Concepts of nerve fiber development, 1839–1930

Conclusion It was thus the combination of observational and experimental approaches that ultimately led to confirmation of the outgrowth theory. The observational method was essential for defining various possible methods of nerve fiber development. The multicellular, protoplasmic bridge and outgrowth theories were each postulated to explain purely observational evidence. However, the lack of truly suitable equipment and techniques to study the developing nervous system made it impossible to agree on a single theory on this basis alone. The experimental method provided a means of choosing between these theories. Without the preceding observations that had led to the formulation of various hypotheses, however, the experimental approach might not have been so successful, for the power of this method is more of selection than of generation.Therefore it is impossible to weigh separately the contributions of the observational and experimental approaches to the question of nerve fiber development. Both were necessary for the ultimate acceptance of the outgrowth theory. *** DIRECT SUPPORT *** A8402051 00004     

THE ANNUAL CARBOHYDRATE CYCLE OF ALPINE PLANTS AS RELATED TO GROWTH

Mooney, H. A., and W. D. Billings. (Duke U., Durham, N. C.) The annual carbohydrate cycle of alpine plants as related to growth. Amer. Jour. Bot. 47(7): 594–598. Illus. 1960.—Analyses were made of the carbohydrate content of roots, rhizomes, and shoots of certain plants in the alpine tundra region of the Medicine Bow Mountains, Wyoming, from the beginning of one growing season until the start of the following one. Principal species investigated were Saxifraga rhomboidea, Polygonum bistortoides, and Geum turbinatum. Results were correlated with phenological events as observed in the field. Growth of these plants was found to be very rapid, commencing in some instances under a cover of old snow. The underground organs contained relatively large amounts of carbohydrate reserves. A great part of this stored carbohydrate was utilized in growth prior to snowmelt and during the grand period of shoot growth immediately following snowmelt. In Polygonum, 50% of the rhizome reserves was used in a 1-wk. period in early growth. Except for this short period of rapid depletion in rhizomes and roots during early growth, high carbohydrate levels were maintained both in the shoot and in the underground organs during most of the growing season. Generally, the lowest carbohydrate reserve level in both root and shoot occurred before flowering, a relatively high level was maintained in the shoot from flowering until after fruiting, while peak storage in underground parts was reached at the start of fall dormancy. The carbohydrate cycle in these alpine plants is quite similar to that in certain arctic plants.     

Seasonal variations in plant nitrogen relations and photosynthesis along a grassland to shrubland gradient in Owens Valley, California

Community composition in semi-arid ecosystems has largely been explained by water availability; however, nitrogen is a common limiting nutrient, and may be an important control on plant function and carbon uptake. We investigated nitrogen relations and photosynthesis of several dominant species at shallow groundwater sites in Owens Valley, California. We measured soil nitrogen (N) availability, leaf N and isotopes, water isotopes, and gas exchange of dominant shrub species Atriplex torreyi and Ericameria nauseosa and grass species Distichlis spicata throughout the summer season in three sites that had similar watertable depths, but that varied in community composition and N availability. Surface soil inorganic N was greatest at the grassland site and declined from June to September at all sites. Leaf N declined throughout the season in all species, and was correlated with soil inorganic N. Photosynthesis of A. torreyi remained relatively constant throughout the season. In contrast, D. spicata and E. nauseosa experienced seasonal declines in photosynthesis at sites with greater inorganic N availability. Leaf N was significantly correlated with photosynthesis in D. spicata across all sites and measurement periods. Controls on N cycling are likely to be an important determinant of photosynthesis of D. spicata in this region.     

ABCA1 overexpression in the liver of LDLr-KO mice leads to accumulation of pro-atherogenic lipoproteins and enhanced atherosclerosis

