Index to NASA Tech Briefs, 1975

This index contains abstracts and four indexes--subject, personal author, originating Center, and Tech Brief number--for 1975 Tech Briefs

Syntaphilin controls a mitochondrial rheostat for proliferation-motility decisions in cancer.

Tumors adapt to an unfavorable microenvironment by controlling the balance between cell proliferation and cell motility, but the regulators of this process are largely unknown. Here, we show that an alternatively spliced isoform of syntaphilin (SNPH), a cytoskeletal regulator of mitochondrial movements in neurons, is directed to mitochondria of tumor cells. Mitochondrial SNPH buffers oxidative stress and maintains complex II-dependent bioenergetics, sustaining local tumor growth while restricting mitochondrial redistribution to the cortical cytoskeleton and tumor cell motility. Conversely, introduction of stress stimuli to the microenvironment, including hypoxia, acutely lowered SNPH levels, resulting in bioenergetics defects and increased superoxide production. In turn, this suppressed tumor cell proliferation but increased tumor cell invasion via greater mitochondrial trafficking to the cortical cytoskeleton. Loss of SNPH or expression of an SNPH mutant lacking the mitochondrial localization sequence resulted in increased metastatic dissemination in xenograft or syngeneic tumor models in vivo. Accordingly, tumor cells that acquired the ability to metastasize in vivo constitutively downregulated SNPH and exhibited higher oxidative stress, reduced cell proliferation, and increased cell motility. Therefore, SNPH is a stress-regulated mitochondrial switch of the cell proliferation-motility balance in cancer, and its pathway may represent a therapeutic target

Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics and Tumor Cell Movements.

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, that is dynamics. Expression of ubiquitination-defective SNPH mutant Lys111!Arg or Lys153!Arg increased the speed and distance traveled by mitochondria, repositioned mitochondria to the cortical cytoskeleton, and supported heightened tumor chemotaxis, invasion, and metastasis in vivo. Interference with SNPH ubiquitination activated mitochondrial dynamics, resulting in increased recruitment of the fission regulator dynamin-related protein-1 (Drp1) to mitochondria and Drp1-dependent tumor cell motility. These data uncover nondegradative ubiquitination of SNPH as a key regulator of mitochondrial trafficking and tumor cell motility and invasion. In this way, SNPH may function as a unique, ubiquitination-regulated suppressor of metastasis

Index to NASA Tech Briefs, January - June 1967

Technological innovations for January-June 1967, abstracts and subject inde

Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces – the role of focal adhesion maturation

The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society. Hence, there is a need for next generation implantable devices to substitute for, or guide, bone repair in vivo. Cellular responses to nanometric topographical cues need to be better understood in vitro in order to ensure the effective and efficient integration and performance of these orthopaedic devices. In this study, the FDA approved plastic polycaprolactone, was embossed with nanometric grooves and the response of primary and immortalised osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 μm wide. Cells cultured on test surfaces followed contact guidance along the length of groove edges, elongated along their major axis and showed nuclear distortion, they formed more focal complexes and a lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalised cells was observed on grooved substrates. Down-regulation appeared to directly correlate with focal adhesion maturation, indicating the involvement of ERK 1/2 negative feedback pathways following integrin mediated FAK activation

Methods and protocols for incremental exercise testing in tetraplegia, using arm-crank ergometry assisted by Functional Electrical Stimulation

Cervical spinal cord injury (SCI) leads to tetraplegia, with paralysis and loss of sensation in the upper and lower limbs. The associated sedentary lifestyle results in an increased risk of cardiovascular disease. To address this, we require the design of exercise modalities aimed specifically at tetraplegia and methods to assess their efficacy. This paper describes methods for arm-crank ergometry (ACE) assisted by Functional Electrical Stimulation (FES) applied to the biceps and triceps. The instrumented ergometer enables work-rate control during exercise, implemented here for incremental exercise testing during FES-ACE. Detailed protocols for the tests are given. Experimental data collected during exercise tests with tetraplegic volunteers are provided to illustrate the feasibility of the proposed approach to testing and data analysis. Incremental tests enabled calculation of peak power output and peak oxygen uptake. We propose that the high-precision exercise testing protocols described here are appropriate to assess the efficacy of the novel exercise modality, FES-ACE, in tetraplegia

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 129, June 1974

This special bibliography lists 280 reports, articles, and other documents introduced into the NASA scientific and technical information system in May 1974

Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.

To enable new blood vessel growth, endothelial cells (ECs) express neuropilin 1 (NRP1), and NRP1 associates with the receptor tyrosine kinase VEGFR2 after binding the vascular endothelial growth factor A (VEGF) to enhance arteriogenesis. We report that NRP1 contributes to angiogenesis through a novel mechanism. In human and mouse ECs, the integrin ligand fibronectin (FN) stimulated actin remodeling and phosphorylation of the focal adhesion component paxillin (PXN) in a VEGF/VEGFR2-independent but NRP1-dependent manner. NRP1 formed a complex with ABL1 that was responsible for FN-dependent PXN activation and actin remodeling. This complex promoted EC motility in vitro and during angiogenesis on FN substrates in vivo. Accordingly, both physiological and pathological angiogenesis in the retina were inhibited by treatment with Imatinib, a small molecule inhibitor of ABL1 which is widely used to prevent the proliferation of tumor cells that express BCR-ABL fusion proteins. The finding that NRP1 regulates angiogenesis in a VEGF- and VEGFR2-independent fashion via ABL1 suggests that ABL1 inhibition provides a novel opportunity for anti-angiogenic therapy to complement VEGF or VEGFR2 blockade in eye disease or solid tumor growth

The Outer Tracker Detector of the HERA-B Experiment Part I: Detector

The HERA-B Outer Tracker is a large system of planar drift chambers with about 113000 read-out channels. Its inner part has been designed to be exposed to a particle flux of up to 2.10^5 cm^-2 s^-1, thus coping with conditions similar to those expected for future hadron collider experiments. 13 superlayers, each consisting of two individual chambers, have been assembled and installed in the experiment. The stereo layers inside each chamber are composed of honeycomb drift tube modules with 5 and 10 mm diameter cells. Chamber aging is prevented by coating the cathode foils with thin layers of copper and gold, together with a proper drift gas choice. Longitudinal wire segmentation is used to limit the occupancy in the most irradiated detector regions to about 20 %. The production of 978 modules was distributed among six different laboratories and took 15 months. For all materials in the fiducial region of the detector good compromises of stability versus thickness were found. A closed-loop gas system supplies the Ar/CF4/CO2 gas mixture to all chambers. The successful operation of the HERA-B Outer Tracker shows that a large tracker can be efficiently built and safely operated under huge radiation load at a hadron collider.Comment: 28 pages, 14 figure