Unequivocal demonstration of fructose-1,6-bisphosphatase in mammalian brain

Fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase; EC 3.1.3.11) has been found in rat brain and identified unequivocally. The enzyme has been purified to 95% homogeneity by standard procedures, including adsorption to a phosphocellulose column followed by elution with substrate. The purified enzyme exhibits a broad optimum above pH 7.6. Both fructose 1,6-bisphosphate and sedoheptulose 1,7-bisphosphate are substrates of this enzyme; the hydrolysis of the latter occurs at about 20% of the rate of the former, and the Km for fructose 1,6-bisphosphate is approximately 1.32 × 10(-4) M. 5'-AMP, an inhibitor of other mammalian-fructose-1,6-bisphosphatases, is without effect, and in further contrast with the other enzymes there is no metal requirement for activity. Purified brain enzyme fails to crossreact with the antibody prepared against the purified liver fructose-1,6-bisphosphatase. On the other hand, antiserum produced against the brain fructose-1,6-bisphosphatase quantitatively precipitates the enzyme activity and forms precipitin bands with preparations of brain fructose-1,6-bisphosphatase

Relativistic Effects in the Scalar Meson Dynamics

A separable potential formalism is used to describe the $\pi\pi$ and $K\overline{K}$ interactions in the scalar-isoscalar states in the energy range from the $\pi\pi$ threshold up to 1.4 GeV. Introduction of relativistic propagators into a system of Lippmann-Schwinger equations leads to a very good description of the data ($\chi^{2}=0.93$ per one degree of freedom). Three poles are found in this energy region: fo(500) ($M=506\pm 10$ MeV, $\Gamma=494\pm 5$ MeV), fo(975) ($M=973\pm 2$ MeV, $\Gamma=29\pm 2$ MeV) and fo(1400) ($M=1430\pm 5$ MeV, $\Gamma=145\pm 25$ MeV). The fo(975) state can be interpreted as a $K\overline{K}$ bound state. The fo(500) state may be associated with the often postulated very broad scalar resonance under the $K\overline{K}$ threshold (sometimes called $\sigma$ or $\epsilon$ meson). The scattering lengths in the $\pi\pi$ and $K\overline{K}$ channels have also been obtained. The relativistic approach provides qualitatively new results (e.g. the appearance of the fo(500)) in comparison with previously used nonrelativistic approach.Comment: 30 pages in LaTeX + 5 figures available on request. Preprint Orsay No IPNO/TH 93-3

Widespread forest vertebrate extinctions induced by a mega hydroelectric dam in lowland Amazonia

Mega hydropower projects in tropical forests pose a major emergent threat to terrestrial and freshwater biodiversity worldwide. Despite the unprecedented number of existing, underconstruction and planned hydroelectric dams in lowland tropical forests, long-term effects on biodiversity have yet to be evaluated. We examine how medium and large-bodied assemblages of terrestrial and arboreal vertebrates (including 35 mammal, bird and tortoise species) responded to the drastic 26-year post-isolation history of archipelagic alteration in landscape structure and habitat quality in a major hydroelectric reservoir of Central Amazonia. The Balbina Hydroelectric Dam inundated 3,129 km2 of primary forests, simultaneously isolating 3,546 land-bridge islands. We conducted intensive biodiversity surveys at 37 of those islands and three adjacent continuous forests using a combination of four survey techniques, and detected strong forest habitat area effects in explaining patterns of vertebrate extinction. Beyond clear area effects, edge-mediated surface fire disturbance was the most important additional driver of species loss, particularly in islands smaller than 10 ha. Based on species-area models, we predict that only 0.7% of all islands now harbor a species-rich vertebrate assemblage consisting of ≥80% of all species. We highlight the colossal erosion in vertebrate diversity driven by a man-made dam and show that the biodiversity impacts of mega dams in lowland tropical forest regions have been severely overlooked. The geopolitical strategy to deploy many more large hydropower infrastructure projects in regions like lowland Amazonia should be urgently reassessed, and we strongly advise that long-term biodiversity impacts should be explicitly included in pre-approval environmental impact assessments

The Warburg Effect Suppresses Oxidative Stress Induced Apoptosis in a Yeast Model for Cancer

BACKGROUND: Otto Warburg observed that cancer cells are often characterized by intense glycolysis in the presence of oxygen and a concomitant decrease in mitochondrial respiration. Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended. Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, colonies of Saccharomyces cerevisiae, which is suitable for manipulation of mitochondrial respiration and shows mitochondria-mediated cell death, were used as a model. Repression of respiration as well as ROS-scavenging via glutathione inhibited apoptosis and conferred a survival advantage during seeding and early development of this fast proliferating solid cell population. In contrast, enhancement of respiration triggered cell death. CONCLUSION/SIGNIFICANCE: Thus, the Warburg effect might directly contribute to the initiation of cancer formation--not only by enhanced glycolysis--but also via decreased respiration in the presence of oxygen, which suppresses apoptosis

Efficiency of complex production in changing environment

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Health care utilization among complementary and alternative medicine users in a large military cohort

<p>Abstract</p> <p>Background</p> <p>Complementary and Alternative Medicine use and how it impacts health care utilization in the United States Military is not well documented. Using data from the Millennium Cohort Study we describe the characteristics of CAM users in a large military population and document their health care needs over a 12-month period. The aim of this study was to determine if CAM users are requiring more physician-based medical services than users of conventional medicine.</p> <p>Methods</p> <p>Inpatient and outpatient medical services were documented over a 12-month period for 44,287 participants from the Millennium Cohort Study. Equal access to medical services was available to anyone needing medical care during this study period. The number and types of medical visits were compared between CAM and non-CAM users. Chi square test and multivariable logistic regression was applied for the analysis.</p> <p>Results</p> <p>Of the 44,287 participants, 39% reported using at least one CAM therapy, and 61% reported not using any CAM therapies. Those individuals reporting CAM use accounted for 45.1% of outpatient care and 44.8% of inpatient care. Individuals reporting one or more health conditions were 15% more likely to report CAM use than non-CAM users and 19% more likely to report CAM use if reporting one or more health symptoms compared to non-CAM users. The unadjusted odds ratio for hospitalizations in CAM users compared to non-CAM users was 1.29 (95% CI: 1.16-1.43). The mean number of days receiving outpatient care for CAM users was 7.0 days and 5.9 days for non-CAM users (<it>p </it>< 0.001).</p> <p>Conclusions</p> <p>Our study found those who report CAM use were requiring more physician-based medical services than users of conventional medicine. This appears to be primarily the result of an increase in the number of health conditions and symptoms reported by CAM users.</p

Optimal Resource Allocation over Networks via Lottery-Based Mechanisms

We show that, in a resource allocation problem, the ex ante aggregate utility of players with cumulative-prospect-theoretic preferences can be increased over deterministic allocations by implementing lotteries. We formulate an optimization problem, called the system problem, to find the optimal lottery allocation. The system problem exhibits a two-layer structure comprised of a permutation profile and optimal allocations given the permutation profile. For any fixed permutation profile, we provide a market-based mechanism to find the optimal allocations and prove the existence of equilibrium prices. We show that the system problem has a duality gap, in general, and that the primal problem is NP-hard. We then consider a relaxation of the system problem and derive some qualitative features of the optimal lottery structure

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach