Purine and pyrimidine antagonism in a pyrimidine-deficient mutant of Neurospora

The present study is concerned with the inhibition of growth of the pyrimidine-deficient Neurospora mutant, No. 1298, by the naturally occurring purine ribonucleotides and ribonucleosides. This experimentally produced strain, unlike the wild type, is unable to synthesize the pyrimidine ribonucleosides on a medium containing inorganic salts, carbohydrate, and biotin. Normal growth takes place, however, when the medium is supplemented with either cytidine or uridine or the corresponding nucleotides. It has been found that adenosine and adenosine-3-phosphate (yeast adenylic acid) inhibit the utilization of the pyrimidine compounds to a varying degree. An amount of adenine nucleoside which is sufficient to inhibit growth completely on the quantity of cytidine used has no inhibitory effect on an equivalent amount of uridine. The addition of an equimolar amount of uridine to a mixture of cytidine and adenosine in which no growth takes place results in the elimination of the antagonism. In contrast to the effect of adenosine and adenylic acid on this mutant strain of Neurospora, adenine shows no inhibitory properties at comparable concentrations. A similar inhibitory effect on the utilization of the pyrimidine nucleosides was found for guanosine and guanylic acid, but larger amounts of these compounds were required to produce inhibition under the same conditions. Guanine like adenine failed to cause inhibition at moderate concentrations

Exploring the Nexus of Energy Burden, Social Capital, and Environmental Quality in Shaping Health in US Counties

The United States spends more on health care than any other OECD country, yet the nation’s health is declining. Recent research has identified multiple sources for this decline, including one’s position in social and economic structures, environmental quality, and individual and collective social capital. This paper assesses the primary hypotheses that the health effects of household energy burden, social capital and environmental quality on aggregated community health levels remain while controlling for other determinants. The analysis moves beyond prior research by integrating multiple secondary data sources to assess those effects across US counties. Three indicators of public health are analyzed (premature mortality, self-reported health, and life expectancy). The county-level energy burden is measured by the percent of household income spent on housing energy bills for low- and moderate-income households. In addition to energy burden, social capital, environmental quality and other determinants are included in the analysis. The results produced by multivariate regression models support the primary hypotheses, even while a number of control variables also have a significant effect on health. The paper concludes that public health is associated with a complex nexus of factors, including environmental quality and social capital, and that energy burden needs to be among the considerations

The Yellowstone Hotspot, Greater Yellowstone Ecosystem, and Human Geography

Active geologic processes associated with the Yellowstone hotspot are fundamental in shaping the landscapes of the greater Yellowstone ecosystem (GYE), a high volcanic plateau flanked by a crescent of still higher mountainous terrain. The processes associated with the Yellowstone hotspot are volcanism, faulting, and uplift and are observed in the geology at the surface. We attribute the driving forces responsible for the northeastward progression of these processes to a thermal plume rising through the Earth’s mantle into the base of the southwest-moving North American plate. This progression began 16 million years ago (Ma) near the Nevada-Oregon border and arrived at Yellowstone about 2 Ma. Before arrival of the hotspot, an older landscape existed, particularly mountains created during the Laramide orogeny about 70–50 Ma and volcanic terrain formed by Absaroka andesitic volcanism mostly between 50–45 Ma. These landscapes were more muted than the present, hotspot-modified landscape because the Laramide-age mountains had worn down and an erosion surface of low relief had developed on the Absaroka volcanic terrain. The Yellowstone Plateau was built by hotspot volcanism of rhyolitic lavas and caldera-forming rhyolite tuffs (ignimbrites). Streams eroding back into the edges of this plateau have created scenic waterfalls and canyons such as the Grand Canyon of the Yellowstone and Lewis Canyon. Rhyolite is poor in plant nutrients and forms sandy, well-drained soils that support the monotonous, fire-adapted lodgepole pine forests of the Yellowstone Plateau. Non-rhyolitic rocks surround this plateau and sustain more varied vegetation, including spruce, fir, and whitebark pine forests broken by grassy meadows. Heat from the hotspot rises upward and drives Yellowstone’s famed geysers, hot springs, and mudpots. These thermal waters are home to specialized, primitive ecosystems, rich in algae and bacteria. The rock alteration associated with hydrothermal systems creates the bright colors of Yellowstone’s Grand Canyon. Basin-and-range-style faulting has accompanied migration of the hotspot to Yellowstone and formed the linear mountains and valleys that occur north and south of the hotspot track, which is the present-day eastern Snake River Plain. High rates of basin-and-range faulting occurred adjacent to the migrating Yellowstone hotspot, creating distinctive landscapes within the GYE such as the Teton Range/Jackson Hole, with characteristic rugged, forested ranges and adjacent flat-floored grassy valleys. The difference in altitude between the mountains and valleys provides a topographic gradient in which vegetation maturation advances with altitude; animal-migration patterns also follow this trend. The valleys provide natural meadows, agricultural land, town sites, and corridors for roads. Uplift of the GYE by as much as 1 km (3,000 ft) during the last 5 million years has resulted in ongoing erosion of deep, steep-walled valleys. Many prominent ecological characteristics of Yellowstone derive from this hotspot-induced uplift, including the moderate- to high- altitude terrain and associated cool temperatures and deep snowfall. Modern and Pleistocene climate and associated vegetation patterns strongly relate to the topography created by the hotspot and its track along the eastern Snake River Plain. Winter air masses from the moist northern Pacific Ocean traverse the topographic low of the Snake River Plain to where orographic rise onto the Yellowstone Plateau and adjacent mountains produces deep snow. A winter precipitation shadow forms on the lee (eastern) sides of the GYE. During Pleistocene glacial times, this moisture conduit provided by the hotspot-track-produced ice-age glaciers that covered the core of the present GYE. These glaciers sculpted bedrock and produced glacial moraines that are both forested and unforested, sand and gravel of ice-marginal streams and outwash gravels that are commonly covered with sagebrush-grassland, and silty lake sediments that are commonly covered by lush grassland such as Hayden Valley. The effects of the Yellowstone hotspot also profoundly shaped the human history in the GYE. Uplift associated with the hotspot elevates the GYE to form the Continental Divide, and streams drain radially outward like spokes from a hub. Inhabitants of the GYE 12,000–10,000 years ago, as well as more recent inhabitants, followed the seasonal green-up of plants and migrating animals up into the mountain areas. During European immigration, people settled around Yellowstone in the lower parts of the drainages and established roads, irrigation systems, and cultural associations. The core Yellowstone highland is too harsh for agriculture and inhospitable to people in the winter. Beyond this core, urban and rural communities exist in valleys and are separated by upland areas. The partitioning inhibits any physical connection of communities, which in turn complicates pursuit of common interests across the whole GYE. Settlements thus geographically isolated evolved as diverse, independent communities

