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At least 919 records · Page 51

MicroRNAs as diagnostic and prognostic biomarkers of age-related macular degeneration: advances and limitations

A main cause of vision loss in the elderly is age-related macular degeneration (AMD). Among the cellular, biochemical, and molecular changes linked to this disease, inflammation and angiogenesis appear as being crucial in AMD pathogenesis and progression. There are two forms of the disease: dry AMD, accounting for 80–90% of cases, and wet AMD. The disease usually begins as dry AMD associated with retinal pigment epithelium and photoreceptor degeneration, whereas wet AMD is associated with choroidal neovascularization resulting in severe vision impairment. The new vessels are largely malformed, leading to blood and fluid leakage within the disrupted tissue, which provokes inflammation and scar formation and results in retinal damage and detachment. MicroRNAs are dysregulated in AMD and may facilitate the early detection of the disease and monitoring disease progression. Two recent reviews of microRNAs in AMD had indicated weaknesses or limitations in four earlier investigations. Studies in the last three years have shown considerable progress in overcoming some of these concerns and identifying specific microRNAs as biomarkers for AMD. Further large-scale studies are warranted using appropriate statistical methods to take into account gender and age disparity in the study populations and confounding factors such as smoking status.

60 APPLIED LIFE SCIENCES↗

Aneuploidy induces premature aging in yeast due to defects in Ribosome Quality Control [RNASeqData]

Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.

aneuploidy↗

Aneuploidy induces premature aging in yeast due to defects in Ribosome Quality Control [MoBYSeqData]

Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.

aneuploidy↗

Premature aging in aneuploid yeast is influenced by aneuploidy-induced defects in Ribosome Quality Control [RiboSeq]

Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.

aneuploidy↗

Proceedings of the Conference on Space-Age Planning: A Part of the Third National Conference on the Peaceful Uses of Space, Chicago, May 1-9, 1963

The Space-Age Planning sessions of the Third National Conference on the Peaceful Uses of Space have been planned by its principal sponsors-the National Aeronautics and Space Administration and the Mayor's Committee for Economic and Cultural Development of Chicago-and the 17 regional participating agencies to meet varied interests and contribute to future planning and profit. Its objectives are as follow: (1) To develop widespread local and regional interest in every phase of man's relationship to outer space (2) To bring about maximum utilization of regional industrial and educational resources in the Nation's space program (3) To obtain full utilization by regional industries and universities of the spin-off research that the Space Age is generating. The papers presented herein are concerned with exploration of space, man in space, the university-industry partnership in space programs, how space activities are changing the economy, business opportunities from space research, the placement and management of research and development projects, and the opportunities and challenges in space procurement.

NASA PROGRAM↗

U, Th, Pb and REE abundances and Pb 207/Pb 206 ages of individual minerals in returned lunar material by ion microprobe mass analysis.

Results of ion microprobe analyses of Apollo 11, 12 and 14 material, showing that U, Th, Pb and REE are concentrated in accessory minerals such as apatite, whitlockite, zircon, baddeleyite, zirkelite, and tranquillityite. Th/U ratios are found to vary by over a factor of 40 in these minerals. K, Ba, Rb and Sr have been localized in a K rich, U and Th poor glass phase that is commonly associated with the U and Th bearing accessory minerals. Li is observed to be fairly evenly distributed between the various accessory phases. The phosphates have been found to have REE abundance patterns (normalized to the chondrite abundances) that are fairly flat, while the Zr bearing minerals have patterns that rise steeply, by factors of ten or more, from La to Gd. All the accessory minerals have large negative Eu anomalies. Radiometric age dates (Pb 207/Pb 206) of the individual U and Th bearing minerals compare favorably with the Pb 207/Pb 206 age of the bulk rocks.

Andersen, C. A.↗

Study of X-ray diffraction on aging alloys with different degrees of volume discrepancy between the precipitation phase and the matrix

Study of the diffraction patterns of X rays diffracted by dispersion-hardened alloys with various degrees of difference between the specific atomic volumes of their precipitation phases and matrices. Experiments were performed on aging alloys KhN77TIuR (nimonic) and KhN67VMTIuO, which have the same types of gamma solid solutions and precipitating gamma prime phases, but differ considerably with respect to the volume factor. It is found that in the decay of supersaturated solid solutions for which the difference between the specific atomic volumes of the precipitation phase and the matrix is small (alloy KhN67VMTIuO) the nature of the intensity distribution of the diffraction lines remains practically unchanged regardless of the aging, while in cases where the volume discrepancy is large (alloy KhN77TIuR) significant changes in the appearance of the diffraction lines are recorded.-

Gitgarts, M. I.↗

Effect of set size, age, and mode of stimulus presentation on information-processing speed.

First, second, and third grade pupils served as subjects in an experiment designed to show the effect of age, mode of stimulus presentation, and information value on recognition time. Stimuli were presented in picture and printed word form and in groups of 2, 4, and 8. The results of the study indicate that first graders are slower than second and third graders who are nearly equal. There is a gross shift in reaction time as a function of mode of stimulus presentation with increase in age. The first graders take much longer to identify words than pictures, while the reverse is true of the older groups. With regard to set size, a slope appears in the pictures condition in the older groups, while for first graders, a large slope occurs in the words condition and only a much smaller one for pictures.

