromised reconstitution ability and propensity to undergo exhaustion. We show that sustained c-Kit and FLT3 signaling in DKO HSCs promotes loss of colony-forming potential, and c-Kit or FLT3 inhibition in vitro protects HSCs from exhaustion. In vivo, treatment with 5-fluorouracil hastens DKO HSC exhaustion and protects mice from death due to MPD. Our data reveal a novel and leukemia therapy-relevant role of Cbl and Cbl-b in the maintenance of HSC quiescence and protection against exhaustion, through negative regulation of tyrosine kinase-coupled receptor signaling

Multifaceted Role of Neuropilins in the Immune System: Potential Targets for Immunotherapy.

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, such as neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class III Semaphorins and for members of the vascular endothelial growth factor family of molecules and are widely known for their role in a wide array of physiological processes, such as cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis, as well as various clinical disorders. Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in normal physiological as well as different pathological conditions, including cancer, immunological disorders, and bone diseases. However, little is known concerning the molecular pathways that govern these functions. In addition, NRP1 expression has been characterized in different immune cellular phenotypes including macrophages, dendritic cells, and T cell subsets, especially regulatory T cell populations. By contrast, the functions of NRP2 in immune cells are less well known. In this review, we briefly summarize the genomic organization, structure, and binding partners of the NRPs and extensively discuss the recent advances in their role and function in different immune cell subsets and their clinical implications

Accelerated Variant of Idiopathic Pulmonary Fibrosis: Clinical Behavior and Gene Expression Pattern

Idiopathic pulmonary fibrosis (IPF) is characterized by the insidious onset of dyspnea or cough. However, a subset of patients has a short duration of symptoms with rapid progression to end-stage disease. In this study, we evaluated clinical and molecular features of "rapid" and "slow" progressors with IPF

Idiopathic interstitial pneumonia: Do community and academic physicians agree on diagnosis?

Rationale: Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult. Objectives: Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers. Methods: Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days. Measurements and Main Results: Each observer’s diagnosis was coded into one of eight categories. A statistic allowing formultiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (Kappa= 0.55–0.71) than within community centers (Kappa=0.32–0.44). Clinically significant disagreement was present between academic and communitybased physicians (Kappa=0.11–0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians. Conclusions: Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91941/1/2007 AJRCCM Idiopathic interstitial pneumonia - Do community and academic physicians agree on diagnosis.pd