Penetrating ulcer of the thoracic aorta: What is it? How do we recognize it? How do we manage it?

AbstractBackground: Although classic type A and B aortic dissections have been well described, less is known about the natural history of penetrating atherosclerotic ulcers of the thoracic aorta. This study differentiates penetrating ulcer from aortic dissection, determines the clinical features and natural history of these ulcers, and establishes appropriate correlates regarding optimal treatment. Methods: A retrospective review of patient records and imaging studies was conducted with 198 patients with initial diagnoses of aortic dissection (86 type A, 112 type B) at our institution from 1985 to 1997. Results: Of the 198 patients, 15 (7.6%) were found to have a penetrating aortic ulcer on re-review of computed tomographic scans, magnetic resonance images, angiograms, echocardiograms, intraoperative findings, or pathology reports. Two ulcers (13.3%) were located in the ascending aorta; the other 13 (86.7%) were in the descending aorta. In comparison with those with type A or B aortic dissection, patients with penetrating ulcer were older (mean age 76.6 years, p = 0.018); had larger aortic diameters (mean diameter 6.5 cm); had ulcers primarily in the descending aorta (13 of 15 patients, 86.7%); and more often had ulcers associated with a prior diagnosed or managed AAA (6 of 15 patients, 40.0%; p = 0.0001). Risk for aortic rupture was higher among patients with penetrating ulcers (40.0%) than patients with type A (7.0%) or type B (3.6%) aortic dissection (p = 0.0001). Conclusions: Accurate recognition and differentiation of penetrating ulcers from classic aortic dissection at initial presentation is critical for optimal treatment of these patients. For penetrating ulcer, the prognosis may be more serious than with classic type A or B aortic dissection. Surgical management is advocated for penetrating ulcers in the ascending aorta and for penetrating ulcers in the descending aorta that exhibit early clinical or radiologic signs of deterioration. (J Vasc Surg 1998;27:1006-16.