The identification of ABCA1 as a key transporter responsible for cellular lipid efflux has led to considerable interest in defining its role in cholesterol metabolism and atherosclerosis. In this study, the effect of overexpressing ABCA1 in the liver of LDLr-KO mice was investigated. Compared with LDLr-KO mice, ABCA1-Tg x LDLr-KO (ABCA1-Tg) mice had significantly increased plasma cholesterol levels, mostly because of a 2.8-fold increase in cholesterol associated with a large pool of apoB-lipoproteins. ApoB synthesis was unchanged but the catabolism of (125)I-apoB-VLDL and -LDL were significantly delayed, accounting for the 1.35-fold increase in plasma apoB levels in ABCA1-Tg mice. We also found rapid in vivo transfer of free cholesterol from HDL to apoB-lipoproteins in ABCA1-Tg mice, associated with a significant 2.7-fold increase in the LCAT-derived cholesteryl linoleate content found primarily in apoB-lipoproteins. ABCA1-Tg mice had 1.4-fold increased hepatic cholesterol concentrations, leading to a compensatory 71% decrease in de novo hepatic cholesterol synthesis, as well as enhanced biliary cholesterol, and bile acid secretion. CAV-1, CYP2b10, and ABCG1 were significantly induced in ABCA1-overexpressing livers; however, no differences were observed in the hepatic expression of CYP7alpha1, CYP27alpha1, or ABCG5/G8 between ABCA1-Tg and control mice. As expected from the pro-atherogenic plasma lipid profile, aortic atherosclerosis was increased 10-fold in ABCA1-Tg mice. In summary, hepatic overexpression of ABCA1 in LDLr-KO mice leads to: 1) expansion of the pro-atherogenic apoB-lipoprotein cholesterol pool size via enhanced transfer of HDL-cholesterol to apoB-lipoproteins and delayed catabolism of cholesterol-enriched apoB-lipoproteins; 2) increased cholesterol concentration in the liver, resulting in up-regulated hepatobiliary sterol secretion; and 3) significantly enhanced aortic atherosclerotic lesions.     

Acm1 is a negative regulator of the CDH1-dependent anaphase-promoting complex/cyclosome in budding yeast

Cdh1 is a coactivator of the anaphase-promoting complex/cyclosome (APC/C) and contributes to mitotic exit and G1 maintenance by facilitating the polyubiquitination and subsequent proteolysis of specific substrates. Here, we report that budding yeast Cdh1 is a component of a cell cycle-regulated complex that includes the 14-3-3 homologs Bmh1 and Bmh2 and a previously uncharacterized protein, which we name Acm1 (APC/CCdh1 modulator 1). Association of Cdh1 with Bmh1 and Bmh2 requires Acm1, and the Acm1 protein is cell cycle regulated, appearing late in G1 and disappearing in late M. In acm1Delta strains, Cdh1 localization to the bud neck and association with two substrates, Clb2 and Hsl1, were strongly enhanced. Several lines of evidence suggest that Acm1 can suppress APC/CCdh1-mediated proteolysis of mitotic cyclins. First, overexpression of Acm1 fully restored viability to cells expressing toxic levels of Cdh1 or a constitutively active Cdh1 mutant lacking inhibitory phosphorylation sites. Second, overexpression of Acm1 was toxic in sic1Delta cells. Third, ACM1 deletion exacerbated a low-penetrance elongated-bud phenotype caused by modest overexpression of Cdh1. This bud elongation was independent of the morphogenesis checkpoint, and the combination of acm1Delta and hsl1Delta resulted in a dramatic enhancement of bud elongation and G2/M delay. Effects on bud elongation were attenuated when Cdh1 was replaced with a mutant lacking the C-terminal IR dipeptide, suggesting that APC/C-dependent proteolysis is required for this phenotype. We propose that Acm1 and Bmh1/Bmh2 constitute a specialized inhibitor of APC/CCdh1.     

The Extracellular Matrix Component Psl Provides Fast-Acting Antibiotic Defense in Pseudomonas aeruginosa Biofilms

Bacteria within biofilms secrete and surround themselves with an extracellular matrix, which serves as a first line of defense against antibiotic attack. Polysaccharides constitute major elements of the biofilm matrix and are implied in surface adhesion and biofilm organization, but their contributions to the resistance properties of biofilms remain largely elusive. Using a combination of static and continuous-flow biofilm experiments we show that Psl, one major polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic first line of defense toward antibiotics with diverse biochemical properties during the initial stages of biofilm development. Furthermore, we show with mixed-strain experiments that antibiotic-sensitive “non-producing” cells lacking Psl can gain tolerance by integrating into Psl-containing biofilms. However, non-producers dilute the protective capacity of the matrix and hence, excessive incorporation can result in the collapse of resistance of the entire community. Our data also reveal that Psl mediated protection is extendible to E. coli and S. aureus in co-culture biofilms. Together, our study shows that Psl represents a critical first bottleneck to the antibiotic attack of a biofilm community early in biofilm development.     

