Profound insulin-induced hypoglycemia is associated with early-onset neuronal damage that resembles excitotoxic lesions and is attenuated in severity by antagonists of N-methyl-D-aspartate receptors. Hypoglycemia increases L-tryptophan concentrations in brain and could increase the concentration of the L-tryptophan metabolite quinolinic acid (QUIN), an agonist of N-methyl-D-aspartate receptors and an excitotoxin in brain. Therefore, we investigated the effects of 40 min of profound hypoglycemia (isoelectric EEG) and 1-2 h of normoglycemic recovery on the concentrations of QUIN in brain tissue, brain extracellular fluid, and plasma in male Wistar rats. Plasma QUIN increased 6.5-fold by the time of isoelectricity (2 h after insulin administration). Regional brain QUIN concentrations increased two- to threefold during hypoglycemia and increased a further two- to threefold during recovery. However, no change in extracellular fluid QUIN concentrations in hippocampus occurred during hypoglycemia or recovery as measured using in vivo microdialysis. Therefore, the increases in brain tissue QUIN concentrations may reflect elevations of QUIN in the intracellular space or be secondary to the increases in QUIN in the vascular compartment in brain per se. L-Tryptophan concentrations increased more than twofold during recovery only. Serotonin decreased greater than 50% throughout the brain during hypoglycemia, while 5-hydroxyindoleacetic acid concentrations increased more than twofold during hypoglycemia and recovery. In striatum, dopamine was decreased 75% during hypoglycemia but returned to control values during recovery, while striatal 3,4-dihydroxyphenylacetic acid and homovanillic acid were increased more than twofold during both hypoglycemia and recovery.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
Hepatic enzymes connected with the formation and metabolism of free D-glucuronic acid were affected in rats after treatment with disulfiram or diethyldithiocarbamate (300 mg/kg, intragastrically, per day, 4 X). The activities of UDPglucose dehydrogenase, UDPglucuronic acid pyrophosphatase, UDPglucuronosyltransferase and L-gulonate dehydrogenase were enhanced, while those of glucose-6-phosphate dehydrogenase, beta-glucuronidase and D-glucuronolactone dehydrogenase were inhibited. These changes were more pronounced with disulfiram than diethyldithiocarbamate. Treatment with phenobarbital (80 mg/kg, i.p., per day, 4 X) enhanced UDP glucuronosyl-transferase, but brought about different effects on the other enzymes. Concurrent administration of phenobarbital with disulfiram or diethyldithiocarbamate led to potentiation or antagonism of the primary effects of each compound when given alone. The results suggest that activation of the D-glucuronic acid pathway may proceed in various ways, and that it is not necessarily followed by a simultaneous induction of the microsomal mixed-function oxygenase activity. 相似文献
The crystallization of macromolecules remains a major bottleneck in structural biology. The routine screening of more than one thousand crystallization conditions and subsequent optimization by fine screening presents a challenge to conventional laboratory notebook keeping. In addition, the development of high-throughput robotic crystallization and imaging systems presents a pressing need for low-cost laboratory information management system (LIMS). Here we describe CLIMS2, a crystallization LIMS that features a simple, user-friendly graphical interface, allowing the storage, management, retrieval and mining of crystallization data. The CLIMS2 executable and documentation is freely available at http://clims.med.monash.edu.au. 相似文献
The temperature‐dependent aggregation behavior of PffBT4T polymers used in organic solar cells plays a critical role in the formation of a favorable morphology in fullerene‐based devices. However, there is little investigation into the impact of donor/acceptor ratio on morphology tuning, especially for nonfullerene acceptors (NFAs). Herein, the influence of composition on morphology is reported for blends of PffBT4T‐2DT with two NFAs, O‐IDTBR and O‐IDFBR. The monotectic phase behavior inferred from differential scanning calorimetry provides qualitative insight into the interplay between solid–liquid and liquid–liquid demixing. Transient absorption spectroscopy suggests that geminate recombination dominates charge decay and that the decay rate is insensitive to composition, corroborated by negligible changes in open‐circuit voltage. Exciton lifetimes are also insensitive to composition, which is attributed to the signal being dominated by acceptor excitons which are formed and decay in domains of similar size and purity irrespective of composition. A hierarchical morphology is observed, where the composition dependence of size scales and scattering intensity from resonant soft X‐ray scattering (R‐SoXS) is dominated by variations in volume fractions of polymer/polymer‐rich domains. Results suggest an optimal morphology where polymer crystallite size and connectivity are balanced, ensuring a high probability of hole extraction via such domains. 相似文献
Although amending biochar into agricultural soils has been regarded as an effective measure to improve crop productivity, it remains unclear why biochar increases crop yield. The objective of this study was to compare the relative contribution of different biochar components in crop growth promotion. Three biochar components were separated: (i) water-soluble biochar extract (BE), (ii) mineral nutrients from biochar ash (BA), and (iii) washed biochar residue (WB). Two soils (Anthrosol and Primosol) with distinctly different organic carbon content, soil texture and land use were amended with the three biochar components and their effects on maize (Zea mays L.) growth were tested in a pot experiment. We hypothesized that (1) plant grown in the Anthrosol benefitted more from the water-soluble compounds of biochar than from its mineral nutrients or washed residue, since the soil is already fertile and has a good structure; (2) plant grown in the Primosol benefitted more from the mineral nutrients of biochar and its washed residual, since the soil is nutrient-poor and has a poor structure. The addition of biochar and its three components increased maize aboveground biomass for both soils. In the Anthrosol, BE, BA, and WB increased the aboveground biomass by 41.6%, 32.7%, and 27.1%; in the Primosol, they increased the aboveground biomass by 41.3%, 24.4%, and 18.2%, respectively. BE had the highest plant growth-promoting effect compared to the other two biochar components, which was regardless of soil condition. In addition, the biomass, total volume, surface area, and number of maize root tips under BE amendment were significantly enhanced, particularly the fine roots (< 0.2 mm in diameter). And a strong positive correlation was observed between maize aboveground biomass and the total length of the fine roots. The results demonstrated that the water-soluble compounds present in biochar, in addition to the mineral nutrients and the washed biochar residue, dominate the plant growth promotion under both soil conditions.
The root of Arabidopsis thaliana is used as a model system to unravel the molecular nature of cell elongation and its arrest. From a micro-array performed on roots that were treated with aminocyclopropane-1-carboxylic acid (ACC), the precursor of ethylene, a Small auxin-up RNA (SAUR)-like gene was found to be up regulated. As it appeared as the 76th gene in the family, it was named SAUR76. Root and leaf growth of overexpression lines ectopically expressing SAUR76 indicated the possible involvement of the gene in the division process. Using promoter::GUS and GFP lines strong expression was seen in endodermal and pericycle cells at the end of the elongation zone and during several stages of lateral root primordia development. ACC and IAA/NAA were able to induce a strong up regulation of the gene and changed the expression towards cortical and even epidermal cells at the beginning of the elongation zone. Confirmation of this up regulation of expression was delivered using qPCR, which also indicated that the expression quickly returned to normal levels when the inducing IAA-stimulus was removed, a behaviour also seen in other SAUR genes. Furthermore, confocal analysis of protein-GFP fusions localized the protein in the nucleus, cytoplasm and plasma membrane. SAUR76 expression was quantified in several mutants in ethylene and auxin-related pathways, which led to the conclusion that the expression of SAUR76 is mainly regulated by the increase in auxin that results from the addition of ACC, rather than by ACC itself. 相似文献
During 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak.
Methods
Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008–2012).
Results
IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998–2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p<0.001). The slope of anti-HCV prevalence in the sentinel populations of IDUs and in “new” drug injectors was found 120 and 1.9-fold (p = 0.007, p = 0.08 respectively) higher in 2008–2012 (economic recession) compared with 2002–2006. The median (25th, 75th) size of transmission networks were 34 (12, 58) and 2 (2, 2) (p = 0.057) in 2008–2012 and 1998–2007, respectively. The coverage of harm reduction services was low throughout the study period.
Conclusions
Scaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur. 相似文献
The morbidity, mortality and economic burden associated with fungal infections, together with the emergence of fungal strains resistant to current antimicrobial agents, necessitate broadening our understanding of fungal pathogenesis and discovering new agents to treat these infections. Using invertebrate hosts, especially the nematode Caenorhabditis elegans and the model insects Drosophila melanogaster and Galleria mellonella, could help achieve these goals. The evolutionary conservation of several aspects of the innate immune response between invertebrates and mammals makes the use of these simple hosts an effective and fast screening method for identifying fungal virulence factors and testing potential antifungal compounds. The purpose of this review is to compare several model hosts that have been used in experimental mycology to-date and to describe their different characteristics and contribution to the study of fungal virulence and the detection of compounds with antifungal properties. This article is part of a Special Issue entitled: Animal Models of Disease. 相似文献
Marine species tend to have extensive distributions, which are commonly attributed to the dispersal potential provided by planktonic larvae and the rarity of absolute barriers to dispersal in the ocean. Under this paradigm, the occurrence of marine microendemism without geographic isolation in species with planktonic larvae poses a dilemma. The recently described Maya hamlet (Hypoplectrus maya, Serranidae) is exactly such a case, being endemic to a 50‐km segment of the Mesoamerican Barrier Reef System (MBRS). We use whole‐genome analysis to infer the demographic history of the Maya hamlet and contrast it with the sympatric and pan‐Caribbean black (H. nigricans), barred (H. puella) and butter (H. unicolor) hamlets, as well as the allopatric but phenotypically similar blue hamlet (H. gemma). We show that H. maya is indeed a distinct evolutionary lineage, with genomic signatures of inbreeding and a unique demographic history of continuous decrease in effective population size since it diverged from congeners just ~3,000 generations ago. We suggest that this case of microendemism may be driven by the combination of a narrow ecological niche and restrictive oceanographic conditions in the southern MBRS, which is consistent with the occurrence of an unusually high number of marine microendemics in this region. The restricted distribution of the Maya hamlet, its decline in both census and effective population sizes, and the degradation of its habitat place it at risk of extinction. We conclude that the evolution of marine microendemism can be a fast and dynamic process, with extinction possibly occurring before speciation is complete. 相似文献