Purine and pyrimidine antagonism in a pyrimidine-deficient mutant of Neurospora

The present study is concerned with the inhibition of growth of the pyrimidine-deficient Neurospora mutant, No. 1298, by the naturally occurring purine ribonucleotides and ribonucleosides. This experimentally produced strain, unlike the wild type, is unable to synthesize the pyrimidine ribonucleosides on a medium containing inorganic salts, carbohydrate, and biotin. Normal growth takes place, however, when the medium is supplemented with either cytidine or uridine or the corresponding nucleotides. It has been found that adenosine and adenosine-3-phosphate (yeast adenylic acid) inhibit the utilization of the pyrimidine compounds to a varying degree. An amount of adenine nucleoside which is sufficient to inhibit growth completely on the quantity of cytidine used has no inhibitory effect on an equivalent amount of uridine. The addition of an equimolar amount of uridine to a mixture of cytidine and adenosine in which no growth takes place results in the elimination of the antagonism. In contrast to the effect of adenosine and adenylic acid on this mutant strain of Neurospora, adenine shows no inhibitory properties at comparable concentrations. A similar inhibitory effect on the utilization of the pyrimidine nucleosides was found for guanosine and guanylic acid, but larger amounts of these compounds were required to produce inhibition under the same conditions. Guanine like adenine failed to cause inhibition at moderate concentrations

Novel patient-centered approach to facilitate same-day discharge in patients undergoing elective percutaneous coronary intervention

Background Same‐day discharge ( SDD ) after elective percutaneous coronary intervention is safe, less costly, and preferred by patients, but it is usually performed in low‐risk patients, if at all. To increase the appropriate use of SDD in more complex patients, we implemented a “patient‐centered” protocol based on risk of complications at Barnes‐Jewish Hospital. Methods and Results Our objectives were as follows: (1) to evaluate time trends in SDD ; (2) to compare (a) mortality, bleeding, and acute kidney injury, (b) patient satisfaction, and (c) hospital costs by SDD versus no SDD ( NSDD ); and (3) to compare SDD eligibility by our patient‐centered approach versus Society for Cardiovascular Angiography and Interventions guidelines. Our patient‐centered approach was based on prospectively identifying personalized bleeding, mortality, and acute kidney injury risks, with a personalized safe contrast limit and mitigating those risks. We analyzed Barnes‐Jewish Hospital's National Cardiovascular Data Registry Cath PCI Registry data from July 1, 2009 to September 30, 2015 (N=1752). SDD increased rapidly from 0% to 77% ( P &lt;0.001), independent of radial access. Although SDD patients were comparable to NSDD patients, SDD was not associated with adverse outcomes (0% mortality, 0% bleeds, and 0.4% acute kidney injury). Patient satisfaction was high with SDD . Propensity score–adjusted costs were 7331 lower/ SDD patient ( P <0.001), saving an estimated 1.8 million annually. Only 16 patients (6.95%) met the eligibility for SDD by Society for Cardiovascular Angiography and Interventions guidelines, implying our patient‐centered approach markedly increased SDD eligibility. Conclusions With a patient‐centered approach, SDD rapidly increased and was safe in 75% of patients undergoing elective percutaneous coronary intervention, despite patient complexity. Patient satisfaction was high, and hospital costs were lower. Patient‐centered decision making to facilitate SDD is an important opportunity to improve the value of percutaneous coronary intervention. </jats:sec

The Missing Heritability in T1D and Potential New Targets for Prevention

Type 1 diabetes (T1D) is a T cell-mediated disease. It is strongly associated with susceptibility haplotypes within the major histocompatibility complex, but this association accounts for an estimated 50% of susceptibility. Other studies have identified as many as 50 additional susceptibility loci, but the effect of most is very modest (odds ratio (OR) 5) and that deletion of V beta 13+ T cells prevents diabetes. A role for the TCR is also suspected in NOD mice, but TCR regions have not been associated with human T1D. To investigate this disparity, we tested the hypothesis in silico that previous studies of human T1D genetics were underpowered to detect MHC-contingent TCR susceptibility. We show that stratifying by MHC markedly increases statistical power to detect potential TCR susceptibility alleles. We suggest that the TCR regions are viable candidates for T1D susceptibility genes, could account for missing heritability, and could be targets for prevention

Winter Movements of Louisiana Pine Snakes (Pituophis ruthveni) in Texas and Louisiana

Despite concerns that the Louisiana Pine Snake (Pituophis ruthveni) has been extirpated from large portions of its historic range, only a limited number of studies on their movement patterns have been published. Winter movement patterns are of particular interest since it has been hypothesized that impacts of management practices would be reduced during the winter. Using radiotelemetry, we determined winter movement patterns of Louisiana Pine Snakes (11 males, 8 females) in 5 study areas (2 in Louisiana and 3 in Texas). Movements during winter (November–February) were greatly curtailed compared to the remainder of the year; however, snakes occasionally undertook substantial movements. Relocations were typically within the snake’s previous active-season home range, and movements were more frequent in the early portion of winter. All hibernation sites were within Baird’s Pocket Gopher (Geomys breviceps) burrow systems at depths ranging from 13–25 cm. Louisiana Pine Snakes did not use communal hibernacula, nor did individual snakes return to previously used sites in successive years