Norton, J. C.↗

Metallurgical evaluation of factors influencing the ductility of aged T-111

The metallurgical factors influencing the ductility of T-111 (Ta-8W-2Hf) alloy following long-time exposures of GTA welds and tubing in the temperature range 982 C (1800 F) through 1316 C (2400 F) were evaluated by means of scanning and transmission electron microscopy, Auger electron emission spectroscopy, and optical metallographic procedures. No classical aging response occurs in the alloy over the temperature range studied. The ductility impairment implied by previous investigations is not the result of microstructural response of the alloy to thermal exposures. Intergranular failure in the GTA sheet welds appears the result of random contamination by silicon, potassium, and/or fluorine at the grain boundaries of the fusion zones. Exposure to lithium at high temperatures had no adverse effects on the ductility of T-111 tubing. These materials were, however, sensitive to post-age handling and testing procedures.

Gold, R. E.↗

The Rb-Sr age of a crystalline rock from Apollo 16.

Sample 68415 is one of the few large crystalline rocks returned from Apollo 16. A meaningful age may be obtained if the sample studied represents silicate material which was isotopically homogenized at the last time it was melted. It is also assumed that the constituent phases of the sample have remained closed systems subsequent to that time. The material was crushed and separated into different fractions with the aid of heavy liquids. It was found that the mineral separates are mixtures of at least three distinct phases with intrinsically different Rb/Sr ratios. An age of 3.84 aeon was determined.

Papanastassiou, D. A.↗

The ages of lunar material from Fra Mauro, Hadley Rille, and Spur Crater.

Ar-40/Ar-39 dating techniques were applied to estimate the age of twelve crystalline and fragmented Fra Mauro rock samples and six Hadley Rille and Spur Crater rock samples provided by the Apollo 14 and 15 missions. Genesis histories of some associated lunar surface features are traced back on the basis of obtained rock age values.

Husain, L.↗

Exposure ages and neutron capture record in lunar samples from Fra Mauro.

Cosmic-ray exposure ages of Apollo 14 rocks and rock fragments obtained by the Kr81-Kr83 method range from 27 to 700 m.y. Rock 14321, collected near the Cone crater rim, is one of the many approximately 27 m.y. old ejecta which were reported at the Third Lunar Science Conference. All the other rocks have considerably higher exposure ages. Isotopic anomalies from neutron capture in gadolinium, bromine, and barium are used to obtain information on the lunar neutron spectrum at various depths below the lunar surface. The flux ratio of resonance and slow (less than 0.3 eV) neutrons is found to be nearly constant in the topmost approximately 100 g/sq cm.

Lugmair, G. W.↗

Crater frequency age determinations for the proposed Apollo 17 site at Taurus-Littrow.

On the assumption that the vast majority of craters are of impact origin, relative age dates can be obtained by counting craters. Returned lunar samples are helping to resolve problems regarding the magnitude of the meteoritic flux. The samples provide a means for empirically calibrating crater count data. The characteristics of the Taurus-Littrow area are considered, giving attention to four different units. The crater frequency distribution is discussed, together with its significance for the age of the corresponding lunar features.

Greeley, R.↗

Lunar volcanism - Age of the glass in the Apollo 17 orange soil.

Glasses on the moon can form either by impact or by volcanic processes. An age determination indicates that the glass of the orange soil formed close in time to the volcanic activity in the Sea of Serenity about 3,750 million years ago. The orange soil was certainly not formed by a recent fumarole. The young exposure age, about 32 million years, found for the glass of the orange soil is in agreement with its fresh appearance on the lunar surface.

Husain, L.↗

Spatial distribution of Ar-40/Ar-39 ages in lunar breccia 14301.

The distribution of stable and radioactive argon isotopes in a lunar breccia has been measured in situ by laser probe mass spectrometry. This new technique determines the spatial distribution of Ar-40/Ar-39 ages on less than .1 milligram of material. Calculated Ar-40/Ar-39 ages of clasts within this breccia are 3.7 and 2.9 b.y. Parentless radiogenic Ar-40 exists within the fine-grained matrix and appears to have been trapped simultaneously with solar argon. This 'atmosphere' of ambient gas appears to have been incorporated into the rock by an impact event not more than 3 b.y. ago.

Megrue, G. H.↗

Relative ages of some near-side Mare units based on Apollo 17 metric photographs

Relative flux ages were determined for 110 areas on parts of Serenitatis, Vaporum, and Imbrium, using Apollo 17 metric photographs. The crater-morphology technique for determining relative ages is described. It is concluded that these maria formed over an interval of 1.5 billion years, extending from 3.7 to 2.2 billion years ago.

Boyce, J. M.↗

Effect of outdoor exposure at ambient and elevated temperatures on fatigue life of Ti-6Al-4V titanium alloy sheet in the annealed and the solution treated and aged condition

Specimens of Ti-6Al-4V titanium alloy sheet in the annealed and the solution-treated and aged heat-treatment condition were exposed outdoors at ambient and 560 K (550 F) temperatures to determine the effect of outdoor exposure on fatigue life. Effects of exposure were determined by comparing fatigue lives of exposed specimens to those of unexpected specimens. Two procedures for fatigue testing the exposed specimens were evaluated: (1) fatigue tests conducted outdoors by applying 1200 load cycles per week until failure occurred and (2) conventional fatigue tests (continuous cycling until failure occurred) conducted indoors after outdoor exposure under static load. The exposure period ranged from 9 to 28 months for the outdoor fatigue-test group and was 24 months for the static-load group. All fatigue tests were constant-amplitude bending of specimens containing a drilled hole (stress concentration factor of 1.6). The results of the tests indicate that the fatigue lives of solution-treated and aged specimens were significantly reduced by the outdoor exposure at 560 K but not by the exposure at ambient temperature. Fatigue lives of the annealed specimens were essentially unaffected by the outdoor exposure at either temperature. The two test procedures - outdoor fatigue test and indoor fatigue test after outdoor exposure - led to the same conclusions about exposure effects.

Phillips, E. P.↗