How interactions between microbial resource demands,soil organic matter stoichiometry,and substrate reactivity determine the direction and magnitude of soil respiratory responses to warming

Recent empirical and theoretical advances inform us about multiple drivers of soil organic matter (SOM) decomposition and microbial responses to warming. Absent from our conceptual framework of how soil respiration will respond to warming are adequate links between microbial resource demands, kinetic theory, and substrate stoichiometry. Here, we describe two important concepts either insufficiently explored in current investigations of SOM responses to temperature, or not yet addressed. First, we describe the complete range of responses for how warming may change microbial resource demands, physiology, community structure, and total biomass. Second, we describe how any relationship between SOM activation energy of decay and carbon (C) and nitrogen (N) stoichiometry can alter the relative availability of C and N as temperature changes. Changing availabilities of C and N liberated from their organic precursors can feedback to microbial resource demands, which in turn influence the aggregated respiratory response to temperature we observe. An unsuspecting biogeochemist focused primarily on temperature sensitivity of substrate decay thus cannot make accurate projections of heterotrophic CO₂ losses from diverse organic matter reservoirs in a warming world. We establish the linkages between enzyme kinetics, SOM characteristics, and potential for microbial adaptation critical for making such projections. By examining how changing microbial needs interact with inherent SOM structure and composition, and thus reactivity, we demonstrate the means by which increasing temperature could result in increasing, unchanging, or even decreasing respiration rates observed in soils. We use this exercise to highlight ideas for future research that will develop our abilities to predict SOM feedbacks to climate.     

Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response

Acute kidney injury (AKI) frequently afflicts patients undergoing cardiopulmonary bypass and independently predicts death. Both hemoglobinemia and myoglobinemia are independent predictors of postoperative AKI. Release of free hemeproteins into the circulation is known to cause oxidative injury to the kidneys. This study tested the hypothesis that postoperative AKI is associated with both enhanced intraoperative hemeprotein release and increased lipid peroxidation assessed by measuring F₂-isoprostanes and isofurans. In a case–control study nested within an ongoing randomized trial of perioperative statin treatment and AKI, we compared levels of F₂-isoprostanes and isofurans with plasma levels of free hemoglobin and myoglobin in 10 cardiac surgery AKI patients to those of 10 risk-matched controls. Peak plasma free hemoglobin concentrations were significantly higher in AKI subjects (289.0 ± 37.8 versus 104.4 ± 36.5 mg/dl, P = 0.01), whereas plasma myoglobin concentrations were similar between groups. The change in plasma F₂-isoprostane and isofuran levels (repeated-measures ANOVA, P = 0.02 and P = 0.001, respectively) as well as the change in urine isofuran levels (P = 0.04) was significantly greater in AKI subjects. In addition, change in peak plasma isofuran levels correlated not only with peak free plasma hemoglobin concentrations (r² = 0.39, P = 0.001) but also with peak change in serum creatinine (r² = 0.20, P = 0.01). Postoperative AKI is associated with both enhanced intraoperative hemeprotein release and enhanced lipid peroxidation. The correlations among hemoglobinemia, lipid peroxidation, and AKI indicate a potential role for hemeprotein-induced oxidative damage in the pathogenesis of postoperative AKI.     

Synthesis and evaluation of antimigratory and antiproliferative activities of lipid-linked [13]-macro-dilactones

The biological activities of a family of novel, lipid-linked 13-membered-ring macro-dilactones are reported. These [13]-macro-dilactones were synthesized by diacylation of functionalized diols, followed by ring-closing metathesis under conditions we had previously reported. Antimigratory, cytostatic and cytotoxic activities of the compounds against cancer cells were evaluated. Compound 13 was the most potent in the series, while compound 10 had the broadest concentration range of subtoxic antiproliferative activity. These compounds share common structural components, namely the [13]-macro-dilactone templated by an octyl α-glucoside 4,6-diol.